The Child and Newborn - WBAPwbap.in/data/Child 18.3.4.pdfThe Child and Newborn West Bengal Academy...

The Child and NewbornWest Bengal Academy of Pediatrics, Oriental Apartments, Flat H115C, Canal Street, Kolkata 700 014Phone : 033 2265 4072, Email : [email protected], Website : www.iapwb.comE-version of this journal available at website.

ISSN 0975-0894 RNI Registration No.:RNI/68911/97

EDITOR IN CHIEFDr Atul Kr Gupta

ASSOCIATE EDITORDr Phalguni DuttaDr Arun Kr Manglik

CIRCULATION SECRETARYDr Sumita Basu

EDITORIAL BOARDDr Debasis MitraDr Kaushik MandalDr Kheya Ghosh UttamDr Madhumita Nandi (Banik)Dr (Col.) R K ThaparDr Sanat GhoshDr Subhasis BhattacharyaDr Subhasis RoyDr Sumantra Sarkar

PAST EDITORSDr Umasankar SarkarDr Dilip MukherjeeDr Tapan Kr GhoshDr Subroto ChakraborttyDr Ranjana ChatterjeeDr Sutapa GangulyDr Sumana Kanjilal (Dutta)

EX-OFFICIODr Madhusmita Sengupta, President, WBAPDr Santanu Bhakta, Hony Secretary, WBAP

Special CorrespondanceDr Atul Kr GuptaEditor-in-Chief, The Child and Newborn10C, Janaki Sha Road, HastingsKolkata 700 022Email : [email protected] : [email protected]

Vol.18, No.3 & 4, July - December 2014 CONTENTS

EditorialIf we are not dreaming reality can be............Atul Kr Gupta ....................................................................................... 63

Original ArticleJuvenile Idiopathic Arthritis- A Clinic Based StudyS Guha, S R Pal, Indranil Das ........................................................... 65

Review� Kawasaki Disease and Cardiovascular Risk: An Update

Sumantra Sarkar ................................................................................. 68� Pediatric Hypertension: Ignorance is NOT Always Bliss !

Madhumita Nandi ................................................................................ 73� Acute Rheumatic Fever : An Update

Atul Kumar Gupta ................................................................................. 85

Neonatology� Management of Patent Ductus Arteriosus in Preterm Baby

Nurul Islam .......................................................................................... 94� Persistent Pulmonary Hypertension of Newborn

Anindya Kumar Saha ............................................................................ 98

PG’s Column� Pediatricians Approach To Emergency Cardiac Conditions

Biswajit Bandyopadhyay .................................................................... 104� Heart Failure in Children

Subhendu Mandal ............................................................................... 109

Case Report� A Case of Galactosemia with Pentalogy of Fallot

Debashis Mondal , Asha Mukherjee , Sadhna Sha, R S Ghose ......... 111� Acute Hemiplegia of Childhood – An Unusual Etiology

Rituparna Das, Madhumita Nandi, Gopal Pandey,Rajarshi Bose, Syamal Kumar Banerjee ............................................ 113

Issues� Uniformity of Practice: National Guidelines And

An Inclination To Follow Them Seem To Be The Need of The HourT Chatterjee, S Bhattacharyya ............................................................ 115

� Life Style Diseases of The YoungT Choudhuri, A K Sethi, D Bandyopadhyay, S Chattopadhyay,Joysima Gupta, P S Mitra ................................................................... 117

UpdateEvidenceArun Manglik ...................................................................................... 119

Editorial

In India with rough estimates about 2, 00,000 children1 are born every year with congenital heart diseases. Thisfigure works out from a crude birth rate of 21.8/1000 population, 8/1000 as incidence of congenital cardiac diseasesin newborn period and a population of 1.22 billion. A congenital heart defect (CHD) comes as a curse to one’sfamily as it tends to bring with it a sense of guilt and huge expenditure on part of the family to the extent of goingin debt as well. To add to the woes is non availability of appropriate centers as well as expertise for treatment. Atpresent cardiac centers present carry out around 11,0001(2012 data) cardiac operations per year. This leaves ahuge gap to be filled up. This forces us to look into the prevailing circumstances and find out possible ways toimprove the situation.

The first thing that comes to our mind is availability of centers. Once we encounter such case - immediately onethinks of going to one of metropolis because the centers are located at only these places. Some of them are welladvertised boasting of number of surgeries done and rates for the surgeries they charge. We need to increase thenumber of centers and get them spread over so that they are available at a near location and follow up is easy andconvenient. Government medical colleges suit the best.

Increasing number of centers brings us to the problem of money and trained manpower. The cost of building acentre for cardiac care is huge. The government should come forward as also some big industrial houses andreligious trusts. Centers on smaller scale add more woes than relief. The initiative of West Bengal government inlinking some cardiac centers with government hospitals and getting surgeries done with cost borne by governmentexchequer is commendable. But this cannot be done forever. Establishing and improving own capabilities andhaving centers spread throughout the state should be the motto.

It has been observed2 that hospitals with larger turnover perform better in terms of results in USA. Low-volumecenters utilize the same personnel and facilities to care for fewer patients, which limits their ability to be economicallyviable. At present, the sheer volume to patients in India with the paucity of highly specialized care centers makesthis a no-lose proposition, especially in urban India. It can be feared that more centers will make centers not viable.It is here that government hospitals can fill up the gap. Moreover smaller centers can be utilized for follow up or forsmaller or not so complicated cases. This needs a strong referral system in place.

In establishing a centre apart from the cost of land and building a big chunk is required for instruments anddisposables which come mostly from abroad. It again needs government’s initiatives to waive or reduce taxes onthem. Involving our own bioengineers, IITians a lot can be done in getting our own machines manufactured (“Makein India”) in India and thus getting less reliant on foreign products can go a long way in reducing costs. Beinginnovative and reuse of some articles will also help in reducing costs2. Disposable needles, scalpels, catheters,intravenous (IV) equipment, chest tubes, etc. are care essentials. In most instances, it is assumed that disposabilitylowers the risk of infection. While this is clearly true in some instances (needles), it is not true in all. Especially,highly engineered pieces of equipment (such as electrophysiology catheters and intra cardiac echocardiographycatheters) need to be scrutinized carefully to see if there are ways they can be re-used by appropriate cleaningand sterilization techniques. The cost of labor to clean such devices may be prohibitive in the west but are reasonablein many developing countries.

If we are not dreaming reality can be ……………….

The Child and New Born, Vol 18 No 3 & 4, July – December 2014 63

Requirement of trained manpower is again a big obstacle in proper expansion of cardiac care. It is recommendedto have one academic center per 2-4 million population, or to have one pediatric cardiac center for 30,000 livebirths, one pediatric cardiologist per 60,000 children, or for 0.2 million children by different groups. A simplisticcalculation suggests that we need about 250-500 academic centers, about 660 pediatric Care Center, 2,000-6,000pediatric cardiologists according to these recommendations3. We do not have infrastructure to meet up this hugeshortage. This is more so because we are highly deficient on teaching manpower although the number of medicalcolleges in India has been increasing steadily. This shortage is in the region of 20%-25% in most departments andas high as 33% in some departments, based on data published in the National Medical Journal of India4. Theshortages are particularly acute at the postgraduate level. We can evolve online teaching and train more specialiststhan the present system of having 1-2 trainees under one teacher. Though medical science needs more directteaching but its help can be taken to get more specialists. Online teaching has advantage of apart from trainingmore people, uniform teaching and best teaching.

Increasing access to appropriate, quality pediatric cardiac care is a health care priority that many low- and middle-income countries face today. In the past, when the infant mortality was more than 100/1,000 live births, the drive forcardiac care was less relevant. With steady decline in the infant mortality, and overall improvement in economicconditions, pediatric cardiac care is gaining in importance, even though the current situation is still very grim.

Congenital heart diseases account to form biggest congenital malformation. As we move to achieve a lower IMR asper MDG goals apart from infections the priority for centers for heart diseases as well as manpower has to increase.Otherwise it will be difficult to achieve single digit IMR in near future.

All said and done the monetary part in cardiac care is prohibitive for an average Indian. On average, the poorestquintile of Indians is 2.6 times more likely than the richest to forgo medical treatment when ill5. In recent years,community health insurance (CHI) has emerged as a possible means of: (1) improving access to health careamong the poor; and (2) protecting the poor from indebtedness and impoverishment resulting from medicalexpenditures. The World Health Report 2000, for example, noted that prepayment schemes represent the mosteffective way to protect people from the costs of health care, and called for investigation into mechanisms to bringthe poor into such schemes (World Health Organisation 2000). This can go long way in providing costly cardiaccare services to our people.

As responsible citizens we dream that every child born with heart defects will be diagnosed and will receive qualitycare with dignity. Diseases like RHD will disappear. Preventable CHDs will cease to occur. Obesity, hypertension,and (future) coronary artery diseases might be prevented right from the childhood. If we are not dreaming realitycan be achieved3.

References

1. Kothari SS. Pediatric cardiac care for the economically disadvantaged in India: Problems and prospects. Ann PediatrCardiol 2009;2:95-8.

2. Seshadri Balaji, Raman Krishna Kumar Partnership in healthcare: What can the west learn from the delivery of pediatriccardiac care in low- and middle-income countries Ann Pediatr Cardiol 2015;8(1) 1-3

3. Kothari S S Future of pediatric cardiac care in India in Ann Pediatr Cardiol 2014;7(1) S3-S8

4. Ananthkrishnan N. Acute shortage of teachers in medical colleges: Existing problems and possible solutions. Natl Med JIndia 2009; 20:25-9.

5. Devadasan N, Ranson K, Damme W V, Bart C Community Health Insurance in India an overview Economic and PoliticalWeekly July 10, 2004 3179-3183.

Prof. Atul Kumar GuptaEditor-in-Chief

64 The Child and New Born, Vol 18 No 3 & 4, July – December 2014

Juvenile Idiopathic Arthritis- A Clinic Based Study

S. Guha*, S R Pal*, Indranil Das***Department of Rheumatology VIMS, **Department of Community Medicine ICAER West Bengal

Correspondance : S Guha, Department of Rheumatology VIMS.Email : [email protected]

Introduction

Arthritis is an inflammation of the joint cavity1. It may bedirectly or indirectly caused by infectious agent, it may beidiopathic or may be associated with other diseases2.Early diagnosis and treatment is necessary to preventchronic life threatening and debilitating conditions3,5.

Aims and Objectives

Data of Juvenile Idiopathic Arthritis (JIA) is lacking fromeastern India4. This study is an attempt to describe earlydisease ,patient characteristics, microbiological features andimmunological factors in children with different subgroupsof childhood arthritis using a clinic based approach

Methods and Materials

This is a cross sectional retrospective study. Pediatricpatients attending the rheumatology clinic of VivekanandaInstitute Of Medical Sciences were enrolled from March2013 to September 2014 and classified as per ILAR(International League Against Rheumatism)1.

Study Population

Children less than 16 years of age with possible orevident arthritis determined on the basis of more than oneor more of the following characteristics were included :

1. Joint swelling2. Limited range of movement in one or more joint3. Pain in one or more joint.These findings should be present for atleast 6 weeks.

Inclusion Criteria

Children <16 yrs of age with at least one of the following3 signs-

1. Swelling of joint.2. Restricted mobility of a joint with warmth, tenderness

or pain.These should atleast last for a period of 6 weeks.

Exclusion Criteria

Patients whose complaints are due to an obvious localcause like trauma or who are suffering from nonrheumatological disorders (malignancy, hemophilia, sicklecell anemia) and patients of rheumatic fever are excludedfrom this study.

Post Streptococcal Reactive Arthritis(PSRA) and post viralreactive arthritis may be classified as undifferentiated arthritisas per ILAR classification. These patients fit the inclusioncriteria of having arthritis of >6 weeks

After careful history taking patients were subjected tometiculous musculoskeletal ophthalmological and systemicexamination.Disease Activity Score (DAS28)15 and JuvenileArtheritis Functional Assessment Scale (JAFAS)16 were noted.

Besides routine investigations all patients were tested forrheumatoid factor(RF), ASO titre by latex agglutination, antinuclear antibody(ANA) using indirect immunoflurosence,and HLA-B27 assay were also done. Among imagingstudies, Echocardiography, ultra sonography power Dopplerand magnetic radio imaging(MRI) were performed. Slit lampexamination of the eyes were performed in all subjects.

Results

Of the 26 patients diagnosed as JIA using ILARclassification 3 presented with oligoarticular arthritis, 5were systemic in onset, 9 of polyarticular variety, 7 wereenthesitis related arthritis(ERA), 1 PSRA, 1 post viral reactivearthritis. There was a male preponderance(8 of 9) inpolyarticular variety and in ERA. Systemic onset varietyand oligoarticular arthritis had a female predominance.Majority of the JIA in our study had a later age ofonset(>10years) except the systemic onset variety whichshowed an earlier presentation(earliest being 3 months).The PSRA and post viral arthritis were oligo articular inonset and mean age of presentation were similar.

50% of the cases were below 3rd percentile of height forage(WHO criteria). This was distributed through out all thesubtypes commonest with systemic onset variety. The total

Original Article


joint scores varied according to age of onset and type ofdisease. They were highest in systemic onset variety(SOJIA)and in poly articular subtypes.

All the SOJIA patients had fever ranging from moderate tohigh grade, mostly of the classical quotidian variety.Evanescent maculopapular rash was universally present. 3of the 5 SOJIA patients had generalized lymphadenopathyand hepatosplenomegaly.

Pan uveitis was present in one case of oligoarticular JIA.One patient with ERA had anterior uveitis.RF was positive in one case of polyarticular JIA.ANA was positive in low titre(1:80) in one case ofoligoarticular JIA with panuveitis. HLA-B27 was positive in4 out of 7 cases of ERA, the youngest being 7 years ofage. One child with polyarticular JIA had overlap withjuvenile dermatomyositis had exhibited gottron papule andheliotrope rash. Muscle enzymes(creatininephosphokinase,CPK, aldolase) were elevated and there wasevidence of muscle inflammation in MRI(T2 ).USPD showed enthesitis in 2 cases of ERA. MRI doneover one year follow up picked up bilateral sacroilitis in 2cases of ERA.

ECHO cardiography revealed grade2 mitral regurgitation(MR)and grade1 mitral valve prolapse in one case ofoligoarticular variety, and grade2 MR was seen in PRSA.None of the patients had any cardiovascular symptoms.

Discussion

JIA is the most common cause of arthritis in children andrepresents upto 65%of arthritic disease in children6. Variousepidemiological studies of JIA report divergent results owingto heterogenecity of the disease, differences in standardiseddiagnostic criteria, patient retrieval and study designs7-10.Although JIA is a rare disease, its true frequency is notknown in our country. In the west its incidence is reportedto be 6-8/100,000 population per year10.

1. JIA has been divided into various subgroups, and thiscategorization helps in diagnosis, follow up andsubsequent care of these children. Like other indianstudies9,10 polyarticular variety was the commonest inour study though Singh and colleuges reportedoligoarticular variety to be more commoner from thenorthern part of the country11. This was closely followedby ERA. Unlike North America and Europe whereoligoarticular represents 50-75% cases of JIA, thisvariety was the least common in our study ,anobservation similarly reported by Aggarwal et al11.

2. The mean age of onset in the west is usually 1-3

years10 and rare below 6 months. It appears that inIndia JIA has a later age of onset. An indian study byKabra et al9 showed that the mean age of onset wasearliest in SOJIA(5.2YRS), followed by oligoarticular(6.8 yrs) and polyarticular(7.2yrs) subtypes. The overallonset of disease in our study tended to peak in laterage groups. The mean age of onset was lowest inSOJIA, with the earliest case report being 3 months.

3. Regarding sex, males predominated over females inall subtypes like other indian studies9,10. Howeverfemales predominated in oligoarticular variety andSOJIA, unlike most indian observations. The malepreponderance of JIA in this part of the subcontinentmay be due to the special characteristic of the diseaseseen in India; another explanation may be that boysin our country are cared more by family members andhence brought early for treatment.

4. Unlike studies from western countries13 we had a verylow incidence of uveitis, a similar finding reportedfrom most parts of the country10,4. Uveitis could beonly detected in 2 cases inspite of thorough slit lampexamination of eyes of all patients .One was anoligoarticular ANA+ case and the other was an HLA-B27 + ERA variety. Probably occurrence of uveitis isclosely related to ANA positivity which is again reportedto be very low in indian children.

5. RF positivity was seen in only 1 child with polyarticularvariety. RF positivity is seen only in 15-20% of JIAcases6. None of our children had rheumatoid nodules.

6. Of all the 26 cases of JIA 7 were ERA. This findingwas at par with other indian studies19. This is incontrast to a similar clinic based study from easternindia by Ghosh et al4 where only 2 cases of ERAwere reported out of 50 JIA cases. Studies from thewest18 report that 6-19% of JIA cases are ERA.Barring one, all were males and >10 years of age.Only one had a family history of spondyloarthropathy.Of the 7 cases of ERA, 6 presented with peripheralarthritis, 2 had history of axial involvement .Enthesitiswas present in 2 cases as demonstrated by UltrasoundPower Dopler (USPD). 2 patients had bilateral sacroilitisin MRI over 1 year follow up. HLA-B27 positivity waspresent in 4 cases. This observation is at par with astudy on ERA in indian children by Agarwal .M et al19

which showed a higher proportion of HLA-B27 positivity,early onset axial involvement, and paucity of familyhistory ,unlike their western counterparts.


Heart disease is a rare complication of JIA. None of thepatients had any history of breathlessness or palpitations.Grade 2 MR was seen in the sole child with PRSA. Thisfinding was not diagnostic of rheumatic carditis. In absenceof any control group this finding cannot be taken assignificant.

11%

19%

35%

27%

4% 4% Oligoarticular

variety

Systemic onset

Polyarticular

Enthesitis related

arthritis

Types of JIA and its distribution :

Table 1: Characteristics of JIA according to different relevant clinico-pathological factors:

JIA Number of Male female Mean age Rash Hepato- Lymphadenopathy Uveitis Rheumatoid ANA HLA B-27cases(%) ratio splenomegaly factor

of onset

Polyarticular 9(35) 8:1 <10 yrs - - - - 1 - -SOJIA 5(19) 1:4 - 5 3 3Oligoarticular 3(11) 1:3 - - - - 1 - 1 -ERA 7(27) 6:1 - - - - 1 - 4PSRA 1(4) All F - - - - - - -

PVRA 1(4) All M - - - - - - - -Table 2: Clinico-Immunological Profile of JIA in Other Studies

Clinico-immunological Present study Singh et al Casidy et al1 Seth et al9 Parkodi et al14

M:F ratio 1.8:1 1:2 1.3:1 1.6:1Pauciarticular (%) 11 42.2 50 30 49Polyarticular (%) 35 37.8 40 46 41Systemic (%) 19 14.8 10 24 10Rheumatoid nodules (%) - 5.4 10 0.8 3Uveritis (%) 7.7 1.3 5 1.1 3ANF* (%) 3.8 0 45 6.5 -Rheumatoid factor* (%) 3.8 0 10 15 9.7

Reference:1. Brewer EJ .Standard methodology for segment I, II and

III,prdiatric rheumatology collobarative study group studies . JRheumatol. 1982:9 (1): 109-113.

2. Kunnamo J,Kallio P et al.Clinical signs and laboratory tests inthe differential diagnosis of arthritis in children. Am. JDis.Child.1987;141 (1) : 34-40.

3. Special Writing Group of the Committee on RheumaticFever,endocarditis and Kawasaki Disease of The council on onCardiovascular Disease in the Young of the Ammerican HeartAssociation .Guidelines Ffor the diagnosis of RheumaticFever.Jones Criteria ,1992 update JAMA.1993;269(4):476.

4. Sircar D,Ghosh B et al. Indian Pediatrics. 2006;43:429-433.5. Martal W,Cassidy JT .Roentgenologic manifestation of juvenile

rheumatoid arthritis. Am J Roentgenol Radium Ther Nuci Med.1962; 88:400-423.

6. Cassidy JT,Petty RE.Textbook of Paed. Rheumatol.Third edition.1995;133-223.

7. Gare BA,Fasth A.Epidemiology of juvenile chronic arthritis insouthwestern Sweden: A 5 year retrospective populationstudy.Pediatrics 1992;90:950-958.

8. Aggarwal A,Misra R.Juvenile chronic arthritis in india:is it differentfrom that seen in Western countries?Rheumatol Int 1994;14:53-56.

10. Singh S,Kumar L et al .Clinico-immunological profile of juvenilerheumatoid arthritis at Chandigarh.Indian Ped.1999;36:449-454.

9. Seth ,V,Kabra SK Clinico-immunological profile in juvenilerheumatoid arthritis –an Indianexperience.Ind.J.Ped,1996;63:293-300.

11. Aggarwal A,Misra R.JRA in India :rarity of ANA anduveitis.IJP.1996;63:301-304.

12. Chandrasekharan AN.JRA Madras experience:1996;63:501-511.13. Anderson GB,Fasth A. Incidence and prevalence of JRA .Annals

of Rhematol1987;46:277-81.14. Pakodi R,Subramanium R.Pattern of rheumatic dis.in South

India.Clinical profile of JRA.J of API.38:771-773.15. Prevoo ML,Kupper HH et al.Modified disease activity scores that

include 28 joint counts.Development and validation in apropespective longitudinal study of patients with rheumatoidarthritis.Arthritis Rheum 1995;38:44-48.

16. Ozher H,Alehan D,Ozme S.Mitral and aortic insufficienc y inpolyarticular juvenile rheumatoid arthritis. Peditr. Cardiol. 1994;15: 151-153.

17. Scaller JG.Rheumatic diseases of childhood.Nelson text bookof Pediatrics vol 15th.

18. Ozen S,Demirkaya E et ai .Distribution of JIA in the in the EasternMediterranean .:Results from the Turkish registry.Clinical andexperimental rheumatology;29:111-115.

19. Agarwal M,Jariwala M. 110 patients with ERA , : A demographicand clinical study from a tertiary level ped rheum.centre inIndia.Annals Of rheum ;2012 ;71:264.


Kawasaki Disease and Cardiovascular Risk: An Update

Sumantra SarkarAssociate Professor, Pediatric Rheumatology Clinic, Dept. of Pediatric Medicine, IPGMER& SSKM, Kolkata

Correspondance : Sumantra Sarkar, Associate Professor, PediatricRheumatology Clinic, Dept. of Pediatric Medicine, IPGMER& SSKM,Kolkata.

the degree of fever) and bilateral conjunctival injection are theusual presenting features. Red eye of KD often shows a limbalsparing.Non-suppurative conjunctivitis, iritis and bilateralanterior uveitis are commonly noted. Keratic precipitates areoften detectable by a slit lamp. Swollen lymph nodes can bethe first manifestation KD. Most of the other features mentionedin the diagnostic criteria are also seen during this phase. Rashesoccur early in the disease, and the cutaneous rash observedin patients with KD is non-specific, polymorphic, non-itchy andnormally observed up to the 5th day of fever. Systemicinflammatory changes are evident in many organs. Myocarditisis common at this time but may not be clinically discernible.Pericarditis, aseptic meningitis, hepatitis, sterile pyuria are alsonoted in this phase.KD patient can rarely present withhypotension which is called Kawasaki Shock Syndrome.Hyponatremia can also be a presenting symptom.

Subacute phase (10-28 days):

Most of the clinical features of acute stage are subsiding in thisphase. Peeling of the skin in the genital area, hands, and feet(especially around the nails and on the palms and soles) mayoccur in this phase. Coronary artery abnormalities if presentcan be demonstrable on echocardiography at this time.Thrombocytosis is sometimes very prominent and this findingin presence of periungual desquamation is said to be virtuallypathognomonic of KD.

Convalescent phase:

Begins when all clinical signs have disappeared and continuestill the acute phase markers (e.g. elevated C-reactive protein,thrombocytosis, erythrocyte sedimentation rate) return tonormal. This usually occurs by the end of 6-8 weeks after theonset of the illness.

The diagnosis of KD is essentially clinical.

American heart Association criteria for diagnosing KD is givenbelow 11

FEVER persisting for at least 5 days

Principal Clinical Findings

1. Bilateral conjunctiva injection (no exudate)

Kawasaki disease (KD), also known as ‘Mucocutaneous lymphnode syndrome’ is an autoimmune systemic vasculitispredominantly affecting medium and small size visceral arteriesand their branches (arterial size range from 50 to 100µm indiameter)1. It affects mainly the children under the age of 5years. Although the disorder was first described in 1967 by Dr.Tomisaku Kawasaki from Japan, it is now known to occur inboth endemic and community-wide epidemic forms in America,Europe, and Asia in all races2.

Causes of Kawasaki disease

The specific etiology of this disorder is still obscure. Theinteraction between genetic and environmental factors, possiblyincluding an infection might play a major role in causation ofthe disease. The current theories center primarily onimmunological causes for the disease. Basically themacrophages and neutrophils are activated by variousinflammatory cytokines mediated by IL-17 produced by T-helpercells (Th17).Super-antigens from virus or bacteria are the likelytriggers for the immune vasculitis3. Recent report suggests thatKD cases are often linked to large-scale wind currentsoriginating in central Asia and traversing the north Pacific.Results suggest that the environmental trigger for KD could bewind-borne4.

Besides the environmental triggers the role of geneticsusceptibility to KD has been strikingly evident. Recentadvances in gene analysis studies have shown links with afew susceptibility genes like ITPKC ( Inositol tri-phosphokinase),CASP3 (Caspase3),BLK (B lymphoid kinase),CD-40,HLA-51 etc 5-7.

Clinical aspects and diagnosis of KD

The clinical profile of KD can be divided into the following 3phases 8-10.

Acute phase (0-10 days):

A remittent fever, often 104°F or higher (unresponsive toantimicrobials), extreme irritability (often out of proportion to

Update


2. Acute cervical lymphadenopathy (unilateral/ bilateral /firm/slightly tender with a diameter of 1.5cm)

3. Strawberry tongue, oropharyngeal erythema, redness andcracking of lips (ulcerative lesions not seen)

4. Polymorphic exanthema: - erythematous maculo papularrash, (sometimes morbilliform/scarletiniform) usuallyappears within 5 days of fever, starting with red palms andsoles and moving to the trunk

5. Red, swollen, indurated hands and feet and laterdesquamation of hands and feet after 1-3 weeks

Fever plus 4/5 Principal criteria or Fever plus 3/5 + Coronaryartery dilatation can be considered for the diagnosis of TypicalKD and Fever + 3/5 Principal criteria is in favor for atypical KD,but both typical and atypical need treatment

Use of terms "incomplete" or "atypical"

The phrase "atypical Kawasaki disease" was initially used todescribe those who do not fulfill the classical diagnostic criteria,but had coronary complications12. Later, the term "atypicalKawasaki disease" has been used to describe patients withincomplete presentation of the disease, regardless of thecoronary complications and is exchangeable for "incompleteKawasaki disease" 13. However Newburger et al. proposedthat "atypical Kawasaki disease" should be reserved for patientswith complications, eg, renal impairment, which are generallynot seen in Kawasaki disease11. This proposition has beensupported by other authors10,14.

Variation of clinical presentation in Indian patients15

(a) Higher proportion of patients in older age group (>5 years)

(b) Early peeling, often with 10 days of onset of fever

(c) Thrombocytosis being more frequent

Cardio-vascular Risk in KD

Coronary artery abnormalities are seen in approximately 15-25% of untreated patients10. Arteritis begins 6-8 days followingthe onset of KD. It leads to inflammation of all the layers ofartery with infiltration of monocytes, lymphocytes andneutrophils. Edematous dissociation of tunica media occurs.Periarteritis further damages elastic lamina, leading to intensedamage. Breakage of internal lamina leads to diffuse dilatation(ectasia) and aneurysm formation. Cellular infiltration continuestill day 25 of the illness and then gradually decreased in severity.Myocarditis is another well recognized component of KDoccurring in more than half of the patient in acute phase. Itmay be transient or may cause left ventricular dysfunction.Myocarditis develop even earlier than coronary artery diseaseand it peaks by the day 10, disappear gradually by day 205,10.

Coronary artery abnormalities (dilatation or aneurysm) can bediagnosed by echocardiography after the first week of illness.

This is an essential investigation for evaluating KD. A repeatechocardiogram is obtained at 2-3 weeks and again at 6-8weeks following the onset of illness 9,10.

The measurement of coronary arteries mentioned by thecardiologist often creates confusion in the minds of a treatingpediatrician. A basic knowledge on the coronary arterydiameters which is based on the body surface area of the childcould be helpful for better understanding.

Table1. Normal coronary artery diameters5

Body Surface Area (BSA) Normal Coronary Artery Diameters

< 0.5 m2 2.5mm

0.5- 1.0 m2 2.5-3.0 mm

Echocardiographic assessment of Coronary arteries in termsof BSA can be best done by using a nomogram designated fordifferent arteries11.

Kato, et al prospectively studied the fate of coronary aneurysmsfollowing KD in Japan 16.

Majority of the aneurysms regress over the next few months.In cases of incomplete resolution of aneurysms, a dreadedcomplication in the form of coronary stenosis may develop.This may be further complicated by premature atherosclerosisand lead to significant coronary obstruction and myocardialischemia later. Aneurysms larger than 8 mm in diameter is

Fig. 1 Mean and prediction limits for 2 and 3 SDs for size of LAD (A),proximal RCA (B), and LMCA (C) according to body surface area forchildren less than 18 years old.[Newburger JW et al.11]


called giant aneurysms, seen in a few cases of KD and oftendo not regress. Stenosis or complete obstruction occurs in halfof these 9,10.

Clinical factors predictive of an increased risk for coronarydisease9,10.

(a) Male gender

(b) Age less than 1 year

(c) Cardiomegaly

(d) prolonged fever

(e) Recurrence of fever following an afebrile period of morethan 48 hours

(f) Arrhythmias other than first-degree heart block

Investigations5,9,10.

There are no laboratory tests that are pathognomonic of KD.Lab tests are done for supportive evidences, detection ofcomplications and sometimes to exclude other differentials.

Blood tests

(a) Complete Hemogram - normocytic anemia .Platelet countmay be found normal initially but eventually thrombocytosisis noted in the second week9,10.

(b) Elevations in erythrocyte sedimentation rate and the C-reactive protein persisting for 4 to 6 weeks

(c) Liver function tests - evidence of hepatic inflammation andlow serum albumin

Other optional tests

(a) Electrocardiogram - evidence of ventricular dysfunctionor, occasionally, arrhythmia due to myocarditis

(b) Echocardiography is used for to identify coronary arterydilatation and aneurysms, valvar regurgitation, myocarditiswith ventricular dysfunction and pericarditis with effusion.Detection of coronary abnormalities in experienced handshas a sensitivity and specificity of more than 95%10.

(c) Ultrasound or computerized tomography may showhydrops (enlargement) of the gallbladder

(d) Urinalysis may show white blood cells and protein in theurine (sterile pyuria and proteinuria)

(e) Lumbar puncture - evidence of aseptic meningitis

(f) Angiography was historically used to detect coronary arteryaneurysms and remains the gold standard for theirdetection, but it is done only when any abnormality isdetected by echocardiography.

Treatment 9-11

Intravenous gammaglobulin (IVIG) 2 g/kg as a singleinfusion over 12 h :

This is very effective when given in the first 10 days of illness.

However, children who present after 10 days of fever still shouldbe treated if fever or other signs of persistent inflammation arepresent, including an elevated ESR or CRP level. With IVIGclinical symptoms improve, irritability decreases and acutephase reactants normalizes. Live vaccines should be delayedfor at least 3 months after IVIG.

Approximately 10% of KD patients remain non-responder toIVIG with persistence of fever even 48 hours after administrationof the drug. Such patients are said to have resistant disease. Asecond or possibly a third dose of IVIG may be considered inthem. Intravenous methyl prednisolone (30 mg/kg daily for 3days) can also be considered in such cases.

Aspirin :

Aspirin is administered for its anti-inflammatory andantithrombotic effects. During the acute phase of illness. Aspirinis administered at 70-80 mg/kg/day in 4 divided doses.Somewhat lower aspirin doses (30-50 mg/kg/day) have beenused in Japan16. In USA 80–100 mg/kg/day in four doses isrecommended following the guideline of American Heartassociation. The aspirin dose should be reduced, either 48 to72 hours after defervescence or 14 days after the onset ofsymptoms and when the child has been afebrile for at least 48to 72 hours. Low-dose aspirin (3 to 5 mg per kg per day, givenas a single dose) has an antiplatelet effect. It should becontinued until ESR and platelet count normalize which usuallytake minimum of 6–8 weeks. If the echocardiography done atthis time shows any abnormality in coronary arteries, aspirinshould be continued.

Newer drugs for refractory KD :

Infliximab - Chimeric IgG1 monoclonal antibody that bindsspecifically with TNF alpha-1.It is reported to be effective inrecrudescent fever after IVIG. A phase 3 randomised trial onInfliximab for intensification of primary therapy for Kawasakidisease has been published17.

Ulinastatin – Markedly activated neutrophils or high level of

plasma neutrophil elastase activity has been shown to be

responsible for IVIG resistance. Ulinastatin, a urinary tripsin

inhibitor, inhibits neutrophil elastase and emerges to be an

option18.

Cyclosporin – suppress the activity of T cells, used in some

resistant cases.

Doxycycline – Recent researches have shown that doxycyclinecan mitigate TNF alpha induced matrix metalloproteinase(MMP)- 9 activity and thereby prevents coronary elastindamage19.

Antioxidants5 – Vitamin A,E and C have definite role in KD.Theproposed dose schedule has been mentioned here. However


Vitamin D, in its active form active form [1,25 (OH)2 D3] exhibitsanti-inflammatory activities in coronary vessels20.

Proposed Dosage ScheduleTable 2: Proposed dosage schedule of antioxidants for the preventionof coronary artery disease in KD along with IVIG and Aspirin (nowunder clinical trial )

Age VIT A VIT E VIT C

Routes and Once daily Once daily Two dividedFrequency x 4 Days x 14 Days doses x 14

Oral Oral days oral

>6 months 25,000 IU 100 IU 500mg6 months to 1-Year 50,000 IU 100IU 500mg1 To 2 –Year 50,000 IU 200IU 500mgAbove 2 Year 50,000 IU 400IU 1000mg

Adapted from ‘Treatment for KD’, Kawasaki Disease Foundation ofIndia http://www.kawasakidiseaseindia.

Current Scenario in the StateKD is emerging as the most common cause of acquired heartdisease10. The author believes that the knowledge and theexpertise among pediatricians and clinicians working in tertiarycare centers has improved a lot which help to diagnose theearly as well as late cases. Even the atypical presentationsare being increasingly recognized21-23. The cases which presentlate in the sub acute or convalescent phases are oftenchallenging with diagnostic dilemma. But these cases are stillbeing diagnosed with accuracy in tertiary care facilities24. A

seven year follow up in our Pediatric Rheumatology Clinic inIPGME&R, had documented KD in 24% children with vasculitisindicating a rising trend in positive diagnosis25. In spite of thisrising trends of early and correct diagnosis, many cases arestill missed in the community. Many are misdiagnosed as urinarytract infections or viral illness. The awareness among thegeneral practitioners and the first contact health care personnelneeds to be improved for early diagnosis and prompt referralwhich could save the child from dreadful cardiac complications.Kawasaki disease registry, as already functioning in Mumbai,has been a suitable way to create awareness among the primarypediatricians and parents26. Setting up of a Kawasaki registry,at the state level in West Bengal, could possibly make a hugeleap forward.Another important issue is the cardiac evaluation following aclinical diagnosis KD. Presently we are not having thestandardized and validated data for the normal size of thecoronary arteries in the Bengali children. But the nomogram interms of body surface area mentioned above could be a usefultool, till we have our own data. The nomogram should alwaysbe used at the time of cardiac evaluation. It is our experiencethat, the cardiologists, mostly conversant with the adult patients,often do not mention the size of the coronary arteries. In otherreports, they mention the size but whether that is normal orabnormal is not at all clarified. The treating pediatrician remainsin a dark. In this respect, a collaborative effort between thepediatrician and the cardiologist with proper use of thediagnostic tools could be of certain benefit for the child.

Reference:1. Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F et

al. 2012 revised International Chapel Hill Consensus ConferenceNomenclature of Vasculitides. Arthritis Rheum. 2013;65:1-11.

2. Kawasaki T. Acute febrile mucocutaneous syndrome withlymphoid involvement with specific desquamation of the fingersand toes in children [in Japanese]. Arerugi. 1967;16:178

3. Natividad MF,Torres-Villanueva CA, Saloma CP. Superantigeninvolvement and susceptibility factors in Kawasaki disease:profiles of TCR Vß2+ T cells and HLA-DRB1, TNF-a and ITPKCgenes among Filipino patients. Int J Mol Epidemiol Genet.2013;4:70-6.

4. Rodó X1, Ballester J, Cayan D, Melish ME, Nakamura Y, UeharaR, Burns JC. Association of Kawasaki disease with troposphericwind patterns.Sci Rep. 2011;1:152.

5. Kawasaki Disease Foundation of India http://www.kawasakidiseaseindia.accessed on 10.12.14

6. Kuo HC, Hsu YW, Wu CM, Chen SH, Hung KS, Chang WP et al.A replication study for association of ITPKC and CASP3 two-locus analysis in IVIG unresponsiveness and coronary arterylesion in Kawasaki disease. PLoS One. 2013 ;8(7):e69685.

7. Chang CJ, Kuo HC, Chang JS, Lee JK, Tsai FJ, Khor CC et al.Replication and meta-analysis of GWAS identified susceptibilityloci in Kawasaki disease confirm the importance of B lymphoidtyrosine kinase (BLK) in disease susceptibility. InternationalKawasaki Disease Genetics Consortium; Korean Kawasaki

Disease Genetics Consortium TaiwanKawasaki Disease GeneticsConsortium, Chen YT, Chen CH, Wu JY, Lee YC. PLoS One.2013;8(8):e72037.

8. Kawasaki T. General review and problems in Kawasaki disease.Jpn Heart J 1995; 36: 1-12.

9. Committee on Rheumatic fever, Endocarditis, and KawasakiDisease of the American Heart Association’s Council onCardiovascular Disease in the Young. Diagnostic guidelinesforKawasaki disease. Am J Dis Child 1990; 144: 1218-1219.

10. Singh S, Kawasaki T. Kawasaki disease - an Indianperspective.Indian Pediatr. 2009;46:563-71.

11. Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY,Burns JC, et al. Diagnosis, treatment, and longterm managementof Kawasaki disease: a statement for health professionals fromthe Committee on Rheumatic Fever, Endocarditis, and KawasakiDisease, Council onCardiovascular Disease in the Young,American Heart Association [Published correction appears inPediatrics 2005;115:1118]. Pediatrics 2004;114:1708-33.

12. Sonobe T, Kawasaki T Atypical Kawasaki disease. Prog Clin BiolRes. 1987; 250:367-78.

13. Barone SR, Pontrelli LR, Krilov LR. The differentiation of classicKawasaki disease, atypical Kawasaki disease, and acuteadenoviral infection: use of clinical features and a rapid directfluorescent antigen test. Arch Pediatr Adolesc Med.2000;154:453–456.

14. Manlhiot C, Christie E, McCrindle BW, Rosenberg H, Chahal N,


Yeung RS. Complete and incomplete Kawasaki disease: twosides of the same coin. Eur J Pediatr. 2012; 171:657-62.

15. Kushner HI, Macnee R, Burns JC.Impressions of Kawasakisyndrome in India. Indian Pediatr. 2006 ;43:939-42.

16. Kato H, Sugimura T, Akagi T. Long-term consequences ofKawasaki disease. A 10- to 21 year follow up study of 594patients. Circulation 1996; 94:1379-1385.

17. Tremoulet AH, Jain S, Jaggi P, Jimenez-Fernandez S, PancheriJM, Sun X. Infliximab for intensification of primary therapy forKawasaki disease: a phase 3 randomised, double-blind, placebo-controlled trial.Lancet. 2014;383:1731-8.

18. Kanai T, Ishiwata T, Kobayashi T, Sato H, Takizawa M, KawamuraY et al. Ulinastatin, a urinary trypsin inhibitor, for the initialtreatment of patients with Kawasaki disease: a retrospectivestudy.Circulation. 2011;124:2822-8.

19. Lau AC, Duong TT, Ito S, Wilson GJ, Yeung RS.Inhibition of matrixmetalloproteinase-9 activity improves coronary outcome in an animalmodel ofKawasaki disease. Clin Exp Immunol. 2009;157:300-9.

20. Suzuki Y, Ichiyama T, Ohsaki A, Hasegawa S, Shiraishi M,Furukawa SAnti-inflammatory effect of 1alpha,25-dihydroxyvitamin D(3) in human coronary arterial endothelialcells: Implication for the treatment of Kawasaki disease. J SteroidBiochem Mol Biol. 2009;113:134-8.

21. Mukherjee D, Pal P, Kundu R, Niyogi P. Macrophage activationsyndrome in Kawasaki disease.Indian Pediatr. 2014;51:148-9.

22. Pal P, Giri PP. Orange-brown chromonychia, a novel finding inKawasaki disease. Rheumatol Int. 2013;33:1207-9.

23. Nandi M, mondal R. Acute renal Failure in a child with KawasakiDisease.Eastern Journal of Medicine.2010;15:122-4

24. Chakrabartty S1, Pramanik S, Thapa R. Difficulties in thediagnosis of Kawasaki disease. Indian Pediatr. 2006;43:728-31.

25. Sarkar S, Mondal R, Nandi M, Ghosh A. Trends of Childhoodvasculitides in Eastern India. Indian Pediatr.2011;48:814

26. Khubchandani RP, Khemani C. Kawasaki disease registries reapresults – experience in Mumbai. Indian J Pediatr 2006; 73: 545.

Counselling In Pediatrics : In Lighter Vein

Charity begins at home! Let us begin counselling at home.

(i) How many of us can counsel successfully our parents notto unduly worry about our problems in life!

(ii) How many times are we successful in counselling our in-laws not to blow out of proportion our small mistakes!

(iii) How many times we can successfully counsel ouradolescent kids to obey in disciplined and realisticbehaviours (as we think)!!

(iv) How many times we can counsel our neighbours not topark his vehicle obstructing our driveway!

(v) How many times we can counsel our neighbours not tomake loud parties during our kid’s exam!

Let us get some clinical examples :

Case : 3mth old healthy, breast fed, active child with normaldevelopment has 6-7 loose motions /day with 1-2 waterymotions without dehydration or toxicity.

Client 1 : Father and sole wage earner( mechanic) and mother(house wife with poor communication skill) with 3 children witha sick child causing father’s absenteeism from work. Need veryquick recovery.

Client 2 : Father (Senior manager) and mother (Professor) withsingle child , both are net-learned and knows rare causes ofdiarrhoea and asking questions for every single motion. Needexplanation for every simple motion.

Client 3 : Family of large business establishment with first malechild and wishes cure within 2 days. Ready to have any

Investigations and admit in corporate hospital if necessary andoverall calls you each time the child passes stool! May requestyou for second opinion if you wish!

My dear colleagues, is it possible to have a uniform protocol(ONE SIZE NEVER FITS ALL!) for counselling in any diseasein pediatrics while practising in a heterogeneous democraticcountry like us?

Finally , the paediatricians counselling is more often than notcentred on whether he/she will be able to counsel the clientsuccessfully so that he will come again in follow up but mostimportant will pay the consultation fees also !

The experience in practice shows that “diagnosis is sciencebut management is an art”. After you have made a correctclinical diagnosis, you have to listen to all the stakeholders(father, mother, grandparents and even neighbours –so calledwell wishers) and first find out who is the decision maker!Counselling with analogy and explaining with commonexamples often helps. Eye to eye contact and judging thecaregivers reflex is of great help. Early follow up with reports inperson rather than phone may help to iron out differenced inopinion.

Finally, it has been established that even a client with whoseunderstanding you are completely satisfied may never turn upagain, but one who has argued and looks dissatisfied with youmay come again with smile and a cured child! That is yourachievement.

Best of luck!! Gautam Ghosh

Consultant Pediatrician,Kolkata.Email [email protected]


Pediatric Hypertension: Ignorance is NOT Always Bliss !

Madhumita NandiAssociate Professor, Department of Pediatric Medicine, NRS Medical College, Kolkata

Introduction

Hypertension is known to be a major cause of morbidity andmortality and the long-term health risks to children withhypertension may be substantial. Therefore, it is important thatclinical measures be taken to reduce these risks and optimizehealth outcomes1,2,3.

The Task Force on Blood Pressure Control in Children,commissioned by the National Heart, Lung, and Blood Institute(NHLBI) of the National Institutes of Health (NIH), developedstandards for BP by using the results of 11 surveys of morethan 83,000 person-visits of infants and children (includingapproximately equal numbers of boys and girls). The percentilecurves were first published in 1987 and describe age-specificdistributions of systolic and diastolic BP in infants and children,with corrections for height and weight3.

The Third Report of the Task Force, published in 1996, providedfurther details regarding the diagnosis and treatment ofhypertension in infants and children.In 2004, the Fourth Reportadded normative data and adapted the data to growth chartsfrom the Centers for Disease Control and Prevention (CDC)for 20003,4.

Definition of Hypertension

In accordance with the recommendations of the Task Force3,BP is considered normal when the systolic and diastolic valuesare less than the 90th percentile for the child’s age, sex, andheight.

(i) Prehypertension in children is defined as average Systolicblood pressure (SBP) or Diastolic blood pressure (DBP)levels that are greater than or equal to the 90th percentile,but less than the 95th percentile.

(ii) Hypertension is defined as average SBP and/or DBP thatis greater than or equal to the 95th percentile for sex, age,and height on three or more occasions.

As with adults, adolescents with BP levels greater than orequal to 120/80 mmHg should be consideredprehypertensive.

(iii) A patient with BP levels above the 95th percentile in aphysician’s office or clinic, who is normotensive outside aclinical setting, has white-coat hypertension.AmbulatoryBP monitoring (ABPM) is usually required to make thisdiagnosis.

The normative values of BP in children according to the taskforce is given in TABLE 1a & b

Pathophysiology

BP is determined by the balance between cardiac output andvascular resistance. A rise in either of these variables, in theabsence of a compensatory decrease in the other, increasesmean BP.

Factors that affect cardiac output include the followiing :

(i) Baroreceptors

(ii) Extracellular volume

(iii) Effective circulating volume - Atrial natriuretic hormones,mineralocorticoids, angiotensin

(iv) Sympathetic nervous system.

Factors that affect vascular resistance include the following :

(i) Pressors – Angiotensin II, calcium (intracellular),catecholamines, sympathetic nervous system, vasopressin

(ii) Depressors – Atrial natriuretic hormones, endothelialrelaxing factors, kinins, prostaglandin E2, prostaglandinI2

The complexity of the system explains the difficulties oftenencountered in identifying the mechanism that accounts forhypertension in a particular patient. These difficulties are themain reason why treatment is often designed to affect regulatoryfactors rather than the cause of the disease.Correspondance : Madhumita Nandi, Associate Professor,

Department of Pediatric Medicine, NRS Medical College, KolkataEmail: [email protected].

Review


Table 1a - BP charts for boys 1-17 years


Table 1a - BP charts for boys 1-17 years (Cont..)


Table 1b - BP charts for girls 1-17 years


Table 1b - BP charts for girls 1-17 years (Cont..)


Etiology

Hypertension can be primary (ie, essential) or secondary. Ingeneral, the younger the child and higher the BP, the greaterthe likelihood that hypertension is secondary to an identifiablecause (see Table 2 below). A secondary cause of hypertensionis most likely to be found before puberty; and after puberty,hypertension is likely to be essential5.

Clinical Presentation

Hypertension in children is mostly asymptommatic unlessseverely high when the child could present with complications.Or else, it is most often an incidental finding by an alert andrational clinician . So it is very important that Blood pressuremeasurement should be a part of every pediatric consultationafter 3 years of age. The conditions which need BP evaluationeven before 3 years of age are enumerated in table 3.

Certain signs and symptoms that should alert the physician tothe possibility of hypertension in children includeheadache,fatigue,blurred vision,epistaxis and Bell’s palsy.

Identification of signs of secondary hypertension

A thorough physical examination should be done to assess forpotential causes of the hypertension:

(a) Body mass index, to assess for metabolic syndrome

(b) Tachycardia, to assess for hyperthyroidism,pheochromocytoma, and neuroblastoma

(c) Growth retardation, to assess for chronic renal failure

(d) Café au lait spots, to assess for neurofibromatosis

(e) Abdominal mass, to assess for Wilms tumor and polycystickidney disease

(f) Epigastric or abdominal bruit, to assess for coarctation ofthe abdominal aorta or renal artery stenosis

(g) BP difference between upper and lower extremities, toassess for coarctation of the thoracic aorta

(h) Thyromegaly, to assess for hyperthyroidism

(i) Virilization or ambiguity, to assess for adrenal hyperplasia

Infants Children Adolescent1-6y 7-12 y

Thrombosis of renal artery or vein Renal artery stenosis Renal parenchymal disease Essential hypertensionCongenital renal anomalies Renal parenchymal Renovascular abnormalities Renal parenchymal diseaseCoarctation of aorta diseaseBronchopulmonary dysplasia Wilms tumor Endocrine causes Endocrine causes

Neuroblastoma Essential hypertensionCoarctation of aorta

(a) History of prematurity, very low birthweight or other neonatalcomplication required intensive care.

(b) Congenital heart disease (repaired or nonrepaired)

(c) Recurrent urinary tract infections, hematuria or proteinuria

(d) Known renal disease or urologic malformations

(e) Family history of congenital renal disease

(f) Solid organ transplant

(g) Malignancy or bone marrow transplant

(h) Treatment with drugs known to raise BP

(i) Other systemic illnesses associated with hypertension(neurofibromatosis, tuberous sclerosis, etc.)

(j) evidence of elevated intracranial pressure

Table 3. Conditions Under Which Children <3 years Old ShouldHave Blood Pressure Measured

(i) Stigmata of Bardet-Biedl, von Hippel-Lindau, Williams, orTurner syndromes

(j) Acanthosis nigricans, to assess for metabolic syndrome

Measurement and recording of blood pressure

Best medical care includes yearly measurement of bloodpressure (BP) in every child older than 3 years, preferably bymeans of auscultation with a mercury gravity manometer.Doppler and oscillometric techniques can be used in childrenin whom auscultatory BP measurements are difficult to obtain.Measurements obtained with oscillometry that exceed the 90thpercentile should be repeated with auscultation. Measurementsrepeated over time are required to obtain meaningfulinformation3,4,5.

Proper cuff size is essential for accurate measurement of BP.The width of the rubber bladder inside the cloth cover shouldcover at least 40% of the patient’s arm circumference at a

Table 2. Common Causes of Hypertension by Age


point midway between the olecranon and the acromion. Thelength of the bladder in the cuff should cover 80-100% of thecircumference of the arm. If a cuff is too small, the next largercuff size should be used, even if it appears too large3.

Interpretation of blood pressure values

Hypertension is defined as an average systolic or diastolic BPabove the 95th percentile. Any child with a BP exceeding the90th percentile requires scrutiny.

Patients with severe hypertension and target-organ damagerequire immediate attention. For other patients, severalmeasurements of BP should be made at weekly intervals todetermine if the elevation is sustained.

The average of multiple measurements should be plotted onan appropriate percentile chart. If the average measurement isbetween the 90th and 95th percentiles (ie, the patient isprehypertensive) the child’s BP should be monitored at 6-monthintervals. If the average BP is greater than the 95th percentile,the child should be evaluated further and therapy considered.

Patients with stage I hypertension should be seen again in 1-2weeks. Those with stage II hypertension should be reevaluatedin 1 week or sooner if the patient is symptomatic.

So-called white-coat hypertension is diagnosed in a patient whohas a BP above the 95th percentile when measured in thephysician’s office but who is normotensive outside the clinicalsetting. Ambulatory monitoring of BP usually is required todiagnose white-coat hypertension3,4.

Investigation : Findings from the patient’s history and physicalexamination should dictate the appropriate choice of tests.

Treatment & Management

Treatment of hypertension should ideally address the causeand correct it. A suggested algorithm is given below.

(i) Nonpharmacologic measures are important in thetreatment of all patients with hypertension, regardless ofits etiology or severity.

(ii) Pharmacologic treatment is indicated in some cases.

(iii) Interventional cardiac catheterization procedures havebeen employed as well.

(iv) Surgery may be required for children with severe renalvascular hypertension, renal segmental hypoplasia,coarctation of the aorta, Wilms tumor, orpheochromocytoma4.

Nonpharmacologic Therapy

In children with mild or moderate hypertension,nonpharmacologic therapy may suffice to lower bloodpressure (BP) to within normal limits. This approach avoidsthe need for drugs that have adverse effects and that require a

Recommended Dimensions for Blood Pressure Cuff Bladders

Age Range Width Length maximum Arm(cm) (cm) Circumference (cm)*

Newborn 4 8 10Infant 6 12 15Child 9 18 22Small adult 10 24 26Adult 13 30 34Large adult 16 38 44Thigh 20 42 52

Table 4. Recommended cuff sizes for various ages.

The child should be relaxed and in a comfortable, preferablysitting, position with the feet on the floor and the back supported.The patient’s right arm should be resting on a supportive surfaceat the level of the heart. Infants can be examined while supine.The cuff should be inflated at a pressure approximately 20 mmgreater than that at which the radial pulse disappears, thenallowed to deflate at a rate of 2-3 mm Hg/s.

The first Korotkoff sound (ie, appearance of a clear tappingsound) defines the systolic pressure, whereas the fifth Korotkoffsound (ie, disappearance of all sounds) defines the diastolicpressure. The fourth (low-pitched, muffled) sound and the fifthsound frequently occur simultaneously, or the fifth sound maynot occur at all. Diastolic BP must be recorded. When Korotkoffsounds can be heard down to 0 mm Hg, the BP measurementshould be repeated with less pressure applied to the head ofthe stethoscope than was applied before.

Systolic BP in the lower extremities must be measured whenelevated systolic BP in the upper extremities is first noted,regardless of whether the amplitude of the arterial pulse seemslower in the legs than in the arms. Increased systolic pressurein the arm suggests coarctation of the aorta. If found, systolicpressure must also be measured in the left arm and leg. Withthe patient in the supine position, place a cuff on the calf. Thecuff should be wide enough to cover at least two thirds of thedistance from knee to ankle.

Doppler sonography can be used to detect onset of blood flow,which reflects systolic BP, in the posterior tibial or dorsalis pedisartery. The value should be compared with a similarly obtainedDoppler systolic BP in the arm, again with the patient supine6,7,8.


Table 5- Recommended laboratory investigations


Table 6. Management algorithm.

degree of compliance difficult to achieve in children4,8,9. Theseinclude-

(i) Weight reduction(ii) Aerobic and isotonic exercises(iii) Potassium supplementation(iv) A low-fat diet

Pharmacologic Therapy

Indications for pharmacologic treatment include symptomatichypertension, secondary hypertension, hypertensive target-organ damage, diabetes, and hypertension that persists despitenonpharmacologic measures.

In children with uncomplicated primary hypertension, BP isconsidered controlled when it is below the 95th percentile. Inchildren with chronic renal disease, diabetes, or hypertensivetarget-organ damage, the goal should be a BP below the 90thpercentile. If BP is not controlled, a drug from another classshould be added. If control is not achieved with 2 drugs,reconsider the possibility of secondary hypertension beforeadding a third drug.

Many antihypertensive drugs are available for the treatment ofchronic hypertension. The choice of drug is usually based onthe mode of action and the potential for adverse effects. Froma pharmacologic point of view, antihypertensive drugs may beclassified in the following categories4,10:

(i) Diuretics, which block sodium reabsorption at variouslevels of the renal tubules

(ii) Adrenergic blockers, which act by competitively inhibitingthe catecholamines

(iii) Direct vasodilators, which act by means of variousmechanisms

(iv) Angiotensin-converting enzyme (ACE) inhibitors, whichblock the conversion of angiotensin I to angiotensin II

(v) Angiotensin II receptor blockers (ARBs), which interferewith the binding of angiotensin II to angiotensin I receptors

(vi) Calcium-channel blockers, which block the entry of calciuminto the cells, producing vasodilation

AMC = Apparent mineralocorticoid excess; GRA = Glucocorticoid remedial aldosteronism; VMA = Vanillylmandelic acid.


Table 7. Suggested monitoring and therapy recommendations

Management of Hypertensive Crisis

Hypertensive crises occur as a result of an acute illness (eg,postinfectious glomerulonephritis or acute renal failure),excessive ingestion of drugs or psychogenic substances, orexacerbated moderate hypertension.

The clinical manifestations may be those of cerebral edema,seizures, heart failure, pulmonary edema, or renal failure.

Accurate assessment of BP in every patient presenting with aseizure is essential, particularly when no seizure disorder hasbeen established in that patient.

Anticonvulsant drugs are usually ineffective in treatment of aseizure due to a hypertensive crisis. However, seizures due tosevere hypertension must be treated with a fast-actingantihypertensive drug. Patients must be supervised closely to


Table 8. Antihypertensive for long term use

avoid an excessively rapid decrease in BP, which may result inunderperfusion of vital organs. The difference between theobserved and the desired(95th centile) is estimated, 25%reduction is achieved with 4 hours, another 25% in next 24hours and the rest in next 48 hours5.

Monitoring

Closely monitor patients with hypertension, particularly duringthe initial phase of therapy. A chemistry panel should be checkedafter therapy with an ACE inhibitor or an ARB is started orincreased. The frequency of visits is dictated by various factors,including the following3:

(i) Degree of BP control

(ii) Extent of understanding of the disease and its treatment

on the part of both the parents or caregivers and the patient

(iii) Adherence to nonpharmacologic and pharmacologictreatments

(iv) Ability to monitor BP properly at home

(v) Likelihood of drug adverse effects

(vi) Need to monitor for complications of hypertension

(vii) Need to monitor for weight loss

After surgical or catheter treatment of coarctation of the aorta,patients must be monitored yearly with accurate measurementof systolic and diastolic pressures in the right arm. For thesemeasurements, the patient should be properly positioned.Systolic pressures in both the right arm and leg should beobtained with the patient supine. Remember that systolic


pressure in the lower leg should exceed that in the arm.

Key Points

1. Considerable advances have been made in detection,evaluation, and management of high blood pressure, orhypertension, in children and adolescents.

2. Because of the development of a large database onnormative blood pressure (BP) level throughout childhood,identification of children who have abnormally elevatedBP has become possible.

3. Primary or essential hypertension is detectable in theyoung and occurs commonly.

4. The long-term health risks for hypertensive children andadolescents can be substantial if not detected andmanaged in time.

5. It is important that interventional measures be taken toreduce these risks and optimize health outcomes.

Reference :1. National High Blood Pressure Education Program Working Group

on Hypertension Control in Children and Adolescents. Update onthe 1987 Task Force Report on High Blood Pressure in Childrenand Adolescents:A working group report from the National High

Blood Pressure Education Program.Pediatrics 1996;98:649–58.2. Chobanian AV, Bakris GL, Black HR,Cushman WC, Green LA,

Izzo JL, Jr., et al. The Seventh Report of the Joint NationalCommittee on Prevention, Detection,Evaluation, and Treatmentof High Blood Pressure: The JNC 7 report. JAMA 2003;289:2560–72.

3. Update on the Task Force Report (1987) on High Blood Pressurein Children and Adolescents. Pediatrics. 1996;98:649–58

4. The fourth report on Diagnosis, Evaluation, and Treatment of HighBlood Pressure in Children and Adolescent. US department ofhealth and human services.National Institute of Health .May 2005

5. Bagga A, Jain R,Vijaykumar M, KanitkarM,Ali U.Evaluation andmanagement of hypertension.Indian Pediatrics 2007;103-120

6. Butani L, Morgenstern BZ. Are pitfalls of oscillometric bloodpressure measurements preventable in children? Pediatr Nephrol2003;18:313–8.

7. Kaufmann MA, Pargger H, Drop LJ. Oscillometric blood pressuremeasurements by different devices are not interchangeable.Anesth Analg 1996;82:377–81.

8. Park MK, Menard SW, Yuan C. Comparisonof auscultatory andoscillometric blood pressures. Arch Pediatr Adolesc Med2001;155:50–3.

9. Simons-Morton DG, Obarzanek E. Diet and blood pressure inchildren and adolescents.Pediatr Nephrol 1997;11:244–9.

10. Wells TG. Trials of antihypertensive therapies in children. BloodPress Monit1999;4:189–92.


1. Trisomy 13 (Patau Syndrome)

2. (a) Midline defect with cleft lip and palate(b) Clenched hand with overlaping fingers(c) Post axial polydactyly(d) Equinovarus deformity(e) Punched out aplasia cutis scalp lesion

3. Incidence 1 : 2000 – 1 : 5000

Answer to Photo Quiz

Acute Rheumatic Fever : An Update

Atul Kumar GuptaProf and HOD Department of Pediatric Medicine, Ramakrishna Mission Seva Pratishthan, Kolkata

Correspondance : Atul Kumar Gupta, Prof and HOD Department ofPediatric Medicine, Ramakrishna Mission Seva Pratishthan, Kolkata .Email : [email protected]

Introduction

Acute Rheumatic Fever (RF) despite higher strides made inadult acquired heart diseases stays a major health problem inchildren and adolescents. Diagnostic criteria even with Jones’criteria fail to diagnose all cases and thus prophylaxis is notproperly given. RF and Rheumatic Heart Disease (RHD) remainsignificant causes of cardiovascular diseases in the world today.Despite a documented decrease in the incidence of acute RFand a similar documented decrease in the prevalence of RHDin industrialized countries during the past five decades, thesenon-suppurative cardiovascular sequel of group A streptococcalpharyngitis remain medical and public health problems in bothindustrialized and industrializing countries even at the beginningof the 21st century. The most devastating effects are on childrenand young adults in their most productive years.Echocardiography which can become a valuable tool todiagnose RF early still does not find its place in diagnosticcriteria. This necessitates a proper review of where do we stand.Our resources and social characteristics necessitate thisproblem to be viewed differently from what the developedcountries look at it.

Incidence:

Considering paucity of proper data collection and social diversityall approximates fail to give a clear picture in our country. Thedata of post mortem findings by Rogers1 at Medical College,Bengal in the year 1910 failed to find any case with RheumaticHeart Disease (RHD) and it was Kutumbaiah2 in 1935 whoreported it to account for 40% of heart cases in males and 52%in females. Unfortunately, diagnosis of past RF is not possibleunless patients give history of arthritis, arthralgia and choreaor have established RHD. Hence, retrospective diagnosis oridentification of past RF is missed or not available in almost 50per cent patients with RHD.

The incidence of rheumatic fever has been on a decline indeveloped countries (less than 5/100,000/yr). It still remains amajor health problem in developing countries.The prevalenceof RHD in school children was given in WHO chronicle in theyear 1980 as in various parts of the world is shown in Table 13

Table 1: WHO chronicle in the year 1980

Area Prevalence Per 1000

United States 0.6

Japan 0.7

India 6.0-11.0

Asia (other) 0.4-21.0

Africa 0.3-15.0

South America 1.0-17.0

The epidemiology of acute rheumatic fever (RF) is linked withthat of group-A beta hemolytic streptococcal pharyngitis provedby the fact that both have a maximum incidence in the agegroup of 5-15 years, share a common seasonal incidence,follow in sequence, antibody titers are high and primary orsecondary prophylaxis prevents the disease process. RF israre before the age of 5 years in the West. In India, the averageage at presentation has been reported by Padmavati4 to bebetween 10 and 14 years. However, the early development(under 5 years) of established rheumatic heart disease andrapid progression to disabling cardiac involvement poses amajor problem in India and has been termed as “Juvenile MitralStenosis”4.

Improved nutrition of children and diminished exposure to theinfecting organism in Western countries has led to steadydecline in its incidence. RF is considered as a social diseasei.e. alteration in socio-economic state of a community willadversely or favorably affect the incidence of this disease.Decline in RF is due to improvement in social factors,availability of Penicillin prophylaxis and also diminishedstreptococcal v irulence and presence of fewer

Review


rheumatogenic serotypes. Mucoid forming colonies have beenassociated with rheumatogenicity.

Aetiopathogenesis:

Though group-A beta haemolytic streptococci (GAS) is theknown etiological agent, the exact pathogenic mechanisms areunknown. Only certain serotypes (e.g. M typesl,3,5,6,14,18,19,24,27,29) are known to cause rheumatic feverwith a higher frequency than others and have been referred toas “rheumatogenic” strains. Evidence of an antecedent GroupA streptococcal (GAS) infection is required for the confirmationof the initial diagnosis of acute rheumatic fever (RF). At thetime of diagnosis of acute RF, only about 11% of patients havethroat cultures positive for GAS. The paucity of positive culturesis due, in part to elimination of the organism by host defensemechanisms during the latent period between the onset ofinfection and the subsequent development of RF. Several rapidGAS antigen detection tests are available. Most of these testshave a high degree of specificity but a low sensitivity in a clinicalsetting. A negative test does not rule out the presence of groupA streptococcal infection in the throat. A positive throat cultureor rapid antigen test does not distinguish between a recentinfection that can be associated with acute RF and chroniccarrier of organism in throat. Because the presence of GAS inthe throat may not reflect active infection, elevated or risingASO titers provide more reliable evidence of a recentstreptococcal infection than a positive culture or a positive rapidantigen test. The most commonly used antibody tests are theantistreptolysin O (ASO) and antideoxyribonuclease B (Anti-DNAase B). The ASO test is usually done first and if notelevated, the anti-DNAase B test is done. Elevated titres forboth tests may persist for weeks or months. ASO titres riseand fall rapidly than anti-DNAase B. Other antibody tests whichare occasionally done are anti hyaluronidase H (AH) andantistreptozyme (ASTZ). It must be stressed that elevated ASOtitre (>250 Todd units (adults) and >333 Todd units (Children)are considered to be significant for diagnosis. ASO level mayrise and fall irrespective of the course of rheumatic fever.

The association between group-A beta haemolytic streptococcalupper respiratory tract infection and the subsequentdevelopment of acute rheumatic fever is well established. Theexact pathogenic mechanisms are unknown largely due to lackof an animal model, though two basic mechanisms areimplicated:

1. Cytotoxic Theory: A toxic effect of the extra-cellular toxinof group-A beta hemolytic streptococci on target organslike myocardium, valves, synovium and brain.

2. Immunologic Theory: An abnormal immune response ofthe host to the streptococcal antigens. The group-AStreptococcus is a complex micro-organism producing alarge number of somatic and extra-cellular antigens.Certain human tissues bear antigenic similarities to theseand hence antibodies produced against the streptococcalantigens cross-react with the tissue antigens to producean autoimmune response. The levels of these antibodiesdecline when the target tissue is experimentally removedfrom the body. The data supporting the cross reactivitytheory of rheumatic fever includes the following:

(i) Group-specific polysaccharide of the GAS wall isantigenically similar to the glycoprotein found in humanand bovine cardiac valves

(ii) The somatic antigens of the streptococcal cell walland cell membrane are similar to the humanmyocardial sarcolemma.

(iii) The M protein of GAS cross-reacts with human tissuesas it shares certain common amino acid sequences.This M protein is the virulence factor that confers onthe organisms the ability to resist phagocytosis andalso the type specific immunity that is conferredagainst the specific M protein type21. In Sydenhamchorea, antibodies directed against antigens found inGAS cell membrane cross-react with tissues in thecaudate nucleus of the brain.

Despite the knowledge of the inciting agent, it is not very wellunderstood why only certain individuals are susceptible todevelopment of rheumatic fever subsequent to streptococcalpharyngitis. The absence of acute rheumatic fever in very youngchildren suggests that repeated exposures of the host to group-A Streptococcus is essential for precipitating the illness. Theimmunological system of the host including both cell-mediatedand humoral, is an important factor for the susceptibility to acuterheumatic fever, but the exact mechanisms are unknown. Also,there are certain genetic influences which play a role sinceonly about 3% of individuals develop acute rheumatic feverfollowing acute streptococcal pharyngitis. There is also a higherconcordance amongst monozygotic twins for the developmentof acute rheumatic fever. Recently, a B-lymphocyte alloantigenhas been implicated in the determination of susceptibility toacute rheumatic fever in 70-90% of rheumatic patients. CertainHLA types viz. HLA-DR 1, 2, 3 and 4 haplotypes have beenimplicated in certain ethnic groups.

The hal lmark of RF is an exudat ive and prol i ferat ive


inflammatory reaction involving the collagen and connectivetissue primarily of the heart, joints, brain and skin. Apart fromthe presence of a generalized vasculitis, the basic change is inthe form of fibrinoid degeneration of the collagen characterizedby the presence of Aschoff cells, which are modifiedfibrohistiocytic cells. Aschoff nodules are pathognomic ofrheumatic carditis but are documented only in 30-40% ofbiopsies from patients with rheumatic fever. Valvulitis is themain lesion accounting for the principal clinical manifestations.Valvulitis is characterized by edema, cellular infiltration of thevalves and the chordae tendinae causing verrucae formationand hyaline degeneration with subsequent regurgitant valves.There is eventual fibrosis and calcification leading to stenoticvalves.

Research to elucidate the pathogenesis has been directedalmost exclusively toward myocarditis and myosin for the lastmore than 60 years without any breakthrough. An alternativeapproach with endothelium as the target of rheumatic damageas well as guidelines for further research have been suggestedin the hope that these may help in identifying the GAS antigen(s) responsible for RF.

Studies strongly suggest that RF does not cause myocarditis.Absence of myocarditis has been documented by (i) absenceof increase in markers of myocardial damage - MB fraction ofcreatinine kinase (CK-MB), troponin I & T and myoglobin, (ii)normal left ventricular systolic function and myocardialcontractility by echocardiographic studies, (iii) radionuclidestudies using technetium pyrophosphate scanning and indiumIII labelled anticardiac myocin Fab (FAB) do not indicatepresence of myocardial damage, (iv) myocardial biopsy studieshave not been able to identify the presence of myocarditis, (v)normalization of heart size and disappearance of congestivefailure following surgical mitral and/or aortic valve replacementin patients deteriorating in spite of aggressive medicalmanagement, (vi) histopathology of the left ventricularmyocardium showing absence of myocardial or inter-myocardialconnective tissue damage and (vii) immunopathology of Aschoffnodule (AN), the diagnostic marker of rheumatic pathology,being derived from mesenchymal cells, complete absence ofcells of myocardial origin in AN and absence of actin, myosinand desmin (of myocardial origin) in the AN indicating that ANis not of myocardial origin. Hence, congestive cardiac failure inacute RF is due to an acute volume overload from mitral and/or aortic regurgitation but not due to myocarditis per se.

Clinical Features:

The American Heart Association (AHA) recommends the

revised Jones criteria as a guide for diagnosis of acuterheumatic fever which has been approved by WHO study groupfor the diagnosis of the initial attack of acute rheumaticfever(Table 2).

Major criteria

Carditis:

The carditis of acute rheumatic fever is a pancarditis withinvolvement of pericardium, epicardium, myocardium andendocardium. Carditis occurs in 50-60% of the cases ofrheumatic fever. Valvular insufficiency is the commonest defect.It most often involves the mitral valve. The Carrey-Coombsmurmur of acute RF is a sign of active mitral valvulitis. It is asoft, high pitched early diastolic murmur, varying from day today. Isolated aortic valvular involvement is rare, while tricuspidand pulmonary valvular involvement is unusual. Pericarditis,pericardial effusion, arrhythmias (1st and 3rd degree heartblocks) are other features of rheumatic carditis. Pericarditis ismanifested by characteristic chest pain, pericardial rub, typicalECG changes or pericardial fluid on echocardiography.Myocarditis manifests itself as disproportionate tachycardia,soft heart sounds, cardiomegaly or congestive cardiac failure.Congestive cardiac failure is the usual complication. Onlymyocarditis or and pericarditis without endocarditis do not favourdiagnosis of RF as also isolated aortic or right sidedinvolvement. RHD is the only residual sequel of acute rheumaticfever.

Polyarthritis:

It occurs in almost 75% of the cases. It presents as red, swollen,warm and tender joints and is typically migratory in nature. Eachjoint is involved for not more than a week. Elbows, knees, anklesand wrist joints are most commonly involved, while fingers,toes or spine are rare sites of affection. Resolution of jointsymptoms usually occurs over 6 weeks. There ispolymorphonuclear leukocytosis in the synovial effusion. Thesechanges do not produce chronic joint disease or deformity. Jointpain may precede and appear to be more disproportionate thanother findings, respond dramatically to salicylates and unusuallymonoarticular except for if aborted by early use of salicylates,usually corresponds well to antibody rise and severity isinversely proportional to severity of cardiac involvement.

Chorea:

It is a late onset manifestation, occurring as late as 3 monthsfollowing throat infection. Emotional lability, incoordination, poorschool performance, uncontrollable movements and facialgrimacing often exacerbated by stress and disappearing


Table 2 : 2002–2003 WHO criteria for the diagnosis of rheumatic fever and rheumatic heart disease (based on the revised Jones criteria5)

Diagnostic categories Criteria

Primary episode of RF.a Two major *or one major and two minor**manifestations plus evidence of a preceding group Astreptococcal infection***.

Recurrent attack of RF in Two major or one major and two minor manifestations plusa patient without established rheumatic heart disease.b evidence of a`preceding group A streptococcal infection.

Recurrent attack of RF in a patient with established Two minor manifestations plus evidence of a preceding group Arheumatic heart disease streptococcal infection.c

Rheumatic chorea. Other major manifestations or evidence of group AInsidious onset rheumatic carditis.b streptococcal infection not required.

Chronic valve lesions of RHD (patients presenting for the Do not require any other criteria to be diagnosed as havingfirst time with pure mitral stenosis or mixed mitral valve rheumatic heart disease.disease and/or aortic valve disease).d

* Major manifestations — carditis— polyarthritis— chorea— erythema marginatum— subcutaneous nodules

** Minor manifestations — clinical: fever, polyarthralgia— laboratory: elevated acute phase reactants (erythrocytesedimentation rate or leukocyte count)

*** Supporting evidence of a preceding — electrocardiogram: prolonged P-R intervalstreptococcal infection within the last 45 days — elevated or rising antistreptolysin-O or other streptococcal

antibody, or— a positive throat culture, or— rapid antigen test for group A streptococci, or— recent scarlet fever.

a Patients may present with polyarthritis (or with only polyarthralgia or monoarthritis) and with several (3 or more) other minor manifestations,together with evidence of recent group A streptococcal infection. Some of these cases may later turnout to be rheumatic fever. It is prudentto consider them as cases of “probable rheumatic fever” (once other diagnoses are excluded) and advise regular secondary prophylaxis.Such patients require close follow up and regular examination of the heart.This cautious approach is particularly suitable for patients in vulnerable age groups in high incidence settings.

b Infective endocarditis should be excluded.c Some patients with recurrent attacks may not fulfil these criteria.d Congenital heart disease should be excluded.

in sleep are seen. At times, chorea may be the only symptomof acute rheumatic fever. It is seen in almost 10-15% of thepatients, and lasts for weeks to months and rarely recurs. It ismore common in boys than in girls. Hand shaking(irregularcontraction of hand-milkmaid’s grip), outstretching upperlimbs(spooning and pronation), and examination of handwritinghelp elicit features of chorea.

Erythema marginatum:

Though unique, it is a very infrequent clinical finding seen in<3% of the patients. It presents as an evanescent,erythematous, non-tender, non-pruritic macular rash over thetrunk. The macules have a pale centre, serpiginous borders

and accentuate with warming. Patients with erythemamarginatum usually have chronic carditis.

Subcutaneous nodules:

These are present as non-tender, firm pea-sized nodules seenon the extensor surfaces of the joints like knees, elbows andspine, and seen in < 1% of the patients. There is usually chroniccarditis in these patients.

Minor criteria

Fever:

It ranges from 101-102 degrees F.


Arthralgia:

It is diagnosed only in the absence of underlying arthritis.

Elevated acute phase reactants (ESR,CRP)

Evidence of group A streptococcal infections:

It requires evidence of preceding streptococcal infection asconfirmed by a positive throat culture, a history of scarlet fever,or elevated streptococcal antibodies such as antistreptolysin-O (ASO), antideoxyribonuclease-B (anti-DNAase-B) orantihyaluronidase (AH)

ECG changes:

Prolonged PR interval in ECG

The components of major, minor and essential criteria for thediagnosis remain more or less as before in AHA guidelines.The updated criteria emphasize the value of indolent carditisand chorea to be accepted as evidence of RF and haveremoved previous RF or presence of RHD as a minormanifestation to simplify the diagnosis of first attack of RF. Inthe presence of previous history of RF/RHD one major or morethan one minor criterion is acceptable for the diagnosis ofrecurrent RF. Additionally echocardiogram based diagnosis ofcarditis has been questioned in the absence of clinical findingsto indicate cardiac involvement. The clinical manifestations ofRF, except for minor differences in frequency, are the same allover the world. In our country erythema marginatum is notrecognized possibly because of the darker skin complexion.

It needs to be emphasized that the diagnostic criteria areguidelines that help in the identification of RF. However,physicians have a right to make a diagnosis of RF on the basisof clinical judgment even if the updated criteria are not satisfied.This may be due to (i) absence of history suggestive of RF inalmost 50 per cent patients of RHD, and (ii) identification ofsubclinical carditis by echocardiographic studies, indicatinginadequacy of clinical diagnosis.

Pitfalls in Jones Criteria

The precise diagnosis of carditis in RF is eluding the clinicianbecause of many pitfalls in Jones’ criteria.

1. It is difficult to diagnose RF when carditis is the onlymanifestation of the disease particularly in a recurrence.

2. When patient has sub clinical carditis the clinicians failto detect clinically.

3. Clinically apparent carditis is present but supportive minorcriteria are not fulfilled.

4. When previous cardiac status is unknown it is not possibleto know in a new case whether the findings are due to

acute carditis or it is recrudescence or it is establishedold case of RHD.

Most prevalence figures indicate that the prevalence of RF insurveys is about one tenth or even less than that of RHD(0.1/1000 vs 1/1000). The inference could be that thediagnosis of RF is being missed more often than desirable oracceptable. Less than half of all RHD patients give history ofpast RF. Unfortunately, diagnosis of past RF is not possibleunless patients give history of arthritis, arthralgia, chorea orhave established RHD. Hence, retrospective diagnosis oridentification of past RF is missed or not available in almost50 per cent patients with RHD.

The physician’s clinical recognition of RF has very importantimplications for the patient’s management and prognosis.RHD places heavy economic burden on the healthcaresystem in low and middle income families in developingcountries, because of the costs of medical, surgical and non-surgical treatment and also because it is a disease of youngadults, who are the most economically active group of anypopulation.

Management is complex and involves different levels of care.Hence, early and precise diagnosis of carditis in RF, thoughdifficult is very important to prevent the serious consequences,morbidity and mortality in the young. But, unfortunately RFdespite its distinctive clinical features, is a syndrome withoutpathognomonic symptoms, signs or laboratory tests. Themodern new technology like ECHO can fill in that grey areafor the diagnosis of carditis. Presence of subclinical carditisdiagnosed using echocardiography in surveys of 5-14 yr oldchildren when combined with the findings of the children withMS suggests that RF is being missed more often thandesirable. Some patients have only one clinical manifestation- fever with valvulitis during the episode of RF and thediagnosis of RF is being missed since the carditis isasymptomatic, mild and not associated with any murmurs(subclinical). The findings suggest that the diagnosis of RFbased on the 1992 guidelines of AHA are necessary butinsufficient in identifying RF in a fairly large number ofpatients5.

Although the American Heart Association (AHA) has notaccepted echocardiographic and Doppler(E&D) studies forthe identification of carditis, many clinicians feel that E&Dstudies are necessary for the care of patients with acute RFsince subclinical carditis(SC) cannot be disregarded6. Followup data on patients of acute RF with SC are unsatisfactory.Available follow up E&D studies indicate that the SC canworsen to become clinically obvious RHD, improve or remainunchanged.


Acute RF: duration of disease

A combination of some clinical manifestations and laboratorytests put together by Jones, revised and modified from time totime by the AHA, identify the syndrome of RF. Elevated ESRand CRP are nonspecific and identify the presence of an activeinflammatory disease. Elevated anti-streptococcal antibodiesindicate streptococcal infection. Thus there is no specificinvestigation, which is diagnostic for RF. Of the clinicalmanifestations arthritis, erythema marginatum and carditissuggest acute and active RF. Subcutaneous nodules andchorea are late manifestations and indicate past RF not activeRF.

The inference that RF lasts 10 to 12 wk in about 80 per centpatients was dependent on the elevated ESR and CRP. As oftoday we do not know the duration of active rheumatic “process”per se. Arthritis suggests active RF, however, if the rheumaticprocess is active why should arthritis subside without treatment?The central nervous system (CNS) damage occurs with acuteRF. At the time patients present with chorea the ESR and CRPmay be normal indicating absence of an active disease process.Is the rheumatic inflammation active or inactive at the time apatient presents as chorea? Hence high or normal ESR andCRP do not identify active or inactive rheumatic process. Whyshould chorea occur three to six months after the CNS damagethat occurs during acute RF? What is the duration of activerheumatic inflammation in RF? The damage resulting fromactive rheumatic process has to be separated from the residualeffect of the damage caused by the rheumatic disease. Theduration of the disease in acute glomerulonephritis, the othernon-suppurative manifestation of GAS infection, is less thanseven to ten days. Majority of patients recover within that time.Urinalysis continues to show microscopic haematuria for severalmonths in spite of clinical recovery. Unfortunately there are noinvestigations, which can identify active rheumatic diseaseprocess itself.

Laboratory Diagnosis of RF:

1. The diagnosis of RF is dependent on some laboratory testsincluded as minor criteria and consist of the following:

(i) Acute phase reactants (leukocytosis, elevatedsedimentation rate and presence of C reactive protein(CRP). Elevated erythrocyte sedimentation rate (ESR) isa nonspecific evidence for an active disease. It is elevatedin acute RF but can be normal if the patient has congestivefailure and can be high in the presence of anemia. NormalCRP is against the diagnosis of active RF.

(ii) Prolonged PR interval in the electrocardiogram can beseen in the electrocardiograms in patients with active RF.Prolonged PR interval is a non specific finding and doesnot indicate the presence of myocarditis.

(2) The diagnosis requires presence of essential criteria in theform of evidence for recent GAS infection and consists of:

(i) elevated antistreptococcal antibodies, Presence of GASin throat culture with low values of ASO suggests a carrierstate. As such a positive throat culture for GAS cannot betaken as recent infection /unless the antibody titres areelevated.

ASO titer is raised in 80% of the patients. Some importantpractical points about ASO test need to be noted. ASOtitres vary with age, geographical area and other feversinfluencing the frequency of streptococcal infection. Araised ASO titre merely indicates a recent streptococcalinfection. The ASO titres are raised to their maximum 2 -3weeks after the streptococcal infection and rapidly fall inthe next few months upto six months. Acute polyarthritisof rheumatic fever occurs at or close to the peak of theantibody response. Therefore, arthritis associated with anormal ASO titre is not in favour of the diagnosis ofrheumatic fever. Anti-DNAase B and AH levels areimportant indicators of recent streptococcal infection. A highlevel or a rising level is significant. A fair amount ofconfusion exists about the exact level of antibodies to beconsidered as high. Generally antistreptolysin O (ASO) isthe commonest antibody measured. It appears in about 7to 10 days and peaks in 2 to 3 wk. It is considered high ifthe figure is more than the baseline value present in thecommunity. In endemic areas the baseline ASO could be250 ( in children 330) Todd units or more whereas in non-endemic areas it could be as low as 50 Todd units.Increasing titres indicate recent GAS infection. Using twoantibody titres, that is, ASO combined withdeoxyribonuclease B titres increases the specificity ofdiagnosis to 90 per cent7.

(ii) positive throat culture for GAS, and

(iii) evidence for recent scarlet fever- rare in India.

Elevated antistreptococcal antibodies identify recentstreptococcal infection.

Presence of active vs. inactive RF in recurrences: Twoinvestigations have been tried to assess the presence orabsence of active RF in patients with recurrences besides ESR,CRP and evidence for recent GAS infection.


(i) Induced subcutaneous nodules (SCN): Massell8 et al triedinducing SCN by injecting 5 dl autologous blood drawnfrom a vein and injecting over the olecranon process ofone elbow and saline in the other elbow. Frictional pressurewas applied to the injected sites. Appearance of a SCN in5 to 10 days was accepted as indicating active RF. Vasanmodified this test and used concentrated leukocyteinjection instead of whole blood with 86 per cent sensitivityand 94 per cent specifically to identify active RF. The testoffers the advantage of being cheap and easily availableeverywhere. The potential utility of the test lies in identifyingactive RF. However, additional validation studies areperhaps needed.

(ii) Myocardial biopsy: A study9 of myocardial histology toidentify active vs. inactive RF was utilized in patients ofRF. Myocardial biopsies were performed in 89 patients ofactive RF and chronic RHD to identify active carditis.Myocardial biopsies failed to improve on clinically assessedpresence of active RF. Myocardial biopsy was felt to beinsensitive for identifying presence of active carditis.

Management:

1. Treatment of group-A streptococcal infection

All patients with acute rheumatic fever should be treated forstreptococcal infection at the time of diagnosis irrespective ofisolation of the organism. Oral penicillin for 10 days or a singleintramuscular injection of benzathine penicillin in a dose of12,00,000 (600,000 U, if weight less than 27 kgs) units can begiven. Patients allergic to penicillin should be given erythromycinfor 10 days.

2. Treatment of clinical manifestations

Aspirin or steroids do not cure RF. These suppress theinflammatory response which lasts for about 12 wk in morethan 80 per cent patients. In the absence of congestive cardiacfailure, salicylates are beneficial, however corticosteroids arerequired if cardiac failure or severe carditis is present.Corticosteroids do not alter the subsequent development ofrheumatic heart disease. Both agents will suppress acute phasereactants during use but there is no evidence that either willshorten the period of rheumatic activity or limit valve damage.When required for symptoms, the doses should be reducedgradually as soon as the symptoms permit. That subsequentdevelopment of RHD does not depend upon whether aspirin,steroids or ACTH was used during the attack of acute RF wasproved by the UK US cooperative study (1965)10. Hence ashas been emphasized by several authorities, to prevent RHD

in a patient who has had acute RF, the emphasis should be onsecondary prophylaxis. According to Braunwald11, the initialdose of acetyl salicylic acid should be continued until asatisfactory clinical response is obtained i.e. until there iscomplete relief of symptoms and signs of arthritis andtemperature have returned to normal range. Thereafter dosesmay be reduced to 2/3 of the initial doses and may bemaintained until all laboratory manifestations of inflammatorydisease has returned to normal. For the remainder of the courseof therapy, the dose may be reduced to half the initial dailydose. Should clinical and laboratory evidence of relapse occur,it is advisable to go back to higher doses.

A) Arthritis

With only arthritis initial treatment should be to reduce painwith some non NSAID drugs till diagnosis is arrived at otherwiseit will mask the manifestations as well as diagnosis. Once RFis diagnosed with only arthritis or carditis without cardiomegalyor Congestive cardiac failure - rest and salicylates are given ina dose of 100mgm/kg to attain a blood level of 20mgm/dl (notdone routinely unless toxicity appears) till clinical and laboratoryparameters like ESR and C-RP fall(usually 3-5 days). Theduration of treatment in rheumatic fever without carditis variesfrom patient to patient and is usually up to few weeks( usually4 wks) at 75mgm/kg. Patients without carditis can have weeklyfollow up of ESR and CRP. If they normalize, the course canbe reduced to a shorter period. Salicylates can be repeated atsimilar dose in case of relapse. A lack of response to full doseas aspirin, within 5 days warrants revaluation of diagnosis ofRF.

B) Carditis

Prednisolone in a dose of 2 mg/kg/day is given 2-3 wks followedby reducing the dose 5mgm/24 hr every 2-3 days.. Salicylatesshould be added during the last 4 weeks of corticosteroidswhen the dose of corticosteroid is being tapered, and thencontinued for another 3-4 weeks in order to prevent rheumaticrebound. The duration of salicylate therapy will depend uponthe patient’s response. There is no evidence that non-steroidalanti-inflammatory drugs are more effective than steroids. Bedrest is indicated during an acute attack of rheumatic fever. Theperiod of rest varies, depending on severity of the carditis.Guidelines for bed rest are given in Table 3. Aspirin is preferredover steroids as long as the carditis is mild and the patient isnot in congestive failure. However, with severe carditis andcongestive failure steroid is the drug of choice because of themore potent suppressive effect. Rebounds on termination oftherapy are best left untreated unless they are severe.


C) Chorea

It has a self limiting course, hence parents need reassurance.The children could be treated with sedatives likephenobarbitone 16-32mg thrice daily. Chlorpromazine,diazepam, diphenhydramine or promethazine can be used as

sedatives. Haloperidol .03-.1 mgm/kg 24 hrs twice daily hasbeen used effectively. Although aspirin and steroids are notsupposed to have a place in the treatment of chorea, somepatients have shown dramatic response to steroids, if they donot show adequate response to sedatives. Since, long termfollow up of chorea patients have identified subclinical carditisin 20 -30 % patients, penicillin prophylaxis is essential andshould be continued on a long term basis

D) Subcutaneous nodules and Erythema marginatum:

These do not require any medical therapy.

Non-steroidal anti-inflammatory drugs (NSAIDs) have not beensystematically utilized to establish their usefulness.Immunosuppressive agents like azathioprine and cyclosporineA have also been considered for acute rheumatic fever. Despiteof the concerns of side effects, toxicity and late onset oflymphomas with the use of these immunosuppressive it ispossible to argue that a short course of 6 to 8 wk may result in

Table 3 : Guidelines for bed test

Carditis status Management

No carditis Bed rest for 2 weeks and gradualambulation over 2 weeks even if nosalicylates

Carditis with no cardiac Bed rest for 4 weeks and gradualenlargement ambulation over 4 weeks

Carditis with no cardiac Bed rest for 6 weeks and gradualenlargement ambulation over 6 weeks

Carditis with heart failure Strict bed rest as long as heart failureis present and gradual ambulation over3 months

Table 4 : Prophylaxis of Rheumatic Fever*Primary prophylaxisIntramuscular Benzathine penicillin G 12,00,000 U (600,000 U, if weight less than 27 kgs)

once (evidence Ib)Oral Penicillin V 500mg bid daily for 10 days, 250mg if weight less than

27 kgs (evidence Ib)Amoxicillin 50mg/kg (max1gm) once daily for 10 days (Ib)Erythromycin 250mg qid daily for 10 days(evidence Ib)Others (Clindamycin Dose variesnafcillin, ampicillin,cephalexin)

Secondary prophylaxisIntramuscular Benzathine penicillin G 12,00,000 U every 3-4 wks (3 wks in high risk patients

and where incidence of RF is high) (evidence IA)Oral Penicillin V 250mg bid daily(evidence IB)

Sulfadiazine l gm od (0.5gm od in children) (evidence IB)Erythromycin stearate 250mg bid dailyAzithromycin Varies(evidence IC)

Table 5: Duration of secondary Prophylaxis*

Type Duration after last attack Evidence rating*

RF with carditis and residual heart 10 years or until age 40 years (whicheverdisease (persistent valvular disease) is longer); lifetime prophylaxis may be needed 1C

RF with carditis but no residual heart 10 years or until age 21 years (whichever is longer) 1Cdisease (no valvular disease)

Rheumatic fever without carditis 5 years or until age 21 years (which ever longer) 1C

*Adapted from Gerber MA, Baltimore RS, Eaton CB, et al. Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcalpharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee ofthe Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and theInterdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation. 2009;119(11):1547.


Reference :1a. Rheumatic fever and rheumatic heart disease. Report of a WHO

Study Group. World Health Organization, Geneva, 2001(Technical Report SeriesNo. 923).

1b. Rogers L, Gleanings from the Calcutta post mortem records III-Diseases of the circulatory system. Indian Med Gaz 1910; 45 :84-90

2 Kutumbiah P. Rheumatic Fever and rheumatic heart disease inIndia. Review of 2 5 years of study and progress. Indian J Pediat1958;25:240-5

3 Rheumatic fever and rheumatic heart disease. Report of a WHOstudy group, Technical Report Series, WHO, Geneva 1988;764:7- 4 Padmawati S. Rheumatic fever andrheumatic disease in development countries. Bull WHO1978;56:543

5 Guidelines for the diagnosis of rheumatic fever. Jone criteria.1992 update. Special Writing Group of the Committee onRheumatic fever, Endocarditis and Kawasaki disease of theCouncil on Cardiovascular Disease in the young of the AmericanHeart Association JAMA 1992; 268 : 2069-73.

6 Vijayalakshmi IB Acute Rheumatic Fever: Current Scenario inIndia in medicine Update 2012;22:199-212

7 Kawakita S, Takeuchi T, Inoue J, Onishi T, Uemura Y. Infectionof group A streptococcus and antibody response to extracellularantigens. Jpn Circ J 1981; 45 : 1384-90.

8 Massell BE, Mote JR, Jones TD. The artificial induction ofsubcutaneous nodules in patients with rheumatic fever. J ClinInvest 1937; 16 : 125-8

9 Narula J, Chopra P, Talwar KK, Reddy KS, Vasan RS, Tandon59. R, et al. Does endomyocardial biopsy aid in the diagnosis ofactive rheumatic carditis? Circulation 1993; 88 : 2198-205.

10 UK and US Cooperative Study. The natural history of rheumaticfever and rheumatic heart disease. 10 year report of a cooperativeclinical trial of ACTH, Cortisone and aspirin. Circulation 1965;32:457-76.

11 Braundwald E - Heart Diseases - A Text Book of CardiovascularMedicine 3rd ed, WB Saunders 1998;1776-1796.

12 Krishnaswami S, Joseph G, Chandy ST, Rajendran G,Zacharious TU - Rheumatic fever chemoprophylaxis in Adults.JAPI 1998;46:593-594.

13 Padmavati S. Rheumatic fever and Rheumatic heart disease inIndia at the turn of the century. Indian Heart Journal 2001;53:35-37.

a greater benefit than harm. However, most ethics committeeswill not permit systematic testing of these agents.

Prevention

Prevention of RF can be considered as

1) Preventing the development of ‘risk factors’ like(i)improvement in socio-economic status, (ii) prevention ofovercrowding, (iii) improving nutritional status, (iv)availability of prompt medical care, and (v) public educationregarding the risk of RF from sore throat specially belowthe age of 15 yr.

2) Primary prevention,is very difficult as it has to be given forall cases of sore throat in whom streptococci are isolatedbut since isolation of streptococci is almost impossiblebefore treatment as also availability of penicillin in ourcountry, primary prevention is very difficult and not inpractice.

An interesting piece of data from USA indicate that as muchas 78 % of GAS sore throats may be asymptomatic, tenday oral penicillin treatment was not followed by welleducated families and 48 % of those given oral penicillindeveloped RF. Unless a sore throat is symptomatic, it wouldnot be treated and could still result in RF.

3) Secondary prophylaxis is the cornerstone of prevention ofRF(Table 4)

Benzathine penicillin is painful, may result in fever and very

rarely in anaphylactic reactions. Most physicians are veryreluctant to give penicillin injections. The necessity of penicillinprophylaxis is due to the fact that RF has a tendency forrecurrences in those who have had RF in the past. Each newattack causes further damage to the valve tissue making thedisease worse than before. Secondary prevention can reducethe damage of recurrences but cannot prevent the initialdamage. Further, secondary prevention cannot reduce theburden of RHD in the community. Secondary prevention hasbeen found to help in disappearance of clinical findings of RHD.However, disappearance of murmurs does not indicate thatthe heart disease has disappeared. Recurrence of RF resultsnot only in appearance of murmurs but also the valve damageis worse than before.

Antistreptococcal vaccine13: ICMR is working on RF vaccineusing Indian strains of GAS. ICMR has initiated Jai VigyanMission Mode Project at Chandigarh and Vellore where thedevelopment of RF vaccine is in progress. Its a challengebecause GAS has a strong tendency for mutation and thevaccine may not be effective if the infection is due to anorganism, which has mutated after being incorporated in thevaccine.

The diversion of emphasis on adult cardiac problems havetaken away our attention from RF and RHD. The problem stillstays and causes significant morbidity and mortality and weare still unable to control this menace effecting youth - a valuablesection of our population.


Introduction

The Ductus Arteriosus (DA) acts as main outflow tract of Rightventricle (RV) in utero, bypassing high resistance pulmonaryfields, diverts ventricular output towards descending aorta. APatent Ductus Arteriosus (PDA) in the first 3 days of life is aphysiological shunt in healthy term and preterm newborninfants. In contrast, a DA in preterm infants can have clinicalconsequences depending on degree of left to right shunting.The increase pulmonary blood flow in the setting of prematuritycan lead to pulmonary edema, decrease lung compliance,deterioration of respiratory status ultimately leading to chroniclung disease, A Patent Ductus Arteriosus (PDA) is a majormorbidity seen in premature infants. Incidence is being inverselyrelated to gestational age and birth weight, 15-40% in very lowbirth weight infants (<1500g) whereas in extremely prematurelow birth weight infants (<28weeks; < 1000g) it is as high as50-65%.

The closure of DA following birth is an important event oftransitional circulation. The entire right ventricular output issent to lungs to facilitate its oxygenation. Postnatal ductalclosure occurs in two stages- First stage is functional closure.It occurs at 10-15 hours of life, medial smooth musclecontraction produces increased wall thickness and shorteningand protrusion of intimal cushion and mucoid lakes. Nextanatomical closure – completed by 2-3 weeks of life, resultsfrom infolding of endothelium, proliferation of subintimal layersand small subintimal hemorrhage, ultimately resulting in fibrousband known as ligamentum arteriosum.

The precise mechanism is mediated by a shift in balance ofvasoconstricting (endothelin) and dilating (PGE2) mediators.This is result of increased oxygenation and reduced flowthrough the DA. Premature infants are at increased risk of PDAdue to elevated levels of PGE2, increased PGE2 receptorlevels and reduced intrinsic vascular tone as a result of weak

actin myosin complex formation. Generally the DuctusArteriosus functionally get closed in term infants by 12-24 hrs,whereas the closure may be delayed by 3-5 days in pretermneonates.

Hemodynamics

The presence of PDA has significant effects on myocardialfunctions as well as systemic and pulmonary blood flow. Pretermnewborns adapts, by increasing the left ventricular contractility,and thereby maintaining the effective systemic blood flow evenwhen the left to right shunts equals 50% of the left ventricularoutput. This is mainly accomplished by increase in strokevolume (SV) rather than heart rate.

The premature baby behaves differently because of immaturesympathetic nervous system innervations in LV myocardium,difference in structure of premature myocardium, lesscontractile elements and less serum Ca+ concentration thanterm babies.

Despite the increased left ventricular output, there is significantredistribution of blood flow to major organ systems, with thepresence of ductal steal due to left to right shunt. There is flowacross the ductus all throughout the cardiac cycle. The directionof shunt depends on the difference between systemic andpulmonary pressure. The amount of shunt is later determinedby pulmonary vascular resistance. The result of stealphenomenon may lead to systemic hypoperfusion, decreasedgut perfusion may increase risk of NEC, stealing from neckvessels may lead to cerebral hypoperfusion and which maylead to injury of the immature brain. Increase stealing of bloodfrom neck vessels lead to less stimulation of stretch receptorssituated in carotid sinus at distal part of carotid body, lessstimulation to VMC lead to uninhibited response- tachycardia,increased BP. This reflex is called Sino-aortic reflex.

Diagnosis of PDA (Pic 1,2,3 see on 3rd cover) :

Clinical diagnosis of PDA and its pitfalls :

The clinical features of a PDA are mainly because of the

Management of Patent Ductus Arteriosus in Preterm Baby

Nurul IslamConsultant & Interventional Pediatric Cardiologist, The Mission Hospital, Durgapur

Correspondance : Nurul Islam, Consultant & Interventional PediatricCardiologist, The Mission Hospital, Durgapur. Email :[email protected]

Neonatology


hyperdynamic circulatory effects caused by left to right shunt,resulting in

(a) bounding peripheral pulses

(b) wide pulse pressure (>25 mm of Hg)

(c) hyperactive precordium (visible precordial pulsations inmore than 2 rib spaces)

(d) systolic murmur (usually ejection systolic; rarely pansystolicor continous)

(e) persistant tachycardia

In a ventilated baby-

(a) fluctuating FiO2

(b) increasing pressure requirements

(c) unexplained CO2 retention

(d) metabolic acidosis

(e) recurrent apnea

Features suggest a symptomatic or significant DuctusArteriosus.. The diagnosis of PDA based on clinical featuresalone has mainly two pitfalls i.e. low sensitivity and delay indetection. In studies comparing clinical examination vsechocardiography, there was a delay of 1-4 days in diagnosisof PDA based on clinical findings alone5. More over these signswere insensitive (sensitivity of 30-40%) and had poor predictivevalue (60%).

Role of Echocardiography

Echocardiography is the gold standard, for diagnosis as wellas for assessing severity of PDA. The features suggestive ofpatent ductus arteriosus include

(a) 2-D and color Doppler- short axis view: Presence of PDAis classically described as ‘three-legged stool’appearance.(Pic: 1). In color Doppler, there is continuousflare in the MPA. (Pic: 2)

(b) Short axis view, Pulsed Doppler: Turbulence in mainpulmonary artery (MPA) due to left to right shunt jet flowinginto MPA.

(c) Four chamber view: Dilated LA, LV. Bowing of IAS towardsRA

(d) Long axis view (M-mode): LA/Ao ratio > 1.5:1 (Pic: 3)

(e) Raised left ventricular stroke volume

The echocardiographic markers of hemodynamically significantPDA and amount of Shunt:

Features of Ductus Arteriosus

Echocardiography No Small Moderate Largeparameters PDA PDA PDA PDA

Ductal diameter (mm) 0 <1.5 1.5-3.0 >3.0Ductal velocity (cm/sec) 0 >2 1.5-2.0 >2.0Antegrade diast PA flow 0 >30 30-50 >50(cm/sec)

Quantification of Left To Right Shunt ByEchocardiography:

small moderate large

LA: Ao ratio <1.4:1 1.4:1 -1.6:1 >1.6:1Mitral inflow- E:A <1 1-1.5 >1.5Diastolic flow inDescending Aorta Antegrade flow Upto 30% of >30% of

forward flow forward flow

Limitations of Echocardiography:

Though echocardiography is the gold standard for diagnosisof PDA, but it has its own limitations especially with regard todecisions on treatment.

(a) There is limited data to prove that functionalechocardiography alters the neonatal outcomes.

(b) Lack of universal consensus regarding the best criteria forinitiating treatment of PDA.

(c) Accessibility to echocardiography is difficult

(d) Highly operator dependent

Recommendations on Use of Echocardiography in PDA:

(a) No data to support routine screening in all preterm infants,as it does not seem to change the long term outcomes.

(b) Echocardiography establishes presence of ducts and itshemodynamic significance, but it cannot be used inisolation to decide on treatment. Treatment decision shouldbe in conjunction with clinical symptoms.

(c) In all infants in whom treatment of PDA is considered,echocardiography before treatment is essential to establishthe diagnosis as well as to rule out other structural heartdisease (e.g. duct dependent condition in which closureof PDA is contraindicated)

(d) Post treatment echocardiography is required to documentthe response to treatment and assess the ductus.

(e) Early targeted treatment based on echocardiographiccriteria alone cannot be recommended at this point of timeeven though some large RCT (DETECT Trial , Australia)is currently evaluating the same.

Other Diagnostic Tests:

The other diagnostic tests have very limited role, especially in


preterm babies with PDA. Chest radiograph findings (non-specific):

(a) cardiomegaly

(b) pulmonary plethora occurs late ( significant PDA)

Brain Natriuretic Peptide (BNP) :

Diagnostic modality- biomarkers- BNP and N-terminal-pro- BNPwhich has shown good sensitivity and specificity. In patientswith significant shunting level rises and following closure ofductus it falls. Though these markers are promising, therewidespread clinical use is yet to emerge9.

Management of PDA:

The management of PDA could be broadly divided into threeaspects- pharmacological closure of ductus, general supportivemeasures and surgical ligation of the PDA.

Despite three decades of intense research enrolling thousandsof preterm infants, yet evidence for the long term benefits ofpharmacological closure of PDA is inconclusive and debatable.The decision to treat PDA depends on the 3 factors- thespontaneous closure rate, adverse effect of ductal patency andrisk benefit of treatment.

In a recent systematic review, Benitz et al evaluated the effectof medical and surgical treatment- either prophylactic ortherapeutic on various outcomes10. Although all modes ofinterventions effectively closed the ductus, there was littlebeneficial effect on the outcomes. Hence the therapeuticdecision to treat ductus arteriosus is complex and there is ahot debate for conservative approach especially in preterminfants more than 1000g in whom the spontaneous closurerate is high.

Pharmacological closure of PDA

Indications for treatment :

Treatment should be considered in preterm infants withechocardiographically proven hemodynamically significantDuctus Arteriosus with one of the following conditions

(a) Features of congestive heart failure

(b) Requiring prolonged respiratory support ( invasive or noninvasive) unlikely to be due to other reasons

(c) Unexplained oxygen requirement(FiO2 = 30%) or risingO2 requirement on respiratory support

(d) Recurrent apnea requiring respiratory support (CPAP/Nasal IMV/invasive ventilation) attributed to PDA

* These indications are based on pragmatic clinical decisionand not based on high quality evidence

* Treatment of all infants otherwise clinically asymptomatic,based on echocardiography findings of Hemodynamically

Significant (HS) - PDA alone is not warranted

* Definition of HS - PDA: Presence of PDA >1.5mm withone of the following LA/Ao ratio >1.5:1, retrograde flowdiastolic flow in descending aorta, celiac or cerebral arteries> 30% of ante grade flow; Left ventricular output >320mL/kg/min.

Recommendation

(a) Both Indomethacin and Iboprufen are equally effective inclosing PDA with closure arte of 70-80%.

(b) Iboprufen currently appears to be the superior option withits better safety profile, especially in terms of avoiding NEC.

(c) Infants

(i) On full enteral feeds (atleast 120ml/kg/day) – OralIboprufen

(ii) On parentral fluids, partial feeds – IV Indomethacin

(d) The question of which drug confers better long term intactsurvival is yet unanswered

Mechanism of Action:

These non selective cyclo-oxygenase (COX) inhibitors whichinhibit prostaglandin synthesis and causes ductal constriction.Dosing

INDOMETHACIN IV infusion Loading dose: 0.2 mg/kg/dose over 30min • Subsequent doses ( adjusted as

per postnatal age)• <2 days: 0.1 mg/kg/dose 12

hourly x 2 doses• 2-7 days: 0.2 mg/kg/dose 12

hourly x 2 doses• >7 days: 0.25 mg/kg/dose 12

hourly x 2 dosesIBOPRUFEN IV or Oral Loading dose: 10 mg/kg/dose

• Subsequent dose: 5mg/kg/dose 24 hourly x 2 doses

Following the first course, a second course with same dosagecould be used in case of persistent PDA needing treatment orre-opening of the ductus with symptoms.

Failure of medical treatment: Persistence of hemodynamicallysignificant ductus or reopening despite two courses of treatmentdefines failure of medical treatment.

Side Effects And MonitoringAdverse effects of treatment with NSAIDS include

(a) Renal compromise due to its effect on COX 1,

(b) Bleeding tendency due to its effect on platelet function and

(c) Increased risk of NEC


MonitoringBaseline • Urine output, RFT, platelet countDaily • Urine outputAlternate day • RFT,

• Platelet counts

Contraindications

Renal: Urine output< 0.6 ml/kg/h, blood urea > 40 mg/dL,creatinine >1.8 mg/dL

Bleeding: Bleeding from IV sites, skin bleeds, gastrointestinalbleeding, enlarging or evolving intraventricular hemorrhage(IVH), platelet count < 60,000/mm3.

Gastrointestinal: necrotizing enterocolitis; blood in stool

General Measures

1. Maintenance of adequate hematocrit and haemoglobin:

It helps in improving hemodynamics, decreases stresson already hyperactive myocardium. Preferably more than45%.

2. Fluid restriction :

In clinically symptomatic or echocardiographicallydiagnosed PDA, it is recommended to restrict parenteralfluid intake to 120 mL/kg/day, provided other parameterslike urine output, serum Na, urine specific gravity etc arewithin normal limits.

Infants on full enteral feeds with hemodynamically

significant PDA, fluid intake of up to 150 ml/kg/day maybe used and calorie dense feed can be used.

3. Role of Digitalis in Preterm baby

Small preterm baby is having relatively ineffectiveresponse to digitalis due to immaturity

4. Role of Furosemide in medical management of PDA

No role for routine use of frusomide in treatment of PDAexcept as decongestive therapy

5. Role of Dopamine in treatment

Low dose dopamine is considered to be beneficial inreversing indomethacin induced oliguria in preterm babieswith PDA. However, there is no evidence to support thisnotion. The use of dopamine had no effect on the rate offailure for ductal closure. The evidence for effect ofdopamine on cerebral circulation, IVH or death beforedischarge is insufficient. Hence use of dopamine forprevention of renal dysfunction induced by COX inhibitorscannot be recommended.

6. Mechanical ventilation strategy

In infants on ventilator support with hemodynamicallysignificant -PDA, use slightly higher PEEP and lower Ti ,which might help in decreasing pulmonary edema anddecreasing left to right shunt. High PEEP increase relativepulmonary vascular resistance and decrease the amountof left to right shunt.

Reference:1. Van Overmeire B, Van de Broek H, Van Laer P, Weyler J,

Vanhaesebrouck P. Early versus late indomethacin treatmentfor patent ductus arteriosus inpremature infants with respiratorydistress syndrome. J Pediatr 2001; 138:205-11.

2. Skinner J. Diagnosis of patent ductus arteriosus. Semin Neonatol.2001;6(1):49–61

3. Fanaroff AA, Stoll BJ, Wright LL, et al. Trends in neonatalmorbidity and mortality for very low birth weight infants. Am JObstet Gynecol. 2007; 196:147e1–e8.

4. Clyman R I. Mechanisms regulating the ductus arteriosus. BiolNeonate 2006; 89: 330–335.

5. Shimada S, Kasai T, Konishi M, Fujiwara T. Effects of patentductus arteriosus on left ventricular output and organ blood flowsin preterm infants with respiratory distress syndrome treated withsurfactant. J Pediatr 1994; 125: 270-277.

6. Skelton R, Evans N, Smythe J. A blinded comparison of clinicaland echocardiographic evaluation of the preterm infant for patentductus arteriosus. J Paediatr Child Health. 1994;30:406–411.

7. Evans N, Malcolm G, Osborn D, Kluckow M· Diagnosis of patentductus arteriosus in preterm infants. NeoReviews 2004; 5: 86-97.

8. Sehgal A, McNamara PJ. Does echocardiography facilitate

determination of hemodynamic significance attributable to theductus arteriosus. Eur J Pediatr 2009; 168: 907–914.

9. Kluckow M, Seri I, Evans N· Functional Echocardiography: Anemerging clinical tool for the Neonatologist. J Pediatr. 2007Feb;150(2):125-30.

10. Sasi A, Deorari AK. Patent ductus arteriosus in preterm infants.Indian Peditr 2011; 48: 301-308.

11. Benitz WE. Treatment of persistent patent ductus arteriosus inpreterm infants: time to accept the null hypothesis. Journal ofPerinatology 2010; 30: 241–252.

12. Narayanan-Sankar M, Clyman RI. Pharmacologic closure ofpatent ductus arteriosus in the neonate. NeoReviews 2003; 4:215-221.

13. Ohlsson A, Walia R, Shah SS. Ibuprofen for the treatment ofpatent ductus arteriosus in preterm and/or low birth weight infants.Cochrane Database Syst Revs. 2010; 4: CD003481.

14. Cherif A, Khrouf N, Jabnoun S, Mokrani C, Amara MB, GuellouzeN ,et al. Randomized pilot study comparing oral ibuprofen withintravenous ibuprofen in very low birth weight infants with patentductus arteriosus. Pediatrics 2008; 122: e1256-e1261.

15. Herrera C, Holberton J, Davis PG. Prolonged versus short courseof indomethacin for the treatment of patent ductus arteriosus inpreterm infants. Cochrane Database Syst Rev. 2007; 2: CD003480.


Persistent Pulmonary Hypertension of Newborn

Anindya Kumar SahaDepartment of Neonatology, IPGME&R , Kolkata

Correspondance : Anindya Kumar Saha, Department of Neonatology,IPGME&R , Kolkata . Email : [email protected]

Definition:

Persistent pulmonary hypertension of the newborn (PPHN)is a syndrome characterized by the presence of raisedpulmonary vascular resistance( PVR) and right to left shuntthrough fetal channels ( ductus arteriosus and/or foramenovale without any presence of congenital heart anomalies .It is not always defined by any specific pressure of thepulmonary artery(PA). Right ventricular compliance toovercome the outflow resistance is the key factor behind theeffect of pulmonary hypertension.

Primary vs. Secondary PPHN:

Primary PPHN is the classical PPHN presenting after birthwith hypoxemia. This is due to a primary dysfunction inpulmonary endothelial vasodilatation mechanisms.

Secondary PPHN is secondary to the disease in theparenchyma of the lung .Most newborn with lung diseaseshave elevated pulmonary pressure. But only the critical babieswith high Oxygenation Index (OI > 25 in term and > 15 inpreterm)will have persistent supra-systemic pulmonarypressure , mostly due to hypoxia, acidosis and high ventilatorpressure .

Incidence:

PPHN affects mostly at term or post term newborn, rarelypresent in preterm. Incidence is 1.9/1000 among termdeliveries (North American data base) with a mortality of 11%.The UK series reported the incidence ranging from 0.4-0.68 /1000 live birth.

Vasodilatation mechanism in endothelium and smoothmuscle cell( Figure 1):

The enzymes, cyclooxygenase (COX) and prostacyclinsynthetase (PGIS), are involved in the production ofprostacyclin. Prostacyclin acts on the smooth muscle cellreceptor and stimulates adenylate cyclase (AC) to produce

cyclic adenosine monophosphate (cAMP). Cyclic AMP isdegraded by phosphodiesterase 3A (PDE 3A) in the smoothmuscle cell. Endothelin acts on ET-A receptors in the smoothmuscle cell and causes vasoconstriction by increasing calciumconcentration. But Endothelin while stimulating secondEndothelin receptor (ET-B) stimulates nitric oxide (NO)releaseand vasodilation. Endothelial nitric oxide synthase (eNOS)produces NO, which diffuses from the endothelium to the smoothmuscle cell and stimulates soluble guanylate cyclase (sGC)enzyme to produce cyclic guanosine phosphate (cGMP). cGMPis broken down by PDE5 enzyme in the smooth muscle cell.Sildenafil inhibits PDE5 and increases cGMP levels. c GMP inin pulmonary arterial smooth muscle cells reduces cytosolic ioniccalcium concentrations and induce smooth muscle cell relaxationand pulmonary vasodilation. Milrinone inhibits PDE 3A andincreases cAMP levels in pulmonary arterial smooth muscle cellsand cardiac cells resulting in pulmonary (and systemic)vasodilation and increases myocardial contractility (inodilator).Nitric oxide is a free radical and can avidly combine with

Fig 1: Vasodilatation mechanism in smooth muscle and endothe-lium

Neonatology


superoxide anions to form a toxic vasoconstrictor, peroxynitrite.

Fetal circulation and transition at birth:

In fetal circulation there is elevated pulmonary vascular pressureand presence of right to left shunting via the ductus arteriosus(DA) and foramen ovale (FO) allowing only 10 % of the RVoutput to pass via pulmonary circulation. The main mechanismbehind elevated fetal pulmonary resistance include low paO2,decreased production of vasodilator like Nitric oxide ( NO) anddilating prostaglandins (prostaclyclins) and increasedproduction of vasoconstrictors like thromboxane andendothelins.

After birth PA pressure and vascular resistance drop to 50 % ofthe systemic pressure and pulmonary blood increases by almost10 times with the onset of breathing at birth. The responsiblefactors are alveolar expansion with oxygenation after birth,continuous respiration and clamping of umbilical cord. Afterbirth the circulating vasodilators prevail more in place of

constricting factors of the fetal circulation.

Risk factors :

Primary PPHN – It is mostly idiopathic but is often associatedwith pregnancy complications like maternal diabetes ,hypertension , obesity and post maturity and fetal or neonatalcomplications like polycythemia , fetal anemia and prematureclosure of ductus arteriosus .

Secondary PPHN – Lung causes:Meconium aspiration,Respiratory distress syndrome, Transient tachypnea of newborn, Broncho pulmonary dysplasia , Congenital diaphragmatichernia, Capillary alveolar dysplasia , Surfactant deficiency.

Other causes: Hypoxic ischemic encephalopathy, Antenatalexposure of drugs like NSAIDs and SSRIs

Pathophysiology – PPHN is a syndrome with multifactorialetiopathology involving factors increasing PVR to the pointof inducing right to left shunt .( Table 1)

Categories Etiopathology Diseases Prognosis / outcome

Pulmonary Increased layer of arterial vascular smooth muscles and Idiopathic PPHN Limited or absentvascular extension to intra acinar arteries Developed in fetal life, symptomatic after response to vasodilatorsremodeling Excessive smooth muscle proliferation and Extra Cellular birth, Caused by chronic fetal hypoxemia, Mortality is high

Matrix deposition . premature closure of DAVascular remodeling by prolonged period of increased PVR

VasoconstrictionNumber and structure of vessel , branching normal : Perinatal asphyxia, sepsis, metabolic Treatment by vasodilatorssmooth muscle of vessel responsible with predominance acidosisof vasoconstrictors

Pulmonary Decrease in vasculogenesis and angiogenesis resulting Congenital diaphragmatic hernia Minimal or absent response tovascular in pulmonary hypoplasia Pulmonary hypoplasia secondary to vasodilatorshypoplasia Increase PVR due to inability of vasculature to cope up early and prolonged oligohydramnios Prognosis guarded

RV outputHypoxia due to right to left shunt and pulmonaryhypoperfusion

Obstruction Normal structure and number of vessels Polycythemia Treatment of primary causePresence of pulmonary edema Pulmonary venous obstruction by Oxygenation worsened by

anomalous drainage pulmonary vasodilators

Pulmonary Blood flow reduced to unventilated area of lung Pneumonia, aspiration, surfactant deficiency Treatment of primaryparenchymal →→→→→ appropriate pulmonary vasoconstriction in diseases Congenital defiency of surfactant protein B Lung diseasepathology with decreased alveolar ventilation →→→→→ high PVR Capillary alveolar dysplasia Oxygenation worsened by

But right to left shunt only in extensive pulmonary vasodilatorsdisease

Iatrogenic High mean airway pressure ( MAP ) during mechanical Mostly in high frequency ventilation Reduction of MAPventilationFailure to reduce MAP when compliance improved

Right ventricular PVR not high RV failure Shunt reduction by therapiesdirecteddysfunction Right ventricular contractility abnormal →→→→→ higher Right improving RV contractility

atrium pressure →→→→→ right to left shunt at FO

Table 1. Etiopathology of PPHN


Clinical features

(a) Level of hypoxemia disproportionate to the degreeof respiratory distress and primary pulmonary findings( clinical or radiological)

(b) Progressive cyanosis in first hours of life in PPHN

(c) Oxygenation or saturation lability

(d) In 50 % of cases right to left shunt through DA → differencein pre and pot ductal oxygenation

SPO2 difference > 5-10 % or PaO2 difference > 20 mmHgbetween pre and post ductal level indicative of right to leftshunting at DA level

(e) Prominent precordial impulse , loud S2, Systolicparasternal murmur due to tricuspid regurgitation ( TR)

(f) In secondary PPHN often there is respiratory failure , needfor high MAP and Fio2

(g) Chest X-Ray( CXR) :

Lung fields are often clear in primary PPHN, ‘black lung’ inidiopathic variety.

CXR is abnormal in secondary PPHN.

Large cardiac shadow due to right ventricular ( RV)changes

Role of point of care ultrasound or Functionalechocardiography :

(a) To exclude Congenital cyanotic heart disease

(b) To determine PA pressure

(i) By using ductal shunt velocities or TR peak velocities

(ii) By using pulmonary artery flow from pulmonary arteryvelocity time integral ( VTI ) in absence of TR ( 30 %of cases )

(c) To determine PVR by measuring the ratio of pulmonaryartery acceleration time ( PA ACT)and right ventricularejection time ( RV ET) ( PA ACT/ RV ET <0.2 abnormal )

(d) To determine presence and degree of right to left shunt (DA or FO)

In case of DA, shunt > 30 % of cardiac cycle indicatessupra systemic PA pressure

(e) To determine Left PA velocity : low velocities predictive ofgood response to inhaled NO( iNO)

(f) To define ventricular output and function :

(i) High PVR leading to low RV output ultimately cutsdown flow in Left atrium (LA)and decrease in leftventricular ( LV )out put. LVoutput < 100 ml/kg/min

indicates high risk for mortality.

(ii) Global myocardial dysfunction with low LV and RVoutput seen in infants with pulmonary hypertension

(iii) Pulmonary hypertension with predominant LVdysfunction requires different management approach

(g) Presence of RV hypertrophy indicates premature closureof ductus in fetus.

Management :

Aim:

(a) To decrease PVR

(b) To maintain normal lung perfusion and oxygenation.

(c) To maintain optimum arterial oxygen level and tissueoxygen delivery.

(d) To maintain systemic pressure above pulmonary pressure

(e) To minimize lesions induced by oxygen and ventilation

(f) Two most potent natural vasodilators are adequate lungrecruitment and oxygen.

General care :

(a) Maintenance of a normal body temperature

(b) Correction of electrolyte and metabolic status such as hypoand hyperglycemia,hypocalcemia, acidosis andpolycythemia.

(c) Covering eyes and ears and maintaining a low- noiseenvironment.

(d) Minimal stimulation along with judicious use of sedationand analgesia with morphine, fentanyl or benzodiazepinessuch as midazolam

(e) Paralysis with muscle relaxants should be avoided as it isassociated with increased mortality

(f) Hyperventilation and alkali infusion to maintain an alkalinepH were followed earlier but now are abandonedconsidering concern of cerebral perfusion andsensorineural deafness with respiratory alkalosis. Alkaliinfusion was associated with increased use of ECMO andneed of oxygen at 28 days. Acidosis is avoided in view ofexaggerated hypoxic pulmonary vasoconstriction withpH<7.25.

(g) Oxygen and optimal oxygen saturation: Oxygen acts aspulmonary vasodilator and providing adequate oxygenforms the mainstay of PPHN. Hypoxia increases PVRand optimal vasodilatation occurs with PaO2 around 100


mm Hg but hyperoxia does not further decrease PVR andin-stead results in free – radical injury by formation ofperoxinitrite. In addition to direct inactivation of NO, thesereactive oxygen species can decrease eNOSand sGCactivity and increase PDE5 activity. Hence it will beoptimum to keep preductal oxygen saturation in low to mid90s and paO2 between 55-80 mmHg while managinginfants with PPHN.

Ventilation :

Optimal lung expansion is essential (not more than 8-9 ribexpansion) for adequate oxygenation as well as effectivedelivery of NO. Conventional and High frequency ventilation(HFOV) may be used but neither mode of ventilation couldsubstitute use of ECMO. Gentle ventilation strategies withoptimal PEEP(4-5 cm H

2O) , relatively low PIP( 25 cm H

2O) ,

rate of 40 and some permissive hypercapnia (Pa CO2 45-60mmHg) are now being used for adequate alveolar recruitmentwithout lung injury.From conventional ventilation HFV is to beconsidered when PIP >28 cm H2O is required to maintainPaCO2<60 cm H2O. Infants with RDS and MAS benefit mostfrom a combination of HFV and iNO therapy. Severity of PPHNand response to therapy is assessed by calculation ofoxygenation index (OI).

Surfactant :

Exogenous surfactant therapy improves oxygenation andreduces the need for ECMO when PPHN is secondary toparenchymal lung disease like RDS, pneumonia, or MAS.This benefit is greatest for infant with mild disease and OI of15-25.

Hemodynamic support:

Myocardial activity is commonly compromised in this disease.Quick correction with crystalloid or colloid is contraindicatedunless there is hypovolemia since RA pressure is already high

and further bolus fluid results in exacerbation of Right to leftshunt. Inotropic and vasopressor agent should be used tooptimize cardiac contractility,stabilize systemic blood pressureand reduce extra pulmonary shunt. Systemic blood pressureshould be normally maintained at normal values for gestationalage. Dopamine, Dobutamine,Adrenaline and recentlynoradrenalin are commonly used. Each inotropic agent hasgot distinct effect and identification of the cause of hypotensionand myocardial performance is necessary in choosing rightdrug. These agents are not selective to systemic circulationand may be associated with pulmonary vasoconstriction andelevation of PVR at high doses. Noradrenaline other than itsvasopressor effect has been shown to decrease PVR andincrease blood flow by NO release.(Table 2)

Pulmonary vasodilator

Inhaled NO:

Nitric oxide(NO) is a naturally occurring vasodilator. It is rapidlyinactivated in the bloodstream with production ofmethaemoglobin and inorganic nitrates and nitrites.Due to theseproperties,when it is given by inhalation (iNO) it dilates onlythe pulmonary blood vessels (Selective effect) without havingany significant effect on the systemic vasculature. Inhaled NOreaches only in ventilated portion of lung increasing pulmonaryblood flow and improving ventilation perfusion mismatch (Microselective effect ). It is the vasodilator of choice in term babieswith persistent pulmonary hypertension.

It has a rapid onset of action, typically within minutes. The safetyand efficacy of iNO for PPHN in term infants studied throughrandomized controlled trials and it is shown that:

(a) Significantly improves oxygenation.

(b) Significantly reduces the need for rescue with ECMO interm or near term infants

Inotrope Function Commonly used dosage

Dobutamine Improves cardiac output Less peripheral vascular effect 5-20µg/kg/min

Adrenalin Improves cardiac output through inotropic effectIncreases BP(alfa effect) & pulmonary resistance in high doses 0.05-1µg/kg/min

Noradrenalin Improves cardiac outputIncreases BP(alfa effect)Improvement in pulmonary blood flow by releasing eNO 0.05-1µg/kg/min

Dopamine Increases myocardial contractility.BPand cardiac outputIncreased systemic vascular resistance and pulmonary venous resistance at high dose 5-20µg/kg/min

Table 2 : Inotropes and vasopressor used in PPHN


The use of iNO in PPHN doesnot reduce mortality,length ofhospitalization, chronic lung disease or alterneurodevelopmental outcomes.

The role of iNO in preterm babies is inconclusive.The Cochranereview has demonstrated that rescue iNO therapy in the veryill preterm infant was ineffective and use of early iNO for RDSdoes not improve survival.There is some evidence to suggestthat later use of iNO to prevent BPD may be useful however,more studies need to be done.

Doses/ duration / weaning:

Initial recommendation is 20 ppm. Higher dose has beenassociated with more adverse side effects. Some studies haveshown concentration as low as 5 ppm may be effective.

Based on current available literature treatment with NO to bestarted with an OI >15-25 with echocardiographic evidence ofPPHN or higher OI with or without evidence of right to left shunts.

Gradual weaning is done for risk of rebound vasoconstriction.If there is oxygenation response, inspired oxygen concentrationfirst weaned to 60% then iNO is gradually weaned @ 5 ppmper 4 hour. Once iNO dose is 5 ppm, then slow weaning @ 1ppm/ 4 hr is attempted.

Contraindication:

Lethal congenital anomalies, major cardiac anomaliesdependent on right to left shunt.

There is also a high risk of worsening with iNO in pre-existingLV dysfunction or pulmonary venous obstruction.

Complication:

Methemoglobinaemia, formation of nitrogen di oxide.Methemoglobin level must be kept below 5 %. Inhibition ofplatelet aggregation has also been reported.

Prostacyclin (PGI2):

It acts as a vasodilator in IV or inhaled form.Intravenousvasodilator is used in adult pulmonary hypertension. Infantstudies show similar or greater effect than NO but often causeshypotension as it is not selective for pulmonary system.InhaledPGI2 (Epoprostenol)described in some case report, may actsynergistically with iNO to prevent rebound pulmonaryhypertension, but has very short half-life.Illeoprost is a longeracting prostacyclin analogue, has been used endotracheallyand in the inhaled form along with iNO in intractable PPHN(dose 0.5-2 mcg /kg/dose).use of oral PGI2 analogue Beraprostsodium is also reported in neonates with PPHN.

Inhaled PGE1:

Aerosolized PGE1 (Alprostadil) has been used in adult forpulmonary hypertension. The pilot trial for use of inhaled PGE1(IPGE trial) in iNO resistant PPHN was not continued.

Systemic vasodilator

Sildenafil:

Sildenafil inhibits PDE5, increases cGMP and thus inducesvasodilatation. In a Cochrane meta analysis of 37 newbornfrom centers without HFOV and iNO, Sildenafil has been shownto improve oxygenation. Its effect on pulmonary vasculatureappears to be independent from underlying cause, thus effectivein pulmonary hypertension associated with PPHN, heart or lungdisease.

Available both in oral and intravenous form. Studies have shownthat oral sildenafil (1-3 mg/kg/dose per 6hr) reduces mortalityand improves oxygenation in infants with PPHN in centerslimited by non-availability of iNO.

Intravenous sildenafil (loading 0.4 mg over 3 hours followed by0.07 mg/ kg/hr) is shown to be effective in neonatal PPHN withor without exposure to iNO.

The risk of side effect like hypotension is high.It may reducerebound pulmonary hypertension during iNO weaning.

It is safe, effective and easy to administer but its vasodilatoreffect extends to poorly ventilated areas of lungs, increasingV/Q mismatch. Animal model shows it increases intrapulmonaryshunt and worsens oxygenation, especially in cases of lobaratelectasis. Oxygenation improves withTadalafil(PDE5inhibitor)as seen in same animal model without lobar atelectasis

Milrinone:

This ionotropic vasodilator is commonly used in pediatric andadult ICU for afterload reduction but not currently licensed fortreatment in PPHN. It inhibits PDE3 and relaxes pulmonaryarteries.. Infants with PPHN refractory to iNO have improvedwith Milrinone. Milrinone is the pulmonary vasodilator of choicein cases with left ventricular dysfunction where selectivepulmonary vasodilator may worsen oxygenation. It alsoimproves right sided cardiac output. As with other systemicvasodilator, hypotension is a concern. A loading dose (50 mcg/kg) followed by 0.33-1 mcg/kg/hr.) is commonly used.

Magnesium sulfate :

There is insufficient evidence to support its use in PPHN

Bosentan:

This non-specific endothein -1 receptor blocker has beenused in adult pulmonary hypertension. In fetal lamb model


this drug has decreased pulmonary pressure. It has alsodecreased RVH and muscularisation in distal arteries andincreased fall in PVR at delivery. Successful use of Bosentanin neonates with PPHN has been described in some casereports.

Determining the therapeutic option :the role ofEchocardiography:

Echocardiography has got a major role to determine appropriatetherapeutic option. Cyanotic congenital heart disease has tobe ruled out in any cyanotic newborn with fixed hypoxemiaprior to initiation of therapy.

(a) In cases of ductal dependent pulmonary circulation likeTricuspid atresia, critical pulmonary stenosis or pulmonaryatresia, there is right to left shunt in foramen ovale and leftto right shunt in ductus. The option in this case is PGE1infusion.

(b) Right to left or bidirectional shunt at foramen ovale or/andductus arteriosus is suggestive of extra pulmonary right toleft shunting. It may respond with pulmonary vasodilatortherapy along with proper lung recruitment.

(c) Right to left shunt at ductal level but left to right shunt atforamen ovale suggest rise in pulmonary pressure withleft ventricular dysfunction. It is seen with pulmonaryvenous hypertension as in some cases of CDH, asphyxiaor sepsis. In some cases of duct dependent or RVdependent systemic circulation also show similar kind ofshunt pattern. iNO is contraindicated in such cases andmay worsen pulmonary venous hypertension and /ordecreased systemic blood flow. Infusion MIlrinone or insome cases PGE1 would be effective in this situation.

(d) Cases with marked hypoxemia but with left to right shuntboth at foramen ovale and ductus suggest intrapulmonaryshunting and treatment is directed to optimum lungrecruitment.

Extra corporeal membrane oxygenation (ECMO):

ECMO is a supportive measure for the heart and lung to recoverfrom the underlying pathology. With improved ventilationtechniques and the use of therapies like HFOV, surfactant, iNO,and other vasodilators, ECMO use for neonatal respiratorydisorders has decreased. The technical details is out of thescope of this write up.

Neurodevelopmental outcome:

PPHN is a disease with significant long-term morbidity,irrespective of the various treatment options. These babiessuffer from long-term sequale in form of developmental,cognitive, and hearing abnormalities.

Acknowledgment :

This write up is an adaptation of the following articles on persistentpulmonary hypertension of the newborn. The present author owes tothe authors of the following articles for the concept and content of thepresent review.

1. Nair J, Lakshminrusimha S. Update on PPHN: Mechanismsand treatment. Seminars in Neonatology. 2014; 38:78-91.

2. Joaquim EB, Cabral A, Jaques B. Persistent pulmonaryhypertension of the newborn: recent advances in pathophysiologyand treatment. Journal of Pediatrics (Rio J). 2013;89(3):226---242

3. Sydney Local Health District -Royal Prince Alfred Hospital.Clinicalguidelines:Persistent pulmonary hypertension of the newborn. 2014.

4. Matthew B, Lakshminrusimha S. persistent pulmonary hypertensionof the newborn and hypoxic respiratory failure. Workbook inPractical Neonatology by Polin& Yoder.5th Ed. 2015;270-298.


Members are generously requested to provide News, Views, Reviews, Case Reports,Articles to our esteemed journal.

Contact :Dr Atul Kr Gupta

Editor-in-Chief, The Child and Newborn

10C, Janaki Sha Road, Hastings, Kolkata 700 022, Email : [email protected]

Pediatricians Approach To Emergency Cardiac Conditions

Biswajit BandyopadhyayHOD & Sr Consultant Pediatric Cardiologist, RTIICS,Kolkata

Correspondance :Biswajit Bandyopadhyay, HOD & Sr ConsultantPediatric Cardiologist, RTIICS,Kolkata. Email :

(A) Cardiac emergencies in the newborn:

The newborn presentation of cardiac emergencies can be inthe form of:

(1) Cyanosis

(2) Low cardiac output

Cardiac Cyanosis

Cyanotic congenital heart diseases (CHD) present as cyanosiswith increased or decreased pulmonary vascularity.

Cyanotic CHDs with decreased pulmonary vascularity:

After birth, as the switch from fetal to neonatal circulation occurs,right sided obstructive lesions may present with profoundcyanosis with decreased pulmonary vascularity such as:Pulmonary atresia, Tricuspid atresia, critical pulmonarystenosis. Transposition of great arteries with intact septum alsocan present with cyanosis and decreased pulmonary vascularityif the inter-atrial communication is restrictive and the ductalclosure ensues. The neonate will present with:

(a) Cyanosis not responding to hyperoxia test

(b) Cyanosis not improving with ventilation

(c) Usually no murmur

(d) Usually no respiratory distress

These neonates present due to restriction of pulmonary bloodflow due to closure of duct in duct dependant pulmonarycirculation. Thus the initial goal of therapy is to startProstaglandin E1 which keeps the duct patent by acting on thereceptors located in the smooth muscles in the ductus arteriosusthus preventing it from constricting. The i.v infusion can bestarted at a dose of 0.1 mcg/kg/min. The dose can be graduallyincreased to a maximum dose of 0.4 mcg/kg/min with a targetto achieve saturation more than 80%. The neonate should be

monitored for any adverse effects of Prostaglandin infusion suchas apnea, hypotension and flushing. Prostaglandins arecontraindicated in obstructed supracardiac TAPVC and TGAwith intact IAS. The neonate should then be transferred to atertiary level cardiac centre for further management. Neonataltransfer is better with a secure airway i.e. endotrachealintubation and ventilation as Prostaglandins are known to causeapnea and hypotension.

Cyanotic CHDs with increased pulmonary vascularity:

Neonates with mixing lesions or abnormal pulmonary venousconnections can present in the neonatal period, such asTGA,VSD or obstructed TAPVC. These neonates will usuallypresent with:

(a) Respiratory distress

(b) Cyanosis not improving with oxygen/ventilation

These neonates require maintaining airway, breathing andperfusion with early referral to tertiary cardiac care unit.

Low cardiac output

The neonate can have features of low cardiac output in thesetting of:

(a) Left sided obstructive lesions

(b) Arrhythmias

Left sided obstructive lesions

During fetal life, the duct supplies the systemic circulation aswell as retrogradely the arch aorta and neck vessels inHypoplastic left heart syndrome, critical aortic stenosis andcritical coarctation of aorta. After birth, as the duct closes, thesystemic circulation is thus decreased and can lead to featuresof low cardiac output, such as:

(a) Shock

(b) Metabolic acidosis

(c) Acute renal failure

(d) NEC

PG’s Column


The treatment should be aimed at:

(a) Maintaing systemic circulation by prostaglandin infusionas discussed above

(b) Maintaining airway and ventilation

(c) Optimizing perfusion

(d) Maintaining acid-base balance

(e) Urgent referral to a tertiary cardiac care unit for furthermanagement

Arrhythmias

Neonates presenting with low cardiac output and arrhythmiascan broadly present as:

Tachyarrhythmias:

(i) Supraventricular tachycardias

(a) Narrow complex

(b) Heart rate usually> 200

Treatment includes stabilization of hemodynamics; securingairway and breathing; followed by pharmacological therapy byadministration of i.v. adenosine 0.1 mg/kg i.v. rapid pushfollowed by saline bolus. Repeat dose can be administered ifthe arrhythmia continues after 5 minutes. Under circumstancesof hemodynamic instability; synchronized cardioversion is thetreatment of choice. For Atrial flutter in neonates synchronizedcardioversion is the treatment of choice.

(ii) Ventricular tachycardias

(a) Broad complex tachycardia

(b) Heart rate usually > 200

Although rare but this life-threatening emergency requiresemergency cardioversion 2 joules/kg alongwith maintainingairway and breathing and optimizing perfusion

Bradyarrhythmias:

Bradyarrhythmia leading to low cardiac output is observed incases of congental complete heart block. Usually seen inneonates with mothers positive for anti Ro/anti La antibodies.If the child presents with cardio-respiratory compromise,immediate cardio-pulmonary resuscitation should be provided.If the child is hemodynamically stable, the treatment includespositive chronotropy/inotropy by i.v. infusion of isoprenaline andpreload and afterload reducing agents. Urgent referral to cardiacunit to rule out congenital heart diseases and for temporarypacing if required.

(B) Cardiac emergencies in infancy and childhood:

(a) Hypercyanotic spells

(b) Congestive cardiac failure

(c) Arrhythmias

(v) Syncope

Hypercyanotic spells

Hypercyanotic spells are characterized by episodes ofhyperapnea (rapid and deep inspiration) with worsening ofcyanosis. The occurrence of spells is increased if the child isdehydrated. On examination the child, the intensity of murmurdecreases or it may not be heard at all. If severe, the spell canlead to transient loss of consciousness, cerebrovascularaccident, convulsions or even death. Mechanism ofhypercyanotic spell can be explained as follows:

Hyperapnea (due to crying)

Stimulation of respiratory Decreases SVRcentre (systemic vascular

resistance)

Decreased PO2 andincreased acidosis Right to left shunt

increases at the VSDlevel

Increased Systemic flowand decreased pulmonary flow

Treatment includes:

(a) Keep infant in knee-chest position which reduces thedeoxygenated blood venous return to heart and increasesthe SVR

(b) Administration of oxygen thereby increasing PO2

(c) Maintain clear airway and breathing

(d) Securing i.v. access and administer Normal Saline bolusto maintain the cardiac output and treat dehydration andacidosis

(e) Morphine sulphate at 0.2 mg/kg can be administered tosuppress the respiratory centre

(f) Correction of acidosis by i.v. NaHCO3 1mEq/kg i.v.

(g) Phenylephrine 0.02 mg/kg can be administered as avasoconstrictor thereby increasing the SVR and thusincreasing blood flow to the lungs

(h) Ketamine 1-3 mg/kg can be administered as it increasesSVR and sedates baby

(i) Propranolol 0.01-0.25 mg/kg slow i.v. is administered to


decrease the heart rate and revert the spell.

(j) If the spell still continues, i.v. anaesthetics need to beadmistered with mechanical ventilation

(k) After stabilization, the child needs urgent referral to atertiary cardiac centre for assessment of requirement ofan aorto-pulmonary shunt.

Congestive cardiac failure

Congestive cardiac failure can be a presentation of:

(a) Left heart obstructive lesions: HLHS, Severe aorticstenosis, Severe coarctation of aorta

(b) Large left to right shunts

(c) Severe AVVR

(d) Myocarditis

(e) ALCAPA

(f) Arrhythmias

(g) Kawasaki’s disease

Treatment requires stabilization of patient and referral forspecific treatment for various heart conditions:

(a) Maintenance of airway and breathing

(b) Oxygen administration as the myocardial oxygen demandincreases (except in HLHS)

(c) Preload reduction: includes diuretics, fluid restriction

(d) Afterload reduction: includes ACE inhibitors

(e) Positive ionotropic agents: i.v. infusion of dobutamine,milrinone

(f) High calorie diet

(g) Treatment of associated infections

Supraventricular tachycardia (SVT) is mostly caused byAbnormal re-entrant mechanism

50% of cases are idiopathic whereas 22% have WPWsyndrome

Cause of SVT in older children are more likely to be WPW,concealed bypass tracts and congenital heart diseases

Management of SVT:

Stable patient :

(a) Vagal manouevres : ice in water to face

(b) Adenosine: start at 0.05 mg /kg dose,

(c) increase by 0.05mg/kg intervals to 0.25mg/kg

(d) Must rapidly infuse, followed by saline bolus

(e) Older child / teen > 50 kg: 6mg , then 12 mg dose

Unstable patient:

DC cardioversion

MANAGEMENT OF TACHYCARDIA(weak pulses and poor perfusion)

Maintain airway, breathing and circulation

Narrow QRS (<0.08 sec) Evaluate QRS duration on ECG Wide QRS (>0.08 sec)

Sinus tachycardia SVT Ventricular tachycardiaP waves normal P waves absent or abnormal Synchronized cardioversionGradual onset Abrupt in onset with 0.5 to 1 joule/kgHR is usually HR is usually if ineffective increase to 2J/kg<220 in infants >220 in infants<180 in children >180 in infants

Treat the cause Consider vagal maneuvers I.V. Amiodarone 5mg/kgover 20-60 minutes

i.v. adenosine 0.1 mg/kg (max dose 6 mg) orDouble the first dose if ineffective I.V. Procainamide 15 mg/kg

Or over 30-60 minutesSynchronized cardioversion


Complications of ADENOSINE:

Cardiac : transient bradycardia , asystole,

Ventricular fibrillation, Atrial fibrillation, ventricular tachycardia.

Non-cardiac : apnea in premature infant, bronchospasm inasthmatic

Syncope

Cardiac causes of syncope

(a) Prolonged QTc <0.44 unlikely >0.48 high risk

(b) Brugada syndrome

(c) Severe aortic stenosis

(d) Severe pulmonary stenosis

(e) HOCM

Management:

If child is unstable

(a) Child should be stabilized with maintenance of airway,breathing and circulation

(b) If the child had wide complex tachycardia, manageaccording to algorithm mentioned above

(c) Optimize perfusion by I.V. Normal saline infusion

(d) Urgent referral to tertiary cardiac unit

If child is stable:

(a) Assess with detailed history to rule out possibility of aseizure as a differential diagnosis

(b) Family history of syncope or sudden death

(c) Investigate with:

Holter monitoring

Tilt table test

Exercise test

Diagnostic Algorithm For Congenital Heart Diseases

Does the child have heart disease?Apply NADA’s criteria:Major: 1) Systolic Murmur > 3

2) Diastolic Murmur 3) Central Cyanosis 4) Congestive Cardiac Failure

Minor: 1) Systolic Murmur<3 2) Abnormal S2 3) Abnormal ECG 4) Abnormal Chest Xray 5) Abnormal Blood Pressure

Diagnostic Algorithm For Acyanotic CHD

HISTORY- Failure to thrive - Fatigue on exertion- Repeated chest infections - Chest pain- Feeding difficulty in a newborn - Syncope- Suck-rest-suck cycles - Feeding difficulty in a newborn

LEFT TO RIGHT SHUNT LESIONS OBSTRUCTIVE LESIONS

Wide fixed split S2 Wide variable splitS2 Delayed A2 Wide variable splitS2 Pulmonary ESM Continuous murmur Aortic ESM Pulmonary ESM Tricuspid MDM Mitral MDM Systolic thrill Systolic thrill rsR’ in V1 q waves in V5-V6 LVH +/-strain pattern RVH+/-strain pattern CM, plethora on CXR CM, plethora on CXR Normal heart size on CXR N heart size on CXR

Wide pulse pressure Narrow pulse pressure

ASD PDA AS PS

Wide variable split S2 Wide fixed split S2 Feeble pulses in lower limbsPSM at left parasternal area Pulmonary ESM +/- PSM ESM in interscapular regionMitral MDM Tricuspid and mitral MDM BP higher in arms than in legsQ waves in v5-v6 in ECG LAD, BVH on ECG LVH +/-strain patternCM, plethora on CXR CM, plethora on CXR Rib notching Nheart size on CXR

VSD AVCD COA


DIAGNOSTIC ALGORITHM FOR CYANOTIC CHDCentral CyanosisClubbingPolycythemia

Hyperoxia test If PO2 improves with oxygenrule out respiratory or central causes

If PO2 does not improve with oxygen

Cyanotic spells Failure to thriveSquatting on walking Poor feedingFatigue on exertion Suck-rest-suck cyclesStunted growth Respiratory distress

Decreased pulmonary vascularity Increased pulmonary vascularity

RAD,RVH LAD,LVH RAD,LVH RVH on ECG LVH or BVH on ECG

TOF TA + PS PA TGA TA without PS

DORV + PS SV + PS SV + PS Taussig-bing SV without PS

TGA + PS TAPVC

TRUNCUS

Splintered qrs, pre-excitation ECG LAD,RVH Pulmonary venous congestionMultiple heart sounds AVCD + PS HLHSMarked CM on CXR

Ebstein’s anomaly

WBAP office has opened 3 renovated Air conditioned guest rooms for stay

Double Bed (LCD TV) available.

Guest Room 1 : Rs.1000/- per nightGuest Room 2 : Rs.1500/- per nightGuet Room 3 : Rs.1200/- per night

Food available on request.

Contact : Smt. Bela Bhattacharya (9830866712)

Announcement


Heart Failure in Children

Subhendu MandalSenior Consultant and Interventionist, B M Birla Heart Research Centre, Kolkata

Correspondance : Subhendu Mandal, Senior Consultant andInterventionist, B M Birla Heart Research Centre, Kolkata. Email :[email protected]

Conventional definition

This has been described as a syndrome where pump functionof the heart is inadequate for oxygenation to meet metabolicdemands of the tissues at rest and exercise. Inadequatepumping action leads to multisystem involvement andhemodynamic effects leading to retention of salt and watercausing congestion of pulmonary vascular bed or periphery asedema or both. Broadly the etio-pathogenesis can be dividedunder two categories

(i) Primarily by disorder of myocardium

(ii) Secondary to abnormal loading conditions

Heart failure in children has heterogeneous causes.Classification based on hemodynamics or etiology alone isinsufficient. An approach based on age of presentation ispragmatic and clinically reasonable.

Newborn

In the immediate newborn period congenital heart diseasepredominate the picture. Pulmonary pressures are high andobstructive lesions of right or left heart present as low outputfailure.

Inflow obstruction

Total Anamalous Pulmonary Venous Return (Obstructive type)or (non obstructed with restrictive IAS)

Congenital Mitral stenosis

Cor Triatrium

Outflow obstruction

Coarctation of Aorta

Interrupted aortic arch

Critical Aortic Stenosis

Hypoplastic Left Heart Syndrome

Initial management of heart failure in this age group is purelysupporting the circulation with adequate fluids and Ionotropeslike dobutamine etc. It is necessary to maintain the homeostasisby correction of acidosis, blood sugar and electrolytes.Supporting the ventilation is a good idea when the myocardiumis at jeopardy. Outflow obstruction conditions are commonerthan inflow obstruction and may have duct dependant systemiccirculation. It is reasonable to start prostaglandin infusion evenif an echocardiography is not available. Surgical relief ofobstruction remains the only option for these sickest neonates.

On the contrary severe hypoxemia and acidosis secondary toinsufficient pulmonary flow lead to myocardial failure and death.Conditions like pulmonary Atresia with intact septum, Fallot’swith pulmonary Atresia, Transposition of Great vessel, TricuspidAtresia with severe pulmonary Stenosis present with severecyanosis following the closure of duct. Most of these can beduct dependent for pulmonary circulation and would needprostaglandin infusion until a specific surgical or catheterintervention is available.

Endocardial fibroelastosis and Hypertrophic Cardiomyopathywith left ventricular outflow obstruction has a similarpresentation. . Arrhythmias presenting as heart failure needspecific attention. Supraventricular arrhythmias are thecommonest cause, which a neonate can withstand hours beforeending in failure.

Premature infants with large duct can go into high output failureand may be difficult to wean from ventilation. Closure of PDAwith at least two courses of Ibuprofen or Indomethacin shouldbe given prior to surgical ligation.

Infancy

At around 4-6 weeks of age pulmonary pressures fall makinglesions with left to right shunt worse. Large Ventricular SeptalDefect(VSD),Large Patent Ductus Arteriosus(PDA) andComplete Atrioventricular Canal defects(AVSD) go in highoutput chronic heart fai lure. Other condit ions where

PG’s Column


Pulmonary artery originates from systemic ventricle and hasnon restrictive flow like DORV, Truncus Arteriosus, TGA withLarge VSD, Single Ventricle present with flooding of the low-pressure pulmonary circuit. Symptoms of such high outputfailure include feeding difficulties with rapid breathing andrecession, poor weight gain and recurrent chest infection.Pulmonary vascular bed when exposed to a high pressure flowof systemic circulation and excessive flow lead to occlusivechanges over time. It becomes essential to protect ongoingpulmonary vascular damage and operate prior to irreversiblechange.

Most of these conditions will need surgical correction butmedical management to optimize the outcome becomes a bigissue and challenge to pediatricians. Liaison with pediatriccardiologist optimizes the quality of care.

Older children

As the child grows, exposure to viruses and environmentpredisposes to Myocarditis and Cardiomyopathy. Heart failureis attributed to intrinsic myocardial damage with poor cardiacoutput and chronic heart failure. In HypertrophicCardiomyopathy there is dynamic outflow obstruction as well.Rheumatic heart disease with sequelae like Mitral or Aortic valveregurgitation has high output failure where as constrictivepericarditis has abnormal diastolic filling conditions.

Management

Initial management of any child with heart failure is stabilizationfollowed by arriving to an etiological diagnosis. Apart from ChestX ray and ECG, echocardiography from trained personnel hasbecome a bedside tool for investigation.

Oxygen therapy is a universal and accepted policy, howeverone has to keep in mind of a duct dependant systemic orpulmonary circulation where oxygen can be detrimental.Accepting a saturation of more than 75% in air is acceptable.

Fluid therapy should be aimed at maintaining adequatehydration status so that filing pressure is adequate for a goodcardiac output. Fluid restriction is reasonable in the presenceof frank congestive heart failure. Sometimes a child may beedematous due to third space loss and restriction of fluid maycompromise the intravascular volume and aggravate the lowcardiac output state.

Diuretics are one of the mainstem in the management of heartfailure. It is beyond doubt about its role in presence of congestion.Even in presence of volume overload on chest X ray andEchocardiography chronic diuretic therapy is beneficial. One mustconsider potassium sparing diuretics in chronic cases.

Ionotropes like Dobutamine, Dopamine and Adrenaline is usedas a Intensive care setting. Noradrenaline’s primary role inseptic shock is undoubted. Phosphodiesterase inhibitors likeMilrinone is of great help where afterload reduction as well asionotropic action is needed specially in post operative cases.Digitalis use is nowadays directed towards antiarrhythmicseffects but it is still recommended in cardiomyopathy or anycondition with intrinsic myocardial pumping defects or in frankcongestive cardiac failure.

Most of the research has been directed towards theneurohormonal damage to the myocardium in chronic heartfailure. Studies have shown the cardioprotective action andremodeling of cardiac muscles with ACE Inhibitors likeCaptopril, Enalapril etc. and Cardioselective Beta blockers likeCarvedilol.

Apart from pharmacological therapy, Nutrition and growth ofchild is essential. Recurrent chest infection should be treatedpromptly. Arrhythmias can be notorious and need specificmedication promptly lest it could have been disastrous in postoperative cases. Normal immunization should be routinelypromoted.

Summary

Causes of cardiac failure in children are heterogeneous. Clinicalappreciation of low or high cardiac output is important to startthe initial management. Early echocardiography assessmentor early referral to a Pediatric Cardiac Centre for diagnosis isessential for an effective and favorable outcome. Cardio-protective drugs in chronic heart failure have added a newdimension. General pediatric issues should not be ignored. Twothird of congenital heart disease can be treated by correctivesurgery and has a normal life expectancy.

Further reading

Martin PO,Laughlin MD. Congestive heart failure in children. Pediatricclin of N. America 1999;2(46) 263-273

Francis GS,Benedict C,Johnstone DE et al for SOLVD Investigators.Comparison of neuroendocrine activation in patients with leftventricular dysfunction with or without congestive heart failure.Circulation 1990;82:1724-1729

URL:http://pediatrics.aappublications.org/content/early/2011/10/06/peds. 2011-1317 .Accrened on 19 september 2012

Alan B Lewis. The failing myocardium. In :Pediatric Cardiac IntensiveCare, Anthony C Chang et al. Lippincort William and Wilkins:1998;


Introduction:

Galactosemia is a rare genetic metabolic disorder withautosomal recessive mode of inheritance characterized byelevated level of galactose in the blood and is found in 3 distinctinborn errors of galactose metabolism.It was first describedby Friedrich Gopert,a German physician in 1917 and later indetail by a group led by Herman Halckar in 1956. Newborn oryoung infant can present with jaundice ,hepatomegaly, vomiting,hypoglycemia, seizures, lethargy, irritability, feeding difficulty,poor weight gain etc. Preliminary diagnosis of galactosemia ismade by demonstrating reducing substance in urine anddiagnosis is confirmed by direct enzyme assay usingerythrocyte.

Pentalogy of Fallot is a congenital cyanotic heart defectconsisting of Tetralogy of Fallot and Atrial septal defect(ASD)or patent foramen ovale (PFO) .

Case report :

A 5 days old male neonate presented with non bilious vomitingsince 3 rd day of life with feed intolerance and jaundice.

On examination no dysmorphic features were noted. The babywas detected to have cyanosis, jaundice, huge hepatomegaly,tachypnoea(78/min), tachycardia(200/min) with pansystolicmurmur at left lower sternal border.

The baby was born from a non consanguineous marriage ,was delivered by caesarean section and had an uneventfulantenatal period. This was their first baby with no h/o fetalloss.

Initial investigations revealed conjugated hyperbilirubinemia(TSB16.9/CB 4.2/UCB12.7), impaired kidney function test (Ur88,Cr 1.2), CRP 24 and absent reducing substance in urine

.ABG was normal. USG whole abdomen revealedhepatomegaly, Chest X-ray showed mild cardiomegaly withupturned apex with oligemic lung field. Echocardiographyrevealed narrow pulmonary artery and branches , malalignedVSD, aorta showing 50% overriding, dilated & hypertrophiedRt ventricle and a 4 mm secundum ASD with a short SVC rim.Thyroid profile was normal ,initial blood c/s was sterile.

The baby was managed initially with i v fluid , supplementalO2 and iv antibiotics and i v furosemide. Pediatric cardiologistwas consulted and adviced to continue with conservativemedical management. We started feed gradually as the babywas improving. After 2 days baby became lethargic anddeveloped respiratory distress and gastrointestinal bleeding.The baby was put on mechanical ventilator as there wascombined respiratory and metabolic acidosis.CXR revealed Rtsided consolidation. Antibiotic upgraded to meropenem

A Case of Galactosemia with Pentalogy of Fallot

Debashis Mondal* , Asha Mukherjee** , Sadhna Sha*** , R S Ghose**** *2 ND yr PGT ,**Professor, ***Medical officer, **** Associate Cardiologist and HOD, Echo Cardiography Unit

Department of Pediatrics,Vivekananda Institute of Medical Sciences, Kolkata

Correspondance : Debashis Mondal, 2 year PGT VIMS, Kolkata.Email : [email protected]

Abstract :

We report a case of a newborn with poor feeding, vomiting ,hepatomegaly ,conjugated hyperbilirubinemia with cyanosis andrespiratory distress, diagnosed as Galactosemia with Pentalogy of Fallot.The case is reported for the rare association of theabove uncommon diseases.

Case Report


and colistin. Inj fluconazole was added as blood culture hadgrowth of Candida. Coagulation profile revealed features ofDIC and supportive management in the form blood componentswere given. Further investigations for persistent conjugatedhyperbilirubinemia revealed deficiency of the enzymeGalactose 1 phosphate uridyl transferase .Other inborn errorsof metabolism were ruled out. So the baby was diagnosed asa case of galactosemia with pentalogy of Fallot withsepticaemia. In spite of our best efforts the baby succumbedon 18 days of life.

Discussion :

Galactosemia is a rare genetic metabolic disorder withautosomal recessive mode of inheritance characterized byelevated level of galactose in the blood and is found in 3 distinctinborn errors of galactose metabolism defective in 1 of thefollowing enzymes : galactose 1 phosphate uridyl transferase ,galactokinase ,uridine diphosphate galactose -4- epimerase1.Without the transferase enzyme, the infant is unable tometabolize galactose 1 phosphate, accumulation of whichresults in injury to kidney, liver and brain7,8.

Classic galactosemia is due to complete or near completedeficiency of the enzyme galactose 1 phosphate uridyltransferase2,5. Symptoms typically appears by the 2nd half ofthe 1st week of life.

The incidence is 1 in 600006. The diagnosis of uridyltransferase deficiency should be considered in newborns orinfants with any of the following features : jaundice,hepatomegaly, vomiting, hypoglycaemia, seizures,lethargy,irritability,feeding difficulty, poor weight gain or failureto regain birth weight, aminoaciduria, nuclear cataracts, vitreoushaemorrhage , hepatic failure, liver cirrhosis, ascites,

splenomegaly or mental retardation1,3,4. These patients are atincreased risk for E coli sepsis. Pseudotumor cerebri withbulging fontanel may present. Death usually occurs from liveror kidney failure and sepsis. Light or electron microscopy ofhepatic tissue reveals fatty infiltration, formation of pseudoacini,macronodular cirrhosis. The Preliminary diagnosis ofgalactosemia is made by demonstrating reducing substancein several urine specimen collected while the the baby isreceiving human milk or formula containing lactose. In our casereducing substance was absent in urine probably because ofthe baby was not on oral feeds during collection of urine sample..Deficient activity of the specific enzyme in erythrocytes clinchesthe diagnosis. Carrier testing and prenatal diagnosis can beperfomed by direct enzyme analysis of erythrocytes, aminocytesor chorionic villi.

Early diagnosis and treatment can improve the prognosis ofgalactosemia .Elimination of galactose from diet reversesgrowth failure and renal and hepatic dysfunction.

On long term follow up , patients manifest ovarian failure withprimary or secondary amenorrhea, hypergonadotrophichypogonadism , decreased bone mineral density,developmental delay with impaired motor function and balance.

Pentalogy of Fallot comprises of Tetralogy of Fallot (VSD, Rightventricular outflow tract obstruction, right ventricularhypertrophy,overriding of aorta) and atrial septal defect (ASD)or patent foramen ovale(PFO)9. Pentalogy of Fallot, althoughrare but contributes for 3.7 % of all CHD. There may be co-existent cardiac paraganglioma with Pentalogy of Fallot.Casereports of association of galactosemia with Pentalogy of Fallot,as in our case, is not found in medical literature.

References :

1. Schweitzer-Krantz S. Early diagnosis of inherited metabolicdisorderstowards improving outcome: the controversialissue of galactosaemia.Eur J Pediatr 2003; 162 (Suppl 1): S50-S53.

2. Bosch AM. Classical galactosaemia revisited. J InheritMetab Dis2006; 29: 516-525.

3. Kaufman FR, Bride-Chang C, Manis FR, Wolff JA, NelsonMD.Cognitive functioning, neurologic status and brainimaging inclassical galactosemia. Eur J Pediatr 1995;154: S2-S5.

4. Bosch AM, Grootenhuis MA, Bakker HD, Heijmans HS,WijburgFA, Last BF. Living with classical galactosemia:health-relatedquality of life consequences. Pediatrics 2004;113: e423-e428.

5. de Jongh WA, Bro C, Ostergaard S, Regenberg B, OlssonL,Nielsen J. The roles of galactitol, galactose-1-phosphate,and

phosphoglucomutase in galactose-induced toxicityinSaccharomyces cerevisiae. Biotechnol Bioeng 2008; 101:317-326, doi: 10.1002/bit.21890.

6. Clague A, Thomas A. Neonatal biochemical screening fordisease.Clin Chim Acta 2002; 315: 99-110.

7. Berry GT, Palmieri M, Gross KC, Acosta PB, HenstenburgJA,Mazur A, et al. The effect of dietary fruits and vegetableson urinarygalactitol excretion in galactose-1-phosphate uridyltransferasedeficiency. J Inherit Metab Dis 1993;16:91-100.

8. Gitzelmann R. Formation of galactose-1-phosphate fromuridinediphosphate galactose in erythrocytes from patientswithgalactosemia. Pediatr Res 1969; 3: 279-286.

9. Topol EJ, Califf RM. Textbook of cardiovascular medicine.Lippincott Williams & Wilkins. (2007).


Acute Hemiplegia of Childhood – An Unusual Etiology

Rituparna Das, Madhumita Nandi, Gopal Pandey, Rajarshi Bose, Syamal Kumar Banerjee

Department of Pediatric Medicine, NRS Medical College, Kolkata

Correspondance : Dr Rituparna Das, Department of PediatricMedicine, NRS Medical College, Kolkata.

Abstract:

Acute hemiplegia of childhood is most often due to cerebrovascular disorders like arterial ischaemic stroke and cerebral sinovenousthrombosis. Acute onset complete hemiplegia due to SOL like multiple tuberculoma is rare. Moreover, multiple tuberculoma isgenerally seen in immunocompromised conditions like HIV. Here we report a case of acute onset right sided complete hemiplegiain an immunocompetent child due to multiple tuberculoma of brain.

Key words: complete hemiplegia; multiple tuberculoma; CNS tuberculosis.

Introduction :

Central nervous system tuberculosis which is caused byhematogenous spread of Mycobacterium tuberculosis maymanifest as meningitis, cerebritis and tuberculous abscessesor tuberculomas. It occurs in approximately 1% of all patientswith TB, mostly affecting children and immunocompromisedpatients1,2. Multiple tuberculoma in an immunocompetent hostis a very rare presentation of CNS tuberculosis and that toopresenting as acute onset complete hemiplegia without anyevidence of primary pulmonary infection is even a rarer clinicalscenario.

Case report:

An 11 year old school going boy presented to the PaediatricEmergency of NRS Medical College, Kolkata with right sidedcomplete hemiplegia. Child was apparently well 6 days back.After getting up from bed, child noticed weakness of right lowerlimb which gradually progressed over next 48 hrs to involveright upper limb and lower part of right half of the face. Therewas no history of fever or convulsion at the onset or alteredsensorium during the course of illness.

There was no past history of headache, fever , vomiting orchronic cough. The child was completely immunised as pernational immunisation schedule, and BCG scar was present.There was no history of weight loss.No history of contact withtuberculosis was obtained.

CNS examination revealed normal higher function and normal

speech.No sign of meningeal irritation was found. Upper motorneuron type of facial nerve palsy of right side was present.Power of right upper limb and lower limb was 2/5.Power ofboth left upper and lower limb was 5/5. Tone was increased inboth upper and lower limb of right side and normal in left side.Knee jerk was brisk on right side and normal on left side. Plantarwas extensor on right side. Rest of CNS examination was withinnormal limits.

Complete blood counts, electrolytes, blood sugar and renalfunction tests were within normal limits. Chest X ray was normal.Mantoux test was negative. HIV 1 and 2 were non reactive.Sputum for AFB was negative. Opthalmoscopic examinationrevealed mild papilloedema.MRI brain revealed abnormal well-defined peripherally enhancing discrete to conglomeratehypointense multiple cystic lesions in brain parenchyma withmild to moderate perifocal oedema suggestive oftuberculoma(Fig 1,2). MR Angiogram was normal.MRSpectroscopy showed no significant elevated choline(cho)peak, or reduced N-acetyl aspartate(NAA) peak, elevated cho/creatine or cho/NAA ratios to suggest any neoplastic lesion.Elevated lipid/lactate peak noted in the lesion in low TE imageswith lactate inversion in moderate TE images which weresuggestive of tubercular granulomatous disease.

The child was put on category I ATDs under DOTS ,inj.dexamethasone and oral acetazolamide. Child graduallyimproved over the next 5-6 days starting from right lower limband then the right upper limb. Facial nerve palsy was the lastto recover. At discharge power of right upper limb was 4/5 and

Case Report


lower limb was 5/5.Oral prednisolone which was given ondischarge was tapered gradually over next six weeks. Duringfollow-up the child had no residual weakness of limbs at 3months. Treatment was continued with anti-tubercular drugsto complete the course.

Fig 1. MRI bran showing multiple tuberculomas

Discussion

Tuberculosis is quite rampant in developing countries likeindia.CNS tuberculosis is a life threatening complication causeddue to hematogenous dissemination of the bacilli tobrain.Tuberculomas usually present with headache, fever andconvulsions3,4. In a study conducted in Sudan, commonestpresentation of multiple intracranial tuberculomas wereheadache(100%) and generalised convulsion(68.7%)5. A casereport in 2012 showed that multiple brain tuberculomas canpresent with prolonged non specific symptoms and diagnosisof such peculiar presentations is very important6. A report byGupta A et al described a case of an immunocompetent hostwith a past history of pulmonary tuberculosis, presenting withheadache and generalized weakness and later was diagnosedas a case of multiple tuberculoma brain. Miliary CNSTuberculoma presenting as acute onset complete hemiplegiawithout evidence of primary pulmonary infection is a very rarescenario in an immunocompetent host. In our case, the childpresented with acute onset hemiplegia mimicking childhoodstroke. Diagnosis of tuberculoma is based on clinical andradiological findings and response to ATDs. Patholgical autopsyis confirmatory. CT was reported to have a sensitivity of 100%and specificity of 85.7% thus it indicated a need for furtheranalysis with MRI that should be the technique of choice and/or histological diagnosis7. In the index case, the diagnosis wasclinical and based on MRI brain and MR Spectroscopy findingsand dramatic response to antitubercular drugs. Surgery isreserved for patients with mass effect and paradoxicalenlargement.

The purpose of reporting this case is to make our fellowclinicians aware of the possibility of multiple tuberculoma as acause of stroke even in an immunocompetent child. Earlyrecognition and timely anti-tubercular drugs can prevent muchof morbidity and mortality.

Fig 2. MR spectroscopy showing lipid peak

Reference :1. Kioumehr F, DadsetanMR,Rooholamini SA, Au A.Central nervous

system tuberculosis: MRI.Neuroradiology 1994; 36: 93-962. Alkhani A,Otaibi FA,Cupler EJ,Lach B.Miliary tuberculosis of the

brain: Case report.Clinical neurol neurosurgery 2006; 108:411-414

3. Lee JE, Ling C, Kosmalski MM, Hulseberg P, Schreiber HA,Sandor M, et al.Intracerebral mycobacterium bovis bacillicalmette guerin infection induced immune responses in the CNS.J Neuroimmunol 2009; 213: 112-122.

4. ThackerMM, Puri AI. Concurrent intra-medullary and intra –cranialtuberculomas. J Postgrad Med 2004; 50: 107-109.

5. Idris MN, Sokrab TE, Arbab MA, Ahmed AE, El RAsoul H, Ali Set al. Tuberculoma of the brain:a series of 16 cases treated withantitubercular drugs, Int J tuberc Lung Dis 2007; 11: 91-95.

6. Togha M, Sahraian MA, Hosseini SJ, Haddadi A. Braintuberculoma: Report of a case presented with prolongednonspe¬cific symptoms and multiple brain tuberculoma. Iran JNeurol. 2012;11:34–5.

7. Gupta A, Singhal S. A case of multiple tuberculomas in brainpre¬senting as hemiparesis. Asian Pac J Trop Dis. 2011;1:83–4.


Introduction

The way in which a pediatric practitioner applies his/herknowledge as well as resources at hand to provide healthcare services is an important determinant of quality of care.This is often held ransom to the differential understanding ofprofessional responsibility among practitioners. Whimsicalimplementation of diverse theoretical therapeutic alternativesthat too with anecdotal or at times no evidence can onlycompromise the quality of care offered. Accumulatingevidence suggests that access to poor quality of healthcareincreases child morbidity and mortality1 and there aremultitudes of problems both commonplace and rare butimportant, which are often improperly managed andaddressed by pediatricians.

Fever and febrile seizure: unnoticed aspects

Fever uncontrolled by paracetamol is a common anddisturbing issue to many. Current evidence does not showany significant benefit obtainable from sponging which on thecontrary may cause discomfort to the child2. It is ironical tosee a child shivering due to the tepid water spongingadministered rather than the fever itself. Similarly, routine useof anticonvulsants in simple febrile seizure is not advisable,as is often practiced3.

Common cold, asthma and mild pneumonia: overlookedissues

Cough remedies in the form of variously concocted

antitussives and mucolytics are often prescribed for childrenirrespective of age while current evidence shows that they areno better than placebo in children with acute cough, let alonethe risk of adverse effects4. Multiple lineages of evidencesuggest that oral salbutamol is ineffective in the treatment ofchildhood asthma and its use is associated with increased riskof adverse effects compared to the inhaled dosage forms5. Inspite of this, oral bronchodilator formulations are still usedrampantly. Mild pneumonia according to existing evidence istreatable by oral amoxicillin alone6. Unfortunately many of ourcolleagues cannot resist themselves from unnecessarilyprescribing broader spectrum antibiotics including oral thirdgeneration cephalosporins. There are several other instancesof antibiotic abuse and we are in immediate need of nationalscale antibiotic stewardship programs.

Transfusion practices

Blood component therapy is another area where wide rangingdiscrepancies with existing evidence based guidelines arenoticeable. Indications of transfusing whole blood are currentlyvery limited and hence should not be used indiscriminately.FFP transfusion in sepsis is of no use and it has got limitedapplicability even in the scenario of hepatocellular failure7,8.

Acute diarrhea: is it better to avoid probiotics?

Acute infectious diarrhea of childhood has rehydration therapyas the mainstay of treatment. Oral zinc as an adjuvant therapyto rehydration has been recommended by WHO, the rationalebeing an associated increased uptake of ORS and reducedseverity and duration of illness. Probiotics, however, are adebatable modality of treatment. Efficacy studies showing

Uniformity of Practice: National Guidelines AndAn Inclination To Follow Them Seem To Be The Need of The Hour

T Chatterjee*, S Bhattacharyya***In-charge, NICU, RSV Hospital, **Registrar, NICU, RSV Hospital, Kolkata

ABSTRACT:

Evidence based scientific management of any disease process ensures maximum probability of obtaining desired outcome. Justas consensus guidelines are necessary for both common and challenging clinical scenarios, a soulful intent to follow those is alsoneeded for uniformity of practice to prevail. In this review, we have taken up some of the frequently encountered scenarios in dayto day pediatric practice and have tried to pin point the acts of omission we often commit and have tried to indicate the appropriatemeasures as well.

Keywords: Intention, Pediatrics, Consensus, Guidelines

Correspondance : Saugata Bhattacharyya, NICU, RSV Hospital Pvt.Ltd, Kolkata. Email : [email protected]

Issues


strain related benefit are mostly from the developed countriesand extrapolation of those results to our settings where normalgut colonization patterns are different is bound to be faulty9,10.

Neonatal practice: we need to remain vigilant

Neonatal practice is also not bereft of such misjudgments.Resuscitation protocol followed is often found to be againstavailable evidence. There is currently no role of routine oro-nasal suctioning of the neonate either on part of the gynecologistor the pediatrician. T-piece positive pressure ventilation shouldbe preferred over AMBU bag when needed. It has now becomemandatory to assess oxygenation during resuscitation by pulseoximetry instead of color. Persistent cyanosis in spite of a heartrate above 100 and/or labored breathing should prompt deliveryroom CPAP11. These points are commonly overlooked and faultypractices indulged. In case of preterm infants enteral feeds areoften delayed in fear of probable NEC. Accumulating evidencesuggests that there is no increased risk of NEC with early enteralfeeding in this group. Moreover, early feeding preventscholestasis and sepsis and also shortens duration of hospitalstay apart from bypassing the ill effects of parenteral nutrition12.Similarly, another neglected part of newborn care is provisioningof developmentally supportive care for premature babies.

Isn’t it time to look at the cost-benefit ratio? Gaps in training

Irrational and unnecessary investigations have becomeuniversal and partly reflect the lacuna in post-graduate trainingprograms of not properly instructing pediatric residents abouthow to treat in a cost effective manner.

Breastfeeding: time to change hospital protocols

The IYCF guidelines 2010 clearly state the need of earlyinitiation of breastfeeding, preferably within the first hour afterdelivery13. Hospitals commonly delay initiation especially in caseof babies born by caesarean section giving excuses of inabilityof the mother to breastfeed in the immediate post-operativephase. Moreover, unnecessary transfer to hospital nurseryinstead of bedding-in is another problem faced in some facilities.The resultant loss of colostrum feeds is a significant issue tobe solved and for that efforts must come from the obstetricianas well as the pediatrician.

Conclusion

A glaring example of non-uniformity in pediatric practice in ourcountry today is the difference that exists between the IAP andthe national immunization schedules. Both may be correct attheir standpoints but it creates a lot of confusion among patientsand practitioners alike. The scenarios discussed reflect only aminiscule fraction of the totality of issues where we need to bemore rational and evidence based in our practice but moreimportantly point towards the necessity of consensus basedguidelines. Moreover, it cannot be overemphasized thatuniformity of practice, is the only conceivable way to providehealthcare with increased likelihood of achieving desiredoutcome which in turn is only possible if there is a whole heartedeffort from our end to follow such uniformly applicable nationalguidelines for most of the common as well as clinicallychallenging scenarios.

References:

1. BansalCP. Improving quality of pediatric care in India: A call foraction. Indian Pediatrics. 2013;50:269-70.

2. Thomas S, Vijaykumar C, Naik R, Moses PD, Antonisamy B.Comparative effectiveness of tepid sponging and antipyretic drugversus only antipyretic drug in the management of fever amongchildren: a randomized controlled trial. Indian Pediatr. 2009Feb;46(2):133-6.

3. WHO. Management of febrile seizures [Internet]. 2012 [citedJanuary 22 2015]; Available from: http://www.who.int/mental_health/mhgap/evidence/epilepsy/q3/en/.

4. Mathew JL. Cough syrups--do they work in acute cough? IndianPediatr. 2009 Aug;46(8):703-6.

5. Herd D. Oral versus inhaled salbutamol for acute paediatricasthma [Internet]. 2011 [cited January 22 2015]; Available from:http://www.bestbets.org/bets/bet.php?id=2283.

6. Mehta PN. Choosing antibiotics for community acquiredpneumonia. Indian Pediatr. 2003 Oct;40(10):958-64.

7. Bhatia V, Bavdekar A, Yachha SK. Management of acute liverfailure in infants and children: consensus statement of the

pediatric gastroenterology chapter, Indian academy of pediatrics.Indian Pediatr. 2013 May 8;50(5):477-82.

8. Jain R, Jose B, Coshic P, Agarwal R, Deorari AK. Blood andblood component therapy in neonates. Indian J Pediatr. 2008May;75(5):489-95.

9. Faure C. Role of Antidiarrhoeal Drugs as Adjunctive Therapiesfor Acute Diarrhoea in Children. International Journal ofPediatrics. 2013;2013:1-14.

10. Bhatnagar S, Alam S, Gupta P. Management of acute diarrhea:from evidence to policy. Indian Pediatr. 2010 Mar;47(3):215-7.

11. Kattwinkel J, Perlman JM, Aziz K, Colby C, Fairchild K, GallagherJ, et al. Neonatal resuscitation: 2010 American Heart AssociationGuidelines for Cardiopulmonary Resuscitation and EmergencyCardiovascular Care. Pediatrics. 2010 Nov;126(5):e1400-13.

12. Early enteral feeding strategies for very preterm infants: currentevidence from Cochrane reviews. Arch Dis Child Fetal NeonatalEd. 2013 Nov;98(6):F470-2.

13. Rajeshwari K, Bang A, Chaturvedi P, Kumar V, Yadav B,Bharadva K, et al. Infant and young child feeding guidelines:2010. Indian Pediatr. 2010 Dec;47(12):995-1004.


Life Style Diseases of The Young

T Choudhuri*, A K Sethi**, D Bandyopadhyay***, S Chattopadhyay****, Joysima Gupta*****, P S Mitra*******Chief Specialist II i/c Ped/BRSinghHospital/E.Rly, **Addl.Chief Health Director/Ped/GardenReachCentralHospital/S.E.Rly, ***Addl.Chief

Health Director/Ped /BRSinghHospital/E.Rly, ****Sr.Divl.Med Officer/Ped/KanchraparaWorkshopHospital/E.Rly, *****Sr.Divl.Med Officer/Ped/MetroRlyHospital, ******Sr.Divl.Med. Officer/AsansolRlyHospital/E.Rly.

Correspondance : D Bandyopadhyay, Addl.Chief Health Director,B R Singh Railway Hospital.Email : [email protected]

Health is a common theme in most cultures. An understandingof health is the basis of all health care. Health determinant ismulti-factorial. Both individual and social factors may be healthpromoting or deleterious.

In recent years, India has managed to control communicablediseases like malaria, cholera and polio. However, the nationnow has to deal with a new breed of diseases like diabetes,cardiovascular ailments, obesity and mental illness. Coupledwith a sedentary urban lifestyle, increased alcoholconsumption and smoking, use of electronic gadgets , theurban youth has become prone to the aforementioneddiseases.

It is an established fact that environmental factors- housing,water supply, psychosocial stress and family structure -have adirect impact on health. Health being the fundamental humanright, is basically an individual responsibility. A recent trend inhealth care is self care. It refers to those activities individualsundertake in promoting their own health, preventing their owndisease. These activities are undertaken without professionalassistance, e.g. awareness related to diet, sleep, exercise,weight, alcohol, smoking, drugs, personal hygiene, cultivationof healthful habits and lifestyle, undergoing selective medicalscreening, accepting immunization, reporting early when sick,etc. Our youth population rarely get proper guidance fromtheir parents, relatives and schools in this regard.

Gorging on junk food, addiction to television and aversion foroutdoor activities are the major reasons why kids aredeveloping these diseases. We are on the alert now and afterhaving done a preliminary assessment of child’s health, havefound out that about 20% of urban kids have variouscombinations of obesity, insulin resistance, hypertension,PCOD (in females), potential to develop heart ailments andmental illness. Such kids are being monitored constantly andthere's a constant dialogue with parents of such children. Insimilar studies by scientists among the rural counterpart,incidence ranged from 0.8% to 2.7%.

In the present day society there has been a marked deviationin the cultural values, customs, habits, beliefs, attitudes, morals,education, community life, health services, social and politicalideologies. These have led to feelings of anxiety, depression,anger and frustration; sometimes these emotional states areleading to physical symptoms of headache, palpitation andconversion reactions. In the long run these may lead topsychosomatic disorders such as bronchial asthma,hypertension, coronary heart disease, mental disorders andsocially deviant behaviour like suicide, crime, violence and drugabuse.

The detection of risk factors should be considered a prelude toprevention or intervention. WHO promotes to identify preciselythe "risk groups" or "target groups", e.g. at risk mothers, at riskinfants, at risk families, in the population by certain definedcriteria and direct appropriate action to them first e.g. populationapproaches to prevention of primary hypertension include areduction in obesity, reduced sodium intake, and an increasein physical activity through school and community-basedprograms. Many adult health problems like obesity andhypertension have their origin in childhood because ofunhealthy lifestyles as mentioned before. This type ofintervention is through individual and mass education. It needsa strong political will to achieve well planned targets.

Hospital settings are for secondary prevention, i.e. earlydiagnosis and treatment. It is an imperfect tool in the control ofthis epidemic . Secondary prevention is expensive and lesseffective . In the long run human health and happiness anduseful longevity will be achieved with more suffering throughsecondary prevention than through primary prevention e.g. asystematic approach for treatment of T2DM can beimplemented according to the natural course of the disease,including adding insulin when hypoglycemic oral agent failureoccurs. Nevertheless, lifestyle modification (diet and exercise)is an essential part of the treatment regimen and consultationwith a dietician is usually necessary, but is ignored. Thesechildren often come from a household environment with apoor understanding of healthy eating habits. Commonlyobserved behaviours include skipping meals, heavy snacking,

Issues


excessive daily television viewing, video game playing, andcomputer use. Treatment in these cases is challenging andmay not be successful unless the entire family is convinced.

The crux of the problem has to be tackled through healtheducation, environmental modification, nutritional interventionsand lifestyle modification. School health service is a powerfulmeans of improving community health. There is a need tointroduce a health card for every child. Periodic monitoring ofkids' weight, documenting the results of exercise on bloodpressure, etc. and related investigations can avert untowardoutcome. Schools should keep vigil on obese children's tiffinboxes. School canteens need to be banned from stocking chips,aerated drinks and junk food. TV commercials promotingunhealthy food habits are to be censored.

A curriculum-based education on healthy lifestyle training may

Reference:1. Park's Text Book of Preventive And Social Medicine; K.Park;

22nd edition 2013.2. Nelson Text Book Of Pediatrics; 19th Edition; 2013.3. http://www.oecd.org/document/11/0,3746.html.OECD. 20124. Pediatr Clin North Am 52:1689–1703, 20055. www.japi.org/may2007/E-323.pdf6. http://pib.nic.in/newsite/efeatures.aspx?relid=102567

be imparted to all children to build a healthy future generation.Regular screening of school students are needed not only toidentify health problems but also to instil awareness amongthem regarding lifestyle disease control. But primordial andprimary prevention of lifestyle diseases cannot be limited tointervention done at schools alone, the change has to startand be promoted by the parents at home as well.

Methods:

Medline and Embase from 1996 to 2013 were used as datasources. Of 159 identified studies, 48 studies of diagnosticaccuracy of GAS RADTs using throat culture on blood agar asa reference standard were selected. Bivariate random-effectsregression was used to estimate sensitivity and specificity with95% confidence intervals (CIs). Additional meta-analyses wereperformed for pediatric data.

Results:

A total of 60 pairs of sensitivity and specificity from 48 studieswere included. Overall summary estimates for sensitivity andspecificity of RADTs were 0.86 (95% CI 0.83 to 0.88) and 0.96(95% CI 0.94 to 0.97), respectively, and estimates for pediatricdata were similar. Molecular-based RADTs had the bestdiagnostic accuracy. Considerable variability exists inmethodology between studies. There were insufficient studiesto allow meta-regression/subgroup analysis within each testtype.

Conclusions:

RADTs can be used for accurate diagnosis of GAS pharyngitisto streamline management of sore throat in primary care.RADTs may not require culture backup for negative tests inmost low-incidence rheumatic fever settings. Newer moleculartests have the highest sensitivity, but are not true point-of-caretests.

Family acceptability of school-based echocardiographicscreening for rheumatic heart disease in a high-riskpopulation in New Zealand.Perelini F1, Blair N, Wilson N, Farrell A, Aitken A.J Paediatr ChildHealth. 2015 Mar 10. doi: 10.1111/jpc.12829.

Aim:

Echocardiographic screening for rheumatic heart disease hasbeen piloted in high-risk areas in New Zealand andinternationally, and fulfils most of the criteria for a targetedscreening programme. The question of acceptability ofrheumaticheart disease screening has not been assessed, andthe aim of our study was to assess parental acceptability of aschool-based echocardiographic screening programme in ahigh-risk population in New Zealand.

Methods:

A post-screening questionnaire was developed to surveyparents of children who underwent echocardiographicscreening. The families of 34 children with abnormal scanresults and a sample of 80 children with normal scan resultswere surveyed by phone within 4 months of screening.

Results:

Positive results were seen in all survey questions in both normaland abnormal scan groups. All families were supportive of anongoing screening programme. Of children with abnormalresults, 62% of their parents reported that they would treat theirchild differently; however, all responses were positive health-promoting outcomes.

Conclusion:

The study showed strong positive support for school-basedechocardiographic screening by a community with high acuterheumatic fever incidence. The study did not detect any short-term negative effects in those with abnormal results. The surveyresult shows family and community support for theestablishment of echocardiographic screening programmes inhigh acute rheumatic fever areas provided there is adequateinfrastructural support.

Continued from page 120


Pulse oximetry screening for congenital heart defects innewborn infants: an evaluation of acceptability to mothers

Rachael Powell,,Helen M Pattison,,AbhayBhoyar, Alexandra TFurmston, Lee J Middleton, Jane P Daniels, Andrew K Ewer Arch DisChild Fetal Neonatal Ed 2013;98:F59-F63

Objective : To assess maternal acceptability of pulse oximetryscreening for congenital heart defects and to identify factorspredictive of participation in screening.

Design and setting : A questionnaire was completed by across-sectional sample of mothers whose babies were recruitedinto the PulseOx Study which investigated the test accuracy ofpulse oximetry screening.

Participants : A total of 119 mothers of babies with false-positive (FP) results, 15 with true-positive and 679 with true-negative results following screening.

Main outcome measures : Questionnaires included measuresof satisfaction with screening, anxiety, depression andperceptions of test results.

Results : Participants were predominantly satisfied withscreening. The anxiety of mothers given FP results was notsignificantly higher than that of mothers given true-negativeresults (median score 32.7 vs 30.0, p=0.09). White British/Irishmothers were more likely to participate in screening, with adecline rate of 5%; other ethnic groups were more likely todecline with the largest increase in declining being for BlackAfrican mothers (21%, OR 4.6, 95% CI 3.8 to 5.5). White Britishmothers were also less anxious (p<0.001) and more satisfied(p<0.001) than those of other ethnicities

Conclusions : Pulse oximetry screening was acceptable tomothers and FP results were not found to increase anxiety.Factors leading to differences in participation and satisfactionacross ethnic groups need to be identified so that staff cansupport parents appropriately.

Propranolol for infantile haemangiomas: single centre

experience of 250 cases and proposed therapeutic protocol

Lea Solman, AmeraMurabit, MariaGnarra, John I Harper, Samira BSyed, Mary Glover Arch Dis Child 2014;99:1132–1136

Objective: To assess the safety and efficacy of systemicpropranolol for the treatment of complicated infantilehaemangiomas.

Design:Retrospective review of case notes of paediatricpatients treated with propranolol for complicated infantilehaemangiomas.

Setting: Tertiary care children’s hospital.

Patients: All paediatric patients with complicated infantilehaemangiomas who commenced treatment with propranololfrom July 2008 to December 2011 and have completedtreatment for at least 3 months.

Results:250 patients were treated with propranolol; 34.4% werepremature and 5.6% postmature.

Indications for propranolol included: vision compromise(42.0%), bleeding and/or ulceration (30.4%) airway obstruction(8.8%), feeding difficulty (8.4%), risk of permanent disfigurement(4.4%) and other (6%) (nasal obstruction, auditory canalobstruction, large haemangioma, compression of neck structureand spinal cord). Median age at beginning of treatment was4.5 months. Median age at end of treatment was16.7 months.Median length of therapy was 11.8 months. Adverse effects(such as wheezing, worsening of ulceration, sleep disturbance,diarrhoea) occurred in 38 patients (15.2%), leading tomodifications in management in 26 patients (10.4%). 240patients (96%) had good to excellent response to treatment.20 patients (8%) experienced regrowth of the haemangiomaon cessation of propranolol and six patients (2.4%) requiredpropranolol to be restarted.

Conclusions:In appropriately selected patients, propranololis a safe and effective treatment for infantile hemangiomas

Evidence

Arun Manglik(Dr Arun Kr Manglik, Associate Editor has taken responsibility to apprise us with updates regularly and here are his collection)

Correspondance : Arun K Manglik, Consultant Pulmonologist,Kolkata. Email : [email protected]

Update


Does Kawasaki Disease have an etiologicalbackground?

Proceedings of the National Academy of Sciences: Vol 111, No 22

Tropospheric winds from northeastern China carry theetiologic agent of Kawasaki disease from its source toJapan

Xavier Rodóa,b,1, Roger Curcollb, Marguerite Robinsonb, JoanBallesterb,c, Jane C. Burnsd, Daniel R. Cayane,f, W. Ian Lipking,Brent L. Williamsg, Mara Couto-Rodriguezg, YosikazuNakamurah,RiteiUeharah, Hiroshi Tanimotoi, and Josep-Anton Morguíb

Kawasaki disease (KD), the leading cause of acquired heartdisease in children worldwide, has remained a mystery for morethan 40 y. No etiological agent has yet been identified. By usingsimulations with the flexible particle dispersion model fromdifferent Japanese cities from each single high (low) KDincidence day, the source region KD is retrieved in cerealcroplands in northeastern China.

Evidence indicates that the densely cultivated region ofnortheastern China acts as a source for the wind-borne agentof Kawasaki disease (KD). KD is an acute, coronary arteryvasculitis of young children, and still a medical mystery aftermore than 40 y. Residence times from simulations with theflexible particle dispersion model were used to pinpoint thesource region for KD. Simulations were generated fromlocations spanning Japan from days with either high or low KDincidence. The postepidemic interval (1987–2010) and theextreme epidemics (1979, 1982, and 1986) pointed to the samesource region.

Results suggest a very short incubation period (<24 h) fromexposure, thus making an infectious agent unlikely. Samplingcampaigns over Japan during the KD season detected majordifferences in the microbiota of the tropospheric aerosolscompared with ground aerosols, with the unexpected findingof the Candida species as the dominant fungus from aloftsamples (54% of all fungal strains). These results, consistentwith the Candida animal model for KD, provide support for theconcept and feasibility of a windborne pathogen. A fungal toxincould be pursued as a possible etiologic agent of KD, consistentwith an agricultural source, a short incubation time andsynchronized outbreaks. This study suggests that the causativeagent of KD is a preformed toxin or environmental agent ratherthan an organism requiring replication. The authors thuspropose a new paradigm whereby an idiosyncratic immuneresponse, influenced by host genetics triggered by anenvironmental exposure carried on winds, results in the clinicalsyndrome known as acute KD.

Applying Manual Pressure before Benzathine PenicillinInjection for Rheumatic FeverProphylaxis Reduces Painin Children.

Derya EY, Ukke K, Taner Y, Izzet AYPain ManagNurs. 2014 Dec 2.pii:S1524-9042(14)00144-1.

The purpose of this study was to evaluate the efficacy ofapplying manual pressure before benzathine penicillin injectionand compare it with the standard injection technique in termsof reducing discomfort in children with rheumatic heart diseasegrouped by age and gender. This was a single-blind,randomized, crossover study. Fifty-one patients aged 7.1-19.9years were recruited for this study carried out in the pediatriccardiology outpatient clinic. Twenty-nine were girls (56.9%).All subjects received an intramuscular injection of benzathinepenicillin with manual pressure to one buttock or with thestandard technique to the other buttock at 3-week intervals.The two techniques were used randomly. The subjects wereblinded to the injection technique and a visual analogue scalewas used after the procedure. Findings demonstrate thatchildren experienced significantly less pain when they receivedinjections with manual pressure (1.3 ± 0.9) compared with thestandard injection (4.4 ± 1.6) technique. The perceived injectionpain was negatively related to the age of the children in bothtechniques. Compared with boys, girls felt more pain, but thedifference between each technique group according to genderwas negligible. The application of manual pressure reducespain in children under the stress of repeated intramuscularinjections, which supports the suggestion that it should be usedin routine practice. Manual pressure to the injection site is asimple, pain-reducing technique. Implementing this techniquein routine practice may also promote adherence to theprophylaxis regimen, especially in children.

Rapid diagnostic tests for group A streptococcalpharyngitis: a meta-analysis.

Lean WL, Arnup S, Danchin M, Steer ACPediatrics. 2014Oct;134(4):771-81. doi: 10.1542/peds.2014-1094.

BACKGROUND AND OBJECTIVE:

Effective management of group A streptococcal (GAS)pharyngitis is hindered by impracticality of the gold standarddiagnostic test: throat culture. Rapid antigen diagnostic tests(RADTs) are a promising alternative, although concerns abouttheir sensitivity and specificity, and variation between testmethodologies, have limited their clinical use. The objective ofthis study was to perform a systematic review with meta-analysis of the diagnostic accuracy of RADTs for GASpharyngitis.

Continued to page 118


The Child and Newborn - WBAPwbap.in/data/Child 18.3.4.pdfThe Child and Newborn West Bengal Academy...

Documents

Transcript of The Child and Newborn - WBAPwbap.in/data/Child 18.3.4.pdfThe Child and Newborn West Bengal Academy...