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  • Pediatr Nephrol (2U00)


    Joseph T. Flynn

    Neonatal hypertension: diagnosis and management

    IPNA 2()()0

    Received: 20 April 1999 / Revised: 2 August 1999 / Accepted: 13 August 1999

    Abstract Hypertension in the term or preterm neonatemay be seen in up to 2% of all infants cared for in themodern neonatal intensive care unit. Although the defini-tion of hypertension in this age group has not been cotn-pleteiy standardized, recent studies have provided newnormative data that may be used to facilitate identifica-tion of such infants. Common causes of hypertcn.sion inneonates include thromboembolic events related to um-bilical catheterization. congenital problems such as aor-tic coarctation. staictural renal malformations and reno-vascular disease, as well as acquired renal disease andcertain medications. A careful history and physical ex-amination will usually identify the probable cause innujst cases without Ihc need for extensive laboratory orradiologic testing. Therapy of neonatal hypertensionshould be tailored to the severity of the blood pressureelevation, and to the underlying cause of hypertension asappropriate. A wide range of therapeutic agents are nowavailable for management of neonatal hypertension inboth the acute and chronic settings. In most cases hyper-tension will resolve, but some infants may require pro-longed treatment.

    Key words HypertensionAntihypertensive therapy

    Neonates Premature infants


    Hypertension as a clinical problem in newborn infantswas first recognized in the 1970s [1]. However, recentadvances in our ability to identify, evaluate and care forhypertensive infants, coupled with advances in the prac-

    J. T. FlynnDivision oi Pediatric Nephrology,Depanmenl of Pediatrics and Communicable Diseases,University of Michigan. Motl F6865 - Box 0297.150. Simpson Rd. East. Ann .Arhor. Ml 48109, USAe-mail: jttiynn@uniich.eduTel.: -^1-734-3321007, Fax: -* 1-734-7636997

    tice of neonatology in general, have lead to an increasedawareness of hypertension in modem neonatal intensivecare units (NICUs). Since most hypertension in infants isrelated to renovascular or renal parenchymal disease |2.3|, the evaluation and management of neonatal hyperten-sion frequently requires the expertise of a pediatric neph-rologist. This review will focus on Ihe differential diag-tiosis of hypertension in the neonate. the optimal diag-nostic evaluation, and both acute and chronic antihyper-tensive therapy.

    Definition and incidence of neonatal hypertension

    Defining what is considered a normal blood pressure innewborn infants is a complex task. Just as blood pressurein older children has been demonstrated to increase withincreasing age and body size |4], studies in both termand preterm infants have demonstrated that blood pres-sure in neonales increases with both gestational andpostconceptual age. as well as with binh weight l ^ - l l ] .Extremely useful data in this regard has recently beenpublished by Zubrow et al. 191, who prospectively ob-tained serial blood pressure meastirements from 695 in-fants admitted to several NICUs in a large metropolitanarea over a period of 3 months. From these data, theywere able to define the mean plus upper and lower 95%confidence limits for blood pressure for the infants stud-ied; their data clearly demonstrated increases in bloodpressure with increasing gestational age, binh weightand postconceptual age (Figs. 1-3). Based on these data,we would consider an infant's blood pres.sure to be ele-vated if it fell above the upper limit of the 95% confi-dence interval for infants of similar gestational or post-conceptual age and size.

    For older infants found to be hypertensive followingdischarge from the NICU 112|. the percentile curves gen-erated by the Second Task Force (Fig. 4) [13) appear tobe the most useful. Based on serial hlood pressure mea-surements obtained from nearly 13.000 infants, thesecurves allow blood pressure to be characterized as nor-

  • 333

    90-80-70-60-50-40-30-20-10-0 - V A

    upper 95% CL


    Lower 95% CL.








    750 1.250 1.750 2,250 2.750 3,250 3.7501.000


    CT 60-

    I 50-a. 40-m^ 30-oS 20-Q lOH

    1.500 2.000 2.500 3.000 3.500 4.000

    Birth weight (kg)

    Upper 95% C.L

    Lower 95% C.L.

    750 1.250 1.750 12.250 2.750 | 3.250 3.7501.000 1.500 2.000 2.500 3.000 3.500 4.000

    Birth weight (kg)

    I'lg. I Lineiir regres.sion of mean systolic and diaslolic bloodpressures by birth weight on day I of life, with 95% confidencelimits (upper and lower dashed lines). Reproduced from Ziibrowet al. [9|, with permission from the copyright holders, StocktonPress, a division of Nature America

    Upper 95% CL

    100-]Ol 90^ 80g 70a. 60- 50^ 40^ 30b 20


    Lower 95% CL,

    24 26 28 30 32 34 36 38 40 42 44 46

    Post conceptional age (weeks)

    Upper 95% C L

    Lower 95% C L

    24 26 28 30 32 34 36 38 40 42 44 46

    Post conceptional age (weeks)

    Fig. 3 Linear regression of mean systolic and diastolic bloodpressures by postconceptual age in weeks, with 95% confidencelimits {upper and lower dasiwd lines). Reproduced from Zubrowet ai. [9], with permission from tbe copyright holders. StocktonPress, a divi.sion of Nature America




    Lower 95% CL.

    22 24 26 28 30 32 34 36 38 40 42

    Gestational age (weeks)

    Upper 95% C.L.

    22 24 26 28 30 32 34 36 38 40 42Gestational age (weeks)

    Fig. 2 Linear regression of mean systolic and diastolic bloodpressures hy gestational age on day 1 of life, with 95'^ confidencelimits {upper and lower dashed lines). Reproduced from Z.uhrowet al. [9], with permission from the copyright holders, StocktonPress, a division of Nature America

    mal or elevated not only by age and gender, but also bysize, albeit to a somewhat limited extent. Hypertensionin this age group would be defined as blood pressure ele-vation above the 95th percentile for infants of similarage, size and gender.

    Although the upper limit of normal blood pressurehas been defined as the 95th percentile. the actual inci-dence of hypertension in neonates is quite low, rangingfrom 0.2% to 3% in most reports [I. 2, 14-16]. It is sounusual in otherwise healthy term infants that routineblood pressure detennination is not advocated for thisgroup | I7 | . For premature and otherwise high-risk new-boms admitted to modetn NICUs, however, the picturecan be quite different. In a review of over 3,000 infantsadmitted to a Chicago NICU, the overall incidence ofhypertension was found to be 0.81% [ 16]. Hypertensionwas considerably more cotnmon in infants with broncho-pulmonary dysplasia. patent ductus arteriosus. intraven-tricular hemorrhage or that had indwelling umbilical ar-terial catheters. In this latter group, approxitnately 9% ofthe infants studied developed hypertension.

    Hypertension tnay also be detected well after dis-charge from the NICU. In a retrospective review of over650 infants seen in follow-up after discharge from ateaching hospital NICU, Friedman and Hustead 112]found an iticidence of hypertension (defined as a systolicblood pressure of greater than 113 mtiiHg on three con-secutive visits over 6 weeks) of 2.6%. Hypertension inthis study was detected at a mean age of approximately

  • 334

    Age-specific percentiles of blood pressuremeasurements in boys birth to 12 months

    115-110-105-1009590-85-80-75-70-6 5 -

    5 6 7Months

    9 10 11 12


    -^ 70-XE 65-1EQ. 60 -Q3

    "5 55-

    5 50-


    75 th

    50 ti l

    0 1

    90 Ih PeitenlSystolic BPDlastoric BPHeight (cm)Weighi (kg)

    5 6 7Months

    10 n 12

    87 101 106 106 106 106 106 106 106 106 106 106 10668 65 63 63 63 65 66 67 68 68 89 69 8951 59 63 66 68 70 72 73 7A 76 77 78 804 4 5 5 6 7 8 9 9 10 10 11 11

    Fig. 4 Age-specifJL- percentiles for blood pressure in boys (a) andgirls (b) from birth lo 12 monihs of age. Reproduced with permis-sion from 113|

    2 months post-term when corrected for prematurity. Al-though the differences were not significant, infant.s inthis study who developed hypertension tended to havelower initial Apgar scores and slightly longer NICUstays than infants who remained normotensive. indicat-ing a somewhat greater likelihood of developing hyper-tension in sicker babies, a finding similar to that of Singhet al. 116]. Eveti with the increasing rates of survival ofpremature infants, however, hypertension remains a rela-tively infrequetit clinieal problem that is primarily con-fitiecj to the NICU.

    Causes of hypertension in neonates

    As in older infants and children, the causes of hyperten-sion in neonates are numerous (Table I). with the twolargest categories being renovaseular and other renal pa-renchymal diseases | l - 3 . 12. 14-16]. More specifically,umbilical artery catheter-as.sociated thromboemboiismaffecting either the aorta and/or the renal arteries proba-bly accounts for the majority of eases of hypertensionseen in the typical NICU. A clear association betweenuse of utnbilical arterial catheters atid development of ar-terial thrombi was first demon.strated in the early 1970s

    Age-specific percentiles of blood pressuremeasurements in girls birth to 12 months

    95 th90 th

    75 th

    50 th







    9 5 -

    9 0 -

    8 5 -

    ao-7 5 -

    7 0 -

    6 5 -

    95 th90th

    75 th


    0 I 5 6 7Months

    9 10 n 12

    75 n

    ^ 70oiXP 65

    50 -

    =5 5 5 -

    D 50 -


    75 th

    50 th

    0 1

    90 th PeicenrlleSyilolJc BP If,Dtastollc BP 68Height (cm