Preterm Labour and

Premature Rupture of Membranes

Date : 17.04.2009

Dr. Pradeep Kumar GargAssistant Professor

Department of Obstetrics and GynaecologyAll India Institute of Medical Sciences

New DelhiEmail:pkgarg_in2004@yahoo.com

Preterm Labour (PTL)Definition

WHO : Regular contractions associated with cervical changes

<37->20 weeks of pregnancy

Incidence - 8-10%60% of all neonatal mortality

Threatened PTL - presence of uterine contractions in absence of cervical changes.

DefinitionsPreterm (or premature) infant

Infant born before 37 completed weeks of gestation

Moderately preterm infantInfant born between 32 and 36 completed weeks of gestation

Very preterm infantInfant born before 32 completed weeks

of gestation

Magnitude of the Problem

The infant mortality rate for very preterm infants (delivered < 32 weeks of gestation) is nearly 75 times the rate for infants born at term

20% all infants born <32 weeks do not survive the first year of lifePreterm birth is directly responsible for 75–90% of all neonatal deaths that are caused by lethal congenital malformations.

Pathways to Preterm labour

Source: Lockwood CL. Unpublished data, 2002.

proteases

PT LUterine

ContractionsCervical Change

• Infection: - Chorion-Decidual - Systemic

DecidualHemorrhage

CRHE1-E3

ThrombinThrombin Rc

Pathological UterineDistention

• Multifetal Pregnancy• Polyhydramnios• Uterine Abnormality

Inflammation

• Maternal-Fetal Stress

• Premature Onset of Physiologic Initiators

Activation of Maternal-Fetal

HPA Axis

CRH+

ChorionDecidua

uterotonins

Mechanical StretchGap jctPG synthaseOxt recep

PPROM

Ils, Fas LTNF

+

Abruption

History of previous preterm birth

Primary risk for a preterm delivery in multiparas is a history of previous preterm birth (relative

risk [RR] 2.62) Mercer BM,Am J Obstet Gynecol.

1999;181:1261–1221

Evaluation of the literature shows that history of a previous preterm delivery is consistently the most important risk factor for subsequent

preterm birth.

CausesMaternal

FeverAcute pyelonephritisAcute appendicitisAbdominal operation

Chronic diseaseHypertension, nephritis, diabetes, severe anemia, decompensated heart disease

Pregnancy complicationsPregnancy induced hypertensionAntepartum hemorrhage

Uterine anomalies

Cervical incompetence

Malformation of uterus

Foetal

Multiple pregnancy

PROM

Hydramnions

Congenital fetal malformation

Idiopathic

INFECTION …

ASCENDING INTRAUTERINE INFECTION IS CONSIDERED TO HAVE FOUR STAGESThe first stage: change in the vaginal/cervical microbial flora or the presence of pathologic

organisms

Second stage: deciduitis.

Third stage (choriovasculitis) or (amnionitis)

Fourth stage: Once in the amniotic cavity, the bacteria may gain access to the fetus by different ports of entry

R Goldenberg NEJM 2000

Risk Factors

Non white race

Previous preterm delivery

Low body mass index

Extremes of ages (<17 and >35)

Strenous work stress

Tobacco use

Hemoglobin < 10 g

Bactereuria

Low socioeconomic status

How do we identify who is at Risk?

Risk Factors

CervicalLength

FetalFibronectin

Symptomsof PTL

Preterm Birth

THE PAPIERNIK-BERKHAUER(1969)SCORING MATRIXMODIFIED BY GONIK –CREASY (1980-1986)

points Socio economic factors

Previous medical history

Daily habits Current pregnancy

1 2 children at home;low s.e status

1 abortion<1 yr since last birth

Works outside Unusual fatigue

2 Age<20/>40 yrSingle parent

2 abortions Smoke>10 cig/day>3 flights of stairs without elevator

Gain<5 kg by 32 wkAlbuminuria,bacteriuria,hypertension

3 V low s.e statusHt<150Wt<45 kg

3 abortions Heavy/stressful workLong daily commutingExtensive travelling

breech@32 wksHead engaged @32 wksFebrile illness

4 Age<18 yrs pyelonephritis Bleeding after 12wkShort cervixOpen int osUterine irritabily

5 Uterine anomalyT2 abortionDesExpCone bx

Placenta praeviahydramnios

10 Ptb,repeated t2 abortion

TwinsAbdominal surgery

0-5:low risk5-9 :medium risk ≥10 :high risk

Signs / Symptoms

Persistent contractions (painful or painless) associated with cervical changes

Intermittent abdominal cramping, pelvic pressure or backache

Increase in vaginal discharge

Vaginal spotting or bleeding

Biological markers for predicting PTL

Fetal fibronectin

Glycoprotein produced by the chorion

Normally present in cervical secretion in early gestation and just before term labor

Presence after >24 weeks is a marker for the disruption of the chorioamnion and underlying decidua due to inflammation with or without infection

If test is negative < 1% will deliver in next week or two and test is positive then risk of PTD on next week or two is 20%.

Fetal fibronectin (cont)

False positive : bleeding, ruptured membranes and digital cervical examFalse negative : lubricant soapScreenigof asymptomatc women at low risk is not recommendedUseful in women when;

Symptom occurs between 24-34 weeksMembranes are intact and cervical dilatation is <3 cmFor short term prediction ( 7-14 days )

Biological markers for predicting PTL (contd…)

Salivary estriol

Maternal levels of serum estradiol and salivary estriol increases before onset of term and PTL

A cut off > 2. 1ng/dl yielded a sensitivity of 40%, specificity of 93%

Levels infuenced

Diurnal pattern (lowest during day , highest in night

Corticosteroids suppresses estriol value

CRH

Source placenta and fetal membranes; highest in T3.

RR 3.3 at 33 weeks

hcg and FP

Increased levels associated with PTL, abnormal placentation, disruption of choriodecidual integrity

Relaxin

Cervical length (CL)

Risk of PTD increases if CL is 30mm or less at 24 weeks,

Manual examination

subjective, interobserver variability 52%

internal os not measurable

Transvaginal USG vs digital examination

TVS can detect shortening of Cx canal earlier

no significant inoculation with bacteria

minimal discomfort

99% agreed for similar procedure

TransaAdominal USG of Cx is inadequate1.fetal can obscure the Cx especially after 20 weeks2.requires UB filling which can elongate Cx and mask funneling3.visualization not clear due to long distance

TransLabial/Transperineal USG is more useful1.fetal parts don’t obscure vision2.bladder filling not required3.no pressure exerted on cervix4.additional transducer not required5.well acceptedDrawback:gas in rectum can hamper vision specially ext os. Difficult to master.

Infection

Ureoplasma

Gonorrhoea

Chlamydia

Syphilis

Untreated UTI

Bacterial vaginosis

Bacterial vaginosis is an alteration of the normal vaginal flora, reduction in lactobacilli with increase in gram negative and anaerobic bacteria (G. vaginalies, bacteroides, mobiluncus, peptostreptococcus, mycoplasma

3 of 4 criteria should be present

Diagnosis

Vaginal pH > 4.5,Amine odour with 10% KOH, Clue cells on wet mount, Homogenous vaginal discharge

Bacterial vaginosis: two fold risk of PTBCochrane meta-analysis : no reduction by routine screening and treatment.But those with history of PTB benefited.screen pts with history of PTB. treat with oral metronidazole for 7 days (vaginal treatment had no effect) .vaginal clindamycin for 3 days or oral 5 day course also effective

Multiple pregnancy

PTL occurs in 50% of twins

76% triplets

90% quadruplets

Those with preterm contractions but without cervical changes do not require tocolytics.

Those in preterm labor : tocolysis + steroids

Greater risk of pulmonary edema with tocolytics

Treatment of PTL

WHY?

To prevent complication of prematurity

e.g.

Respiratory distress syndrome (RDS)

Intraventricular haemorrhage (IVH)

Bronchopulmonary dysplasia (BPD)

Patent ductus arteriosus (PDA)

Necrotizing enterocolitis (NEC)

Retinopathy of prematurity (ROP)

Sepsis

Tocolytics

EducationTargetingHigh RiskWomen

Bedrest

HomeUterineMonitoring

FrequentDigitalExam

Hydration

PopulationBased

strategies

Prevention/Intervention Strategies

Prevention of PTBPrimary Prevention

1.improve quality of life and nutritional status2.reduction in physical and emotional stress. bed rest. 3.education programs for signs and symptoms, contractions, pelvic pressure, vaginal discharge4.hydration 5.progesterone6.antioxidants and omega-3 fatty acids : uncertain7.cerclage8.diagnosis & treatment of infections9.role of ART10.twins and high order multiples

Secondary prevention

1.cerclage

2.antibiotics

3.tocolysis

Prophylactic therapy like bed rest, hydration and sedation in asymptomatic women at increased risk for preterm delivery has not been demonstrated to be effective.

ACOG practice bulletin 2003, Cochrane review 2003

Stop smoking and substance abuse and reduce heavy work load

Role of ART : reduce rate of multiple pregnancies, single embryo transfer

Progesterone therapy to prevent PTL

decrease in myometrial progesterone receptor with PTL and term labor.

antinflammatory response,

immunosuppression : suppresses cytokine pathways thus preventing rejection of fetus in utero.

17 alpha hydroxyprogesterone caproate weekly I.m.to women at high risk for PTL results in lower rates of PTB

Cervical CerclageRCOG study concluded that 96% of elective cerclages were unnecessary,with no perinatal improvement . In a post-hoc analysis those with three or more pregnancy losses seemed to have improved outcomeRecommendations

high risk patients can be followed by serial Cervical USGTVS during 2nd trimester. Except:anatomic defect at or near internal os, 3 or more losses, inability to follow with TVS

Cervical cerclage cont.

high risk patients screened 1 to 4 weekly

between 16 and 24 weeks

Elective transabdominal cerclage

lacerations upto LUS,

cervical surgical amputation

Cx Length < or =2.5 at 24 weeks (10th

percentile) is the critical threshold for

increased risk for PTB)

Cervical cerclage cont.Adjuntive treatment

Antibiotics: multiple urogenital cultures should be obtained . Short course of antibiotics before cerclage placement or as empiric medical therapy can be considered, but no evidence to support it. Long-term antibiotics avoided (increases resistance)Tocolytics: short-term indomethacin anti-inflammatory properties and tocolytic, but no data to support empiric use. Absence of anti-inflammatory properties of beta blocker, nifedipine, Mg sulphate precludes there useCorticosteroids: not used before 24 weeks

Cerclage in Multifetal pregnancy : no evidence to support use of elective, urgent, emergent cerclage

After delivery:

if during pregnancy urogenital infection documented then evaluation for subclinical gynecologic infection indicated.

Anatomical evaluation using HSG,hysteroscopy, MRI, TVS

Infection and preterm birth

50% of PTB associated with ascending genital

tract infection eg. intrauterine, lower genital

tract infection, distant infection like

periodontitis

polymicrobial ureaplasma urealyticum,

Mycoplasma hominis, anaerobes, group B

streptococci, Gardenella vaginalis, E. coli,

peptostreptococci, Bacteroides

Treatment of infections

antibiotics should not be given routinely in PTL with intact membranes for prolonging pregnancy

definitely diagnosed intra-amniotic infection either by clinical criteria (fever, uterine tenderness, maternal or fetal tachycardia) or by amniocentesis, give i.v. antibiotics and deliver regardless of gestation

Consider amniocentesis if

any signs and symptoms of chorioamnionitis

early gestation <28 wks

failure of tocolysis (eg. before a second tocolytic)

Tocolytics in PRL

1.beta agonist

2.magnesium sulphate

3.antiprostaglandins

4.calcium channel antagonists

5.oxytocin antagonists

6.nitric oxide donors

Goals

1.allow administration of corticosteroids

2.allow time for transfer to tertiary care

3.during maternal antenatal surgeries

4.uterine relaxation during ECV

BetamimeticMOA : b2 activatorTerbutaline 0.25mg s/c every 20 min to 3 hrsRitodrine : start at 50-100 mg/min, increase 50µg/ every 10min, max 350µgCI : cardiac disease, poorly controlled diabetes and thyroid diseaseMat S/E : arrhythmias, pulmonary edema, hypotension, tachycardia, hyperglycemia, hypokalemiaFetal S/E : Tachycardia, hyperglycemia, myocardial and septal hypertrophyNeonatal : tachycardia, hypoglycemia, hypocal, hyperbil, IVH

Magnesium sulphate

MOA : calcium antagonist;

Inhibits calcium refluxat cell membrane, competes for binding sites

Increased intracellular c AMP which further decreases calcium.

Dose : 4-6gm bolus IV for 20 min then 2-3g/hr

CI : myasthenia gravis, impaired renal function

Mat S/E : flushing, lethargy, headache

Muscle weakness, pulmonary edema, cardiac arrest

Fetal S/E : lethargy, hypotonia, respi depression

Calcium channel blockers

Blocking Voltage dependent L-type calcium channels in smooth muscles; nifedipine and ritodrin.

Dose : 30mg loading dose, then 10-20mg 4-6 hr

CI : cardiac, renal disease, maternal hypotension, concomitant use with magnesium sulphate

Mat S/E : flushing, headache, dizziness

Transient hypotension

Fetal S/E none

Antiprostaglandin drugs

inhibit prostaglandin synthetase or cyclooxygenase (COX)

PG facilitate entry of calcium into cell, enhance development of gap junctions

Prostaglandin synthetase inhibitors

Indomethacin 50mg rectally or 50-100 mg orally, 25-50mg every 6 hr for 48 hrs

CI : sig hepatic or renal disease, peptic ulcer disease, coagulation disorder, thrombocytopenia, sensitivity

Mat S/E : nausea, heartburn

Fetal S/E : constriction of DA, pulmonary hypertension, reversible decrease in renal function, hyperbil, NEC, IVH

Summary

Although tocolytics may prolong pregnancy they don’t improve perinatal outcomes, but do have adverse maternal effect

As a rule they should be given with corticosteroids

Most do not recommend use of tocolytics >= 34 weeks POG

No role of maintenance tocolysis

Antenatal corticosteroids

All fetuses between 24 – 34 wks POG at risk of preterm delivery should be considered

Decision should not be altered by race, gender, availability of surfactant replacement therapy

Those eligible for tocolysis are eligible for corticosteroids

Optimal benefit begins 24 hrs after initiation

Significant decrease in incidence and severity of RDS, IVH, NEC

Until data establish a favorable benefit-to-risk ratio,repeat courses of steroids including rescue therapy should be reserved for patients enrolled in clinical trials. Multiple courses lead to worse outcome or no benefitLong-term FU of infants given single course show no adverse effects

Betamethasone and dexamethasone Readily cross placentaHave long half lives Limited mineralocoticoid activitySimilar efficacy in decreasing RDS ( 51% vs 44%)Betamethasone is more effective in reducing IVH, PVL than dexamethasone so betamethasone is a better choice

Conduct of Delivery

Tertiary care centre, specialized staff

Cesarean delivery to obviate trauma from labor and vaginal delivery has not been validated

CS did not lower risk of mortality or ICH in <1500 gm

Episiotomy may be necessary in absence of relaxed vagina outlet

No use of routine forceps

Cesarean section for preterm breech

Preterm Premature Rupture of MembranesRisk factors

SESSmokingVaginal bleeding x 2-7Short cervixPrior cervical surgeryVitamin C, copper and zinc deficiencyMultifetal pregnancyPrevious history of PTB or PPROMPre-existing medical illnessGenital tract infection, BV, chlamydia, mycoplasma

Complications

Maternal infection

Abruptio

Prematurity

Fetal distress, cord compression

Deformation and contractures

Pulmonary hypoplasia

Fetal infection

Management

Diagnosis

Speculum examination

Nitrazine test

Ferning,

Ultrasound

-fetoprotein, FFN

Gestational age

Presence of labour

Infection

Maternal infection

Fever, uterine tenderness, fetal or maternal

tachycardia, foul smelling, vaginal discharge,

leukocytosis, uterine contractions

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