Preterm BirthMedical Paper PresentationAssociate Professor, Maternal Fetal MedicineUTHSC

Preterm birth rates in the United States< 37 weeks12.9%%

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Preterm birth in the USOne preterm birth every minute!

To put it in perspective..One preterm birth each minute60 preterm births by the time this talk is overHealthy people 2010 objective is to reduce rate to 7.6%

Preterm birth

75-80% of all perinatal mortality50% of all long term neurodevelopmental morbidityTremendous financial, emotional burden on society

Infants born preterm are at increased risk of:Respiratory Distress syndromeChronic lung diseaseIntraventricular hemorrhageNecrotizing enterocolitisRetinopathy of prematuritySevere brain injury

Newborn morbidity

50% of long term major morbidity among non-anomalous fetuses:Cerebral palsyMental retardationBlindnessDeafnessSensory deficitsDevelopmental delayLong term consequences

EtiologiesStressInfectionBleedingUterine overdistension

Preterm birth is a syndrome

Inflammation/Infection (~40%)Maternal/fetal stress (~25%)Uteroplacental ischemia (~25%)Thrombophilia, decidual hemorrhage, abruptionAbnormal uterine distension (~10%)

Some pathways through which preterm birth may occur

Some pathways through which preterm birth may occur

Risk factorsPrior preterm birthPoor socio-economic statusBlack raceLow educationSmokingBleedingAssisted reproductionMultiple gestationGenital tract infectionsPeriodontal diseaseCervical surgeryPregnancy terminationUterine anomalies

Preterm babies are more likely to have preterm births as adultsPorter et al. Obstet Gynecol 1997;90:63-671405 preterm mothers2781 term mothers

Maternal and Paternal Influences77,452 boys and girls in Norway who later became parentsGestational age of the child at birth increased 0.58 days for each additional week in the fathers GA1.22 days for each additional week in the mothers GALie et al. Obstet Gynecol 2006

Over 80% of patients who present with regular painful contractions go on to deliver at term

Most interventions do not prevent preterm birth and are potentially harmful

How then do we determine who will actually deliver preterm (isnt THAT the question?)

More than 1/2 of patients who deliver preterm have no risk factorsMore than 2/3 of patients with traditional risk factors do not deliver pretermMost important traditional risk factor is preterm delivery in a prior pregnancy

Fetal fibronectin

Fetal fibronectin

Cervical Length as Predictor of SPB

The risk of SPB is increased in women with short cervix. Abnormal cervical length

Transvaginal sonographic cervical assessment

Interventions that have been usedBed restIntravenous hydration

Are there any therapeutic interventions to prevent SPTB?

Types of Cervical CerclageHistory-indicatedPhysical exam-indicatedUltrasound-indicated

The Use of Cervical Cerclage for a Short Cervix (Ultrasound-Indicated Cerclage) 4 RCTsRust-2000 Unselected No benefitAlthuisius-2001 High-risk Benefit* To-2004 UnselectedNo benefitBerghella-2004 Unselected No benefitAUTHOR-YEARPOPULATIONOUTCOME*REDUCTION OF PREMATURITY, MORTALITY & MORBIDITY

Multicenter RCT on the Use of Cervical Cerclage in High Risk Pregnancies (Report of the MRC/RCOB, Br J Obstet Gynaecol 1993; 100:516)Benefit observed in 1:25 cases

Cerclage is beneficial only in women with a history of >3 second trimester losses/preterm births History-Indicated Cerclage

Cerclage for dilated cervix with membranes at or beyond the external osAlthusius et al, Am J Obstet Gynecol 2003

Cerclage & Indomethacin(n=13) Bedrest alone (n=10)Prolongation (weeks)7.73.0Neonatal survival56%28%Preterm birth

Management of Cervical Insufficiency and Bulging Fetal Membranes (at 18-26 weeks)(Daskalakis et al Obstet Gynecol 2006;107:219)Prolongation (wks)8.83.1Mean BW (g)2,101739Live birth86%41%Neon survival96%57%PTB

Use of Cerclage for Prevention of SPB in Women With Prior SPB. A Meta-analysis of 4 RCTs (Berghella V, Odibo A, To M, Rust O and Althiusius S) Obstet Gynecol 2005;106:181 4 RCTs (n=208 women with prior SPB)

SPB

Multicenter Randomized Trial of Cerclage For Preterm Birth Prevention In High-Risk Women With Shortened Mid-Trimester Cervical Length(Owen J, Abst #4, Am J Obstet Gynecol Suppl Dec 2008)Reduction in PTB < 35 wks in cerclage patients

OR (95% CI)If CL < 15 mm0.23 (0.08, 0.66)If CL 16-24 mm0.84 (0.49, 1.40)P=0.05CONCLUSION:Cerclage will mostly benefit high-risk women with mid-trimester CL < 15 mm (77% reduction in PTB rate)

Tocolytics-adrenergic agentsMagnesium sulfateProstaglandin synthetase inhibitorsCalcium channel blockersNitroglycerinOxytocin antagonists

Magnesium sulfate!Good or evil?

Contraindications to TocolysisConditions where delivery is indicated such asSevere preeclampsia/hypertensionFetal non-reassuring statusMaternal non-reassuring statusSignificant hemorrhageMaternal cardiac diseaseGestational age >36 weeks (? >34 weeks)Infection/ chorioamnionitisFetal demise or lethal anomaly

Goals of tocolysisTo allow steroid administrationTo allow transport or to facilitate delivery under safer circumstancesTo prolong gestation in very preterm pregnancies

Calcium channel blockersInhibit calcium entry into cellsNifedipine most commonly usedRapidly absorbed after oral adminstrationPeak concentration in 15-90 minutesHalf life of 81 minutesDuration of action of single dose 6 hoursGood contraction suppression and few side effects12 reported trials show reduced deliveries within 7 days (RR 0.76; CI 0.60, 0.97)Reduced deliveries before 34 weeks (RR 0.83, CI 0.69, 0.99)Reduced fetal RDS, IVH, NEC, jaundice, when compared with other tocolyticsFewer women stop treatment due to side effects

Calcium channel blockersSide effects:HypotensionHeadachesDizzinessNauseaNo significant fetal effects

Administration10 -20 mg every 4-6 hours

Cyclooxgenase inhibitorsInhibit prostaglandin synthesisVary in activity/potencyIndomethacin most widely usedPowerful tocolyticCrosses placentaAssociated with reduction in births before 37 weeks, increased gestational age, birth weightMaternal side effects:GI disturbancesBleeding ThrombocytopeniaAsthmaRenal injury

Cyclooxgenase inhibitorsFetal side effects:OligohydramniosPremature closure of ductus arteriosusThese complications are rareGenerally not recommended beyond 37 weeksNECTreatment protocol50 mg loading25-50 mg every 6 hoursAssess AFI, ductus if using for prolonged periodsStop treatment if delivery is imminent

SteroidsReduce risk of :Respiratory distress syndromeIntraventricular hemorrhageNecrotizing enterocolitis

Progesterone

Progesterone for the reduction of risk of preterm birth

Reduction of SPTBs By Progesterone Administration Among Asymptomatic High Risk Women60% reduction for births < 37 weeks-daily 100mg progesterone vaginal suppositories (da Fonseca et al, Am J Obstet Gynecol 2003;188:419)

34% reduction for births < 37 weeks-weekly IM injections of 17-P (Meis PJ & NICHD MFMU Network, N Engl J Med 2003;348:2379)

CL unknown (was not reported) in the above two studies

Prevention of Recurrent Preterm Delivery by Progesterone Vaginal Gel-A R-DB-PC Trial (OBrien et al Ultrasound Obstet Gynecol 2007;30:687 DeFranco et al Ultrasound Obstet Gynecol 2007;30:697)N=659 women with Hx of SPTB

No reduction in PTB at

It is possible that progesterone administration in women with history of SPTB may benefit only those with a short cervix in the current pregnancySpeculation

Use of Progesterone to Reduce Preterm Birth (ACOG Committee Opinion, Number 419, October 2008)It should be offered to women with a singleton pregnancy and a history of spontaneous preterm birth < 37 weeks gestationProgesterone supplementation for asymptomatic women with an incidentally identified very short cervical length (< 15 mm) may be considered; however, routine cervical length screening is not recommended

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