Christopher R. Graber, MD

Salina Women’s Clinic

September 27, 2011

(revised from Mar 2010)

Pre-Term Labor

DefinitionsRandom FactsRisk Factors for PTLTocolytics

Gr. tokos: childbirth, lytic: capable of dissolvingIdentifying patients at high riskPreterm contractions aloneRecommendationsReferences

Introduction

Term: 37-42 wgaPreterm: between 20 and 37 wgaLabor: contractions causing cervical changeInsufficient cervix: painless cervical dilation,

usually before 20 weeksTocolytic: any medicine given to inhibit

myometrial contractionsEtOH, MgSO4, CCA, betamimetics, NSAIDs

Definitions

Preterm birth is a leading cause of neonatal morbidity and mortality

In the US, 11.5% of all births are preterm35% of health care $$ for infants75% of neonatal mortality50% of long-term neurologic impairments

The incidence of preterm birth is essentially the same as 40 years ago

Random Facts

Multiple gestationsPrior preterm birthPreterm premature ROMBacterial vaginosis (unclear if Rx helps)Genitial infectionsPeriodontal diseaseEnvironmental factors

Smoking, drug useLong periods of standing – 1 study

Risk Factors for PTL

Etoh – mid 20th centuryMgSO4 – most commonly used, controversialCalcium Channel Blockers – newer

Nifedipine (Procardia)Betamimetics – most common outpatient

Ritodrine, turbutalineOxytocin antagonists – experimental

Atosiban

Tocolytics

May prolong gestation for 2-7 daysAllow for steroids and/or transport

Betamethasone 12mg IM q24h x 2 doses

No clear “first-line” drugSide effects are common, adverse events are

rare but seriousDo NOT combine tocolytics

Tocolytics

Controversy for MgSO4

2005: 192 patients, 24 to 33.6 wga, randomized to MgSO4 or Nifedipine

Primary outcome: arrest of preterm labor – prevention of delivery for 48 hours with uterine quiesence

Primary outcome – MgSO4 87% vs. Nifedipine (72%)

No differences – del within 48h, gestational age at del, birth prior to 37 or 32 weeks.

MgSO4 newborns spent more time in NICUMild and severe adverse effects more

common in MgSO4 group

MgSO4 vs. Nifedipine

ACOG Committee Opinion 455, March 2010Observational studies in ‘90’s showed fewer

neurologic complications if MgSO4 exposure for preterm del

Led to several large studiesMeta-analysis suggests that MgSO4

decreases risk for cerebral palsy (RR 0.71, 95% confidence 0.55-0.91)

No effect on fetal/infant deathSerious maternal complications not more

common

MgSO4 for Neuroprotection

MgSO4 for Neuroprotection

Who to treat?Probability of progressive labor, gestational

age, risks of treatmentRegular uterine activity that does not decrease

with bed rest and hydrationContraindications

Severe preeclampsia, active vaginal bleeding (abruption), chorio, lethal abnormalities, advanced dilation, fetal indications

High Risk?

Document cervical dilation (?change)Consider fetal fibronectin

NPV 99%, PPV 50% for delivery in 2 weeksNo bleeding, cvx <3cm, NPV for 24h

Consider cervical sonoTransvaginal most accurate

Identify High Risk Patients

Cervical Length (mm)

Fetal Fibronectin + (%)

Fetal Fibronectin – (%)

25 65 25

26-35 45 14

>35 25 7

Prior Preterm Birth

Fetal fibronectin and cervical length (transvaginal) assessed at 24wga. From: Iams JD, et al. The Preterm Prediction Study: recurrence risk of spontaneous preterm birth. Am Journal of Obstetrics and Gynecology. 1998; 178: 1035-1040.

Recurrence risk of spontaneous preterm birth at <35wga in women with a prior preterm birth

Preterm contractions do not reliably predict cervical changeStudy: 760 women presenting with symptoms

18% delivered before 37wga3% delivered within 2 weeks of first presentation

Bed rest, pelvic rest, hydrationUncertain benefits, never provenPossible side effects: DVT, no income

Preterm Contractions

Women with multiple gestations are at high risk for PTL but are also at high risk for pulmonary edema with MgSO4 or turbutaline.

Repeated courses of tocolysis?Limited benefits for initial courseOnly for transportMgSO4 for neuroprotection?

Consider amniocentesis for FLM

Other random facts

No clear “first-line” tocolytic drugsAntibiotics do not appear to prolong gestation

Reserve for GBS prophylaxisNeither maintenance treatment with

tocolytics nor repeated acute tocolysis improve perinatal outcomes

Recommendations – Level A

Tocolytics may prolong pregnancy 2-7 days to allow for transport and ANCS (the most beneficial intervention for true PTL)

There are no current data to support the use of salivary estriol, Home Uterine Activity Monitoring (HUAM), or BV screening as strategies to identify or prevent PTL

Recommendations – Level A

Cervical ultrasound and/or fetal fibronectin have good negative predictive value and may be useful in determining women at high risk

Amniocentesis for FLM may be used during preterm labor episodes

Bed rest, hydration, and pelvic rest do not appear to improve the rate of preterm birth

Recommendations – Level B

ACOG Practice Bulletin. Assessment of Risk Factors for Preterm Birth. Number 31, October 2001, reaffirmed 2008.

ACOG Practice Bulletin. Management of Preterm Labor. Number 43, May 2003, reaffirmed 2008.

ACOG Committee Opinion . Magnesium Sulfate Before Anticipated Preterm Birth for Neuroprotection. Number 455, March 2010.

Elliott, JP, et al. In Defense of Magnesium Sulfate. Obstetrics & Gynecology. 113(6):1341-1348, June 2009.

Grimes, DA, et al. Magnesium Sulfate Tocolysis: Time to Quit . Obstetrics & Gynecology. 108(4):986-989, October 2006.

Iams JD, et al. The Preterm Prediction Study: recurrence risk of spontaneous preterm birth. Am erican Journal of Obstetrics and Gynecology. 1998; 178: 1035-1040.

Lyell DJ. Magnesium sulfate compared with nifedipine for acute tocolysis of preterm labor: a randomized controlled trial. Obstetrics & Gynecology July 2007; 110(1): 61-7.

References