1. Preterm Delivery: An Update on Prevention and Treatment Tara Lehman, MD MPH CCRMC June 3, 2009

2. Objectives Identify risk factors for PTD that can be modified in prenatal care Describe the use of progesterone to prevent PTD Understand the use of FFN and cervical length in the diagnosis of preterm labor Be familiar with the controversy surrounding Magnesium Sulfate as the go to drug in PTL

3. Importance of Preterm Birth Complications of prematurity/preterm birth are the number one cause of neonatal mortality in the US More 12% of births are preterm (<37 weeks) Rate of preterm birth has been steadily rising since 1980 Estimated $13.6 billion in health care expenditure in 2001

4. Risk Factors History of preterm delivery Maternal age (extremes) Multifetal gestations/ART Polyhydramnios Cervical surgery/LEEP/D&E Uterine anomalies/Lyomata Substance abuse (cocaine) Low SES

5. Risk Factors – What we can change Pregnancy Interval of <6mos Tobacco Substance use 25%in polysubstance users Anemia < 9.5 at 12 weeks High Work Stress Index >36 hrs/week, prolonged standing, heavy lifting, skipped meals Genital Infections GC/CT BV – maybe in select groups Trichomonas - only for symptom control ASYMPTOMATIC BACTURIA

6. Progesterone and the prevention of recurrent preterm birth Meis et al (NEJM 2003) 459 women with history of PTD 250 mg IM weekly 17 alpha-hydroxyprogesterone caproate vs. placebo 16-20 weeks through 36 weeks RR 0.66 in treatment group Also showed decreased NEC, IVH, O2 needs in treatment group Multiple others have confirmed decreased PTD if started up to 26 weeks

7. Progesterone and the prevention of recurrent preterm birth - limitations Meta-analyses have NOT confirmed the decrease in the complications of prematurity 17 alpha-OH progesterone no longer manufactured in US Recent studies focused on vaginal progesterone gel have not found a benefit Early cessation increases risk of PTD (OR 2.11) No role in prolonging multifetal or FFN + pregnancies

8. Diagnosis of Preterm Labor : FFN Trophoblast glue present in cervical secretions prior to 20 wks gestation and at term Absent between 22 and 34 weeks Negative predictive value of 99.5% for 7 days and 99.2% for 14 days Positive predictive value is ONLY 29% Can use to direct steroid administration NNT to prevent RDS = 17

9. Diagnosis of Preterm Labor: Cervical Length Cervical length of >3 cm has a NPV of nearly 100% Cervical length of </= 2.5 cm has a strong association with PTD and warrants active management 2.5 -3 cm is a grey zone where FFN can guide steroid use

10. Magnesium Sulfate: Friend of Foe? Tocolytics have never been shown to significantly prolong labor Large meta-analyses of Mg++ have failed to show even the 48hr delay of delivery necessary for steroid administration Beta-blockers delay c. 48hrs Calcium channel blockers delay 1-4 days, with less side effects Simhan et al (NEJM August 2007) recommended AGAINST Mg++ use for preterm labor

11. Cervical Length for screening of High Risk Patients TV sono with EMPTY BLADDER 16-20 weeks Result >3 cm is reassuring Result </=2.5 cm is concerning Serial sonos ?Cerclage in pre-viable Steroids RF modification Result </=1.5 cm is the highest risk group where treatment shown to improve outcomes Progesterone supplementation (OR 0.56)

12. Magnesium and Neonatal Neuroprotection Rouse et al (NEJM Aug 2008) 2241 women in preterm labor with expected delivery 24-31 weeks randomized to Mg++ or placebo No difference in overall CP (11%) Decrease in moderate - severe CP 1.9% vs. 3.5% (OR 0.55) No difference in neonatal death No life threatening maternal complications