Preterm Labor Prediction, Prevention, and Management

1. Preterm Labor Prediction, Prevention, and Management Jennifer Hernandez, M.D. Maternal-Fetal Medicine Obstetrix Medical Group of Texas Fort Worth, Texas

2. Objectives • To review the background and epidemiology of preterm birth • To discuss risk factors and screening methods available for predicting women at risk and to review preventative options for those women at risk • To review how to diagnose preterm labor and treatment options available for those women • To discuss preterm labor in multi-fetal gestations and how these differ from singleton pregnancies

3. Overview

4. Preterm Birth: Background • Preterm birth is defined as delivery prior to 37 completed weeks’ gestation • Early preterm birth is defined as delivery prior to 34 weeks gestation • Late preterm birth is defined as delivery between 34 0/7- 36 6/7 weeks’ gestation • Preterm birth can be due to PTL (40-45%), PPROM (20-255%), or medically indicated deliveries (30-35%)

5. Preterm Birth: Epidemiology • The incidence of preterm birth increased more than 20% from 1990 to 2006 • This was largely due to a rise in multiple gestations and medically indicated late preterm deliveries

6. Preterm Birth: Epidemiology • Fortunately, the overall rate of preterm birth in the United States is decreasing, down to 11.7 percent in 2011 • This rate of preterm birth still remains higher than other industrialized countries • The U.S. ranks 131st out 184 countries with reported rates of preterm birth • It’s not just a disparity between countries • Vermont, New Hampshire, Oregon, and Maine all have preterm birth rates < 9.6% • Louisiana, Mississippi, and Alabama all have rates >14.6%

7. Preterm Birth: Significance • Why does it matter? • Preterm birth is the leading cause of neonatal morbidity and mortality • Long-term sequelae include neurodevelopmental deficits and increased risk of chronic disease in adulthood • Preterm birth costs the health care system $26 billion annually

8. Preterm Birth: Significance • The risk of morbidity and mortality decrease as gestational age increases, but the relationship is non-linear • The point with the lowest risk is between 39 0/7 and 40 6/7 weeks

9. Prediction

10. Preterm Birth: Risk Factors • Prior preterm birth • The number one risk factor for preterm birth • The more preterm births, the stronger the risk of recurrence: • One prior preterm birth: 14-22% • Two prior preterm births: 28-42% • More than 3 prior preterm births: 67% • Most recurrent preterm births occur within 2 weeks of the gestational age of the prior preterm birth

11. Preterm Birth: Risk Factors • Cervical and Uterine Factors • Short cervix • There is an inverse relationship between cervical length by ultrasound and gestational age at delivery • More to come on this later…. • Cervical surgery • Ablative and excisional procedures for treatment of cervical intraepithelial neoplasia have been associate with increased risk of preterm birth • Uterine malformations • Congenital and acquired malformations are associated with preterm birth

12. Preterm Birth: Risk Factors • Lifestyle factors • Smoking, Substance abuse • Body mass index • Physical activity, work, and stress • Demographic factors • Race • African Americans are at the highest risk for preterm birth • Socioeconomic status • Educational status

13. Preterm Birth: Risk Factors • Infection • Bacterial vaginosis and other vaginal infections • Asymptomatic bacteruria • Peridontal disease • Multiple gestation • Birth defects • Threatened abortion • Inter-pregnancy interval • Genetic factors

14. Preterm Birth: Screening • Transvaginal cervical ultrasonography • An increased risk of PTB as cervical length shortens has been observed in all populations • Cervical length below the 10th percentile (25 mm) is consistently associated with an increased risk of PTB • 90th percentile: 45 mm • 50th percentile: 35 mm • 10th percentile: 25 mm • 5th percentile: 20 mm • 2nd percentile: 15 mm

16. Preterm Birth: Screening • Cervical length screening by history • High risk population: Prior preterm birth < 34 weeks • Transvaginal ultrasound for cervical length every 2 weeks from 16 to 24 weeks • Low risk population: No history of preterm birth • One time transabdominal screening at anatomy ultrasound (usually ~18 weeks) with transvaginal ultrasound only if first measurement concerning

17. Preterm Birth: Screening • Fetal Fibronectin • A basement membrane protein produced by the fetal membranes • Thought to act as an adhesion molecule that binds the placenta and membranes to the uterine decidua • Rarely found in the vagina after 20 weeks gestation in a normal pregnancy • When found in the vagina after 20 weeks, it has been associated with an increased risk of spontaneous PTB • Low sensitivity, high specificity • ACOG no longer recommends its use as a screening tool

18. Preterm Birth: Screening • Home uterine activity monitoring • Not recommended • Bacterial vaginosis screening • Not recommended

19. Prevention

20. Preterm Birth: Prevention • History • 17α-hydroxyprogesterone caproate injections • Any woman with a singleton gestation and prior spontaneous preterm delivery should receive weekly progesterone injections from 16 to 36 weeks • Use of progesterone in these high risk patients has been shown to significantly reduce the risk of recurrent preterm birth • This is thought to reduce inflammation, maintain cervical integrity, and antagonize oxytocin

21. Preterm Birth: Prevention • Cervical length • High risk patients • Cerclage • If cervical length < 25 mm prior to 24 weeks • Associated with a 30% reduction in preterm birth along with decreased perinatal morbidity and mortality • Low risk patients • Vaginal progesterone • If cervical length is < 20 mm prior to 24 weeks • Associated with ~ 45% reduction in preterm birth • Cerclage • Has not been shown to significantly reduce preterm birth rate, even at cervical lengths < 15 mm

22. Management

23. Preterm Birth: Symptoms • Cramping • Contractions • Low back pain • Lower abdominal pressure • Vaginal discharge

24. Preterm Birth: Diagnosis • It’s not preterm labor without cervical change • Contractions alone without cervical change carry a 40-70% false-positive rate • Fetal fibronectin • The value is in its negative predictive value • >99% for delivery within 14 days • Positive predictive value • Only 13-33% (!) for delivery in 7-10 days

25. Preterm Birth: Intervention • Tocolytics • The goal of tocolysis is for short-term prolongation of pregnancy to allow administration of antenatal steroids a well as maternal transport if needed • No evidence exists that tocolytic therapy has any direct favorable effect on neonatal outcomes • Long-term use of any of these agents carries a high risk for side effects– both maternal and fetal • A few examples: Magnesium sulfate, Calcium channel blockers (Nifedipine), NSAIDs (Indomethacin), Beta-adrenergic receptor antagonists (Terbutaline)

26. Preterm Birth: Intervention • Antenatal corticosteroids • This is the single most beneficial intervention for improved neonatal outcomes in patients who deliver preterm • Neonates whose mothers receive steroids have significantly lower severity and frequency of respiratory distress syndrome, intracranial hemorrhage, necrotizing enterocolitis, and death (compared to those who do not receive steroids) • Betamethasone and Dexamethasone are the most widely studied corticosteroids and are equivalent in efficacy

27. Preterm Birth: Intervention • Antenatal corticosteroids • A single course of steroids is recommended for any woman at risk for preterm delivery between 24 and 34 weeks • A single rescue course at least 2 weeks after the first course has additional neonatal benefit • However, regularly scheduled repeat courses are not recommended

28. Preterm Birth: Intervention • Antibiotics • It has been theorized that infection or inflammation are associated with contractions • However, it has never been shown that antibiotic treatment in women with preterm labor and intact membranes have any benefit in prolonging the pregnancy • This is different than the important antibiotic prophylaxis for GBS prophylaxis and in the setting of rupture of membranes

29. Preterm Birth: Intervention • Neuroprotection • Pre-delivery administration of magnesium sulfate reduces the occurrence of cerebral palsy • Magnesium sulfate should be given with the intent for neuroprotection when birth is anticipated prior to 32 weeks • Same protocol essentially as magnesium for tocolysis and preeclampsia seizure prophylaxis

30. Multiples

31. Preterm Birth: Multiples • In 2006, 60% of twins and 93% of triplets were born preterm • Unfortunately, many of the strategies listed previously are ineffective or actually detrimental in a multi-fetal pregnancy • Progesterone treatment does not reduce the incidence of preterm birth • Cerclage may actually increase the risk of preterm birth– not recommended • Tocolytics carry a much higher risk of side effects in this population

32. Preterm Birth: Multiples • There is not even adequate data to demonstrate benefit from the use of antenatal steroids in multiple gestations • However, because of the clear benefit attributable to corticosteroids in singleton gestations, steroids are readily utilized in multiple gestations • The same concept applies to magnesium sulfate for neuroprotection

33. Conclusions

34. Preterm Birth: Conclusions • Preterm birth remains a common complication for many women in the United States • It carries a huge financial burden for families affected as well as the health care system as a whole • There are multiple risk factors for preterm birth, but a prior history of this event is the strongest predictor of recurrence

35. Preterm Birth: Conclusions • There are few reliable methods of prediction available– maternal history and cervical length • There are even fewer reliable methods of prevention once an increased risk of preterm delivery is identified– progesterone and cerclage • Preterm labor can be elusive at times

36. Preterm Birth: Conclusions • Once preterm labor is diagnosed, several treatments are available to reduce the neonatal morbidity and mortality if preterm birth occurs– antenatal steroids and magnesium sulfate • Multifetal gestations have a very high risk of preterm birth, but unfortunately, effective prevention and management options are limited in this setting

37. Questions?

38. Thank you!

39. References • Prediction and prevention of preterm birth. ACOG Practice Bulletin Number 130, October 2012. • Cunningham FG, Leveno KJ, Bloom SL, et al. Williams Obstetrics. 23rd edition. McGraw Hill. 2010. • Goldenberg RL, Mercer BM, Meis PJ., et al. The preterm prevention study: fetal fibronectin testing and spontaneous preterm birth. Obstet Gynecol. 1996;87:643-48. • Goldenberg RL, Iams JD, Das A., et al. The preterm prevention study: sequential cervical length and fetal fibronectin testing for the prediction of spontaneous preterm birth. Am J Obstet Gynecol 2000;182:636-43. • Iams JD, Geldenberg RL, Meis PJ, et al. The length of the cervix and the risk of spontaneous premature delivery. NEJM 1996;334:567-72. • Lockwood CJ, Senyei AE, Dische MR, et al. Fetal fibronectin in cervical and vaginal secretions as a predictor of preterm delivery. NEJM 1991;325:669-74. • To MS, Alfirevic Z, Heath VC, et al. Cervical cerclage for prevention of preterm delivery in women with short cervix: a randomised controlled trial. Lancet 2004;363:1849-53. • Goya M, Pratcorona L, Merced c, et al. Cervical pessary in pregnant women with a short cervix (PECEP): an open label randomised controlled trial. Lancet 2012;379:1800-6. • Rouse DJ, Caritis SN, Peaceman aM, et al. A trial of 17 alpha-hydroxyprogesterone caproate to prevent prematurity in twins. NEJM 2007:357:454-61.