Preterm Labor and Delivery

1. Preterm Labor and Delivery UNC School of Medicine Obstetrics and Gynecology Clerkship Case Based Seminar Series

2. Objectives for Preterm Labor • Identify the risk factors and causes for preterm labor • Describe the signs and symptoms of preterm labor • Describe the initial management of preterm labor • List indications and contraindications of medications used in preterm labor • Identify the adverse outcomes associated with preterm birth • Counsel the patient regarding risk reduction for preterm birth

3. Definition: Preterm Labor • “Regular” uterine contractions • With • Cervical “change” or • > 2 cm dilation or • > 80% effacement

4. Preterm Delivery • Preterm birth: < 37completed weeks • Very Preterm birth: < 32 weeks • Extremely Preterm birth: < 28 weeks

5. Incidence • 12.5% USA (2004) • 2% < 32 weeks • Fetal growth • Small for gestational age < 10th % for GA • Birthweight: • Low BWT < 2500 grams • Very low BWT < 1500 grams • Extremely low BWT < 1000 grams

6. Incidence • 13% Rise in PTB since 1992 • Multiple gestation (20% increase) • 50 % twins, 90% triplets born preterm • Changes in Obstetric management • Ultrasound, induction • Sociodemographic factors • AMA! • No improvement with physician interventions!

7. Leading Causes of Neonatal Death (USA) Neonatal deaths: death within 28 days of birth .Data adapted from: the Centers for Disease Control and Prevention, 2000.

8. Significance • Infant mortality • Over 50% of infant deaths occur among the 1.5% infants < 1500 grams • 70 % of infant deaths occur among the 7.7% of infants < 2500 grams • Morbidity • 60%: 26 weeks • 30%: 30 weeks

9. Infant Mortality

10. Infant Morbidity

11. Infant Morbidity

12. Risk Factors for Preterm Birth

13. Stress Single women Low socioeconomic status Anxiety Depression Life events (divorce, separation, death) Abdominal surgery during pregnancy Occupational fatigue Upright posture Use of industrial machines Physical exertion Mental or environmental stress Excessive or impaired uterine distention Multiple gestation Polyhydramnios Uterine anomaly or fibroids Diethystilbesterol Cervical factors History of second trimester abortion History of cervical surgery Premature cervical dilatation or effacement Infection Sexually transmitted infections Pyelonephritis Systemic infection Bacteriuria Periodontal disease Placental pathology Placenta previa Abruption Vaginal bleeding Risk Factors for Preterm Birth

14. Miscellaneous Previous preterm delivery Substance abuse Smoking Maternal age (<18 or >40) African-American race Poor nutrition and low body mass index Inadequate prenatal care Anemia (hemoglobin <10 g/dL) Excessive uterine contractility Low level of educational achievement Genotype Fetal factors Congenital anomaly Growth restriction Risk Factors for Preterm Birth

15. Risk Factors for Preterm Birth • Prior preterm birth: • Increases risk in subsequent pregnancy • Risk increases with • more prior preterm births • earlier GA of prior preterm birth (s)

16. Prediction/Recurrence • Prior PTD @ (23-27 wks) 27% • Prior PPROM 13.5%

17. Prediction/Recurrence

18. Pathogenesis • 80% of Preterm births are spontaneous • 50% Preterm labor • 30% Preterm premature rupture of the membranes • Pathogenic processes • Activation of the maternal or fetal hypothalamic pituitary axis • Infection • Decidual hemorrhage • Pathologic uterine distention

19. Activation of the HPA Axis • Premature activation • Major maternal physical/psychologic stress • Stress of uteroplacentalvasculopathy • Mechanism • Increased Corticotropin-releasing hormone • Fetal ACTH • Estrogens (incrmyometrial gap junctions)

20. Inflammation • Clinical/subclinicalchorioamnionitis • Up to 50% of preterm birth < 30 wks GA • Proinflammatory mediators • Maternal/fetal inflammatory response • Activated neutrophils/macrophages • TNF alpha, interleukins (6) • Bacteria • Degradation of fetal membranes • Prostaglandin synthesis

21. Prediction of Preterm Delivery • History: Current and Historical Risk Factors • Mechanical • Uterine contractions • Home uterine activity monitoring • Biochemical • Fetal fibronectin • Ultrasound • Cervical length

22. Fetal Fibronectin (fFN) • Glycoprotein in amnion, decidua, cytotrophoblast • Increased levels secondary to breakdown of the chorionic-decidual interface • Inflammation, shear, movement

23. Delivery <7 days Delivery <14 days Sensitivity Specificity Sensitivity Specificity (percent), (percent), 95 (percent), 95 (percent), 95 95 percent CI percent CI percent CI percent CI Study group All studies 71 (57-84) 89 (84-93) 67 (51-82) 89 (85-94) Women with preterm labor 77 (67-88) 87 (84-91) 74 (67-82) . 87 (83-92) Asymptomatic 63 (26-90)* 97 (97-98) 51 (33-70) . 96 (92-100) (low risk or high-risk) women CI: confidence interval. * Only one study included in analysis. Fixed-effects model used (homogeneity test P >0.10). Data from: Leitich, H, Kaider, A. Fetal fibronectin - how useful is it in the prediction of preterm birth? BJOG 2003; 110 (Suppl 20):66. Fetal fibronectin as a predictor for delivery within 7 and 14 days after sampling, combined results

24. Fetal fibronectin vs. Clinical assessment of Preterm Labor Parameter Sensitivity (percent) PPV (percent) NPV (percent) Fetal fibronectin 93 29 99 Cervical dilatation >1 cm 29 11 94 Contraction frequency 8/h 42 9 94 PPV: positive predictive value; NPV: negative predictive value. Data derived from symptomatic women and reflect the ability to predict delivery within seven days. Adapted from: Iams, JD, Casal, D, McGregor, JA, et al. Am J Obstet Gynecol 1995; 173:141.

25. Sonographic Assessment of Cervical Length • Transvaginal • Reproducible • Simple

26. Sonographic Assessment of Cervical Length (Dijkstra et al Am J Obstet Gynecol 1999)

27. Sonographic Assessment of Cervical Length

30. Assessment of Risk • Integration of ….. • History • Cervical length • Fibronectin

31. Prediction of spontaneous preterm delivery before 35 weeks gestation among asymptomatic low risk women Adapted from: Iams, JD, Goldenberg, RL, Mercer, BM, et al. Am J Obstet Gynecol 2001; 184:652.

32. Risk of Preterm Birth (< 35 wks)

33. Clinical Diagnosis of Preterm Labor • Clinical Criteria • Persistent Ctx 4 q 20 min or 8 q 60 min • Cervical change/80% effacement/> 2cm dil. • Among the most common admission Dx • Inexact diagnosis: PTL is not PTD • 30% PTL resolves spontaneously • 50% of hospitalized PTL deliver @ term

34. Management of Preterm Labor • Two goals of management: • Detection and treatment of disorders associated with PTL • Therapy for PTL itself • Bedrest, hydration, sedation • NO evidence to support in the literature

35. Evaluation of Patient in Suspected PTL • Prompt eval is critical • Fetal heart monitor – to help quntify frequency and duration of contractions • Determine status of cervix – visual inspection with speculum* • *perform first if suspected ROM b/c digital exam may increase the risk of infection in the setting of PROM • UA and urine culture • Rectovaginal swab for GBS • Gonorrhea and Chlamydia cultures if inidcated by history or PE • Ultrasound exam – assess GA of fetus, cervical length, estimate amniotic fluid volume, fetal presentation and placental location • Monitor patients for bleeding – placental abruption and previa may be associated with PTL

36. Options for medical management

38. Antenatal Steroids • Recommended for: • Preterm labor 24 – 34 weeks • PPROM 24 – 32 weeks • Reduction in: • Mortality, IVH, NEC, RDS • Mechanism of action: • Enhanced maturation lungs • Biochemical maturation

39. Antenatal Steroids • Dosage: • Dexamethasone 6 mg q 12 h • Betamethasone 12.5 mg q 24 h • Repeated doses - NO • Effect: • Within several hours • Max @ 48 hours

40. Progesterone for History of PTB • 17 alpha OH Progesterone • Women with prior PTB (singleton) 24 – 26 wks • (16 – 20 wks) – 36 weeks • Reduces the risk of recurrent preterm birth • < 37 wks 36% vs 55% • < 35 wks 21% vs 31% • < 32 wks 11% vs 20%

41. Case #1 • A 36 year old black female G2 P 0101 presents at 8 weeks gestation. • History: Chronic hypertension, no meds • Smokes 1 ppd, Drugs (-) ETOH (+) • STI – history of chlamydia, HIV positive • Surgical history : LEEP, tuballigation

42. Bottom Line Concepts • Preterm labor - “Regular” uterine contractions, with cervical “change” or > 2 cm dilation or > 80% effacement, occurring before 37 weeks • There are numerous risk factors – both modifiable and non-modifiable. Counsel patients regarding ways to reduce their modifiable risk factors • Clinical assessment of risk includes consideration and evaluation of history, cervical length and fetal fibronectin • There are a variety of tocolytic drugs available, though most have unproven efficacy • Antenatal steroids are recommended for: Preterm labor 24 – 34 weeks and PPROM 24 – 32 weeks

43. References and Resources • APGO Medical Student Educational Objectives, 9th edition, (2009), Educational Topic 24 (p50-51). • Beckman & Ling: Obstetrics and Gynecology, 6th edition, (2010), Charles RB Beckmann, Frank W Ling, Barabara M Barzansky, William NP Herbert, Douglas W Laube, Roger P Smith. Chapter 20 (p201-205). • Hacker & Moore: Hacker and Moore's Essentials of Obstetrics and Gynecology, 5th edition (2009), Neville F Hacker, Joseph C Gambone, Calvin J Hobel. Chapter 12 (p146-150).