1. Christopher R. Graber, MD Salina Women’s Clinic September 27, 2011 (revised from Mar 2010)

2. Definitions Random Facts Risk Factors for PTL Tocolytics Gr. tokos: childbirth, lytic: capable of dissolving Identifying patients at high risk Preterm contractions alone Recommendations References

3. Term: 37-42 wga Preterm: between 20 and 37 wga Labor: contractions causing cervical change Insufficient cervix: painless cervical dilation, usually before 20 weeks Tocolytic: any medicine given to inhibit myometrial contractions EtOH, MgSO4, CCA, betamimetics, NSAIDs

4. Preterm birth is a leading cause of neonatal morbidity and mortality In the US, 11.5% of all births are preterm 35% of health care $$ for infants 75% of neonatal mortality 50% of long-term neurologic impairments The incidence of preterm birth is essentially the same as 40 years ago

5. Multiple gestations Prior preterm birth Preterm premature ROM Bacterial vaginosis (unclear if Rx helps) Genitial infections Periodontal disease Environmental factors Smoking, drug use Long periods of standing – 1 study

6. Etoh – mid 20 th century MgSO4 – most commonly used, controversial Calcium Channel Blockers – newer Nifedipine (Procardia) Betamimetics – most common outpatient Ritodrine, turbutaline Oxytocin antagonists – experimental Atosiban

8. May prolong gestation for 2-7 days Allow for steroids and/or transport Betamethasone 12mg IM q24h x 2 doses No clear “first-line” drug Side effects are common, adverse events are rare but serious Do NOT combine tocolytics

10. 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 NICU Mild and severe adverse effects more common in MgSO4 group

11. ACOG Committee Opinion 455, March 2010 Observational studies in ‘90’s showed fewer neurologic complications if MgSO4 exposure for preterm del Led to several large studies Meta-analysis suggests that MgSO4 decreases risk for cerebral palsy (RR 0.71, 95% confidence 0.55-0.91) No effect on fetal/infant death Serious maternal complications not more common

13. Who to treat? Probability of progressive labor, gestational age, risks of treatment Regular uterine activity that does not decrease with bed rest and hydration Contraindications Severe preeclampsia, active vaginal bleeding (abruption), chorio, lethal abnormalities, advanced dilation, fetal indications

14. Document cervical dilation (?change) Consider fetal fibronectin NPV 99%, PPV 50% for delivery in 2 weeks No bleeding, cvx <3cm, NPV for 24h Consider cervical sono Transvaginal most accurate

16. Cervical Length (mm)Fetal Fibronectin + (%)Fetal Fibronectin – (%) 256525 26-354514 >35257 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

17. Preterm contractions do not reliably predict cervical change Study: 760 women presenting with symptoms 18% delivered before 37wga 3% delivered within 2 weeks of first presentation Bed rest, pelvic rest, hydration Uncertain benefits, never proven Possible side effects: DVT, no income

18. 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 course Only for transport MgSO4 for neuroprotection? Consider amniocentesis for FLM

19. No clear “first-line” tocolytic drugs Antibiotics do not appear to prolong gestation Reserve for GBS prophylaxis Neither maintenance treatment with tocolytics nor repeated acute tocolysis improve perinatal outcomes

20. 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

21. 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

22. 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.