1. StatenIsland Universiaty Hospital Diagnosis and Management of Preterm Labor James Ducey MD Staten Island University Hospital

2. StatenIsland Universiaty Hospital Making The Diagnosis Labor is a retrospective diagnosis Once vaginal delivery has occurred we can be sure the woman was in labor There are a variety of methods we use to diagnose labor None of them are foolproof

3. StatenIsland Universiaty Hospital Clinical Factors Used to Predict Preterm Labor Risk assessment is a concept first proposed by Papiernik ( Presse Med 1969 ) The hope was that identification of women at increased risk to give birth early prior to the onset of labor would lead to interventions that would prevent preterm birth

4. StatenIsland Universiaty Hospital Risk Assessment The frequency of a large # of demographic and epidemiological markers in women who did and did not give birth were compared Scoring systems to predict which women were at increased risk for preterm birth

5. StatenIsland Universiaty Hospital Economic Poor Unemployed Father is either Not insured No access to care Not well fed

6. StatenIsland Universiaty Hospital Behavioral Poor education Not compliant with prenatal care Substance abuse Old or young Life stresses

7. StatenIsland Universiaty Hospital Medical Mom was small at birth Short Underweight or overweight? Chronic illnesses

8. StatenIsland Universiaty Hospital Obstetric Previous preterm birth Multiple birth Acute infections Hypertensive disorders of pregnancy Uterine anomalies

9. StatenIsland Universiaty Hospital Risk Assessment Creasy and co-workers have published a number of more simplified scoring systems( ObGyn 1980,1982,Birth Defects 1983 ) Prospective studies have reported sensitivities of 40 – 60% Positive predictive values between 15 – 30%

10. StatenIsland Universiaty Hospital History Pain-abdominal,back,pelvic,vaginal,gas Vaginal bleeding, staining Pelvic pressure Urinary frequency Diarrhea or constipation

11. StatenIsland Universiaty Hospital History Many normal women who deliver at term have similar symptoms Iams etal ( ObGyn 1990 ) reported that 1/3 of the women they studied that developed preterm labor had no symptoms at all

12. StatenIsland Universiaty Hospital Physical Examination Asymptomatic effacement and dilation of the cervix frequently occurs prior to labor It may be the first sign of labor, cervical incompetence or normal variation especially in multiparous women Buekens ( Lancet 1994 ) in a randomized study of over 5000 women showed no difference in outcome when cervical exam was performed at every visit

13. StatenIsland Universiaty Hospital Uterine Activity Frequency and duration of uterine contractions can be monitored accurately in an ambulatory setting There is an increase in uterine activity in 24 hours prior to preterm labor ( Katz ObGyn 1986 )

14. StatenIsland Universiaty Hospital Uterine Activity Initial studies were promising In addition to uterine activity monitoring there was a lot of nursing contact Much controversy ensued May diagnose preterm labor sooner Not clinically significant

15. StatenIsland Universiaty Hospital Biochemical Markers Estrogen Progesterone Prostaglandins and their metabolites Activan Inhibin Collagenase Tissue inhibitors of metaloproteinases Fetal Fibronectin

16. StatenIsland Universiaty Hospital Fetal Fibronectin Component of extra cellular matrix Lockwood ( NEJM 1991 ) found that levels were elevated in cervicovaginal secretions in women who delivered early AHRQ published a review of the data

17. StatenIsland Universiaty Hospital Fetal Fibronectin 7 Days <37 Weeks Sensitivity 89.4% 54.7% Specificity 83.3% 85.6% PPV 22.9% 58.8% NPV 99.3% 83.4%

18. StatenIsland Universiaty Hospital Fetal Fibronectin AT SIUH 81 Test in 71 women 20 have delivery data 13 Negatives 8 were term 5 preterm (all 35 – 36 weeks) None within 7 days 7 positives 3 were term 4 preterm (all <32 weeks) 2 within 7 days

19. StatenIsland Universiaty Hospital Endovaginal Ultrasound Cervix visualized in great detail Funneling of the internal cervical os Length of the cervix Sensitivity, specificity, positive and negative predictive values similar to fetal fibronectin

20. StatenIsland Universiaty Hospital Treatment Surgery Pharmacological agents Behavioral changes

21. StatenIsland Universiaty Hospital Correction of Uterine Malformations Women with defects in lateral fusion of the Mullarian ducts appear to be at increased risk for preterm labor Surgery is usually reserved only for habitual abortion

22. StatenIsland Universiaty Hospital Cervical Incompetence History of cervical trauma or surgery Two subsequent pregnancies that terminated spontaneously in the late second or early third trimester and the loss was characterized by days of pelvic pressure followed by spontaneous rupture of the membranes and quick painless labor

23. StatenIsland Universiaty Hospital Cerclage Has become the standard treatment Large prospective randomized study was carried out by RCOG 1992( BJOG 1993 ) A heterogeneous group of women felt to be at increased risk for preterm birth

24. StatenIsland Universiaty Hospital Cerclage A very safe operation There was a significant decrease in delivery prior to 35 weeks in women who under went cerclage 25 operations to prevent 1 preterm birth

25. StatenIsland Universiaty Hospital Pharmacological Agents Tocolytics Glucocorticoids Thyrotropin-releasing hormone Antibiotics Others

26. StatenIsland Universiaty Hospital Tocolytics Magnesium sulfate Beta adrenergic agonists Prostaglandin inhibitors Calcium channel blockers Oxytocin-receptor antagonist Ethanol Progesterone

27. StatenIsland Universiaty Hospital Tocolytics All these drugs seem to delay delivery 48 hours None is superior in efficacy Delay of 48 hours improves neonatal outcome when corticosteroids are used in conjunction

28. StatenIsland Universiaty Hospital Magnesium Sulfate Maternal side effects are nausea, uncomfortable sensation of heat, weakness, pulmonary edema(1%) and respiratory arrest Fetal side effects are hypotonia and hypocalcemia

29. StatenIsland Universiaty Hospital Beta Adrenergic Agonists Ritodrine and Terbutaline Maternal side effects include myocardial ischemia, pulmonary edema(4%), hypotension, tachycardia, hypokalemia, hyperglycemia and acidosis Fetal effects include hypotension, tachycardia, hypoglycemia and hyperbilirubinemia

30. StatenIsland Universiaty Hospital Prostaglandin Synthetase Inhibitors Indomethacin Maternal side effects include GI upset, rash, headache and interstitial nephritis Fetal effects include oliguria, oligohydramnios, premature closure of the ductus arteriosus and pulmonary hypertension

31. StatenIsland Universiaty Hospital Calcium Channel Blockers Nifedipine Maternal side effects include headache, nausea,flushing,hypotension,tachycardia and hepatotoxicity Fetal effects are not clear

32. StatenIsland Universiaty Hospital Oxytocin Receptor Blockers Atosiban new drug that appears to be effective Causes nausea, headache, chest pain, arthralgias and may inhibit lactation

33. StatenIsland Universiaty Hospital Ethanol No longer used Caused acute intoxication in the mother May be toxic to the fetus

34. StatenIsland Universiaty Hospital Progesterones Has been used for many years to prevent miscarriage without proven efficacy Keirse ( BrJObGyn 1990 ) found that when used routinely on initial registration resulted in a significant decrease in preterm labor and birth No effect on neonatal morbidity or mortality however

35. StatenIsland Universiaty Hospital Antenatal Steroids Crowley etal( BrJObGyn 1990 ) meta-analysis of 12 controlled studies There was a significant decrease in RDS,IVH,NEC and NND NIH conference 1995 concluded that all women at risk for preterm birth between 24 and 34 weeks are candidates

36. StatenIsland Universiaty Hospital TRH Knight etal ( AJOG 1994 )reported that adding TRH to corticosteroids improved fetal lung maturation Crowther etal ( Lancet 1995 ) was unable to reproduce the results and had a high incidence of hypertension develop in treated women

37. StatenIsland Universiaty Hospital Antibiotics Several studies have looked at the use of various drugs to treat subclinical infections and prevent neonatal sepsis Results have been inconsistent Has not gained acceptance

38. StatenIsland Universiaty Hospital Behavioral Changes Bed rest Coitus Substance abuse Obesity

39. StatenIsland Universiaty Hospital Obesity Will kill more Americans in the next 50 years than cancer, cigarette smoking and HIV combined

40. StatenIsland Universiaty Hospital Obesity Schieve etal ( Epid 1999 ) women with increased weight gain during pregnancy were at increased risk for preterm birth Rothacker etal ( ADA2000 ) mean weight gain of women 20 – 30 years of age from 1992 to 1997 increased 12.1 kg

41. StatenIsland Universiaty Hospital The Future Tocolysis will only impact on <5% of preterm birth Fetal fibronectin and/or endovaginal ultrasound needs to be used to identify objectively women for randomized studies

42. StatenIsland Universiaty Hospital The Future Reproductive endocrinologist need to limit the # of embryos they implant Iatrogenic prematurity continues in some places despite many of our best efforts