1. Antepartum trials that changed clinical practice Catherine Y Spong, MD Pregnancy and Perinatology Branch, NICHD National Institutes of Health

2. Objectives To describe antepartum trials and studies that resulted in stopping a practice that was not beneficial (BV/TV; HUAM, FOX) To describe trials that provided evidence for a new treatment or preventative therapy (Abx in PPROM, progesterone, BEAM, GDM) To describe other studies and trials that result in changes in practice

3. The mission of the NICHD is to ensure that every person is born healthy and wanted, that women suffer no harmful effects from reproductive processes, and that all children have the chance to achieve their full potential for healthy and productive lives, free from disease or disability, and to ensure the health, productivity, independence, and well-being of all people through optimal rehabilitation.

4. Obstetrical management, especially for high-risk patient, has often adopted practices without objective evaluation In an attempt to respond to the need for well-designed clinical trials in maternal fetal medicine, the NICHD established the MFMU Network in 1986 NICHD MFMU Origins

5. NICHD’s MFMU Network centers 2006-11 14 Clinical sites Data center NICHD ~120,000 deliveries/yr Re-competition: 5 yrs Columbia Case Western Magee Women Northwestern Ohio State Oregon HSU U Alabama U North Carolina U Texas-Houston U Texas SW-Dallas U Utah U TMB Galveston Wayne State Women and Infants

6. NICHD MFMU Trials & clinical practice BEARS trial BV/TV PPROM antibiotic trial HUAM FOX trial Progesterone trial BEAM trial Fox: Bloom et al NEJM 2006 Progesterone: Meis et al NEJM 2003 BEAM: Rouse et al NEJM 2008 BEARS: Wapner et al, AJOG 2006 Wapner et al, NEJM 2007 PPROM: Mercer et al JAMA 1997

7. BEARS Beneficial Effects of Antenatal Repeat corticoSteroids Aim: To determine if repeat courses of antenatal corticosteroids will decrease neonatal morbidity vs single course Design: double-masked, placebo-controlled trial Eligibility criteria: 23 - 31 6 wks gestation at risk for PTD who are pregnant >7d after initial steroid course Intervention: weekly betamethasone or placebo Primary outcome: composite outcome including mortality, severe RDS, CLD, grade III/IV IVH, PVL Secondary outcome: 2yr followup Wapner et al, AJOG 2006 Wapner et al NEJM 357: 1190-8 Sep 20 2007

8. BEARS Beneficial Effects of Antenatal Repeat corticoSteroids Wapner et al, AJOG 2006 Wapner et al NEJM 357: 1190-8 Sep 20 2007 495 randomized No reduction in composite (8% vs 9%, P=0.67) Reduction in surfactant with repeat ACS (P=.02) <10 th centile (24% vs 15%, P=.02) Repeat ACS significantly reduced specific neonatal morbidities but do not improve composite neonatal outcome with reduction in birthweight and increase in SGA

9. BEARS Followup At 24 to 36 months infants exposed to weekly courses show no significant difference in: Anthropometric Measurements Weight, Length, Head circumference Neurodevelopmental Evaluation Bayley II PDI and MDI results A non significant increase in cerebral palsy in infants exposed to 4 or more courses RR: 5.7 (0.7 – 46.8) Wapner et al NEJM 357: 1190-8 Sep 20 2007

10. BEARS Followup Caution Is Warranted In Using Repeat Courses Of Antenatal Corticosteroids Until Additional Information Is Available Wapner et al NEJM 357: 1190-8 Sep 20 2007

11. Repeat courses should not be used routinely but should be reserved for women enrolled in clinical trials.

12. NICHD MFMU Trials & clinical practice BEARS trial BV/TV PPROM antibiotic trial HUAM FOX trial Progesterone trial BEAM trial Stopped a practice Fox: Bloom et al NEJM 2006 Progesterone: Meis et al NEJM 2003 BEAM: Rouse et al NEJM 2008 BEARS: Wapner et al, AJOG 2006 Wapner et al, NEJM 2007 PPROM: Mercer et al JAMA 1997

13. Infection/inflammation and sPTD Evidence supports infection cause of PTD: Clinical & subclinical chorioamnionitis Bacterial vaginosis in pregnancy associated with poor perinatal outcome, in particular an increased risk of PTD Antibiotic trials RCT metronidazole +BV with hx prior sPTD PTD 18% v 39%, p<.05 Morales et al 1994 RCT metronidazole+erythromycin in high risk women, +BV PTD 23% v 37%, p<.001 Hauth et al 1994 McGregor 1990, Kurki 1992, Hay 1994, Hillier 1995

14. NICHD: MFMU BV/TV Trials Aim: To establish whether metronidazole therapy will reduce the risk of PTD in women with asymptomatic bacterial vaginosis or trichomonas vaginalis Design: double-masked, placebo-controlled trial Eligibility criteria: <24 wks, BV or TV positive Intervention: Four doses of 2g metronidazole or placebo Primary outcome: delivery at < 37 weeks’ Sample: BV: 1900 pregnant women (950/group) BV: Carey et al, N Engl J Med 2000 TV: Klebanoff et al, N Engl J Med 2001 TV: 1900 pregnant women (950/group)

15. Rates of Preterm Birth Asymptomatic BV Asymptomatic TV Placebo Metronidazole PTD BV: Carey et al, N Engl J Med 2000 TV: Klebanoff et al, N Engl J Med 2001 P<0.004

16. BV/TV trials TV trial stopped by DSMC after interim analysis found increased PTD in metronidazole group Effectiveness of treatment BV: 78% negative for BV TV: 93% negative for trichonomiasis BV: Carey et al, N Engl J Med 2000 TV: Klebanoff et al, N Engl J Med 2001

17. BV/TV trials: Conclusions Treatment of asymptomatic BV does not reduce PTD or adverse perinatal outcomes TV increased the risk of PTD Results from these trials changed the practice of indiscriminate use of antibiotics in pregnancy BV: Carey et al, N Engl J Med 2000 TV: Klebanoff et al, N Engl J Med 2001

18. NICHD MFMU Trials & clinical practice BEARS trial BV/TV PPROM antibiotic trial HUAM FOX trial Progesterone trial BEAM trial Stopped a practice Fox: Bloom et al NEJM 2006 Progesterone: Meis et al NEJM 2003 BEAM: Rouse et al NEJM 2008 BEARS: Wapner et al, AJOG 2006 Wapner et al, NEJM 2007 PPROM: Mercer et al JAMA 1997 Stopped a practice

19. Preterm PROM (<32 w) Occurs in 3% of pregnancies Responsible for one third of PTD Important cause of perinatal morbidity/mortality >70% deliver within one week of ROM Complications of prematurity & related to pPROM Antibiotic therapy Treat/prevent ascending decidual infection to prolong pregnancy Offer opportunity for reduced neonatal infectious and GA dependent morbidity

20. n= 611 pPROM <32 w RCT antibiotics vs conservative mgmt Antibiotics: Prolonged latency Reduced neonatal complications Reduced gestational age dependent morbidity Broad spectrum antibiotic therapy in pPROM prolongs latency and improves neonatal outcome The NICHD PPROM Study Ampicillin 2gm + Erythromycin 250mg IV q6h x 48h Amoxicillin 250mg q8h + erythromycin base 333mg q8h po x 5d Mercer et al JAMA 1997

21. Preterm PROM: Antibiotics are recommended to prolong latency if there are no contraindications

22. NICHD MFMU Trials & clinical practice BEARS trial BV/TV PPROM antibiotic trial HUAM FOX trial Progesterone trial BEAM trial Stopped a practice Therapy / treatment Fox: Bloom et al NEJM 2006 Progesterone: Meis et al NEJM 2003 BEAM: Rouse et al NEJM 2008 BEARS: Wapner et al, AJOG 2006 Wapner et al, NEJM 2007 PPROM: Mercer et al JAMA 1997 Stopped a practice

23. Home Uterine Activity Monitoring Premise: Uterine activity higher in women destined for PTD Uterine activity increases 24-48h before an episode of PTL RCTs: No difference in PTB Dyson et al 2,400 high risk women NEJM 1998 CHUMS: 1,292 high risk women AJOG 1995

24. NICHD MFMU The NICHD HUAM Prediction Study Blinded monitoring of women w/ risk of PTD  Contraction frequency was related to risk of PTD  Contractions predicted PTD poorly  Sensitivity = 9.3% for  4 Contractions / hr  PPV = 26.7% to predict birth < 35 weeks Iams et al NEJM 2002 Deliver < 35 w Deliver > 35 w

25. UC frequency is increased in women who will deliver < 35 w Magnitude too small to be clinically useful Contractions are common in pregnancy Contractions occur late in process HUAM not clinically useful to predict patients who will deliver preterm The NICHD HUAM Prediction Study

26. HUAM not clinically useful to predict patients who will deliver preterm

27. NICHD MFMU Trials & clinical practice BEARS trial BV/TV PPROM antibiotic trial HUAM FOX trial Progesterone trial BEAM trial Stopped a practice Therapy / treatment Fox: Bloom et al NEJM 2006 Progesterone: Meis et al NEJM 2003 BEAM: Rouse et al NEJM 2008 BEARS: Wapner et al, AJOG 2006 Wapner et al, NEJM 2007 PPROM: Mercer et al JAMA 1997 Stopped a practice

28. FOX Fetal Pulse Oximetry trial Aim: To determine if fetal pulse oximetry affects overall cesarean delivery rate; CS for FD Design: RCT, 2-arm trial Eligibility criteria: Singleton, >36 wks Primary outcome: Cesarean delivery Status: 5087 patients enrolled Findings: Fetal oximetry not beneficial in reducing CD or CD for fetal distress Bloom et al, NEJM 11/2006

29. Background May 2000 – Conditional FDA approval* Randomized trial by Garite et al (Am J Obstet Gynecol 2000;183:1049) * Conditional requires post-marketing surveillance

30. Women Enrolled n = 1010 EFM alone n = 502 EFM + Oximetry n = 508 C/S Distress 10% C/S Dystocia 9% C/S Total 26% 5% 19% 29% P = 0.007 P < 0.001 P = 0.49 Garite et al, AJOG 2000

31. ACOG cannot endorse adoption…encourages trials

32. Eligible, consented participant EFM + “Open” Fetal Oximetry EFM + “Masked” Fetal Oximetry STUDY DESIGN Bloom et al, NEJM 11/2006

33. Women screened n = 27,570 Women consenting to study and sensor insertion attempted n = 5,553 Exclusion criteria n = 10,804 Randomized n = 5,341 Not randomized n = 212 Prolonged FHR decelerations during sensor insertion n = 42 Open arm n = 2,629 Masked arm n = 2,712 Declined participation n = 11,425 Failed sensor insertion n = 170

34. 0.31 0.30 0.59 747 (27.5) 214 ( 7.9) 521 (19.2) 692 (26.3) 187 ( 7.1) 490 (18.6) Cesarean delivery: Overall Non-reassuring FHR Dystocia 0.76 400 (15) 380 (15)Forceps or vacuum 0.261565 (58)1557 (59)Spontaneous birth P value Masked Arm n=2712 (%) Open Arm n=2629 (%) Method of Delivery Bloom et al, NEJM 11/2006

35. Infant Composite Outcome 0.7592 (3.4)85 (3.2)Composite outcome* P value Masked Arm n=2712 (%) Open Arm n=2629 (%) Characteristic * Composite outcome includes one or more of: 5-minute Apgar ≤ 3 Umbilical artery pH < 7.0 Seizures Ventilator use > 24 hours Admission to neonatal intensive care > 48 hours Bloom et al, NEJM 11/2006

36. Conclusions Fetal Oximetry: Did not lower cesarean rates Did not modify infant outcomes Bloom et al, NEJM 11/2006 Fetal pulse oximetry not clinically useful as FHR monitoring adjunct to prevent Cesarean delivery

37. NICHD MFMU Trials & clinical practice BEARS trial BV/TV PPROM antibiotic trial HUAM FOX trial Progesterone trial BEAM trial Stopped a practice Therapy / treatment Fox: Bloom et al NEJM 2006 Progesterone: Meis et al NEJM 2003 BEAM: Rouse et al NEJM 2008 BEARS: Wapner et al, AJOG 2006 Wapner et al, NEJM 2007 PPROM: Mercer et al JAMA 1997 Stopped a practice

38. Progesterone Steroid hormone In target cells (endometrium) becomes tightly bound to progesterone receptor forms a transcription factor.transcription factor Actions of Progesterone on the Myometrium Decreases conduction of contractions Increases threshold for stimulation Decreases spontaneous activity Decreases number of oxytocin receptors Prevents formation of gap junctions

39. NICHD: MFMU Progesterone Trial Aim: To establish if weekly progesterone injections in women with prior spontaneous preterm delivery (sPTD) reduces the risk of PTD Design: double-masked, placebo-controlled trial Eligibility criteria: singleton pregnancy 16-20 wks with documented previous sPTD Intervention: progesterone or placebo Meis et al, N Engl J Med 2003 1 o outcome: delivery <37 wks Sample: 463 pregnant women

40. Characteristics Qualifying delivery (wks) 30.5 31.3 Maternal age (yrs) 26.0 26.5 Married51% 46% African American59% 58% Mean BMI26.9 25.9 Smoking22% 19% 17-PPlacebo Meis et al, N Engl J Med 2003

41. Progesterone: Rates of Preterm Birth P<0.0001P<0.016P<0.018 Meis et al, N Engl J Med 2003 17P P=0.010P=0.004 African American Non African American

42. Progesterone prevents neonatal complications 17 P Placebo Meis et al, N Engl J Med 2003

43. Effectiveness of Progesterone 5-6 women with a previous sPTB would need to be treated to prevent one birth <37 wks 12 women with a previous sPTB birth would need to be treated to prevent one birth <32 wks Low dose ASA to prevent CVA, NNT=102 B-blocker use in MI patients to prevent cardiac death NNT=42

44. Progesterone prevents recurrent preterm delivery Weekly injections of progesterone prevented recurrent preterm birth and improved the neonatal outcome for pregnancies at risk Effective in preventing very early as well as later preterm birth Effective in both African American and Non-African American women Meis et al, N Engl J Med 2003

45. ACOG Committee Opinion: Use of Progesterone to Reduce Preterm Birth Obstet Gynecol 2003;102:1115-6 Recommends the use of progesterone to prevent PTD for women with prior sPTD

46. Impact of progesterone to prevent recurrent preterm birth 10,000 preterm births could have been prevented in 2002 if all eligible pregnant women at high risk for PTD received 17P Resulting in reduction of preterm birth of ~2% Petrini et al, Obstet Gynecol 2005; 105(2)

47. STTARS Seventeen alpha-hydroxyprogesterone caproate in Twins and Triplets: A Randomized Study) Double-masked placebo-controlled trial to determine whether 17  hydroxyprogesterone prevents preterm birth in multifetal pregnancies. Intervention: 17-OHPC (250mg IM) or placebo weekly beginning at 16-20 weeks Primary outcome: Preterm delivery < 35 wks Status: complete, 661 women randomized Rouse et al, NEJM 2007; 357:454-61

48. Twins: Delivery or Fetal Death Prior to 37, 35, 32 or 28 weeks Rouse et al, NEJM 2007; 357:454-61 17-OHPC Placebo

49. Delivery or Fetal Death Before 35 Weeks By Conception Method & Chorionicity Rouse et al, NEJM 2007; 357:454-61

50. STTARS Seventeen alpha-hydroxyprogesterone caproate in Twins and Triplets: A Randomized Study) 17P did not reduce the rate of PTB in women with twins This lack of benefit applied: - whether conception was spontaneous or after ART or - whether there was a di- or monochorionic placentation - regardless of gestational age cutoff 17-OHPC was well tolerated with side effects limited to the injection site The rate of PTB in the placebo group was similar to national norms (34.9 vs 35.2 weeks) Rouse et al, NEJM 2007; 357:454-61

51. Recommends the use of progesterone to prevent PTD for women with prior sPTD May be considered for use in asymptomatic women with a very short cervix Obstet Gynecol 2008;112:963-5

52. NICHD MFMU Trials & clinical practice BEARS trial BV/TV PPROM antibiotic trial HUAM FOX trial Progesterone trial BEAM trial Stopped a practice Preventative therapy Therapy / treatment Fox: Bloom et al NEJM 2006 Progesterone: Meis et al NEJM 2003 BEAM: Rouse et al NEJM 2008 BEARS: Wapner et al, AJOG 2006 Wapner et al, NEJM 2007 PPROM: Mercer et al JAMA 1997 Stopped a practice

53. BEAM Beneficial Effects of Antenatal Magnesium Aim: To determine if antenatal MgSo 4 can reduce the risk of cerebral palsy in offspring Design: double-masked, placebo-controlled trial Eligibility criteria: 24 - 31 wks gestation with PROM, PTL or planned delivery Intervention: MgSo 4 or placebo Primary outcome: composite outcome of death <1 yr or cerebral palsy at 24 months Sample size: 2220, 2241 enrolled! co-funded by NINDS

54. BEAM To determine if antenatal MgSO 4 can reduce the risk of cerebral palsy * co-funded by NINDS Beneficial Effects of Antenatal Magnesium N Engl J Med. 2008 August 28; 359 2,241 women randomized 95.6% follow up Significant reduction in moderate/severe CP from 3.5% to 1.9% RR(95%CI) 0.55(0.32-0.95) Risk of death not different NNT=63

56. NICHD MFMU Trials & clinical practice BEARS trial BV/TV PPROM antibiotic trial HUAM FOX trial Progesterone trial BEAM trial GDM trial Stopped a practice Preventative therapy Therapy / treatment Fox: Bloom et al NEJM 2006 Progesterone: Meis et al NEJM 2003 BEAM: Rouse et al NEJM 2008 Potential preventative therapy BEARS: Wapner et al, AJOG 2006 Wapner et al, NEJM 2007 PPROM: Mercer et al JAMA 1997 Stopped a practice

57. Mild gestational diabetes trial Aim: To test whether identification and dietary treatment of mild GDM reduces composite outcome Design: RCT with additional observational cohorts Eligibility criteria: 24-29 wks gestation, normal FBS, abnormal 3h-GTT Intervention: treatment (counseling, dietary management) vs standard non-GDM care Primary outcome: Fetal composite Status: 1,889 patients enrolled Submitted to SMFM 2008

58. Mild gestational diabetes trial Treatment of mild GDM reduced Birthweight Macrosomia by 50% Neonatal fat mass Shoulder dystocia Cesarean delivery Preeclampsia and gestational hypertension

59. Treatment of mild GDM % P<.001 P>.4 n=28 n=65n=34n=65n=29n=36

60. SECONDARY OUTCOMES % P=.021 P=.011 P=.019 P=.86 Shoulder dystocia: 7/476 Treated 18/455 Untreated P=0.019

61. NNT95% CI Macrosomia12(8, 22) Shoulder Dystocia40(21, 262) Cesarean Delivery14(8, 95) Gest HTN/ Preeclampsia20(11, 103) Identification and treatment of mild GDM associated with significant benefits:

62. NICHD MFMU Trials & clinical practice BEARS trial BV/TV PPROM antibiotic trial HUAM FOX trial Progesterone trial BEAM trial GDM trial Stopped a practice Preventative therapy Therapy / treatment Fox: Bloom et al NEJM 2006 Progesterone: Meis et al NEJM 2003 BEAM: Rouse et al NEJM 2008 Potential preventative therapy BEARS: Wapner et al, AJOG 2006 Wapner et al, NEJM 2007 PPROM: Mercer et al JAMA 1997 Stopped a practice Provided data to support therapy

63. Findings that Impact Clinical Practice Timing repeat CD – ACOG Committee Opinion Induction of labor/VBAC – ACOG committee opinion Periviable calculator – website calculator Inhaled NO – limitation of use in preterm infants SIDS – AAP initiatives, policy statements Cesarean on maternal request – ACOG Committee Opinion Late preterm infants – AAP+ACOG committee opinion Perinatal risks + ART – ACOG committee opinion Screening for fetal chromosomal abN – ACOG com opinion Subclinical hypothyroidism – ACOG committee opinion Hypothermia for HIE – AAP statement

64. Timing of Repeat Elective CD 13,258 women with elective repeat CD >37 35.8% delivered before 39 weeks Complications increased 2 fold at 37 weeks 20% increase still at 38 4/7- 38 6/7 15% at 37w; 11% at 38w; 8% 39wks Tita, A for MFMU. NEJM, Vol. 360, No. 2, January 8, 2009;111-20 Respiratory, mechanical ventilation, sepsis, hypoglycemia, NICU, >5d hospitalized Affirmed ACOG recommendation of delivery at/after 39 weeks

65. N Engl J Med, 2008;358, 1672-1681 http://www.nichd.nih.gov/about/org/cdbpm/pp/prog_epbo/epbo_case.cfm?renderforprint=1 23 555 NRN: Extremely Preterm Birth Outcome Data

66. N Engl J Med, 2008;358, 1672-1681 http://www.nichd.nih.gov/about/org/cdbpm/pp/prog_epbo/epbo_case.cfm?renderforprint=1 24 780 NRN: Extremely Preterm Birth Outcome Data

67. NICHD NRN: Whole Body Hypothermia To assess the safety and effectiveness of whole body hypothermia in term infants with moderate or severe HIE. Infants enrolled between July 2000 and May 2003 Randomized to whole body cooling or standard care. Cooling blanket to esophageal temperature 33.5 0 C for 72 hours then slow re-warming Standard ICU care for control infants. N Engl J Med. 2005 Oct 13;353(15):1574-84

68. Hypothermia Trial Whole Body Cooling N Engl J Med. 2005 Oct 13;353(15):1574-84 n=106 n=102 RR(95%CI) 0.72 (0.55-0.93) Death or Moderate/Severe disability Significant reduction in moderate/severe disability from 62% to 45% Effect persistent after adjustment for clinical site and level of HIE at randomization NNT=6

69. Combined Death Or Disability Rates PERCENT OF INFANTS Higgins, Ob Gyn 2005

70. Current evidence supports the conclusion that mild to moderate hypothermia holds promise for the amelioration of neural injury after a perinatal hypoxic-ischemic insult

71. Electronic Fetal Heart Rate Monitoring: Revisited Obstet Gynecol 2008:112 661-665

72. ART & Pregnancy Outcomes Obstet Gynecol 2007:109; 967-977

73. Weight Gain During Pregnancy: Reexamining the Guidelines Committee to Reexamine IOM Pregnancy Weight Guidelines

74. New recommendations Prepregnancy BMI category Total weight gain (lb, kg) Rate of weight gain 2 nd and 3 rd trimester (lb/wk, kg/wk) Underweight (< 18.5 kg/m 2 ) 28-40, 12.5-181.0 (1.0-1.3), 0.51 (0.44-0.58) Normal-weight (18.5-24.9 kg/m 2 ) 25-35, 11.5-161.0 (0.8-1.0), 0.42 (0.35-0.50) Overweight (25.0-29.9 kg/m 2 ) 15-25, 7-11.50.6 (0.5-0.7), 0.28 (0.23-0.33) Obese (≥ 30.0 kg/m 2 ) 11-20, 5-90.5 (0.4-0.6), 0.22 (0.17-0.27) *Calculations assume a first-trimester weight gain of 1.1-4.4 lb (0.5-2.0 kg) Use of WHO BMI categories Closed interval for obese women Category names changed from “low” “normal” “high” and “obese”

75. Provisional guidelines*: mothers of twins Prepregnancy BMI categoryWeight gain at term Normal-weight37-54 lb,17-25 kg Overweight31-50 lb,14-23 kg Obese25-42 lb,11-19 kg *Based on the interquartile (25 th -75 th percentile) of gains of women who delivered twins at term (37-42 wk gestation) with birth weights ≥ 2,500 g Note: Insufficient data are available to offer a guideline for underweight women

76. Recommendations for special populations Short stature: no modification Young age: no modification; use adult BMI tables Racial/ethnic subgroups: no modification Primiparity: no modification, but trade-off should be studied further Smokers: no modification, but stop smoking

78. Consensus Conference: Vaginal Birth After Cesarean (VBAC) Consensus Conference March 8-10, 2010 Bethesda, Maryland http://consensus.nih.gov/future.htm

79. MOMS Centers The Children’s Hospital Of Philadelphia University Of California- San Francisco Vanderbilt University Medical Center Coordinating Center The George Washington University Biostatistics Center NICHD Pregnancy and Perinatology Branch

80. Management of Myelomeningocele Study (MOMS) Aim: To compare the safety and efficacy of in utero repair of open neural tube defects with standard postnatal repair Intervention: Unmasked randomized clinical trial Primary outcome: Infant death or need for ventricular shunt by 1 year of life; Bayley Scales of Infant Developmental MDI and functional anatomic level of lesion at 30 months corrected age Sample size: 200 (100/group) Screening and randomization: Central preliminary screening and central randomization to MOMS center Outcome evaluation by blinded independent investigators

81. MOMS Study Update Recruitment started in March 2003 As of August 2010, 178 patients randomized 12 and 30-month follow-up exams underway with 99% compliance Supplemental funding for more extensive urological follow-up began April 2005

82. MOMS Screening and Recruitment >240 referred to MOMS center 16% refused consent 21% not eligible 178 randomized -Other fetal anomaly found (31%) -No hindbrain herniation (25%) -Risks too high (30%) -Cannot comply with travel/FU (23%) -Termination/likely termination (23%)

83. MOMS Contact for Potential Patients Call toll free: 1-866-ASK-MOMS e-mail: MOMS@biostat.bsc.gwu.edu web: http://www.spinabifidamoms.com The George Washington University Biostatistics Center 6110 Executive Blvd, Suite 750 Rockville, MD 20852

84. Objectives Accomplished! To describe trials and studies that resulted in stopping a practice that was not beneficial (BV/TV; HUAM, FOX) To describe trials that provided evidence for a new treatment or preventative therapy (Abx in PPROM, progesterone, BEAM, GDM) To describe other studies and trials that result in changes in practice

85. The goal: healthy children, mothers and families