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Antepartum trials that changed clinical practice
Catherine Y Spong, MD
Pregnancy and Perinatology Branch, NICHD
National Institutes of Health
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
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.
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
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
NICHD MFMU Trials & clinical practice BEARS trial BV/TV PPROM antibiotic trial HUAM FOX trial Progesterone trial BEAM trial
Fox: Bloom et al NEJM 2006Progesterone: Meis et al NEJM 2003BEAM: Rouse et al NEJM 2008
BEARS: Wapner et al, AJOG 2006 Wapner et al, NEJM 2007PPROM: Mercer et al JAMA 1997
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 - 316 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
BEARS Beneficial Effects of Antenatal Repeat corticoSteroids
Wapner et al, AJOG 2006Wapner 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) <10th 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
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
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
Repeat courses should not be used routinely but should be reserved for
women enrolled in clinical trials.
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 2006Progesterone: Meis et al NEJM 2003BEAM: Rouse et al NEJM 2008
BEARS: Wapner et al, AJOG 2006 Wapner et al, NEJM 2007PPROM: Mercer et al JAMA 1997
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
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 2000TV: Klebanoff et al, N Engl J Med 2001
TV: 1900 pregnant women (950/group)
Rates of Preterm Birth
0%
4%
8%
12%
16%
20%
<37 <35 <32
0%
4%
8%
12%
16%
20%
<37 <35 <32
Asymptomatic BVAsymptomatic BV Asymptomatic TVAsymptomatic TV
PlaceboMetronidazole
PTD
BV: Carey et al, N Engl J Med 2000TV: Klebanoff et al, N Engl J Med 2001
P<0.004
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 2000TV: Klebanoff et al, N Engl J Med 2001
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 2000TV: Klebanoff et al, N Engl J Med 2001
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 2006Progesterone: Meis et al NEJM 2003BEAM: Rouse et al NEJM 2008
BEARS: Wapner et al, AJOG 2006 Wapner et al, NEJM 2007PPROM: Mercer et al JAMA 1997
Stopped a practice
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
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 pPROMprolongs latency and improves neonatal outcome
The NICHD PPROM Study
Ampicillin 2gm + Erythromycin 250mg IV q6h x 48hAmoxicillin 250mg q8h + erythromycin base 333mg q8h po x 5d
Mercer et al JAMA 1997
Preterm PROM:Antibiotics are recommended to prolong latency if there are no contraindications
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 2006Progesterone: Meis et al NEJM 2003BEAM: Rouse et al NEJM 2008
BEARS: Wapner et al, AJOG 2006 Wapner et al, NEJM 2007PPROM: Mercer et al JAMA 1997
Stopped a practice
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
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 poorlySensitivity = 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
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
HUAM not clinically useful to predict patients who will
deliver preterm
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 2006Progesterone: Meis et al NEJM 2003BEAM: Rouse et al NEJM 2008
BEARS: Wapner et al, AJOG 2006 Wapner et al, NEJM 2007PPROM: Mercer et al JAMA 1997
Stopped a practice
Stopped a practice
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
Background
• May 2000 – Conditional FDA approval*
• Randomized trial by Garite et al (Am J Obstet Gynecol 2000;183:1049)
* Conditional requires post-marketing surveillance
Women Enrolledn = 1010
EFM alonen = 502
EFM + Oximetryn = 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
ACOG cannot endorse adoption…encourages trials
Eligible, consented participant
EFM + “Open”Fetal Oximetry
EFM + “Masked”Fetal Oximetry
STUDY DESIGN
Bloom et al, NEJM 11/2006
Women screenedn = 27,570
Women consenting to study and sensor
insertion attemptedn = 5,553
Exclusioncriteria
n = 10,804
Randomizedn = 5,341
Not randomizedn = 212
Prolonged FHR decelerations during
sensor insertion n = 42
Open arm
n = 2,629
Masked arm
n = 2,712
Declined participationn = 11,425
Failed sensor insertionn = 170
0.310.300.59
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
Pvalue
Masked Armn=2712 (%)
Open Armn=2629 (%)
Method of Delivery
Bloom et al, NEJM 11/2006
Infant Composite Outcome
0.7592 (3.4)85 (3.2)Composite outcome*
P value
Masked Armn=2712 (%)
Open Armn=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
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
NICHD MFMU Trials & clinical practice BEARS trial BV/TV PPROM antibiotic trial HUAM FOX trial Progesterone trial BEAM trial
Stopped a practice
Stopped a practice
Therapy / treatment
Fox: Bloom et al NEJM 2006Progesterone: Meis et al NEJM 2003BEAM: Rouse et al NEJM 2008
BEARS: Wapner et al, AJOG 2006 Wapner et al, NEJM 2007PPROM: Mercer et al JAMA 1997
Stopped a practice
Stopped a practice
Progesterone
•Steroid hormone•In target cells (endometrium)
•becomes tightly bound to progesterone receptor•forms a transcription factor.
•Actions of Progesterone on the MyometriumDecreases conduction of contractionsIncreases threshold for stimulationDecreases spontaneous activityDecreases number of oxytocin receptorsPrevents formation of gap junctions
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
1o outcome: delivery <37 wks Sample: 463 pregnant women
Characteristics
Qualifying delivery (wks) 30.5 31.3 Maternal age (yrs) 26.0 26.5 Married 51% 46% African American 59% 58% Mean BMI 26.9 25.9 Smoking 22% 19%
17-P Placebo
Meis et al, N Engl J Med 2003
Progesterone: Rates of Preterm Birth
0%
10%
20%
30%
40%
50%
60%
70%
< 37 <35 <32 Afr.American
Non Afr-Am
P<0.0001 P<0.016 P<0.018
Meis et al, N Engl J Med 2003Meis et al, N Engl J Med 2003
17P
17P17P
17P
17P
P=0.010 P=0.004
AfricanAmerican
Non AfricanAmerican
Progesterone prevents neonatal complications
0%
2%
4%
6%
8%
10%
12%
14%
16%
neonataldeath
RDS BPD IVH* NEC*
17 P
17 P17 P 17 P
Placebo
Placebo
Placebo
Placebo
Placebo
Meis et al, N Engl J Med 2003
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=102B-blocker use in MI patients to prevent cardiac death NNT=42
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
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
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)
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
0%
20%
40%
60%
80%
100%
<37 wks <35 wks <32 wks <28 wks
Twins: Delivery or Fetal Death Prior to 37, 35, 32 or 28 weeks
Rouse et al, NEJM 2007; 357:454-61
17-OHPC
Placebo
Delivery or Fetal Death Before 35 WeeksBy Conception Method & Chorionicity
0%
20%
40%
60%
80%
100%
Spont. ART MonoChor DiChor
17-OHPC Placebo
Rouse et al, NEJM 2007; 357:454-61
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
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
NICHD MFMU Trials & clinical practice BEARS trial BV/TV PPROM antibiotic trial HUAM FOX trial Progesterone trial BEAM trial
Stopped a practice
Stopped a practice
Preventative therapy
Therapy / treatment
Fox: Bloom et al NEJM 2006Progesterone: Meis et al NEJM 2003BEAM: Rouse et al NEJM 2008
BEARS: Wapner et al, AJOG 2006 Wapner et al, NEJM 2007PPROM: Mercer et al JAMA 1997
Stopped a practice
Stopped a practice
BEAM Beneficial Effects of Antenatal Magnesium
Aim: To determine if antenatal MgSo4 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: MgSo4 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
BEAM To determine if antenatal MgSO4 can reduce the risk of cerebral palsy
*co-funded by NINDS0%
2%
4%
6%
8%
10%
12%
14%
Placebo MgSO4
Cerebral Palsy Death
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
NICHD MFMU Trials & clinical practice BEARS trial BV/TV PPROM antibiotic trial HUAM FOX trial Progesterone trial BEAM trial GDM trial
Stopped a practice
Stopped a practice
Preventative therapy
Therapy / treatment
Fox: Bloom et al NEJM 2006Progesterone: Meis et al NEJM 2003BEAM: Rouse et al NEJM 2008
Potential preventative therapy
BEARS: Wapner et al, AJOG 2006 Wapner et al, NEJM 2007PPROM: Mercer et al JAMA 1997
Stopped a practice
Stopped a practice
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
Mild gestational diabetes trial
Treatment of mild GDM reduced• Birthweight
• Macrosomia by 50%• Neonatal fat mass• Shoulder dystocia • Cesarean delivery • Preeclampsia and gestational hypertension
Treatment of mild GDMTreatment of mild GDM
0
2
4
6
8
10
12
14
16
BW>4000g LGA SGA
Treated Untreated
%
P<.001 P<.001
P>.4
n=28 n=65 n=34 n=65 n=29n=36
SECONDARY OUTCOMESSECONDARY OUTCOMES
05
10152025303540
Induction CD CD adj Shoulderdystocia
Treated Untreated
%
P=.021
P=.011
P=.019
P=.86
Shoulder dystocia:
7/476 Treated
18/455 Untreated
P=0.019
NNT 95% CI
Macrosomia 12 (8, 22)
Shoulder Dystocia 40 (21, 262)
Cesarean Delivery 14 (8, 95)
Gest HTN/ Preeclampsia 20 (11, 103)
Identification and treatment of mild GDM associated with significant benefits:
NICHD MFMU Trials & clinical practice BEARS trial BV/TV PPROM antibiotic trial HUAM FOX trial Progesterone trial BEAM trial GDM trial
Stopped a practice
Stopped a practice
Preventative therapy
Therapy / treatment
Fox: Bloom et al NEJM 2006Progesterone: Meis et al NEJM 2003BEAM: Rouse et al NEJM 2008
Potential preventative therapy
BEARS: Wapner et al, AJOG 2006 Wapner et al, NEJM 2007PPROM: Mercer et al JAMA 1997
Stopped a practice
Stopped a practice
Provided data to support therapy
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
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 hospitalizedAffirmed ACOG recommendation of delivery at/after 39 weeks
N Engl J Med, 2008;358, 1672-1681
http://www.nichd.nih.gov/about/org/cdbpm/pp/prog_epbo/epbo_case.cfm?renderforprint=1
23555
NRN: Extremely Preterm Birth Outcome Data
N Engl J Med, 2008;358, 1672-1681
http://www.nichd.nih.gov/about/org/cdbpm/pp/prog_epbo/epbo_case.cfm?renderforprint=1
24780
NRN: Extremely Preterm Birth Outcome Data
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 33.50 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
Hypothermia TrialWhole Body Cooling
N Engl J Med. 2005 Oct 13;353(15):1574-84
0%
10%
20%
30%
40%
50%
60%
70%
Standard care Hypothermia
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
Combined Death Or Disability Rates
0
10
20
30
40
50
60
70
80
90
COOL CAP NICHD
Standard Care Hypothermia
PE
RC
EN
T O
F IN
FA
NT
S
Higgins, Ob Gyn 2005
Current evidence supports the conclusion that mild to moderate hypothermia holds promise for the amelioration of neural injury after a perinatal hypoxic-ischemic insult
Electronic Fetal Heart Rate Monitoring: Revisited
Obstet Gynecol2008:112661-665
ART & Pregnancy OutcomesObstet Gynecol 2007:109; 967-977
Weight Gain During Pregnancy:Reexamining the Guidelines
Committee to Reexamine IOM Pregnancy Weight Guidelines
New recommendationsPrepregnancy BMI category
Total weight gain
(lb, kg)
Rate of weight gain
2nd and 3rd trimester
(lb/wk, kg/wk)
Underweight
(< 18.5 kg/m2)
28-40, 12.5-18 1.0 (1.0-1.3),
0.51 (0.44-0.58)
Normal-weight
(18.5-24.9 kg/m2)
25-35, 11.5-16 1.0 (0.8-1.0),
0.42 (0.35-0.50)
Overweight
(25.0-29.9 kg/m2)
15-25, 7-11.5 0.6 (0.5-0.7),
0.28 (0.23-0.33)
Obese
(≥ 30.0 kg/m2)
11-20, 5-9 0.5 (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”
Provisional guidelines*:mothers of twins
Prepregnancy BMI category Weight gain at term
Normal-weight 37-54 lb,17-25 kg
Overweight 31-50 lb,14-23 kg
Obese 25-42 lb,11-19 kg
*Based on the interquartile (25th-75th percentile) of gains of women who delivered twins at term (37-42 wk gestation) with birth weights ≥ 2,500 gNote: Insufficient data are available to offer a guideline for underweight women
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
Consensus Conference:Vaginal Birth After Cesarean (VBAC)
Consensus Conference March 8-10, 2010
Bethesda, Marylandhttp://consensus.nih.gov/future.htm
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
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
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
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%)
MOMS Contact for Potential Patients
Call toll free: 1-866-ASK-MOMS e-mail: [email protected]
web: http://www.spinabifidamoms.com
The George Washington University Biostatistics Center 6110 Executive Blvd, Suite 750 Rockville, MD 20852
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
The goal: healthy children, mothers and families