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Oral Plenary Session I www.AJOG.orgThursday, February 14, 2013 • 8:00 am – 10:00 am • Continental Ballroom

GENERAL

Abstracts 1 – 8Moderators: Kate Menard, MD, President, SMFM; George Saade, MD, Immediate Past President, SMFM; Michael Lu, MD,

2013 Honorary Member

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1 Pessaries in multiple pregnancy as a prevention ofreterm birth (ProTWIN): a randomized controlled trial

Sophie Liem1, Ewoud Schuit2, Joke Bais3, Karin de Boer4, KittyBloemenkamp5, Josien Brons6, Hans Duvekot7, Bas Nij Bijvanck8,

aureen Franssen9, Ingrid Gaugler10, Jan Molkenboer11, Martijnudijk12, Dimitri Papatsonis13, Paula Pernet14, Martina Porath15,iesbeth Scheepers16, Marko Sikkema17, Jan Sporken18, Harryisser19, Wim van Wijngaarden20, Mallory Woiski21, Marielle vanampus22, Ben Willem Mol1, Dick Bekedam22

1Academic Medical Center, Obstetrics and Gynaecology, Amsterdam,etherlands, 2University Meical Center Utrecht, Julius Center for Health

Sciences and Primary Care, Utrecht, Netherlands, 3Medical Center Alkmaar,bstetrics and Gynaecology, Alkmaar, Netherlands, 4Hospital Rijnstate,

Obstetrics and Gynaecology, Arnhem, Netherlands, 5Leiden UniversityMedical Center, Obstetrics and Gynaecology, Leiden, Netherlands, 6MedicalSpectrum Twente, Obstetrics and Gynaecology, Enschede, Netherlands,7Erasmus Medical Center, Obstetrics and Gynaecology, Rotterdam,

etherlands, 8Isala Clinics, Obstetrics and Gynaecology, Zwolle,Netherlands, 9University Medical Center Groningen, Obstetrics andGynaecology, Groningen, Netherlands, 10Jeroen Bosch Hospital, Obstetricsand Gynaecology, Den Bosch, Netherlands, 11Spaarne Hospital, Obstetricsand Gynaecology, Hoofddorp, Netherlands, 12University Medical Center

trecht, Obstetrics and Gynaecology, Utrecht, Netherlands, 13Amphiaospital, Obstetrics and Gynaecology, Breda, Netherlands, 14Kennemerasthuis, Obstetrics and Gynaecology, Haarlem, Netherlands, 15Maximaedical Center, Obstetrics and Gynaecology, Veldhoven, Netherlands,

16Academic Hospital Maastricht, Obstetrics and Gynaecology, Maastricht,etherlands, 17Hospital Group Twente, Obstetrics and Gynaecology,

Almelo, Netherlands, 18Canisius Hospital, Obstetrics and Gynaecology,ijmegen, Netherlands, 19Tergooi Hospital, Obstetrics and Gynaecology,laricum, Netherlands, 20Bronovo Hospital, Obstetrics and Gynaecology,en Haag, Netherlands, 21St Radboud University Medical Center, Obstetrics

and Gynaecology, Nijmegen, Netherlands, 22Onze Lieve Vrouwe Gasthuis,bstetrics and Gynaecology, Amsterdam, Netherlands

OBJECTIVE: To evaluate whether prophylactic use of a cervical pessary canrevent preterm birth in women with a multiple pregnancy.

STUDY DESIGN: We performed a randomized trial in 40 hospitals in theNetherlands (ProTWIN NTR1858). Women with a multiple preg-nancy were randomly assigned to a cervical pessary or no interven-tion. The primary outcome was a composite adverse neonatal out-come defined as PVL, IRDS, BPD, IVH II B or worse, NEC, provensepsis or death before discharge. Secondary outcomes included timeto delivery, and birth rates before 32 and 37 weeks. We performed aprespecified subgroup analysis for women with a CL� the 25th per-centile at 16-20 weeks of gestation. We needed 800 women to show areduction in the adverse neonatal outcome rate from 12.4% till 6.7%.Analysis was by intention to treat.RESULTS: We allocated 403 women to the pessary group and 410 to nontervention, and as writing the abstract 97% of the outcome data areomplete. There were 42 (11%) women in the pessary group and 4211%) in the control group who had at least one child with a compos-te adverse neonatal outcome (RR 1.0; CI 95% 0.67-1.5). A pessary didot significantly reduce the delivery rate � 32 weeks (9% vs 12%, RR

0.76; 0.50-1.1) or 37 weeks of gestation (54% vs 57%, RR 0.93; 0.82-1.0). However, in the prespecified subgroup of women with a CL �25th percentile (38 mm), the pessary group (N�78) had a lower ad-verse neonatal outcome rate as compared the non-intervention group(N�65) (10% vs 25%, RR 0.41; 0.19-0.90). This was accompanied by

S2 American Journal of Obstetrics & Gynecology Supplement to JANUARY 201

a significantly reduced preterm delivery rate �32 wk (12% vs 28%, RR0.43; 0.21-0.89), but not �37 wk (61% vs 75%, RR 0.80; 0.54-1.2).CONCLUSION: In an unselected population of women with a multiplepregnancy we found no proof for effectiveness of the use of a cer-vical pessary in the prevention of preterm birth. However, inwomen with a cervical length � the 25th percentile at 16-20 weeks,a pessary significantly reduced both adverse neonatal outcome andsevere preterm birth rates.

2 Multiple Courses of Antenatal Corticosteroids forreterm birth study: 5-year outcomes (MACS-5)

Elizabeth Asztalos1, Kellie Murphy2, Mary Hannah1, Andrewillan5, Stephen Matthews6, Arne Ohlsson3, Edmond Kelly3,

aroj Saigal7, Sue Ross9, Marie-France Delisle10, Patricia Guselle1,. Anthony Armson11, Shoo Lee3, Amiram Gafni8, Reneeananes4, Joanne Rovet4, Kofi Amankwah1

1Sunnybrook Health Sciences Centre, University of Toronto, Women &abies Program, Toronto, ON, Canada, 2Mt. Sinai Hospital, University of

Toronto, Obstetrics & Gynecology, Toronto, ON, Canada, 3Mt. SinaiHospital, University of Toronto, Paediatrics, Toronto, ON, Canada,4Hospital for Sick Children, University of Toronto, Psychology, Toronto, ON,

anada, 5SickKids Research Institute, University of Toronto, Child HealthEvaluative Sciences, Toronto, ON, Canada, 6University of Toronto,Physiology, Toronto, ON, Canada, 7McMaster University, Paediatrics,

amilton, ON, Canada, 8McMaster University, Clinical Epidemiology &Biostatistics, Hamilton, ON, Canada, 9University of Alberta, Obstetrics &

ynecology, Edmonton, AB, Canada, 10University of British Columbia,bstetrics & Gynecology, Vancouver, BC, Canada, 11Dalhousie University,bstetrics & Gynecology, Halifax, NS, Canada

OBJECTIVE: Recent trials of repeated courses of antenatal cortico-teroid therapy show some benefits in the reduction of respiratoryistress but have raised concerns regarding potential harm. Long-erm outcomes at 2 years of age have shown no benefit in theeurodevelopmental status of the children. The aim of this studyas to determine the effects of repeated courses of antenatal cor-

icosteroid therapy versus placebo on death or neurodevelopmen-al impairment among the children enrolled in the Multipleourses of Antenatal Corticosteroids for Preterm Birth Study

MACS) at 5 years of age.STUDY DESIGN: The primary outcome was a combined outcome of

death or survival with a severe disability in at least one of the following

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www.AJOG.org General Oral Plenary Session I

domains: non-ambulatory cerebral palsy, blindness in at least one eye,deafness, need for visual or hearing aids, neuro-cognitive disability at5 years of age. Five year follow-up was conducted from 2006-2012 in52 of the initial 80 centers worldwide, where 2141 of 2304 fetuses/infants (93%) were enrolled. A total of 1728(80.7%) had adequatedata for the main outcome at 5 years of age.RESULTS: There was no significant difference between the two treat-

ent groups in the risk of death or neurodevelopmental difficulty:17 (24.9%) of the 873 in the repeat courses group vs. 210 (24.6%) ofhe 855 in the placebo group, [odds ratio 1.025, 95% confidence in-erval 0.81-1.29, p�0.83]. The rates of death or individual neurode-elopmental difficulties did not differ significantly between the tworoups.

CONCLUSION: Multiples courses of antenatal corticosteroid therapygiven, every 14 days, do not increase or decrease the risk of death orneurodevelopmental difficulties by 5 years of age compared with asingle course. Because there has been no clear benefit seen in the neo-natal period, as well as at 2 and 5 years of age, this approach of ante-natal corticosteroids is not recommended for routine use. Future re-search may be warranted for a more specified use of repeated coursesof antenatal corticosteroids.

3 Prevention of preterm delivery by 17 alpha-ydroxyprogesterone caproate in asymptomaticwin pregnancies with a short cervix: aandomized controlled trial

Marie Victoire Senat1, Philippe Deruelle2,orbert Winer3, Patrick Rozenberg4

1Hopital Bicêtre, Hopital Antoine Béclère, APHP, Paris Sud, Faculté deedecine Paris XI, Department of Obstetrics and Gynecology, Clamart,

rance, 2Hôpital Jeanne de Flandre, CHU Lille, F-59000, EA2694, UDSL,Université Lille Nord de France, Department of Obstetrics and Gynecology,Lille, France, 3Hôpital Mère-Enfant, Department of Obstetrics and

ynecology, Nantes, France, 4Hôpital Poissy saint-Germain, Department ofObstetrics and Gynecology, Poissy, FranceOBJECTIVE: To evaluate the use of 17 alpha-hydroxyprogesteroneaproate (17P) to reduce the risk of preterm delivery in asymptomaticwin pregnancy with short cervix.

STUDY DESIGN: This open-label multicenter randomized controlledrial took place at 10 university hospitals between June 2006 and Jan-ary 2010. Women older than 18 years and carrying twins were eligi-le between 24�0 through 31�6 weeks of gestation if they weresymptomatic, presented a cervical length less than 25 mm as mea-ured by routine transvaginal ultrasound and provided a written in-ormed consent. Women were randomly assigned in a 1:1 ratio toeceive 500 mg of intramuscular 17P, and repeated twice a week until6 weeks or preterm delivery, whichever occurred first, or to no treat-ent with 17P (control group). The primary outcome was time from

andomization to delivery.RESULTS: Maternal characteristics of the 82 women in the 17P group

*Apart from a death, child may have more than 1 disability; **10 cases were reviewed by an adjudi-cation committee to determine whether they met the primary outcome; 5 cases were determined tohave met the primary outcome.

nd the 83 women in the control group were similar. Outcome data

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were available for 161 of the 165 women (97,6%). The intent-to-treatanalysis with censoring at last follow up showed no significant differ-ence between the 17P and controls group in median [Q1-Q3] time todelivery (45 [26-62] and 51 [36-66] days, respectively; mean differ-ence, �7; 95% CI, �15; �1). Treatment with 17P was associated witha significantly increase in the rate of preterm deliveries before 32weeks of gestation (29% vs 12%, p�0.007), but not before 37 weeks ofgestation (80% vs 77%, p�0.70) or 34 weeks of gestation (44 % vs 28%, p�0.10). Median [Q1-Q3] birth weight did not differ between 17Pand controls groups for twin 1 (2120 [1750-2471]g and 2215 [1982-2535] g, p�0,06) but differ significantly for twin 2 (2090 [1540-2425]and 2230 [1985-2535] g, p�0,027). There was a non significant trendto an increase of neonatal morbidity in a 17P group.CONCLUSION: 17P is ineffective in women with asymptomatic twinsand short cervix for prevention of preterm delivery and possiblyharmful.

4 Antenatal origins of metabolic syndromen fetuses of obese women

Andrea Edlow1, Neeta Vora1, Lisa Hui2, Heather Wick3,anet Cowan4, Diana Bianchi2

1Tufts Medical Center, Mother Infant Research Institute, and Division ofaternal-Fetal Medicine, Boston, MA, 2Tufts Medical Center, Mother Infant

esearch Institute, Boston, MA, 3Tufts University, Department of Computercience, Medford, MA, 4Tufts Medical Center, Department of Pathology,

Boston, MAOBJECTIVE: Molecular mechanisms that predispose offspring of obese

regnant women to insulin resistance, appetite dysregulation, andatty liver disease are poorly understood. We sought to understand theffects of maternal obesity on fetal gene expression by analyzing cell-ree fetal RNA (cffRNA) in amniotic fluid supernatant (AFS).

STUDY DESIGN: We prospectively studied cffRNA in AFS of womenith singleton fetuses undergoing clinically indicated 2nd trimesterenetic amniocenteses. Eight obese gravidas (Ob, BMI �30) and 8ean controls (L, BMI �25) were matched for gestational age and fetalex. Exclusion criteria included abnormal karyotype and structuralnomalies. CffRNA was extracted, amplified, and hybridized to wholeenome expression arrays. Genes significantly differentially regulatedn 8/8 pairs were identified using paired t-test with the Benjamini-

ochberg (BH) correction. Functional analyses were performed us-ng Ingenuity Pathways Analysis™ software. Genes and transcriptionactors associated with bias-corrected absolute Z-scores �2.0 or BH� .05 were called significant.

RESULTS: Demographic characteristics are shown in Table 1. Thereere 205 differentially regulated genes in fetuses of obese gravidas.he most up-regulated gene (9-fold) in Ob was APOD, which encodeslipoprotein integral to lipid regulation, glucose metabolism, and

nflammatory response. Upstream regulator analyses demonstratedignificant activation of the estrogen receptor and the transcriptionactors STAT3 and FOS in fetuses of obese women.

CONCLUSION: Expression of APOD, STAT3, and FOS is implicated ininsulin resistance, hyperleptinemia, hepatic steatosis, atherosclerosis,toll-like receptor signaling, and inflammatory response. Analysis ofcffRNA in AFS demonstrates a pro-estrogenic, pro-inflammatory mi-lieu for fetuses of obese women. Molecular mechanisms predisposingoffspring of obese women to metabolic complications may be initi-ated as early as the second trimester.

Subject demographics and array hybridizationcharacteristics

ement to JANUARY 2013 American Journal of Obstetrics & Gynecology S3