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Oral Concurrent Session 5 Diabetes www.AJOG.org

60 Myoinositol supplementation in pregnancies atisk for gestational diabetes. Interim analysisf a randomized controlled trial (RCT)

Fabio Facchinetti1, Lucrezia Pignatti1, Maria Lieta Interdonato2,sabella Neri1, Giulia Bellei1, Rosario D’Anna2

1University of Modena and Reggio Emilia, Mother-Infant Department,odena, Italy, 2University of Messina, Obstetric/Gynecological Sciences and

eproductive Medicine Department, Messina, ItalyOBJECTIVE: Myoinositol (MI), a polycyclic alcohol, is an insulin-sen-itizer agent. In a small RCT we tested the hypothesis that overweight/bese women could benefit from its supplementation, as far as theccurrence of Gestational Diabetes Mellitus (GDM) is concerned.

STUDY DESIGN: Single pregnant women with BMI�27 and normalglucose and Glycosylated Hemoglobin, in absence of any chronic dis-order or a previous GDM were randomized to receive, orally, 2 gramsMI�0.2 g folic acid (Treated) or folic acid alone (Controls), twice/day, in a 1:2 ratio. Randomization was done at each Center . Treat-ment started at first prenatal exam, before 11th week of pregnancy.Simple diet counseling was provided to every women. A 75 g glucosetest (OGTT) was planned at 24th-26th gestational week (main out-come). Obese women also received OGTT at 16th-18th week (nonetested positive).RESULTS: This analysis was performed at 50% recruitment. Random-zation occurred at the same time in both Centers (10.1�1.9 and.5�1.7 weeks). Age, ethnicity, BMI and parity distribution were sim-lar in Treated and Controls. Also positive family history of diabetesas equally represented. Blood glucose at OGTT is reported in theigure. Treated group showed a significantly better tolerance thanontrols. GDM was found lesser in Treated group (6/31, 19.4%) than

n Controls (24/60, 40.0%) (p�0.047). At logistic regression, both aounger age (p�0.023) and MI treatment (p�0.047) predicted fewerDM diagnoses (R square�0.053).

CONCLUSION: In women with BMI�27, MI supplementation early inpregnancy favors a better tolerance to glucose, thus lowering the rateof GDM.

S36 American Journal of Obstetrics & Gynecology Supplement to JANUARY 20

61 Intrauterine programming of diabetesnduced cardiac embryopathy

Rolanda Lister1, Bin Zhou2, Alyssa Chamberlain2,rancine Einstein2

1Montefiore Medical Center, Obstetrics & Gynecology/Women’s Health,ronx, NY, 2Albert Einstein College of Medicine, Genetics, Bronx, NY

OBJECTIVE: Maternal hyperglycemia is a well-recognized risk factoror congenital heart disease. However, the underlying cellular and

olecular mechanisms are not well characterized. Our aim is to de-ermine if maternal hyperglycemia induces changes in DNA methyl-tion in regions associated with known genes essential for normaleart development.

STUDY DESIGN: Hyperglycemia was induced in normal 8-week old ICRfemale mice with a one time intraperitoneal injection of 150 mg/kg ofstreptozotocin (STZ) prior to mating. Histological analysis of fetalcardiac morphology was evaluated for malformations on embryonic(E) 16.5 day of controls and pups exposed to maternal hyperglycemia.We used the massively-parallel sequencing-based HELP assay to ex-amine cytosine methylation levels at �1.65 million loci in neonatalhearts on post-natal (P) day 1 to assess genome-wide cytosine meth-ylation profiles.RESULTS: Various cardiac structure defects occurred in 71% of the

ups (n�14) of hyperglycemic dams. The phenotypes noted wereortic stenosis (36%), hypoplastic left heart (36%), transposition ofhe great arteries (14%), double outlet right ventricle (7%), and ven-ricular septal defect (7%). There was also a 10-fold increase in DNA

ethylation of over three hundred genes in the experimental versusontrols on P1 neonates. Several of these genes are implicated in car-iac development. Selected gene candidates known to be involved inardiac formation or function include Fhl2, Ttn, Actc1, Pitx2,mpr1b, Pdgfra, Bmp10, Myh 10, and Adrb1.

CONCLUSION: Maternal hyperglycemia alters DNA methylation ofsome cardiac genes during heart development, which may contributeto increased risk for congenital heart defects. Quantitative, genome-wide assessment of cytosine methylation may be used as a discoveryplatform to gain insight into the mechanisms of hyperglycemia-in-duced cardiac anomalies.

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