buride were identified namely, 4-trans-(M1) and 3-cis-(M2b) hydroxycyclohexyl glyburide. Recently, we reported on the identification and kinetics for formation of.
SMFM Abstracts
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DELAYED VILLOUS MATURATION OF THE PLACENTA-ASSOCIATION WITH DIABETES AND PERINATAL DEATH MARY HIGGINS1, FIONNUALA MCAULIFFE1, EOGHAN MOONEY2, 1University College Dublin, Dublin, Ireland, 2National Maternity Hospital, Dublin, Ireland OBJECTIVE: Delayed villous maturation (DVM) of the placenta is defined as reduced vascularisation of the chorionic villi with decreased syncytiocapillary membranes. There is little data on its significance, but in some series it is associated with an increased risk of stillbirth in the late third trimester. The aim of this study was to assess perinatal factors associated with, and the clinical significance of, the finding of DVM on placental histology. STUDY DESIGN: This is a retrospective study investigating all pregnancies with DVM diagnosed on placental histology in a tertiary level unit from December 2000 to August 2006. Delayed villous maturation is defined as a morphological spectrum varying from mild to severe in relation to vascular syncytial membranes with decreased tertiary villi and increased large bullous villi in the more severe grades. RESULTS: Over 6 years 2,915 placentas were triaged for histopathological assessment, representing 6.1% of all 48,054 deliveries in this time period. 183 (6.3%) of these selected cases showed DVM. Fifteen preterm placentas (⬍34 weeks) were excluded, leaving 168 remaining for further analysis. When compared with all deliveries during the study period (48,054) DVM was significantly associated with pre-gestational diabetes (RR 17.56, 95% CI 10.32 to 29.37, p⬍0.001), gestational diabetes (RR 7.26, 95% CI 4.5-11.5, p⬍0.001), and antenatal or intrapartum intrauterine death (RR 5.51, 95% CI 2.08-14.43, p⬍0.005). CONCLUSION: Delayed Villous Maturation is associated with diabetes mellitus and perinatal death. The association with diabetes may be mediated by hyperglycaemia. The increased risk of in-utero hypoxia and fetal death in pre-gestational diabetic pregnancy may be mediated through placental pathology such as delayed villous maturation and merits further investigation.
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0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.378
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FETAL CENTRAL OBESITY MEASURED BY V.O.C.A.L. IN DIABETIC AND NON-DIABETIC PATIENTS ANDRZEJ LYSIKIEWICZ1, MARK PETRYGA2, BARAK ROSENN1, RICHARD JAFFE1, ODED LANGER1, 1Roosevelt Hospital, New York, New York, 2University of Poznan, Poland OBJECTIVE: To test the hypothesis that fetal fat accumulation is accelerated in diabetic pregnancy as compared with non diabetics. STUDY DESIGN: Volume scans of 332 patients were obtained at gestational age 18 - 22 weeks, prior to diabetic screening. Within this group 17 diabetic patients (16 GDM ⫹ 1 pregestational) were identified and compared with 20 randomly selected non-diabetic controls. 4D view software was used to measure fat layer volume of the fetal trunk. Fetal trunk volumes were obtained using Virtual Organ Computer Analysis (VOCAL) and fetal abdominal subcutaneous (fat) layer volumes were obtained using the VOCAL surface thickness feature (Fig.1). The index of fetal central obesity was defined as the ratio of fetal subcutaneous fat volume to the total fetal trunk volume.
IDENTIFICATION OF THE MAJOR HUMAN HEPATIC AND PLACENTAL ENZYMES RESPONSIBLE FOR THE METABOLISM OF GLYBURIDE OLGA ZHARIKOVA1, VALENTINA FOKINA1, TATIANA NANOVSKAYA1, SELVAN RAVINDRAN1, RONALD HILL2, DONALD MATTISON3, GARY D.V. HANKINS1, MAHMOUD AHMED1, 1University of Texas Medical Branch, Obstetrics and Gynecology, Galveston, Texas, 2University of Louisiana at Monroe, Basic Pharmaceutical Sciences, College of Pharmacy, Monroe, Louisiana, 3 Obstetric-Fetal Pharmacology Research Units (OPRU) Network, Center for Research For Mother and Children NICHD, Bethesda, Maryland OBJECTIVE: A clinical trial to determine the pharmacokinetics of glyburide in treatment of gestational diabetes is underway. Previously, two metabolites of glyburide were identified namely, 4-trans-(M1) and 3-cis-(M2b) hydroxycyclohexyl glyburide. Recently, we reported on the identification and kinetics for formation of five additional and identical metabolites by human hepatic and placental microsomes. However, the major product/metabolite formed was different: M1 by hepatic and M5 (ethyl-hydroxy glyburide) by placental microsomes. The aim of this investigation is to identify the major hepatic and placental CYP isozymes that catalyze the biotransformation of glyburide to each of its metabolites. STUDY DESIGN: The amounts of metabolites formed by the two microsomal preparations were determined by HPLC/MS utilizing a method developed and reported earlier by our laboratory. The identification of the major CYP isozymes responsible for the formation of each metabolite was achieved by chemicals and antibodies selective for each isozyme. RESULTS: CYP19/aromatase is the enzyme responsible for the formation of the major placental metabolite M5. In the liver, CYP3A4 accounts for most M5 formation. Preliminary data on the other metabolites suggest the following: CYP2C19 and 1A1 are responsible for the formation of all the metabolites including M1 and M2b, but their contribution to the formation of M5 is much less than that by CYP3A4. CYP2C9 is responsible for the formation of M1, M2a (4-cis-hydroxycyclohexyl glyburide) and M2b. CYP2C9 contribution to the total metabolites formed is less than 3A4, 2C19 and 1A1. CONCLUSION: Several CYP isozymes are responsible for the metabolism of glyburide by human hepatic and placental microsomes. The formation of M5 by placental CYP19/aromatase could render this metabolite more accessible to the fetal circulation. The multiplicity of CYP isozymes responsible for the metabolism of glyburide could also increase the chances of drug interactions. Supported by the Obstetrics Pharmacology Research Units (OPRU) Network of NICHD. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.380
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DIABETES IN PREGNANCY: DO DIFFERENT HISPANIC ETHNICITIES HAVE DIFFERENT OUTCOMES? YVONNE CHENG1, KATHERINE BIANCO1, INGIRD KURBISCH-BLOCK1, SANAE NAKAGAWA1, TANIA ESAKOFF1, AARON CAUGHEY1, 1University of California, San Francisco, San Francisco, California OBJECTIVE: To examine perinatal outcomes associated with diabetes in pregnancy among different Hispanic ethnicities. STUDY DESIGN: This is a retrospective cohort study of Hispanic women with term, singleton pregnancy complicated by diabetes who delivered in the United States in 2003. Maternal ethnicity was self-reported and categorized into Mexican, Puerto Rican, Cuban, and South/Central American. Categorical outcomes were compared using chi-square test and multivariable logistic regression analyses were used to control for potential confounders with non-Hispanic White designated as the reference comparison group. A p-value ⬍0.05 and 95% confidence intervals (CI) were used to indicate statistical significance. RESULTS: There were 25,636 women meeting study criteria. Of these, 76.4% were Mexican, 8.2% Puerto Rican, 1.3% Cuban, and 14.1% South/Central American. Compared to non-Hispanic Whites, Mexicans and South/Central Americans have decreased odds of undesirable maternal and neonatal outcomes while Cubans have increased odds of pregnancy-associated hypertension and cesarean delivery.
aOR 95% CI Preg-HTN RESULTS: Mean fetal trunk volume was 93.6cc ⫹⫺ 18.7cc in non diabetic patients and 102.2cc ⫹⫺22.3cc in diabetic. Fetal abdominal fat mean volume was 18.5cc ⫹⫺ 4.0cc in non diabetic and 22.1cc ⫹⫺ 4.9cc in GDM. Fetal central adiposity mean index was 19.4%⫹⫺4.5% (non diabetic) and 22.3% ⫹⫺ 5.1% in GDM. CONCLUSION: Fetal central obesity can be measured by VOCAL with consistent results and expressed as fetal central obesity index. In second trimester there was a trend of increased fetal central obesity in GDM fetuses. We speculate that increased fetal central obesity may identify future metabolic syndrome. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.379
Cesarean Bwt⬎1000 gm Apgar⬍7 Neo Injury
Mexican (n ⫽ 19,581)
Puerto Rican (n ⫽ 2,103)
Cuban (n ⫽ 329)
So/Cen Am (n ⫽ 3,623)
0.72 0.68-0.77 0.91 0.88-0.94 0.92 0.88-0.97 0.89 0.72-1.11 0.73 0.54-0.98
0.85 0.72-1.01 1.27 1.16-1.38 0.75 0.80-0.86 0.99 0.67-1.48 0.98 0.53-1.78
1.45 1.04-2.01 1.61 1.29-2.01 1.08 0.80-1.46 0.78 0.25-2.44 —
0.74 0.65-0.85 0.91 0.85-0.97 0.91 0.83-1.00 0.94 0.65-1.36 0.21 0.08-0.56
CONCLUSION: Women of different Hispanic ethnicities with diabetes had different odds of perinatal complications often associated with diabetes in pregnancy. These findings can be used to counsel women with varying ethnic Hispanic subgroups with diabetes and pregnancy and should lead to further study into the etiology of these differences. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.381
Supplement to DECEMBER 2007 American Journal of Obstetrics & Gynecology
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