SMFM Abstracts S149 479 VASCULAR ENDOTHELIAL GROWTH FACTOR GENE D936 C/T POLYMORPHISM IS ASSOCIATED WITH PREECLAMPSIA IN KOREAN WOMEN JAE-YOON SHIM1, JONG KWAN JUN2, HYE-SUNG WON1, PIL RYANG LEE1, AHM KIM1, HEE CHUL SYN2, 1 University of Ulsan College of Medicine, Asan Medical Center, Obstetrics & Gynecology, Seoul, South Korea, 2Seoul National University College of Medicine, Obstetrics & Gynecology, Seoul, South Korea OBJECTIVE: The objective of this study was to evaluate potential associations of vascular endothelial growth factor (VEGF) gene polymorphisms with preeclampsia. STUDY DESIGN: One-hundred and ten patients with preeclampsia and 209 healthy pregnant controls were enrolled in the study. All women were of Korean origin, which is made up of a single ethnic group. After peripheral blood was obtained from all women and the genomic DNA was isolated, we genotyped C936 C/T polymorphisms of 30 -untranslated region in the VEGF gene, using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: The distribution of genotypes of the C936 C/T polymorphism was signiﬁcantly diﬀerent between women with preeclampsia and control group (p!0.001). The carriage rate of the 936T allele was signiﬁcantly more frequent in preeclamptic patients than healthy pregnant controls (OR=2.06, 95% CI: 1.38-3.08). In dominant model, carriers of the T allele were signiﬁcantly more frequent in preeclamptic women (OR=2.28, 95% CI: 1.41-3.69). We performed logistic regression analysis, including the VEGF genotype and clinical parameter such as age, educational status, body mass index, neonatal sex. The carriage rate of the 936T allele was signiﬁcantly more frequent in preeclamptic patients than healthy pregnant controls (Adjusted OR=2.23, 95% CI: 1.46-3.42). In dominant model, carriers of the T allele were signiﬁcantly more frequent in preeclamptic women (Adjusted OR=2.53, 95% CI: 1.51-4.23). CONCLUSION: These ﬁndings suggest that the carriage of C936T allele of the VEGF gene is associated with susceptibility to developing preeclampsia and is an independent risk factor of preeclampsia.
481 RANDOMIZED CONTROLLED TRIAL OF ACARBOSE VS. PLACEBO IN THE TREATMENT OF GESTATIONAL DIABETES JACQUELYN CORTEZ1, MARYAM TARSA1, SALLY AGENT1, RAMEN CHMAIT2, THOMAS MOORE1, 1University of California, San Diego, Reproductive medicine, San Diego, California, 2University of Southern California, Los Angeles, California OBJECTIVE: Up to 50% of patients with gestational diabetes require medical treatment for glycemic control. Currently, glyburide and insulin are the mainstay of treatment for gestational diabetes. The primary aim of this study was to compare to placebo the eﬀectiveness of acarbose, a minimally absorbed alpha glucosidase inhibitor, in achieving glycemic targets without need for additional medication. STUDY DESIGN: This was an intent-to-treat double blinded randomized controlled trial. Patients diagnosed with gestational diabetes between 12-34 weeks were randomized to placebo or acarbose at doses of 50 mg three times daily and increased by 50mg per dose when 50% of target plasma glucose levels (fasting !95, 1 hr postprandial !135 mg/dl) were exceeded in a week. Failure was deﬁned when additional medication was indicated after 300 mg daily was reached. Power analysis (a = .05, b = 0.8) to ﬁnd a 38% diﬀerence in failure rates required 25 subjects per arm. RESULTS: 29 patients were randomized to acarbose and 30 patients to placebo. Both groups were similar in age (30.5 vs. 29.2), gestational age at recruitment (24.1 vs. 26.2), and body mass index (29.6 vs. 29.9) respectively. The acarbose group had fewer failures (42.3% vs. 66.6%, r=0.05) and less weight gain (12.9 vs. 21.7 lbs r=0.04) when compared to placebo group. There were no statistically signiﬁcant diﬀerences in side eﬀects, gestational age at delivery, Apgar scores, birth weight, and mode of delivery. CONCLUSION: Acarbose is an eﬀective agent in medical treatment of gestational diabetes, but with a higher failure rate than reported for glyburide (4-18%). 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.524
0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.522
480 CHANGES IN BIOCHEMICAL MARKERS OF BONE TURN OVER AND BONE MINERAL DENSITY DURING PREGNANCY AND POSTPARTUM IN KOREAN WOMEN JAE HYUG YANG1, SIWON LEE2, MOON-YOUNG KIM2, JUNE SEEK CHOI3, JINHOON CHUNG2, JUNG HAN KIM2, DAL SOO HONG2, 1Sungkyunkwan University, Seoul, South Korea, 2Cheil General Hospital and Women’s Healthcare Center, Sungkyunkwan University School of Medicine, Obstetrics and Gynecology, Seoul, South Korea, 3Sungkyunkwan University, OB & GYN, Seoul, South Korea OBJECTIVE: To investigate the amount of change in biochemical markers of bone turn over and bone mineral density(BMD) during pregnancy and postpartum in normal pregnant Korean women. STUDY DESIGN: 41 healthy singleton pregnant women were included. BMD of the calcaneous bone was measured by ultrasound in 22 pregnant women (in the ﬁrst and second trimester). Markers of bone resorption (urinary crosslinked type I collagen N-telopeptides) and bone formation (total alkaline phosphatase, osteocalcin), total serum calcium, serum phosphorus and serum parathyroid hormone (PTH) were analyzed during (once in each trimester) and after pregnancy (postpartum 2 days, and 2 months). RESULTS: During pregnancy, BMD signiﬁcantly decreased (P!0.05) at the calcaneous bone. Urinary cross-linked type I collagen N-telopeptides and serum PTH progressively increased towards term and showed peak levels in the immediate postpartum period (P!0.001 and P!0.05 respectively). Total alkaline phosphatase levels steadily increased as gestational weeks increased and showed peak levels in the third trimester of pregnancy and decreased in the postpartum period (P!0.001). Osteocalcin levels declined toward the second trimester, gradually increased in the third trimester, and showed peak levels in the immediate postpartum period and returned to normal in the postpartum two months period (P!0.001). The total calcium levels were low throughout pregnancy and postpartum 2 day period, but they increased to the peak level in the postpartum 2 months period. Serum phosphorus levels were lowest in the second trimester and showed the highest level in the postpartum 2 months period. CONCLUSION: Pregnancy is characterized by high bone turnover and bone metabolism is very active in pregnant women. Calcium needed for infant growth during pregnancy may be achieved from the maternal skeleton. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.523
482 MANNOSE-BINDING LECTIN CODON 54 GENE POLYMORPHISM PROTECTS AGAINST PREECLAMPSIA, HELLP SYNDROME AND INTRAUTERINE GROWTH RESTRICTION ISTVAN SZILLER1, OKSANA BABULA2, PETRONELLA HUPUCZI1, GABOR SZABO´1, BARBARA RIGO´1, ZOLTAN PAPP1, IARA LINHARES2, STEVEN WITKIN2, 1 Semmelweis University, 1st Department of Obstetrics and Gynecology, Budapest, Hungary, 2Weill Medical College of Cornell University, Obstetrics and Gynecology, New York, New York OBJECTIVE: Increasing evidence suggests a prominent role for insuﬃcient invasion of the spiral arteries by trophoblast cells in the etiology of preeclampsia (PEC), HELLP syndrome and PEC-associated intrauterine growth restriction (IUGR). Mannose-binding lectin (MBL) is a component of the innate immune system. MBL-mediated activation of the complement cascade is an important event in the destruction of invading trophoblasts. The gene coding for MBL is polymorphic, and variant alleles result in greatly reduced circulating MBL levels. The aim of this study was to test the association between an MBL polymorphism and PEC, HELLP syndrome and IUGR. STUDY DESIGN: DNA was extracted from buccal swabs from 51 women with preeclampsia, 81 women with HELLP syndrome and 184 healthy pregnant controls in Budapest, Hungary. Aliquots were tested by polymerase chain reaction and endonuclease digestion for the single nucleotide MBL gene polymorphism at codon 54. Investigators were blinded to clinical outcomes. RESULTS: Homozygosity for the wild type allele was more frequent in patients with preeclampsia (P=0.01) and HELLP syndrome (P=0.02) as compared to healthy controls. The presence of the variant allele was more prevalent among healthy controls than in preeclamptics (p=0.02) or women with HELLP syndrome (p=0.02). Among patients with PEC, IUGR was diagnosed in 22 (55%) of neonates born to mothers who delivered before, compared to 0% of those who delivered after, 37 weeks. MBL-54 heterozygosity was more frequent in controls (27.2%) than in preeclamptic women who delivered an IUGR neonate before 37 weeks (4.5 %) (P=0.02). CONCLUSION: Carriage of the MBL codon 54 polymorphism protects against preeclampsia, IUGR and HELLP syndrome and implies that MBLmediated complement activation and/or another MBL-mediated event is involved in the pathogenesis of these disorders. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.525