67: Single nucleotide polymorphisms (SNPs) in endothelial nitric oxide synthase (eNOS) gene and unexplained stillbirth

Abstract

nitric oxide synthase (eNOS) gene and unexplained stillbirth Francesca Ferrari, Fabio Facchinetti, Huaizhi Yin, George Saade, Monica Longo Obstetrics and Gynaecology, University of Modena and Reggio Emilia, Mother-Infant department, Modena, Italy, The University of Texas Medical Branch, Obstetrics & Gynecology, Galveston, TX OBJECTIVE: Altered utero-placental perfusion has been implicated in the pathogenesis of unexplained stillbirth (SB). We previously reported that genetic polymorphisms of VEGF affecting placental vasculogenesis are associated with unexplained SB. Nitric oxide (NO) plays a critical role in regulation of uterine perfusion, and eNOS is the rate limiting enzyme in the NO production cascade. Previous studies suggest that eNOS gene SNPs may be associated with preeclampsia and idiopathic recurrent pregnancy loss. Our objective was to evaluate the presence and distribution of eNOS gene SNPs between unexplained SB and controls in a well-characterized cohort. STUDY DESIGN: Placentas were obtained from 50 unexplained SB and 46 livebirth controls. Classification of “unexplained” stillbirth was by Wigglesworth and Aberdeen criteria and included both appropriate (AGA-SB) and small for gestational age (SGA-SB, 10th%) SB. Placental DNA was extracted (Qiagen) and evaluated for 4 eNOS SNPs (rs1007311 A/G, rs891512 A/G, rs1800779 A/G and rs1800783 A/T) by real time PCR using specific taqman probes. The genotype and allelic distributions were compared between the groups using Chisquare (significance: p 0.05). RESULTS: All SNPs were in Hardy-Weinberg equilibrium. None of the SNPs were associated with SB overall. However, significant different genotype distribution emerged for eNOS-SNP rs1800783 A/T when comparing the subgroups of SGA-SB and AGA-SB to controls (p 0.004). Allele-A carriers of rs1800783 were more frequent in AGA-SB compared to both controls (p 0.003) and SGA-SB (p 0.001)(Fig. 1). CONCLUSION: This is the first study to report on placental eNOS polymorphisms and unexplained SB. Importantly we found that Allele A of rs1800783 eNOS SNP might play a role in the occurrence of unexplained stillbirth in the setting of adequate growth. Our results warrant further population-based analysis. 68 The influence of a mediolateral episiotomy during an operative vaginal delivery on the risk for Obstetric Anal Sphincter Injuries (OASIS) Joey de Vogel, Anneke van Beek, Dirk Gietelink, Marijana Vujkovic, Jan Willem de Leeuw, Dimitri Papatsonis Amphia hospital, Department of Obstetrics and Gynecology, Breda, Netherlands, Erasmus Medical Center, Department of Obstetrics and Gynecology, Rotterdam, Netherlands, Ikazia Hospital, Department of Obstetrics and Gynecology, Rotterdam, Netherlands OBJECTIVE: Operative vaginal delivery is associated with an increased risk of Obstetric Anal Sphincter Injuries (OASIS). It’s unclear if structural use of a mediolateral episiotomy at operative vaginal delivery will decrease this risk. The aim of our study was to evaluate the incidence of OASIS in women with operative vaginal delivery, and to assess if a mediolateral episiotomy is preventive for OASIS in these deliveries. STUDY DESIGN: A retrospective cohort study was performed using the obstetric-database of the Amphia Hospital, The Netherlands of deliveries from 2001 up to 2009. All patients with live born infants delivered by an operative vaginal delivery at a gestational age 34 weeks were included. Exclusion criteria were: multiple gestations, breech deliveries and the use of a median episiotomy. Continuous variables were compared using the Students t test or Mann-Whitney U test, the 2 test for categorical variables. Continuous variables were summarized as means with standard deviations, or medians with interquartile ranges. A logistic regression model was used for the risk assessment for OASIS when a mediolateral episiotomy was performed. Treatment effect was presented as adjusted odds ratio with 95% confidence interval. RESULTS: There were 2970 operative vaginal deliveries in the study period meeting the inclusion and exclusion criteria (Figure 1). The prevalence of OASIS was 5.7%. The absolute risk was 3.3% in the MLE group, compared to 15.5% in the MLEgroup (OR 0.19; 95% CI: 0.14-0.26). The risk estimation for OASIS remained similar (adjusted OR 0.20; 95% CI: 0.12-0.34), after logistic regression analysis with correction for gestational age, parity, birth weight, maternal age, use of epidural analgesia, indication for operative vaginal delivery, cephalic fetal position, and duration of the second stage. CONCLUSION: The use of a mediolateral episiotomy in operative vaginal delivery is associated with a fivefold decreased risk for developing OASIS. Therefore we advocate the structural use of a mediolateral episiotomy during an operative vaginal delivery in order to prevent OASIS. www.AJOG.org Intrapartum Fetal/Clinical Obstetrics Oral Concurrent Session 6