GENOMICS OF ENDOGLIN PATHWAY IN PREECLAMPSIA

THE GENOMICS OF ENDOGLIN PATHWAY IN PREECLAMPSIA Mandy J. Bell, PhD, RN University of Pittsburgh, 2012 Preeclampsia is a pregnancy disorder that greatly impacts maternal and fetal/neonatal health and wellbeing. This case-control candidate gene association study investigated endoglin pathway genetic variation and its association with preeclampsia. Tagging single nucleotide polymorphisms (tSNPs) in ENG, TGFβ1, TGFβR1, ALK1, and TGFβR2 were genotyped with iPLEX® and TaqMan® in maternal/fetal dyads. The Prenatal Exposures and Preeclampsia Prevention study provided maternal DNA extracted from peripherally collected white blood cell pellets, along with umbilical cord serum we used for fetal DNA extraction. Data on 355 white (181 cases/174 controls) and 60 black (30 cases/30 controls) women matched on ancestry, age, and parity were analyzed. Separate subgroup allele/genotype/haplotype tests were conducted with Chi-square or Fisher’s exact tests. Binary logistic regression provided odds ratios for tSNPs with significant genotype tests. Analysis of maternal/fetal dyads was not conducted, because unlike the maternal samples, the fetal samples did not provide a quality template suitable for iPLEX® data collection. In white women, variation in ENG (rs11792480, rs10121110) and TGFβR2 (rs6550005) was associated with preeclampsia. Allelic frequency distributions in rs11792480, rs10121110, and rs6550005 were significantly different among cases and controls while genotype distributions of rs10121110 and rs6550005 were further associated with preeclampsia (p-values < .05). For rs10121110, women with the AA genotype were 2.290 times more likely to develop preeclampsia compared to the GG genotype (99% CI [1.022, 5.133], p = .008). ENG haplotype TACGA, which contains rs11792480 and rs10121110 risk alleles, was also over-represented in cases (p = .022). In black women, variation in TGFβ1 (rs4803455, rs4803457), TGFβR1 (rs10739778), and TGFβR2 (rs6550005, rs1346907, rs877572) was associated with preeclampsia. Allelic frequency distributions in rs10739778, rs6550005, rs1346907, and rs877572 were significantly different among cases and controls while genotype distributions of rs10739778, rs4803455, and rs4803457 were further associated with preeclampsia (p-values < .05). For rs4803457, women with the CT genotype were 7.437 more times likely to develop preeclampsia compared to the CC genotype (99% CI [1.192, 46.408], p = .005). These results demonstrate that variation in ENG pathway genes is associated with preeclampsia, with different genes from the same pathway contributing to preeclampsia in white compared to black women

Effect of maternal posture on breech presentation in pregnancy

Breech malpresentation is associated with maternal-infant morbidity and mortality. Maternal knee-chest posture is a clinical practice intended to reduce the incidence of breech presentation and its concomitant risks in pregnancy. However, research on postural management has been inconclusive. This randomized clinical trial investigated whether knee-chest posture is associated with a higher proportion of breech infants converting to cephalic presentation during pregnancy. The study was conducted with 25 pregnant women whose infants were in breech presentation at 34–38 weeks gestation. Gestational age, parity, race, and treatment were evaluated for effect on version using Fisher exact tests. Gestational age, parity and treatment met screening criteria (p ≤ .25) for significance in the univariate analyses. Logistic regression was not employed due to zero cells in some of the univariate contingency tables. Effects of the intervention on infant presentation in labor, mode of delivery, birthweight, and 5-minute Apgar were examined by Fisher exact tests. There was no significant effect of intervention on birth outcomes at the p ≤ .05 level. Data from this study of 25 women were combined with data from two previous randomized trials for the same intervention. There was no effect of knee-chest posture on breech presentation in pregnancies over 36 weeks gestation. Implications for nurses and obstetric care providers include knowing that postural management of breech pregnancy is not yet adequately tested, advising clients accordingly and participating in the research to establish whether knee-chest posture promotes cephalic version of breech presentation