Abstract:
BACKGROUND:Abruptio placentae is a complex multifactorial disease that is associated with maternal and neonatal death and morbidity. Abruptio placentae's high recurrence rate, high prevalence of heritable thrombophilia among women with abruptio placentae, and aggregation of cases in families of women with the disease support the possibility of a genetic predisposition. Previous genome-wide and candidate gene association studies have identified single nucleotide polymorphisms in mitochondrial biogenesis and oxidative phosphorylation genes that potentially are associated with abruptio placentae risk. Perturbations in mitochondrial biogenesis and oxidative phosphorylation, which results in mitochondrial dysfunction, can lead to the impairment of differentiation and invasion of the trophoblast and to several obstetrics complications that include abruptio placentae. OBJECTIVE:The purpose of this study was to determine whether the results of a candidate genetic association study that indicated a link between DNA variants (implicated in mitochondrial biogenesis and oxidative phosphorylation) and abruptio placentae could be replicated. STUDY DESIGN:The study was conducted among participants (507 abruptio placentae cases and 1090 control subjects) of the Placental Abruption Genetic Epidemiology study. Weighted genetic risk scores were calculated with the use of abruptio placentae risk-increasing alleles of 11 single nucleotide polymorphisms in 9 mitochondrial biogenesis and oxidative phosphorylation genes (CAMK2B, NR1H3, PPARG, PRKCA, THRB, COX5A, NDUFA10, NDUFA12, and NDUFC2), which previously was reported in the Peruvian Abruptio Placentae Epidemiology study, a study with similar design and study population to the Placental Abruption Genetic Epidemiology study. Logistic regression models were fit to examine associations of weighted genetic risk scores (quartile 1, <25th percentile; quartile 2, 25-50th percentile; quartile 3, 50-70th percentile, and quartile 4, >75th percentile) with risk of abruptio placentae, adjusted for population admixture (the first 4 principal components), maternal age, infant sex, and preeclampsia. The weighted genetic risk score was also modeled as a continuous predictor. To assess potential effect modification, analyses were repeated among strata that were defined by preeclampsia status, maternal age (≥35 vs 18-34 years), and infant sex. RESULTS:Abruptio placentae cases were more likely to have preeclampsia, shorter gestational age, and lower infant birthweight. Participants in quartile 2 (score, 12.6-13.8), quartile 3 (score, 13.9-15.0) and quartile 4 (score, ≥15.1) had a genetic risk score of 1.45-fold (95% confidence interval, 1.04-2.02; P=.03), a 1.42-fold (95% confidence interval, 1.02-1.98; P=.04), and a 1.75-fold (95% confidence interval, 1.27-2.42; P=7.0E-04) higher odds of abruptio placentae, respectively, compared with those in quartile 1 (score,<12.6; P-for trend=.0003). The risk of abruptio placentae was 1.12-fold (95% confidence interval, 1.05-1.19; P=3.0×1004) higher per 1-unit increase in the score. Among women with preeclampsia, those in quartile 4 had a 3.92-fold (95% confidence interval, 1.48-10.36; P=.01) higher odds of abruptio placentae compared with women in quartile 1. Among normotensive women, women in quartile 4 had a 1.57-fold (95% confidence interval, 1.11-2.21; P=.01) higher odds of abruptio placentae compared with those in quartile 1 (P-for interaction=.12). We did not observe differences in associations among strata defined by maternal age or infant sex. CONCLUSION:In this study, we replicated previous findings and provide strong evidence for DNA variants that encode for genes that are involved in mitochondrial biogenesis and oxidative phosphorylation pathways, which confers risk for abruptio placentae. These results shed light on the mechanisms that implicate DNA variants that encode for proteins in mitochondrial function that are responsible for abruptio placentae risk. Therapeutic efforts to reduce risk of abruptio placentae can be enhanced by improved biologic understanding of maternal mitochondrial biogenesis/oxidative phosphorylation pathways and identification of women who would be at high risk for abruptio placentae.
journal_name
Am J Obstet Gynecoljournal_title
American journal of obstetrics and gynecologyauthors
Workalemahu T,Enquobahrie DA,Gelaye B,Thornton TA,Tekola-Ayele F,Sanchez SE,Garcia PJ,Palomino HG,Hajat A,Romero R,Ananth CV,Williams MAdoi
10.1016/j.ajog.2018.08.042subject
Has Abstractpub_date
2018-12-01 00:00:00pages
617.e1-617.e17issue
6eissn
0002-9378issn
1097-6868pii
S0002-9378(18)30721-Xjournal_volume
219pub_type
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journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/j.ajog.2016.05.035
更新日期:2016-10-01 00:00:00
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journal_title:American journal of obstetrics and gynecology
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doi:10.1016/s0002-9378(84)90357-0
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更新日期:2010-10-01 00:00:00
abstract:OBJECTIVE:Our aim was to determine the accuracy of cervical length and funneling of the internal os in the prediction of the spontaneous very preterm birth of twin pregnancies. STUDY DESIGN:In a prospective study at 13 centers, routine transvaginal ultrasound scanning was used to examine 251 women with twin pregnancie...
journal_title:American journal of obstetrics and gynecology
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abstract::Patients with prolonged decelerations after bupivacaine epidural anesthesia were matched with control patients. It was found that there were no differences in the decrease in mean arterial blood pressure after epidural anesthesia between those with prolonged decelerations (5 +/- 9 mm Hg) and those without (5 +/- 9 mm ...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(90)91073-l
更新日期:1990-09-01 00:00:00
abstract::Behavioral states in the near-term human fetus have been described during pregnancy. The aim of this study was to observe whether these same states are present during labor. Nine patients with uncomplicated singleton pregnancies participated. Fetal heart rate and uterine contractions were recorded. Fetal eye, mouth, r...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/s0002-9378(85)80071-5
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更新日期:2013-01-01 00:00:00
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journal_title:American journal of obstetrics and gynecology
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doi:10.1016/s0002-9378(16)33032-0
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更新日期:2019-04-01 00:00:00
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journal_title:American journal of obstetrics and gynecology
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更新日期:2004-04-01 00:00:00
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doi:10.1016/0002-9378(79)90056-5
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更新日期:2020-01-01 00:00:00
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journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(86)90799-4
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更新日期:1996-06-01 00:00:00
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更新日期:1977-10-15 00:00:00
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pub_type: 杂志文章
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更新日期:1995-10-01 00:00:00
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journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章,评审
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更新日期:2020-09-29 00:00:00
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更新日期:2011-11-01 00:00:00
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journal_title:American journal of obstetrics and gynecology
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更新日期:1976-06-15 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2011-10-01 00:00:00