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Risk of fetal death with preeclampsia.

ABSTRACT: OBJECTIVE:To estimate gestational age-specific risks of fetal death in pregnancies complicated by preeclampsia. METHODS:Population-based cohort study comprising all singleton births (N=554,333) without preexisting chronic hypertension recorded in the Norwegian Medical Birth Registry from 1999 to 2008. Additional data come from a subset of preeclamptic pregnancies enrolled in the Norwegian Mother and Child Cohort Study with available medical records (n=3,037). The risk of fetal death, expressed per 1,000 fetuses exposed to preeclampsia, was calculated using a life table approach. RESULTS:Preeclampsia was recorded in 3.8% (n=21,020) of all pregnancies. Risk of stillbirth was 3.6 per 1,000 overall and 5.2 per 1,000 among pregnancies with preeclampsia (relative risk 1.45, 95% confidence interval [CI] 1.20-1.76). However, relative risk of stillbirth was markedly elevated with preeclampsia in early pregnancy. At 26 weeks of gestation, there were 11.6 stillbirths per 1,000 pregnancies with preeclampsia compared with 0.1 stillbirths per 1,000 pregnancies without (relative risk 86, 95% CI 46-142). Fetal risk with preeclampsia declined as pregnancy advanced, but at 34 weeks of gestation remained more than sevenfold higher than pregnancies without preeclampsia. CONCLUSION:For clinical purposes, the fetal risk of death associated with preeclampsia begins when preeclampsia becomes clinically apparent. Using a method that takes into account the clinical diagnosis of preeclampsia and the population of fetuses at risk, we find a remarkably high relative risk of fetal death among pregnancies diagnosed with preeclampsia in the preterm period. LEVEL OF EVIDENCE:II.

SUBMITTER: Harmon QE

PROVIDER: S-EPMC4347876 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Risk of fetal death with preeclampsia.

Harmon Quaker E QE Huang Lisu L Umbach David M DM Klungsøyr Kari K Engel Stephanie M SM Magnus Per P Skjærven Rolv R Zhang Jun J Wilcox Allen J AJ

Obstetrics and gynecology 20150301 3

<h4>Objective</h4>To estimate gestational age-specific risks of fetal death in pregnancies complicated by preeclampsia.<h4>Methods</h4>Population-based cohort study comprising all singleton births (N=554,333) without preexisting chronic hypertension recorded in the Norwegian Medical Birth Registry from 1999 to 2008. Additional data come from a subset of preeclamptic pregnancies enrolled in the Norwegian Mother and Child Cohort Study with available medical records (n=3,037). The risk of fetal dea ...[more]

PMID: 25730226

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Project description:Preeclampsia is a leading cause of perinatal morbidity and mortality. This disorder is thought to be multifactorial in origin, with multiple genes, environmental and social factors, contributing to disease. One proposed mechanism is placental hypoxia-driven imbalances in angiogenic and anti-angiogenic factors, causing endothelial cell dysfunction. Catechol-O-methyltransferase (Comt)-deficient pregnant mice have a preeclampsia phenotype that is reversed by exogenous 2-methoxyestradiol (2-ME), an estrogen metabolite generated by COMT. 2-ME inhibits Hypoxia Inducible Factor 1?, a transcription factor mediating hypoxic responses. COMT has been shown to interact with methylenetetrahydrofolate reductase (MTHFR), which modulates the availability of S-adenosylmethionine (SAM), a COMT cofactor. Variations in MTHFR have been associated with preeclampsia. By accounting for allelic variation in both genes, the role of COMT has been clarified. COMT allelic variation is linked to enzyme activity and four single nucleotide polymorphisms (SNPs) (rs6269, rs4633, rs4680, and rs4818) form haplotypes that characterize COMT activity. We tested for association between COMT haplotypes and the MTHFR 677 C ? T polymorphism and preeclampsia risk in 1103 Chilean maternal-fetal dyads. The maternal ACCG COMT haplotype was associated with reduced risk for preeclampsia (P = 0.004), and that risk increased linearly from low to high activity haplotypes (P = 0.003). In fetal samples, we found that the fetal ATCA COMT haplotype and the fetal MTHFR minor "T" allele interact to increase preeclampsia risk (p = 0.022). We found a higher than expected number of patients with preeclampsia with both the fetal risk alleles alone (P = 0.052) and the fetal risk alleles in combination with a maternal balancing allele (P<0.001). This non-random distribution was not observed in controls (P = 0.341 and P = 0.219, respectively). Our findings demonstrate a role for both maternal and fetal COMT in preeclampsia and highlight the importance of including allelic variation in MTHFR.

Project description:BackgroundAntipsychotic medications are increasingly used during pregnancy. Nevertheless, fetal risks are still not fully studied. It is currently unclear whether the antipsychotic treatment might induce a higher risk of fetal death. We aimed to determine if use of antipsychotic medication during pregnancy is associated with an increased risk of spontaneous abortion or stillbirth.MethodsIn a historical cohort study, we identified all clinically recognized pregnancies registered in the nationwide Danish registries from 1997 to 2008 (N = 1,005,319). Exposure was defined as any prescription of antipsychotic medications redeemed by the pregnant women during the exposure window, and recorded in the Danish National Prescription Register. Outcome was defined as any spontaneous abortion or stillbirth recorded in the Danish National Hospital Register and the Danish Medical Birth Register respectively.ResultsWomen exposed to antipsychotic medications during pregnancy had a 34% higher risk of spontaneous abortion (adjusted relative risk = 1.34; 95% confidence interval = 1.22; 1.46) compared to unexposed women, but a similar risk compared to women exposed prior to (but not during) pregnancy (adjusted relative risk = 1.04; 95% confidence interval = 0.93; 1.17). The risk of spontaneous abortion was not increased in exposed pregnancies when compared to unexposed pregnancies in the same women (adjusted hazard ratio = 1.11; 95% CI = 0.94; 1.31). A twofold higher risk of stillbirth was found in women exposed to antipsychotic medications compared with unexposed women (relative risk = 2.27; 95% confidence interval = 1.45; 3.55) and compared with women exposed only prior to pregnancy (relative risk = 2.06; 95% confidence interval = 1.01; 4.19).ConclusionsThe increased risk of spontaneous abortion found in women treated with antipsychotic medications during pregnancy is most likely due to confounding factors. The risk of stillbirth was twofold higher in pregnancies exposed to antipsychotic medication during pregnancy. Treatment with antipsychotic medications during pregnancy requires careful consideration.

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Risk of fetal death with preeclampsia.

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Risk of fetal death with preeclampsia.

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