Association of FOXD1 variants with adverse pregnancy outcomes in mice and humans.
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ABSTRACT:
SUBMITTER: Laissue P
PROVIDER: S-EPMC5090055 | biostudies-literature | 2016 Oct
REPOSITORIES: biostudies-literature
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Association of FOXD1 variants with adverse pregnancy outcomes in mice and humans.
Laissue Paul P Lakhal Besma B Vatin Magalie M Batista Frank F Burgio Gaëtan G Mercier Eric E Santos Esther Dos ED Buffat Christophe C Sierra-Diaz Diana Carolina DC Renault Gilles G Montagutelli Xavier X Salmon Jane J Monget Philippe P Veitia Reiner A RA Méhats Céline C Fellous Marc M Gris Jean-Christophe JC Cocquet Julie J Vaiman Daniel D
Open biology 20161001 10
Recurrent spontaneous abortion (RSA) is a common cause of infertility, but previous attempts at identifying RSA causative genes have been relatively unsuccessful. Such failure to describe RSA aetiological genes might be explained by the fact that reproductive phenotypes should be considered as quantitative traits resulting from the intricate interaction of numerous genetic, epigenetic and environmental factors. Here, we studied an interspecific recombinant congenic strain (IRCS) of Mus musculus ...[more]
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Project description:ObjectiveTo evaluate the relationship between acculturation and adverse pregnancy outcomes, and whether these relationships differ across racial or ethnic groups.MethodsThis is a planned secondary analysis of the nuMoM2b study (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be), a prospective observational cohort study of 10,038 pregnant women at eight academic health care centers in the United States. Nulliparous pregnant women with singleton gestations were recruited between 6 0/7 and 13 6/7 weeks of gestation from October 2010-September 2013. Acculturation was defined by birthplace (United States vs non-United States), language used during study visits (English or Spanish), and self-rated English proficiency. The adverse pregnancy outcomes of interest were preterm birth (less than 37 weeks of gestation, both iatrogenic and spontaneous), preeclampsia or eclampsia, gestational hypertension, gestational diabetes, stillbirth, small for gestational age, and large for gestational age. Multivariable regression modeling was performed, as was an interaction analysis focusing on the relationship between acculturation and adverse pregnancy outcomes by maternal race or ethnicity.ResultsOf the 10,006 women eligible for this analysis, 8,100 (80.9%) were classified as more acculturated (eg, born in the United States with high English proficiency), and 1,906 (19.1%) were classified as having less acculturation (eg, born or not born in the United States with low proficiency in English or use of Spanish as the preferred language during study visits). In multivariable logistic regression modeling, more acculturation was significantly associated with higher frequency of preterm birth (odds ratio [OR] 1.46, adjusted odds ratio [aOR] 1.50, 95% CI 1.16-1.95); spontaneous preterm birth (OR 1.54, aOR 1.62, 95% CI 1.14-2.24); preeclampsia or eclampsia (OR 1.39, aOR 1.31, 95% CI 1.03-1.67); preeclampsia without severe features (OR 1.44, aOR 1.43, 95% CI 1.03-2.01); and gestational hypertension (OR 1.68, aOR 1.48, 95% CI 1.22-1.79). These associations did not differ by self-described race or ethnicity.ConclusionIn a large cohort of nulliparous women, more acculturation, regardless of self-described race or ethnicity, was associated with increased odds of several adverse pregnancy outcomes.Clinical trial registrationClinicalTrials.gov, NCT01322529.
| S-EPMC7054005 | biostudies-literature
Project description:Poor oral health is not only associated with diabetes and cardiovascular disease but adverse pregnancy outcomes. However the influence of dental caries on pregnancy is unknown. The aim of this study was to evaluate the association between dental caries and adverse pregnancy outcomes and the effect of treatment for dental caries on adverse pregnancy outcomes. Primiparas who delivered a singleton between January 1, 2010 and December 31, 2014 and underwent both general health examination and oral health examination during a National Korea Health Screening Examination within 1 year of pregnancy were eligible. The data of the women who met the inclusion criteria were linked to the data of their offspring contained within the National Korea Health Screening Program for Infants and Children database. Among 120,622 women who delivered during the study period, 28,623 (23.7%) women had dental caries. Among them, 4,741 (16.6%) women were treated for dental caries after diagnosis. In a multivariable analysis, women with dental caries had an increased risk of delivering large-for-gestational-age infants (odds ratio, 1.15; 95% confidence interval, 1.07, 1.23) compared to those without dental caries. When women with dental caries were divided on the basis of the treatment of dental caries, women with dental caries but no treatment had an increased risk of delivering large-for-gestational-age infants (odds ratio, 1.15; 95% confidence interval, 1.06, 1.24); conversely, there was no increased risk in women with dental caries and treatment compared with those without. Dental caries and its treatment were not associated with preterm birth and preeclampsia. Untreated dental caries was not associated with preterm birth or preeclampsia but with the risk of delivering large-for-gestational-age infants. These whole observation may be attributed to the various characteristics of mothers who develop dental caries are not treated.
| S-EPMC7093420 | biostudies-literature
Project description:We report abnormal pregnancy outcomes in mice lacking NKG2A, including altered placental transcription. In humans, we find HLAB-21T snp to be associated with an increased risk of pre-eclampsia.
2021-04-29 | GSE173478 | GEO
Project description:Interindividual variation in DNA-methylation level is widespread in the human genome, despite its critical role in regulating gene expression. The nature of this variation, including its tissue-specific nature, and the role it may play in human phenotypic variation and disease is still poorly characterized. The placenta plays a critical role in regulating fetal growth and development in ways that have lifelong effects on health. To identify genes with a high degree of interindividual DNA methylation variation in the human placenta, we surveyed the human genome using the Illumina GoldenGate Methylation Cancer panel targeting 1505 CpG sites of 807 genes. While many sites show a continuous pattern of methylation levels, WNT2, TUSC3 and EPHB4 were identified to have a polymorphic "on-or-off" pattern of DNA methylation variation at their promoter region which was confirmed by pyrosequencing. Methylation of these genes can be found in 7%-25% of over 100 placentas tested. The methylation state at the promoter of these genes is concordant with mRNA allelic expression. In three informative cases TUSC3 was observed to be methylated on the maternal allele, and it is thus possible this represents a polymorphically imprinted gene. Furthermore, TUSC3 promoter methylation showed evidence for association with preeclampsia. A biological significance of these methylation allelic polymorphisms (MAPs) to human placental diversity is further implied by their placental specificity and absence in mouse. An extended study of blood suggests that MAPs may also be found in other tissues, implicating their utility for tissue-specific association with complex disorders. The identification of such "epipolymorphism" in other tissues and their use in association studies, should improve our understanding of interindividual phenotypic variability and complex disease susceptibility.
| S-EPMC2760756 | biostudies-literature
Project description:This study investigated the association between pre-pregnancy body mass index (BMI) and adverse pregnancy outcomes among women participated in the National Free Preconception Health Examination Project in Guangdong Province, China, and explored these associations according to maternal age. Pre-pregnancy BMI was classified into underweight (BMI < 18.5 kg/m2), healthy weight (18.5-23.9 kg/m2), overweight (24.0-27.9 kg/m2), and obesity (≥ 28.0 kg/m2) according to Chinese criteria. Outcomes were preterm birth (PTB, delivery before 37 weeks of gestation), large for gestational age (LGA, birthweight above the 90th percentile for gestational age by infants' sex), small for gestational age (SGA, birthweight below the 10th percentile for gestational age by infants' sex), primary caesarean delivery, shoulder dystocia or birth injury, and stillbirth. Adjusted incidence risk ratios (aIRR) were calculated for underweight, overweight and obesity, respectively. Compared with healthy weight, underweight was associated with increased risk of PTB (aIRR 1.06, 95%CI 1.04-1.09) and SGA (1.23, 1.22-1.26) but inversely associated with LGA (0.83, 0.82-0.85), primary caesarean delivery (0.88, 0.87-0.90) and stillbirth (0.73, 0.53-0.99). Overweight was associated with increased risk of LGA (1.17, 1.14-1.19), primary caesarean delivery (1.18, 1.16-1.20) and stillbirth (1.44, 1.03-2.06), but inversely associated with SGA (0.92, 0.90-0.95) and shoulder dystocia or birth injury (0.86, 0.79-0.93). Obesity was associated with increased risk of PTB (1.12, 1.05-1.20), LGA (1.32, 1.27-1.37), primary caesarean delivery (1.45, 1.40-1.50), but inversely associated with SGA (0.92, 0.87-0.97). The aIRRs for underweight, overweight and obesity in relation to these adverse pregnancy outcomes ranged from 0.65 to 1.52 according to maternal age. In Chinese population, maternal pre-pregnancy BMI was significantly associated with the risk of adverse pregnancy outcomes and the risk differs according to maternal age. Further investigation is warranted to determine whether and how counselling and interventions for women with low or increased BMI before pregnancy can reduce the risk of adverse pregnancy outcomes.
| S-EPMC7884680 | biostudies-literature
Project description:Background Identifying pregnancy-associated risk factors before the development of major cardiovascular disease events could provide opportunities for prevention. The objective of this study was to determine the association between outcomes in first pregnancies and subsequent cardiovascular health. Methods and Results The Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be Heart Health Study is a prospective observational cohort that followed 4484 women 2 to 7 years (mean 3.2 years) after their first pregnancy. Adverse pregnancy outcomes (defined as hypertensive disorders of pregnancy, small-for-gestational-age birth, preterm birth, and stillbirth) were identified prospectively in 1017 of the women (22.7%) during this pregnancy. The primary outcome was incident hypertension (HTN). Women without adverse pregnancy outcomes served as controls. Risk ratios (RR) and 95% CIs were adjusted for age, smoking, body mass index, insurance type, and race/ethnicity at enrollment during pregnancy. The overall incidence of HTN was 5.4% (95% CI 4.7% to 6.1%). Women with adverse pregnancy outcomes had higher adjusted risk of HTN at follow-up compared with controls (RR 2.4, 95% CI 1.8-3.1). The association held for individual adverse pregnancy outcomes: any hypertensive disorders of pregnancy (RR 2.7, 95% CI 2.0-3.6), preeclampsia (RR 2.8, 95% CI 2.0-4.0), and preterm birth (RR 2.7, 95% CI 1.9-3.8). Women who had an indicated preterm birth and hypertensive disorders of pregnancy had the highest risk of HTN (RR 4.3, 95% CI 2.7-6.7). Conclusions Several pregnancy complications in the first pregnancy are associated with development of HTN 2 to 7 years later. Preventive care for women should include a detailed pregnancy history to aid in counseling about HTN risk. Clinical Trial Registration URL: http://www.clinicaltrials.gov Unique identifier: NCT02231398.
| S-EPMC6806043 | biostudies-literature
Project description:BackgroundPostterm pregnancy has been associated with higher risk of perinatal mortality and morbidity, but its long-term health effects on offspring are poorly understood.ObjectivesThe aim of the study was to investigate the prospective associations between maternal postterm pregnancy and adverse growth outcomes in children.MethodsThe Jiaxing Birth Cohort is part of a large population-based health surveillance system in China and recruited pregnant females resident in the Jiaxing area between 1999 and 2013; newborns were followed up for a median duration of 5.8 y until they went to school. Mother-child pairs with maternal gestational information and offspring's anthropometric data at 4-7 y old were included. Postterm pregnancy was defined as maternal gestational age ≥42 and <47 wk, and its associations with offspring obesity, overweight/obesity, and thinness during childhood were determined by using Poisson regression models.ResultsOf the 101,505 included mother-child pairs, 2369 (2.3%) children were born at postterm. Children born at postterm had significantly lower BMI-for-age z score, weight-for-age z score, and height-for-age z score than those born at term; the mean difference (95% CI) was -0.11 (-0.15, -0.06), -0.17 (-0.21, -0.13), and -0.16 (-0.20, -0.12), respectively. When comparing postterm with term pregnancy, the multivariable-adjusted RRs and 95% CIs among preschool-age children were 0.87 (0.68, 1.11) for obesity, 0.82 (0.72, 0.94) for overweight/obesity, and 1.18 (1.09, 1.28) for thinness, respectively. These risk estimates were robust in sensitivity analyses, but were attenuated in several subgroups stratified by age, sex, mode of delivery, and fetal distress.ConclusionsPostterm pregnancy was associated with a higher risk of thinness, and a lower risk of overweight/obesity, as well as lower growth parameters in preschool-age children. These findings imply that postterm pregnancy may impede the long-term growth of offspring.
| S-EPMC9348988 | biostudies-literature
Project description:ObjectiveWe reviewed the literature on the association between pre-pregnancy multimorbidity (co-occurrence of two or more chronic conditions) and adverse maternal outcomes in pregnancy and postpartum.Data sourcesMedline, EMBASE, and CINAHL were searched from inception to September, 2021.Study selectionObservational studies were eligible if they reported on the association between ≥ 2 co-occurring chronic conditions diagnosed before conception and any adverse maternal outcome in pregnancy or within 365 days of childbirth, had a comparison group, were peer-reviewed, and were written in English.Data extraction and synthesisTwo reviewers used standardized instruments to extract data and rate study quality and the certainty of evidence. A narrative synthesis was performed.ResultsOf 6,381 studies retrieved, seven met our criteria. There were two prospective cohort studies, two retrospective cohort studies, and 3 cross-sectional studies, conducted in the United States (n=6) and Canada (n=1), and ranging in size from n=3,110 to n=57,326,681. Studies showed a dose-response relation between the number of co-occurring chronic conditions and risk of adverse maternal outcomes, including severe maternal morbidity or mortality, hypertensive disorders of pregnancy, and acute health care use in the perinatal period. Study quality was rated as strong (n=1), moderate (n=4), or weak (n=2), and the certainty of evidence was very low to moderate.ConclusionGiven the increasing prevalence of chronic disease risk factors such as advanced maternal age and obesity, more research is needed to understand the impact of pre-pregnancy multimorbidity on maternal health so that appropriate preconception and perinatal supports can be developed.
| S-EPMC9106308 | biostudies-literature
Project description:ObjectiveTo investigate whether intervening miscarriages and induced abortions impact the associations between interpregnancy interval after a live birth and adverse pregnancy outcomes.DesignPopulation-based cohort study.SettingNorway.ParticipantsA total of 165 617 births to 143 916 women between 2008 and 2016.Main outcome measuresWe estimated adjusted relative risks for adverse pregnancy outcomes using log-binomial regression, first ignoring miscarriages and induced abortions in the interpregnancy interval estimation (conventional interpregnancy interval estimates) and subsequently accounting for intervening miscarriages or induced abortions (correct interpregnancy interval estimates). We then calculated the ratio of the two relative risks (ratio of ratios, RoR) as a measure of the difference.ResultsThe proportion of short interpregnancy interval (<6 months) was 4.0% in the conventional interpregnancy interval estimate and slightly increased to 4.6% in the correct interpregnancy interval estimate. For interpregnancy interval <6 months, compared with 18-23 months, the RoR was 0.97 for preterm birth (PTB) (95% confidence interval [CI] 0.83-1.13), 0.97 for spontaneous PTB ( 95% CI 0.80-1.19), 1.00 for small-for-gestational age ( 95% CI 0.86-1.14), 1.00 for large-for-gestational age (95% CI 0.90-1.10) and 0.99 for pre-eclampsia (95% CI 0.71-1.37). Similarly, conventional and correct interpregnancy intervals yielded associations of similar magnitude between long interpregnancy interval (≥60 months) and the pregnancy outcomes evaluated.ConclusionNot considering intervening pregnancy loss due to miscarriages or induced abortions, results in negligible difference in the associations between short and long interpregnancy intervals and adverse pregnancy outcomes.Tweetable abstractNot considering pregnancy loss in interpregnancy interval estimation resulted no meaningful differences in observed risks of adverse pregnancy outcomes.
| S-EPMC9541236 | biostudies-literature
Project description:ImportanceThe Mediterranean diet pattern is inversely associated with the leading causes of morbidity and mortality, including metabolic diseases and cardiovascular disease, but there are limited data on its association with adverse pregnancy outcomes (APOs) among US women.ObjectiveTo evaluate whether concordance to a Mediterranean diet pattern around the time of conception is associated with lower risk of developing any APO and individual APOs.Design, setting, and participantsThis prospective, multicenter, cohort study, the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be, enrolled 10 038 women between October 1, 2010, and September 30, 2013, with a final analytic sample of 7798 racially, ethnically, and geographically diverse women with singleton pregnancies who had complete diet data. Data analyses were completed between June 3, 2021, and April 7, 2022.ExposuresAn Alternate Mediterranean Diet (aMed) score (range, 0-9; low, 0-3; moderate, 4-5; and high, 6-9) was computed from data on habitual diet in the 3 months around conception, assessed using a semiquantitative food frequency questionnaire.Main outcomes and measuresAdverse pregnancy outcomes were prospectively ascertained and defined as developing 1 or more of the following: preeclampsia or eclampsia, gestational hypertension, gestational diabetes, preterm birth, delivery of a small-for-gestational-age infant, or stillbirth.ResultsOf 7798 participants (mean [SD] age, 27.4 [5.5] years), 754 (9.7%) were aged 35 years or older, 816 (10.5%) were non-Hispanic Black, 1294 (16.6%) were Hispanic, and 1522 (19.5%) had obesity at baseline. The mean (SD) aMed score was 4.3 (2.1), and the prevalence of high, moderate, and low concordance to a Mediterranean diet pattern around the time of conception was 30.6% (n=2388), 31.2% (n=2430), and 38.2% (n=2980), respectively. In multivariable models, a high vs low aMed score was associated with 21% lower odds of any APO (adjusted odds ratio [aOR], 0.79 [95% CI, 0.68-0.92]), 28% lower odds of preeclampsia or eclampsia (aOR, 0.72 [95% CI, 0.55-0.93]), and 37% lower odds of gestational diabetes (aOR, 0.63 [95% CI, 0.44-0.90]). There were no differences by race, ethnicity, and prepregnancy body mass index, but associations were stronger among women aged 35 years or older (aOR, 0.54 [95% CI, 0.34-0.84]; P = .02 for interaction). When aMed score quintiles were evaluated, similar associations were observed, with higher scores being inversely associated with the incidence of any APO.Conclusions and relevanceThis cohort study suggests that greater adherence to a Mediterranean diet pattern is associated with lower risk of APOs, with evidence of a dose-response association. Intervention studies are needed to assess whether dietary modification around the time of conception can reduce risk of APOs and their downstream associations with future development of cardiovascular disease risk factors and overt disease.
| S-EPMC9857221 | biostudies-literature