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Fetal growth and preterm birth in children exposed to maternal or paternal rheumatoid arthritis: a nationwide cohort study.

ABSTRACT: To assess indicators of fetal growth and risk of preterm birth in children of parents with rheumatoid arthritis (RA).Through linkage of Danish national registries, we identified all children born in Denmark between 1977 and 2008. We used general linear regression models to estimate mean differences in indicators of fetal growth among children with a parent with RA compared to unexposed children. Odds ratios (ORs) and 95% confidence intervals (95% CIs) of preterm birth were calculated using a logistic regression model.Of the 1,917,723 children included, a total of 13,556 children were exposed to maternal RA or maternal preclinical RA. Children exposed to maternal RA (n = 2,101) had approximately similar length, head circumference, and abdominal circumference at birth compared with children of mothers without RA. Birth weight was 87 gm lower (mean difference -87.04 gm [95% CI -111.23, -62.84]) and placenta weight was 14 gm lower (-13.45 gm [95% CI -21.46, -5.43]) than those in children of mothers without RA. Rather similar results were found in children exposed to maternal preclinical RA (n = 11,455). Compared with unexposed children, a higher risk of preterm birth was found in children exposed to maternal RA (OR 1.48 [95% CI 1.20, 1.84]) and preclinical RA (OR 1.32 [95% CI 1.07, 1.64]). No associations were found with paternal RA.Children exposed to either maternal RA or maternal preclinical RA are more often born preterm. However, indicators of fetal growth measured at birth were only slightly lower than those in unexposed children.

SUBMITTER: Rom AL

PROVIDER: S-EPMC4245456 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Fetal growth and preterm birth in children exposed to maternal or paternal rheumatoid arthritis: a nationwide cohort study.

Rom Ane L AL Wu Chun S CS Olsen Jørn J Kjaergaard Hanne H Jawaheer Damini D Hetland Merete L ML Vestergaard Mogens M Mørch Lina S LS

Arthritis & rheumatology (Hoboken, N.J.) 20141201 12

<h4>Objective</h4>To assess indicators of fetal growth and risk of preterm birth in children of parents with rheumatoid arthritis (RA).<h4>Methods</h4>Through linkage of Danish national registries, we identified all children born in Denmark between 1977 and 2008. We used general linear regression models to estimate mean differences in indicators of fetal growth among children with a parent with RA compared to unexposed children. Odds ratios (ORs) and 95% confidence intervals (95% CIs) of preterm ...[more]

PMID: 25393524

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Project description:BackgroundPhenol exposure during pregnancy has been associated with preterm birth, but the potential effect of preconception exposure in either parent is unknown. There is a growing body of evidence to suggest that the preconception period is a critical window of vulnerability for adverse pregnancy outcomes.ObjectiveWe examined whether maternal and paternal preconception urinary concentrations of select phenols were associated with the risk of preterm birth among couples attending fertility care.MethodsThe analysis included 417 female and 229 male participants of the Environment and Reproductive Health (EARTH) Study who gave birth to 418 singleton infants between 2005 and 2018 and for whom we had phenol biomarkers quantified in at least one urine sample collected before conception. Mothers and fathers provided an average of 4 and 3 urine samples during the preconception period, respectively. We calculated the geometric mean of bisphenol A (BPA), bisphenol S (BPS), benzophenone-3, triclosan, and the molar sum of parabens (ΣParabens) urinary concentrations to estimate each participant's preconception exposure. Risk ratios (RRs) of preterm birth (live birth before 37 completed weeks' gestation) were estimated using modified Poisson regression models adjusted for covariates.ResultsThe mean (SD) gestational age among singletons was 39.3 (1.7) weeks with 8% born preterm. A natural log-unit increase in maternal preconception BPA (RR 1.94; 95% CI: 1.20, 3.14) and BPS (RR 2.42; 95% CI: 1.01, 5.77) concentration was associated with an increased risk of preterm birth. These associations remained after further adjustment for maternal prenatal and paternal preconception biomarker concentrations. Paternal preconception ΣParabens concentrations showed a possible elevated risk of preterm birth (RR 1.36; 95% CI: 0.94, 1.96). No consistent pattern of association was observed for benzophenone-3 or triclosan biomarkers in either parent.DiscussionMaternal preconception urinary BPA and BPS concentrations, as well as paternal preconception urinary parabens concentrations were prospectively associated with a higher risk of preterm birth. Subfertile couples' exposure to select phenols during the preconception period may be an unrecognized risk factor for adverse pregnancy outcomes.

Project description:Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, precise phenotyping of the preterm birth is hampered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. The studyâ??s aim was to comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor using precisely phenotyped samples. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified the four groups of patients: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). The largest differences in gene expression among the four groups occurred in decidua, chorion and amnion. The gene expression profiles showed suppression of chemokines expression in TNL, withdrawal of this suppression in TL, activation of multiple pathways of inflammation in PL, and an immune rejection profile in PNL. The genes constituting expression signatures showed over-representation of three putative regulatory elements in their 5â?? and 3â??UTR regions. The results suggest that pregnancy is maintained by downregulation of chemokines at the maternal-fetal interface. Withdrawal of this downregulation results in the term birth and its overriding by the activation of multiple pathways of the immune system in the preterm birth. Complications of the pregnancy associated with impairment of placental function, which necessitated premature delivery of the fetus in the absence of labor, show gene expression patterns associated with immune rejection. 183 total RNA samples from 8 tissue types collected from 35 women grouped into six categories of pregnancy outcome. One microarray replicate per sample. Other Contributors: Radek Bukowski, Sam Parry and the NICHD Genomic and Proteomic Network for Preterm Birth Research

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Fetal growth and preterm birth in children exposed to maternal or paternal rheumatoid arthritis: a nationwide cohort study.

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Fetal growth and preterm birth in children exposed to maternal or paternal rheumatoid arthritis: a nationwide cohort study.

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