59 research outputs found

    Maternal history of miscarriages and measures of fertility in relation to childhood asthma

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    Background: it remains unclear what underlies the greater risk of asthma reported among children conceived by assisted reproductive technologies (art). Objective: Our aim was to clarify the role of parental subfertility and unmeasured confounding on the association between art and childhood asthma, and to examine the possibility for common mechanisms underlying parental subfertility and miscarriages influencing asthma pathogenesis. Methods: We used data from national norwegian health registries (n=474 402) and the norwegian Mother and child cohort Study (MoBa) (n=75 797). We used log-linear regression to estimate overall associations, and fixed-effects logistic regression to estimate associations within siblings. Results: ART offspring had greater asthma risk, the adjusted relative risk (arr) was 1.20 (95% ci 1.09 to 1.32) in the registry-based cohort, and 1.42 (95% ci 1.14 to 1.76) in MoBa. the sibling analysis yielded similar associations, although the ci included the null value. the elevated asthma risk among art offspring was attenuated when they were compared with spontaneously conceived offspring with time to conception >12 months, arr 1.22 (95% ci 0.95 to 1.57). asthma risk also increased with maternal history of early miscarriages (≤12 weeks), with an arr of 1.07 (95% ci 1.03 to 1.11) for one, arr 1.18 (95% ci 1.10 to 1.26) for two and arr 1.24 (95% ci 1.12 to 1.37) for three or more. Conclusion: Our findings indicate that both parental subfertility and characteristics related to the art procedure itself might increase offspring asthma risk, although this needs to be confirmed in future studies, and further suggest that common mechanisms underlying parental subfertility and recurrent miscarriages might influence offspring asthma pathogenesis

    DNA Methylation Score as a Biomarker in Newborns for Sustained Maternal Smoking during Pregnancy

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    Background: Maternal smoking during pregnancy, especially when sustained, leads to numerous adverse health outcomes in offspring. Pregnant women disproportionately underreport smoking and smokers tend to have lower follow-up rates to repeat questionnaires. Missing, incomplete, or inaccurate data on presence and duration of smoking in pregnancy impairs identification of novel health effects and limits adjustment for smoking in studies of other pregnancy exposures. An objective biomarker in newborns of maternal smoking during pregnancy would be valuable. Objectives: We developed a biomarker of sustained maternal smoking in pregnancy using common DNA methylation platforms. Methods: Using a dimension reduction method, we developed and tested a numeric score in newborns to reflect sustained maternal smoking in pregnancy from data on cotinine, a short-term smoking biomarker measured mid-pregnancy, and Illumina450K cord blood DNA methylation from newborns in the Norwegian Mother and Child Cohort Study (MoBa). Results: This score reliably predicted smoking status in the training set (n = 1,057; accuracy = 96%, sensitivity = 80%, specificity = 98%). Sensitivity (58%) was predictably lower in the much smaller test set (n = 221), but accuracy (91%) and specificity (97%) remained high. Reduced birth weight, a well-known effect of maternal smoking, was as strongly related to the score as to cotinine. A three-site score had lower, but acceptable, performance (accuracytrain = 82%, accuracytest = 83%). Conclusions: Our smoking methylation score represents a promising novel biomarker of sustained maternal smoking during pregnancy easily calculated with Illumina450K or IlluminaEPIC data. It may help identify novel health impacts and improve adjustment for smoking when studying other risk factors with more subtle effects.publishedVersio
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