Prenatal exposure to tobacco smoke has lifelong health consequences. Epigenetic signatures such as differences in DNA methylation (DNAm) may be a biomarker of exposure and, further, might have functional significance for how in utero tobacco exposure may influence disease risk. Differences in infant DNAm associated with maternal smoking during pregnancy have been identified. Here we assessed whether these infant DNAm patterns are detectible in early childhood, whether they are specific to smoking, and whether childhood DNAm can classify prenatal smoke exposure status. Using the Infinium 450 K array, we measured methylation at 26 CpG loci that were previously associated with prenatal smoking in infant cord blood from 572 children, aged 3–5, with differing prenatal exposure to cigarette smoke in the Study to Explore Early Development (SEED). Striking concordance was found between the pattern of prenatal smoking associated DNAm among preschool aged children in SEED and those observed at birth in other studies. These DNAm changes appear to be tobacco-specific. Support vector machine classification models and 10-fold cross-validation were applied to show classification accuracy for childhood DNAm at these 26 sites as a biomarker of prenatal smoking exposure. Classification models showed prenatal exposure to smoking can be assigned with 81% accuracy using childhood DNAm patterns at these 26 loci. These findings support the potential for blood-derived DNAm measurements to serve as biomarkers for prenatal exposure.

Using data from a large multi-site study in the US-the Study to Explore Early Development-we found that women with a history of eczema/psoriasis and asthma are more likely to have children with ASD or DD. In addition, children with ASD are more likely to have a history of psoriasis/eczema or allergies than typically developing children. These data support a link between maternal and child immune conditions and adverse neurodevelopmental outcomes.

Background The Study to Explore Early Development (SEED) is designed to enhance knowledge of autism spectrum disorder characteristics and etiologies. Objective This paper describes the demographic profile of enrolled families and examines sociodemographic differences between children with autism spectrum disorder and children with other developmental problems or who are typically developing. Methods This multi-site case-control study used health, education, and birth certificate records to identify and enroll children aged 2–5 years into one of three groups: 1) cases (children with autism spectrum disorder), 2) developmental delay or disorder controls, or 3) general population controls. Study group classification was based on sampling source, prior diagnoses, and study screening tests and developmental evaluations. The child's primary caregiver provided demographic characteristics through a telephone (or occasionally face-to-face) interview. Groups were compared using ANOVA, chi-squared test, or multinomial logistic regression as appropriate. Results Of 2768 study children, sizeable proportions were born to mothers of non-White race (31.7%), Hispanic ethnicity (11.4%), and foreign birth (17.6%); 33.0% of households had incomes below the US median. The autism spectrum disorder and population control groups differed significantly on nearly all sociodemographic parameters. In contrast, the autism spectrum disorder and developmental delay or disorder groups had generally similar sociodemographic characteristics. Conclusions SEED enrolled a sociodemographically diverse sample, which will allow further, in-depth exploration of sociodemographic differences between study groups and provide novel opportunities to explore sociodemographic influences on etiologic risk factor associations with autism spectrum disorder and phenotypic subtypes.

Background Per- and polyfluoroalkyl substances (PFASs) have been widely produced, many of them persist in the environment, and have been associated with various health effects. Previous studies have identified inverse associations between perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and breastfeeding duration, but have been limited in investigation of other PFASs. Methods We measured the associations between plasma concentrations of 9 different PFASs and cessation of breastfeeding before 3 and 6 complete months using women from the Norwegian Mother and Child Cohort Study (MoBa). The study population includes 1716 primarily nulliparous women from two previous studies of MoBa participants, enrolled from 2003–2007. The association was measured using Cox proportional hazards model. Mixtures analyses were performed using Elastic net regularization to identify interactive effects and control for co-pollutant confounding. Results Concentrations of PFASs in this population were lower than concentrations in the previous studies on this topic. We found associations between increasing concentrations of perfluorononanoic acid (PFNA), perfluorodecaconic acid (PFDA), perfluoroundecanoic acid (PFUnDA) and decreased breastfeeding cessation (increased duration). The strongest associations were seen between PFDA and PFUnDA and cessation before 3 months: (both hazard ratios = 0.73, 95% confidence intervals: 0.62, 0.86). In our population, the other PFASs appeared to be unassociated with breastfeeding cessation. The mixtures analyses identified meaningful interactions between PFUnDA:PFDA, perfluorohexane sulfonate (PFHXS):PFOA and PFOA:PFOS. Conclusions The identification of associations between previously unexamined PFASs concentrations and increased breastfeeding duration is novel and may be explained by differences in transplacental transfer rates.

Background Prenatal alcohol exposure can affect neurodevelopment, but few studies have examined associations with autism spectrum disorder (ASD). Methods We assessed the association between maternal alcohol use and ASD in the Study to Explore Early Development, a multi-site case-control study of children born September 2003 – August 2006 in the U.S. Regression analyses included 684 children with research clinician-confirmed ASD, 869 children with non-ASD developmental delays or disorders (DDs) and 962 controls ascertained from the general population (POP). Maternal alcohol exposure during each month from three months prior to conception until delivery was assessed by self-report. Results Mothers of POP children were more likely to report any prenatal alcohol use than mothers of children with ASD or DD. In trimester one, 21.2% of mothers of POP children reported alcohol use compared to 18.1% and 18.2% of mothers of children with ASD or DD, respectively (adjusted OR for ASD versus POP 0.8, 95% confidence interval 0.6, 1.1). During preconception and the first month of pregnancy, 1–2 drinks on average per week was inversely associated with ASD risk. Conclusions These results do not support an adverse association between low-level alcohol exposure and ASD, though these findings were based retrospective self-reported alcohol use. Unmeasured confounding or exposure misclassification may explain inverse associations with 1–2 drinks per week. Pregnant or potentially pregnant women should continue to follow recommendations to avoid alcohol use because of other known effects on infant health and neurodevelopment.