Abstract Maternal stress and depression during pregnancy and the first year of the infant’s life affect a large percentage of mothers. Maternal stress and depression have been associated with adverse fetal and childhood outcomes as well as differential child DNA methylation (DNAm). However, the biological mechanisms connecting maternal stress and depression to poor health outcomes in children are still largely unknown. Here we aim to determine whether prenatal stress and depression are associated with changes in cord blood mononuclear cell DNAm (CBMC-DNAm) in newborns (n = 119) and whether postnatal stress and depression are associated with changes in peripheral blood mononuclear cell DNAm (PBMC-DNAm) in children of 12 months of age (n = 113) from the Canadian Healthy Infant Longitudinal Development (CHILD) cohort. Stress was measured using the 10-item Perceived Stress Scale (PSS) and depression was measured using the Center for Epidemiologic Studies Depression Questionnaire (CESD). Both stress and depression were measured at 18 weeks and 36 weeks of pregnancy and six months and 12 months postpartum. We conducted epigenome-wide association studies (EWAS) using robust linear regression followed by a sensitivity analysis in which we bias-adjusted for inflation and unmeasured confounding using the bacon and cate methods. To investigate the cumulative effect of maternal stress and depression, we created composite prenatal and postnatal adversity scores. We identified a significant association between prenatal stress and differential CBMC-DNAm at 8 CpG sites and between prenatal depression and differential CBMC-DNAm at 2 CpG sites. Additionally, we identified a significant association between postnatal stress and differential PBMC-DNAm at 8 CpG sites and between postnatal depression and differential PBMC-DNAm at 11 CpG sites. Using our composite scores, we further identified 2 CpG sites significantly associated with prenatal adversity and 7 CpG sites significantly associated with postnatal adversity. Several of the associated genes, including PLAGL1, HYMAI, BRD2, and ERC2 have been implicated in adverse fetal outcomes and neuropsychiatric disorders. This suggested that differential DNAm may play a role in the relationship between maternal mental health and child health.
Maternal stress and depression during pregnancy and the first year of the infant's life affect a large percentage of mothers. Maternal stress and depression have been associated with adverse fetal and childhood outcomes as well as differential child DNA methylation (DNAm). However, the biological mechanisms connecting maternal stress and depression to poor health outcomes in children are still largely unknown. Here we aim to determine whether prenatal stress and depression are associated with differences in cord blood mononuclear cell DNAm (CBMC-DNAm) in newborns (n = 119) and whether postnatal stress and depression are associated with differences in peripheral blood mononuclear cell DNAm (PBMC-DNAm) in children of 12 months of age (n = 113) from the Canadian Healthy Infant Longitudinal Development (CHILD) cohort. Stress was measured using the 10-item Perceived Stress Scale (PSS) and depression was measured using the 20-item Center for Epidemiologic Studies Depression Questionnaire (CESD). Both stress and depression were measured longitudinally at 18 weeks and 36 weeks of pregnancy and six months and 12 months postpartum. We conducted epigenome-wide association studies (EWAS) using robust linear regression followed by a sensitivity analysis in which we bias-adjusted for inflation and unmeasured confounding using the bacon and cate methods. To quantify the cumulative effect of maternal stress and depression, we created composite prenatal and postnatal adversity scores. We identified a significant association between prenatal stress and differential CBMC-DNAm at 8 CpG sites and between prenatal depression and differential CBMC-DNAm at 2 CpG sites. Additionally, we identified a significant association between postnatal stress and differential PBMC-DNAm at 8 CpG sites and between postnatal depression and differential PBMC-DNAm at 11 CpG sites. Using our composite scores, we further identified 2 CpG sites significantly associated with prenatal adversity and 7 CpG sites significantly associated with postnatal adversity. Several of the associated genes, including PLAGL1, HYMAI, BRD2, and ERC2 have been implicated in adverse fetal outcomes and neuropsychiatric disorders. These data further support the finding that differential DNAm may play a role in the relationship between maternal mental health and child health.
Objective Estimate the prevalence of allergic, neurodevelopmental, and autoimmune diagnoses in children born to anti‐Ro antibody positive mothers. Methods A cohort study of children born to anti‐Ro antibody positive mothers followed in the Neonatal Lupus Erythematosus clinic (NLE) at SickKids Hospital. Participants ≥ 1 year of age were invited to complete a health status questionnaire. Prevalence of allergic, neurodevelopmental, and autoimmune disease diagnoses were compared between from the NLE cohort and the non‐NLE population‐based CHILD Cohort Study. Descriptive statistics were used for demographics, NLE manifestations and outcomes. Fisher's exact tests compared the prevalence of diagnoses between subgroups. We tested the association between allergies and neurodevelopmental conditions and NLE with logistic regression models. A P‐value of <0.006 was considered significant. Results We included 321 participants with anti‐Ro antibody positive mothers. Median age at survey completion: 6 years, 51% female, 50% (n=162) NLE. No significant difference in any disease prevalence between children with and without NLE manifestations (p = 0.57) nor between children born to mothers with and without a rheumatic disease (p = 0.11). Disease prevalence was similar between the NLE and CHILD cohorts, allergic disease 30% vs 22%, p= 0.25, neurodevelopmental conditions 5% vs 2%, p=0.45, autoimmune disease 4% vs 2%, p=0.68. Conclusions In a large, multiethnic cohort of infants born to anti‐Ro antibody positive mothers, there was no significant difference in the prevalence of allergic, neurodevelopmental, or autoimmune diseases between children with and without NLE, nor between those born to anti‐Ro antibody positive mothers and a population‐based, non‐NLE cohort.
