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Early life antibiotic exposure may increase obesity risk. We investigated if prenatal, intrapartum, or childhood antibiotic use is associated with child zBMI score at 4 yrs of age. We included data from the Alberta Pregnancy Outcomes and Nutrition (APrON) study, a prospective cohort study, on maternal and child antibiotic exposure and clinic measures of height and weight at age 4 (n = 408). Prenatal and childhood antibiotic exposure was not associated with zBMI score. Maternal intrapartum antibiotic exposure was associated with a zBMI score increase of 0.12 (95 % CI; 0.04, 0.46) in children at 4 years of age compared to non-exposure intrapartum., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Raylene Reimer and Gerald Giesbrecht report financial support was provided by the Canadian Institutes of Health Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Competing interests The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The maternal status of multiple micronutrients during pregnancy and postpartum and their potential associations with maternal health outcomes are largely undescribed., Objectives: This study aimed to examine associations between maternal iron and vitamin D status, individually and in combination, on depression symptoms in pregnant individuals., Methods: The Alberta Pregnancy Outcomes and Nutrition cohort study included pregnant participants and their children from Calgary and Edmonton, Canada. Iron biomarkers (serum ferritin [SF], soluble transferrin receptor, and hepcidin) were measured via immunoassays and vitamin D [25-hydroxyvitamin D3 (25(OH)D3) and 3-epi-25-hydoxyvitamin D3 (3-epi-25(OH)D3)] metabolites were quantifed using liquid chromatography with tandem mass spectroscopy. Four categories of maternal iron and vitamin D status during the second trimester were conceptualized using concentrations of SF and total 25-hydoxyvitamin D [25(OH)D], respectively. Maternal Edinburgh Postnatal Depression Scale (EPDS) scores during the third trimester (n = 1920) and 3 mo postpartum (n = 1822) were obtained., Results: Concentrations of maternal 25(OH)D3, 3-epi-25(OH)D3, and the ratio of both metabolites were significantly higher during the second trimester compared with their status at 3 mo postpartum. Higher second trimester maternal concentrations of SF (β: -0.8; 95% confidence interval [CI]: -1.5, -0.01), hepcidin (β: -0.5; 95% CI: -0.9, -0.2), and 25(OH)D3 (β: -0.01; 95% CI: -0.02, -0.004) predicted lower maternal EPDS scores during the third trimester. Pregnant individuals with a low iron (SF <15 μg/L) and replete vitamin D (25(OH)D ≥75 nmol/L) (β: 1.1; 95% CI: 0.03, 2.1) or low iron (SF <15 μg/L) and vitamin D (25(OH)D <75 nmol/L) (β: 2.2; 95% CI: 0.3, 4.2) status during midpregnancy had higher third trimester EPDS scores compared with those that were replete in both micronutrients., Conclusions: A higher midpregnancy maternal iron and vitamin D status, independently or in combination, predicted fewer maternal depression symptoms in the third trimester. Concentrations of maternal 25(OH)D3 and 3-epi-25(OH)D3 may be lower in the postpartum period compared with midpregnancy., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: On May 19, 2011, Calgary, Canada stopped fluoridating its drinking water. This prospective ecological study examined if maternal exposure to fluoride during pregnancy from drinking water that was fluoridated at the recommended level of 0.7 mg/L was associated with children's intelligence and executive function at 3-5 years of age., Methods: Participants were 616 maternal-child pairs enrolled in the Calgary cohort of the Alberta Pregnancy Outcomes and Nutrition (APrON) study between 2009 and 2012. Maternal-child pairs were classified as fully exposed to fluoridated drinking water throughout pregnancy (n = 295); exposed to fluoridated drinking water for at least part of the pregnancy plus an additional 90 days (n = 220); or not exposed to fluoridated drinking water during pregnancy plus the 90 days prior to pregnancy (n = 101). Children's Full Scale IQs were assessed using the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition: Canadian (WPPSI-IV CDN ). Children's executive functions were also assessed: working memory (WPPSI-IV CDN Working Memory Index), inhibitory control (Gift Delay, NEPSY-II Statue subtest), and cognitive flexibility (Boy-Girl Stroop, Dimensional Change Card Sort (DCCS))., Results: No associations were found between exposure group and Full Scale IQ. However, compared to no exposure, full exposure to fluoridated drinking water throughout pregnancy was associated with poorer performance on the Gift Delay (B = 0.53, 95 % CI = 0.31, 0.93). Sex-specific analyses revealed that girls in the fully exposed (AOR = 0.30, 95 % CI = 0.13, 0.74) and partially exposed groups (AOR = 0.42, 95 % CI = 0.17, 1.01) performed more poorly than girls in the not exposed group. Sex effects were also found on the DCCS; girls in the fully exposed (AOR = 0.34, 95 % CI = 0.14, 0.88) and partially exposed groups (AOR = 0.29, 95 % CI = 0.12, 0.73) performed more poorly., Conclusion: Maternal exposure to drinking water throughout pregnancy fluoridated at the level of 0.7 mg/L was associated with poorer inhibitory control and cognitive flexibility, particularly in girls, suggesting a possible need to reduce maternal fluoride exposure during pregnancy., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Developmental responses to nutrient deprivation may differ by fetal sex. Despite this, relationships between maternal prenatal iron biomarkers and birth outcomes when stratifying by offspring sex are poorly described, especially in healthy cohorts., Objectives: This study aimed to determine associations between maternal iron biomarkers and birth weights (BWs) and birth head circumferences (BHCs) among female and male newborns to assess whether the potential predictive ability of iron biomarkers on birth outcomes differs by offspring sex., Methods: The Alberta Pregnancy Outcomes and Nutrition (APrON) cohort study recruited 2189 pregnant individuals from Calgary and Edmonton, Canada. Maternal blood was drawn at each trimester and 3 mo postpartum. Maternal serum ferritin (SF) concentrations were measured using chemiluminescent immunoassays and erythropoietin (EPO), hepcidin, and soluble transferrin receptor (sTfR) using enzyme-linked immunosorbent assays. Ratios of sTfR:SF and hepcidin:EPO were calculated and birth outcomes accessed through delivery records. Directed acyclic graphs informed multivariate regression models., Results: The risk of maternal iron deficiency increased throughout pregnancy because ∼61% showed depleted iron stores (SF < 15 μg/L) by the third trimester. Maternal hepcidin, SF, sTfR, and sTfR:SF concentrations changed across time (P < 0.01), and participants carrying female fetuses consistently (across 6 biomarkers) showed a lower iron status during the third trimester compared with those with male fetuses (P < 0.05). Higher maternal SF and hepcidin:EPO during the third trimester was associated with lower BWs in males (P = 0.006 for SF; P = 0.03 for hepcidin:EPO) and females (P = 0.02 for SF; P = 0.02 for hepcidin:EPO). There were additional inverse associations between BWs and third trimester maternal hepcidin (P = 0.03) and hemoglobin (P = 0.004) and between BHCs and maternal SF (second trimester; P < 0.05) and Hb (third trimester P = 0.02) but only in males., Conclusions: Relationships between maternal iron biomarkers and BWs and BHCs may depend on the timing of pregnancy and offpsring sex. There was a high risk of third trimester iron storage depletion among generally healthy pregnant individuals., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: The COVID-19 pandemic has caused substantially elevated distress in pregnant individuals, which has the potential to affect the developing infant brain. Our main objective was to understand how prenatal distress was related to infant brain structure and function and whether social support moderated the associations., Methods: The Pregnancy during the COVID-19 Pandemic (PdP) cohort study collected Patient-Reported Outcomes Measurement Information System Anxiety scale, Edinburgh Postnatal Depression Scale, and Social Support Effectiveness Questionnaire data from a population-based sample of pregnant individuals living in Canada (N = 8602). For a subsample of participants, their infants (n = 75) underwent magnetic resonance imaging at 3 months of age to examine whether prenatal maternal distress was associated with infant brain architecture, including the role of social support as a potential protective factor., Results: Overall, 33.4% of participants demonstrated clinically elevated depression symptoms and 47.1% of participants demonstrated clinically elevated anxiety symptoms. We identified lower social support as a significant predictor of clinically elevated prenatal maternal distress (t 8598  = -22.3, p < .001). Fifty-eight diffusion image datasets (20 female/38 male, 92 ± 14 days old) and 41 functional datasets (13 female/28 male, 92 ± 14 days old) were included in our analysis after removal of poor-quality images and infants without postpartum maternal distress scores. We found significant relationships between prenatal maternal distress and infant amygdala-prefrontal microstructural and functional connectivity measures, and we demonstrate for the first time that social support moderates these relationships., Conclusions: Our findings suggest a potentially long-lasting impact of the COVID-19 pandemic on children and show that social support acts as a possible mediator not just for pregnant individuals but also developing infants. These findings provide timely evidence to inform clinical practice and policy surrounding the care of pregnant individuals and highlight the importance of social support., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Exposure to adverse childhood experiences (ACEs) increases risk for mental and physical health problems. Intergenerationally, mothers' ACEs predict children's health problems including neurodevelopmental and behavioural problems and poorer physical health. Theories of intergenerational trauma suggest that ACEs experienced in one generation negatively affect the health and well-being of future generations, with DNA methylation (DNAm) being one of several potential biological explanations. To begin exploring this hypothesis, we tested whether infant DNA methylation associated with intergenerational trauma. Secondary analysis employed data from the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Subsample data were collected from mothers during pregnancy and postpartum on measures of distress, stress and ACEs and from infants at 3 months of age on DNAm from blood (n = 92) and buccal epithelial cells (BECs; n = 124; primarily nonoverlapping individuals between tissues). Blood and BECs were examined in separate analyses. Preliminary associations identified in blood and BECs suggest that infant DNAm patterns may relate to maternal ACEs. For the majority of ACE-related DNAm sites, neither maternal perinatal distress, nor maternal cortisol awakening response (CAR; a measure of hypothalamic-pituitary-adrenocortical axis function), substantially reduced associations between maternal ACEs and infant DNAm. However, accounting for maternal perinatal distress and cortisol substantially changed the effect of ACEs in a greater proportion of blood DNAm sites than BEC DNAm sites in the top ACEs-associated correlated methylated regions (CMRs), as well as across all CMRs and all remaining CpGs (that did not fall into CMRs). Possible DNAm patterns in infants, thus, might capture a signature of maternal intergenerational trauma, and this effect appears to be more dependent on maternal perinatal distress and CAR in blood relative to BECs., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Secretory Immunoglobulin A (sIgA) plays a critical role to infant gut mucosal immunity. Delayed IgA production is associated with greater risk of allergic disease. Murine models of stressful events during pregnancy and infancy show alterations in gut immunity and microbial composition in offspring, but little is known about the stress-microbiome-immunity pathways in humans. We investigated differences in infant fecal sIgA concentrations according to the presence of maternal depressive symptoms during and after pregnancy. A subsample of 403 term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) cohort were studied. Their mothers completed the Center of Epidemiologic Studies Depression Scale when enrolled prenatally and again postpartum. Quantified by Immundiagnostik sIgA ELISA kit, sIgA from infant stool was compared across maternal depressive symptom categories using Mann-Whitney U-tests and logistic regression models that controlled for various covariates. Twelve percent of women reported clinically significant depressive symptoms only prenatally, 8.7% had only postpartum symptoms and 9.2% had symptoms both pre and postnatally. Infants born to mothers with pre and postnatal symptoms had significantly lower median sIgA concentrations than those in the reference group (4.4 mg/g feces vs. 6.3 mg/g feces; p = 0.033). The odds for sIgA concentrations in the lowest quartile was threefold higher (95% CI: 1.25-7.55) when mothers had pre and postnatal symptoms, after controlling for breastfeeding status, infant age, antibiotics exposure and other covariates. Postnatal symptoms were not associated with fecal sIgA, independently of breastfeeding status. Infants born to mothers with depressive symptoms appear to have lower fecal sIgA concentrations, predisposing them to higher risk for allergic disease., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Perinatal maternal depression is a serious health concern with potential lasting negative consequences for children. Prenatal depression is associated with altered brain gray matter in children, though relations between postpartum depression and children's brains and the role of white matter are unclear., Methods: We studied 52 women who provided Edinburgh Postnatal Depression Scale (EPDS) scores during each trimester of pregnancy and at 3 months postpartum and their children who underwent magnetic resonance imaging at age 2.6 to 5.1 years. Associations between maternal depressive symptoms and magnetic resonance imaging measures of cortical thickness and white matter structure in the children were investigated., Results: Women's second trimester EPDS scores negatively correlated with children's cortical thickness in right inferior frontal and middle temporal regions and with radial and mean diffusivity in white matter emanating from the inferior frontal area. Cortical thickness, but not diffusivity, correlations survived correction for postpartum EPDS. Postpartum EPDS scores negatively correlated with children's right superior frontal cortical thickness and with diffusivity in white matter originating from that region, even after correcting for prenatal EPDS., Conclusions: Higher maternal depressive symptoms prenatally and postpartum are associated with altered gray matter structure in children; the observed white matter correlations appear to be uniquely related to the postpartum period. The reduced thickness and diffusivity suggest premature brain development in children exposed to higher maternal perinatal depressive symptoms. These results highlight the importance of ensuring optimal women's mental health throughout the perinatal period, because maternal depressive symptoms appear to increase children's vulnerability to nonoptimal brain development., (Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Bisphenol A (BPA) is associated with dysregulation of hypothalamic-pituitary-adrenal (HPA) axis activity in rodents, but evidence in humans is lacking., Objective: To determine whether BPA exposure during pregnancy is associated with dysregulation of the HPA-axis, we examined the association between urinary BPA concentrations and diurnal salivary cortisol in pregnant women. Secondary analyses investigated whether the association between BPA and cortisol was dependent on fetal sex., Methods: Diurnal salivary cortisol and urinary BPA were collected during pregnancy from 174 women in a longitudinal cohort study, the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Associations between BPA and daytime cortisol and the cortisol awakening response (CAR) were estimated using mixed models after adjusting for covariates., Results: Higher concentrations of total BPA uncorrected for urinary creatinine were associated with dysregulation of the daytime cortisol pattern, including reduced cortisol at waking, β=-.055, 95% CI (-.100, -.010) and a flatter daytime pattern, β=.014, 95% CI (.006, .022) and β=-.0007 95% CI (-.001, -.0002) for the linear and quadratic slopes, respectively. Effect sizes in creatinine corrected BPA models were slightly smaller. None of the interactions between fetal sex and BPA were significant (all 95% CI's include zero)., Conclusions: These findings provide the first human evidence suggesting that BPA exposure is associated with dysregulation of HPA-axis function during pregnancy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Mental disorders are one of the leading contributors to the global burden of disease. The Alberta Pregnancy Outcomes and Nutrition (APrON) study was initiated in 2008 to better understand perinatal environmental impacts on maternal mental health and child development., Aims: This pregnancy cohort was established to investigate the relationship between the maternal environment (e.g. nutritional status), maternal mental health status, birth outcomes, and child development. The purpose of this paper is to describe the creation of this longitudinal cohort, the data collection tools and procedures, and the background characteristics of the participants., Subjects: Participants were pregnant women age 16 or older, their infants and the biological fathers., Outcome Measures: For the women, data were collected during each trimester of pregnancy and at 3, 6, 12, 24, and 36months after the birth of their infant. Maternal measures included diet, stress, current mental and physical health, health history, and lifestyle. In addition, maternal biological samples (DNA, blood, urine, and spot breast milk samples) were banked. Paternal data included current mental and physical health, health history, lifestyle, and banked DNA samples. For infants, DNA and blood were collected as well as information on health, development and feeding behavior., Results: At the end of recruitment in 2012, the APrON cohort included 2140 women, 2172 infants, and 1417 biological fathers. Descriptive statistics of the cohort, and comparison of women who stayed in the study and those who dropped out are discussed., Conclusion: Findings from the longitudinal cohort may have important implications for health policy and clinical practice., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: The Infant Behavior Questionnaire-Revised (IBQ-R) is a widely used parent report measure of infant temperament. Items marked 'does not apply' (NA) are treated as missing data when calculating scale scores, but the effect of this practice on assessment of infant temperament has not been reported., Aims: To determine the effect of NA responses on assessment of infant temperament and to evaluate the remedy offered by several missing data strategies., Study Design: A prospective, community-based longitudinal cohort study., Subjects: 401 infants who were born>37 weeks of gestation., Outcome Measures: Mothers completed the short form of the IBQ-R when infants were 3-months and 6-months of age., Results: The rate of NA responses at the 3-month assessment was three times as high (22%) as the rate at six months (7%). Internal consistency was appreciably reduced and scale means were inflated in the presence of NA responses, especially at 3-months. The total number of NA items endorsed by individual parents was associated with infant age and parity. None of the missing data strategies completely eliminated problems related to NA responses but the Expectation Maximization algorithm greatly reduced these problems., Conclusions: The findings suggest that researchers should exercise caution when interpreting results obtained from infants at 3 months of age. Careful selection of scales, selecting a full length version of the IBQ-R, and use of a modern missing data technique may help to maintain the quality of data obtained from very young infants., (Copyright © 2014 Elsevier Ltd. All rights reserved.)