Early Life Surgency, but not Effortful Control or Negative Affectivity, Is a Mediating Variable Between Maternal Pre-Pregnancy Body Mass Index and Childhood Obesity Risk.

Maternal gestational obesity is related to risk of obesity in the child. This risk may be in part mediated by altered child temperament, which can affect mother-child interactions, including feeding and soothing behaviors that affect obesity risk. Our objective was to examine the association between maternal pre-pregnancy BMI and child zBMI and determine if child temperament, specifically positive Affectivity/Surgency, mediates this association. Using conditional process modeling, we analyzed data from 408 mother-child dyads enrolled in the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Child temperament was assessed at 3 years of age via a parent report measure, the Child Behavior Questionnaire (CBQ), and child zBMI was calculated from in-person measurements of child height and weight at 4-5 years of age. Bivariate correlations showed that there was a significant positive correlation between zBMI and Surgency (r = 0.11, p = 0.03), and zBMI was also correlated with maternal pre-pregnancy BMI (r = 0.12, p = 0.02). Multivariable regression revealed that maternal pre-pregnancy BMI (adjusted ß = 0.15, 95% confidence interval [CI]; 0.00-0.05, p = 0.02) and Surgency scores (adjusted ß = 0.14, 95% CI; 0.02-0.28, p = 0.03) were associated with higher child zBMI at 4-5 years of age. Mediation analysis showed that Surgency mediated the association between pre-pregnancy BMI and child zBMI. Our models controlled for maternal gestational weight gain, gestational diabetes, socioeconomic status, maternal anxiety and depression, and gestational age at birth. Overall, maternal pre-pregnancy BMI was positively associated with child zBMI, and this association was mediated by higher child Surgency scores.

Intrapartum antibiotic use is associated with higher child body mass index (BMI) z-score at 4 years of age.

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.

Maternal pre-pregnancy diet and prenatal depression: The mediating role of pre-pregnancy weight status and prenatal inflammation.

Depression is a common prenatal psychological complication. We aimed to investigate if maternal pre-pregnancy diet can impact prenatal depressive symptoms, and the mediating role of pre-pregnancy body mass index (BMI) and inflammation. We used data (N=1141) from the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort study. We calculated Mediterranean diet adherence (MED) and dietary inflammatory index (DII) scores using data from pre-pregnancy food frequency questionnaire (FFQ). In the 3rd-trimester, we assessed depressive symptoms using Edinburgh Postpartum Depression Scale (EPDS), and inflammation through serum C-reactive protein (CRP) levels. BMI was calculated from self-reported pre-pregnancy weight. Race-stratified analyses (white and people of color) were run. We observed no association between MED or DII tertiles and depressive symptoms. However, white participants in the MED tertile-3 had lower risk of depression (EPDS<10) compared to tertile-1 (OR=0.56, 95% CI, 0.33, 0.95). White individuals in MED tertile-3 had lower BMI (MD=-1.08; 95%CI, -1.77, -0.39), and CRP (MD=-0.53; 95%CI, -0.95, -0.11) than tertile-1, and those in DII tertile-2 (MD=0.44;95%CI, 0.03, 0.84) and tertile-3 (MD=0.42; 95%CI, 0.01, 0.83) had higher CRP than tertile-1. Among people of color, neither MED nor DII were associated with BMI or CRP, but BMI was negatively associated with depressive symptoms (ß=-0.25, 95%CI, -0.43, -0.06). We found no association between diet and depressive symptoms through BMI or CRP, in either race. Pre-pregnancy diet might affect the risk of prenatal depression in a race-specific way. Further research is required to explore the racial differences in the association between maternal diet and prenatal depressive symptoms/depression risk.

Cluster-specific associations between the gut microbiota and behavioral outcomes in preschool-aged children.

BACKGROUND: The gut microbiota is recognized as a regulator of brain development and behavioral outcomes during childhood. Nonetheless, associations between the gut microbiota and behavior are often inconsistent among studies in humans, perhaps because many host-microbe relationships vary widely between individuals. This study aims to stratify children based on their gut microbiota composition (i.e., clusters) and to identify novel gut microbiome cluster-specific associations between the stool metabolomic pathways and child behavioral outcomes. METHODS: Stool samples were collected from a community sample of 248 typically developing children (3-5 years). The gut microbiota was analyzed using 16S sequencing while LC-MS/MS was used for untargeted metabolomics. Parent-reported behavioral outcomes (i.e., Adaptive Skills, Internalizing, Externalizing, Behavioral Symptoms, Developmental Social Disorders) were assessed using the Behavior Assessment System for Children (BASC-2). Children were grouped based on their gut microbiota composition using the Dirichlet multinomial method, after which differences in the metabolome and behavioral outcomes were investigated. RESULTS: Four different gut microbiota clusters were identified, where the cluster enriched in both Bacteroides and Bifidobacterium (Ba2) had the most distinct stool metabolome. The cluster characterized by high Bifidobacterium abundance (Bif), as well as cluster Ba2, were associated with lower Adaptive Skill scores and its subcomponent Social Skills. Cluster Ba2 also had significantly lower stool histidine to urocanate turnover, which in turn was associated with lower Social Skill scores in a cluster-dependent manner. Finally, cluster Ba2 had increased levels of compounds involved in Galactose metabolism (i.e., stachyose, raffinose, alpha-D-glucose), where alpha-D-glucose was associated with the Adaptive Skill subcomponent Daily Living scores (i.e., ability to perform basic everyday tasks) in a cluster-dependent manner. CONCLUSIONS: These data show novel associations between the gut microbiota, its metabolites, and behavioral outcomes in typically developing preschool-aged children. Our results support the concept that cluster-based groupings could be used to develop more personalized interventions to support child behavioral outcomes. Video Abstract.

Mixed-methods study exploring health service access and social support linkage to the mental well-being of Canadian Indigenous pregnant persons during the COVID-19 pandemic.

OBJECTIVES: This study aimed to explore how the unprecedented stressors associated with the COVID-19 pandemic may have contributed to heightened levels of depression and anxiety among pregnant Indigenous persons, and identify protective individual-level factors. DESIGN: The current study used a mixed-methods design including standardised questionnaires and open-ended response questions. Using hierarchical regression models, we examined the extent to which COVID-19-related factors of service disruption (ie, changes to prenatal care, changes to birth plans and social support) were associated with mental well-being. Further, through qualitative analyses of open-ended questions, we examined the coping strategies used by pregnant Indigenous persons in response to the pandemic. SETTING: Participants responded to an online questionnaire consisting of standardised measures from 2020 to 2021. PARTICIPANTS: The study included 336 self-identifying Indigenous pregnant persons in Canada. RESULTS: Descriptive results revealed elevated rates of clinically relevant depression (52.7%) and anxiety (62.5%) symptoms among this population. 76.8% of participants reported prenatal care service disruptions, including appointment cancellations. Thematic analyses identified coping themes of staying informed, social and/or cultural connections and activities, and internal mental well-being strategies. Disruptions to services and decreased quality of prenatal care negatively impacted mental well-being of Indigenous pregnant persons during the COVID-19 pandemic. CONCLUSIONS: Given the potential for mental well-being challenges to persist and long-term effects of perinatal distress, it is important to examine the quality of care that pregnant individuals receive. Service providers should advance policies and practices that promote relationship quality and health system engagement as key factors linked to well-being during the perinatal period for Indigenous persons.

Sex-Specific Associations between Prenatal Exposure to Di(2-ethylhexyl) Phthalate, Epigenetic Age Acceleration, and Susceptibility to Early Childhood Upper Respiratory Infections.

Di(2-ethylhexyl) phthalate (DEHP) is a common plasticizer that can affect immune system development and susceptibility to infection. Aging processes (measured as epigenetic age acceleration (EAA)) may mediate the immune-related effects of prenatal exposure to DEHP. This study's objective was to examine associations between prenatal DEHP exposure, EAA at three months of age, and the number of upper respiratory infections (URIs) from 12 to 18 months of age using a sample of 69 maternal-child pairs from a Canadian pregnancy cohort. Blood DNA methylation data were generated using the Infinium HumanMethylation450 BeadChip; EAA was estimated using Horvath's pan-tissue clock. Robust regressions examined overall and sex-specific associations. Higher prenatal DEHP exposure (B = 6.52, 95% CI = 1.22, 11.81) and increased EAA (B = 2.98, 95% CI = 1.64, 4.32) independently predicted more URIs. In sex-specific analyses, some similar effects were noted for boys, and EAA mediated the association between prenatal DEHP exposure and URIs. In girls, higher prenatal DEHP exposure was associated with decreased EAA, and no mediation was noted. Higher prenatal DEHP exposure may be associated with increased susceptibility to early childhood URIs, particularly in boys, and aging biomarkers such as EAA may be a biological mechanism. Larger cohort studies examining the potential developmental immunotoxicity of phthalates are needed.

Maternal pre-pregnancy weight status and gestational weight gain in association with child behavior: The mediating role of prenatal systemic inflammation.

BACKGROUND AND AIMS: Maternal pre-pregnancy obesity and excessive gestational weight gain (EGWG) may predispose children to behavioral problems through increased prenatal inflammation. We investigated the association between maternal body mass index (BMI) and gestational weight gain (GWG), and child behavioral problems (primary aim), and the mediating role of prenatal inflammation (secondary aim). METHODS: We used self-reported pre-pregnancy BMI and estimated-GWG data (N = 1137) from a longitudinal cohort study. Maternal serum C-reactive protein (CRP) was measured in the 3rd-trimester. Parent-reported Child Behavior Checklist (CBCL) was used to assess child internalizing and externalizing behaviors at 3-years-of-age. We used analysis of covariance (ANCOVA), multiple linear regression, and mediation analyses for data analysis. RESULTS: Maternal obesity (F = 21.98, df 3836), EGWG (F = 6.53, df 2764), and their combination (F = 18.51, df 3764) were associated with the 3rd trimester CRP, but not child behavior in the whole sample. Maternal underweight was associated with withdrawal problems in all children (ß = 0.56, 95%CI, 0.11,1.00) and aggressive behaviors in female children (ß = 2.59, 95%CI, 0.28,4.91). Obesity had a significant association with externalizing behaviors in female children after controlling for maternal CRP (ß = 3.72, 95%CI, 0.12,7.32). Both inadequate and EGWG were associated with somatic complaints in male children (ß = 0.50, 95%CI, 0.05,0.95; ß = 0.36, 95%CI, 0.01,0.71, respectively). Combined obesity/EGWG was associated with externalizing (ß = 6.12, 95%CI, 0.53,11.70) and aggressive (ß = 4.23, 95%CI, 0.90,7.56) behaviors in female children. We found no significant effects through CRP. CONCLUSIONS: Maternal pre-pregnancy BMI and GWG showed sex-specific associations with child behavioral problems. Prenatal CRP, although increased in obesity and EGWG, did not mediate these associations.

Maternal Iron and Vitamin D Status during the Second Trimester Is Associated with Third Trimester Depression Symptoms among Pregnant Participants in the APrON Cohort.

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 (ß: -0.8; 95% confidence interval [CI]: -1.5, -0.01), hepcidin (ß: -0.5; 95% CI: -0.9, -0.2), and 25(OH)D3 (ß: -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) (ß: 1.1; 95% CI: 0.03, 2.1) or low iron (SF <15 µg/L) and vitamin D (25(OH)D <75 nmol/L) (ß: 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.

Maternal Pre-Pregnancy BMI and Gestational Weight Gain Are Associated with Preschool Children's Neuropsychological Outcomes in the APrON Cohort.

This study examined the associations between maternal pre-pregnancy BMI and gestational weight gain (GWG) and children's neuropsychological outcomes at 3 to 5 years of age. A total of 379 women and their children from the Alberta Pregnancy Outcomes and Nutrition (APrON) study participated. Covariate-adjusted robust regressions examined associations between maternal pre-pregnancy BMI, GWG class, interaction terms, and child outcomes. Each unit increase in maternal BMI was linked to a 0.48-point decrement (95% CI: -0.75 to -0.21) in children's Full Scale IQ. Higher pre-pregnancy BMI was related to poorer performance on the other intelligence indexes (B = -0.35 to -0.47, 95% CIs: -0.75, -0.02) and lower performance on measures of language (B = -0.08 to -0.09, 95% CIs: -0.16, -0.02), motor skills (B = -0.08 to -0.11, 95% CIs: -0.18, -0.01), and executive function (B = -0.09 to -0.16, 95% CIs: -0.26, -0.01). GWG below the recommended range was associated with a 4.04-point decrement (95% CI: 7.89, -0.11) in Full Scale IQ, but better performance on a spatial working memory test (B = 0.27, 95% CI: 0.02, 0.52). GWG above the recommended range was associated with lower language (B = -0.79, 95% CI: -1.52, -0.06) and memory scores (B = -0.93, 95% CI: -1.64, -0.22). Interactions were found between pre-pregnancy BMI and GWG on measures of intelligence and executive function. Maternal pre-pregnancy BMI and GWG are related to children's performance in various neuropsychological domains and may interact to predict outcomes. Optimizing maternal health and weight prior to conception and during pregnancy may enhance children's neuropsychological outcomes.

Perinatal Trajectories of Maternal Depressive Symptoms in Prospective, Community-Based Cohorts Across 3 Continents.

Importance: Depressive symptoms during pregnancy influence the development and health of the offspring, underscoring the need for timely intervention. However, the course of depressive symptoms across the perinatal period remains unclear, thus complicating screening and referral guidelines. Objective: To examine the course and stability of depressive symptoms across the perinatal period in multiple, ethnically diverse independent observational cohorts. Design, Setting, and Participants: This cohort study included self-reported depressive symptoms at multiple time points from 7 prospective cohorts spanning 3 continents (United Kingdom: Avon Longitudinal Study of Parents and Children from 1991 to 1995; Canada: Maternal Adversity, Vulnerability and Neurodevelopment from 2003 to 2007; Montreal Antenatal Well-being Study from 2019 to 2022; Alberta Pregnancy Outcomes and Nutrition from 2009 to 2014; and Singapore: Growing Up in Singapore Toward Healthy Outcomes from 2009 to 2013; Singapore Preconception Study of Long-Term Maternal and Child Outcomes from 2015 to 2019; and Mapping Antenatal Maternal Stress from 2019 to 2022). Participants were recruited either during preconception or pregnancy and observed into the postnatal period. All data from each cohort were analyzed from July 2022 to April 2023. Main Outcomes and Measures: Self-reported depressive symptoms from pregnancy to 2 years following childbirth using either the Edinburgh Postnatal Depression Scale or the Center for Epidemiological Studies Depression were analyzed independently within each cohort using item response theory (IRT) techniques. K-means clustering was used to identify groups of participants with similar trajectories. Results: A total of 11 563 pregnant women (mean [SD] age, 29 [5] years; 569 [4.9%] East Asian women; 304 [2.6%] Southeast Asian women; 10 133 [87.6%] White women) self-reported depressive symptoms from pregnancy to 2 years following childbirth. Analytic methods from Item Response Theory identified 3 groups of mothers based on depressive symptoms: low, mild, and high levels in each of the 7 cohorts. Mothers within and across all cohorts had stable trajectories of maternal depressive symptoms from pregnancy onwards. Mothers with clinical levels of depressive symptoms likewise showed stable trajectories from pregnancy into the postnatal period. Conclusions and Relevance: In this study, trajectories of depressive symptoms remained stable from pregnancy across the perinatal period, a finding that conflicts with a continuing emphasis on postpartum or postnatal onset of depression that persists in some health policy guidelines. Interventions and public health initiatives should focus on reducing depressive symptoms during pregnancy in addition to following birth.

Long-term and trimester-specific effects of prenatal stress on the child gut microbiota.

OBJECTIVE: Stress is common among pregnant individuals and is associated with an altered gut microbiota composition in infants. It is unknown if these compositional changes persist into the preschool years when the gut microbiota reaches an adult-like composition. This study aimed to investigate if indicators of prenatal stress (i.e., psychological distress and stress-related physiology) are associated with children's gut microbiota composition and metabolites at 3-4 years of age. METHODS: Maternal-child pairs (n = 131) were from the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort. Each trimester, psychological distress was measured as symptoms of anxiety (Symptom Checklist-90-R) and depressed mood (Edinburgh Postnatal Depression Scale), whereas salivary cortisol was quantified as a measure of stress-related physiology. Child stool samples were collected at 3-4 years to evaluate gut microbiota composition using 16S rRNA gene sequencing and fecal metabolome using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Associations between prenatal distress and cortisol with the gut microbiota were determined using Pearson and Spearman correlations and corrected for multiple testing. Associations between prenatal distress and cortisol with the fecal metabolome were assessed using Metaboanalyst. RESULTS: Symptoms of depressed mood during the 2nd and 3rd trimesters and anxiety during the 2nd trimester of pregnancy were associated with increased alpha diversity of the child's gut microbiota. Cortisol levels during the 1st trimester were also associated with increased Faith PD diversity (r = 0.32), whereas cortisol levels during the 2nd trimester were associated with reduced Shannon diversity (r = -0.27). Depression scores during the 2nd and 3rd trimesters were associated with reductions in the relative abundances of Eggerthella, Parasutterella, and increases in Ruminococcaceae (rs = -0.28, rs = -0.32, rs = 0.32, respectively), as well as the fecal metabolome (e.g., branched-chain amino acid metabolism). Cortisol levels during the 2nd trimester correlated with 7 bacterial taxa, whereas 1st-trimester cortisol levels were associated with the child's fecal metabolome. CONCLUSIONS: Prenatal distress and cortisol were associated with both child gut microbiota composition and fecal metabolome at preschool age. Understanding these associations may allow for the identification of microbiota-targeted interventions to support child developmental outcomes affected by prenatal stress.

Prenatal mental health data and birth outcomes in the pregnancy during the COVID-19 Pandemic dataset.

The COVID-19 pandemic was a substantial stressor, especially for pregnant individuals. We aimed to understand the impact of COVID-19-related stresses on pregnant individuals and their infants and collected survey-based data across Canada as part of the Pregnancy during the COVID-19 Pandemic (PdP) project. The dataset described here provides baseline prenatal data and basic birth outcomes from PdP participants. This data includes information from pregnant individuals as well as their infants. At enrolment and time of completion of the baseline survey, participants were pregnant, ≥17 years of age, ≤35 weeks of gestation, living in Canada, and able to read and write in English or French. Baseline data were collected between April 2020-April 2021. Infant data were collected between May 2020-December 2021. All data were collected via self-report using online questionnaires in REDCAP. Questionnaires were available in both English and French. Data were checked for completeness and plausibility, and duplicates were removed. The dataset described here includes age, education, and household income of the pregnant individuals reported at the baseline/enrollment survey. Raw scores are provided for the Edinburgh Postnatal Depression Scale (EPDS) and the PROMIS Anxiety scale. Ratings are also given for three variables describing fear of the COVID-19 virus. Birth outcomes are provided for infants, including gestational age at birth, birthweight, length, mode of delivery, and whether the infant spent time in the neonatal intensive care unit (NICU). Delivery date is reported as month and year. These data will be beneficial for anyone interested in researching stress during pregnancy or birth outcomes in the context of the COVID-19 pandemic. They will also be useful to researchers interested in examining more general effects of prenatal distress on birth outcomes in children. Data could also be compared to other datasets from the COVID-19 pandemic to establish generalizability, or to pre-pandemic datasets to determine the extent of changes during the COVID-19 pandemic.

Sex-specific associations between maternal phthalate exposure and neurodevelopmental outcomes in children at 2 years of age in the APrON cohort.

BACKGROUND: There is inconsistent evidence regarding the sex-specific associations between prenatal phthalate exposure and children's neurodevelopment. This could be due to differences in the phthalate exposures investigated and the neurodevelopmental domains assessed. OBJECTIVE: To evaluate the associations between prenatal phthalate exposure and sex-specific outcomes on measures of cognition, language, motor, executive function, and behaviour in children 2 years of age in the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort. METHODS: We evaluated the associations between prenatal phthalate exposure and sex-specific neurodevelopmental outcomes in children at 2 years of age using data from 448 mothers and their children (222 girls, 226 boys). Nine phthalate metabolites were measured in maternal urine collected in the second trimester of pregnancy. Children's cognitive, language, and motor outcomes were assessed using the Bayley Scales of Infant Development - Third Edition (Bayley-III). Parents completed questionnaires on children's executive function and behavior, the Behavior Rating Inventory of Executive Function- Preschool Version (BRIEF-P) and Child Behavior Checklist (CBCL), respectively. Sex-stratified robust multivariate regressions were performed. RESULTS: Higher maternal concentrations of ΣDEHP and its metabolites were associated with lower scores on the Bayley-III Cognitive (ß's from -11.8 to -0.07 95% CI's from -21.3 to -0.01), Language (ß's from -11.7 to -0. 09, 95% CI's from -22.3 to -0.02) and Motor (ß's from -10.9 to -0.07, 95% CI from -20.4 to -0.01) composites in boys. The patterns of association in girls were in the opposite direction on the Cognitive and Language composites; on the Motor composite they were in the same direction as boys, but of reduced strength. Higher concentrations of ΣDEHP and its metabolites were associated with higher scores (i.e., more difficulties) on all measures of executive function in girls: inhibitory self-control (B's from 0.05 to 0.11, 95% CI s from -0.01 to 0.15), flexibility (B's from 0.04 to 0.11, 95% CI s from 0.01 to 0.21) and emergent metacognition (B's from -0.01 to 0.06, 95% CIs from -0.01 to 0.20). Similar patterns of attenuated associations were seen in boys. Higher concentrations of ΣDEHP and its metabolites were associated with more Externalizing Problems in girls and boys (B's from 0.03 to 6.82, 95% CIs from -0.08 to 12.0). Two phthalates, MMP and MBP, had sex-specific adverse associations on measures of executive function and behaviour, respectively, while MEP was positively associated with boys' cognitive, language, and motor performance. Limited associations were observed between mixtures of maternal phthalates and sex-specific neurodevelopmental outcomes. CONCLUSIONS: Maternal prenatal concentrations of DEHP phthalates were associated with sex specific difference on measures of cognition and language at 2 years of age, specifically, poorer outcomes in boys. Higher exposure to DEHP was associated with poorer motor, executive function, and behavioural outcomes in girls and boys but the strength of these associations differed by sex. Limited associations were noted between phthalate mixtures and child neurodevelopment.

Risk for Developmental Delay Among Infants Born During the COVID-19 Pandemic.

OBJECTIVE: Attempts by governments around the world to mitigate the spread of COVID-19 have substantially altered the early rearing environment, raising concerns about potential negative consequences for babies born during this time. The objective of this study was to determine whether infants born during the COVID-19 pandemic were at greater risk of screening positive for developmental delay compared with infants born before the pandemic. METHODS: Participants were from 2 longitudinal cohorts. The prepandemic cohort, Impact of Maternal and Paternal Postpartum Depression, recruited postpartum individuals in the period between 2015 and 2018. Infant development milestone data (Ages and Stages Questionnaire [ASQ-3]) were collected at 1-year postpartum (n = 2903), between 2016 and 2019. The pandemic cohort, Pregnancy during the Pandemic, recruited pregnant individuals between April 2020 and April 2021. Infant development milestone data (ASQ-3) were collected at 1-year postpartum (n = 3742), between May 2021 and December 2022. Sociodemographic information, pregnancy outcomes, and depression symptom data were also collected. RESULTS: In covariate-adjusted analyses, pandemic-born infants had lower mean scores and higher odds of screening positive for delay on the Communication, Gross Motor, and Personal-Social domains of the ASQ-3 compared with prepandemic infants. Sex differences showed that males and females screened "at risk" in different domains. CONCLUSION: Most pandemic-born infants display typical development, and differences between prepandemic and pandemic-born infants were small. Nevertheless, an increased risk for delayed development among pandemic-born infants suggests the need for ongoing monitoring to determine what, if any, resources and interventions are needed to support healthy child development.

Maternal Iron Status Is Dynamic Throughout Pregnancy and Might Predict Birth Outcomes in a Sex Dependent Manner: Results from the Alberta Pregnancy Outcomes and Nutrition (APrON) Cohort Study.

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.

Understanding COVID-19 vaccination decisions during pregnancy and while breastfeeding in a Canadian province.

BACKGROUND: Vaccination in pregnancy is important for preventing illness for mothers and babies; however, vaccine uptake in pregnant individuals is lower than non-pregnant females of fertile age. Given the devastating effects of COVID-19 and the increased morbidity and mortality risk for pregnant individuals, it is important to understand the determinants of vaccine hesitancy in pregnancy. The focus of our study was to explore COVID-19 vaccination among pregnant and breastfeeding individuals and its association with their reasons (psychological factors) for vaccination using the 5C scale and other factors. METHODS: An online survey investigating prior vaccinations, level of trust in healthcare providers, demographic information, and the 5C scale was used for, pregnant and breastfeeding individuals in a Canadian province. RESULTS: Prior vaccinations, higher levels of trust in medical professionals, education, confidence, and collective responsibility predicted increased vaccine uptake pregnant and breastfeeding individuals. CONCLUSIONS: There are specific psychological and socio-demographic determinants that affect COVID-19 vaccine uptake in pregnant populations. Implications of these findings include targeting these determinants when informing and developing intervention and educational programs for both pregnant and breastfeeding individuals, as well as healthcare professionals who are making vaccine recommendations to patients. Study limitations include a small sample and lack of ethnic and socioeconomic diversity.

Exploring associations between the gut microbiota and full-scale intelligence in preschool children.

The relationship between the gut microbiota and neurocognitive outcomes is becoming increasingly recognized; however, findings in humans are inconsistent. In addition, few studies have investigated the gut microbial metabolites that may mediate this relationship. The objective of this study was to investigate associations between full-scale intelligence (FSIQ) and the composition of the gut microbiota and metabolome in preschool children. Stool samples were collected from a community sample of 245 typically developing children (3-5 years) from the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort. The faecal microbiome was assessed using 16S rRNA sequencing and the metabolome using LC-MS/MS. FSIQ and scores on the Verbal Comprehension, Visual Spatial, Working Memory indices of the Wechsler Preschool and Primary Scale of Intelligence-IV were used to assess neurocognition. Associations between the gut microbiota and FSIQ were determined using Pearson and Spearman correlations, which were corrected for multiple testing and relevant covariates. Verbal Comprehension correlated negatively with both Shannon alpha diversity (r = -0.14, p = 0.032) and the caffeine-derived metabolite paraxanthine (r = -0.22, p < 0.001). No other significant correlations were observed. Overall, the weak to modest correlations between Verbal Comprehension with alpha diversity and paraxanthine provide limited evidence of an association between the gut microbiota and neurocognitive outcomes in typically developing preschool children.

Prenatal depressive symptoms are associated with altered structural brain networks in infants and moderated by infant sleep.

BACKGROUND: The prevalence of prenatal depressive symptoms has more than doubled during the COVID-19 pandemic, raising substantial concerns about child outcomes including sleep problems and altered brain development. The objective of this work was to determine relationships between prenatal depressive symptoms, infant brain network structure, and infant sleep. METHODS: Pregnant individuals were recruited as part of the Pregnancy during the Pandemic (PdP) study. Maternal depressive symptoms were measured in pregnancy and postpartum. When infants of those participants were 3 months of age (n=66; 26 females), infants underwent diffusion magnetic resonance imaging and infant sleep was evaluated. Using tractography, we calculated structural connectivity matrices for the default mode (DMN) and limbic networks. We examined associations between graph theory metrics of infant brain networks and prenatal maternal depressive symptoms, with infant sleep as a moderator. RESULTS: Prenatal depressive symptoms were negatively related to average DMN clustering coefficient and local efficiency in infant brains. Infant sleep duration was related to DMN global efficiency and moderated the relationship between prenatal depressive symptoms and density of limbic connections such that infants who slept less had a more negative relationship between prenatal depressive symptoms and local brain connectivity. CONCLUSIONS: Prenatal depressive symptoms appear to impact early topological development in brain networks important for emotion regulation. In the limbic network, sleep duration moderated this relationship, suggesting sleep may play a role in infant brain network development.

Fluoride exposure during pregnancy from a community water supply is associated with executive function in preschool children: A prospective ecological cohort study.

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-IVCDN). Children's executive functions were also assessed: working memory (WPPSI-IVCDN 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.