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 influences the associations between bisphenol and phthalate exposures and maternal weight changes and fat accumulation.

BACKGROUND: Bisphenols and phthalates are two classes of endocrine-disrupting chemicals (EDCs) thought to influence weight and adiposity. Limited research has investigated their influence on maternal weight changes, and no prior work has examined maternal fat mass. We examined the associations between exposure to these chemicals during pregnancy and multiple maternal weight and fat mass outcomes. METHODS: This study included a sample of 318 women enrolled in a Canadian prospective pregnancy cohort. Second trimester urinary concentrations of 2 bisphenols and 12 phthalate metabolites were quantified. Self-reported and measured maternal weights and measured skinfold thicknesses were used to calculate gestational weight gain, 3-months and 3- to 5-years postpartum weight retention, late pregnancy fat mass gain, total postpartum fat mass loss, and late postpartum fat mass retention. Adjusted robust regressions examined associations between chemicals and outcomes in the entire study population and sub-groups stratified by pre-pregnancy body mass index (BMI). Bayesian kernel machine regression examined chemical mixture effects. RESULTS: Among women with underweight or normal pre-pregnancy BMIs, MBzP was negatively associated with weight retention at 3- to 5-years postpartum (B = -0.04, 95%CI: -0.07, -0.01). Among women with overweight or obese pre-pregnancy BMIs, MEHP and MMP were positively associated with weight retention at 3-months and 3- to 5-years postpartum, respectively (B's = 0.12 to 0.63, 95%CIs: 0.02, 1.07). DEHP metabolites and MCNP were positively associated with late pregnancy fat mass gain and late postpartum fat mass retention (B's = 0.04 to 0.18, 95%CIs: 0.001, 0.32). Further, the mixture of EDCs was positively associated with late pregnancy fat mass gain. CONCLUSION: In this cohort, pre-pregnancy BMI was a key determinant of the associations between second trimester exposure to bisphenols and phthalates and maternal weight changes and fat accumulation. Investigations of underlying physiological mechanisms, windows of susceptibility, and impacts on maternal and infant health are needed.

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.

Prenatal depressive symptoms and childhood development of brain limbic and default mode network structure.

Prenatal depressive symptoms are linked to negative child behavioral and cognitive outcomes and predict later psychopathology in adolescent children. Prior work links prenatal depressive symptoms to child brain structure in regions like the amygdala; however, the relationship between symptoms and the development of brain structure over time remains unclear. We measured maternal depressive symptoms during pregnancy and acquired longitudinal T1-weighted and diffusion imaging data in children (n = 111; 60 females) between 2.6 and 8 years of age. Controlling for postnatal symptoms, we used linear mixed effects models to test relationships between prenatal depressive symptoms and age-related changes in (i) amygdala and hippocampal volume and (ii) structural properties of the limbic and default-mode networks using graph theory. Higher prenatal depressive symptoms in the second trimester were associated with more curvilinear trajectories of left amygdala volume changes. Higher prenatal depressive symptoms in the third trimester were associated with slower age-related changes in limbic global efficiency and average node degree across childhood. Our work provides evidence that moderate symptoms of prenatal depression in a low sociodemographic risk sample are associated with structural brain development in regions and networks implicated in emotion processing.

The distribution of dietary choline intake and serum choline levels in Australian women during pregnancy and associated early life factors.

BACKGROUND: Maternal dietary choline has a central role in foetal brain development and may be associated with later cognitive function. However, many countries are reporting lower than recommended intake of choline during pregnancy. METHODS: Dietary choline was estimated using food frequency questionnaires in pregnant women participating in population-derived birth cohort, the Barwon Infant Study (BIS). Dietary choline is reported as the sum of all choline-containing moieties. Serum total choline-containing compounds (choline-c), phosphatidylcholine and sphingomyelin were measured using nuclear magnetic resonance metabolomics in the third trimester. The main form of analysis was multivariable linear regression. RESULTS: The mean daily dietary choline during pregnancy was 372 (standard deviation (SD) 104) mg/day. A total of 236 women (23%) had adequate choline intake (440 mg/day) based on the Australian and New Zealand guidelines, and 27 women (2.6%) took supplemental choline ([Formula: see text] 50 mg/dose) daily during pregnancy. The mean serum choline-c in pregnant women was 3.27 (SD 0.44) mmol/l. Ingested choline and serum choline-c were not correlated (R2) = - 0.005, p = 0.880. Maternal age, maternal weight gain in pregnancy, and a pregnancy with more than one infant were associated with higher serum choline-c, whereas gestational diabetes and environmental tobacco smoke during preconception and pregnancy were associated with lower serum choline-c. Nutrients or dietary patterns were not associated with variation in serum choline-c. CONCLUSION: In this cohort, approximately one-quarter of women met daily choline recommendations during pregnancy. Future studies are needed to understand the potential impact of low dietary choline intake during pregnancy on infant cognition and metabolic intermediaries.

Associations between the chemical exposome and pregnancy induced hypertension.

Exposure to environmental chemicals has been linked to an increased risk of pregnancy-induced hypertension (PIH). This prospective cohort study examined the associations between PIH and maternal chemical exposure to four classes of chemicals (i.e., phthalates, bisphenols, perfluoroalkyl acids, non-essential metals and trace minerals). Participants included 420 pregnant women from the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort who had data available on diagnosed PIH and environmental chemical exposure. Twelve phthalate metabolites, two bisphenols, eight perfluoroalkyl acids and eleven non-essential metals or trace minerals were quantified in maternal urine or blood samples collected in the second trimester of pregnancy. Associations between the urinary and blood concentrations of these chemicals and PIH were assessed using multiple logistic and LASSO regression analyses in single- and multi-chemical exposure models, respectively. Thirty-five (8.3%) participants were diagnosed with PIH. In single chemical exposure models, two phthalate metabolites, mono-methyl phthalate (MMP) and monoethyl phthalate (MEP), three perfluoroalkyl acids, perfluoroheptanoic acid (PFHpA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA), and one metal, manganese, were associated with increased odds of PIH. The metabolites of di (2-ethylhexyl) phthalate (DEHP) and the molar sum of these metabolites, as well as antimony, displayed trend associations (p < 0.10). In multi-chemical exposure models using LASSO penalized regressions and double-LASSO regressions, MEP (AOR: 1.43, 95% CI: 1.09-1.88, p = 0.009) and PFNA (AOR: 2.03, 95% CI: 1.01-4.07, p = 0.04) were selected as the chemicals most highly associated with PIH. These findings suggest that maternal levels of phthalates and perfluoroalkyl acids may be associated with the diagnosis on PIH. Future research should consider both individual and multi-chemical exposures when examining predictors of PIH and other maternal cardiometabolic health disorders, such as preeclampsia, eclampsia, HELLP syndrome, and gestational diabetes.

Functional connectivity based brain signatures of behavioral regulation in children with ADHD, DCD, and ADHD-DCD.

Behavioral regulation problems have been associated with daily-life and mental health challenges in children with neurodevelopmental conditions such as attention-deficit/hyperactivity disorder (ADHD) and developmental coordination disorder (DCD). Here, we investigated transdiagnostic brain signatures associated with behavioral regulation. Resting-state fMRI data were collected from 115 children (31 typically developing (TD), 35 ADHD, 21 DCD, 28 ADHD-DCD) aged 7-17 years. Behavioral regulation was measured using the Behavior Rating Inventory of Executive Function and was found to differ between children with ADHD (i.e., children with ADHD and ADHD-DCD) and without ADHD (i.e., TD children and children with DCD). Functional connectivity (FC) maps were computed for 10 regions of interest and FC maps were tested for correlations with behavioral regulation scores. Across the entire sample, greater behavioral regulation problems were associated with stronger negative FC within prefrontal pathways and visual reward pathways, as well as with weaker positive FC in frontostriatal reward pathways. These findings significantly increase our knowledge on FC in children with and without ADHD and highlight the potential of FC as brain-based signatures of behavioral regulation across children with differing neurodevelopmental conditions.

Association of sedation and anesthesia on cognitive outcomes in very premature infants: a retrospective observational study.

PURPOSE: Cognitive outcomes in preterm infants may be adversely affected by use of sedation and anesthetic agents. We investigated the associations between anesthetics/sedatives and full-scale intelligence quotient (FSIQ) measured at 36 months corrected age (CA) in very preterm infants (born < 29 weeks gestational age). METHODS: This retrospective cohort study included preterm infants born at < 29 weeks of gestation between 1 January 2006 and 31 December 2012, whose cognitive outcomes were assessed at 36 months CA. Imputed and complete case univariable and adjusted multivariable linear regressions were used to investigate the associations between FSIQ [standardized to mean (standard deviation) 100 (15)] and exposure to volatile anesthetics, propofol, benzodiazepines, barbiturates, and ketamine. These agents were the subject of a 2016 warning from regulatory authorities in the USA recommending caution for administration to children and pregnant women. RESULTS: A total of 731 infants met the inclusion criteria. Unadjusted associations were -7 (95% confidence interval [CI], -10 to -4; P < 0.001) and -6 (95% CI, -10 to -3; P < 0.001) FSIQ points with exposure to warned medications using imputed and complete case analyses, respectively. Imputed and complete case adjusted associations between FSIQ and warned medications were -3 (95% CI, -7 to 0; P = 0.045) and -4 (95% CI, -8 to 0; P = 0.071) FSIQ points, respectively. Adjusted associations between volatile anesthetic exposure only and FSIQ were -3 (95% CI, -6 to 0; P = 0.072) and -5 (95% CI, -9 to -2; P = 0.004) FSIQ points using imputed and complete case data sets, respectively. FSIQ was not associated with opioid exposure. CONCLUSION: Exposure of very preterm infants to anesthetics/sedatives on the United States Food and Drug Administration warning list was associated with a decrease in FSIQ points at 36 months CA. There was no association between opioid exposure and FSIQ.

RéSUMé: OBJECTIF : L'utilization d'agents sédatifs et anesthésiques pourrait avoir une incidence défavorable sur l'évolution cognitive des nourrissons prématurés. Nous avons analysé les associations existantes entre les anesthésiques/sédatifs et le quotient d'intelligence global (QIg) mesuré à 36 mois d'âge corrigé (AC) chez des enfants nés grands prématurés (nés < 29 semaines d'âge gestationnel). MéTHODES: Cette étude de cohorte rétrospective a inclus des nourrissons prématurés nés avant 29 semaines d'âge gestationnel entre le 1er janvier 2006 et le 31 décembre 2012 et dont les critères d'évaluation cognitifs ont été évalués à 36 mois d'AC. Des régressions linéaires à une seule variable et multivariables ajustée, sur les cas imputés et sur les cas complets, ont été utilisées pour rechercher les associations entre le QIg (standardisé à la moyenne 100 [± écart-type] [15]) et l'exposition à des anesthésiques volatils, du propofol, des benzodiazépines, des barbituriques et de la kétamine. Ces molécules ont fait l'objet d'une mise en garde en 2016 par les autorités de réglementation aux États-Unis, recommandant la prudence concernant leur administration à des enfants et à des femmes enceintes. RéSULTATS: Un total de 731 nourrissons présentait les critères d'inclusion. Les associations non ajustées ont été de -7 (intervalle de confiance [IC] à 95 % : -10 à -4; P < 0,001) et -6 (IC à 95 % : -10 à -3; P < 0,001) points de QIg avec l'exposition aux médicaments sous avertissement en utilisant, respectivement, des analyses de cas imputés et de cas complets. Les associations ajustées de cas imputés et complets entre le QIg et les médicaments sous avertissement ont été, respectivement, de -3 (IC à 95 % : -7 à 0; P = 0,045) et -4 (IC à 95 % : -8 à 0; P = 0,071) points de QIg. Les associations ajustées entre l'exposition aux anesthésiques volatiles, uniquement, et le QIg ont été de -3 (IC à 95 % : -6 à 0; P = 0,072) et -5 (IC à 95 % : -9 à 2; P = 0,004) points de QIg en utilisant, respectivement, les ensembles de données des cas imputés et des cas complets. Le QIg n'a pas été associé à une exposition aux opioïdes. CONCLUSION: L'exposition des nourrissons grands prématurés aux anesthésiques/sédatifs figurant sur la liste d'avertissement de la Food and Drug Administration des États-Unis a été associée à une diminution des points de QIg à 36 mois d'AC. Il n'y a pas eu d'association entre l'exposition aux opioïdes et le QIg.

Antenatal corticosteroid therapy, delivery intervals and perinatal mortality in low-resource settings.

BACKGROUND: Uncertainty exists regarding the ideal interval between the administration of antenatal corticosteroids (ACS) and delivery. The study's objective was to assess the risks of perinatal mortality and respiratory distress syndrome (RDS) among preterm neonates whose mothers gave birth within 48 h of the administration of ACS and those whose mothers gave birth between 48 h and 7 days. METHODS: The study design was a secondary analysis of data from an observational prospective chart review study that was carried out in Tanzania in 2020. Preterm infants born to mothers who got at least one dose of ACS between 28 and 34 weeks of pregnancy were included. RESULTS: A total of 346 preterm neonates (294 singletons and 52 twins) were exposed to ACS. Compared to infants born 48 h following the first dose of ACS, those exposed to the drug between 48 h and 7 days had significantly decreased rates of perinatal mortality and RDS. Multivariable analysis revealed that infants exposed ACS between 48 h and 7 days prior to delivery had lower risk of perinatal mortality (aRR 0.30, 95% CI 0.14-0.66) and RDS (aRR 0.27, 95% CI 0.14-0.52). CONCLUSION: The first dose of ACS given between 48 h and 7 days before delivery was associated with a lower risk of perinatal mortality and RDS than when the first dose was given <48 h before delivery. To improve neonatal outcomes, healthcare providers should consider administering ACS to mothers at the appropriate time.

Preterm infants exposed to antenatal corticosteroids (ACS) have lower rates of perinatal mortality and morbidity. Uncertainty exists regarding the ideal interval between the administration of ACS and delivery. We conducted a secondary analysis of data from a study that included preterm infants born in four hospitals in Tanzania. We investigated whether there were differences in perinatal mortality and respiratory distress syndrome between preterm neonates whose mothers delivered within 48 h of receiving a partial course of ACS and those whose mothers delivered between 48 h and 7 days after a full course of ACS therapy. Participants were the preterm infants of women who received ACS between 28 and 34 weeks of gestation. Neonates exposed to ACS between 48 h and 7 days prior to delivery had significantly lower risks of perinatal mortality and respiratory distress syndrome compared to infants who were delivered <48 h after ACS administration. This finding highlights the importance of optimizing the timing of ACS administration to maximize its potential benefits and minimize risks to preterm neonates. To improve neonatal outcomes, healthcare providers should consider administering ACS to mothers at the appropriate time.

Functional connectomes become more longitudinally self-stable, but not more distinct from others, across early childhood.

Functional connectomes, as measured with functional magnetic resonance imaging (fMRI), are highly individualized, and evidence suggests this individualization may increase across childhood. A connectome can become more individualized either by increasing self-stability or decreasing between-subject-similarity. Here we used a longitudinal early childhood dataset to investigate age associations with connectome self-stability, between-subject-similarity, and developmental individualization, defined as an individual's self-stability across a 12-month interval relative to their between-subject-similarity. fMRI data were collected during an 18-minute passive viewing scan from 73 typically developing children aged 4-7 years, at baseline and 12-month follow-up. We found that young children had highly individualized connectomes, with sufficient self-stability across 12-months for 98% identification accuracy. Linear models showed a significant relationship between age and developmental individualization across the whole brain and in most networks. This association appeared to be largely driven by an increase in self-stability with age, with only weak evidence for relationships between age and similarity across participants. Together our findings suggest that children's connectomes become more individualized across early childhood, and that this effect is driven by increasing self-stability rather than decreasing between-subject-similarity.

Associations Between the Gut Microbiota and Internalizing Behaviors in Preschool Children.

OBJECTIVE: Emerging evidence points toward a connection between mental health and the gut microbiota and its metabolites (e.g., short-chain fatty acids). It is unknown whether the gut microbiota is associated with the development of mental health problems (e.g., internalizing or externalizing behaviors) in preschool children. The objective of this study was to evaluate associations between the gut microbiota and internalizing and externalizing behaviors in preschool-aged children. METHODS: A community sample of 248 typically developing children (3-5 years of age) provided a stool sample for gut microbiota and SCFA analysis. Parents reported child internalizing and externalizing behaviors using the Child Behavior Checklist. Associations between child behaviors and gut microbiota measures were analyzed using Spearman correlations followed by an adjustment for multiple testing, with subanalysis conducted in children clinically "at risk" for behavioral problems compared with those who were not. RESULTS: There was a correlation between Shannon alpha diversity with internalizing behaviors (rs = -0.134, p = .035) and its subscale somatic complaints (rs = -0.144, p = .023). In addition, children clinically "at risk" for internalizing problems had decreased alpha diversity (U = 551, p = .017). Internalizing behaviors correlated with valerate and isobutyrate (rs = -0.147, p = .021; rs = -0.140, p = .028, respectively). Furthermore the somatic complaints subscale additionally correlated with acetate and butyrate (rs = -0.219, p = .001; rs = -0.241, p < .001, respectively). These findings were also present in children "at risk" for internalizing problems (U = 569, p = .026; U = 571, p = .028) and somatic complaints (U = 164, p = .004; U = 145, p = .001). CONCLUSIONS: These analyses reveal novel associations between internalizing behaviors and the gut microbiota in preschool children. Furthermore, a relationship between somatic complaints and acetate and butyrate was identified, indicating that interventions that increase SCFA production warrant future investigation.

Altered gray matter development in pre-reading children with a family history of reading disorder.

Reading disorders are common in children and can impact academic success, mental health, and career prospects. Reading is supported by network of interconnected left hemisphere brain regions, including temporo-parietal, occipito-temporal, and inferior-frontal circuits. Poor readers often show hypoactivation and reduced gray matter volumes in this reading network, with hyperactivation and increased volumes in the posterior right hemisphere. We assessed gray matter development longitudinally in pre-reading children aged 2-5 years using magnetic resonance imaging (MRI) (N = 32, 110 MRI scans; mean age: 4.40 ± 0.77 years), half of whom had a family history of reading disorder. The family history group showed slower proportional growth (relative to total brain volume) in the left supramarginal and inferior frontal gyri, and faster proportional growth in the right angular, right fusiform, and bilateral lingual gyri. This suggests delayed development of left hemisphere reading areas in children with a family history of dyslexia, along with faster growth in right homologues. This alternate development pattern may predispose the brain to later reading difficulties and may later manifest as the commonly noted compensatory mechanisms. The results of this study further shows our understanding of structural brain alterations that may form the neurological basis of reading difficulties.

Perinatal arterial ischemic stroke and periventricular venous infarction in infants with unilateral cerebral palsy.

AIM: To explore clinical factors associated with perinatal arterial ischemic stroke (AIS) and periventricular venous infarction (PVI) in infants who develop unilateral cerebral palsy (CP). METHOD: This was a case-control study. Data current to 2019 was extracted from the Canadian Cerebral Palsy Registry (CCPR). Cases were infants born at term with confirmed unilateral CP. Magnetic resonance images were stratified by expert review of reports as definitive perinatal stroke (AIS or PVI). Controls with common data elements were recruited from a population-based study in Alberta. Multivariable regression analyses were performed to estimate associations expressed as odds ratios with 95% confidence intervals. RESULTS: Of 2093 cases from the CCPR, 662 had unilateral CP, of whom 299 (45%) had perinatal stroke: AIS 169 (57%) and PVI 130 (43%). Median age at diagnosis for AIS was 11.9 months (interquartile range: 6.2-25.7mo; range 0.17-104.1mo), and 58.6% were male. Median age at diagnosis for PVI was 25.3 months (interquartile range: 14.5-38mo, range 0.7-114.7mo) and 57.7% were male. Independent associations for both AIS and PVI on multivariable analysis were chorioamnionitis, illicit drug exposure, diabetes, gestational age, and maternal age. Variables associated with AIS alone were low Apgar score and prolonged rupture of membranes. Variables associated with PVI alone were small for gestational age and primigravida. INTERPRETATION: Controlled analysis of disease-specific unilateral CP may offer unique perspectives on its pathophysiology. Acute intrapartum factors are mainly associated with AIS, while in utero factors are associated with PVI.

The effects of prenatal bisphenol A exposure on brain volume of children and young mice.

Bisphenol A (BPA) is a synthetic chemical used for the manufacturing of plastics, epoxy resin, and many personal care products. This ubiquitous endocrine disruptor is detectable in the urine of over 80% of North Americans. Although adverse neurodevelopmental outcomes have been observed in children with high gestational exposure to BPA, the effects of prenatal BPA on brain structure remain unclear. Here, using magnetic resonance imaging (MRI), we studied the associations of maternal BPA exposure with children's brain structure, as well as the impact of comparable BPA levels in a mouse model. Our human data showed that most maternal BPA exposure effects on brain volumes were small, with the largest effects observed in the opercular region of the inferior frontal gyrus (ρ = -0.2754), superior occipital gyrus (ρ = -0.2556), and postcentral gyrus (ρ = 0.2384). In mice, gestational exposure to an equivalent level of BPA (2.25 µg BPA/kg bw/day) induced structural alterations in brain regions including the superior olivary complex (SOC) and bed nucleus of stria terminalis (BNST) with larger effect sizes (1.07≤ Cohens d ≤ 1.53). Human (n = 87) and rodent (n = 8 each group) sample sizes, while small, are considered adequate to perform the primary endpoint analysis. Combined, these human and mouse data suggest that gestational exposure to low levels of BPA may have some impacts on the developing brain at the resolution of MRI.

Latent class trajectories of infant temperament and associations with problem behavior at two years of age.

Individual differences in temperament have been well-described, but individual differences in temperament trajectories require elaboration. Specifically, it is unknown if subgroups of infants display different developmental patterns and if these patterns relate to later behavioral problems. The aims were to identify distinct developmental patterns in broad dimensions of temperament among typically developing infants, to determine whether these developmental patterns differ by sex, to evaluate how developmental patterns within each dimension of temperament relate to developmental patterns within other dimensions of temperament, and to determine whether developmental patterns of infant temperament are associated with internalizing and externalizing behavior at 2 years of age. Data from the longitudinal Alberta Pregnancy Outcomes and Nutrition study (n = 1,819) were used to model latent class trajectories of parent-reported infant temperament at 3, 6, and 12 months. Four to five unique latent trajectories were identified within each temperament dimension. Sex was not associated with trajectory groups. Developmental coordination was observed between trajectories of negative emotionality and regulatory capacity, and between regulatory capacity and positive affect, but not between positive affect and negative emotionality. Negative emotionality and regulatory capacity predicted internalizing and externalizing behavior. Patterns of development in infant temperament, and not just intensity of temperament, contribute toward later problem behavior.

Provision of inadequate information on postnatal care and services during antenatal visits in Busega, Northwest Tanzania: a simulated client study.

BACKGROUND: Most (94%) of global maternal deaths occur in low- and middle-income countries due to preventable causes. Maternal health care remains a key pillar in improving survival. Antenatal care (ANC) guidelines recommend that pregnant women should be provided with information about postnatal care in the third trimester. However, the utilization of postnatal care services is limited in developing countries including Tanzania. The aim of this study was to investigate the practice of health care workers in providing information on postnatal care to pregnant women during antenatal care visits. METHODS: A cross sectional study was conducted among health care workers from 27 health facilities that offer reproductive and child health services in Busega district Northwest Tanzania. A simulated client approach was utilized to observe quality of practice among health care workers with minimal reporting bias (i.e., the approach allows observing participants at their routine practices without pretending). Selected pregnant women who were trained to be simulated clients from the community within facility catchment area attended antenatal care sessions and observed 81 of 103 health care workers. Data analyses were carried out using STATA 13. RESULTS: Only 38.73% (95% CI; 28.18-49.49%) of health care workers were observed discussing subtopics related to postnatal care during the ANC visit. Few health care workers (19.35%), covered all eight subtopics recommended in the ANC guidelines. Postnatal danger signs (33.33%) and exclusive breast feeding (33.33%) were mostly discussed subtopics by health care workers. Being a doctor/nurse/clinical officer is associated by provision of postnatal education compared to medical attendant, aOR = 3.65 (95% CI; 1.21-12.14). CONCLUSION: The provision of postnatal education during ANC visits by health care workers in this district was limited. This situation could contribute to the low utilization of postnatal care services. Health care workers need to be reminded on the importance of delivering postnatal education to pregnant women attending ANC clinic visits. On job training can be used to empower health care workers of different cadres to deliver postnatal health education during ANC visits. These efforts could increase women's utilization of postnatal care and improve outcomes for mothers and newborns.

Amygdala-Prefrontal Structural Connectivity Mediates the Relationship between Prenatal Depression and Behavior in Preschool Boys.

Prenatal depression is common, underrecognized, and undertreated. It has negative consequences on child behavior and brain development, yet the relationships among prenatal depression, child behavior, and children's brain structure remain unclear. The aim of this study was to determine whether altered brain connectivity mediates relationships between prenatal maternal depressive symptoms and child behavior. This study included 54 human mother-child pairs. Mothers completed the Edinburgh Postnatal Depression Scale during the second and third trimesters of pregnancy and 3 months postpartum. Their children had diffusion MRI at age 4.1 ± 0.8 years, and children's behavior was assessed using the Child Behavior Checklist within 6 months of their MRI scan. Structural brain connectivity of the amygdala, fornix, uncinate fasciculus, and cingulum was assessed using fractional anisotropy and mean diffusivity and analyzed with maternal prenatal depressive symptoms as well as child behavior. Third trimester maternal Edinburgh Postnatal Depression Scale scores were positively associated with mean diffusivity in the amygdala-frontal tract and the cingulum, controlling for postpartum depression. Externalizing behavior had a sex interaction in the amygdala-frontal pathway; weaker connectivity (lower fractional anisotropy, higher mean diffusivity) was associated with worse behavior in boys. Amygdala-frontal connectivity mediated the relationship between third trimester depressive symptoms and child externalizing behavior in males. These findings suggest that altered brain structure is a mechanism via which prenatal depressive symptoms can impact child behavior, highlighting the importance of both recognition and intervention in prenatal depression.SIGNIFICANCE STATEMENT Understanding how prenatal maternal depression impacts child behavior is critical for appropriately treating prenatal maternal mental health problems and improving child outcomes. Here, we show white matter changes in young children exposed to maternal prenatal depressive symptoms. Children of mothers with worse depressive symptoms had weaker white matter connectivity between areas related to emotional processing. Furthermore, connectivity between the amygdala and prefrontal cortex mediated the relationship between maternal depressive symptoms and externalizing behavior in boys, showing that altered brain structure is a possible mechanism via which maternal prenatal depression impacts children's behavior. This provides important information for understanding why children of depressed mothers may be more vulnerable to depression themselves and may help shape future guidelines on maternal prenatal care.

Association between breastfeeding during infancy and white matter microstructure in early childhood.

INTRODUCTION: Associations between breastfeeding and brain development, in the context of child, perinatal, and sociodemographic variables, remain unclear. This study investigated whether exclusive breastfeeding for the first 6 months and total duration of breastfeeding were associated with brain white matter microstructure in young children. METHODS: This study included 85 typically developing children (42 males) born to 83 mothers that were predominantly white, highly educated, and in high income households. Children underwent their first diffusion tensor imaging scan between ages 2.34 and 6.97 years; some children returned multiple times, providing a total of 331 datasets. Feeding information was collected from mothers at 3, 6, and 12 months postpartum and at their child's scan to calculate breastfeeding status at 6 months (exclusive or not) as well as total duration of any breastfeeding. Linear regression was used to investigate associations between breastfeeding exclusivity/duration and fractional anisotropy (FA) for the whole brain and 10 individual white matter tracts. RESULTS: Breastfeeding exclusivity and duration were associated with global and regional white matter microstructure, even after controlling for perinatal and sociodemographic factors. Greater exclusivity was associated with higher FA in females and lower FA in males. CONCLUSIONS: These findings suggest white matter differences associated with breastfeeding that differ by sex. These may stem from different trajectories in white matter development between males and females in early childhood and suggest possible long-term white matter differences associated with breastfeeding.

Rates of Developmental Coordination Disorder in Children Born Very Preterm.

OBJECTIVE: To examine the stability of developmental coordination disorder (DCD) throughout childhood in children born very preterm and term. Further, in the very preterm group, to compare perinatal variables and neurobehavioral outcomes at 13 years of age for children with persisting DCD and those with typical motor development. STUDY DESIGN: Prospective study of 180 very preterm and 73 term-born children assessed at 5, 7, and/or 13 years of age using the Movement Assessment Battery for Children, with scores ≤16th percentile used to classify DCD. Children with cerebral palsy or an IQ of <80 were excluded. RESULTS: Children born very preterm had increased odds for DCD at 5 (OR, 5.53; 95% CI, 2.53-12.0; P < .001), 7 (OR, 3.63; 95% CI, 1.43-9.18; P = .06), and 13 years (OR, 4.34; 95% CI, 1.61-11.7; P = .004) compared with term-born children. The rates of DCD in very preterm children reduced from 47.9% at 5 years of age, to 28.5% at 7 years and 27.8% at 13 years of age (OR per year of age, 0.81; 95% CI, 0.75-0.87; P < .001), but less so for term-born children (15.3%, 10.0%, and 8.5% at 5, 7, and 13-years respectively [OR, 0.91; 95% CI, 0.75-1.09; P = .31]). Within the very preterm group at 13 years of age, there was evidence that children with persisting DCD performed poorer across several cognitive domains compared with children with typical motor development, with differences in the order of 0.5-1.0 SD. CONCLUSIONS: Although the rates of DCD decreased across middle childhood for both groups, the odds for DCD were consistently higher for very preterm children compared with term, with important implications for cognitive functioning in the very preterm group.

Postnatal BPA is associated with increasing executive function difficulties in preschool children.

BACKGROUND: Early bisphenol exposure may have consequences for executive function development, but less is known about potential sex effects. We hypothesized that early bisphenol A (BPA) and bisphenol S (BPS) exposures would be associated with sex-dependent changes in preschool executive function. METHODS: A subsample of the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort (n = 312) provided maternal second trimester (prenatal) and 3-month postpartum (postnatal) urine samples, from which BPA and BPS concentrations were quantified. When children were age 2 and 4, mothers completed the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P). Changes in standardized T scores on the BRIEF-P indexes of inhibitory self-control, flexibility, and emergent metacognition were investigated. RESULTS: Adjusted multivariate regression analyses showed that child sex modified the associations between maternal postnatal BPA and changes in executive function. Higher maternal postnatal BPA concentrations predicted increasing difficulties from age 2 to 4 in the domains of inhibitory self-control and emergent metacognition in female, but not male children. The other bisphenol concentrations were not associated with changes in executive function. CONCLUSION: Due to the ubiquity of BPA exposure among breastfeeding women, these findings justify further investigation on the effects of postnatal bisphenol exposure on child cognitive development. IMPACT: Higher concentrations of maternal BPA at 3-month postpartum were associated with increasing difficulties in inhibitory self-control and emergent metacognition from age 2 to 4 in girls, but not boys. Prenatal BPA and prenatal/postnatal BPS were not significant predictors of changes in executive function in boys and girls. The current study extends previous research to show that maternal postnatal BPA could also impact child executive function. Due to the ubiquity of BPA exposure among breastfeeding women, the current findings suggest that additional precautions may be needed to protect infants' neurodevelopment from indirect exposure to BPA.