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Abstract 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

Abstract Background Maternal mental health concerns and parenting stress in the first few years following childbirth are common and pose significant risks to maternal and child well-being. The COVID-19 pandemic has led to increases in maternal depression and anxiety and has presented unique parenting stressors. Although early intervention is crucial, there are significant barriers to accessing care. Methods To inform a larger randomized controlled trial, the current open-pilot trial investigated initial evidence for the feasibility, acceptability, and efficacy of a newly developed online group therapy and app-based mental health and parenting program (BEAM) for mothers of infants. Forty-six mothers 18 years or older with clinically elevated depression scores, with an infant aged 6–17 months old, and who lived in Manitoba or Alberta were enrolled in the 10-week program (starting in July 2021) and completed self-report surveys. Results The majority of participants engaged in each of the program components at least once and participants indicated relatively high levels of app satisfaction, ease of use, and usefulness. However, there was a high level of attrition (46%). Paired-sample t-tests indicated significant pre- to post-intervention change in maternal depression, anxiety, and parenting stress, and in child internalizing, but not externalizing symptoms. Effect sizes were in the medium to high range, with the largest effect size observed for depressive symptoms (Cohen’s d = .93). Discussion This study shows moderate levels of feasibility and strong preliminary efficacy of the BEAM program. Limitations to program design and delivery are being addressed for testing in adequately powered follow-up trials of the BEAM program for mothers of infants. Trial registration NCT04772677 . Registered on February 26 2021.

Abstract Background The prevalence of maternal depression and anxiety has increased during the COVID-19 pandemic, and pregnant individuals are experiencing concerningly elevated levels of mental health symptoms worldwide. Many individuals may now be at heightened risk of postpartum mental health disorders. There are significant concerns that a cohort of children may be at-risk for impaired self-regulation and mental illness due to elevated exposure to perinatal mental illness. With both an increased prevalence of depression and limited availability of services due to the pandemic, there is an urgent need for accessible eHealth interventions for mothers of young children. The aims of this trial are to evaluate the efficacy of the Building Emotion Awareness and Mental Health (BEAM) app-based program for reducing maternal depression symptoms (primary outcome) and improve anxiety symptoms, parenting stress, family relationships, and mother and child functioning (secondary outcomes) compared to treatment as usual (TAU). Methods A two-arm randomized controlled trial (RCT) with repeated measures will be used to evaluate the efficacy of the BEAM intervention compared to TAU among a sample of 140 mothers with children aged 18 to 36 months, who self-report moderate-to-severe symptoms of depression and/or anxiety. Individuals will be recruited online, and those randomized to the treatment group will participate in 10 weeks of psychoeducation modules, an online social support forum, and weekly group teletherapy sessions. Assessments will occur at 18–36 months postpartum (pre-test, T1), immediately after the last week of the BEAM intervention (post-test, T2), and at 3 months after the intervention (follow-up, T3). Discussion eHealth interventions have the potential to address elevated maternal mental health symptoms, parenting stress, and child functioning concerns during and after the COVID-19 pandemic and to provide accessible programming to mothers who are in need of support. This RCT will build on an open pilot trial of the BEAM program and provide further evaluation of this evidence-based intervention. Findings will increase our understanding of depression in mothers with young children and reveal the potential for long-term improvements in maternal and child health and family well-being. Trial registration ClinicalTrials.gov NCT05306626 . Registered on April 1, 2022

Abstract Background Insomnia and sleep disturbances are common in pregnancy and have potentially significant consequences for both maternal and infant health. There is limited research examining the effectiveness of cognitive behavioral therapy for insomnia (CBT-I) during pregnancy. With increased distress and limited access to services during the COVID-19 pandemic, there is also an unprecedented need for telehealth delivery of treatment programs for pregnant women. The aims of this trial are to evaluate the impact of the Sleeping for Two adaptation of CBT-I in pregnancy (in-person or telehealth) versus treatment as usual (TAU) in reducing symptoms of insomnia (primary outcome), as well as increasing gestational length and reducing symptoms of depression (secondary outcomes). Methods A two-arm, single-blinded, parallel group randomized controlled trial (RCT) design with repeated measures will be used to evaluate the impact of CBT-I compared to TAU among a sample of 62 pregnant women, enrolled between 12 and 28 weeks of gestation, who self-identify as experiencing insomnia. Five weekly individual sessions of CBT-I will be delivered in person or via telehealth depending on physical distancing guidelines. Assessment of insomnia diagnosis by structured interview, self-reported insomnia symptom severity and sleep problems, and sleep quantity and quality as measured by a daily diary and actigraphy will occur at 12–28 weeks of pregnancy (T1), 1 week post-treatment (T2), and 6 months postpartum (T3). Discussion CBT-I delivered in pregnancy has the potential to reduce symptoms of insomnia and depression and could lead to reduced risk of preterm birth, all of which can minimize risk of negative maternal and child health and developmental consequences in the short (e.g., infant death) and long terms (e.g., developmental delays). This RCT builds on a successful open pilot trial conducted by our team and will provide further evaluation of a novel evidence-based treatment for pregnancy-related insomnia, which can be widely disseminated and used to treat individuals that are most in need of intervention. Findings will enhance understanding of pregnancy-related sleep problems, as well as means by which to improve the health and sleep of mothers and their children. Trial registration ClinicalTrials.gov NCT03918057. Registered on 17 April 2019.

Abstract Background Prenatal and postnatal depressive symptoms are common in expectant and new mothers and fathers. This study examined the association between four patterns of probable perinatal depression (mother depressed, father depressed, both depressed, neither depressed) in co-parenting mothers and fathers and their children’s internalizing and externalizing behaviours at 24 and 36 months of age. The influence of sociodemographic, risk and protective factors was also examined. Methods Depressive symptoms were measured during pregnancy and at 3 months postpartum and children’s behaviour was assessed at 24 and 36 months of age. Families (n = 634) provided data on their children’s internalizing (i.e. emotionally reactive, anxious/depressed, somatic complaints, withdrawn and total) and externalizing (i.e. attention problems, aggression and total) behaviour. Marginal models were employed to determine the relationship between children’s behaviour over the two time points and the four patterns of probable parental depression. Sociodemographic variables as well as risk (stress) and protective (social support) factors were included in these models. Results In the perinatal period 19.40% (n = 123) of mothers scored as probably depressed and 10.57% (n = 67) of fathers. In 6.31% (n = 40) of the participating families, both parents scored as probably depressed and in 63.72% (n = 404) neither parent scored as depressed. For children’s emotionally reactive, withdrawn and total internalizing behaviours, both mothers’ probable depression and mothers and fathers’ co-occurring probable depression predicted higher scores, while for children’s aggressive behaviour, attention problems, and total externalizing behaviours, only mothers’ probable depression predicted higher scores, controlling for sociodemographic, risk and protective factors. Conclusions While probable perinatal depression in mothers predicted 2 and 3 year-old children’s behavioural problems, co-occurrence of depression in mothers and fathers had an increased association with internalizing behavioural problems, after considering sociodemographic, risk and protective factors. Health care providers are encouraged to consider the whole family in preventing and treating perinatal depression.

Abstract Background Many studies have identified associations between qualities of maternal–child relationships and childhood asthma, but few have examined associations with childhood atopic dermatitis (AD), a common precursor to asthma. Moreover, maternal psychological distress, including prenatal and postnatal depression, anxiety and stress, may increase risk, while social support from partners may reduce risk for childhood AD. We sought to uncover the association between maternal–infant relationship qualities (maternal sensitivity towards infant behavioral signals, controlling behavior, and unresponsiveness) and child AD after accounting for risk (i.e., prenatal and postnatal maternal depression, anxiety and stress) and protective (i.e., social support) factors. Methods We conducted a secondary analysis of data collected on a subsample of 242 women and their infants enrolled during pregnancy in the ongoing Alberta Pregnancy Outcomes and Nutrition cohort study. Inclusion criteria required mothers to be >16 years of age, English speaking and

Abstract Background Animal models show that prenatal bisphenol A (BPA) exposure leads to sexually dimorphic disruption of the neuroendocrine system in offspring, including the hypothalamic-pituitary-adrenal (HPA) neuroendocrine system, but human data are lacking. In humans, prenatal BPA exposure is associated with sex-specific behavioural problems in children, and HPA axis dysregulation may be a biological mechanism. The objective of the current study was to examine sex differences in associations between prenatal maternal urinary BPA concentration and HPA axis function in 3 month old infants. Methods Mother-infant pairs (n = 132) were part of the Alberta Pregnancy Outcomes and Nutrition study, a longitudinal birth cohort recruited (2010–2012) during pregnancy. Maternal spot urine samples collected during the 2nd trimester were analyzed for total BPA and creatinine. Infant saliva samples collected prior to and after a blood draw were analyzed for cortisol. Linear growth curve models were used to characterize changes in infant cortisol as a function of prenatal BPA exposure. Results Higher maternal BPA was associated with increases in baseline cortisol among females (β = 0.13 log μg/dL; 95% CI: 0.01, 0.26), but decreases among males (β = −0.22 log μg/dL; 95% CI: -0.39, −0.05). In contrast, higher BPA was associated with increased reactivity in males (β = .30 log μg/dL; 95% CI: 0.04, 0.56) but decreased reactivity in females (β = −0.15 log μg/dL; 95% CI: -0.35, 0.05). Models adjusting for creatinine yielded similar results. Conclusions Prenatal BPA exposure is associated with sex-specific changes in infant HPA axis function. The biological plausibility of these findings is supported by their consistency with evidence in rodent models. Furthermore, these data support the hypotheses that sexually dimorphic changes in children’s behaviour following prenatal BPA exposure are mediated by sexually dimorphic changes in HPA axis function.