Search Results (143)

Background: There is considerable evidence that breast feeding has a beneficial effect on the neurocognition of a child. However, most studies have confined their attention to the Intelligence Quotient (IQ), tending to ignore other aspects of neurodevelopment. Methodology: Here we present the relationship between breast feeding for at least 6 months with 373 neurocognitive outcomes measured from infancy through to late adolescence using data collected in the Avon Longitudinal Study of Parents and Children (ALSPAC). We first examined unadjusted regression associations with breast feeding at age 6 months. Where the unadjusted p-value was < 0.0001 (n = 152 outcomes), we adjusted for social and other factors. Results: This resulted in 42 outcomes with adjusted associations at p < 0.001. Specifically, these included associations with full-scale IQ at ages 8 and 15 years (adjusted mean differences [95% confidence interval (CI)] +4.11 [95% CI 2.83, 5.39] and +5.12 [95% CI 3.57, 6.67] IQ points, respectively, compared to not breastfeeding for 6 months). As well as the components of IQ, the other phenotypes that were strongly related to breast feeding for at least 6 months were measures of academic ability (reading, use of the English language and mathematics). In accordance with the literature, we show that children who are breast fed are more likely to be right-handed. The one association that has not been recorded before concerned aspects of pragmatic speech at 9 years where the children who had been breast fed were shown to perform more appropriately. Conclusions: We conclude that breast feeding for at least 6 months has beneficial effects on a number of neurocognitive outcomes that are likely to play a major part in the offspring’s future life course. We point out, however, the possibility that by using such stringent p-value criteria, other valid associations may have been ignored. Full article

Background: The fetal period is critical for neurodevelopment, with maternal diet emerging as a key environmental factor influencing long-term child health. This study investigated the associations between maternal dietary patterns during pregnancy and neurocognitive and behavioral outcomes in 4-year-old children, with a particular focus on sex-related differences. Methods: We used data from the Piccolipiù Italian birth cohort, including 2006 mother/child pairs. Maternal dietary intake during pregnancy was assessed via a questionnaire and categorized into distinct patterns using Principal Component Analysis (PCA). Child neurodevelopment was evaluated at age 4 using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) and the Child Behavior Checklist (CBCL 1.5–5). Linear and logistic regression models were employed, adjusting for potential confounders and stratifying by child sex. Results: Two major maternal dietary patterns were identified: “Processed and high-fat foods” and “Fresh foods and fish”. Higher maternal adherence to the “Processed and high-fat foods” pattern was associated with increased externalizing behaviors in offspring (β = 0.88; 95%CI 0.28–1.49; p = 0.004). In males, this pattern was associated with an increased clinical risk of Attention Deficit Hyperactivity Disorder (ADHD) (OR (Odds Ratio) = 1.13; 95%CI: 1.02–1.26; p = 0.021). Conclusions: Our findings indicate that maternal consumption of a diet rich in processed and high-fat foods during pregnancy is associated with increased behavioral problems in children, with sex-specific vulnerabilities: slightly higher externalizing behaviors in girls and an increased risk of ADHD in boys. These results underscore the importance of promoting healthy maternal dietary patterns during pregnancy as a targeted early prevention strategy for supporting child neurodevelopment. Full article

Tuberous sclerosis complex (TSC) is a systemic disease caused by mutations in either the TSC1 (encoding hamartin) or TSC2 (encoding tuberin) gene, with mutations in the TSC2 gene potentially leading to more severe clinical symptoms. Neurological symptoms are a common clinical manifestation of TSC, and neuroinflammation is thought to play an important role. Glial cells are a major source of neuroinflammation, but whether microglia are involved in the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome and the expression of interleukin-1β (IL-1β) in TSC patients remains unclear. We used a transcriptome sequencing dataset for bioinformatics analysis to explore the differences in the expression of microglial inflammasome-associated hub genes. TSC2 knockdown (TSC2 KD) microglia (HMC3 cell line) were generated by lentivirus, and the expression of inflammasome-associated hub genes, microglial activation, and NLRP3 inflammasome activation were verified. In addition, experiments were performed to explore the regulatory effects of rapamycin. Bioinformatics analysis identified a total of eight inflammasome-associated hub genes. By detecting GFP fluorescence, TSC2 mRNA, TSC2 protein expression, and the phosphorylation of the mammalian target of rapamycin (p-mTOR)/mTOR, we confirmed that the TSC2 KD microglia model was successfully established. Compared with the control group, the TSC2 KD group presented higher mRNA levels and fluorescence intensities of microglia AIF1 and CD68, as well as greater reactive oxygen species (ROS) production. Eight inflammasome-associated hub gene mRNA assays revealed that the expression of the NLRP3 and IL1B genes was increased. Compared with the control group, the TSC2 KD group presented increased levels of NLRP3 and Pro-IL-1β proteins in cells and Cleaved-Caspase 1 and Cleaved-IL-1β proteins in the supernatant, suggesting NLRP3 inflammasome activation. Rapamycin intervention alleviated these changes, demonstrating that the TSC2 gene regulation of microglial activation and NLRP3 inflammasome activation are correlated with mTOR phosphorylation. In conclusion, microglia are activated in TSC patients and participate in the NLRP3 inflammasome-associated neuroinflammatory response, and rapamycin treatment can alleviate these changes. Full article

While gestational Bisphenol A (BPA) exposure has been associated with autism, limited work has focused on dietary sources. Here, we sought to develop a summary metric to capture dietary exposure specifically and test its associations with measured levels, as well as child traits related to autism. Participants (n = 116) were from the Early Autism Risk Longitudinal Investigation (EARLI) Study, which recruited pregnant women who previously had a child diagnosed with autism. Maternal concentrations of BPA were quantified in urine, and dietary sources of BPA were ascertained via food frequency questionnaires during gestation. A novel BPA “dietary burden score” was developed based on reported intake of foods known to contribute to BPA exposure (i.e., canned foods) from a Dietary History Questionnaire modified for pregnancy. Child autism-related traits were assessed via the Social Responsiveness Scale (SRS-2). We examined associations between BPA biomarkers, dietary burden scores, and child SRS scores. Dietary burden scores were weakly correlated with urinary BPA concentrations (R = 0.19, p = 0.05) but were not associated with child SRS scores. Our work suggests that more detailed dietary assessments may be needed to fully capture diet-based BPA exposures and address diet as a modifiable source of chemical exposure to reduce associated health impacts of BPA. Full article

Trauma exposure has severe consequences for the exposed individuals as well as their children. The current paper is a conceptual narrative review that uses the intergenerational transmission of trauma (ITT) framework to synthesize the literature on the association between a parent’s exposure to trauma and the brain and behavioral outcomes in their children. There are likely multiple mechanisms for the ways in which parental history of trauma exposure can lead to these negative outcomes. However, this review highlights parenting as a key pathway through which caregiver trauma conveys both the risk and resilience in the child’s neurodevelopment, emphasizing the need for trauma-informed, relationship-focused interventions. Full article

Background: Childhood neglect is a pervasive yet often overlooked form of maltreatment that exerts profound and lasting effects on neurodevelopment. Unlike other types of abuse, neglect is characterized by the absence of essential stimuli and caregiving, which are critical for normal brain maturation, particularly in regions involved in executive function. Objective: This narrative review aims to critically explore the neurobiological mechanisms through which early-life neglect impairs the development of executive functions. Special emphasis is placed on alterations in brain structure and function, dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, and emerging epigenetic evidence. Methods: A comprehensive literature search (170 articles) was conducted across PubMed, Scopus, Web of Science, and PsycINFO, including studies published between 1 January 2000 to 31 March 2025. Relevant empirical and review articles were selected based on methodological rigor, relevance to executive functioning, and focus on child neglect. Results: Evidence reveals that neglect disrupts key neural circuits, particularly those involving the prefrontal cortex and amygdala, leading to deficits in attention, working memory, impulse control, and cognitive flexibility. Chronic stress associated with neglect also induces HPA axis dysregulation and elevated cortisol levels, which further compromise neural plasticity. Additionally, epigenetic modifications appear to mediate long-term cognitive and emotional consequences. Conclusions: Childhood neglect represents a distinct and critical risk factor for executive dysfunction. Understanding the neurodevelopmental consequences of neglect is essential for developing targeted prevention strategies and therapeutic interventions aimed at supporting cognitive resilience in affected populations. Full article

The increasing incidence of autism spectrum disorder (ASD) increases the urgency of establishing the mechanism of its development for effective prevention and treatment. ASD’s etiology includes genetic predisposition and environmental triggers, both of which can play a role in the changed microbiota. Recent research has proved the impact of maternal microbiota on the neurodevelopment of the child. To investigate the co-play of genetic and microbiota factors in ASD development, we performed fecal microbiota transplantation (FMT) from children with ASD to female Shank3b^+/− mice and studied the autism-like symptoms in the male Shank3b^−/− and wild-type (WT) offspring. WT animals with prenatal exposure to ASD microbiota had delayed neurodevelopment and impaired food intake behavior, but also elevated plasma leptin concentration and body weight. Shank3b^−/− mice after FMT ASD exhibited impaired learning and exacerbated anxiety-like behavior in adulthood. Interestingly, FMT ASD improved learning in adolescent Shank3b^−/− mice. Prenatal exposure to ASD microbiota decreased the activity of hypocretin neurons of the lateral hypothalamic area in both genotypes. The combination of genetic predisposition and FMT ASD led to an increased colon permeability, evaluated by zonula occludens (ZO1, ZO3) and claudin factors. These results suggest the effect of parental FMT exposure on shaping offspring behavior in Shank3b^−/− mice and the potential of microbiota in the modulation of ASD. Full article

Objective: To comprehensively evaluate the interaction between diet quality and multivitamin intake during pregnancy on offspring neurodevelopment. Methods: This analysis was grounded in mother-child dyads from the 3D Cohort Study in Quebec, Canada. Among the 2366 participants initially enrolled in the 3D study, 1535 women successfully completed the 3-day food record during 20–24 weeks of gestation. A Canadian adaptation of the Healthy Eating Index (HEI-C) 2010 was used to quantify diet quality. The total HEI-C score was dichotomized into low and high diet quality by median split. Cognitive and motor development in childhood were assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Language abilities were measured using the toddler short-form version of the MacArthur–Bates Communicative Development Inventories (MCDI) questionnaire, administered in either English or French. After excluding participants with missing covariate data, cognitive, motor, and language development scores at 2 years of age were available for 1066, 1040, and 981 children, respectively. Multiple linear regression models were employed to calculate adjusted effect estimates. The interaction on an additive scale was assessed by incorporating a product term into the linear regression model. Results: Statistically significant interactions were detected between diet quality and multivitamin intake in relation to the cognitive and language development outcomes of the offspring (interaction p-values were 0.018 and 0.023, respectively). The lowest cognitive and language scores were observed in the group of women who neither took multivitamins nor maintained a high-quality diet. Among women not taking multivitamins, a high-quality diet was associated with improved offspring cognitive and language scores (mean difference [95% CI] = 4.2 [0.1, 8.2], p = 0.04; and 11.3 [3.1, 19.5], p = 0.01, respectively). However, among women taking multivitamins, no such associations were identified. Conversely, in participants with a low-quality diet, multivitamin intake was associated with a 3.0-point increase in cognitive composite scores (95% CI: 0.3, 5.8, p = 0.03), but this was not the case for those with a high-quality diet. No statistically significant interactions were observed between maternal diet quality and multivitamin intake for motor development outcomes. Conclusions: Adequate nutritional supply during pregnancy, achieved either through a high-quality diet or multivitamin supplementation, is fundamental for the neurodevelopment of children. Full article

Background/Objectives: Dietary patterns rich in plant-based foods during pregnancy have been associated with neurodevelopmental outcomes in offspring. However, not all components of these diets are healthy, and the impact of their quality on behavioral outcomes remains unexplored. Therefore, this study aimed to examine the association between healthy and unhealthy plant-based diets and offspring behavioral problems at the age of four. Methods: This research involved 201 mother–child pairs from the ECLIPSES study. Maternal diet during pregnancy was assessed using a validated food frequency questionnaire, from which the healthy plant-based diet index (hPDI) was calculated, emphasizing the consumption of fruits, vegetables, legumes and nuts, along with the unhealthy plant-based diet index (uPDI), highlighting the intake of sugary drinks and refined grains. Children’s behavior was evaluated using the Child Behavior Checklist 1.5-5. Multivariable logistic regression analyses were conducted to estimated odds ratios (ORs) and their 95% confidence intervals (CIs). Results: Greater adherence to the uPDI during pregnancy was associated with higher odds for externalizing problems, including attention-deficit/hyperactivity problems (OR = 1.08; 95%CI from 1.01 to 1.16) and oppositional defiant behavior (OR = 1.09; 95%CI from 1.00 to 1.19) in offspring, particularly girls. Higher adherence to the hPDI was not associated with children’s behavior. Conclusions: The consumption of unhealthy components of a plant-based dietary pattern during gestation has been associated with adverse behavioral outcomes in children at age four. These findings underscore the importance of discerning between the healthy and unhealthy components of plant-based diets when assessing their impact on child development. Full article

Background/Objectives: Postpartum depression (PPD) significantly impacts maternal well-being and child neurodevelopment. While the etiology of PPD is well understood, the precise neurodevelopmental consequences, particularly differentiating prenatal and postnatal effects, remain unclear. This systematic review aims to synthesize the existing literature on the neurophysiological effects of maternal PPD on infant neurodevelopment, focusing on electroencephalography (EEG) biomarkers to identify consistent patterns and potential mediating factors. Methods: A comprehensive literature search across PubMed/MEDLINE, Web of Science, and Scopus identified studies investigating infants (0–12 months) exposed to maternal depressive symptoms (assessed via validated psychometric instruments) with quantitative EEG data. Study quality was assessed using the Newcastle–Ottawa Scale. Results: Twelve studies met the inclusion criteria. Eleven investigated EEG asymmetry, predominantly frontal alpha asymmetry (FAA). The findings consistently showed greater right FAA in the infants of mothers with PPD, suggesting increased negative affectivity and avoidance behaviors. This association was stronger with prolonged or combined prenatal/postnatal exposure. However, EEG power and connectivity findings were less consistent, with some studies reporting altered occipital power at 1 month and frontal power at 3 months in the infants of depressed mothers. No significant associations were found between maternal depression and functional connectivity. Conclusions: This review demonstrates a robust association between maternal PPD and altered infant EEG patterns, particularly increased right FAA. However, methodological heterogeneity necessitates future research with standardized protocols and longitudinal designs to establish causality and investigate long-term effects. Further research should also explore the underlying neural mechanisms and evaluate the efficacy of targeted interventions. These findings underscore the need for early identification and intervention to mitigate the negative impact of PPD on infant neurodevelopment. Full article

The widespread implementation of antiretroviral therapy has significantly reduced HIV-related mortality and mother-to-child transmission. Despite being HIV-uninfected, HIV-exposed children (HEU) seem to face heightened risks of immune dysfunction, cardiometabolic diseases, growth delays, reduction in bone mineral density, and neurocognitive impairments compared to HIV-unexposed uninfected peers. These vulnerabilities can be attributed to maternal immune dysregulation during pregnancy, antiretroviral (ART) toxicity, HIV exposure, and adverse socioeconomic and nutritional environments. Emerging evidence highlights the impact of antiviral therapy exposure, particularly tenofovir disoproxil fumarate, on HEU mitochondrial dysfunction, bone resorption, neurocognitive delays, and zidovudine on cardiac abnormalities. This narrative review explores the multisystem effects of ART exposure in HEU children, focusing on immune function, neurodevelopment, cardiovascular health, growth, and bone metabolism. By synthesizing findings from diverse studies, the review aims to provide a comprehensive understanding of the potential risks associated with ART regimens and identify future research priorities to improve outcomes for HEU children. Full article

Background: Emerging evidence suggests that the maternal microbiome plays a crucial role in shaping fetal neurodevelopment, immune programming, and metabolic health. Dysbiosis during pregnancy—whether gastrointestinal, oral, or vaginal—can significantly influence pregnancy outcomes and long-term child health. Materials and Methods: The search was performed using databases such as PubMed, Scopus, and Google Scholar including research published from January 2000 to January 2025. The keywords used were “Fetal Programming”, “ Maternal Immune Activation”, “Maternal microbiome”, “Microbiota–Gut–Brain Axis”, and “Pregnancy Dysbiosis”. Results: The maternal microbiome undergoes substantial changes during pregnancy, with alterations in microbial diversity and function linked to conditions such as gestational diabetes, obesity, and preeclampsia. Pregnancy-related dysbiosis has been associated with adverse neurodevelopmental outcomes, including an increased risk of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and cognitive impairments in offspring. Conclusions: Understanding the intricate relationship between maternal microbiota and fetal health is essential for developing targeted interventions. Personalized microbiome-based strategies, including dietary modifications and probiotic supplementation, hold promise in optimizing pregnancy outcomes and promoting health in offspring. Full article

Vitamin D is an essential nutrient, involved in various biological processes including calcium homeostasis, bone health, immune function, and brain development. Vitamin D from the mother crosses the placenta during pregnancy, directly impacting the neurodevelopment of the fetus. Vitamin D insufficiency is a substantial global health problem, influencing almost 47.9% of individuals, with especially high predominance rates among pregnant women. Background/Objectives: Preclinical studies suggest that maternal vitamin D deficiency results in significant alterations in the development of the offspring’s brain. Nonetheless, randomized clinical trials in humans have produced conflicting results on the beneficial effect of high-dose vitamin D supplementation during pregnancy on neurodevelopmental outcomes. This review aims to evaluate the association of maternal prenatal vitamin D levels and vitamin D supplementation during pregnancy with offspring neurodevelopment. Methods: This study thoroughly reviewed the literature and searched throughout PubMed, ScienceDirect, Cochrane Library, and Google Scholar, adhering to PRISMA guidelines. Studies assessing maternal vitamin D levels, supplementation, and offspring neurodevelopmental outcomes were included based on predefined eligibility criteria. Results: Among 9686 screened studies, only 20 met the inclusion criteria, representing 18,283 mother–child pairs. A small, non-significant trend suggested a positive association between higher maternal vitamin D levels and offspring cognitive, language, motor, and social-emotional development. The strongest associations were observed in cognitive performance and language acquisition, though inconsistencies emerged across studies. Cord blood vitamin D levels showed no consistent effects on neurodevelopment. Maternal vitamin D supplementation during pregnancy demonstrated no reliable benefits for offspring neurodevelopment, with results varying by study design and participant characteristics. Conclusions: Large-scale, multicenter randomized trials, with standardized neurodevelopmental assessments at multiple ages are needed to define the effects of vitamin D deficiency and supplementation during pregnancy on offspring neurodevelopmental outcomes. Future research should investigate the confounding factors contributing to inconsistencies, including supplementation protocols, genetic variations, and assessment methodologies. Clarifying these aspects will enhance the understanding of maternal vitamin D’s role in fetal neurodevelopment and aid in refining prenatal supplementation guidelines. Full article

Background: Most pregnant women have choline intakes below recommendations. Animal studies suggest that choline supplementation during pregnancy improves cognitive outcomes in the offspring. This review aims to determine whether higher choline levels during pregnancy are associated with improved child brain development. Methods: We systematically reviewed the evidence for the role of choline in pregnancy for human neurodevelopment in clinical trials and observational studies. Results: We identified four randomized trials of choline supplementation in pregnancy and five observational studies of prenatal choline. Neurodevelopmental assessments of these studies were reported across 20 eligible publications. Within both the trials and observational studies, most neurodevelopmental outcomes assessed did not support the hypothesis that higher prenatal choline benefits neurodevelopment. Among identified clinical trials, there were some instances where children whose mothers received choline supplementation had a better score on a neurodevelopmental measure. Still, each trial included multiple outcomes, and most were null. Observational studies were mixed as to whether an association between prenatal choline and an aspect of child neurodevelopment was identified. Critical limitations were present across clinical trials and observational studies, preventing confidence in the results and evidence base. Conclusions: Current evidence is insufficient to support or refute the hypothesis that increasing choline intake in pregnancy improves the neurodevelopmental outcomes of the child. Full article

Background/Objectives: Iodine is essential for thyroid hormone (TH) synthesis, and THs in pregnant women are critical for fetal brain development. It is unclear whether urinary iodine concentrations (UICs) are associated with thyroid parameters in pregnant women and neurodevelopment in their 3–4-year-old children. Methods: In the Canadian Maternal–Infant Research on Environmental Chemicals (MIREC) cohort, we categorized UIC adjusted for urinary creatinine (UIC/Cr) in the first two trimesters as <150, 150–500, or ≥500 µg/g. We used multivariable regression to quantify associations between UIC/Cr and thyroid parameters in maternal plasma (n = 1501), including thyroid stimulating hormone (TSH), total T4 (tT4), free T4 (fT4), thyroglobulin (Tg) and Tg antibodies (TgAb), and thyroid peroxidase antibodies (TPOAb). We defined positive thyroid autoantibodies as TgAb ≥ 4.11 or TPOAb ≥ 5.61 IU/mL. We also examined the associations between UIC/Cr with the Wechsler Preschool and Primary Scale of Intelligence (n = 503), Behavior Assessment System for Children (n = 751), and the Social Responsiveness Scale (n = 498). Results: Twenty-two percent of women had UIC/Cr < 150 and 17% ≥ 500 µg/g. UIC/Cr was not associated with TSH, tT4, or fT4. After excluding women with positive thyroid autoantibodies, those with UIC/Cr < 150 µg/g had higher tT4 compared to those with 150–500 µg/g. Compared to women with UIC/Cr 150–500 µg/g, those with UIC/Cr < 150 had higher Tg and, those with UIC/Cr ≥ 500 had less frequent positive thyroid autoantibodies. Neurodevelopmental outcomes were not associated with maternal Tg, nor did they differ for maternal UIC/Cr < 150 and ≥500 compared to 150–500 µg/g. Conclusions: In this cohort, Tg and tT4 were higher in women with UIC/Cr < 150 µg/g compared to those with UIC/Cr 150–500 µg/g. Urinary iodine in pregnant women was not associated with neurodevelopment in their 3–4-year-old children. Full article