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Purpose: To examine the associations between infants' dietary nutrient trajectories and subsequent neurodevelopment during childhood in the Growing Up in Singapore Towards healthy Outcomes study.Methods: One-day food records were collected at ages 6, 9 and 12 months, whilst Bayley Scales of Infant and Toddler Development-III and Kaufman Brief Intelligence Test-2 were conducted at ages 24 and 54 months respectively. Nutrient trajectories were constructed using multi-level mixed modelling and associations with neurodevelopment (24 months: n = 484; 54 months: n = 444) were examined using adjusted multivariable linear regression.Results: At age 24 months, higher protein intake (at 6 months) and increasing rate of intake (from 6 to 12 months) were associated with higher fine motor score [β = 0.17 SD (95% CI 0.03, 0.31) and 0.62 SD (0.10, 1.14) respectively]. Higher fat intake was associated with higher receptive language score [0.04 SD (0.003, 0.07)], but increasing rate of intake was associated with lower expressive language [- 0.20 SD (- 0.39, - 0.01)] and fine motor [- 0.29 SD (- 0.48, - 0.10)] scores. Higher carbohydrate intake was associated with lower gross motor score [- 0.07 SD (- 0.14, - 0.005)], but increasing rate of intake was associated with higher receptive language [0.44 SD (0.08, 0.81)] and fine motor [0.56 SD (0.18, 0.93)] scores. Increasing rate of dietary fibre intake was associated with higher fine motor scores [0.63 SD (0.16, 1.10)]. No significant associations were observed with neurodevelopment at 54 months.Conclusion: Our findings provide greater understanding of how nutrition over time could have varying effects on child neurodevelopment.

The complex interaction between brain and behaviour in language disorder is well established. Yet to date, the imaging literature in the language disorder field has continued to pursue heterogeneous and relatively small clinical cross-sectional samples, with emphasis on cortical structures and volumetric analyses of subcortical brain structures. In our current work, we aimed to go beyond this state of knowledge to focus on the microstructural features of subcortical brain structures (specifically the caudate nucleus) in a large cohort of neonates and study its association with emerging language skills at 24 months. Variations in neonatal brain microstructure could be interpreted as a proxy for in utero brain development. As language development is highly dependent on cognitive function and home literacy environment, we also examined their effect on the caudate-language function relationship utilizing a conditional process model. Our findings suggest that emerging language development at 24 months is influenced by the degree of left lateralization of neonatal caudate microstructure, indexed by diffusion tensor imaging (DTI)-derived fractional anisotropy (FA). FA is an indirect measure of neuronal and dendritic density within grey matter structures. We also found that the caudate-language function relationship is partially mediated by cognitive function. The conditional indirect effect of left caudate FA on language composite score through cognitive function was only statistically significant at low levels of home literacy score (-1 standard deviation [SD]). The authors proposed that this may be related to 'compensatory' development of cognitive skills in less favourable home literacy environments.

Study Objectives Examine how different trajectories of reported sleep duration associate with early childhood cognition. Methods Caregiver-reported sleep duration data (n = 330) were collected using the Brief Infant Sleep Questionnaire at 3, 6, 9, 12, 18, and 24 months and Children’s Sleep Habits Questionnaire at 54 months. Multiple group-based day-, night-, and/or total sleep trajectories were derived—each differing in duration and variability. Bayley Scales of Infant and Toddler Development-III (Bayley-III) and the Kaufman Brief Intelligence Test- 2 (KBIT-2) were used to assess cognition at 24 and 54 months, respectively. Results Compared to short variable night sleep trajectory, long consistent night sleep trajectory was associated with higher scores on Bayley-III (cognition and language), while moderate/long consistent night sleep trajectories were associated with higher KBIT-2 (verbal and composite) scores. Children with a long consistent total sleep trajectory had higher Bayley-III (cognition and expressive language) and KBIT-2 (verbal and composite) scores compared to children with a short variable total sleep trajectory. Moderate consistent total sleep trajectory was associated with higher Bayley-III language and KBIT-2 verbal scores relative to the short variable total trajectory. Children with a long variable day sleep had lower Bayley-III (cognition and fine motor) and KBIT-2 (verbal and composite) scores compared to children with a short consistent day sleep trajectory. Conclusions Longer and more consistent night- and total sleep trajectories, and a short day sleep trajectory in early childhood were associated with better cognition at 2 and 4.5 years.

Parasympathetic nervous system (PNS) activity is important to physiological regulation. Limbic structures are important in determining what information the PNS receives, potentially influencing concurrent physiological responsivity and, ultimately, shaping PNS development. Yet, whether individual differences in these structures are linked to PNS activity in early childhood remains unclear. Here, in an exploratory capacity, we examined the association between neonatal limbic structures (i.e., the left and right amygdala and hippocampus) and preschoolers’ resting-state respiratory sinus arrhythmia (RSA). RSA is a measure of heart-rate variability, a physiological marker that reflects fluctuation in the PNS and is often found predictive of emotion regulation and psychological wellbeing. Data were extracted from the “Growing Up in Singapore towards Healthy Outcomes” (GUSTO) cohort (n = 73, 39 girls). Neonatal limbic volume was collected within two weeks after birth while infants were asleep. Resting-state RSA was collected during a colouring session at 42 months of age. After controlling for potential confounders, a Bonferroni-corrected significant association between neonatal left hippocampal volume and resting-state RSA emerged wherein larger hippocampal volume was associated with higher resting-state RSA. No significant associations were present between resting-state RSA and right or left amygdala, or right hippocampal volume. These findings contribute to an increasing body of evidence aiming at enhancing our understanding of neurobiological underpinnings of parasympathetic activity and modulation. Results are also discussed with reference to ideas concerning biological sensitivity to context, as both left hippocampal volume and resting-state RSA were previously found to moderate associations between adversity and psychological function.

Attachment theory and research are drawn upon in many applied settings, including family courts, but misunderstandings are widespread and sometimes result in misapplications. The aim of this consensus statement is, therefore, to enhance understanding, counter misinformation, and steer family-court utilisation of attachment theory in a supportive, evidence-based direction, especially with regard to child protection and child custody decision-making. The article is divided into two parts. In the first, we address problems related to the use of attachment theory and research in family courts, and discuss reasons for these problems. To this end, we examine family court applications of attachment theory in the current context of the best-interest-of-the-child standard, discuss misunderstandings regarding attachment theory, and identify factors that have hindered accurate implementation. In the second part, we provide recommendations for the application of attachment theory and research. To this end, we set out three attachment principles: the child’s need for familiar, non-abusive caregivers; the value of continuity of good-enough care; and the benefits of networks of attachment relationships. We also discuss the suitability of assessments of attachment quality and caregiving behaviour to inform family court decision-making. We conclude that assessments of caregiver behaviour should take center stage. Although there is dissensus among us regarding the use of assessments o attachment quality to inform child custody and child-protection decisions, such assessments are currently most suitable for targeting and directing supportive interventions. Finally, we provide directions to guide future interdisciplinary research collaboration. info:eu-repo/semantics/publishedVersion

ImportanceResearch evidence is mounting for the association between infant screen use and negative cognitive outcomes related to attention and executive functions. The nature, timing, and persistence of screen time exposure on neural functions are currently unknown. Electroencephalography (EEG) permits elucidation of the neural correlates associated with cognitive impairments.ObjectiveTo examine the associations between infant screen time, EEG markers, and school-age cognitive outcomes using mediation analysis with structural equation modeling.Design, Setting, and ParticipantsThis prospective maternal-child dyad cohort study included participants from the population-based study Growing Up in Singapore Toward Healthy Outcomes (GUSTO). Pregnant mothers were enrolled in their first trimester from June 2009 through December 2010. A subset of children who completed neurodevelopmental visits at ages 12 months and 9 years had EEG performed at age 18 months. Data were reported from 3 time points at ages 12 months, 18 months, and 9 years. Mediation analyses were used to investigate how neural correlates were involved in the paths from infant screen time to the latent construct of attention and executive functioning. Data for this study were collected from November 2010 to March 2020 and were analyzed between October 2021 and May 2022.ExposuresParent-reported screen time at age 12 months.Main Outcomes and MeasuresPower spectral density from EEG was collected at age 18 months. Child attention and executive functions were measured with teacher-reported questionnaires and objective laboratory-based tasks at age 9 years.ResultsIn this sample of 437 children, the mean (SD) age at follow-up was 8.84 (0.07) years, and 227 children (51.9%) were male. The mean (SD) amount of daily screen time at age 12 months was 2.01 (1.86) hours. Screen time at age 12 months contributed to multiple 9-year attention and executive functioning measures (η2, 0.03-0.16; Cohen d, 0.35-0.87). A subset of 157 children had EEG performed at age 18 months; EEG relative theta power and theta/beta ratio at the frontocentral and parietal regions showed a graded correlation with 12-month screen use (r = 0.35-0.37). In the structural equation model accounting for household income, frontocentral and parietal theta/beta ratios partially mediated the association between infant screen time and executive functioning at school age (exposure-mediator β, 0.41; 95% CI, 0.22 to 0.59; mediator-outcome β, −0.38; 95% CI, −0.64 to −0.11), forming an indirect path that accounted for 39.4% of the association.Conclusions and RelevanceIn this study, infant screen use was associated with altered cortical EEG activity before age 2 years; the identified EEG markers mediated the association between infant screen time and executive functions. Further efforts are urgently needed to distinguish the direct association of infant screen use compared with family factors that predispose early screen use on executive function impairments.

Maladaptive offspring emotion regulation has been identified as one pathway linking maternal and child psychological well-being in school-aged children. Whether such a pathway is present earlier in life still remains unclear. The present study investigated the role of preschoolers’ emotion reactivity and regulation in the association between maternal psychological distress and child internalizing and externalizing problems. Children’s emotion reactivity and regulation were assessed through both observed behavior and physiology. At 42 months of age, children (n = 251; 128 girls) completed a fear induction task during which their heart-rate variability was assessed and their behavior was monitored, and maternal self-reports on depressive mood and anxiety were collected. At 48 months mothers and fathers reported on their children’s internalizing and externalizing problems. Higher maternal depressive mood was associated with lower child fear-related reactivity and regulation, as indexed by heart-rate variability. The latter mediated the association between higher maternal depressive mood and higher preschoolers’ externalizing problems. Overall, our findings support the role of preschoolers’ emotion reactivity and regulation in the relationship between maternal psychological distress and children’s socio-emotional difficulties. This role may also depend on the discrete emotion to which children react or seek to regulate as, here, we only assessed fear-related reactivity and regulation.

We suggest that prior to school entry, our earliest “teachers” and “learning settings” —that is, our parents, caregivers, and homes—provide signals about our environmental conditions. In turn, our ...

Objectives: Adequate sleep duration and good sleep quality are considered essential for development, especially during periods of major neurodevelopmental change. Still, relations between parent-reported habitual sleep and emerging cognitive abilities within the first year of life are not well studied. Here, we examined relations between habitual sleep measures and an aspect of cognitive functioning, relational memory, which emerges as early as 6 months of age, as compared to other abilities (ie, recognition memory and attentional orienting), both of which are considered to emerge earlier in development. Participants: Participants were a subset of 267 healthy typically developing 6-month-olds taking part in the Growing Up in Singapore towards Healthy Outcomes cohort study. Measurements: Sleep duration, sleep latency, and number and duration of night awakenings were derived from the Brief Infant Sleep Questionnaire (BISQ). Short sleep was defined as

Perinatal maternal symptoms of depression and anxiety compromise psychosocial function and influence developmental outcomes in the offspring. The onset of symptoms remains unclear with findings that suggest a preconceptual origin. We addressed this issue with a prospective analysis of anxiety and depressive symptom profiles from preconception through to parturition. Women were recruited into a preconception study to assess (a) variation in symptom levels of depression and anxiety from pre- to post-conception and (b) if the symptom network profiles of depression and anxiety change from pre-conception to post-conception. A within-subject intraclass correlation analyses revealed that symptoms of depression or anxiety in the preconception phase strongly predicted those across pregnancy and into the early postnatal period. The symptom network analysis revealed that the symptom profiles remained largely unchanged from preconception into the second trimester. Our findings suggest that for a significant portion of women, maternal mental health remains stable from preconception into pregnancy. This finding highlights the need for early intervention studies on women’s mental health to be targeted during the preconception period and to be extended across the population.

From a conditional adaptation vantage point, early life caregiving adversity likely enhances aspects of cognition needed to manage interpersonal threats. Yet, research examining early life care and offspring cognition predominantly relies upon experiments including affectively neutral stimuli, with findings generally interpreted as “early-life caregiving adversity is, de facto, ‘bad’ for cognitive performance.” Here, in a Southeast Asian sample, we examined observed maternal sensitivity in infancy and cognitive performance 3 years later as preschoolers took part in three tasks, each involving both a socioemotional (SE) and non-socioemotional (NSE) version: relational memory (n = 236), cognitive flexibility (n = 203), and inhibitory control (n = 255). Results indicate the relation between early life caregiving adversity and memory performance significantly differs (Wald test = 7.67, (1), P = 0.006) depending on the SE versus NSE context, with maternal sensitivity in infancy highly predictive of worse memory for SE stimuli, and amongst girls, also predictive of better memory when NSE stimuli are used. Results concerning inhibitory control, as well as cognitive flexibility in girls, also tentatively suggest the importance of considering the SE nature of stimuli when assessing relations between the caregiving environment and cognitive performance. As not all approaches to missing data yielded similar results, implications for statistical approaches are elaborated. We conclude by considering how an adaptation-to-context framework approach may aid in designing pedagogical strategies and well-being interventions that harness pre-existing cognitive strengths.

Objectives: Minerals deficiencies during pregnancy have been shown to be associated with poorer cognitive outcomes in offspring. This study aimed to investigate associations of maternal plasma zinc and magnesium concentrations with cognitive development in 4-year old children from the Growing Up in Singapore Towards healthy Outcome cohort.Methods: Maternal plasma zinc and magnesium concentrations were measured at 26–28 weeks’ gestation. The Lollipop test of school readiness, tests of working memory, number knowledge, receptive vocabulary, and phonological awareness were performed in children at 4 years. Associations were examined in 715 mother-offspring pairs using linear regressions adjusted for key confounders.Results: Maternal plasma zinc and magnesium concentrations were 812 ± 144 µg/L and 19.9 ± 1.8 mg/L (mean±SD); 19% and 71% of mothers were zinc deficient and magnesium insufficient, respectively. After adjustment for multiple testing, higher maternal zinc concentrations (per SD increment) were associated with 0.35 higher scores in Lollipop subtest 2 of picture description and spatial identification (95% CI: 0.13, 0.58); higher maternal magnesium concentrations (per SD increment) were associated with 0.65 higher scores in Lollipop subtest 4 of letters and writing identification (95% CI: 0.23, 1.07).Discussion: No significant associations were observed for other tests, suggesting little long term influences of maternal zinc and magnesium on child's cognitive development.

The Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO) is a preconception, longitudinal cohort study that aims to study the effects of nutrition, lifestyle, and maternal mood prior to and during pregnancy on the epigenome of the offspring and clinically important outcomes including duration of gestation, fetal growth, metabolic and neural phenotypes in the offspring. Between February 2015 and October 2017, the S-PRESTO study recruited 1039 Chinese, Malay or Indian (or any combinations thereof) women aged 18 to 45 years and who intended to get pregnant and deliver in Singapore, resulting in 1032 unique participants and 373 children born in the cohort. The participants were followed up for 3 visits during the preconception phase and censored at 12 months of follow up if pregnancy was not achieved (N=557 censored). Women who successfully conceived (N=475) were characterised at gestational weeks 6-8, 11-13, 18-21, 24-26, 27-28 and 34-36. Follow up of their index offspring (N=373 singletons) is on-going at birth, 1, 3 and 6 weeks, 3, 6, 12, 18, 24 and 36 months and beyond. Women are also being followed up post-delivery. Data is collected via interviewer-administered questionnaires, metabolic imaging (magnetic resonance imaging), standardized anthropometric measurements and collection of diverse specimens, i.e. blood, urine, buccal smear, stool, skin tapes, epithelial swabs at numerous timepoints. S-PRESTO has extensive repeated phenotypic data collected which include genetic and epigenetic sampling from preconception which is unique in mother-offspring epidemiological cohorts This enables prospective assessment of a wide array of potential determinants of future health outcomes in women from preconception to post-delivery and in their offspring across the earliest development from embryonic stages into early childhood. In addition the S-PRESTO study, draws from the three major Asian ethnic groups that represent 50% of the global population, increasing the relevance of its findings to global efforts to address non-communicable diseases.

The aim of this study is to assess whether positive emotional exchanges (i.e., emotion coregulation) within the mother-child dyad play a protective role in children's physiological response to a distressing task. Specifically, we test whether positive emotion coregulation among mothers and their preschool-aged children is associated with children's respiratory sinus arrhythmia (RSA) at baseline, during, and following a frustration task. One hundred Singaporean mother-child dyads (Mchildage = 3.5 years) participated in a standardized "Laughing Task" in which positive emotional constructs were measured. Children also participated in a frustration task while RSA was continuously monitored. Hierarchical linear regressions revealed that greater maternal positive emotional responses to children were associated with child RSA at baseline and in recovery from frustration, but not during frustration. These findings have implications for the important role that positive emotion responsivity from mothers may play in children's developing autonomic response systems, and underscore the need for longitudinal work on this topic.

Purpose To explore the associations between type of milk feeding (the “nutrients”) and mode of breast milk feeding (the “nursing”) with child cognition. Methods Healthy children from the GUSTO (Growing Up in Singapore Toward healthy Outcomes) cohort participated in repeated neurodevelopmental assessments between 6 and 54 months. For “nutrients”, we compared children exclusively bottle-fed according to type of milk received: formula only (n = 296) vs some/all breast milk (n = 73). For “nursing”, we included only children who were fully fed breast milk, comparing those fed directly at the breast (n = 59) vs those fed partially/completely by bottle (n = 63). Results Compared to infants fed formula only, those who were bottle-fed breast milk demonstrated significantly better cognitive performance on both the Bayley Scales of Infant and Toddler Development (Third Edition) at 2 years [adjusted mean difference (95% CI) 1.36 (0.32, 2.40)], and on the Kaufman Brief Intelligence Test (Second Edition) at 4.5 years [7.59 (1.20, 13.99)]. Children bottle-fed breast milk also demonstrated better gross motor skills at 2 years than those fed formula [1.60 (0.09, 3.10)]. Among infants fully fed breast milk, those fed directly at the breast scored higher on several memory tasks compared to children bottle-fed breast milk, including the deferred imitation task at 6 months [0.67 (0.02, 1.32)] and relational binding tasks at 6 [0.41 (0.07, 0.74)], 41 [0.67 (0.04, 1.29)] and 54 [0.12 (0.01, 0.22)] months. Conclusions Our findings suggest that nutrients in breast milk may improve general child cognition, while nursing infants directly at the breast may influence memory. Electronic supplementary material The online version of this article (10.1007/s00394-019-01929-2) contains supplementary material, which is available to authorized users.

Caregiving insensitivity and fear dysregulation predict anxiety symptoms in children. It is unclear, however, whether sensitive parental care during infancy predicts fear regulation later in childhood. To address this question, we asked whether observed maternal sensitivity, measured at 6 months, predicts 42-month-old children's laboratory-induced fear responses (n=213) during a fear-eliciting episode. We predicted that higher levels of maternal sensitivity would be associated with greater fear regulation. We operationalized fear regulation as decreases in fear over repeated trials of a novel, potentially frightening, stimulus. Two aspects of fear responses were considered: expressed fear and startle. Expressed fear scores did not decrease over time but children exhibited less startle behavior in the second half of the task. Maternal sensitivity predicted this startle attenuation across trials. These findings highlight the contribution of maternal sensitivity during infancy to the development of fear regulation in early childhood, further suggesting its influence on offspring anxiety problems.

While many studies focus on the association between early life adversity and the later risk for psychopathology, few simultaneously explore diverse forms of environmental adversity. Moreover, those studies that examined the cumulative impact of early life adversity focus uniquely on postnatal influences. The objective of this study was to focus on the fetal period of development to construct and validate a cumulative prenatal adversity score in relation to a wide range of neurodevelopmental outcomes. We also examined the interaction of this adversity score with a biologically informed genetic score based on the serotonin transporter gene. Prenatal adversities were computed in two community birth cohorts using information on health during pregnancy, birth weight, gestational age, income, domestic violence/sexual abuse, marital strain, as well as maternal smoking, anxiety, and depression. A genetic score based on genes coexpressed with the serotonin transporter in the amygdala, hippocampus, and prefrontal cortex during prenatal life was constructed with an emphasis on functionally relevant single nucleotide polymorphisms, that is, expression quantitative trait loci. Prenatal adversities predicted a wide range of developmental and behavioral alterations in children as young as 2 years of age in both cohorts. There were interactions between the genetic score and adversities for several domains of the Child Behavior Checklist (CBCL), with pervasive developmental problems remaining significant adjustment for multiple comparisons. Scores combining different prenatal adverse exposures predict childhood behavior and interact with the genetic background to influence the risk for psychopathology.

Past research indicates that socioeconomic status (SES) accounts for differences in sensitivity across ethnic groups. However, comparatively little work has been conducted in Asia, with none examining whether ethnicity moderates the relation between SES and sensitivity. We assessed parenting behavior in 293 Singaporean citizen mothers of 6-month olds (153 Chinese, 108 Malay, 32 Indian) via the Maternal Behavioral Q-Sort for video interactions. When entered into the same model, SES (F(1,288) = 17.777, p .001), but not ethnicity, predicted maternal sensitivity (F(2,288) = .542, p = .582). However, this positive relation between SES and sensitivity was marginally moderated by ethnicity. SES significantly positively predicted sensitivity in Chinese, but not Malay dyads. Within Indian dyads, SES marginally positively predicted sensitivity only when permanent residents were included in analyses. We discuss the importance of culture on perceived SES-associated stress. However, because few university-educated Malays participated, we also consider whether university education, specifically, positively influences sensitivity.

Despite claims concerning biological mechanisms sub-serving infant attention, little experimental work examines its underpinnings. This study examines how candidate polymorphisms from the cholinergic ( CHRNA4 rs1044396) and dopaminergic ( COMT rs4680) systems, respectively indicative of parietal and prefrontal/anterior cingulate involvement, are related to 6-month-olds’ ( n = 217) performance during a visual expectation eye-tracking paradigm. As previous studies suggest that both cholinergic and dopaminergic genes may influence susceptibility to the influence of other genetic and environmental factors, we further examined whether these candidate genes interact with one another and/or with early caregiving experience in predicting infants’ visual attention. We detected an interaction between CHRNA4 genotype and observed maternal sensitivity upon infants’ orienting to random stimuli and a CHRNA4 - COMT interaction effect upon infants’ orienting to patterned stimuli. Consistent with adult research, we observed a direct effect of COMT genotype on anticipatory looking to patterned stimuli. Findings suggest that CHRNA4 genotype may influence susceptibility to other attention-related factors in infancy. These interactions may account for the inability to establish a link between CHRNA4 and orienting in infant research to date, despite developmental theorizing suggesting otherwise. Moreover, findings suggest that by 6 months, dopamine, and relatedly, the prefrontal cortex/anterior cingulate, may be important to infant attention.

There is accumulating evidence of a prospective relation between early language problems and ADHD, a disorder associated with deficits in executive functioning. However, little is known regarding this link among bilingual children. Here, we investigate whether (i) the prediction from language to ADHD may be lower among bilinguals, and (ii) explore if this moderation can be explained by differential executive functioning ability. Utilising a prospective sample of 408 South-East Asian toddlers, bilingual exposure as a moderator of the link between language delay at 24 months to ADHD intermediate diagnosis at 54 months was first examined with an interaction model. Next, structural equation mediated moderation models examined if the proposed moderation could be explained by executive function measures of Snack Delay and Dimensional Change Card Sort (DCCS) task, when children were 41 months. Results indicate that higher levels of bilingual exposure moderated the prospective risk of language delay to ADHD diagnosis (Predominantly single-language exposed OR = 6.37; p =.011; Predominantly dual-language exposed OR = 0.30, p =.156). Thus, language delay associated with ADHD among toddlers predominantly exposed to one but not two languages. However, this could not be explained by differential executive functioning, as this moderation was not mediated by performance on Snack Delay or DCCS. Unexpectedly, bilingual exposure associated with ADHD among toddlers of typical language development. Possible explanations, including variation in the degree of social stigma and persistence of language delay between bilingual and monolingual children, and bilingualism as an additional cognitive load for ADHD, are discussed.

IntroductionPro-vitamin A carotenoids namely α-, β-carotene and β-cryptoxanthin have potential roles in neurocognitive development, but current literature on these carotenoids mainly focused on preventing cognitive decline in the elderly. This study examined the associations of maternal plasma pro-vitamin A carotenoids concentrations with offspring cognitive development up to 54 months in the GUSTO mother-offspring cohort study.Materials and MethodsMaternal plasma pro-vitamin A carotenoids concentrations at delivery were determined by ultra-performance liquid chromatography. At age 24 months, the Bayley Scales of Infant and Toddler Development (BSID-III) was used to assess children's development for the following domains: cognitive, receptive and expressive language, and fine and gross motor. At age 54 months, the Kaufman Brief Intelligence Test (KBIT-2) was used to assess children's verbal and non-verbal intelligence. Associations of maternal pro-vitamin A carotenoids with offspring cognitive development at each time point were examined in 419 mother-offspring pairs using linear regressions adjusted for confounders (e.g. maternal demographics, antenatal mental health and breastfeeding duration).ResultsMedian (IQR) maternal plasma concentrations (mg/L) were: α-carotene 0.052 (0.032–0.081), β-carotene 0.189 (0.134–0.286), and β-cryptoxanthin 0.199 (0.123–0.304). In 24 months old infants, higher maternal β-cryptoxanthin (per SD increment) were associated with higher scores in most of BSID-III domains: cognitive [β 0.18, (0.08, 0.28) SD], receptive language [β 0.17 (0.07, 0.27) SD], fine motor [β 0.16 (0.06, 0.27) SD], and gross motor [β 0.16 (0.06, 0.27) SD]. Additionally, a 1-SD increment in maternal β-carotene concentrations were associated with 0.16 SD higher scores in BSID-III cognitive domain (95%: 0.04, 0.28), which was attenuated after adjusting for breastfeeding duration. No significant associations were observed between maternal α-carotene concentrations and BSID-III in children at 24 months of age, or between maternal pro-vitamin A carotenoids and KBIT-2 in children at 54 months of age.DiscussionOur study provides novel data suggesting a role of maternal pro-vitamin A carotenoids, especially β-cryptoxanthin, in offspring early cognitive development. This adds support to the importance of consuming sufficient amounts of red- and orange-coloured fruit and vegetables (rich sources of β-cryptoxanthin and β-carotene) during pregnancy. Further studies are required in other mother-offspring cohort with larger sample sizes, and intervention trials to confirm an effect of pro-vitamin A carotenoids on neurocognitive development.

OBJECTIVE: Maternal anxiety is a well-known risk factor for early childhood behavior problems. In this study, we explore (1) whether parenting stress mediates this relation and also (2) whether child factors, namely self-regulation, modify the influence of maternal well-being on child externalizing and internalizing problems at 4 years of age. METHOD: Mothers taking part in the Growing Up in Singapore Towards Healthy Outcomes cohort completed the Spielberger State-Trait Anxiety Inventory when their children were 24 months of age. At 42 months of age, children performed a self-regulation task (n = 391), and mothers completed the Parenting Stress Index. When children were 48 months old, both parents completed the Child Behavior Checklist. RESULTS: As predicted, parenting stress mediated the relation between maternal trait anxiety and child externalizing and internalizing problems. This mediating effect was further moderated by child self-regulation. The indirect effect of maternal trait anxiety through parenting stress on child externalizing problems was stronger among children with low self-regulation. CONCLUSION: Parenting stress is an additional pathway connecting maternal trait anxiety and children's externalizing and internalizing behavior problems. The risk for child externalizing problems conveyed by elevated maternal trait anxiety and parenting stress may be buffered by better self-regulation in 4-year-olds. These results suggest that interventions that include decreasing parenting stress and enhancing child self-regulation may be important to limiting the transgenerational impact of maternal trait anxiety.

Attachment disorganization is a risk factor for difficulties in attention, social relationships, and mental health. Conceptually, attachment disorganization may indicate a breakdown in fear regulation resulting from repeated exposure to frightening maternal care. In addition, past research has examined the influence of stress-inducing contextual factors and/or child factors upon the development of disorganization. However, no past work has assessed whether infant neuroanatomy, important to stress regulation, moderates the association between maternal care and levels of disorganized behavior. Here, utilizing data from a subsample of 82 dyads taking part in the “Growing Up in Singapore towards Healthy Outcomes” (GUSTO) cohort, we assessed the prediction from maternal sensitive caregiving at 6 mo and levels of attachment disorganization at 1.5 y, as moderated by hippocampal and amygdala volume determined within the first 2 weeks of life. Results indicate a significant interaction between neonatal left hippocampal volume and maternal sensitivity upon levels of disorganized behavior. Although these results require substantiation in further research, if replicated, they may enable new strategies for the identification of processes important to child mental health and points for intervention. This is because neonatal neuroanatomy, as opposed to genetic variation and sociodemographic risk, may be more directly linked to stress responses within individuals.

Evidence on long-term influences of maternal vitamin B12 deficiency or concentrations on infant cognition is limited. We examined associations between maternal plasma vitamin B12 and cognitive development in 24-month-old infants. Maternal plasma vitamin B12 concentrations were measured at 26–28 weeks’ gestation; infant cognitive development was assessed with the Bayley Scales of Infant and Toddler Development-III at 24 months, for 443 mother–infant pairs from the Growing Up in Singapore Towards Healthy Outcomes cohort. Linear regressions adjusted for key confounders examined associations of maternal vitamin B12 with cognitive, receptive and expressive language, fine and gross motor subscales. Co-occurrence of maternal vitamin B12 with folate or vitamin B6 insufficiencies on child’s cognition was explored. Average maternal plasma vitamin B12 concentrations was 220·5 ± 80·5 pmol/l; 15 % and 41 % of mothers were vitamin B12 deficient (12 deficiency had 0·42 (95 % CI −0·70, −0·14) sd lower cognitive scores, compared with infants of mothers with sufficient vitamin B12. Co-occurrence of maternal vitamins B12 and B6 insufficiencies was associated with 0·37 (95 % CI −0·69, −0·06) sd lower cognitive scores in infants compared with infants of mothers sufficient in both vitamins. No significant associations were observed with other subscales. Study findings suggest the possible need to ensure adequate vitamin B12 during pregnancy. The impact of co-occurrence of maternal B-vitamins insufficiencies on early cognitive development warrants further investigation.

Maternal antenatal mood is associated with negative infant temperament. This link has not been substantiated in Asian populations. We evaluated the association between antenatal maternal mood and infant temperament among Asian mother-infant pairs. Antenatal maternal depression and anxiety were assessed using the Edinburgh Postnatal Depression Scale (J. Cox, J. Holden, & R. Sagovsky, 1987) and the State-Trait Anxiety Inventory (C. Spielberger, R. Gorsuch, R. Lushene, P. Vagg, & G. Jacobs, 1983), respectively, at 26 weeks of pregnancy and 3 months' postnatally. Infant temperament was evaluated with the Early Infant Temperament Questionnaire (B. Medoff-Cooper, W.B. Carey, & S.C. McDevitt, 1993) at 3 months. Factor analysis was performed to extract culturally relevant categories of temperamental traits. Linear regression was performed to examine the influences of antenatal maternal mood on the factor-model-derived infant temperament. Of the 609 mothers, 11% met risk criteria for depression, 17% for state-anxiety, and 19% for trait-anxiety during pregnancy. Factor analysis yielded three infant temperament factors: Emotionality and Attentional Regulation, Sensory Reactivity, and Regularity and Motor Expression, Cronbach's αs = 0.613, 0.712, and 0.752, respectively. Maternal antenatal state-anxiety, p < .001, and trait anxiety, p = .005, were associated with negative emotionality and poor attentional regulation, especially among Chinese, whereas depression was not, p = .090. There was an association between maternal antenatal anxiety and negative infant temperamental traits in this Asian sample.

Maternal care may predict limbic development, though relations may vary by age and type of assessment. Here, we examined maternal behavior during early infancy (i.e., six months postpartum) in relation to offspring hippocampal and amygdala volume and microstructure development between 4.5 (n = 99) and 6 (n = 111) years. In interaction with offspring sex, maternal sensitivity predicted left amygdala volume at 6.0 years (β=-0.214, p = 0.032, df = 89) and independently predicted predominately left lateralized aspects of amygdala and hippocampal microstructure at both time points (hippocampus: left FA at 4.5 years [β=-0.241, p = 0.043, df = 68], and, in interaction with sex, left [(β = 0.349, p = 0.022, df = 86) and right FA at 6 years (β = 0.357, p = 0.016, df = 86] and left MD growth [β = -0.517, p = 0.021, df = 37]; amygdala: left MD at 4.5 years [β = -0.319, p = 0.007, df = 69] and, in interaction with offspring sex, left MD growth [β = -0.546, p = 0.019, df = 37]). Results suggest exposure to non-extreme, early insensitive care impacts neuroanatomy important to learning and stress regulation, perhaps by accelerating development. This underscores the need to promote sensitive caregiving during early infancy within community samples. Keywords: Maternal sensitivity, Infancy, Hippocampus, Amygdala, MRI, DTI, Accelerated development

Maternal care influences child hippocampal development. The hippocampus is functionally organized along an anterior–posterior axis. Little is known with regards to the extent maternal care shapes offspring anterior and posterior hippocampal (aHPC, pHPC) functional networks. This study examined maternal behavior, especially maternal sensitivity, at 6 months postpartum in relation to aHPC and pHPC functional networks of children at age 4 and 6 years. Maternal sensitivity was assessed at 6 months via the “Maternal Behavior Q Sort (MBQS) mini for video”. Subsequently, 61 and 76 children underwent resting-state functional magnetic resonance imaging (rs-fMRI), respectively, at 4 and 6 years of age. We found that maternal sensitivity assessed at 6 months postpartum was associated with the right aHPC functional networks in children at both 4 and 6 years of age. At age 4 years, maternal sensitivity was associated positively with the right aHPC’s functional connectivity with the sensorimotor network and negatively with the aHPC’s functional connectivity with the top–down cognitive control network. At 6 years of age, maternal sensitivity was linked positively with the right aHPC’s functional connectivity with the visual-processing network. Our findings suggested that maternal sensitivity in infancy has a long-term impact on the anterior hippocampal functional network in preschool children, implicating a potential role of maternal care in shaping child brain development in early life.