Maternal asthma symptoms during pregnancy on child behaviour and executive function: A Bayesian phenomics approach.

OBJECTIVE: Maternal history of inflammatory conditions has been linked to offspring developmental and behavioural outcomes. This phenomenon may be explained by the maternal immune activation (MIA) hypothesis, which posits that dysregulation of the gestational immune environment affects foetal neurodevelopment. The timing of inflammation is critical. We aimed to understand maternal asthma symptoms during pregnancy, in contrast with paternal asthma symptoms during the same period, on child behaviour problems and executive function in a population-based cohort. METHODS: Data were obtained from 844 families from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort. Parent asthma symptoms during the prenatal period were reported. Asthma symptoms in children were reported longitudinally from two to five years old, while behavioural problems and executive functioning were obtained at seven years old. Parent and child measures were compared between mothers with and without prenatal asthma symptoms. Generalized linear and Bayesian phenomics models were used to determine the relation between parent or child asthma symptoms and child outcomes. RESULTS: Children of mothers with prenatal asthma symptoms had greater behavioural and executive problems than controls (Cohen's d: 0.43-0.75; all p < 0.05). This association remained after adjustments for emerging asthma symptoms during the preschool years and fathers' asthma symptoms during the prenatal period. After adjusting for dependence between child outcomes, the Bayesian phenomics model showed that maternal prenatal asthma symptoms were associated with child internalising symptoms and higher-order executive function, while child asthma symptoms were associated with executive function skills. Paternal asthma symptoms during the prenatal period were not associated with child outcomes. CONCLUSIONS: Associations between child outcomes and maternal but not paternal asthma symptoms during the prenatal period suggests a role for MIA. These findings need to be validated in larger samples, and further research may identify behavioural and cognitive profiles of children with exposure to MIA.

Plasma lipidomic profiling reveals metabolic adaptations to pregnancy and signatures of cardiometabolic risk: a preconception and longitudinal cohort study.

BACKGROUND: Adaptations in lipid metabolism are essential to meet the physiological demands of pregnancy and any aberration may result in adverse outcomes for both mother and offspring. However, there is a lack of population-level studies to define the longitudinal changes of maternal circulating lipids from preconception to postpartum in relation to cardiometabolic risk factors. METHODS: LC-MS/MS-based quantification of 689 lipid species was performed on 1595 plasma samples collected at three time points in a preconception and longitudinal cohort, Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO). We mapped maternal plasma lipidomic profiles at preconception (N = 976), 26-28 weeks' pregnancy (N = 337) and 3 months postpartum (N = 282) to study longitudinal lipid changes and their associations with cardiometabolic risk factors including pre-pregnancy body mass index, body weight changes and glycaemic traits. RESULTS: Around 56% of the lipids increased and 24% decreased in concentration in pregnancy before returning to the preconception concentration at postpartum, whereas around 11% of the lipids went through significant changes in pregnancy and their concentrations did not revert to the preconception concentrations. We observed a significant association of body weight changes with lipid changes across different physiological states, and lower circulating concentrations of phospholipids and sphingomyelins in pregnant mothers with higher pre-pregnancy BMI. Fasting plasma glucose and glycated haemoglobin (HbA1c) concentrations were lower whereas the homeostatic model assessment of insulin resistance (HOMA-IR), 2-h post-load glucose and fasting insulin concentrations were higher in pregnancy as compared to both preconception and postpartum. Association studies of lipidomic profiles with these glycaemic traits revealed their respective lipid signatures at three physiological states. Assessment of glycaemic traits in relation to the circulating lipids at preconception with a large sample size (n = 936) provided an integrated view of the effects of hyperglycaemia on plasma lipidomic profiles. We observed a distinct relationship of lipidomic profiles with different measures, with the highest percentage of significant lipids associated with HOMA-IR (58.9%), followed by fasting insulin concentration (56.9%), 2-h post-load glucose concentration (41.8%), HbA1c (36.7%), impaired glucose tolerance status (31.6%) and fasting glucose concentration (30.8%). CONCLUSIONS: We describe the longitudinal landscape of maternal circulating lipids from preconception to postpartum, and a comprehensive view of trends and magnitude of pregnancy-induced changes in lipidomic profiles. We identified lipid signatures linked with cardiometabolic risk traits with potential implications both in pregnancy and postpartum life. Our findings provide insights into the metabolic adaptations and potential biomarkers of modifiable risk factors in childbearing women that may help in better assessment of cardiometabolic health, and early intervention at the preconception period. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03531658.

Mid-pregnancy and postpartum maternal mental health and infant sleep in the first year of life.

Perinatal depression and anxiety are common and associated with sleep problems in the offspring. Depression and anxiety are commonly comorbid, yet often studied independently. Our study used an integrative measure of anxiety and depressive symptoms to examine the associations of maternal mental health (mid-pregnancy and postnatal) with infant sleep during the first year of life. A total of 797 mother-child dyads from the 'Growing Up in Singapore Towards healthy Outcome' cohort study provided infant sleep data at 3, 6, 9 and 12 months of age, using the caregiver reported Brief Infant Sleep Questionnaire. Maternal mental health was assessed at 26-28 weeks gestation and 3 months postpartum using the Edinburgh Postnatal Depression Scale, Beck Depression Inventory and State-Trait Anxiety Inventory. Bifactor modelling with the individual questionnaire items produced a general affect factor score that provided an integrated measure of anxiety and depressive symptoms. Linear mixed models were used to model the sleep outcomes, with adjustment for maternal age, education, parity, ethnicity, sex of the child and maternal sleep quality concurrent with maternal mental health assessment. We found that poorer mid-pregnancy, but not postpartum, maternal mental health was associated with longer wake after sleep onset duration across the first year of life (ß = 49, 95% confidence interval 13-85 min). Poor maternal mental health during mid-pregnancy is linked to longer period of night awakening in the offspring during infancy. Interventions that aim to improve maternal antenatal mental health should examine infant sleep outcomes.

Nutrient trajectories during infancy and their associations with childhood neurodevelopment.

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 [ß = 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.

Family-focused contextual factors associated with lifestyle patterns in young children from two mother-offspring cohorts: GUSTO and EDEN.

BACKGROUND: Integrated patterns of energy balance-related behaviours of preschool children in Asia are sparse, with few comparative analyses. PURPOSE: Using cohorts in Singapore (GUSTO) and France (EDEN), we characterized lifestyle patterns of children and investigated their associations with family-focused contextual factors. METHODS: Ten behavioural variables related to child's diet, walking, outdoor play and screen time were ascertained by parental questionnaires at age 5-6 years. Using principal component analysis, sex-specific lifestyle patterns were derived independently for 630 GUSTO and 989 EDEN children. Contextual variables were organised into distal (family socio-economics, demographics), intermediate (parental health, lifestyle habits) and proximal (parent-child interaction factors) levels of influence and analysed with hierarchical linear regression. RESULTS: Three broadly similar lifestyle patterns were identified in both cohorts: "discretionary consumption and high screen time", "fruit, vegetables, and low screen time" and "high outdoor playtime and walking". The latter two patterns showed small differences between cohorts and sexes. The "discretionary consumption and high screen time" pattern was consistently similar in both cohorts; distal associated factors were lower maternal education (EDEN boys), no younger siblings (GUSTO boys) and Malay/Indian ethnicity (GUSTO), while intermediate and proximal associated factors in both cohorts and sexes were poor maternal diets during pregnancy, parents allowing high child control over food intake, snacking between meals and having television on while eating. CONCLUSIONS: Three similar lifestyle patterns were observed among preschool children in Singapore and France. There were more common associated proximal factors than distal ones. Cohort specific family-focused contextual factors likely reflect differences in social and cultural settings. Findings will aid development of strategies to improve child health.

Maternal Adverse Childhood Experience and Depression in Relation with Brain Network Development and Behaviors in Children: A Longitudinal Study.

Maternal childhood maltreatment and depression increase risks for the psychopathology of the offspring. This study employed a longitudinal dataset of mother-child dyads to investigate the developmental trajectories of brain functional networks and behaviors of children in relation with maternal childhood adverse experience and depression. Maternal childhood trauma was retrospectively assessed via childhood trauma questionnaire, whereas maternal depressive symptoms were prospectively evaluated during pregnancy and after delivery (n = 518). Child brain scans were acquired at age of 4.5, 6, and 7.5 years (n = 163) and behavioral problems were measured at 7.5 years using the Child Behavior Checklist. We found the functional connectivity of the language network with the sensorimotor, frontal, and attentional networks as a function of maternal adverse experience that interacted with sex and age. Girls exposed to mothers with depressive symptoms or childhood abuse showed the increased development of the functional connectivity of the language network with the visual networks, which was associated with social problems. Girls exposed to mothers with depressive symptoms showed the slower growth of the functional connectivity of the language network with the sensorimotor networks. Our findings, in a community sample, suggest the language network organization as neuroendophenotypes for maternal childhood trauma and depression.

Food allergy across the globe.

The prevalence of food allergy (FA) is increasing in some areas of the globe, highlighting the need for better strategies for prevention, diagnosis, and therapy. In the last few decades, we have made great strides in understanding the causes and mechanisms underlying FAs, prompting guideline updates. Earlier guidelines recommended avoidance of common food allergens during pregnancy and lactation and delaying the introduction of allergenic foods in children aged between 1 and 3 years. Recent guidelines for allergy prevention recommend consumption of a healthy and diverse diet without eliminating or increasing the consumption of allergenic foods during pregnancy or breast-feeding. Early introduction of allergenic foods is recommended by most guidelines for allergy prevention after a period of exclusive breast-feedng (6 months [World Health Organization] or 4 months [European Academy of Allergy and Clinical Immunology]). New diagnostics for FA have been developed with varied availability of these tests in different countries. Finally, the first oral immunotherapy drug for FA was approved by the US Food and Drug Administration and European Medicines Agency in 2020. In this review, we will address the global prevalence of FA, our current understanding of the causes of FA, and the latest guidelines for preventing, diagnosing, and treating FA. We will also discuss similarities and differences between FA guidelines.

Integrated structural and functional atlases of Asian children from infancy to childhood.

The developing brain grows exponentially in the first few years of life. There is a need to have age-appropriate brain atlases that coherently characterize the geometry of the cerebral cortex, white matter tracts, and functional organization. This study employed multi-modal brain images of an Asian cohort and constructed brain structural and functional atlases for 6-month-old infants, 4.5-, 6-, and 7.5-year-old children. We exploited large deformation diffeomorphic metric mapping and probabilistic atlas generation approaches to integrate structural MRI and diffusion weighted images (DWIs) and to create the atlas where white matter tracts well fit into the cortical folding pattern. Based on this structural atlas, we then employed spectral clustering to parcellate the brain into functional networks from resting-state fMRI (rs-fMRI). Our results provided the atlas that characterizes the cortical folding geometry, subcortical regions, deep white matter tracts, as well as functional networks in a stereotaxic coordinate space for the four different age groups. The functional networks consisting of the primary cortex were well established in infancy and remained stable to childhood, while specific higher-order functional networks showed specific patterns of hemispherical, subcortical-cerebellar, and cortical-cortical integration and segregation from infancy to childhood. Our multi-modal fusion analysis demonstrated the use of the integrated structural and functional atlas for understanding coherent patterns of brain anatomical and functional development during childhood. Hence, our atlases can be potentially used to study coherent patterns of brain anatomical and functional development.

High placental inositol content associated with suppressed pro-adipogenic effects of maternal glycaemia in offspring: the GUSTO cohort.

BACKGROUND/OBJECTIVES: Maternal glycaemia promotes fetal adiposity. Inositol, an insulin sensitizer, has been trialled for gestational diabetes prevention. The placenta has been implicated in how maternal hyperglycaemia generates fetal pathophysiology, but no studies have examined whether placental inositol biology is altered with maternal hyperglycaemia, nor whether such alterations impact fetal physiology. We aimed to investigate whether the effects of maternal glycaemia on offspring birthweight and adiposity at birth differed across placental inositol levels. METHODS: Using longitudinal data from the Growing Up in Singapore Towards healthy Outcomes cohort, maternal fasting glucose (FPG) and 2-hour plasma glucose (2hPG) were obtained in pregnant women by a 75-g oral glucose tolerance test around 26 weeks' gestation. Relative placental inositol was quantified by liquid chromatography-mass spectrometry. Primary outcomes were birthweight (n = 884) and abdominal adipose tissue (AAT) volumes measured by neonatal MRI scanning in a subset (n = 262) of term singleton pregnancies. Multiple linear regression analyses were performed. RESULTS: Placental inositol was lower in those with higher 2hPG, no exposure to tobacco smoke antenatally, with vaginal delivery and shorter gestation. Positive associations of FPG with birthweight (adjusted ß [95% CI] 164.8 g [109.1, 220.5]) and AAT (17.3 ml [11.9, 22.6] per mmol glucose) were observed, with significant interactions between inositol tertiles and FPG in relation to these outcomes (p < 0.05). Stratification by inositol tertiles showed that each mmol/L increase in FPG was associated with increased birthweight and AAT volume among cases within the lowest (birthweight = 174.2 g [81.2, 267.2], AAT = 21.0 ml [13.1, 28.8]) and middle inositol tertiles (birthweight = 202.0 g [103.8, 300.1], AAT = 19.7 ml [9.7, 29.7]). However, no significant association was found among cases within the highest tertile (birthweight = 81.0 g [-21.2, 183.2], AAT = 0.8 ml [-8.4, 10.0]). CONCLUSIONS: High placental inositol may protect the fetus from the pro-adipogenic effects of maternal glycaemia. Studies are warranted to investigate whether prenatal inositol supplementation can increase placental inositol and reduce fetal adiposity.

Role of maternal tryptophan metabolism in allergic diseases in the offspring.

BACKGROUND: Nicotinamide (vitamin B3) is a metabolite of tryptophan and dietary precursor of enzymes involved in many regulatory processes, which may influence fetal immune development. OBJECTIVE: We examined whether maternal plasma concentrations of nicotinamide, tryptophan or nine related tryptophan metabolites during pregnancy were associated with the risk of development of infant eczema, wheeze, rhinitis or allergic sensitization. METHODS: In the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study, we analysed the associations between maternal plasma levels of nicotinamide, tryptophan and tryptophan metabolites at 26-28 weeks of gestation and allergic outcomes collected through interviewer-administered questionnaires at multiple time-points and skin prick testing to egg, milk, peanut and mites at age 18 months. Multivariate analysis was undertaken adjusting for all metabolites measured and separately adjusting for relevant demographic and environmental exposures. Analyses were also adjusted for multiple comparisons using the false discovery method. RESULTS: Tryptophan metabolites were evaluated in 976/1247 (78%) women enrolled in GUSTO. In multivariate analysis including all metabolites, maternal plasma 3-hydrokynurenine was associated with increased allergic sensitization at 18 months (AdjRR 2.6, 95% CI 1.3-5.2 for highest quartile) but the association with nicotinamide was not significant (AdjRR 1.8, 95% CI 0.9-3.6). In analysis adjusting for other exposures, both 3-hydrokynurenine and nicotinamide were associated with increased allergic sensitization (AdjRR 2.0, 95% CI 1.1-3.6 for both metabolites). High maternal plasma nicotinamide was associated with increased infant eczema diagnosis by 6 and 12 months, which was not significant when adjusting for all metabolites measured, but was significant when adjusting for relevant environmental and demographic exposures. Other metabolites measured were not associated with allergic sensitization or eczema, and maternal tryptophan metabolites were not associated with offspring rhinitis and wheeze. CONCLUSIONS AND CLINICAL RELEVANCE: Maternal tryptophan metabolism during pregnancy may influence the development of allergic sensitization and eczema in infants.

Severity of nausea and vomiting in pregnancy and early childhood neurobehavioural outcomes: The Growing Up in Singapore Towards Healthy Outcomes study.

BACKGROUND: Nausea and vomiting of pregnancy (NVP) affects 50 to 80 per cent of women. The existing literature has examined NVP from the perspective of the mother, and relatively less is known about offspring outcomes. OBJECTIVES: To study the relationships of NVP with social-emotional, behavioural, and cognitive outcomes of the offspring in a multi-ethnic Asian cohort. METHODS: In the Growing Up in Singapore Towards Healthy Outcomes prospective mother-offspring cohort study, mothers responded to a structured NVP questionnaire at 26-28 weeks' gestation (n = 1172) and participants with severe NVP were confirmed using medical records. Children underwent multiple neurodevelopmental assessments throughout childhood. We conducted multivariable regressions with post-estimation predictive margins to understand the associations of NVP with offspring neurobehavioural outcomes, which included 1-year Infant-Toddler Social and Emotional Assessment, 1.5-year Quantitative Checklist for Autism in Toddlers, 2-year Bayley Scales of Infant and Toddler Development, 2- and 4-year Child Behavior Checklist, and 4.5-year Kaufman Brief Intelligence Test. Analyses were adjusted for household income, birth variables, maternal mental health, and other relevant medical variables. Cohen's d effect sizes were calculated using standardised mean differences (µd ). RESULTS: Mothers were categorised into no (n = 296, 25.3%), mild-moderate (n = 686, 58.5%), and severe NVP (n = 190, 16.2%), of whom 67 (5.7%) required admission. Compared to children of mothers who had no or mild-moderate NVP, children with exposure to severe NVP exhibited more externalising behaviours (µd 2.0, 95% CI 0.3, 3.6; Cohen's d = 0.33) and social communication difficulties before 2 years (µd 4.1, 95% Cl 0.1, 8.0; Cohen's d = 0.38), both externalising (µd 1.5, 95% CI 0.4, 2.6; Cohen's d = 0.43) and internalising behaviours at 2 years (µd 1.2, 95% CI 0.1, 2.2; Cohen's d = 0.35), and only internalising behaviours after 2 years (µd 1.1, 95% CI 0.4, 2.0; Cohen's d = 0.37). CONCLUSIONS: Severe NVP is highly prevalent in this Asian cohort and may be adversely associated with multiple offspring neurobehavioural outcomes.

Higher maternal plasma ß-cryptoxanthin concentration is associated with better cognitive and motor development in offspring at 2 years of age.

PURPOSE: Current literature on the roles of α-, ß-carotene and ß-cryptoxanthin in neurocognitive function has largely focused on preventing cognitive decline in older people, and less on neuro-development in children. We examined the relations of maternal plasma carotenoids concentrations with offspring cognitive development up to age 4.5 years in the Growing Up in Singapore Towards healthy Outcomes mother-offspring cohort study. METHODS: Maternal plasma α-, ß-carotene and ß-cryptoxanthin concentrations at delivery were determined by ultra-performance liquid chromatography. Children's cognition was assessed at ages 2 (Bayley Scales of Infant and Toddler Development) and 4.5 (Kaufman Brief Intelligence Test) years. Associations were examined in 419 mother-offspring pairs using linear regressions adjusting for key confounders. RESULTS: Median and interquartile range of maternal plasma concentrations (mg/L) were: α-carotene 0.052 (0.032, 0.081), ß-carotene 0.189 (0.134, 0.286), and ß-cryptoxanthin 0.199 (0.123, 0.304). In 2 years old children, higher maternal carotenoids [per standard deviation (SD) log-concentration] were positively associated with neurocognitive functions: ß-cryptoxanthin with higher scores in cognitive [ß = 0.18, (0.08, 0.28) SD], receptive language [ß = 0.17 (0.07, 0.27) SD], fine motor [ß = 0.16 (0.05, 0.26) SD], and gross motor [ß = 0.16 (0.06, 0.27) SD] scales; ß-carotene with higher cognitive score [ß = 0.17 (0.05, 0.29) SD]. No significant associations were observed with neurocognitive functions at age 4.5 years. CONCLUSION: Our study provides novel data suggesting a potential role of prenatal carotenoids, particularly ß-cryptoxanthin, on early offspring cognitive and motor development. Whether the prenatal influences sustain beyond early childhood requires further investigation in longer term studies.

Sex-Dependent Associations among Maternal Depressive Symptoms, Child Reward Network, and Behaviors in Early Childhood.

Maternal depression is associated with disrupted neurodevelopment in offspring. This study examined relationships among postnatal maternal depressive symptoms, the functional reward network and behavioral problems in 4.5-year-old boys (57) and girls (65). We employed canonical correlation analysis to evaluate whether the resting-state functional connectivity within a reward network, identified through an activation likelihood estimation (ALE) meta-analysis of fMRI studies, was associated with postnatal maternal depressive symptoms and child behaviors. The functional reward network consisted of three subnetworks, that is, the mesolimbic, mesocortical, and amygdala-hippocampus reward subnetworks. Postnatal maternal depressive symptoms were associated with the functional connectivity of the mesocortical subnetwork with the mesolimbic and amygdala-hippocampus complex subnetworks in girls and with the functional connectivity within the mesocortical subnetwork in boys. The functional connectivity of the amygdala-hippocampus subnetwork with the mesocortical and mesolimbic subnetworks was associated with both internalizing and externalizing problems in girls, while in boys, the functional connectivity of the mesocortical subnetwork with the amygdala-hippocampus complex and the mesolimbic subnetworks was associated with the internalizing and externalizing problems, respectively. Our findings suggest that the functional reward network might be a promising neural phenotype for effects of maternal depression and potential intervention to nurture child behavioral development.

Neural Transcription Correlates of Multimodal Cortical Phenotypes during Development.

During development, cellular events such as cell proliferation, migration, and synaptogenesis determine the structural organization of the brain. These processes are driven in part by spatiotemporally regulated gene expression. We investigated how the genetic signatures of specific neural cell types shape cortical organization of the human brain throughout infancy and childhood. Using a transcriptional atlas and in vivo magnetic resonance imaging (MRI) data, we demonstrated time-dependent associations between the expression levels of neuronal and glial genes and cortical macro- and microstructure. Neonatal cortical phenotypes were associated with prenatal glial but not neuronal gene expression. These associations reflect cell migration and proliferation during fetal development. Childhood cortical phenotypes were associated with neuronal and astrocyte gene expression related to synaptic signaling processes, reflecting the refinement of cortical connections. These findings indicate that sequential developmental stages contribute to distinct MRI measures at different time points. This helps to bridge the gap between the genetic mechanisms driving cellular changes and widely used neuroimaging techniques.

Associations of maternal zinc and magnesium with offspring learning abilities and cognitive development at 4 years in GUSTO.

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.

Increasing nausea and vomiting of pregnancy is associated with sex-dependent differences in early childhood growth: the GUSTO mother-offspring cohort study.

BACKGROUND: Nausea and vomiting of pregnancy (NVP) is common and underlying mechanisms are poorly understood. Longer-term offspring outcomes are also not well documented. This study aimed to determine if NVP, even in milder forms, is associated with adverse pregnancy and childhood growth outcomes. METHODS: In the GUSTO prospective mother-offspring cohort, women with singleton pregnancies (n = 1172) recruited in first trimester responded to interviewer-administered questions at 26-28 weeks' gestation about earlier episodes of NVP since becoming pregnant. Pregnancy outcomes were obtained from medical records. Offspring height and weight measured at 15 time-points between birth to 72 months (m) were standardised for age and sex. RESULTS: 58.5% (n = 686) reported mild-moderate vomiting (mNVP), 10.5% (n = 123) severe vomiting (sNVP) and 5.7% (n = 67) severe vomiting with hospitalisation (shNVP). There was no difference in odds of gestational diabetes, hypertensive disorders of pregnancy, labour induction or caesarean section after adjustment for covariates. sNVP was associated with late preterm delivery [34+ 0-36+ 6 weeks', adjusted OR = 3.04 (95% CI 1.39,6.68)], without increased odds of neonatal unit admission. Compared with no NVP, boys born to mothers with sNVP were longer at birth [adjusted ß = 0.38 standard deviations (SDs) (95% CI 0.02,0.73)], remained taller [0.64 SDs (0.23,1.04) at 72 m] and heavier [0.57 SDs (0.05,1.08) at 60 m] without differences in BMI. Conversely, girls born to mothers with shNVP were lighter from 48 m [- 0.52 SDs (- 1.00, - 0.03)] onwards with lower BMI [- 0.61 SDs (- 1.12,-0.09)]. Conditional growth modelling revealed significant sex-divergence in weight-gain at birth-3 m, 6-9 m and 4-5 years. CONCLUSIONS: Severe NVP was associated with late preterm delivery, and both mild-moderate and severe NVP associated with sex-dependent differences in early childhood growth. Boys whose mothers had NVP were taller and heavier from birth with faster growth in the first year, whereas, girls had poorer weight gain and were lighter by 48 m. As even milder severities of NVP could have long-term impact on offspring growth, further research is needed to determine mechanisms involved and implications on future health. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01174875 .

A Web-Based Time-Use Application to Assess Diet and Movement Behavior in Asian Schoolchildren: Development and Usability Study of My E-Diary for Activities and Lifestyle (MEDAL).

BACKGROUND: Web-based time-use diaries for schoolchildren are limited, and existing studies focus mostly on capturing physical activities and sedentary behaviors but less comprehensively on dietary behaviors. OBJECTIVE: This study aims to describe the development of My E-Diary for Activities and Lifestyle (MEDAL)-a self-administered, web-based time-use application to assess diet and movement behavior-and to evaluate its usability in schoolchildren in Singapore. METHODS: MEDAL was developed through formative research and an iterative user-centric design approach involving small groups of schoolchildren (ranging from n=5 to n=15, aged 7-13 years). To test the usability, children aged 10-11 years were recruited from 2 primary schools in Singapore to complete MEDAL for 2 weekdays and 2 weekend days and complete a 10-item usability questionnaire. RESULTS: The development process revealed that younger children (aged <9 years) were less able to complete MEDAL independently. Of the 204 participants (118/204, 57.8% boys, and 31/201, 15.4% overweight) in the usability study, 57.8% (118/204) completed 3 to 4 days of recording, whereas the rest recorded for 2 days or less. The median time taken to complete MEDAL was 14.2 minutes per day. The majority of participants agreed that instructions were clear (193/203, 95.1%), that MEDAL was easy to use (173/203, 85.2%), that they liked the application (172/202, 85.1%), and that they preferred recording their activities on the web than on paper (167/202, 82.7%). Among all the factors evaluated, recording for 4 days was the least satisfactory component reported. Compared with boys, girls reported better recall ability and agreed that the time spent on completing 1-day entry was appropriate. CONCLUSIONS: MEDAL appears to be a feasible application to capture diet and movement behaviors in children aged 10-12 years, particularly in the Asian context. Some gender differences in usability performance were observed, but the majority of the participants had a positive experience using MEDAL. The validation of the data collected through the application is in progress.

Nutrients or nursing? Understanding how breast milk feeding affects child cognition.

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.

Multiple modifiable lifestyle factors and the risk of perinatal depression during pregnancy: Findings from the GUSTO cohort.

BACKGROUND: Studies have identified lifestyle risk factors for perinatal depression, but none have examined the cumulative effect of these risk factors in pregnant women. METHODS: We considered the following six factors during pregnancy: poor diet quality (Healthy eating index for Singapore pregnant women 5), physical inactivity (<600 MET-minutes/week), vitamin D insufficiency (<50 nmol/l), smoking before or during pregnancy, and the perceived need for social support. Probable depression was assessed using the Edinburgh postnatal depression scale during pregnancy (>15) and at three months postpartum (≥13). Prevalence risk ratios were calculated with Poisson regressions while adjusting for potential confounders. RESULTS: Of 535 pregnant women, 207 (39%) had zero or one risk factor, 146 (27%) had two, 119 (22%) had three, 48 (9%) had four, and 15 (3%) had ≥5 risk factors at 26-28 weeks' gestation. These six lifestyle habits contributed to 32% of the variance in depressive symptoms during pregnancy. The prevalence of being probably depressed was 6.4 (95% CI 2.1, 19.8; ptrend < 0.001) for expecting women who had ≥4 risk factors compared to women who had ≤1 risk factor. No association was observed between the number of risk factors and depressive symptoms at 3 months postpartum (ptrend = 0.746). CONCLUSION: Pregnant women with ≥4 lifestyle risk factors showed a higher prevalence of depression during pregnancy, while no associations were observed for postpartum depression. CLINICAL TRIAL REGISTRATION: This cohort is registered under the Clinical Trials identifier NCT01174875; http://www.clinicaltrials.gov/ct2/show/NCT01174875?term=GUSTO&rank=2.

Is breastfeeding associated with later child eating behaviours?

Individual differences in children's eating behaviours emerge early. We examined the relationship between breastfeeding exposure and subsequent eating behaviours among children from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. Children (n = 970) were grouped according to their breastfeeding exposure: high (full breastfeeding ≥ 4 months with continued breastfeeding ≥ 6 months), low (any breastfeeding < 3 months or no breastfeeding) and intermediate (between low and high breastfeeding categories). Aspects of eating behaviour from ages 15 months to 6 years were captured using a combination of maternal reports (Child Eating Behaviour Questionnaire; Infant Feeding Questionnaire; Preschooler Feeding Questionnaire) and laboratory-based measures of meal size, oral processing behaviours (e.g. average eating speed and bite size) and tendency to eat in the absence of hunger. Most children had low (44%) or intermediate (44%) breastfeeding exposure; only 12% had high exposure. After adjusting for confounders, multivariable linear regression analyses indicated the high (but not intermediate) breastfeeding group was associated with significantly lower reported food fussiness at 3 years compared to low breastfeeding group (-0.38 [-0.70, -0.06]), with similar but non-significant trends observed at 6 years (-0.27 [-0.66, 0.11]). At 3 years, mothers in the high breastfeeding group also reported the least difficulty in child feeding compared to low breastfeeding group (-0.22 [-0.43, -0.01]). However, high breastfeeding was not associated with any other maternal-reports of child feeding or eating behaviours, and no significant associations were observed between breastfeeding exposure and any of the laboratory measures of eating behaviour at any of the time points. These results do not strongly support the view that increased breastfeeding exposure alone has lasting and consistent associations with eating behaviours in early childhood.