Birit F. P. Broekman

Determinants of Successful Aging Using a Multidimensional Definition Among Chinese Elderly in Singapore

OBJECTIVE Most studies of successful aging have used restricted definitions based on the absence of disability and identified a small number of predictors. The authors aimed to examine whether a broad multidimensional definition of successful aging has good construct validity and identified a wider range of predictors that are relevant for multifaceted interventions. METHODS Cross-sectional and longitudinal data analyses were performed on 1,281 community-living Chinese elderly of 65 years and above in the Singapore Longitudinal Aging Study cohort. Successful aging was measured in multiple dimensions of functioning and wellness: cognitive and affective status, physical health, social functioning and engagement and life satisfaction, and a summary composite measure created across dimensions to form a dichotomous variable. Potential determinants included sociodemographic, psychosocial, behavioral variables. RESULTS Successful aging was determined in 28.6% of respondents and in multivariate models was significantly (p <0.05) associated with age (OR = 0.90), female gender (OR = 1.37), > or =6 years of education (OR = 2.31), better housing (OR = 1.41), religious or spiritual beliefs (OR = 1.64), physical activities and exercise (OR = 1.90), and low or no nutritional risk (OR = 2.16). CONCLUSION In contrast to findings based on more restricted biomedical definitions of successful aging, a multidimensional definition of successful aging identified more variables including demographic status, psychosocial support, spirituality, and nutrition as salient determinants.

Influence of maternal obesity on the long-term health of offspring

In addition to immediate implications for pregnancy complications, increasing evidence implicates maternal obesity as a major determinant of offspring health during childhood and later adult life. Observational studies provide evidence for effects of maternal obesity on her offsprings risks of obesity, coronary heart disease, stroke, type 2 diabetes, and asthma. Maternal obesity could also lead to poorer cognitive performance and increased risk of neurodevelopmental disorders, including cerebral palsy. Preliminary evidence suggests potential implications for immune and infectious-disease-related outcomes. Insights from experimental studies support causal effects of maternal obesity on offspring outcomes, which are mediated at least partly through changes in epigenetic processes, such as alterations in DNA methylation, and perhaps through alterations in the gut microbiome. Although the offspring of obese women who lose weight before pregnancy have a reduced risk of obesity, few controlled intervention studies have been done in which maternal obesity is reversed and the consequences for offspring have been examined. Because the long-term effects of maternal obesity could have profound public health implications, there is an urgent need for studies on causality, underlying mechanisms, and effective interventions to reverse the epidemic of obesity in women of childbearing age and to mitigate consequences for offspring.

Prenatal maternal depression alters amygdala functional connectivity in 6-month-old infants.

Prenatal maternal depression is associated with alterations in the neonatal amygdala microstructure, shedding light on the timing for the influence of prenatal maternal depression on the brain structure of the offspring. This study aimed to examine the association between prenatal maternal depressive symptomatology and infant amygdala functional connectivity and to thus establish the neural functional basis for the transgenerational transmission of vulnerability for affective disorders during prenatal development. Twenty-four infants were included in this study with both structural magnetic resonance imaging (MRI) and resting-state functional MRI (fMRI) at 6 months of age. Maternal depression was assessed at 26 weeks of gestation and 3 months after delivery using the Edinburgh Postnatal Depression Scale. Linear regression was used to identify the amygdala functional networks and to examine the associations between prenatal maternal depressive symptoms and amygdala functional connectivity. Our results showed that at 6 months of age, the amygdala is functionally connected to widespread brain regions, forming the emotional regulation, sensory and perceptual, and emotional memory networks. After controlling for postnatal maternal depressive symptoms, infants born to mothers with higher prenatal maternal depressive symptoms showed greater functional connectivity of the amygdala with the left temporal cortex and insula, as well as the bilateral anterior cingulate, medial orbitofrontal and ventromedial prefrontal cortices, which are largely consistent with patterns of connectivity observed in adolescents and adults with major depressive disorder. Our study provides novel evidence that prenatal maternal depressive symptomatology alters the amygdalas functional connectivity in early postnatal life, which reveals that the neuroimaging correlates of the familial transmission of phenotypes associated with maternal mood are apparent in infants at 6 months of age.

The Influence of Birth Size on Intelligence in Healthy Children

OBJECTIVE. Birth parameters have been hypothesized to have an influence on IQ. However, studies within the range of normal birth size have been sparse. With this study we examined the associations between birth length, birth weight, head circumference, and gestational age within the normal birth size range in relation to childhood IQ in Asian children. METHODS. A cohort of 1979 of 2913 Asian children aged 7 to 9 years, recruited from 3 schools in Singapore, were followed yearly from 1999 onward. Birth parameters were recorded by health personnel. Childhood IQ was measured with the Ravens Standard Progressive Matrices at ages 8 to 12. RESULTS. The mean IQ score across the sample (n = 1645) was 114.2. After controlling for multiple confounders for every 1-cm increment in birth length, 1 kg in birth weight, or 1 cm in head circumference, there was a corresponding increase in IQ of 0.49 points (P for trend < .001), 2.19 points (P for trend = .007) and .62 points (P for trend = .003), respectively. These associations persisted even after exclusion of premature children and children with extreme weights and head circumferences. CONCLUSIONS. Longer birth length, higher birth weight, or larger head circumferences within the normal birth size range are associated with higher IQ scores in Asian children. Our results suggest that antenatal factors reflected in altered rates of growth but within the normative range of pregnancy experiences play a role in generating cognitive potential. This has implications for targeting early intervention and preventative programs.

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism influences the association of the methylome with maternal anxiety and neonatal brain volumes

Early life environments interact with genotype to determine stable phenotypic outcomes. Here we examined the influence of a variant in the brain-derived neurotropic factor (BDNF) gene (Val66Met), which underlies synaptic plasticity throughout the central nervous system, on the degree to which antenatal maternal anxiety associated with neonatal DNA methylation. We also examined the association between neonatal DNA methylation and brain substructure volume, as a function of BDNF genotype. Infant, but not maternal, BDNF genotype dramatically influences the association of antenatal anxiety on the epigenome at birth as well as that between the epigenome and neonatal brain structure. There was a greater impact of antenatal maternal anxiety on the DNA methylation of infants with the methionine (Met)/Met compared to both Met/valine (Val) and Val/Val genotypes. There were significantly more cytosine-phosphate-guanine sites where methylation levels covaried with right amygdala volume among Met/Met compared with both Met/Val and Val/Val carriers. In contrast, more cytosine-phosphate-guanine sites covaried with left hippocampus volume in Val/Val infants compared with infants of the Met/Val or Met/Met genotype. Thus, antenatal Maternal Anxiety × BDNF Val66Met Polymorphism interactions at the level of the epigenome are reflected differently in the structure of the amygdala and the hippocampus. These findings suggest that BDNF genotype regulates the sensitivity of the methylome to early environment and that differential susceptibility to specific environmental conditions may be both tissue and function specific.

Infant feeding effects on early neurocognitive development in Asian children

BACKGROUND Breastfeeding has been shown to enhance global measures of intelligence in children. However, few studies have examined associations between breastfeeding and specific cognitive task performance in the first 2 y of life, particularly in an Asian population. OBJECTIVE We assessed associations between early infant feeding and detailed measures of cognitive development in the first 2 y of life in healthy Asian children born at term. DESIGN In a prospective cohort study, neurocognitive testing was performed in 408 healthy children (aged 6, 18, and 24 mo) from uncomplicated pregnancies (i.e., birth weight >2500 and <4000 g, gestational age ≥37 wk, and 5-min Apgar score ≥9). Tests included memory (deferred imitation, relational binding, habituation) and attention tasks (visual expectation, auditory oddball) as well as the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Children were stratified into 3 groups (low, intermediate, and high) on the basis of breastfeeding duration and exclusivity. RESULTS After potential confounding variables were controlled for, significant associations and dose-response relations were observed for 4 of the 15 tests. Higher breastfeeding exposure was associated with better memory at 6 mo, demonstrated by greater preferential looking toward correctly matched items during early portions of a relational memory task (i.e., relational binding task: P-trend = 0.015 and 0.050 for the first two 1000-ms time bins, respectively). No effects of breastfeeding were observed at 18 mo. At 24 mo, breastfed children were more likely to display sequential memory during a deferred imitation memory task (P-trend = 0.048), and toddlers with more exposure to breastfeeding scored higher in receptive language [+0.93 (0.23, 1.63) and +1.08 (0.10, 2.07) for intermediate- and high-breastfeeding groups, respectively, compared with the low-breastfeeding group], as well as expressive language [+0.58 (-0.06, 1.23) and +1.22 (0.32, 2.12) for intermediate- and high-breastfeeding groups, respectively] assessed via the BSID-III. CONCLUSIONS Our findings suggest small but significant benefits of breastfeeding for some aspects of memory and language development in the first 2 y of life, with significant improvements in only 4 of 15 indicators. Whether the implicated processes confer developmental advantages is unknown and represents an important area for future research. This trial was registered at www.clinicaltrials.gov as NCT01174875.

COMT Haplotypes Modulate Associations of Antenatal Maternal Anxiety and Neonatal Cortical Morphology

OBJECTIVE Exposure to antenatal maternal anxiety and complex genetic variations may shape fetal brain development. In particular, the catechol-O-methyltransferase (COMT) gene, located on chromosome 22q11.2, regulates catecholamine signaling in the prefrontal cortex and is implicated in anxiety, pain, and stress responsivity. This study examined whether individual single-nucleotide polymorphisms (SNPs) of the COMT gene and their haplotypes moderate the association between antenatal maternal anxiety and in utero cortical development. METHOD A total of 146 neonates were genotyped and underwent MRI shortly after birth. Neonatal cortical morphology was characterized using cortical thickness. Antenatal maternal anxiety was assessed using the State-Trait Anxiety Inventory at week 26 of pregnancy. RESULTS Individual COMT SNPs (val158met, rs737865, and rs165599) modulated the association between antenatal maternal anxiety and the prefrontal and parietal cortical thickness in neonates. Based on haplotype trend regression analysis, findings also showed that among rs737865-val158met-rs165599 haplotypes, the A-val-G (AGG) haplotype probabilities modulated positive associations of antenatal maternal anxiety with cortical thickness in the right ventrolateral prefrontal cortex and the right superior parietal cortex and precuneus. In contrast, the G-met-A (GAA) haplotype probabilities modulated negative associations of antenatal maternal anxiety with cortical thickness in bilateral precentral gyrus and the dorsolateral prefrontal cortex. CONCLUSIONS These results suggest that the association between maternal anxiety and in utero neurodevelopment is modified through complex genetic variation in COMT. Such genetic moderation may explain, in part, the variation in phenotypic outcomes in offspring associated with maternal emotional well-being.

The influence of anxiety and depressive symptoms during pregnancy on birth size.

BACKGROUND Mental health problems during pregnancy can influence fetal growth. However, studies examining the influence of maternal mental health across the normal range of birth outcomes are uncommon. This study examined the associations between symptoms of maternal depression and anxiety during pregnancy on birth size among term Asian infants. METHODS One thousand forty-eight Asian pregnant women from a cohort Growing Up in Singapore Towards Healthy Outcomes were recruited between 2009 to 2010 at two Singaporean maternity hospitals. At 26 weeks gestation, depressive symptoms were measured with the Edinburgh Postnatal Depression Scale (EPDS) and the Beck Depression Inventory II (BDI-II), and anxiety was measured with the Spielberger State-Trait Anxiety Inventory (STAI). Health personnel recorded birthweight, birthlength, gestational age, and head circumference at birth. RESULTS Nine hundred forty-six women who delivered term infants had complete data. For this sample, the mean birthweight was 3146.6 g [standard deviation (SD) 399.0], the mean birthlength was 48.9 cm (SD 2.0). After controlling for several potential confounders, there was a significant negative association between STAI and birthlength [β = -0.248, confidence interval (CI) [-0.382, -0.115], P < 0.001] and a small negative association between EPDS and birthlength (β = -0.169, CI [-0.305, -0.033], P = 0.02). No associations were found between scores on the EPDS, BDI-II, and STAI with birthweight or head circumference. CONCLUSIONS Our preliminary data suggest that among term infants, anxiety and depressive symptoms are not associated with birthweight, while anxiety and depressive symptoms are associated with a shorter birthlength.

Maternal sensitivity, infant limbic structure volume and functional connectivity: a preliminary study.

Mechanisms underlying the profound parental effects on cognitive, emotional and social development in humans remain poorly understood. Studies with nonhuman models suggest variations in parental care affect the limbic system, influential to learning, autobiography and emotional regulation. In some research, nonoptimal care relates to decreases in neurogenesis, although other work suggests early-postnatal social adversity accelerates the maturation of limbic structures associated with emotional learning. We explored whether maternal sensitivity predicts human limbic system development and functional connectivity patterns in a small sample of human infants. When infants were 6 months of age, 20 mother–infant dyads attended a laboratory-based observational session and the infants underwent neuroimaging at the same age. After considering age at imaging, household income and postnatal maternal anxiety, regression analyses demonstrated significant indirect associations between maternal sensitivity and bilateral hippocampal volume at six months, with the majority of associations between sensitivity and the amygdala demonstrating similar indirect, but not significant results. Moreover, functional analyses revealed direct associations between maternal sensitivity and connectivity between the hippocampus and areas important for emotional regulation and socio-emotional functioning. Sensitivity additionally predicted indirect associations between limbic structures and regions related to autobiographical memory. Our volumetric results are consistent with research indicating accelerated limbic development in response to early social adversity, and in combination with our functional results, if replicated in a larger sample, may suggest that subtle, but important, variations in maternal care influence neuroanatomical trajectories important to future cognitive and emotional functioning.

Faster eating rates are associated with higher energy intakes during an ad libitum meal, higher BMI and greater adiposity among 4-5 year-old children: results from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) cohort

Faster eating rates are associated with increased energy intake, but little is known about the relationship between childrens eating rate, food intake and adiposity. We examined whether children who eat faster consume more energy and whether this is associated with higher weight status and adiposity. We hypothesised that eating rate mediates the relationship between child weight and ad libitum energy intake. Children (n 386) from the Growing Up in Singapore Towards Healthy Outcomes cohort participated in a video-recorded ad libitum lunch at 4·5 years to measure acute energy intake. Videos were coded for three eating-behaviours (bites, chews and swallows) to derive a measure of eating rate (g/min). BMI and anthropometric indices of adiposity were measured. A subset of children underwent MRI scanning (n 153) to measure abdominal subcutaneous and visceral adiposity. Children above/below the median eating rate were categorised as slower and faster eaters, and compared across body composition measures. There was a strong positive relationship between eating rate and energy intake (r 0·61, P<0·001) and a positive linear relationship between eating rate and childrens BMI status. Faster eaters consumed 75 % more energy content than slower eating children (Δ548 kJ (Δ131 kcal); 95 % CI 107·6, 154·4, P<0·001), and had higher whole-body (P<0·05) and subcutaneous abdominal adiposity (Δ118·3 cc; 95 % CI 24·0, 212·7, P=0·014). Mediation analysis showed that eating rate mediates the link between child weight and energy intake during a meal (b 13·59; 95 % CI 7·48, 21·83). Children who ate faster had higher energy intake, and this was associated with increased BMI z-score and adiposity.