Patterns of Exposure to Cumulative Risk Through Age 2 and Associations with Problem Behaviors at Age 4.5: Evidence from Growing Up in New Zealand.

Exposure to cumulative risk (CR) has important implications for child development, yet little is known about how frequency, persistence, and timing of CR exposure during early childhood predict behavioral problems already before school start. We examine prospective longitudinal associations between patterns of CR exposure from third trimester through 2 years and subsequent behavior problems at 4.5 years. In 6156 diverse children in the Growing Up in New Zealand longitudinal study, the presence of 12 risk factors, spanning maternal health, social status, and home and neighborhood environment, defined CR and were assessed at last trimester and 9 months and 2 years of age. At child age 4.5 years, mothers completed the Strengths and Difficulties Questionnaire, where a score ≥ 16 indicated an abnormal level of problem behaviors (ALPB). Children exposed to a CR ≥ 1 at least once in early development, compared to those with consistent CR = 0, showed a significantly higher likelihood of ALPB at 4.5 years. Consistent high exposure to CR ≥ 4 across all three assessments had the highest prevalence (44%) of ALPB at age 4.5. Children with high CR exposure on two of three, compared to on all three, time points in early development did not evidence a significantly reduced prevalence (32%-41%) of ALPB. The common co-occurrence of risk factors and their significant developmental impact when accumulated early in life underscore the need for systematic multisector intervention and policy implementation during pregnancy and shortly after birth to improve outcomes for vulnerable children

Caesarean section delivery and childhood obesity in a British longitudinal cohort study

Background: Several studies reported an association between Caesarean section (CS) birth and childhood obesity. However, there are several limitations in the current literature. These include an inability to distinguish between planned and emergency CS, small study sample sizes and not adjusting for pre-pregnancy body-mass-index (BMI). We examined the association between CS delivery and childhood obesity using the United Kingdom Millennium Cohort Study (MCS). Methods: Mother-infant pairs were recruited into the MCS. Use of sampling weights ensured the sample was representative of the population. The exposure was categorised as normal vaginal delivery (VD) [reference], assisted VD, planned CS and emergency CS. Childhood obesity prevalence, at age three, five, seven, eleven and fourteen years was calculated using the International Obesity Taskforce criteria. Mixed-effects linear regression models were fitted with associations adjusted for several potential confounders like maternal age, pre-pregnancy BMI, education and infant macrosomia. Linear regression models were fitted evaluating body fat percentage (BF%), at age seven and fourteen years. Results: Of the 18,116 infants, 3872 (21.4%) were delivered by CS; 9.2% by planned CS. Obesity prevalence was 5.4%, 5.7%, 6.5%, 7.1% and 7.6% at age three, five, seven, eleven and fourteen years respectively. The mixed-effects linear regression model showed no association between planned (adjusted mean difference = 0.00; [95% confidence interval (CI) -0.10; 0.10], p-value = 0.97) or emergency CS (adjusted mean difference = 0.08; [95% CI -0.01; 0.17], p-value = 0.09) and child BMI. At age seven years, there was no association between planned CS and BF% (adjusted mean difference = 0.13; [95% CI -0.23; 0.49]); there was no association at age fourteen years. Conclusions: Infants born by planned CS did not have a significantly higher BMI or BF% compared to those born by normal VD. This may suggest that the association, described in the literature, could be due to the indications/reasons for CS birth or residual confounding

Age-Related Changes in the Epithelial and Stromal Compartments of the Mammary Gland in Normocalcemic Mice Lacking the Vitamin D3 Receptor

The vitamin D3 receptor (VDR) serves as a negative growth regulator during mammary gland development via suppression of branching morphogenesis during puberty and modulation of differentiation and apoptosis during pregnancy, lactation and involution. To assess the role of the VDR in the aging mammary gland, we utilized 12, 14, and 16 month old VDR knockout (KO) and wild type (WT) mice for assessment of integrity of the epithelial and stromal compartments, steroid hormone levels and signaling pathways. Our data indicate that VDR ablation is associated with ductal ectasia of the primary mammary ducts, loss of secondary and tertiary ductal branches and atrophy of the mammary fat pad. In association with loss of the white adipose tissue compartment, smooth muscle actin staining is increased in glands from VDR KO mice, suggesting a change in the stromal microenviroment. Activation of caspase-3 and increased Bax expression in mammary tissue of VDR KO mice suggests that enhanced apoptosis may contribute to loss of ductal branching. These morphological changes in the glands of VDR KO mice are associated with ovarian failure and reduced serum 17β-estradiol. VDR KO mice also exhibit progressive loss of adipose tissue stores, hypoleptinemia and increased metabolic rate with age. These developmental studies indicate that, under normocalcemic conditions, loss of VDR signaling is associated with age-related estrogen deficiency, disruption of epithelial ductal branching, abnormal energy expenditure and atrophy of the mammary adipose compartment

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

ISSN exercise & sport nutrition review: research & recommendations

Sports nutrition is a constantly evolving field with hundreds of research papers published annually. For this reason, keeping up to date with the literature is often difficult. This paper is a five year update of the sports nutrition review article published as the lead paper to launch the JISSN in 2004 and presents a well-referenced overview of the current state of the science related to how to optimize training and athletic performance through nutrition. More specifically, this paper provides an overview of: 1.) The definitional category of ergogenic aids and dietary supplements; 2.) How dietary supplements are legally regulated; 3.) How to evaluate the scientific merit of nutritional supplements; 4.) General nutritional strategies to optimize performance and enhance recovery; and, 5.) An overview of our current understanding of the ergogenic value of nutrition and dietary supplementation in regards to weight gain, weight loss, and performance enhancement. Our hope is that ISSN members and individuals interested in sports nutrition find this review useful in their daily practice and consultation with their clients

Intergenerational determinants of offspring size at birth: a life course and graphical analysis using the Aberdeen Children of the 1950s Study (ACONF).

BACKGROUND: Size at birth has taken on renewed significance due to its now well-established association with many health and health-related outcomes in both the immediate perinatal period and across the entire life course. Optimizing fetal growth to improve both neonatal survival and population health is the focus of much research and policy development, although most efforts have concentrated on either the period of pregnancy itself or the period immediately preceding it. METHODS: Intergenerational data linked to the Aberdeen Children of the 1950s (ACONF) study were used to examine the influence of grandparental and parental life course biological and social variables on the distribution of offspring size at birth. Guided stepwise multivariable methods and a graphical approach were used to assess the relative importance of these temporally ordered and highly correlated life course measures. RESULTS: Both distal and proximal grandparental and parental life course biological and social factors predicted offspring size at birth. Inequalities in size at birth, according to adult maternal socioeconomic indicators, were found to be largely generated by the continuity of the social environment across generations, and the inequalities in maternal early life growth were predicted by the adult grandparental social environment during the mother's early life. Mother's own size at birth predicted her offspring's intrauterine growth, independent of her adult biological and social characteristics. CONCLUSIONS: A mother's childhood social environment and her early growth are both important predictors of her offspring's size at birth. Population strategies aimed at optimizing size at birth require broader social and intergenerational considerations, in addition to focusing on the health of mothers in the immediate pregnancy period

Early life predictors of childhood intelligence: evidence from the Aberdeen children of the 1950s study.

OBJECTIVE: To identify the early life predictors of childhood intelligence. DESIGN: Cohort study of 10 424 children who were born in Aberdeen (Scotland) between 1950 and 1956. RESULTS: Social class of father around the time of birth, gravidity, maternal age, maternal physical condition, whether the child was born outside of marriage, prematurity, intrauterine growth, and childhood height were all independently associated with childhood intelligence at ages 7, 9, and 11. The effect of social class at birth was particularly pronounced, with a graded linear association across the distribution even with adjustment for all other covariates (p<0.001 for linear trend). Those from the lowest social class (V) had intelligence scores that were on average 0.9-1.0 of a standard deviation lower than those from the higher groups (I and II) at each of the three ages of intelligence testing. Collectively, the early life predictors that were examined explained 16% of the variation in intelligence at each age. CONCLUSIONS: Father's social class around the time of birth was an important predictor of childhood intelligence, even after adjustment for maternal characteristics and perinatal and childhood factors. Studies of the association of childhood intelligence with future adult disease need to ensure that the association is not fully explained by socioeconomic position

Patterns of risk exposure in first 1,000 days of life and health, behavior, and education-related problems at age 4.5: evidence from Growing Up in New Zealand, a longitudinal cohort study.

BackgroundChildren who are high priority candidates for early intervention need to be identified to reduce their risk for experiencing problems in development. Those exposed to multiple risk factors are more likely to exhibit problems in development than those exposed to a single or no risk factor. We examined the longitudinal associations between persistence and timing of exposure to cumulative risk (CR) on three occasions by age 2 and problems in development at age 4.5 in health, behavior, and education-related domains.MethodsData are from Growing Up in New Zealand (NZ), a prospective longitudinal study of a birth cohort first assessed during their last trimester in 2009-10 and followed at ages 9 months and 2 and 4.5 years. All women with an expected delivery date in a 12-month period who resided within a defined region were invited to participate, with no additional eligibility criteria. Exposure was measured for 12 sociodemographic and maternal health risk factors at third trimester and ages 9 months and 2 years, from which developmental trajectories were constructed capturing persistence and timing of CR exposure. Ten developmental outcomes were measured at age 4.5 to classify problems in overall health status, obesity, and injuries; internalizing and externalizing behavior problems; and letter naming, counting forward and backward, and expectations for starting school and completing education.ResultsAnalyses of data from 6156 children (49% female, 33% Non-European ethnicity) who participated in the 4.5-age assessment uniformly showed associations between exposure to more than consistently zero CR across early development and higher prevalence of being classified with problems for 9 of 10 outcomes. Persistent exposure to a CR ≥ 4 was generally associated with a higher prevalence of problems for 7 of 10 outcomes, whereas the timing of first exposure to CR ≥ 4 showed a less consistent association with problem outcomes.ConclusionsThese findings are concerning because over 50% of NZ children are exposed to at least one of these risk factors at some point in early development. Routine screening of most of these risk factors during pregnancy is feasible and can identify priority candidates for intervention

Patterns of Exposure to Cumulative Risk Through Age 2 and Associations with Problem Behaviors at Age 4.5: Evidence from Growing Up in New Zealand.

Exposure to cumulative risk (CR) has important implications for child development, yet little is known about how frequency, persistence, and timing of CR exposure during early childhood predict behavioral problems already before school start. We examine prospective longitudinal associations between patterns of CR exposure from third trimester through 2&nbsp;years and subsequent behavior problems at 4.5&nbsp;years. In 6156 diverse children in the Growing Up in New Zealand longitudinal study, the presence of 12 risk factors, spanning maternal health, social status, and home and neighborhood environment, defined CR and were assessed at last trimester and 9&nbsp;months and 2&nbsp;years of age. At child age 4.5&nbsp;years, mothers completed the Strengths and Difficulties Questionnaire, where a score ≥ 16 indicated an abnormal level of problem behaviors (ALPB). Children exposed to a CR ≥ 1 at least once in early development, compared to those with consistent CR = 0, showed a significantly higher likelihood of ALPB at 4.5&nbsp;years. Consistent high exposure to CR ≥ 4 across all three assessments had the highest prevalence (44%) of ALPB at age 4.5. Children with high CR exposure on two of three, compared to on all three, time points in early development did not evidence a significantly reduced prevalence (32%-41%) of ALPB. The common co-occurrence of risk factors and their significant developmental impact when accumulated early in life underscore the need for systematic multisector intervention and policy implementation during pregnancy and shortly after birth to improve outcomes for vulnerable children