Heritability of urinary amines, organic acids, and steroid hormones in children

Variation in metabolite levels reflects individual differences in genetic and environmental factors. Here, we investigated the role of these factors in urinary metabolomics data in children. We examined the effects of sex and age on 86 metabolites, as measured on three metabolomics platforms that target amines, organic acids, and steroid hormones. Next, we estimated their heritability in a twin cohort of 1300 twins (age range: 5.7-12.9 years). We observed associations between age and 50 metabolites and between sex and 21 metabolites. The monozygotic (MZ) and dizygotic (DZ) correlations for the urinary metabolites indicated a role for non-additive genetic factors for 50 amines, 13 organic acids, and 6 steroids. The average broad-sense heritability for these amines, organic acids, and steroids was 0.49 (range: 0.25-0.64), 0.50 (range: 0.33-0.62), and 0.64 (range: 0.43-0.81), respectively. For 6 amines, 7 organic acids, and 4 steroids the twin correlations indicated a role for shared environmental factors and the average narrow-sense heritability was 0.50 (range: 0.37-0.68), 0.50 (range; 0.23-0.61), and 0.47 (range: 0.32-0.70) for these amines, organic acids, and steroids. We conclude that urinary metabolites in children have substantial heritability, with similar estimates for amines and organic acids, and higher estimates for steroid hormones.Analytical BioScience

No association between glucocorticoid receptor polymorphisms and long-term respiratory outcome after very preterm birth

Developmen

Preterm birth, early growth and adult metabolic health

Children born small-for-gestational-age (SGA) are at risk for short stature, and cardiovascular disease and type 2 diabetes in later life. There is some preliminary evidence for a similar phenotype in survivors of preterm birth. In contrast to children born SGA, preterm infants born appropriate-for-gestational-age who experienced neonatal growth retardation, resulting in a small size at term, are excluded from growth hormone therapy if they fail to catch up in height subsequently. We tested in 19-year-olds born before 32 gestational weeks from the Project On Preterm and Small-for-gestational-age infants cohort the effect of early growth on the growth pattern and adult metabolic health. Childhood growth and adult height were similar in preterm infants born SGA and those with neonatal growth retardation (weight and/or length at 3 months <-2 SD score). Young adults born preterm had a waist circumference and a waist-to-hip ratio much greater than the population reference mean, especially women. In addition, they showed a tendency towards insulin resistance and a high prevalence of hypertension. These findings were not explained by antenatal glucocorticoid treatment. Carriers of the 23K variant of the R23K polymorphism in the glucocorticoid receptor, associated with a mild glucocorticoid resistance, were less insulin-resistant and showed complete catch-up growth early in infancy and attained height was similar to the population reference mean, whereas stature in non-carriers was on average 0.5 SD below this mea

Maternal hypothyroxinemia in early pregnancy predicts reduced performance in reaction time tests in 5- to 6-year-old offspring

Context: Overt hypothyroidism in pregnant women is associated with poorer neurodevelopment in their children. Findings from studies investigating the effect of less severe impairments in the maternal thyroid function on cognitive functioning in offspring are difficult to interpret for a number of reasons, including lack of objective cognitive tests, preschool age at assessment, and small sample sizes. Objective: We aimed to assess the effect of the maternal thyroid status in early pregnancy on their offspring's cognitive performance at 5 to 6 years of age. Design and Participants: This was a prospective study that included the data of 1765 healthy 5- to 6-year-old children from the Amsterdam Born Children and their Development study. Maternal serum free T4 and TSH were obtained at a median gestational age of 90 (interquartile range, 83 to 100) days. Main Outcome Measures: Cognitive performance was tested using a computerized assessment program that measured response speed, response speed stability, visuomotor skills, response selection, and response inhibition. Results: Maternal hypothyroxinemia (ie, maternal free T4 in the lowest 10% of distribution) was associated with a 41.3 (95% confidence interval, 20.3–62.4) ms slower response speed in a simple reaction time task. In this test, it was also associated with a decreased stability in response speed. The relations found persisted after adjustment for family background and perinatal conditions. The effect of hypothyroxinemia on these outcomes was dependent on its interaction with TSH level. Conclusions: Lower maternal free T4 concentration at the end of the first trimester predicted slower response speed and decreased stability in response speed in offspring at 5 to 6 years of age. Keywords: pregnancy, child, mothers, reaction time, thyrotropin, free thyroxin, early stage of pregnancy, cognitive ability, offsprin

Falsely elevated plasma testosterone concentrations in neonates: importance of LC-MS/MS measurements

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