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ABSTRACT Background: There are multiple potential regulators of neonatal vitamin D status of environmental, genetic, and epigenetic origins. The relation between these factors and circulating neonatal vitamin D has yet to be fully characterized. Objective: The aim of this study was to examine the relative contribution of genetic factors, maternal circulating 25-hydroxyvitamin D [25(OH)D] concentrations, and the placental methylation level of the gene that encodes the primary catabolic enzyme of active vitamin D [25(OH)D-24-hydroxylase encoded by CYP24A1] to neonatal 25(OH)D concentrations. Design: We used the classical twin study design to determine the genetic contribution to neonatal 25(OH)D. A total of 86 twin pairs (32 monozygotic and 54 dizygotic twin pairs) were included in this study. Serum 25(OH)D was measured by using a 25(OH)D kit. CYP24A1 promoter DNA methylation was measured by means of matrix-assisted laser desoiption time-of-flight mass spectrometry. Results: Maternal and neonatal 25(OH)D showed a strong association {R2 = 0.19). Monozygotic and dizygotic within-pair serum 25(OH)D correlations were similar (R2 = 0.71 and 0.67, respectively), which suggested no genetic effect. Placental CYP24A1 methylation did not show an association with maternal or neonatal 25(OH)D concentrations. Conclusions: Our results suggest that maternal circulating 25(OH)D is the most significant regulator of neonatal circulating 25(OH)D concentrations, with underlying genetic factors playing a limited role. The placental methylation of the CYP24A1 promoter appears subject to a genetic influence, although no evidence of a relation between the methylation level of this gene and circulating maternal or neonatal 25(OH)D was apparent. Am J Clin Nutr 2012; 96:188-95. [ABSTRACT FROM AUTHOR]

Summary: We hypothesise that the risk of placental dysfunction/insufficiency rises cumulatively in response to several interdependent risk factors that convergently regulate 1,25-dihydroxyvitamin D (the biologically active form of vitamin D, [1,25-(OH)2D]) levels at the feto-maternal interface. These factors include; (i) disturbances in genetic or epigenetic regulation of one-carbon metabolism and/or vitamin D metabolism and (ii) insufficiency in maternal vitamin D or in dietary intake of micronutrients that are involved in one-carbon donation. We predict that the sub-optimal functioning of folate and vitamin D metabolic pathways, in concert, represents a potential novel risk pathway for adverse pregnancy outcomes. We base this prediction on five observations: [(i)] evidence linking polymorphisms in genes regulating one-carbon donor production and vitamin D metabolism with adverse pregnancy outcomes involving placental dysfunction; [(ii)] evidence linking sub-optimal maternal levels of both one-carbon donor and 1,25-(OH)2D precursors to adverse pregnancy outcomes involving placental dysfunction; [(iii)] the requirement for adequate one-carbon donor molecules (produced solely from dietary sources) to establish epigenetic markings involving DNA methylation, in the developing placenta and fetus; [(iv)] the demonstrated modulation of vitamin D pathway regulatory genes by DNA methylation; and [(v)] data demonstrating specific DNA methylation-induced epigenetic silencing of the 24-hydroxylase gene (CYP24A1), encoding the major catabolic enzyme of 1,25-(OH)2D, and 25-hydroxyvitamin D (25-(OH)2D) in the placenta. It is anticipated that this ‘uncouples’ vitamin D homeostasis at the feto-maternal interface, allowing accumulation of the higher levels of 1,25-(OH)2D seen in pregnancy. In order to test this model, future epidemiological studies aimed at identifying risk factors for disorders linked to sub-optimal placental development and functioning, should: (a) measure circulating precursor molecules (including folate, vitamin B12, homocysteine, and vitamin D) in maternal and cord blood; (b) collect samples for examination of genotypic variation in both one-carbon and vitamin D regulatory genes and, (c) collect samples for examination of epigenetic status of genes regulating vitamin D homeostasis and action in the placenta. [Copyright &y& Elsevier]

Objective: To test the hypothesis that effects of early diet on cognition observed at age 8 years persist in adolescents born preterm at ≤ 30 weeks gestational age. Study design: A subgroup from a preterm infant cohort recruited for a randomized trial studying the effects of early dietary intervention was assessed at age 16 years. IQ scores were compared between those assigned a high-nutrient diet (n = 49) or standard-nutrient diet (n = 46) in infancy at both 8 and 16 years. Results: At age 8 years, the high-nutrient group had higher mean Verbal IQ (VIQ; P = .03), Performance IQ (P = .01), and Full-Scale IQ (P = .02) scores compared with the standard-nutrient group; the VIQ difference persisted at adolescence (P = .02). This effect was accounted for principally by a significant difference in the mean Verbal Comprehension Index score (P < .008). Conclusions: A brief period of dietary intervention after preterm birth, principally between 26 and 34 weeks of gestation, affected IQ at age 16 years. A standard-nutrient diet was associated with lower VIQ, accounted for mainly by differences in verbal comprehension, which persisted after control of social factors. [Copyright &y& Elsevier]

Summary: Osteoporotic fractures, falls and obesity are major health problems in developed nations. Evidence suggests that there are antenatal factors predisposing to these conditions. Data are emerging from Australia and elsewhere to suggest that maternal vitamin D status in pregnancy affects intrauterine skeletal mineralisation and skeletal growth together with muscle development and adiposity. Given that low levels of vitamin D have been documented in many urbanised populations, including those in countries with abundant sunlight, an important issue for public health is whether maternal vitamin D insufficiency during pregnancy has adverse effects on offspring health. The developing fetus may be exposed to low levels of vitamin D during critical phases of development as a result of maternal hypovitaminosis D. We hypothesise that this may have adverse effects on offspring musculoskeletal health and other aspects of body composition. Further research focused on the implications of poor gestational vitamin D nutrition is warranted as these developmental effects are likely to have a sustained influence on health during childhood and in adult life. We suggest that there is a clear rationale for randomised clinical trials to assess the potential benefits and harmful effects of vitamin D supplementation during pregnancy. [Copyright &y& Elsevier]

Abstract: There is increasing interest in life course epidemiology. In this article we investigated the relationship between characteristics at birth and survival and year of birth and survival. We have detailed information about birth characteristics and cause of death for 8584 subjects from a cohort of 16,272 registered live births to European Australians in a charity hospital in Melbourne between 1857 and 1900. Women giving birth at the hospital were among the poorest in Melbourne, with almost half unmarried. The adult death certificates of the subjects were traced until 1985. We found that infant mortality was substantially higher in babies who were illegitimate, firstborn, had younger mothers, a birth weight <6lb or were a preterm birth. These factors had a weaker association with child mortality and were not associated with adult survival time. Infant mortality was substantially lower in the cohort born 1891–1900 (36%) than previously (58%), a major improvement not seen for child mortality or adult lifespan. Likely reasons for this improvement are the introduction of antisepsis in maternity wards, enforced registration and police supervision of persons other than their mother who cared for babies, strictly monitored feeding practices and a mandatory autopsy and coronial enquiry for such babies who died. We conclude that this is an early example of a successful public health intervention. [Copyright &y& Elsevier]

Summary: The term ‘fetal origins of adult disease’ was coined on the basis of the inverse association between low birth weight and blood pressure, adult-onset diabetes, coronary heart disease, and stroke seen in numerous epidemiological studies. However, it seems unlikely that birth weight is involved in causal pathways underlying these observations, and if it were then the significance to public health of these findings is very limited because of our inability to modify birth weight to a relevant extent in humans. There has been a major focus on maternal nutrition. Despite evidence that experimental manipulation of maternal nutrition in animals influences offspring birth weight and programme measures related to cardiovascular disease, human studies in general provide limited and unconvincing evidence that differences in maternal macronutrient intake are important. Nevertheless there is a need to understand the underlying causal pathways, and the utility of studies of twins and possible mechanisms are discussed. [Copyright &y& Elsevier]

Background: Small-for-gestational-age (SGA) term infants are at risk of long-term growth deficits. Objective: The objectives were to test the hypothesis that postnatal growth in SGA term infants can be altered by dietary intervention and to examine whether there is a critical window for nutritional programming of the growth trajectory during the first 9 mo postnatally. Design: Healthy term (gestation ≥37 wk) infants with birth weights below the 10th centile were randomly assigned to receive standard term formula (TF; n = 147) or nutrient-enriched formula (EF; n = 152) for the first 9 mo; 175 breast-fed SGA term infants formed a reference group. The main outcome measures were weight, length, and occipitofrontal head circumference (OFC) at 9 and 18 mo. Results: The infants fed the EF showed greater gains in length by 9 (1.1 cm; 95% CI: 0.38, 1.79) and 18 (1.0 cm; 0.25, 1.83) mo and in OFC by 9 (0.5 cm; 0.1, 0.9) and 18 (0.6 cm; 0.2, 1.1) mo than did infants fed the TF; the differences were larger in females. The dietary effects were independent of the pattern of growth retardation. Breast-fed infants showed greater gains in weight and OFC by 18 mo than did infants fed the TF; however, these differences disappeared after adjustment for age, parental size, and birth order. Conclusions: Linear growth and OFC gains in SGA term infants improve after nutritional intervention during the first 9 mo of life and the effects persist for ≥9 mo beyond the intervention period. Further information on whether catch-up growth is beneficial or detrimental to long-term outcomes is required before public health interventions can be recommended. [ABSTRACT FROM AUTHOR]

Tests the hypothesis that for preterm infants, the neonatal period is a critical one for programming growth performance and that early diet influences long-term growth. Growth in the neonatal period according to randomized diet for children; Comparison of growth performance of pre-term formula-fed infants with that of banked donor breast milk or standard term formula.