The purpose of this investigation was to test the hypothesis that maternal exercise training during pregnancy enhances endothelial function in offspring at birth. Six-month-old gilts (n = 8) were artificially inseminated and randomized into exercise-trained (n = 4) and sedentary groups (n = 4). Exercise training consisted of 15 weeks of treadmill exercise. The thoracic aorta of offspring were harvested within 48 h after birth and vascular responsiveness to cumulative doses of endothelium-dependent (bradykinin: 10−11–10−6 M) and independent (sodium nitroprusside: 10−10–10−4 M) vasodilators were assessed using in vitro wire myography. Female offspring from the exercised-trained gilts had a significantly greater endothelium-dependent relaxation response in the thoracic aorta when compared with the male offspring and female offspring from the sedentary gilts. The results of this investigation demonstrate for the first time that maternal exercise during pregnancy produces an enhanced endothelium-dependent vasorelaxation response in the thoracic aortas of female offspring at birth.

Fat mass and obesity-associated (FTO) gene variants are associated with childhood and adult obesity; however, the influence of FTO polymorphisms on foetal growth is unknown. Associations between the FTO variant rs9939609 and the foetal growth trajectories, maternal pregnancy weight gain, anthropometric measures at birth and body mass index (BMI) at age 14 years were assessed in 1079 singleton-birth Australian Caucasians. Analyses were repeated in 3512 singleton-birth Dutch Caucasians. The rs9939609 obesity-risk AA genotype was associated with symmetrical intrauterine growth restriction; an effect reversed in mothers who smoked during pregnancy. The effect increased over time and was modified by maternal smoking for head circumference (P = 0.007), abdominal circumference (P = 0.007), femur length (P = 0.02) and estimated foetal weight (P = 0.001). The modification of the association between the AA genotype and birth anthropometrics by maternal smoking was consistent across birth weight (P = 0.01) and birth length (P = 0.04) and neonatal day 2 anthropometry. Consistent associations were replicated in the Generation R cohort. Maternal pregnancy weight gain matched the pattern of birth weight and was independent of placental weight. In adolescents, the AA genotype was associated with increased BMI-adjusted-for-age in males (P = 0.00009), but no effect was detected in females. A variant in the FTO gene influences foetal growth trajectories in the third trimester, early postnatal growth and adiposity in adolescence. Maternal smoking during pregnancy reversed the direction of association of rs9939609 on foetal growth, which was probably mediated by maternal energy intake. The detection of genetic variants associated with foetal growth has the potential to identify novel molecular mechanisms underlying growth and targeted early life intervention.

Obesity has origins extending to antenatal and early postnatal periods; however, the relationship between early postnatal diet and subsequent obesity is not well defined. The aims of this study were to determine whether early childhood dietary quality was associated with (a) infant and adolescent nutrition and (b) body mass index (BMI) in childhood and adolescence. The degree to which early nutrition and growth factors determine BMI throughout childhood and adolescence was also explored. This research was conducted using the Raine Study, a longitudinal survey of Australian children assessed from mid-gestation to 17 years of age. A dietary quality index, the Raine Eating Assessment in Toddler score, was assigned to 2562 participants to assess early nutrition. Linear regression determined that breastfeeding was associated with dietary quality at 1–3 years. Dietary elements at 14 years of age were related to earlier dietary quality. There were no consistent associations between early diet and BMI at 3, 5, 8, 10, 14 or 17 years. In contrast, birth weight and infant weight gain were significantly associated with BMI at these ages. This study suggests that early dietary patterns are associated with aspects of diet in adolescence, likely reflecting the influence of maternal reporting. Birth weight and early growth appear to be more important determinants of adolescent BMI than early diet and nutrition. While optimizing early diet by maternal nutritional education has potential to influence later nutrition, interventions focussing on early weight gain may have a greater impact on the obesity epidemic.

Longitudinal studies investigating vitamin B12 and folate status of mothers and their offspring will provide a better understanding of intergenerational nutrition. During pregnancy and 2 years (2y) after delivery, we measured plasma vitamin B12 and folate concentrations in 118 women [aged (mean ± s.d.) 22.9 ± 3.9y] who attended a rural (n = 68) or an urban (n = 50) antenatal clinic in Pune, India. Cord blood vitamin B12 and folate were measured, and when the child was 2y total homocysteine (tHcy) was also measured. Demographic and diet measurements were recorded using standard methods.

Pregnancy plasma vitamin B12 concentration at 34 weeks was low [median (25th, 75th), 115 (95, 147) pm]; 75% had low status (<150 pm). Plasma folate was high (mean ± s.d., 33 ± 21 nm); one had a folate concentration <7 pm. Cord plasma vitamin B12 and folate concentrations were higher than and positively associated with maternal concentrations. In stepwise regression, higher child vitamin B12 at 2y was predicted (total R 2 15.7%) by pregnancy vitamin B12 (std β 0.201, R 2 7.7%), current consumption of cow's milk (std β 0.194, R 2 3.3%) and whether breast feeding was stopped before 2y (std β −0.234 R 2 7.2%). Child's 2y tHcy concentration was high (11.4 ± 3.6 μm) and predicted by lower pregnancy vitamin B12 (std β −0.206, R 2 4.1%), lack of vitamin supplementation (std β −0.256, R 2 5.6%) in pregnancy and whether currently breastfed (std β 0.268, R 2 8.4%).

Low maternal vitamin B12 status in pregnancy and prolonged breast-feeding results in disturbed one-carbon metabolism in offspring at 2y. Supplementation of women of child-bearing age, particularly during pregnancy and lactation, may improve the homocysteine status of these children.

Foetal growth restriction impairs skeletal muscle development and adult muscle mitochondrial biogenesis. We hypothesized that key genes involved in muscle development and mitochondrial biogenesis would be altered following uteroplacental insufficiency in rat pups, and improving postnatal nutrition by cross-fostering would ameliorate these deficits. Bilateral uterine vessel ligation (Restricted) or sham (Control) surgery was performed on day 18 of gestation. Males and females were investigated at day 20 of gestation (E20), 1 (PN1), 7 (PN7) and 35 (PN35) days postnatally. A separate cohort of Control and Restricted pups were cross-fostered onto a different Control or Restricted mother and examined at PN7. In both sexes, peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α), cytochrome c oxidase subunits 3 and 4 (COX III and IV) and myogenic regulatory factor 4 expression increased from late gestation to postnatal life, whereas mitochondrial transcription factor A, myogenic differentiation 1 (MyoD), myogenin and insulin-like growth factor I (IGF-I) decreased. Foetal growth restriction increased MyoD mRNA in females at PN7, whereas in males IGF-I mRNA was higher at E20 and PN1. Cross-fostering Restricted pups onto a Control mother significantly increased COX III mRNA in males and COX IV mRNA in both sexes above controls with little effect on other genes. Developmental age appears to be a major factor regulating skeletal muscle mitochondrial and developmental genes, with growth restriction and cross-fostering having only subtle effects. It therefore appears that reductions in adult mitochondrial biogenesis markers likely develop after weaning.

Poor maternal nutrition during pregnancy can result in increased disease risk in adult offspring. Many of these effects are proposed to be mediated via altered hypothalamo–pituitary–adrenal axis (HPAA) function, and are sex and age specific. Maternal undernutrition around the time of conception alters HPAA function in foetal and early postnatal life, but there are limited conflicting data about later effects. The aim of this study was to investigate the effect of moderate periconceptional undernutrition on HPAA function of offspring of both sexes longitudinally, from juvenile to adult life. Ewes were undernourished from 61 days before until 30 days after conception or fed ad libitum. HPAA function in offspring was assessed by arginine vasopressin plus corticotropin-releasing hormone challenge at 4, 10 and 18 months. Plasma cortisol response was lower in males than in females, and was not different between singles and twins. Periconceptional undernutrition suppressed offspring plasma cortisol but not adrenocorticotropic hormone responses. In males, this suppression was apparent by 4 months, and was more profound by 10 months, with no further change by 18 months. In females, suppression was first observed at 10 months and became more profound by 18 months. Maternal undernutrition limited to the periconceptional period has a prolonged, sex-dependent effect on adrenal function in the offspring.

In Western society, impaired uteroplacental blood flow is the major cause of human intrauterine growth restriction. Infants born small and who experience late childhood accelerated growth have an increased risk of developing adult diseases. Recent studies also suggest a link between birth weight and altered adult behavior, particularly relating to motor function, learning and memory, depression and schizophrenia. The aim of this study was to determine the relative influence of prenatal and postnatal growth restriction on adult behavioral outcomes in male and female rats. Uteroplacental insufficiency was induced in Wistar Kyoto rats by bilateral uterine vessel ligation on day 18 of gestation producing growth-restricted offspring (Restricted group). The Control group had sham surgery. Another group underwent sham surgery, with a reduction in litter size to five at birth equivalent to the Restricted litter size (Reduced Litter group). At 6 months of age, a series of behavioral tests were conducted in male and female offspring. Growth restriction did not impair motor function. In fact, Restricted and Reduced Litter males showed enhanced motor performance compared with Controls (P < 0.05). Spatial memory was greater in Restricted females only (P < 0.05). The Porsolts test was unremarkable, however, males exhibited more depressive-like behavior than females (P < 0.05). A reduction in sensorimotor gating function was identified in Reduced Litter males and females (P < 0.05). We have demonstrated that growth restriction and/or a poor lactational environment can affect adult rat behavior, particularly balance and coordination, memory and learning, and sensorimotor gating function, in a sex-specific manner.