New findings on the maternal and placental programming of chronic disease lead to four conclusions: (1) Growth of the placental surface is polarized from the time of implantation, so that growth along the major axis, the length, is qualitatively different from growth along the minor axis, the breadth. (2) The human fetus may attempt to compensate for undernutrition by expansion of the placental surface along its minor axis. This only occurs if the mother was well nourished before conception, and may have long-term costs that include hypertension. (3) The effects of placental size on long-term health are conditioned by the mother’s nutritional state, as indicated by her socio-economic status, height and body mass index. (4) The maternal–placental programming of chronic disease differs in boys and girls. Boys invest less than girls in placental growth but more readily expand the placental surface if they become undernourished in mid-late gestation. Boys are more responsive to their mothers’ current diets while girls respond more to their mothers’ lifetime nutrition and metabolism.

While early-life estrogens are thought to play a physiologic role in prostate gland development, inappropriate estrogenic exposures either in dose, type or temporally can reprogram the prostate gland and increase susceptibility to abnormal prostate growth with aging including carcinogenesis. This review discusses the evidence for developmental estrogenic reprogramming that leads to adult prostate disease in a rat model. We propose that estrogen imprinting of the prostate is mediated through both structural reorganization of the gland early in life and epigenomic reprogramming that permits life-long memory of the inappropriate developmental exposures including heightened sensitivity to rising estradiol levels with aging. Complex interactions between early epigenetic programming and later-life experiences results in an emergence of multiple epigenomic outcomes, with some contributing to carcinogenesis with aging.

Gene markers for cardiomyocyte growth, proliferation and remodeling were examined in mouse fetuses and adult male offspring exposed to maternal low-protein (LP) diet during pregnancy. Whole heart volume, measured by magnetic resonance imaging, was smaller in day 15 LP fetuses v. those from chow-fed dams (C), whereas heart volume was greater in adult LP v. C offspring. These LP offspring were hypertensive and had larger cardiomyocytes v. C animals. The mRNA levels of cyclin G1, a marker for cell growth, were lower in LP fetal hearts v. C hearts, but similar in the left ventricle of adult LP and C offspring. Opposite trends were found in brain natriuretic peptide levels (a marker of cardiac hypertrophy). Thus, maternal LP during pregnancy results in smaller fetal hearts and is accompanied by changes in expression of genes involved in cardiomyocyte growth, which are associated with cardiac hypertrophy and hypertension in adulthood.

To investigate the mechanisms for the previously reported development of adult cardiac hypertrophy in male rats following growth restriction, the levels of oxidative stress and activation of signaling kinases were measured in the left ventricle (LV) of adult rat offspring. In experiment one, bilateral uterine vessel ligation to induce uteroplacental insufficiency and growth restriction in the offspring (Restricted) or sham surgery was performed during pregnancy. Litters from sham mothers had litter size either reduced (Reduced Litter), which also restricted postnatal growth, or were left unaltered (Control). In males, Reduced Litter offspring had increased LV phosphorylation of AMPKα, p38 MAPK and Akt compared with Restricted and Controls (P < 0.05). In females, both Restricted and Reduced Litter adult offspring had increased LV phosphorylation of p38 MAPK and Akt, however, only Restricted offspring had increased phosphorylation of AMPKα (P < 0.05). In addition, only Restricted male offspring displayed LV oxidative stress (P < 0.05). Experiment two investigated in mothers exposed to uteroplacental insufficiency or sham surgery the effects of cross-fostering offspring at birth, and therefore the effects of the postnatal lactational environment. Surprisingly, the cross-fostering itself resulted in increased LV phosphorylation of AMPKα and Akt in females and increased phosphorylation of Akt in males compared with Control non-cross-fostered offspring (P < 0.05). In conclusion, kinase signaling in the adult LV can be programmed by uteroplacental insufficiency induced growth restriction in a gender-specific manner. In addition, the heart of adult rats is also sensitive to programming following the postnatal intervention of cross-fostering alone as well as by postnatal growth restriction.

The hypothesis that vitamin content of the diet during gestation alters macronutrient choice, food intake and the expression of serotonin receptors and proopiomelanocortin (POMC) in the hypothalamus of the offspring was investigated. Pregnant Wistar rats (n = 10/group) were fed the AIN-93G diet containing a multivitamin mix at the recommended (RV) content or10-fold higher (high vitamin, HV) content. Male offspring were weaned to a choice of 10% and 60% casein diets. Intake regulation by the serotonergic system was determined by measuring food choice daily for 7 weeks, and following tryptophan (TRP) or mCPP (a serotonin receptor agonist) injections at 4 and 6 weeks post-weaning. mRNA expressions of hypothalamic serotonin receptor and POMC were measured at birth, weaning and sacrifice (7 weeks post-weaning). No differences were found in body weight at birth or weaning. HV offspring had lower food intake for the duration of the study (P < 0.001), and 11% lower body weight (P < 0.05) and 23% lower fat pad mass (P < 0.05) at 7 weeks post-weaning. They selected less protein following 12 h of food deprivation (P < 0.05) and were less responsive to TRP (P = 0.05) and mCPP (P < 0.05) injections at 6 weeks post-weaning. Expressions of mRNA for serotonin receptors 5-HT1A/2A/2C at weaning (P < 0.01) and of POMC at weaning and 7 weeks post-weaning (P < 0.05) were lower. In conclusion, intake of multivitamins above the requirements during pregnancy affected macronutrient choice, food intake and the expression of serotonin receptors and POMC in the hypothalamus.

The objectives of this study were to determine compliance rate in a uniform, urban African-American patient population at environmental risk for adverse neurodevelopmental outcome and to define risk factors for non-compliance with neurodevelopmental follow-up. A retrospective chart review was performed which included 481 infants with birth weight (BW) of 495–4195 g and gestational ages (GAs) between 23 and 42 weeks born at our hospital. Statistical analysis was performed using the Jonckheere–Terpstra test for ordinal variables. For 2 × 2 tables, χ2 test and Fisher’s exact test (P < 0.05) were used. To determine significant predictive variables, data were analyzed by multiple logistic regression with one independent variable at a time. Infants compliant with follow-up had significantly more morbidities in the very low BW category (⩽1500 g) than infants with larger BW. The highest compliance rate (70%) was found among the smallest and most immature (GA ⩽28 weeks) infants. Based on this finding, we postulate that the number of infants with severe disability is not likely to be underestimated. The significantly more frequent developmental anomalies found in the largest BW (⩽2500 g) category raises significant concern, though findings in this subset of infants may not be representative of the whole population. There was no significant difference between the compliant and non-compliant groups regarding socio-economic status. Severe or multiple morbidities and prolonged hospital stay may provide parents with greater opportunity to learn and understand about the infant’s condition which may lead to greater compliance.

Lower birthweight, and rapid childhood weight gain predict elevated cardiovascular risk factors in children. We examined associations between serial, detailed, anthropometric measurements from birth to 9.5 years of age and cardiovascular risk markers in Indian children. Children (n = 663) born at the Holdsworth Memorial Hospital, Mysore, India were measured at birth and 6–12 monthly thereafter. At 9.5 years, 539 (255 boys) underwent a 2-h oral glucose tolerance test, and blood pressure (BP) and fasting lipid concentrations were measured. Insulin resistance was calculated using the HOMA equation. These outcomes were examined in relation to birth measurements and changes in measurements (growth) during infancy (0–2 years), 2–5 years and 5–9.5 years using conditional s.d. scores. Larger current weight, height and skinfold thickness were associated with higher risk markers at 9.5 years (P < 0.05). Lower weight, smaller length and mid-arm circumference at birth were associated with higher fasting glucose concentrations at 9.5 years (P ⩽ 0.01). After adjusting for current weight/height, there were inverse associations between birthweight and/or length and insulin concentrations, HOMA, systolic and diastolic BP and plasma triglycerides (P < 0.05). Increases in conditional weight and height between 0–2, 2–5 and 5–9.5 years were associated with higher insulin concentrations, HOMA and systolic BP. In conclusion, in 9–10-year-old Indian children, as in other studies, cardiovascular risk factors were highest in children who were light or short at birth but heavy or tall at 9 years. Greater infant and childhood weight and height gain were associated with higher risk markers.

The Chinese Famine of 1959–1961 caused up to 30 million deaths. It varied in intensity across China and affected rural areas disproportionately. Data from the China–U.S. Collaborative Project for Neural Tube Defect Prevention on 31, 449 women (born 1957–1963) and their offspring birth size were recorded in 1993–1996. We used a measure of famine intensity at county level based on the size of famine-born cohorts relative to cohorts preceding and following the famine in a difference-in-difference model that compared offspring birth size of pre-famine (1957–1958; exposed between 0.5 and 4.5 years), famine (1959–1961; prenatal and up to 2.5 years) and post-famine (1962; some exposed in early pregnancy) cohort groups to that of the unexposed 1963 cohort. The model corrected for age and cohort trends and estimated associations between maternal famine exposure and offspring birth size for the average level of famine intensity across counties, and included adjustment for clustering. In rural areas and in pre-famine and famine cohorts, exposure to famine was associated with larger weight (69 g; 95% CI 30, 108), length (0.3 cm; 95% CI −0.0, 0.5) and birth body mass index (0.1 kg/m2; 95% CI 0.0, 0.2). In urban areas, however, exposure to famine was not associated with offspring birth size. Our findings in rural areas suggest that severe and prolonged famine leads to larger newborn size in the offspring of mothers exposed to famine in utero and during the first few years of life; less severe famine in urban areas however, appeared to have no impact. The markedly increased mortality in rural areas may have resulted in the selection of hardier mothers with greater growth potential, which becomes expressed in their offspring.