We report on life course stress determinants of overweight in children, using data from the longitudinal follow-up of the nested case–control arm of the SAGE (study of asthma genes and the environment) birth cohort in Manitoba, Canada. Waist and hip measurements were obtained during a clinic visit at age 9–11 years. Multiple linear regression was conducted to determine the relationship between the waist-to-hip ratio and maternal smoking during pregnancy, postpartum maternal distress and stress reactivity in children (cortisol, cortisol-DHEA [dihydroepiandrostrenone] ratio quartiles) following a clinic stressor at age 8–10 years. We found waist-to-hip risk at age 9–11 years to be elevated among boys and girls whose mothers had experienced distress in the postnatal period. This association varied by gender and asthma status. In healthy girls, postpartum distress increased waist-to-hip ratio by a factor of 0.034 (P < 0.01), independent of the child's stage of puberty and adrenarche, cortisol-DHEA ratio and duration of exclusive breastfeeding. Among girls with asthma, maternal smoking during pregnancy was associated with an increased waist-to-hip ratio, if the mother also experienced distress in the postpartum period (0.072, P = 0.038). Among asthmatic boys, an association between maternal distress and waist-to-hip ratio was evident at the highest cortisol-DHEA ratios. Stress-induced changes to leptin and infant over-eating pathways were proposed to explain the postnatal maternal distress effects. Drawing on the theories of evolutionary biology, our findings underscore the significance of postnatal stress in disrupting hypothalamic–pituitary–adrenal axis function in infants and increasing risk for child overweight.

Undernutrition during pregnancy is associated with detrimental pregnancy and neonatal outcomes, which can have long-term implications for the infant. Hyperemesis gravidarum may severely limit nutritional intake. The aim of this study was to investigate the effect of hyperemesis on pregnancy and neonatal outcome, particularly gestation length and infant size at birth. Seventy-five prospectively recruited women admitted to a tertiary level hospital in Auckland, with hyperemesis gravidarum between March 2003 and October 2005, were compared to 142 controls matched for age, parity, ethnicity and expected date of delivery. Data were obtained from electronic records and analysed by Student's t-test, χ2, Wilcoxon, Fisher's exact tests and linear regression. Length of gestation, birth weight and crown-heel length were not different between participants and controls. Infants born to women with hyperemesis gravidarum had smaller head circumferences (Z-score mean (s.d.) 0.02 (0.16) v. 0.43 (0.11), P = 0.04 in all infants and −0.02 (1.24) v. 0.48 (1.29), P = 0.01 in-term infants). This study found hyperemesis gravidarum to be associated with smaller head circumferences in offspring. Given the reported associations between smaller head circumference at birth and lower cognitive ability and higher risk of cardiovascular disease in later life, further study is necessary to confirm these results and to determine whether there are any long-term implications for the offspring.

Fetal growth restriction is a risk factor for development of adulthood diseases, but the biological mechanism of this association remains unknown. Limited biomarkers have been studied in settings of preterm birth and maternal inflammation, but the relationship between a wide range of immune biomarkers and fetal growth has not been studied. The hypothesis of this study was that fetal growth restriction is associated with altered immune biomarker levels. We examined the relationship between small for gestational age (SGA) status and 27 umbilical cord blood immune biomarkers. This study was part of a large-scale cohort study of preterm birth and low birth weight conducted at Boston Medical Center, an inner city, predominantly minority patient population. Growth status was determined based on birth weight standardized to an internal reference. There were 74 SGA births and 319 appropriate for age (AGA) births with complete clinical and biomarker data. Adjusting for covariates and using AGA as reference, SGA births had lower levels of log IL-1β (ng/l; β −0.38, 95% CI −0.57, −0.19, P < 0.01), log BDNF (β −0.29, 95% CI −0.55, −0.03, P < 0.05) and log NT-3 (β −0.46, 95% CI −0.77, −0.15, P < 0.01). No associations were found between other biomarkers and SGA. In conclusion, three biomarkers were selectively associated with SGA status. Our results provide information that could be used to guide additional studied aimed at determining mechanisms that contribute to fetal growth.

Growing evidence suggests obesity may have its roots in early life but it is still uncertain whether prenatal factors operate primarily though altering early infant growth. It is also still unclear if rapid growth during selected time periods is more important than other time periods in predicting future body size. Using prospectively collected data on 20,523 participants born from 1959 to 1966 (10,327 boys; 10,196 girls) of the Collaborative Perinatal Project, we investigated the associations between pre- and postnatal factors and childhood body size at age 7 years and compared these associations across linear, logistic and quantile regression models. Maternal body mass index (BMI), maternal pregnancy weight gain, birth weight and postnatal weight change for three time periods (birth to 4 months; 4–12 months; 1–4 years) were all positively and independently associated with BMI at age 7 years. Rapid growth during each time period had a similar association BMI at age 7 years. For example, a 10-percentile increase in weight increased the probability of being overweight at age 7 years by approximately two-fold regardless of time period (OR = 1.8–2.2 for boys and girls). Using same-sex siblings (n = 571 boy sets; n = 651 girl sets) from the same cohort, we observed that siblings with higher BMI at age 7 years than their same-sex siblings were more likely to have higher maternal pregnancy weight gain, higher maternal pre-pregnancy BMI, higher birth weight and increased rate of weight gain during the three time periods. These consistent findings both from the overall cohort and the sibling analyses suggest that there are multiple, rather than specific critical periods of influence shaping childhood body size.

Linoleic acid and α-linolenic acid are essential fatty acids (eFAs) and have to be acquired from the diet. eFAs are the precursors for long-chain polyunsaturated fatty acids (lcPUFAs), which are important immune-modulating compounds. lcPUFAs can be converted into eicosanoids and other mediators. They affect membrane structure and fluidity and can alter gene expression. There has been a marked change in dietary fatty acid intake over the last several decades. Since eFAs are acquired from the diet and immune development occurs mainly perinatally, the maternal diet may influence fetal and neonatal eFA levels, and thereby lcPUFA status, and thus immune development and function. To study whether early exposure to eFAs can program immune function, mice were fed diets varying in the ratio of ω-3 to ω-6-eFAs during pregnancy and/or lactation. After weaning, pups received a Western-style diet. At 11 weeks of age, the effects of maternal diet on the offspring's allergic and vaccination responses were examined using the T-helper 2 driven ovalbumin-induced allergy model and the T-helper 1 driven influenza-vaccination model, respectively. Offspring of dams fed a high α-linolenic acid diet during lactation showed an enhanced vaccination response. As diets with either low or high ω-3/ω-6-eFA ratio attenuated the T-helper 2 allergic response, the high α-linolenic acid diet fed during lactation had the most pronounced effect. These results indicate that there is a programming effect of maternal diet on the offspring's immune response and that in mice the window of greatest susceptibility to maternal dietary intervention is the lactation/suckling period.

Malnutrition during pregnancy causes intrauterine growth restriction and long-term changes in the offspring's physiology and metabolism. To explore molecular mechanisms by which the intrauterine environment conveys programming in fetal kidneys, an organ known to undergo substantial changes in many animal models of late gestational undernutrition, we used a microswine model of maternal protein restriction (MPR) in which sows were exposed to isocaloric low protein (LP) diet during late gestation/early lactation to encompass the bulk of nephrogenesis. To define general v. model-specific effects, we also used a sheep model of placental insufficiency. In kidneys from near-term fetal and neonatal microswine LP offspring, per cell levels of total RNA, poly(A)+ mRNA and transcripts of several randomly chosen housekeeping genes were significantly reduced compared to controls. Microarray analysis revealed only a few MPR-resistant genes that escape such downregulation. The ratio of histone modifications H3K4m3/H3K9m3 (active/silenced) was reduced at promoters of downregulated but not MPR-resistant genes suggesting that transcriptional suppression is the point of control. In juvenile offspring, on a normal diet from weaning, cellular RNA levels and histone mark patterns were recovered to near control levels, indicating that global repression of transcription is dependent on ongoing MPR. Importantly, cellular RNA content was also reduced in ovine fetal kidneys during placental insufficiency. These studies show that global repression of transcription may be a universal consequence of a poor intrauterine environment that contributes to fetal restriction.