Mitochondrial dysfunction and resulting changes in adiposity have been observed in the offspring of animals fed a high fat (HF) diet. As iron is an important component of the mitochondria, we have studied the offspring of female rats fed complete (Con) or iron-deficient (FeD) rations for the duration of gestation to test for similar effects. The FeD offspring were ~12% smaller at weaning and remained so because of a persistent reduction in lean tissue mass. The offspring were fed a complete (stock) diet until 52 weeks of age after which some animals from each litter were fed a HF diet for a further 12 weeks. The HF diet increased body fat when compared with animals fed the stock diet, however, prenatal iron deficiency did not change the ratio of fat:lean in either the stock or HF diet groups. The HF diet caused triglyceride to accumulate in the liver, however, there was no effect of prenatal iron deficiency. The activity of the mitochondrial electron transport complexes was similar in all groups including those challenged with a HF diet. HF feeding increased the number of copies of mitochondrial DNA and the prevalence of the D-loop mutation, however, neither parameter was affected by prenatal iron deficiency. This study shows that the effects of prenatal iron deficiency differ from other models in that there is no persistent effect on hepatic mitochondria in aged animals exposed to an increased metabolic load.

The present study used a sheep model of intrauterine growth restriction, combining maternal undernutrition and twinning, to determine possible markers of early damage to the fetal kidney. The occurrence of early deviations in fetal hemodynamics which may be indicative of changes in blood perfusion was assessed by Doppler ultrasonography. A total of 24 sheep divided in two groups were fed with the same standard grain-based diet but fulfilling either their daily maintenance requirements for pregnancy (control group; n=12, six singleton and six twin pregnancies) or only the 50% of such quantity (food-restricted group; n=12; four singleton and eight twin pregnancies). All the fetuses were assessed by both B-mode and Doppler ultrasonography at Day 115 of pregnancy. Fetal blood supply was affected by maternal undernutrition, although there were still no evidences of brain-sparing excepting in fetuses at greatest challenge (twins in underfed pregnancies). However, there were early changes in the blood supply to the kidneys of underfed fetuses and underfed twins evidenced decreases in kidney size.

Early life stress has been shown to contribute to alterations in biobehavioral regulation. Whereas many different forms of childhood adversities have been studied in relation to cardiovascular outcomes, very little is known about potential associations between caregivers’ verbally aggressive behavior and heart rate and blood pressure in the child. This prospective study examined whether maternal verbally aggressive behavior in early infancy is associated with heart rate or blood pressure at age 5–6. In the Amsterdam Born Children and their Development study, a large prospective, population-based birth cohort, maternal verbally aggressive behavior was assessed by questionnaire in the 13th week after birth. The child’s blood pressure and heart rate were measured during rest at age 5–6 (n=2553 included). Maternal verbally aggressive behavior in infancy was associated with a higher systolic blood pressure (SBP) both in supine and sitting position after adjustment for sex, height and age (SBP supine B=1.01 mmHg; 95% CI [0.06; 1.95] and SPB sitting B=1.29 mmHg; 95% CI [0.12; 2.46]). Adjustment for potential confounding variables, such as other mother–infant dyad aspects, family hypertension and child’s BMI, only slightly attenuated the associations (SBP supine B=0.99 mmHg; 95% CI [0.06; 1.93] and SPB sitting B=1.11 mmHg; 95% CI [−0.06; 2.27]). Maternal verbally aggressive behavior was not associated with diastolic blood pressure or heart rate at age 5–6. Maternal verbally aggressive behavior might be an important early life stressor with negative impact on blood pressure later in life, which should be further investigated. Possible underlying mechanisms are discussed.

It is now well accepted that exposure to adverse environmental conditions in utero can predispose a fetus to disease later in life. Using an avian model to study the programming of disease has a unique advantage as it allows isolation of the direct effects of adverse conditions on fetal physiology, without any confounding effects via the mother or placenta. However, experiments in avian models are limited by the lack of well-established surgical protocols for the adult bird, which we have established in this study. Surgery was performed on seven young adult Bovan Brown chickens (body weight 1617±214 g, mean±s.d.) in order to instrument them with femoral arterial and venous catheters and a femoral arterial flow probe. Isoflurane and lidocaine were both found to have depressive effects on chicken cardiovascular function. Optimised methods of anaesthesia, intraoperative monitoring, surgical approach, postoperative care, and experimentation are described. Chickens recovered rapidly from surgery without significant blood gas perturbation, and basal in vivo cardiovascular studies were performed following 5 days of recovery. These techniques allow detailed investigation of avian cardiometabolic function, permitting determination of the consequences in later life of direct environmental insults to fetal physiology, isolated from additional effects on maternal physiology and/or placental endocrinology.

Intrauterine growth restriction in animal models reduces heart size and cardiomyocyte number at birth. Such incomplete cardiomyocyte endowment is believed to increase susceptibility toward cardiovascular disease in adulthood, a phenomenon referred to as developmental programming. We have previously described a mouse model of impaired myocardial development leading to a 25% reduction of cardiomyocyte number in neonates. This study investigated the response of these hypoplastic hearts to pressure overload in adulthood, applied by abdominal aortic constriction (AAC). Echocardiography revealed a similar hypertrophic response in hypoplastic hearts compared with controls over the first 2 weeks. Subsequently, control mice develop mild left ventricular (LV) dilation, wall thinning and contractile dysfunction 4 weeks after AAC, whereas hypoplastic hearts fully maintain LV dimensions, wall thickness and contractility. At the cellular level, controls exhibit increased cardiomyocyte cross-sectional area after 4 weeks pressure overload compared with sham operated animals, but this hypertrophic response is markedly attenuated in hypoplastic hearts. AAC mediated induction of fibrosis, apoptosis or cell cycle activity was not different between groups. Expression of fetal genes, indicative of pathological conditions, was similar in hypoplastic and control hearts after AAC. Among various signaling pathways involved in cardiac hypertrophy, pressure overload induces p38 MAP-kinase activity in hypoplastic hearts but not controls compared with the respective sham operated animals. In summary, based on the mouse model used in this study, our data indicates that adult hearts after neonatal cardiac hypoplasia show an altered growth response to pressure overload, eventually resulting in better functional outcome compared with controls.

Animal and cross-sectional epidemiological studies suggest that prenatal lead exposure is related to delayed menarche, but this has not been confirmed in longitudinal studies. We analyzed this association among 200 girls from Mexico City who were followed since the first trimester of gestation. Maternal blood lead levels were analyzed once during each trimester of pregnancy, and daughters were asked about their first menstrual cycle at a visit between the ages of 9.8 and 18.1 years. We estimated hazard ratios (HRs) and 95% confidence intervals (CI) for probability of menarche over the follow-up period using interval-censored Cox models, comparing those with prenatal blood lead level ⩾5 µg/dl to those with prenatal blood lead <5 µg/dl. We also estimated HRs and 95% CI with conventional Cox regression models, which utilized the self-reported age at menarche. In adjusted analyses, we accounted for maternal age, maternal parity, maternal education, and prenatal calcium treatment status. Across trimesters, 36−47% of mothers had blood lead levels ⩾5 µg/dl. Using interval-censored models, we found that during the second trimester only, girls with ⩾5 µg/dl prenatal blood lead had a later age at menarche compared with girls with prenatal blood lead levels <5 µg/dl (confounder-adjusted HR=0.59, 95% CI 0.28–0.90; P=0.05). Associations were in a similar direction, although not statistically significant, in the conventional Cox regression models, potentially indicating measurement error in the self-recalled age at menarche. In summary, higher prenatal lead exposure during the second trimester could be related to later onset of sexual maturation.

An inverse association between offspring birth weight (BW) and higher risk of parental cardiovascular disease (CVD) mortality and morbidity has been reported. Shared environmental, genetic and intrauterine factors may be responsible for explaining these associations. We studied the role of parental CVD risk factors in the association between offspring BW and CVD mortality among mothers and fathers. All births registered in Medical Birth Registry Norway (1967–2012) were linked to three health surveys, National Educational Registry and Cause of Death Registry. Number of births with information of parental CVD risk factors available for the analyses was 1,006,557 (520,670 for mothers and 485,887 for fathers). Cox proportional hazards regression models were used, following CVD deaths in parents from 1974 to 2012. An inverse association between offspring BW and CVD mortality was observed among both parents: hazard ratio 1.60 (1.44–1.75) for mothers and 1.16 (1.10–1.23) for fathers. Among mothers, adjustment for smoking, triglycerides and diabetes reduced the risk to 1.36 (1.25–1.52), 1.57 (1.43–1.73) and 1.58 (1.43–1.79), respectively. Adjustment for diastolic blood pressure (DBP) and systolic blood pressure (SBP) both reduced the risk to 1.53 (1.37–1.66). Among fathers, adjustments for smoking, DBP, SBP reduced the risk to 1.08 (1.02–1.15), 1.13 (1.06–1.19) and 1.14 (1.08–1.22), respectively. Triglycerides and diabetes both reduced the risk to 1.15 (1.09–1.12). Our results indicate that shared environmental factors might be important in the association. A stronger association in mothers suggest that intrauterine factors also are at play.