Offspring Adult Health Research Articles

Prediction, medical illness and the risk of pre-eclampsia.

Preeclampsia, the leading cause of maternal and perinatal morbidity and mortality, has been recently considered not only a pregnancy disease but also a risk factor for developing diseases later in life. Preeclampsia is becoming a disease of interest to internists and not just obstetricians. Women who have had preeclampsia seem to be at higher risk of premature death, mortality from ischemic heart disease, cardiovascular diseases including ischemic heart disease and hypertension, fatal and non-fatal stroke, venous thromboembolism.renal failure, type 2 diabetes mellitus, hypothyroidism, and cognitive defects, although they appear surprisingly protected from cancer. Furthermore, having had preeclampsia isa problem not only for the mother's future health, but it also affects the offspring's adult health. Children born from preeclamptic pregnancies are more prone to hypertension, insulin resistance and diabetes mellitus, neurological problems, stroke, and mental disorders along their life.Whether preeclampsia is a risk factor for disease later in life or it creates long-term organ damage is an intriguing question. Understanding the etiological background may provide guidance for the prevention and follow-up of women who experience preeclampsia.

241 EFFECT OF MATERNAL PERICONCEPTIONAL UNDERNUTRITION ON MALE OFFSPRING PHYSIOLOGY AND TESTICULAR DEVELOPMENT

Epidemiological studies in humans, as well as animal models, have shown that maternal environment at critical periods of fetal development can condition offspring adult health. Previous studies have shown effects of maternal undernutrition during early to mid gestation on Sertoli cell proliferation and seminiferous tubule diameter in male lambs of 10 months of age. Delayed follicular maturation and meiosis in female fetuses have been reported after maternal undernutrition from mating. The aim of this project was to evaluate the long-term effects of maternal periconceptional undernutrition on offspring physiology and reproductive function. Postnatal development of male offspring is presented here. Fifty-two control females of Merinos d’Arles breed (R100) were fed a normal diet adapted to their needs, and 64 restricted females (R50) received 50% of their dietary needs from 15 days before until 30 days after synchronized breeding. Thereafter, both groups were fed to meet their nutritional requirements. Males were weighed at birth and every week. Blood samples were collected monthly to monitor plasma leptin and cortisol concentrations. Organ weights were recorded at commercial slaughter (35 kg) and histological analysis was performed on testicles and adrenals. Data were analysed by ANOVA or Student’s test. Twenty-two live R100 and 34 live R50 male lambs were obtained. Gestation was significantly longer in the restricted group (P < 0.01). Growth rate, live weight, and age at slaughter were not significantly different between groups. Plasma leptin concentrations were significantly lower at birth (P < 0.001) and tended to be higher at 4 months of age (P = 0.09) in R50. There was a significant interaction between group, age, and litter size for basal cortisol concentrations: in singletons (n = 15 R50 and n = 8 R100), cortisol was significantly lower in R50 at 3 months of age (P < 0.05) and tended to be higher at 4 months whereas in twins (n = 17 R50 and n = 10 R100), cortisol was significantly lower at birth (P < 0.05) but not thereafter (triplets were not considered here because of low numbers). There was no statistical difference for carcass, testicle, or kidney weight. In contrast, carcass to live weight ratio and perirenal fat to live weight ratio were increased in all R50 (P < 0.05). Adrenal to live weight ratio tended to be increased in R50 lambs (P = 0.06). Histological examination revealed no statistical difference between groups for adrenal corticomedullary ratio, zona glomerulosa to medulla ratio, and zona fasciculata to medulla ratio. There was no significant difference for the analysis of testicular tissue (diameter and surface of seminiferous tubules). The expression of genes involved in testicular differentiation (SRY, 3β-HSD, OCT3/4, VASA, stra8, SOX9) is currently being studied by quantitative PCR and will be presented. These results confirm the effects of periconceptional undernutrition on metabolic function but so far, no effect has been demonstrated on testicular histology. Litter size seems to play an important role, because effects were different between singletons and twins.

Early onset of coronary artery disease after prenatal exposure to the Dutch famine1–3

Limited evidence suggests that maternal undernutrition at the time of conception is associated with increased cardiovascular disease risk in adult offspring. We investigated whether persons conceived during the Dutch famine of World War II had an early onset of coronary artery disease (CAD). We compared the age at onset and cumulative incidence of CAD between persons born as term singletons who were exposed to the 1944-1945 Dutch famine during late (n = 160), mid- (n = 138), or early (n = 87) gestation and 590 unexposed subjects at age 50 or 58 y. Age at CAD onset was defined as the age at which angina pectoris was identified (according to the Rose questionnaire), Q waves were observed on an electrocardiogram (Minnesota codes 1-1 or 1-2), or coronary revascularization was performed (by angioplasty or bypass surgery). Of the 83 CAD cases identified, persons conceived during the famine were 3 y younger than the unexposed persons at the time of CAD diagnosis (47 y compared with 50 y) and had a higher cumulative incidence of CAD [13%; hazard ratio (HR) adjusted for sex: 1.9; 95% CI: 1.0, 3.8] than did the unexposed persons. The HR changed little after adjustment for smoking (HR: 1.8), social class (HR: 2.0), or size at birth (HR: 2.0). We found an earlier onset of CAD among persons conceived during the famine, which suggests that maternal nutrition in early gestation may play a role in the onset of CAD. This finding agrees with evidence from animal experiments that identify periconceptional maternal diet as important in the offspring's adult health.