Objective We previously showed that maternal under-nutrition during gestation is associated with increased metabolic and cardiovascular disease in the offspring. Also, we found increased neonatal adiposity among the grandchildren of women who had been undernourished during pregnancy. In the present study we investigated whether these transgenerational effects have led to altered body composition and poorer health in adulthood in the grandchildren.Design Historical cohort study.Setting Web-based questionnaire.Population The adult offspring (F2) of a cohort of men and women (F1) born around the time of the 1944-45 Dutch famine.Methods We approached the F2 adults through their parents. Participating F2 adults (n = 360, mean age 37 years) completed an online questionnaire.Main outcome measures Weight, body mass index (BMI), and health in F2 adults, according to F1 prenatal famine exposure.Results Adult offspring (F2) of prenatally exposed F1 fathers had higher weights and BMIs than offspring of prenatally unexposed F1 fathers (+4.9 kg, P = 0.03; +1.6 kg/m², P = 0.006). No such effect was found for the F2 offspring of prenatally exposed F1 mothers. We observed no differences in adult health between the F2 generation groups.Conclusions Offspring of prenatally undernourished fathers, but not mothers, were heavier and more obese than offspring of fathers and mothers who had not been undernourished prenatally. We found no evidence of transgenerational effects of grandmaternal under-nutrition during gestation on the health of this relatively young group, but the increased adiposity in the offspring of prenatally undernourished fathers may lead to increased chronic disease rates in the future.
Background There is evidence that hyperemesis gravidarum (HG) is associated with a predominance of female fetuses, lower birthweights and shorter gestational ages at birth. As the adverse effects of prematurity and low birthweight on disease risk in later life have become increasingly clear, the repercussions of HG might not be limited to adverse perinatal outcomes.Objectives To summarise the evidence on short-and long-term outcomes of pregnancies with HG.Search strategy A literature search was conducted in the electronic databases Medline and Embase.Selection criteria Studies were included that reported on the fetal, neonatal and long-term outcome of pregnancies complicated by HG.Data collection and analysis Two authors independently selected studies and extracted data. Meta-analysis was performed using review manager.Main results Women with HG during pregnancy were more likely to have a female child (OR 1.27; 95% CI 1.21-1.34). They were also more likely to have a baby with low birthweight (LBW, <2500 kg; OR 1.42; 95% CI 1.27-1.58) that was small for gestational age (SGA; OR 1.28; 95% CI 1.02-1.60), and to deliver prematurely (OR 1.32; 95% CI 1.04-1.68). There was no association with Apgar scores, congenital anomalies or perinatal death. One study described an association between HG and testicular cancer in the offspring.Author's conclusions There is evidence that HG is associated with a higher female/male ratio of offspring and a higher incidence of LBW, SGA and premature babies. Little is known about the longterm health effects of babies born to mothers whose pregnancies were complicated by HG.
Poor nutrition during fetal development can permanently alter growth, cardiovascular physiology and metabolic function. Animal studies have shown that prenatal undernutrition followed by balanced postnatal nutrition alters deoxyribonucleic acid (DNA) methylation of gene promoter regions of candidate metabolic control genes in the liver. The aim of this study was to investigate whether methylation status of the proximal promoter regions of four candidate genes differed between individuals exposed to the Dutch famine in utero. In addition, we determined whether methylation status of these genes was associated with markers of metabolic and cardiovascular disease and adult lifestyle. Methylation status of the GR1-C (glucocorticoid receptor), PPARγ (peroxisome proliferator-activated receptor gamma), lipoprotein lipase and phosphatidylinositol 3 kinase p85 proximal promoters was investigated in DNA isolated from peripheral blood samples of 759 58-year-old subjects born around the time of the 1944-45 Dutch famine. We observed no differences in methylation levels of the promoters between exposed and unexposed men and women. Methylation status of PPARγ was associated with levels of high-density lipoprotein cholesterol and triglycerides as well as with exercise and smoking. Hypomethylation of the GR promoter was associated with adverse adult lifestyle factors, including higher body mass index, less exercise and more smoking. The previously reported increased risk of cardiovascular and metabolic disease after prenatal famine exposure was not associated with differences in methylation status across the promoter regions of these candidate genes measured in peripheral blood. The adult environment seems to affect GR and PPARγ promoter methylation.
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