Adults who had non-edematous severe acute malnutrition (SAM) during infancy (i.e., marasmus) have worse glucose tolerance and beta-cell function than survivors of edematous SAM (i.e., kwashiorkor). We hypothesized that wasting and/or stunting in SAM is associated with lower glucose disposal rate (M) and insulin clearance (MCR) in adulthood.

We recruited 40 nondiabetic adult SAM survivors (20 marasmus survivors (MS) and 20 kwashiorkor survivors (KS)) and 13 matched community controls. We performed 150-minute hyperinsulinaemic, euglycaemic clamps to estimate M and MCR. We also measured serum adiponectin, anthropometry, and body composition. Data on wasting (weight-for-height) and stunting (height-for-age) were abstracted from the hospital records.

Children with marasmus had lower weight-for-height z-scores (WHZ) (−3.8 ± 0.9 vs. −2.2 ± 1.4; P < 0.001) and lower height-for-age z-scores (HAZ) (−4.6 ± 1.1 vs. −3.4 ± 1.5; P = 0.0092) than those with kwashiorkor. As adults, mean age (SD) of participants was 27.2 (8.1) years; BMI was 23.6 (5.0) kg/m2. SAM survivors and controls had similar body composition. MS and KS and controls had similar M (9.1 ± 3.2; 8.7 ± 4.6; 6.9 ± 2.5 mg.kg−1.min−1 respectively; P = 0.3) and MCR. WHZ and HAZ were not associated with M, MCR or adiponectin even after adjusting for body composition.

Wasting and stunting during infancy are not associated with insulin sensitivity and insulin clearance in lean, young, adult survivors of SAM. These data are consistent with the finding that glucose intolerance in malnutrition survivors is mostly due to beta-cell dysfunction.

Prenatal low vitamin D may have consequences for bone health. By means of a nationwide mandatory vitamin D fortification programme, we examined the risk of fractures among 10–18-year-old children from proximate birth cohorts born around the date of the termination of the programme. For all subjects born in Denmark during 1983–1988, civil registration numbers were linked to the Danish National Patient Registry for incident and recurrent fractures occurring at ages 10–18 years. Multiplicative Poisson models were used to examine the association between birth cohort and fracture rates. The variation in fracture rates across birth cohorts was analysed by fitting an age-cohort model to the data. We addressed the potential modification of the effect of vitamin D availability by season of birth. The risk of fractures was increased among both girls and boys who were born before the vitamin D fortification terminated in 1985 (rate ratio (RR) exposed v. non-exposed girls: 1·15 (95 % CI 1·11, 1·20); RR exposed v. non-exposed boys: 1·11 (95 % CI 1·07, 1·14). However, these associations no longer persisted after including the period effects. There was no interaction between season of birth and vitamin D availability in relation to fracture risk. The study did not provide evidence that prenatal exposure to extra vitamin D from a mandatory fortification programme of 1·25 µg vitamin D/100 g margarine was sufficient to influence the risk of fractures in late childhood, regardless of season of birth. Replication studies are needed.

People who were small at birth have been shown to have an increased risk of CHD and chronic bronchitis in later life. These findings have led to the fetal origins hypothesis that proposes that the fetus adapts to a limited supply of nutrients, and in doing so it permanently alters its physiology and metabolism, which could increase its risk of disease in later life. The Dutch famine — though a historical disaster — provides a unique opportunity to study effects of undernutrition during gestation in humans. People who had been exposed to famine in late or mid gestation had reduced glucose tolerance. Whereas people exposed to famine in early gestation had a more atherogenic lipid profile, somewhat higher fibrinogen concentrations and reduced plasma concentrations of factor VII, a higher BMI and they appeared to have a higher risk of CHD. Though the latter was based on small numbers, as could be expected from the relatively young age of the cohort. Nevertheless, this is the first evidence in humans that maternal undernutrition during gestation is linked with the risk of CHD in later life. Our findings broadly support the hypothesis that chronic diseases originate through adaptations made by the fetus in response to undernutrition. The long-term effects of intrauterine undernutrition, however, depend upon its timing during gestation and on the tissues and systems undergoing critical periods of development at that time. Furthermore, our findings suggest that maternal malnutrition during gestation may permanently affect adult health without affecting the size of the baby at birth. This gives the fetal origins hypothesis a new dimension. It may imply that adaptations that enable the fetus to continue to grow may nevertheless have adverse consequences for health in later life. CHD may be viewed as the price paid for successful adaptations to an adverse intra-uterine environment. It also implies that the long-term consequences of improved nutrition of pregnant women will be underestimated if these are solely based on the size of the baby at birth. We need to know more about what an adequate diet for pregnant women might be. In general, women are especially receptive to advice about diet and lifestyle before and during a pregnancy. This should be exploited to improve the health of future generations.

Both intra-uterine and early childhood development contribute to the risk of developing CVD in adult life. We therefore evaluated the maternal, placental, fetal, birth, infant and childhood determinants of cardiovascular risk in a cohort of Afro-Jamaican children. The Vulnerable Windows Cohort is a longitudinal survey of 569 mothers and their offspring recruited from the first trimester. The offspring's anthropometry was measured at birth, at 6 weeks, every 3 months to 1 year and then every 6 months. At mean age 11·5 years, fasting blood was sampled for glucose, insulin and lipids. Analyses were confined to 296 women and their offspring who had complete data. Waist circumference (WC) was related to maternal weight and BMI, placental weight and to the size of the offspring in utero, at birth and the rate of growth in childhood (P < 0·05). Total cholesterol, TAG and glucose concentrations were unrelated to maternal, placental, fetal, neonatal and childhood measurements. Fasting insulin and homeostasis model assessment of insulin resistance were related to maternal weight and BMI (P < 0·05), but not after adjusting for WC. HDL-cholesterol was inversely related to placental and birth weight, and inversely related to weight and BMI throughout childhood (P < 0·001), but not after adjusting for WC. Systolic blood pressure was directly related to maternal weight, child's height, weight and BMI (P < 0·05), but not after adjustment for WC. Systolic blood pressure and fasting glucose concentration were inversely related to birth weight in boys but directly associated in girls. We concluded that maternal anthropometry during pregnancy, fetal size, and childhood growth rate contribute to cardiovascular risk factors in childhood.

Environmental perturbations during early mammalian development can affect aspects of offspring growth and cardiovascular health. We have demonstrated previously that maternal gestational dietary protein restriction in mice significantly elevated adult offspring systolic blood pressure. Therefore, the present study investigates the key mechanisms of blood pressure regulation in these mice. Following mating, female MF-1 mice were assigned to either a normal-protein diet (NPD; 18 % casein) or an isocaloric low-protein diet throughout gestation (LPD; 9 % casein), or fed the LPD exclusively during the pre-implantation period (3·5 d) before returning to the NPD for the remainder of gestation (Emb-LPD). All offspring received standard chow. At 22 weeks, isolated mesenteric arteries from LPD and Emb-LPD males displayed significantly attenuated vasodilatation to isoprenaline (P = 0·04 and P = 0·025, respectively), when compared with NPD arteries. At 28 weeks, stereological analysis of glomerular number in female left kidneys revealed no significant difference between the groups. Real-time RT-PCR analysis of type 1a angiotensin II receptor, Na+/K+ ATPase transporter subunits and glucocorticoid receptor expression in male and female left kidneys revealed no significant differences between the groups. LPD females displayed elevated serum angiotensin-converting enzyme (ACE) activity (P = 0·044), whilst Emb-LPD males had elevated lung ACE activity (P = 0·001), when compared with NPD offspring. These data demonstrate that elevated offspring systolic blood pressure following maternal gestational protein undernutrition is associated with impaired arterial vasodilatation in male offspring, elevated serum and lung ACE activity in female and male offspring, respectively, but kidney glomerular number in females and kidney gene expression in male and female offspring appear unaffected.