Limitations of models used to examine the influence of nutrition during pregnancy and adult disease

Compromised growth in utero is associated with prematurity and complications after birth. It has been proposed that poor intrauterine growth not only contributes to increased morbidity and mortality during infancy but also has the potential to compromise adult health and wellbeing. Over the past decade, epidemiological studies in several countries have shown that size at birth and/or placental weight predict adult health and disease. It has also been proposed that maternal undernutrition at critical stages of gestation can aVect fetal growth and body shape. These eVects may be mediated in part by changes in placental growth, as some studies have suggested that fetal:placental weight ratio at birth is a predictor of adult disease. Fetal:placental weight ratio in healthy human pregnancies at term is approximately 5:1 but disease states can lead to alterations in this ratio. Intrauterine growth restriction is often accompanied by a light placenta in both humans and sheep, whereas the hydropic infant may have a large oedematous placenta and diabetic women produce a large infant and a heavy placenta. As recently stated by Leon, there is a large weight of evidence linking altered size at birth to adult cardiovascular disease. However, scepticism still persists as to the influence of maternal and/or fetal nutrition as a potential cause of adverse fetal growth. A major reason for this scepticism is that the findings from Barker’s and related studies are largely based on epidemiological evidence. Attempts to confirm or refute Barker’s hypothesis using data from human pregnancies have only made limited progress because long term experimental, and/or intervention studies, are diYcult to undertake or ethically not possible. Consequently, investigators have used alternative human studies including prospective cohort studies or “experiments of nature” such as twinning. It is the aim of the present discussion to consider the potential problems of such approaches in view of related findings from complementary animal models.