Commentary: are birthweight and cardiovascular associations due to fetal programming?

for an association between low birthweight (LBW) and various measures of cardiovascular risk. In addition, they suggest potential interactions between LBW and a positive family history of premature cardiovascular disease and maternal pre-eclampsia or hypertension during pregnancy in increasing offspring blood pressure. They conclude that ‘from a public health perspective, heredity was more important than low birthweight (LBW) for elevated systolic blood pressure’. The observation that birthweight is inversely associated with blood pressure is one of the most consistent and convincing features of the ‘fetal origins hypothesis’. 2 However, similar associations with other features of the insulin resistance syndrome (glucose intolerance, elevated triglycerides, central adiposity) remain more controversial. McKeigue has argued that ‘small baby syndrome’, the association of birthweight with high blood pressure, hyperinsulinaemia and glucose intolerance, does not generally include lipid abnormalities.3 In the study by Mogren and colleagues,1 raised triglycerides and cholesterol levels were seen for LBW but were inconsistent by gender. Low birthweight was paradoxically associated with reduced obesity. Measures of central adiposity, such as waist-hip ratio were not available but do correlate moderately with body mass index. The novel findings that a positive family history of cardiovascular disease and pre-eclampsia or pregnancy hypertension may interact with LBW in increasing risk of hypertension require replication. The markedly wide confidence intervals around both synergy indices indicate that there is no statistically significant interaction. Despite this, it is important to consider what these results tell us, assuming they are not merely chance occurrences. Foetal programming argues that undernutrition in utero permanently changes the body’s structure, physiology and metabolism and leads to a variety of chronic diseases in adult life.2 However, another possibility is the role of a common genetic mechanism that determines both intrauterine growth and later adult disease.3,4 In this case, a small baby with a positive family history or maternal hypertension may be a better marker for genetic factors contrary to the fetal programming hypothesis. Alternatively, genetic influences on blood pressure may influence intrauterine growth through the intermediary phenotype of maternal pre-eclampsia and hypertension. Higher maternal blood pressure, but not paternal blood pressure, has been shown to be associated with birthweight, but both maternal and paternal blood pressure were associated with offspring blood pressure with relatively similar effect estimates.5 Similarly, birthweight of offspring is inversely associated with both maternal and paternal risk of cardiovascular mortality, although the maternal association appears to be stronger.6 Previous studies have tried to differentiate inappropriately small babies by examining whether the effect of birth dimensions on adult outcomes is greater for small babies who are tall as compared to short in adulthood. The assumption is that such babies have experienced some form of uterine growth restraint which has resulted in worse growth in relation to their genetic potential. Post-natally, however, subsequent catch-up growth has enabled them to reach their appropriate growth trajectory. Mogren and colleagues1 claim to find further evidence in support of this observation,7 but in fact they cannot compare the risk of systolic hypertension (>160 mmHg) for LBW subjects with and without short stature as there were no subjects in the latter category. Their data for diastolic hypertension (>95 mmHg), however, (provided by authors in response to reviewers) show 862 INTERNATIONAL JOURNAL OF EPIDEMIOLOGY