Low Birth Weight
A Novel Cardiovascular Risk Factor?
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See Article by Zanetti et al
Low birth weight has long been associated with increased risk for coronary artery disease (CAD), type 2 diabetes mellitus (T2D), and arterial hypertension in adult life.1 The fetus origins hypothesis launched by Barker was a paradigm shift proposing that undernutrition in utero or during infancy may be an important determinant for major chronic diseases. Epidemiological studies have previously demonstrated an inverse association between low birth weight and occurrence of diabetes mellitus, ischemic heart disease, hypertension, or stroke.2,3
Association, however, does not show the presence of a causative relationship. Despite strong accumulating evidence that intrauterine growth is associated with cardiovascular disease, causality is yet to be proven. Observational studies face inherent problems of confounding, reverse causality, and information bias. Although a randomized clinical trial is considered the gold standard to establish causality between a biomarker and a disease outcome, this is not always feasible, like in the case of birth weight.
Genome-wide associated studies provide evidence of whether a genetic variant is associated with a trait by unbiased genome screening of the population. Recently, a multiancestry genome-wide association study meta-analysis of birth weight in 153 781 individuals has identified 60 loci where fetal genotype was associated with birth weight accounting for up to 15% of variance in birth weight.4 Most importantly, using genetic association alone, the same study reported a strong inverse association between low birth weight and systolic blood pressure (BP), T2D or CAD, possibly by interfering with insulin signaling, glucose homeostasis, glycogen biosynthesis, and chromatin remodeling. …