Evidence of Arteriolar Narrowing in Low-Birth-Weight Children

Abstract

Background-Cardiovascular disease may have its origins in utero, but the influence of in utero growth on microvascular structure in children is unknown. We hypothesized that poor in utero growth is associated with narrower arteriolar caliber, which may help explain the established association of low birth weight with hypertension and cardiovascular disease in adulthood. Methods and Results-We examined the relation of birth weight and other markers of in utero growth to microvascular caliber in the retina in a population-based study of 1369 6-year-old children in Sydney, Australia (Sydney Childhood Eye Study). Birth weight, birth length, and head circumference were obtained from parental records. Retinal arteriolar and venular calibers were measured from digitized retinal photographs by a validated computer-assisted method. Lower birth weight, shorter birth length, and smaller head circumference were associated with narrower retinal arteriolar caliber. Each kilogram decrease in birth weight was associated with a 2.3-m (95% CI 0.6 to 3.9, Pϭ0.01) narrower retinal arteriolar caliber after controlling for age, gender, ethnicity, height, body mass index, axial length, mean arterial blood pressure, and prematurity. Similar associations were observed between shorter birth length and smaller head circumference with narrower retinal arteriolar caliber. Conclusions-Children who had lower birth weight, shorter birth length, and smaller head circumference had narrower retinal arteriolar calibers. These data support the concept that poor in utero growth may have an adverse influence on microvascular structure. (Circulation. 2008;118:518-524.)

Effect of Birth Parameters on Retinal Vascular Caliber

“…31 The relatively small sample size and the issue of statistical power in this study highlight the need for larger twin studies of more precise analysis in this area. Because our cohort was not large, some of the null findings reported may partially reflect inadequate statistical power, although the lack of influence of birth parameters on retinal venular caliber is consistent across all twin subtypes and is in agreement with estimates from singletons 7,8 and with previous observations of no association of venular caliber with blood pressure. 32,33 The association between gestational duration and retinal arteriolar caliber in this study was not independent of birth weight.…”

“…Twin studies provide insights into whether the association between birth size and retinal vascular structure reported in previous studies in children and adults 7-10 is because of shared environment (eg, maternal factors), common genetic factors, or other pathways associated with individual twins. Thus, our findings add further insights into studies from a 6-year-old singleton childhood population 7 and the Atherosclerosis Risk in Communities Study (general population aged 51 to 72 years), which found that lower birth size (eg, birth weight) was associated with narrower retinal arterioles. 8 We found that the overall associations strengthened with increased magnitude in models with further adjusting for mean arterial blood pressure, BMI, and child height, reflecting that it was not the individual-specific differences in these later child factors that contributed to the association between shorter birth length and narrower arteriolar caliber.…”

“…Using new computer-based retinal imaging techniques, we have shown that precisely measured retinal arteriolar narrowing is a strong marker for the development of hypertension and cardiovascular events, including myocardial infarction. 4 -6 New studies now demonstrate that lower birth weight is associated with narrower retinal arterioles, 7,8 narrower bifurcation angle, 9 higher retinal vessel tortuosity, and optimality deviance, 10 providing initial evidence that fetal origins of cardiovascular disease may partly be mediated by the microcirculation. However, it could be argued that the association between birth weight and microvascular alternation may be confounded by genetic or shared environmental factors (eg, maternal nutrition) that affect both birth size and abnormal microvascular structural development.…”

Retinal nerve fiber layer thickness in prematurity is correlated with stage of retinopathy of prematurity

“…Another possible explanation for the thinning of the RNFL in the sectors except for the temporal sector is artifacts from the vessels. It has been reported that children with low birth weight have narrower arterioles, 19 and arteriolar caliber is positively correlated with RNFL thickness and macular thickness. [20][21][22] Therefore, narrower vessels in preterm children compared with normal full-term controls could induce artifactually thinned RNFL measured by OCT. 23 Further histologic studies could help to clarify this idea.…”

Effects of early-life environment and epigenetics on cardiovascular disease risk in children: highlighting the role of twin studies

“…However, the cross-sectional nature of these studies does not allow for causal inferences. A recent study also demonstrates that poor growth in utero may have an adverse influence on retinal vasculature in children (29).…”