Birth weight, physical morbidity, and mortality: a population-based sibling-comparison study

Abstract

Associations between low birth weight (≤2,500 g) and increased risk of mortality and morbidity provided the foundation for the "developmental origins of health and disease" hypothesis. Previous between-family studies could not control for unmeasured confounders. Therefore, we compared differentially exposed siblings to estimate the extent to which the associations were due to uncontrolled factors. Our population cohort included 3,291,773 persons born in Sweden from 1973 to 2008. Analyses controlled for gestational age, among other covariates, and considered birth weight as both an ordinal and a continuous variable. Outcomes included mortality after 1 year, cardiac-related death, hypertension, ischemic heart disease, pulmonary circulation problems, stroke, and type 2 diabetes mellitus. We fitted fixed-effects models to compare siblings and conducted sensitivity analyses to test alternative explanations. Across the population, the lower the birth weight, the greater the risk of mortality (e.g., cardiac-related death (low birth weight hazard ratio = 2.69, 95% confidence interval: 2.05, 3.53)) and morbidity (e.g., type 2 diabetes mellitus (low birth weight hazard ratio = 1.79, 95% confidence interval: 1.50, 2.14)) outcomes in comparison with normal birth weight. All associations were independent of shared familial confounders and measured covariates. Results emphasize the importance of birth weight as a risk factor for subsequent mortality and morbidity.

Keywords: birth weight; cardiovascular diseases; diabetes mellitus; fetal development; stroke.

Figure 1.

Associations derived from continuous (lines) and ordinal (columns) representations of birth weight when predicting mortality outcomes among offspring born in Sweden during 1973–2007 (death after first year; part A) and 1973–1995 (cardiac-related death; part B). Baseline, population-wide estimates are shown via the solid lines and dark gray columns. Results from sibling-comparison, fixed-effects models are shown via the dotted lines and light gray columns. I-shaped bars, 95% confidence intervals.

Figure 2.

Associations derived from continuous (lines) and ordinal (columns) representations of birth weight when predicting hypertension (A), ischemic heart disease (B), pulmonary circulation problems (C), stroke (D), and type 2 diabetes mellitus (E) among offspring born in Sweden during 1973–1995. Baseline, population-wide estimates are shown via the solid lines and dark gray columns. Sibling-comparison, fixed-effects models are shown via the dotted lines and light gray columns. I-shaped bars, 95% confidence intervals.