Birth Weight and Risk of Type 2 Diabetes Mellitus, Cardiovascular Disease, and Hypertension in Adults: A Meta-Analysis of 7 646 267 Participants From 135 Studies

Abstract

Background Low birth weight has been associated with increased risk of type 2 diabetes mellitus, cardiovascular disease, and hypertension, but the risk at high birth weight levels remains uncertain. This systematic review and meta-analysis aimed to clarify the shape of associations between birth weight and aforementioned diseases in adults and assessed sex-specific risks. Methods and Results We systematically searched PubMed, EMBASE , and Web of Science for studies published between 1980 and October 2016. Studies of birth weight and type 2 diabetes mellitus (T2 DM ), cardiovascular disease ( CVD ), and hypertension were included. Random-effects models were used to derive the summary relative risks and corresponding 95% confidence intervals.We identified 49 studies with 4 053 367 participants assessing the association between birth weight and T2 DM , 33 studies with 5 949 477 participants for CVD , and 53 studies with 4 335 149 participants for hypertension and high blood pressure. Sex-specific binary analyses showed that only females had an increased risk of T2 DM and CVD at the upper tail of the birth weight distribution. While categorical analyses of 6 birth weight groups and dose-response analyses showed J-shaped associations of birth weight with T2 DM and CVD , the association was inverse with hypertension. The lowest risks for T2 DM , CVD , and hypertension were observed at 3.5 to 4.0, 4.0 to 4.5, and 4.0 to 4.5 kg, respectively. Conclusions These findings indicate that birth weight is associated with risk of T2 DM and CVD in a J-shaped manner and that this is more pronounced among females.

Keywords: birth weight; cardiovascular disease; hypertension; type 2 diabetes mellitus.

Figure 1

Summary of article selection process. DM indicates diabetes mellitus.

Figure 2

Meta‐analyses of sex‐neutral (N) and sex‐specific (M/F) associations between birth weight and type 2 diabetes mellitus, cardiovascular disease, and hypertension. Birth weight is presented as a continuous variable to assess risk per 1 kg increase in birth weight and as a binary variable with 3 different cut‐offs (2.5, 4.0, and 4.5 kg). Circles represent the pooled exponentiated log‐transformed risk estimates from a random‐effects model, horizontal lines their confidence interval, and I² the heterogeneity detected in each meta‐analysis. The “n” is the number of studies contributing to the pooled risk estimate. Several studies only provide sex‐neutral estimates. Therefore, the number of studies contributing to sex‐specific meta‐analyses do not add up to the number of studies for the corresponding sex‐neutral meta‐analysis. CI indicates confidence interval; M, male; N, neutral; F, female.

Figure 3

Shape of association between birth weight and type 2 diabetes mellitus, cardiovascular disease, and hypertension. The circles represent the exponentiated log‐transformed pooled‐risk estimate within 6 birth weight groups and the vertical lines their confidence interval. The “n” is the number of studies contributing to the pooled risk estimate within a birth weight group. Risk estimates (95% confidence interval) in (A) (risk of type 2 diabetes mellitus): <2.5 kg (1.507 [1.331; 1.706]), 2.5 to 3.0 kg (1.205 [1.115; 1.302]), 3.0 to 3.5 kg (1.064 [0.963; 1.176]), 3.5 to 4.0 kg (0.989 [0.954; 1.026]), 4.0 to 4.5 kg (ref.), >4.5 (1.189 [1.044; 1.355]). Risk estimates (95% confidence interval) in (B) (risk of cardiovascular disease): <2.5 kg (1.335 [0.972; 1.834]), 2.5 to 3.0 kg (1.171 [0.993; 1.381]), 3.0 to 3.5 kg (1.118 [1.064; 1.175]), 3.5 to 4.0 kg (1.095 [0.979; 1.224]), 4.0 to 4.5 kg (ref.), >4.5 (1.221 [1.086; 1.372]). Risk estimates (95% confidence interval) in (C) (risk of hypertension): <2.5 kg (1.422 [1.231; 1.642]), 2.5 to 3.0 kg (1.216 [1.082; 1.368]), 3.0 to 3.5 kg (1.303 [1.222; 1.389]), 3.5 to 4.0 kg (1.065 [0.998; 1.138]), 4.0 to 4.5 kg (ref.), >4.5 (1.058 [0.914; 1.226]).

Figure 4

Dose‐response relationship between birth weight and type 2 diabetes mellitus, cardiovascular disease, and hypertension. The solid regression curves represent point estimates of association, and the dashed lines are the corresponding 95% confidence interval. Grey circles are risk estimates within birth weight groups relative to the reference group (4.0–4.5 kg), which has been connected (grey lines) for the individual studies. A total of 15, 12, and 12 studies provided 73, 71, and 54 estimates of the association between birth weight and type 2 diabetes mellitus (A), cardiovascular disease (B) and hypertension (C), respectively.