Maternal caffeine intake during pregnancy is associated with risk of low birth weight: a systematic review and dose-response meta-analysis

Background: Considerable controversy exists regarding the relation between maternal caffeine intake during pregnancy and risk of low birth weight (birth weight <2,500 g). We aim to assess this association using a systematic review and dose-response meta-analysis of prospective studies. Methods: Potential articles were identified by searching MEDLINE and SCOPUS databases through 17 July 2013. Two authors independently extracted information on study design, participant characteristics and estimates of associations. Random-effects models were used to derive the summary relative risks (RRs) and corresponding 95% confidence intervals (CIs). Dose-response relationships were assessed using generalized least-squares trend estimation. Results: In our meta-analysis, we included 13 prospective studies: 9 with low birth weight as a binary outcome variable (90,747 participants and 6,303 cases) and 6 with birth weight as a continuous outcome variable (10,015 participants; 2 studies reported both types of outcomes). Compared with the reference category with no or very low caffeine intake, the RR (95% CI) of low birth weight was 1.13 (1.06 to 1.21; I-2 0.0%) for low intake (50 to 149 mg/day), 1.38 (1.18 to 1.62; I-2 31.9%) for moderate intake (150 to 349 mg/day), and 1.60 (1.24 to 2.08; I-2 65.8%) for high intake (>= 350 mg/day). In the dose-response analysis, each 100-mg/day increment in maternal caffeine intake (around one cup of coffee) was associated with 13% (RR 1.13, 1.06 to 1.21) higher risk of low birth weight. The association persisted in strata defined according to various study characteristics. Moderate (-33 g, 95% CI -63 to -4; I-2 0.3%) and high (-69 g, 95% CI -102 to -35; I-2 0.0%) caffeine intakes were also associated with a significantly lower birth weight as compared with the reference category. Conclusions: Higher maternal caffeine intake during pregnancy was associated with a higher risk of delivering low birth weight infants. These findings support recommendations to restrict caffeine intake during pregnancy to low levels.