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

Abstract

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.

Figure 1

Flow chart of study selection.

Figure 2

Relative risks of low birth weight/IUGR/SGA according to maternal caffeine intake. Low caffeine intake: 50 to 149 mg/day; moderate caffeine intake: 150 to 349 mg/day; high caffeine intake: ≥350 mg/day. Black dots indicate study-specific effect estimates, sizes of the grey squares correspond to the weights of the studies, horizontal lines indicate 95% CIs, and diamonds indicate the summary estimates with their corresponding 95% CIs. CI, confidence interval; IUGR, intrauterine growth restriction; SGA, small for gestational age.

Figure 3

Dose–response relationship between maternal caffeine intake and low birth weight/IUGR/SGA (n = 7). Adjusted relative risks (RRs) and 95% CIs (dashed lines) are reported. Caffeine intake was modeled with a linear trend (P-value for non-linearity = 0.89) in a random-effects model. The vertical axis is on a log scale. The open circles represent the effect estimates from each study (the number of circles for a study depends on the number of caffeine intake categories in the study) and the size of the circles is proportional to the precision of the estimates. Mills et al.’s [23] and Sengpiel et al.’s [9] studies were not included in this graph as they did not provide sufficient results for categories of caffeine intake. CI, confidence interval; IUGR, intrauterine growth restriction; LBW, low birth weight; SGA, small for gestational age.

Figure 4

Birth weight difference according to maternal caffeine intake. Low caffeine intake: 50 to 149 mg/day; moderate caffeine intake: 150 to 349 mg/day; high caffeine intake: ≥350 mg/day. Black dots indicate study-specific effect estimates, sizes of the grey squares correspond to the weights of the studies, horizontal lines indicate 95% CIs and diamonds indicate the summary estimates with their corresponding 95% CIs. CI, confidence interval.