Maternal caffeine intake during pregnancy and risk of pregnancy loss: a categorical and dose-response meta-analysis of prospective studies

Abstract

Objective: To assess the association between maternal caffeine intake and risk of pregnancy loss using a systematic review and meta-analysis.

Design: Categorical and dose-response meta-analysis of prospective studies.

Setting: Relevant articles were identified by searching MEDLINE and SCOPUS databases through 30 January 2015. Two authors independently extracted information from eligible studies. Random-effects models were used to derive the summary relative risks (RR) and corresponding 95% CI for specific categories of caffeine consumption and for a continuous association using generalized least-squares trend estimation.

Subjects: A total of 130 456 participants and 3429 cases in fourteen included studies.

Results: Compared with the reference category with no or very low caffeine intake, the RR (95% CI) of pregnancy loss was 1·02 (0·85, 1·24; I(2)=28·3%) for low intake (50-149 mg/d), 1·16 (0·94, 1·41; I 2=49·6%) for moderate intake (150-349 mg/d), 1·40 (1·16, 1·68; I(2)=18·6%) for high intake (350-699 mg/d) and 1·72 (1·40, 2·13; I(2)=0·0%) for very high intake (≥ 700 mg/d). In the dose-response analysis, each 100 mg/d increment in maternal caffeine intake (~1 cup of coffee) was associated with 7% (95% CI 3%, 12%) higher risk of pregnancy loss. Our results may have been affected by publication bias, but the association remained significant for the subset of larger studies. Furthermore, adjustment for smoking and pregnancy symptoms may have been incomplete, potentially resulting in residual confounding.

Conclusions: Albeit inconclusive, higher maternal caffeine intake was associated with a higher risk of pregnancy loss and adherence to guidelines to avoid high caffeine intake during pregnancy appears prudent.

Keywords: Caffeine; Coffee; Miscarriage; Pregnancy; Pregnancy loss; Spontaneous abortion; Stillbirth.

Fig. 1

Flowchart of study selection

Fig. 2

Relative risk (RR) of pregnancy loss according to maternal caffeine intake: low caffeine intake, 50–149 mg/d; moderate caffeine intake, 150–349 mg/d; high caffeine intake, 350–699 mg/d; very high caffeine intake, ≥700 mg/d. The study-specific estimates and 95 % CI are indicated by the black dots and the horizontal lines, respectively; the size of the grey squares corresponds to the weight of the studies in the meta-analysis. The centre of the diamonds indicates the summary estimates and the width of the diamonds the corresponding 95 % CI

Fig. 3

Dose–response relationship between maternal caffeine intake and pregnancy loss (n 11). Adjusted relative risk (RR; ————) and 95 % CI (- - - - - -) are reported. Caffeine intake was modelled with a linear trend (P for non-linearity=0·44) in a random-effects model. The vertical axis is on a log scale; — — — — indicates RR=1. The open circles represent the effect estimates from each study and the size of the circles is proportional to the precision of the estimates. The studies by Mills et al.^{( 40 )} and Pollack et al.^{( 36 )} were not included in this plot as they did not provide results for categories of caffeine intake

Fig. 4

Funnel plot with pseudo 95 % confidence limits (– – – – –) for maternal caffeine intake and pregnancy loss (RR, relative risk). There was a suggestion of publication bias in Egger’s (P<0·01) and Begg’s test (P=0·047)