Mendelian randomization study of maternal coffee consumption and its influence on birthweight, stillbirth, miscarriage, gestational age and pre-term birth

Abstract

Background: Coffee consumption has been associated with several adverse pregnancy outcomes, although data from randomized-controlled trials are lacking. We investigate whether there is a causal relationship between coffee consumption and miscarriage, stillbirth, birthweight, gestational age and pre-term birth using Mendelian randomization (MR).

Methods: A two-sample MR study was performed using summary results data from a genome-wide association meta-analysis of coffee consumption (N = 91 462) from the Coffee and Caffeine Genetics Consortium. Outcomes included self-reported miscarriage (N = 49 996 cases and 174 109 controls from a large meta-analysis); the number of stillbirths [N = 60 453 from UK Biobank (UKBB)]; gestational age and pre-term birth (N = 43 568 from the 23andMe, Inc cohort) and birthweight (N = 297 356 reporting own birthweight and N = 210 248 reporting offspring's birthweight from UKBB and the Early Growth Genetics Consortium). Additionally, a one-sample genetic risk score (GRS) analysis of coffee consumption in UKBB women (N up to 194 196) and the Avon Longitudinal Study of Parents and Children (N up to 6845 mothers and 4510 children) and its relationship with offspring outcomes was performed.

Results: Both the two-sample MR and one-sample GRS analyses showed no change in risk of sporadic miscarriages, stillbirths, pre-term birth or effect on gestational age connected to coffee consumption. Although both analyses showed an association between increased coffee consumption and higher birthweight, the magnitude of the effect was inconsistent.

Conclusion: Our results suggest that coffee consumption during pregnancy might not itself contribute to adverse outcomes such as stillbirth, sporadic miscarriages and pre-term birth or lower gestational age or birthweight of the offspring.

Keywords: ALSPAC; Mendelian randomization; UK Biobank; birthweight; coffee; gestational age; maternal genetic effect; miscarriage; pre-term birth; stillbirth.

Figure 1

Overview of data sources and phenotypes used in the two-sample MR, individual-level MR and traditional observational analysis. GRS, genetic risk score; MR, Mendelian randomization; UKBB, UK Biobank; ALSPAC, Avon Longitudinal Study of Parents and Children; EEG, Early Growth Genetics.

Figure 2

Overview of the effect estimates and 95% confidence intervals for the two-sample MR analyses per cup of coffee consumed per day. We did not observe a causal effect of coffee consumption (defined as cups per day) on any of the traits analyzed, although there was evidence of a small effect of increased coffee consumption on increased birthweight for the six SNP analysis. Birthweight was analyzed as a Z-score. Miscarriages were defined as the log(OR) of having had one to two spontaneous miscarriages [case control Genome Wide Association Study (GWAS)], stillbirth was defined as the number of self-reported incidents of stillbirth [http://www.nealelab.is/uk-biobank (10 December 2020, date last accessed)], gestational age was defined as self-reported length of gestation and preterm birth was defined as the log(OR) (log of the odds ratio) of having any birth at <37 weeks of gestation (case control GWAS). The units for the causal effects are per unit increase in the outcome per extra cup of coffee consumed per day. MR, Mendelian randomization; SNP, single nucleotide polymorphism.