Caffeine, Coffee, and Pregnancy Loss
This is the first meta-analysis published in seven years to examine dose-response associations between caffeine or coffee consumption and pregnancy loss.
Study Background
WHAT
Is there a dose-response relationship between caffeine (including coffee) and pregnancy loss?
WHY
To update and expand upon existing research that examines the associations between caffeine, coffee, and miscarriage risks
HOW
“new one-stage random effect dose-response analytic approach”
Utilized PRISMA and MOOSE guidelines for overall approach to designing meta-analysis- see Supplementary Index
Searched Medline/Pubmed, Scopus, and ISI Web of Knowledge
Included observational studies published through May 2022
Evaluated evidence quality using GRADE approach
Did NOT limit studies based on publication language
Study selection, data extraction, and risk of bias discussed further in study here
Studies included: cohort or case-control studies of pregnant women with dietary caffeine or coffee intake, with outcomes of pregnancy loss (PL), miscarriage, or stillbirth
Statistics
Measured Odds Ratio (OR) in case-control studies and Relative Risk (RR) in cohort studies*
*OR and RR were considered practically equal in cohort studies due to low incidence of PL
Subgroup analyses controlled for BMI, smoking, alcohol, race, employment, education, and vitamin supplements
Additional details found on pages 3-4 of meta-analysis
Results
2253 records originally identified —> excluded all but 46 publications due to irrelevance, duplications, and not meeting inclusion criteria —> excluded all but 34 studies (18 cohort, 16 case-control) after a full review
7 included coffee consumption effect sizes; 25 included caffeine intake effect sizes; 2 included coffee AND caffeine intake effect sizes; 6 included prenatal coffee consumption; 10 included prenatal caffeine consumption; 12 included perinatal coffee consumption; 24 reported perinatal caffeine consumption
12 US studies (31, 544 participants) and 22 non-US studies (261,251 participants)
26 studies used dietary records or recall, 8 used food frequency questionnaire
Variable control of risk factors based on study —> 27/34 studies had a serious risk of bias; 7/34 showed moderate risk of bias, with the main issue being confounding
GRADE assessments: low for prenatal coffee and caffeine intake; moderate for perinatal coffee intake; very low for perinatal caffeine intake
Prenatal coffee consumption: significantly higher risk of PL (Pooled Effect Size (ES): 1.21; 95% CI: 1.01–1.43) but not case-control studies
Perinatal coffee consumption: significantly higher risk of PL (Pooled ES: 1.26; 95% CI: 1.04–1.57) in cohort and case-control (Pooled ES: 1.20; 95% CI: 1.19–6.41)
Prenatal caffeine consumption: association not of statistical significance
Perinatal caffeine consumption: significantly higher risk of PL in cohort (Pooled ES: 1.58; 95% CI: 1.23–2.01) and case-control studies (Pooled ES: 2.39; 95% CI: 1.69–3.37, P < 0.001)
Dose-response analysis:
each increase of 1 cup of coffee (cup measurements not defined in study) per day associated with 3% increased risk of PL (Pooled ES: 1.03, 95% CI 0.99-1. 07, P =0.002)
100 mg caffeine per day associated with 14% increase (cohort) and 26% increase (case-control) in PL
Authors’ Thoughts
Caffeine and coffee consumption in pregnancy may be associated with increased risks of PL
More research is needed to understand coffee’s and caffeine’s mechanisms and activity
This Pharmacist’s Thoughts
(+) wisely assumed they hadn’t captured all data and used random effects model, used multiple search methods (three databases) to locate data, included non-English studies, followed multiple tools and guidelines to guide study design
not a fault of this study, but most of the included studies could be subject to recall bias; confounding also noted
Conclusions
Higher quality studies will aid in more definitively understanding how much coffee and/or caffeine a woman can safely consume before or while pregnant.
Resources
Blehar MC, Spong C, Grady C, Goldkind SF, Sahin L, Clayton JA. Enrolling pregnant women: issues in clinical research. Womens Health Issues. 2013;23(1):e39-e45. doi:10.1016/j.whi.2012.10.003
Jafari A, Naghshi S, Shahinfar H, et al. Relationship between maternal caffeine and coffee intake and pregnancy loss: A grading of recommendations assessment, development, and evaluation-assessed, dose-response meta-analysis of observational studies. Front Nutr. 2022;9:886224. Published 2022 Aug 9. doi:10.3389/fnut.2022.886224
New World Encyclopedia contributors, "Caffeine," New World Encyclopedia, , https://www.newworldencyclopedia.org/p/index.php?title=Caffeine&oldid=794371 (accessed November 27, 2022).
Sasaki S, Limpar M, Sata F, Kobayashi S, Kishi R. Interaction between maternal caffeine intake during pregnancy and CYP1A2 C164A polymorphism affects infant birth size in the Hokkaido study. Pediatr Res. 2017;82(1):19-28. doi:10.1038/pr.2017.70
White JR Jr, Padowski JM, Zhong Y, et al. Pharmacokinetic analysis and comparison of caffeine administered rapidly or slowly in coffee chilled or hot versus chilled energy drink in healthy young adults. Clin Toxicol (Phila). 2016;54(4):308-312. doi:10.3109/15563650.2016.1146740
Yang A, Palmer AA, de Wit H. Genetics of caffeine consumption and responses to caffeine. Psychopharmacology (Berl). 2010;211(3):245-257. doi:10.1007/s00213-010-1900-1
