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European Journal of Epidemiology

, Volume 29, Issue 10, pp 725–734 | Cite as

Caffeine intake during pregnancy and adverse birth outcomes: a systematic review and dose–response meta-analysis

  • Darren C. Greenwood
  • Natalie J. Thatcher
  • Jin Ye
  • Lucy Garrard
  • Georgina Keogh
  • Laura G. King
  • Janet E. Cade
META-ANALYSIS

Abstract

Caffeine is commonly consumed during pregnancy, crosses the placenta, with fetal serum concentrations similar to the mother’s, but studies of birth outcome show conflicting findings. We systematically searched Medline and Embase for relevant publications. We conducted meta-analysis of dose–response curves for associations between caffeine intake and spontaneous abortion, stillbirth, preterm delivery, low birth weight and small for gestational age (SGA) infants. Meta-analyses included 60 unique publications from 53 cohort and case–control studies. An increment of 100 g caffeine was associated with a 14 % (95 % CI 10–19 %) increase in risk of spontaneous abortion, 19 % (5–35 %) stillbirth, 2 % (−2 to 6 %) preterm delivery, 7 % (1–12 %) low birth weight, and 10 % (95 % CI 6–14 %) SGA. There was substantial heterogeneity in all models, partly explained by adjustment for smoking and previous obstetric history, but not by prospective assessment of caffeine intake. There was evidence of small-study effects such as publication bias. Greater caffeine intake is associated with an increase in spontaneous abortion, stillbirth, low birth weight, and SGA, but not preterm delivery. There is no identifiable threshold below which the associations are not apparent, but the size of the associations are generally modest within the range of usual intake and are potentially explained by bias in study design or publication. There is therefore insufficient evidence to support further reductions in the maximum recommended intake of caffeine, but maintenance of current recommendations is a wise precaution.

Keywords

Caffeine Pregnancy Miscarriage Stillbirth Preterm birth Birth weight Small for gestational age infant Meta-analysis 

Notes

Acknowledgments

This review was funded by the Food Standards Agency (Contract T01033). We would like to acknowledge the contribution of Alastair Hay, Kay White and Nigel Simpson from the University of Leeds for comments on preliminary analyses and Gary Welsh from the Food Standards Agency Information Services and the University of Leeds Health Sciences Library for assistance with the literature searches.

Conflict of interests

The authors have no competing interests.

Supplementary material

10654_2014_9944_MOESM1_ESM.docx (128 kb)
Supplementary material 1 (DOCX 128 kb)
10654_2014_9944_MOESM2_ESM.docx (25 kb)
Supplementary material 2 (DOCX 25 kb)

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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Darren C. Greenwood
    • 1
  • Natalie J. Thatcher
    • 2
  • Jin Ye
    • 1
  • Lucy Garrard
    • 1
  • Georgina Keogh
    • 1
  • Laura G. King
    • 1
  • Janet E. Cade
    • 3
  1. 1.Division of Epidemiology and Biostatistics, School of MedicineUniversity of LeedsLeedsUK
  2. 2.Food Standards AgencyLondonUK
  3. 3.Nutritional Epidemiology Group, School of Food Science and NutritionUniversity of LeedsLeedsUK

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