Intended for healthcare professionals


Maternal caffeine intake during pregnancy and risk of fetal growth restriction: a large prospective observational study

BMJ 2008; 337 doi: (Published 03 November 2008) Cite this as: BMJ 2008;337:a2332

This article has a correction. Please see:

  1. CARE Study Group
  1. Correspondence to: Justin C Konje, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester LE2 7LX, jck4{at} Alternative correspondence: Janet E Cade, Centre for Epidemiology and Biostatistics, University of Leeds, Leeds LS2 9JT, j.e.cade{at}
  • Accepted 24 October 2008


Objective To examine the association of maternal caffeine intake with fetal growth restriction.

Design Prospective longitudinal observational study.

Setting Two large UK hospital maternity units.

Participants 2635 low risk pregnant women recruited between 8-12 weeks of pregnancy.

Investigations Quantification of total caffeine intake from 4 weeks before conception and throughout pregnancy was undertaken with a validated caffeine assessment tool. Caffeine half life (proxy for clearance) was determined by measuring caffeine in saliva after a caffeine challenge. Smoking and alcohol were assessed by self reported status and by measuring salivary cotinine concentrations.

Main outcome measures Fetal growth restriction, as defined by customised birth weight centile, adjusted for alcohol intake and salivary cotinine concentrations.

Results Caffeine consumption throughout pregnancy was associated with an increased risk of fetal growth restriction (odds ratios 1.2 (95% CI 0.9 to 1.6) for 100-199 mg/day, 1.5 (1.1 to 2.1) for 200-299 mg/day, and 1.4 (1.0 to 2.0) for >300 mg/day compared with <100 mg/day; test for trend P<0.001). Mean caffeine consumption decreased in the first trimester and increased in the third. The association between caffeine and fetal growth restriction was stronger in women with a faster compared to a slower caffeine clearance (test for interaction, P=0.06).

Conclusions Caffeine consumption during pregnancy was associated with an increased risk of fetal growth restriction and this association continued throughout pregnancy. Sensible advice would be to reduce caffeine intake before conception and throughout pregnancy.


  • We thank Gordon Gibson, Fred Kadlubar, and Mark Klebanoff for their useful comments during the study. The Leicester team of the CARE Study Group thank Vilas Misty, Clare Lawrence, Bhavin Daudia, and the Department of Chemical Pathology, University Hospitals of Leicester NHS Trust, for sample handling and processing.

  • Members of the CARE Study Group:

  • Leeds team: Sinead Boylan, Janet E Cade, Vivien A Dolby, Darren C Greenwood, Alastair W M Hay, Sara F L Kirk, Susan Shires, Nigel Simpson, James D Thomas, James Walker, Kay L M White, Christopher P Wild, Centre for Epidemiology and Biostatistics, University of Leeds, Leeds LS2 9JT

  • Leicester team: Neelam Potdar, Justin C Konje, Nicholas Taub, Jim Charvill, Karen C Chipps, Shabira Kassam, Chetan Ghandi, , Marcus S Cooke, Departments of Cancer Studies and Molecular Medicine and Health Sciences, University of Leicester, Leicester LE2 7LX

  • Steering group: Justin C Konje (chair), Marcus Cooke (principal investigator), Leicester; Janet Cade (principal investigator), Leeds; David Gott, Natalie Thatcher, Stuart Creton, Caroline Tahourdin, Food Standards Agency, London; Gordon Gibson, University of Surrey

  • Statisticians: Darren Greenwood, Leeds; Nicholas Taub, Leicester; Clifton Gay, Food Standards Agency

  • Clinicians: Neelam Potdar, Justin C Konje, Leicester; Nigel Simpson, James Walker, Leeds

  • Research midwives: Viv Dolby, Heather Ong, Leeds; Shabira Kassam, Karen Chipps, Leicester

  • Nutritional methods: Sinead Boyland, Sara Kirk, Janet Cade, Leeds

  • Laboratory methods: Kay White, Susan Shires, Alastair Hay, Christopher Wild, Leeds; Marcus Cooke, Leicester

  • Database management: James Thomas, Ellen Hill, nutritionist students, Leeds; Jim Charvill, Chetan Ghandi, Leicester.

  • Funding: Food Standards Agency, United Kingdom, Grant contract No T01032/33.

  • Competing interests: None declared.

  • Ethical approval: Obtained from the local ethics committees, Directorate of Research and Development, Leicester and Leeds, LREC Ref 7260. Participants gave signed informed consent before enrolment into the study.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

View Full Text