title: Maternal caffeine intake during pregnancy is associated with risk of low birth weight: a systematic review and dose-response meta-analysis.
abstract: BACKGROUND
  Considerable controversy exists regarding the relation between maternal caffeine intake during pregnancy and risk of low birth weight (birth weight <2,500 g). We aim to assess this association using a systematic review and dose-response meta-analysis of prospective studies.
  
  
  METHODS
  Potential articles were identified by searching MEDLINE and SCOPUS databases through 17 July 2013. Two authors independently extracted information on study design, participant characteristics and estimates of associations. Random-effects models were used to derive the summary relative risks (RRs) and corresponding 95% confidence intervals (CIs). Dose-response relationships were assessed using generalized least-squares trend estimation.
  
  
  RESULTS
  In our meta-analysis, we included 13 prospective studies: 9 with low birth weight as a binary outcome variable (90,747 participants and 6,303 cases) and 6 with birth weight as a continuous outcome variable (10,015 participants; 2 studies reported both types of outcomes). Compared with the reference category with no or very low caffeine intake, the RR (95% CI) of low birth weight was 1.13 (1.06 to 1.21; I 2 0.0%) for low intake (50 to 149 mg/day), 1.38 (1.18 to 1.62; I 2 31.9%) for moderate intake (150 to 349 mg/day), and 1.60 (1.24 to 2.08; I 2 65.8%) for high intake (≥350 mg/day). In the dose-response analysis, each 100-mg/day increment in maternal caffeine intake (around one cup of coffee) was associated with 13% (RR 1.13, 1.06 to 1.21) higher risk of low birth weight. The association persisted in strata defined according to various study characteristics. Moderate (-33 g, 95% CI -63 to -4; I 2 0.3%) and high (-69 g, 95% CI -102 to -35; I 2 0.0%) caffeine intakes were also associated with a significantly lower birth weight as compared with the reference category.
  
  
  CONCLUSIONS
  Higher maternal caffeine intake during pregnancy was associated with a higher risk of delivering low birth weight infants. These findings support recommendations to restrict caffeine intake during pregnancy to low levels.
authors.forename: Ling-Wei
authors.initials: LW
authors.lastname: Chen
authors.forename: Yi
authors.initials: Y
authors.lastname: Wu
authors.forename: Nithya
authors.initials: N
authors.lastname: Neelakantan
authors.forename: Mary Foong-Fong
authors.initials: MF
authors.lastname: Chong
authors.forename: An
authors.initials: A
authors.lastname: Pan
authors.forename: Rob M
authors.initials: RM
authors.lastname: van Dam
mesh_terms: D001724:Birth Weight / Q000187:drug effects*; D002110:Caffeine / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011446:Prospective Studies; D012306:Risk
chemical_list: D002110:Caffeine