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

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