Objective: To examine the association of maternal caffeine intake with fetal growth restriction. \ud Design Prospective longitudinal observational study. \ud \ud Setting: Two large UK hospital maternity units. \ud \ud Participants: 2635 low risk pregnant women recruited between 8-12 weeks of pregnancy. \ud \ud 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. \ud \ud Main outcome measures: Fetal growth restriction, as defined by customised birth weight centile, adjusted for alcohol intake and salivary cotinine concentrations. \ud \ud 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). \ud \ud 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. \ud \u
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