Effect of diuretics on fetal growth: A drug effect or confounding by indication? Pooled Danish and Scottish cohort data

Aims The diabetogenic effect of diuretics, as well as the indication for pr escribing them, may impact on fetal growth. We analysed whether the purchas e of prescription drugs for diuretics during pregnancy was associated with measures of fetal growth. Methods During 1991-98 all women who purchased prescription drugs for diure tics during pregnancy were identified in the Northern Jutland Prescription Database (NJDP), Denmark, and in the Medicines Monitoring Unit's Database ( MEMO), Scotland. Information on birth weight and gestational age was obtain ed from the Danish Birth Registry, the Danish Hospital Discharge Registry a nd the Scottish Tayside Neonatal Database. information on diabetes, hyperte nsion and prepregnancy weight were obtained by hospital record review in a sample of women in the Danish cohort. Women who did not purchase prescripti on diuretics during pregnancy were used as a reference group in both cohort s. Results Danish women who purchased prescription loop diuretics during pregn ancy gave birth to infants with higher birth weights than women who did not use diuretics; mean difference 104.7 g (95% CI; 2.6, 206.9). However, the high prevalence of diabetes (10.3%) among Danish women who purchased prescr iption loop diuretics during pregnancy might explain this result. Both the Danish and the Scottish women who purchased prescription diuretics during t heir pregnancy were at increased risk of preterm delivery (<37 completed we eks); ORs: 1.8 (CI; 1.2, 2.7)(NJDP), 1.9 (CI; 0.9, 4.3)(MEMO). The proporti on of hypertension among women who purchased prescription thiazides was 15. 8%, and the risk of having an infant with a birth weight (BW) <2500 g was i ncreased; ORs: 2.6 (CI; 1.4, 5.0)(NJDP), 24 (CI; 0.8, 7.8)(MEMO). Conclusions Prescribing diuretics during pregnancy was associated with diff erences in birth weight and incidence of preterm delivery. Confounding by i ndication may explain the findings.