Maternal urinary paracetamol concentrations and self-reported paracetamol use in mid-gestation: Association to reduced anogenital distance in Offspring from infancy to 9 years

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Studies have found associations between self-reported paracetamol use during pregnancy and shorter anogenital distance (AGD) in male infants, suggesting paracetamol have antiandrogenic properties. We investigated whether self-reported paracetamol use or quantified paracetamol concentration in maternal urine was associated with AGD in offspring from infancy to 9 years. In the Odense Child Cohort, women completed three questionnaires about paracetamol use during pregnancy and provided urine samples around GW28. AGDs were assessed in offspring at 3, 18 months, 3, 5, 7 and 9 years. Maternal self-reported paracetamol use was available for 931 boys and 793 girls with 6292 AGD measurements. Maternal urine concentrations were available for 281 boys and 233 girls with 2298 AGD measurements. Associations were analysed using propensity score-weighted linear regression adjusted for child height. 65 % of women reported using paracetamol during pregnancy. Detectable paracetamol was found in all participants, with 6 % (>4000 ng/ml) indicating recent use. Paracetamol concentrations indicating recent use were non-significantly associated with -1.71 % and -2.25 % shorter AGD in boys and girls. Self-reported paracetamol use anytime during pregnancy was significantly associated with -1.56 % shorter AGD in girls. Use before GW14 and between GW15-29 was non-significantly associated with -1.71 % and -1.79 % shorter AGD in boys, while use between GW15-29 and after GW30 was significantly associated with -2.52 % and -2.72 % shorter AGD in girls. The observed AGD changes were modest with little impact for the individual. However, as 65 % of pregnant women used paracetamol, these findings raise public health concerns given the increasing prevalence of reproductive disorders.

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