Exposure to specific nonsteroidal anti-inflammatory drugs during pregnancy, such as indomethacin in the first trimester and ibuprofen in the third, may increase the risk of chronic kidney disease in children, according to a recent study.
Researchers examined the association between maternal nonsteroidal anti-inflammatory drug (NSAID) use during pregnancy and the risk of chronic kidney disease (CKD) in offspring. Using data from 1,025,255 children born in Taiwan between 2007 and 2017, the study, published in JAMA Pediatrics, assessed CKD risk through maternal prescription records. The findings were analyzed using Cox proportional hazards regression models with inverse probability of treatment weighting (IPTW).
Among 680,696 singleton children included in the primary analysis, 163,516 (24%) had prenatal NSAID exposure. Gestational NSAID use was associated with a modestly increased risk of childhood CKD (weighted hazard ratio [wHR], 1.10; 95% confidence interval [CI], 1.05-1.15). The risk varied by trimester, with second-trimester exposure showing a wHR of 1.19 (95% CI, 1.11-1.28) and third-trimester exposure a wHR of 1.12 (95% CI, 1.03-1.22). Specific NSAIDs linked to increased CKD risk included indomethacin (wHR, 1.69; 95% CI, 1.10-2.60) and ketorolac (wHR, 1.28; 95% CI, 1.01-1.62) in the first trimester, diclofenac (wHR, 1.27; 95% CI, 1.13-1.42) and mefenamic acid (wHR, 1.29; 95% CI, 1.15-1.46) in the second trimester, and ibuprofen (wHR, 1.34; 95% CI, 1.07-1.68) in the third trimester.
However, sibling comparisons—which control for shared genetic and environmental factors—revealed no significant association between NSAID exposure and CKD (wHR, 1.05; 95% CI, 0.97-1.13), suggesting familial factors may influence some of the observed risks. During the median follow-up of 9.75 years, 10,547 children (1.6%) were diagnosed with CKD. The attributable risk was 1.79 per 1,000 person-years for the NSAID-exposed group compared to 1.61 per 1,000 person-years in the nonexposed group.
The findings suggest differences in CKD risk by sex, with females (wHR, 1.17; 95% CI, 1.09-1.25) showing higher risk than males (wHR, 1.05; 95% CI, 0.98-1.12). The study authors recommend cautious NSAID prescribing during pregnancy, particularly for indomethacin and ketorolac in the first trimester, diclofenac and mefenamic acid in the second trimester, and ibuprofen in the third trimester.
The study’s reliance on prescription data limits its generalizability and excludes laboratory-confirmed CKD diagnoses. The authors recommend further research to confirm these associations and investigate potential factors influencing kidney development.
Full disclosures can be found in the published study.