Gestational Exposure to Maternal Systemic Glucocorticoids and Childhood Risk of CKD

Rationale & Objective: The potential effects of antenatal glucocorticoid exposure on the health of children are unclear. We examined the association of gestational exposure to maternal systemic glucocorticoids and the risk of developing chronic kidney disease (CKD) in childhood. Study Design: Retrospective cohort study. Setting & Participants: Newborns cared for at the largest health care delivery system in Taiwan between 2004 and 2018. Exposure: Maternal prescriptions for systemic glucocorticoids between the last menstrual period and birth as a proxy for gestational exposure. Outcome: Incidence of childhood CKD, including congenital anomalies of the kidney and urinary tract (CAKUT) and other kidney diseases (non-CAKUT), over 10 years. Analytical Approach: Cox proportional hazards models with stabilized inverse probability of treatment weighting and robust sandwich estimator were used to estimate the average association between systemic glucocorticoids and incident CKD after adjustment for offspring characteristics (adjusted HR: AHR). Results: Among 23,363 singleton-born children, gestational systemic glucocorticoid exposure was significantly associated with a higher risk of childhood CKD (AHR, 1.69 [95% CI, 1.01-2.84]). Stratified analyses showed stronger associations between systemic glucocorticoids and childhood CKD within the strata of birth < 37 weeks’ gestational age (AHR, 2.38 [95% CI, 1.19-4.78]), male sex (AHR, 1.89 [95% CI, 1.00-3.55]), gestational exposure in the second trimester (AHR, 6.70 [95% CI, 2.17-20.64]), and total dose of >24 mg hydrocortisone equivalent (AHR, 1.91 [95% CI, 1.05-3.47]). Limitations: Study was limited to the Taiwan health care delivery system and childhood CKD events through the age of 10 years. Conclusions: The findings of this study suggest that gestational exposure to systemic glucocorticoids is associated with the occurrence of kidney disease in childhood. If these findings are confirmed, they may inform clinicians who are considering prescribing systemic glucocorticoids during pregnancy. Plain-Language Summary: In a singleton-born cohort of neonates, maternal exposure to antenatal systemic glucocorticoids was significantly associated with a 1.7-fold increased risk of the children developing chronic kidney disease over the first 10 years of life. Children of mothers who received >24 mg of hydrocortisone equivalent, systemic glucocorticoid treatment in second trimester of gestation, and children born at <37 weeks of gestational age had a higher risk of childhood kidney disease after gestational systemic glucocorticoid exposure. If these findings are confirmed, they may inform clinicians who are considering prescribing systemic glucocorticoids during pregnancy.