Neurocognitive Development of Children Following In-Utero Exposure to Labetalol for Maternal Hypertension: A Cohort Study Using a Prospectively Collected Database

Abstract

Objective: To identify the effect of prenatal labetalol exposure on children's long-term neurodevelopment. Design: A cohort study with matched controls using a prospectively collected database. Methods: Participants were women counseled for hypertension in pregnancy at the Motherisk Program at The Hospital for Sick Children, and The Sunnybrook Health Sciences Centre, Toronto, Canada and their children. Mother-child pairs were divided into groups based on in-utero exposure to labetalol (n = 32), non-teratogenic substances (n = 42), and methyldopa (n = 25). The main outcome measures were children's Full-Scale IQ, Performance IQ and Verbal IQ assessed with the Wechsler Preschool and Primary Scale of Intelligence. Results: There were no statistically significant differences in scores on Full-Scale IQ, Performance IQ, or Verbal IQ between children exposed in utero to labetalol and to non-teratogenic substances (Full-Scale IQ: 109.60 ± 8.20 vs. 111.90 ± 11.39, p = 0.647; Performance IQ: 104.80 ± 8.69 vs. 110.19 ± 12.91, p = 0.186; Verbal IQ: 112.27 ± 11.05 vs. 11.21 ± 11.98, p = 0.922, respectively). Children in the methyldopa group achieved lower scores on measures of Full-Scale IQ and Performance IQ when compared to children exposed to non-teratogenic substances (Full-Scale IQ: 105.24 ± 12.46 vs. 111.90 ± 11.39, p = 0.043; Performance IQ: 98.80 ± 16.16 vs. 110.19 ± 12.91, p = 0.002, respectively). Linear regression analysis revealed that maternal Full Scale IQ was a significant predictor of children's Full-Scale IQ (p = 0.020, beta = 0.229). Maternal Performance IQ and duration of treatment with methyldopa were significant predictors of children's Performance IQ (p = 0.028, beta = 0.232; p = 0.16, beta = –0.255, respectively). Conclusion: In-utero exposure to labetalol does not appear to adversely affect the neurocognitive development of young children. These reassuring results may aid disease management for pregnant women with hypertension.