A transgenerational, epigenetic effect of anesthesia, particularly fluorinated agents, has been examined in rat models, but translation to humans is unclear. This study examined associations of maternal lifetime exposure to anesthesia and pregnancy exposure to fluorinated anesthetics with child cognitive and educational outcomes. Women in the US Collaborative Perinatal Project (1959-1963) reported lifetime history of surgeries, and the obstetric record captured pregnancy exposure to anesthetics. Children were followed to age 7 for global cognitive ability and educational outcomes (n=47,977). Logistic and linear regressions were adjusted for maternal and child birth years, race and ethnicity, smoking, education, parity, study site. Many outcomes were not associated with exposure to maternal surgery that occurred at various life stages. However, maternal surgery in early childhood was associated both with being in a special school or not in school (adj OR=1.42; 95% CI 1.02, 1.98) and with slightly better cognitive ability across childhood (e.g., WISC IQ (adj β=0.59; CI 0.13, 1.04) (especially among boys)). Maternal surgery in puberty was associated with slightly lower IQ (adj β = -0.42; CI -0.79, -0.05) and poorer spelling at age 7. Children’s prenatal exposure to fluorinated anesthetics was associated with slightly better spelling ability (adj β = 1.20; CI 0.02, 2.38) but lower performance IQ at age 7 (only among boys, adj β = -1.97; CI -3.88, -0.06). This study shows inconsistent evidence of effects of maternal exposure to surgery or prenatal exposure to fluorinated agents on child developmental and educational outcomes Residual confounding by indication and socioeconomic status may explain observed associations.

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Kravets, Klebanoff, & Keim.
Journal of Developmental Origins of Health and Disease August 2022