(180) Maternal Preeclampsia and Offspring Neurological Morbidity: A Sibling-Matched Cohort Study

Emerging evidence links maternal preeclampsia to offspring neurological disorders; however, many studies are limited by residual confounding. This study used a sibling-matched design to control for unmeasured familial and environmental factors and assess whether preeclampsia is independently associated with long-term neurological morbidity, including autism.

Study Design:

We conducted a retrospective population-based cohort study of singleton siblings born to the same mother, where one sibling was exposed to preeclampsia and the other was not. Neurological diagnoses during childhood—including autism spectrum disorder (ASD), epilepsy, and ADHD—were assessed using Kaplan-Meier survival analysis and generalized estimating equation (GEE) models adjusted for maternal age and preterm delivery.

Results:

Among 8,544 siblings (4,272 exposed to preeclampsia), there was no significant difference in cumulative neurological-related hospitalizations between groups (log-rank P = 0.217). Crude hospitalization rates were 4.0% in the exposed group vs. 3.4% in the unexposed (OR = 0.86; 95% CI, 0.70–1.09; P = 0.237). Adjusted analysis confirmed no significant association between preeclampsia exposure and long-term neurological morbidity (aHR = 0.94; 95% CI, 0.76–1.17; P = 0.305). Specifically, no increased risk for autism was observed.

Conclusion:

In this sibling-matched cohort study, maternal preeclampsia was not associated with increased long-term neurological morbidity in offspring. These findings challenge prior associations and suggest earlier studies may have been influenced by unmeasured confounding. The absence of increased autism risk is particularly reassuring. Sibling-matched analyses offer a valuable approach to strengthen causal inference in perinatal epidemiology.