Second trimester maternal serum biomarkers and the risk of cerebral palsy.

ABSTRACT

AIMS: To investigate whether second trimester maternal serum screening (2TMSS) biomarkers are associated with cerebral palsy (CP) and identify CP characteristics associated with abnormal biomarker levels. METHOD: In this retrospective case-control data linkage study, we linked mothers of 129 singleton CP cases from a population register to their 2TMSS records and selected 10 singleton pregnancy controls per case (n = 1290). We compared mean and abnormal levels of alpha-fetoprotein (AFP), beta subunit of human chorionic gonadotrophin (ß-hCG), unconjugated estriol (uE3), and inhibin between cases and controls and within CP subgroups. RESULTS: Compared to control pregnancies, CP pregnancies had higher mean levels of AFP (1.10 vs. 1.01 multiple of the population median [MoM], p = 0.01) and inhibin (1.10 vs. 0.98 MoM, p ≤ 0.01). CP pregnancies were 2.5 times more likely to be associated with high levels of AFP (OR 2.52 [95% confidence interval [CI] 1.30, 4.65]; p < 0.01) and 2.6 times for inhibin (OR 2.63 [95% CI 1.37, 4.77]; p < 0.01), and 6.8 times when AFP and inhibin were both elevated (OR 6.75 [95% CI 2.41, 18.94]; p < 0.01). In CP cases, high AFP and high inhibin levels were associated with preterm birth and low birthweight. INTERPRETATION: Abnormal second-trimester biomarker levels suggest abnormal placentation plays a role in the causal pathway of some CP cases.