ABBREVIATIONS cFTS Combined first-trimester screening MoM Multiple of the median PAPP-A Pregnancy-associated plasma protein-A b-hCG Beta subunit of human chorionic gonadotrophin AIM To investigate whether combined first-trimester screening (cFTS) biomarkers are associated with cerebral palsy (CP) and to identify CP characteristics associated with abnormal biomarker levels. METHOD In this retrospective case-control data linkage study, we matched mothers of 435 singletons with CP from a population register to their cFTS records and selected 10 singleton pregnancy controls per case. We compared mean and abnormal levels (expressed as multiples of the median [MoMs]) of pregnancy-associated plasma protein-A (PAPP-A), beta subunit of human chorionic gonadotrophin (b-hCG), and nuchal translucency between cases and controls and between CP subgroups. RESULTS Compared with control pregnancies, CP pregnancies had lower mean levels of PAPP-A (0.95 vs 1.01 MoM, p=0.02) and b-hCG (0.93 vs 0.99 MoM, p=0.02). Biomarker levels in CP pregnancies were 1.8 times more likely to be associated with abnormally low levels of PAPP-A (p<0.01), 1.4 times for b-hCG (p=0.12), and 2.6 times for low PAPP-A and b-hCG together (p=0.04). In cases with CP, an abnormally low PAPP-A level was associated with moderate preterm birth, low Apgar scores, and Gross Motor Function Classification System level V. Low b-hCG was associated with very low birthweight.

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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 (β‐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.