First-trimester maternal serum biomarkers and the risk of cerebral palsy

Abstract

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 (β-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 β-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 β-hCG (p=0.12), and 2.6 times for low PAPP-A and β-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 β-hCG was associated with very low birthweight. Interpretation: Low first-trimester biomarker levels suggest a role for early pregnancy factors in some causal pathways to CP. What this paper adds: Low first-trimester levels of biomarkers in maternal serum are associated with later cerebral palsy (CP). Early pregnancy factors have potential importance in causal pathways to CP. Causal pathways involving preterm birth, term neonatal encephalopathy, and genetic syndromes may be implicated.