Association of first-trimester screening biomarkers and the prevalence of cerebral palsy and other neurodevelopmental conditions: A systematic review

Abstract

To determine the association between first-trimester screening biomarkers and the prevalence of cerebral palsy and other neurodevelopmental disorders. Methods: This study was registered at PROSPERO (CRD42021268911). A systematic literature search was performed using PubMed, Cochrane, CINAHL databases, and Google Scholar between May 2021 and January 2022. Observational studies included pregnant participants with recorded maternal serum markers (hCG and PAPP-A) and outcome measures on the prevalence of cerebral palsy, or other neurodevelopmental conditions. Results: The review identified 248 non-duplicate studies, with only five studies having met the inclusion criteria. Based on this review, combined low levels of β-hCG were correlated with an increased risk of the development of cerebral palsy [OR] of 2.63 (95%CI 1.07, 6.46, p=0.04), and autism spectrum disorder [OR] of 1.16 (95% CI: 1.02 to 1.32, p<0.05) in infants. PAPP-A levels were also correlated with cerebral palsy [OR] of 1.81 (95%CI: 1.22-2.64, p<0.01). There are non-significant associations between β-hCG and CP and first-trimester screening markers and risk of neurodevelopmental conditions [OR] of 0.48 (95% CI: 0.3-0.8, p=0.05). Conclusion: There are only limited studies that showed plausible associations between hCG and autism; and PAPP-A alone and combined hCG and PAPP-A with cerebral palsy. More studies are needed to search for potential mechanisms behind abnormal FTS markers and the CNS development of infants with neurodevelopmental conditions.