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Published on: November 20, 2015
First-trimester biomarkers and the risk of cerebral palsy
Mads Langager Larsen1, Gija Rackauskaite2, Kasper Pihl3
1Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; Department of Obstetrics and Gynaecology, Copenhagen University Hospital - Amager-Hvidovre, Hvidovre, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Insights
First-trimester biomarkers like beta-hCG and PAPP-A show weak associations with cerebral palsy (CP). These common biomarkers have inadequate predictive abilities for early CP detection.
Area of Science:
- Obstetrics and Gynecology
- Neonatal Neurology
- Developmental Pediatrics
Background:
- Cerebral palsy (CP) is the leading cause of severe motor disability in children, stemming from early brain damage.
- Identifying early indicators for CP is crucial for timely intervention and improved outcomes.
Purpose of the Study:
- To investigate the association between first-trimester biomarker levels and the subsequent development of cerebral palsy (CP).
- To assess the clinical utility of these biomarkers in developing an early prediction model for CP.
Main Methods:
- A nationwide cohort study analyzed data from 258,057 singleton live births with first-trimester assessments.
- Biomarkers including beta-hCG, PAPP-A, nuchal translucency, and biparietal diameter (BPD) were measured in multiples of the median (MoM).
- Logistic regression was employed to construct an early prediction model for CP.
Main Results:
- Lower mean beta-hCG levels were significantly associated with CP (0.96 MoM vs. 1.04 MoM, p=0.01).
- Mean PAPP-A levels showed a trend towards lower values in CP cases (0.96 MoM vs. 1.01 MoM, p=0.07).
- A higher likelihood of CP was observed in fetuses with BPD measurements below the fifth percentile (7.5% vs. 5%, p=0.045). The developed prediction model demonstrated poor discrimination.
Conclusions:
- First-trimester pregnancies diagnosed with CP exhibited lower beta-hCG and PAPP-A values, though associations varied.
- The predictive capability of common first-trimester biomarkers for CP is limited, rendering them inadequate for early prediction models.
Background:
Cerebral palsy (CP) is the most common severe motor disability and a manifestation of early brain damage.
Aims:
To analyze if abnormal levels of first-trimester biomarkers were associated with CP. Furthermore, to investigate their clinical applicability in early predicting of CP.
Study Design:
Nationwide cohort study.
Subjects:
We included 258.057 singleton live births, born during 2008-2013 with completed first-trimester assessments.
Outcome Measures:
Data on beta subunit of human chorionic gonadotropin (beta-hCG), pregnancy-associated plasma protein-A (PAPP-A), nuchal translucency thickness, and biparietal diameter (BPD) were converted to multiple of the medians (MoM). Associations were analyzed by comparing mean and extreme levels between pregnancies with and without CP. All CP diagnoses were validated by trained neuropediatricians. Logistic regression was used to create an early prediction model.
Results:
The mean beta-hCG value was significantly lower in pregnancies with CP (0.96MoM [95% CI 0.91-1.02] vs 1.04MoM [1.04-1.04], p = 0.01) and the mean PAPP-A value tended to be lower (0.96MoM [0.91-1.01] vs 1.01MoM [1.00-1.01], p = 0.07). Moreover, fetuses that developed CP more likely had a BPD measurement below the fifth percentile (7.5% vs 5%, p = 0.045). The final prediction model had poor discrimination.
Conclusions:
Pregnancies with CP tend to have lower values of beta-hCG and PAPP-A in the first trimester, however, the associations are mediated differently. Nonetheless, abnormal levels of the most common first-trimester biomarkers only have weak associations with CP; resulting in inadequate predictive abilities when included in an early prediction model.
