Folate Receptor Alpha Autoantibodies in Early Pregnancy: First-Trimester Reference Intervals and Proposed Clinical...

Area of Science:

• Obstetrics and Gynecology
• Immunology
• Neurodevelopmental Disorders

Background:

• Maternal folate receptor alpha autoantibodies (FRAA) are implicated in placental folate transport issues, potentially leading to fetal cerebral folate deficiency (CFD) and neurodevelopmental risks like autism spectrum disorder (ASD).
• Establishing first-trimester reference intervals for FRAA is crucial for early identification of at-risk pregnancies, but remains undefined.

Purpose of the Study:

• To establish week-specific normative percentile curves for maternal FRAA during the first trimester of pregnancy.
• To provide data that may support prioritizing FRAA assessment before 15 weeks gestation.

Main Methods:

• A prospective, single-center study involving 534 healthy pregnant women between 10 and 15 weeks gestation.
• Utilized a CE-IVDR compliant FRAA ELISA assay following CLSI and IFCC protocols.
• Employed non-parametric estimation and log-smoothed regression with a 1-week rolling window to determine week-specific percentiles (P5, P50, P95, P99).

Main Results:

• Median FRAA levels showed a slight decline from 29 ng/mL at week 10 to 25 ng/mL at week 14.
• Provisional clinically actionable thresholds were identified as P95 ≈ 120 ng/mL and P99 ≈ 150 ng/mL.
• The study provides the first normative percentile curves for maternal FRAA in the first trimester.

Conclusions:

• These findings present the first first-trimester normative percentile curves for maternal FRAA.
• The data suggest prioritizing FRAA assessment before 15 weeks gestation, coinciding with accelerated transplacental IgG transfer.
• Proposed thresholds and clinical implications require external validation due to study limitations, including cross-sectional design and absence of long-term outcome data.