Microarray analysis: first-trimester maternal serum free β-hCG and the risk of significant copy number variants.

Objective To determine whether abnormal levels of first-trimester maternal serum free beta-hCG and PAPP-A are associated with significant copy number variants (CNVs) on chromosomal microarray analysis (CMA). Methods Results Retrospective cohort of singleton prenatal CMA studies (n = 2880). Cases with an abnormal karyotype, benign familial or de novo variants, and absence of heterozygosity were excluded. The prevalence of abnormal serum analytes was compared between patients with significant CNVs (n = 56) and those with normal CMA (n = 884). Odds ratios (ORs) and 95% confidence intervals (CI) were calculated using Fisher's exact test. Mantel-Haenszel method was utilized to adjust ORs for prenatal diagnostic procedure type and indications for testing. Statistical significance was determined as P value Abnormally low serum free beta-hCG (<= 0.45 MoM) was associated with an increased risk of significant CNVs (OR 3.53, 95% CI, 1.25-8.66, P < 0.01). This association remained significant after adjusting for abnormal nuchal translucency and advanced maternal age (AMA) (adjusted OR 3.04, 95% CI, 1.05-7.48, P < 0.05) or procedure type and AMA (adjusted OR 3.21, 95% CI 1.13-8.16, P < 0.05). The associations of abnormally high serum free beta-hCG, low PAPP-A, and high PAPP-A with significant CNVs were not statistically significant. Conclusion Low first-trimester serum beta-hCG is associated with an increased risk of significant CNVs on CMA.