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Objective <p>To assess the diagnostic yield of chromosomal microarray analysis (CMA) and exome sequencing (ES) in fetuses with central nervous system (CNS) anomalies across two study periods (January 2008 to June 2016 and July 2016 to December 2024), and to evaluate long-term outcomes.</p> Methods <p>This retrospective study included cases with fetal CNS anomalies undergoing invasive testing by G-banded karyotyping and, in selected cases, additional CMA and/or ES. Fetuses were classified into four groups: isolated CNS malformations, isolated CNS plus (additional minor abnormalities and dynamic findings), complex CNS anomalies, and multisystem malformations.</p> Results <p>Among 780 cases, causative findings were identified in 23.8% (25/105) by CMA and 39.0% (73/187) by ES. Use of CMA/ES increased in the second study period (16.3% vs. 59.7%), resulting in more pathogenic findings (26 vs. 72 cases), whereas diagnostic yield among tested cases decreased without significance. The highest ES yield was observed in multisystem CNS anomalies; isolated CNS plus cases showed higher yields than truly isolated CNS cases.&#xa0;In an exploratory subgroup analysis, isolated CNS plus cases with polyhydramnios had a higher CMA/ES yield than truly isolated cases. Among 91 live-born children with follow-up, 49.5% (45/91) had global developmental delay, which was more frequent with pathogenic findings (90.0%, 18/20; <i>p</i> = 0.002) and increasing anomaly complexity (11.1 to 81.8%; <i>p</i> &lt; 0.001).</p> Conclusion <p>Uptake of CMA and ES increased over time and resulted in more etiologic diagnoses. In tested cases, both methods provided meaningful diagnostic yield in fetuses with CNS anomalies and may contribute to prognostic assessment and prenatal counseling.</p>

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Diagnostic yield of chromosomal microarray analysis and exome sequencing in fetuses with central nervous system anomalies, with long-term follow-up: a single-center study over a 17-year period

  • 期刊论文

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  • 发表日期：

    2026年6月2日

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  • Karla Feodorovici,
  • Hannah Klinkhammer,
  • Brigitte Strizek,
  • Ulrich Gembruch,
  • Annegret Geipel

摘要

Objective

To assess the diagnostic yield of chromosomal microarray analysis (CMA) and exome sequencing (ES) in fetuses with central nervous system (CNS) anomalies across two study periods (January 2008 to June 2016 and July 2016 to December 2024), and to evaluate long-term outcomes.

Methods

This retrospective study included cases with fetal CNS anomalies undergoing invasive testing by G-banded karyotyping and, in selected cases, additional CMA and/or ES. Fetuses were classified into four groups: isolated CNS malformations, isolated CNS plus (additional minor abnormalities and dynamic findings), complex CNS anomalies, and multisystem malformations.

Results

Among 780 cases, causative findings were identified in 23.8% (25/105) by CMA and 39.0% (73/187) by ES. Use of CMA/ES increased in the second study period (16.3% vs. 59.7%), resulting in more pathogenic findings (26 vs. 72 cases), whereas diagnostic yield among tested cases decreased without significance. The highest ES yield was observed in multisystem CNS anomalies; isolated CNS plus cases showed higher yields than truly isolated CNS cases. In an exploratory subgroup analysis, isolated CNS plus cases with polyhydramnios had a higher CMA/ES yield than truly isolated cases. Among 91 live-born children with follow-up, 49.5% (45/91) had global developmental delay, which was more frequent with pathogenic findings (90.0%, 18/20; p = 0.002) and increasing anomaly complexity (11.1 to 81.8%; p < 0.001).

Conclusion

Uptake of CMA and ES increased over time and resulted in more etiologic diagnoses. In tested cases, both methods provided meaningful diagnostic yield in fetuses with CNS anomalies and may contribute to prognostic assessment and prenatal counseling.