New insight about early miscarriage: a prenatal data-based study

Early miscarriage, a common pregnancy complication predominantly occurring before 12 weeks, is conclusively linked to embryonic chromosomal abnormalities. Given the rising proportion of pregnancies at advanced maternal age, a contemporary re-examination of the relationships among early miscarriage, sex chromosomal anomalies, and maternal age is imperative to optimize clinical counseling strategies. This retrospective study analyzed cases from the Medical Genetics and Prenatal Diagnosis Center at the Third Affiliated Hospital of Zhengzhou University (July 2022–December 2024). Inclusion criteria required fetal samples with < 10% maternal cell contamination confirmed by fluorescent PCR-capillary electrophoresis. Exclusion criteria included absence of CNV-seq/CMA testing results, discordant results, incomplete documentation, or donor oocyte pregnancies. Cases were stratified into early miscarriage (EM) group and non-EM (NEM) group. Chromosomal abnormalities (triploidy/tetraploidy, uniparental disomy and aneuploidies involving chromosomes 21, 18, 13, X, and Y), fetal sex, and maternal age were compared between groups. In a cohort of 21,311 fetuses undergoing genetic testing, the overall prevalence of sex chromosome aneuploidies (SCAs) was 2.07%. Fetuses with EM exhibited significantly higher SCAs prevalence (7.5%) compared to NEM (1.4%, P < 0.001). Stratified analysis demonstrated elevated 45, X/mosaic 45, X frequency in EM (7.03% vs. 0.40% NEM, P < 0.001), whereas XYY/XXY/XXX/mosaic XXX was significantly lower in EM (0.34% vs. 0.97% NEM, P = 0.002). The EM rate increased with maternal age from 15 to 27 years, stabilized around 13% thereafter, and showed minor fluctuations. Maternal age was significantly lower in cases with 45,X compared to other cases (29.88 ± 4.15 vs. 31.43 ± 4.50 years, P < 0.001). This observational study identified an overall SCAs prevalence of 2.07% in the cohort. Beyond sex chromosome trisomies, autosomal trisomies and 45, X demonstrated higher prevalence in the EM compared to NEM. A positive correlation existed between chromosomal trisomies prevalence and advancing maternal age, whereas 45, X exhibited inverse association with maternal aging. Distinct age-stratified pattern emerged: early miscarriage rates increased with maternal age before 27 years, stabilizing thereafter at approximately 13% without further age-dependent fluctuations.