Maternal Age-Related Gender Bias in Trisomy 21 and Trisomy 18

IF 1.6 4区医学 Q4 DEVELOPMENTAL BIOLOGY

Birth Defects Research Pub Date : 2025-06-02 DOI:10.1002/bdr2.2489

Yun Pan, Changshui Chen, Haibo Li

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Abstract

Background

The aim of this study was to investigate the underlying factors contributing to gender-based disparities in the prevalence of trisomy 21 (Downs's syndrome) and trisomy 18 (Edwards's syndrome).

Methods

Overall, 551 cases of trisomy 21 (T21) and 154 cases of trisomy 18 (T18) diagnosed through amniotic fluid karyotyping and chromosomal microarray analysis (CMA) between 2005 and 2023 at the Affiliated Women and Children's Hospital of Ningbo University. The study population consisted of fetuses at 19–23 gestational weeks across various maternal age groups. A control group comprising 662,453 newborns from the same institution between 2011 and 2018 was established for sex ratio comparison. Parental origin of diploids in T21 and T18 cases was determined using quantitative fluorescence-polymerase chain reaction (QF-PCR) analysis. Statistical significance of gender bias was evaluated using chi-squared tests, with a threshold of p < 0.05 considered statistically significant.

Results

The study revealed distinct sex ratio patterns across different maternal age groups. The control group exhibited a sex ratio of 1.06 (male:female), while the overall sex ratio for T21 cases was significantly elevated at 1.32. Notably, the highest sex ratio (1.84) was observed in T21 cases among women aged 20–25 years, with a progressive decline in sex ratio corresponding to increasing maternal age. The sex ratio of newborns born to women aged ≥ 35 years approximated that of the control. In contrast, T18 cases demonstrated an overall female predominance, with a sex ratio of 0.67, reaching its lowest value (0.56) in the 25–30 years maternal age group. Regarding the parent origin of diploids, maternal meiosis errors accounted for > 90% of cases in both T21 and T18. However, a higher prevalence of paternal origin was observed in younger women (≤ 35 years). Male fetuses of paternal diploid origin of T21 were 2.5 times more than female fetuses.

Conclusion

In our sample of over 500,000 births, between 2005 and 2023 in Ningbo, China, fetuses with T21 were more likely to be males while fetuses with T18 were more likely to be females. However, this gender bias exhibited a significant age-dependent pattern, being predominantly observed in women under 35 years of age. Specifically, in T21 cases of paternal origin among women ≤ 35 years, the frequency of nondisjunction involving Y-chromosome-bearing sperm was 2.5-fold higher than that involving X-chromosome-bearing sperm.

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21三体和18三体中母亲年龄相关的性别偏见

本研究的目的是探讨21三体（唐氏综合征）和18三体（爱德华兹综合征）患病率的性别差异的潜在因素。方法对2005 - 2023年宁波大学附属妇幼医院经羊水核型和染色体微阵列分析（CMA）确诊的21三体（T21） 551例和18三体（T18） 154例进行分析。研究人群包括不同年龄段的19-23孕周的胎儿。建立了2011年至2018年来自同一机构的662453名新生儿的对照组，进行性别比例比较。采用定量荧光聚合酶链反应（QF-PCR）分析T21和T18病例二倍体亲本来源。采用卡方检验评估性别偏倚的统计学意义，p <； 0.05的阈值认为有统计学意义。结果本研究揭示了不同年龄产妇的性别比例模式。对照组的性别比为1.06（男：女），而T21病例的总体性别比显著升高，为1.32。值得注意的是，T21例中20-25岁女性的性别比最高（1.84），随着产妇年龄的增加，性别比逐渐下降。年龄≥35岁妇女所生新生儿的性别比与对照组相近。T18病例总体上以女性为主，性别比为0.67，在25-30岁产妇年龄组达到最低值（0.56）。对于二倍体的亲本来源，在T21和T18中，母体减数分裂错误占90%。然而，在年轻女性（≤35岁）中观察到较高的父系起源患病率。父系二倍体来源的T21的男性胎数是女性胎数的2.5倍。在我们2005年至2023年在中国宁波超过50万的出生样本中，T21胎儿更有可能是男性，而T18胎儿更有可能是女性。然而，这种性别偏见表现出明显的年龄依赖模式，主要见于35岁以下的女性。具体而言，在T21例≤35岁的父系起源女性中，含有y染色体的精子不分离的频率是含有x染色体的精子的2.5倍。

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来源期刊

Birth Defects Research Medicine-Embryology

CiteScore

3.60

自引率

9.50%

发文量

153

期刊介绍： The journal Birth Defects Research publishes original research and reviews in areas related to the etiology of adverse developmental and reproductive outcome. In particular the journal is devoted to the publication of original scientific research that contributes to the understanding of the biology of embryonic development and the prenatal causative factors and mechanisms leading to adverse pregnancy outcomes, namely structural and functional birth defects, pregnancy loss, postnatal functional defects in the human population, and to the identification of prenatal factors and biological mechanisms that reduce these risks. Adverse reproductive and developmental outcomes may have genetic, environmental, nutritional or epigenetic causes. Accordingly, the journal Birth Defects Research takes an integrated, multidisciplinary approach in its organization and publication strategy. The journal Birth Defects Research contains separate sections for clinical and molecular teratology, developmental and reproductive toxicology, and reviews in developmental biology to acknowledge and accommodate the integrative nature of research in this field. Each section has a dedicated editor who is a leader in his/her field and who has full editorial authority in his/her area.