Severe Early-Onset Fetal Growth Restriction: The Yield of Antenatal and Postnatal Genetic Testing.

IF 3.1 2区医学 Q2 GENETICS & HEREDITY

Prenatal Diagnosis Pub Date : 2026-09-01 Epub Date: 2026-05-19 DOI:10.1002/pd.70182

Matthew H Mossayebi, Sophie J Adams, Megan E Bunnell, Stephanie H Guseh, Louise E Wilkins-Haug

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引用次数: 0

Abstract

Objectives: We evaluated the diagnostic yield of karyotype (KT) and chromosomal microarray (CMA) with isolated severe FGR diagnosed before 32 weeks' gestation. Exome and genome sequencing (ES/GS) level data were available in a subset of this population.

Method: We performed a retrospective review of singleton pregnancies (delivered 2022-2025) with estimated fetal weight or abdominal circumference < 3rd percentile before 32 weeks' gestation, no sonographic structural anomalies, and diagnostic testing (KT, CMA, ES, or GS) via amniocentesis or cord blood. Cases with abnormal cell-free DNA were excluded.

Results: Forty cases were included (mean diagnosis 26.8 weeks). Testing was performed via amniocentesis in 42% and cord blood in 58%. All KT (27/40) were normal. CMA (39/40) identified one pathogenic CNV (2.5%) and three (7.5%) variants of uncertain significance (VUS). Four (10%) showed ≥ 1 region of absence of heterozygosity (AOH) > 10Mb; one revealed maternal uniparental disomy of chromosome 6. Sequencing (N = 10) detected one VUS in COL1A1. Acute viral infection was not observed in any of the cases.

Conclusions: CMA was diagnostic in 2/39 (5.1%) cases, a pathogenic CNV implicating the SHOX gene, and maternal UPD 6, which were consistent with FGR. There was a remarkable rate (10%) of AOH. Further investigation, including placental studies and genome sequencing, may elucidate whether AOH is a contributing factor for FGR.

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严重早发型胎儿生长受限：产前和产后基因检测的产量。

目的：评价核型（KT）和染色体微阵列（CMA）对妊娠32周前确诊的分离性严重FGR的诊断率。外显子组和基因组测序（ES/GS）水平数据可用于该人群的一个子集。方法：我们对估计胎儿体重或腹围的单胎妊娠（2022-2025年分娩）进行回顾性分析。结果：纳入40例（平均诊断26.8周）。42%通过羊膜穿刺术进行检测，58%通过脐带血进行检测。所有KT（27/40）均正常。CMA（39/40）鉴定出1个致病性CNV（2.5%）和3个不确定意义变异（VUS）（7.5%）。4例（10%）显示≥1个杂合缺失区（AOH） bbb10mb；其中一项发现母亲6号染色体单亲二体。测序（N = 10）在COL1A1中检测到1个VUS。所有病例均未见急性病毒感染。结论：2/39（5.1%）的病例诊断出CMA，为一种涉及SHOX基因的致病性CNV，以及母体upd6，与FGR一致。AOH发生率显著（10%）。进一步的研究，包括胎盘研究和基因组测序，可能会阐明AOH是否是FGR的一个促进因素。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Prenatal Diagnosis 医学-妇产科学

CiteScore

5.80

自引率

13.30%

发文量

204

审稿时长

2 months

期刊介绍： Prenatal Diagnosis welcomes submissions in all aspects of prenatal diagnosis with a particular focus on areas in which molecular biology and genetics interface with prenatal care and therapy, encompassing: all aspects of fetal imaging, including sonography and magnetic resonance imaging; prenatal cytogenetics, including molecular studies and array CGH; prenatal screening studies; fetal cells and cell-free nucleic acids in maternal blood and other fluids; preimplantation genetic diagnosis (PGD); prenatal diagnosis of single gene disorders, including metabolic disorders; fetal therapy; fetal and placental development and pathology; development and evaluation of laboratory services for prenatal diagnosis; psychosocial, legal, ethical and economic aspects of prenatal diagnosis; prenatal genetic counseling