在生长受限的情况下，患有先天性心脏病的胎儿是否存在遗传异常的风险增加？

Is there an increased risk of genetic abnormalities in fetuses with congenital heart disease in the setting of growth restriction?

机构信息

Richard D. Wood Jr Center for Fetal Diagnosis & Treatment, Department of General, Thoracic & Fetal Surgery, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

出版信息

Prenat Diagn. 2024 Jun;44(6-7):879-887. doi: 10.1002/pd.6597. Epub 2024 May 28.

DOI:10.1002/pd.6597

PMID:38804584

Abstract

OBJECTIVE

To determine if the presence of fetal growth restriction (FGR) is associated with an increased risk of genetic abnormalities in the setting of congenital heart disease (CHD).

METHODS

This was a retrospective cohort study involving pregnancies that met the following criteria: (i) prenatal diagnosis of CHD, (ii) singleton live-birth, and (iii) genetic testing was performed either pre- or postnatally. Genetic results were reviewed by a clinical geneticist for updated variant classification. Fetal growth was stratified as appropriate for gestational age (AGA) or FGR.

RESULTS

Of the total of 445 fetuses that met the study criteria, 325 (73.0%) were AGA and 120 (27.0%) were FGR. Genetic abnormalities were detected in 131 (29.4%) pregnancies. There was a higher rate of genetic abnormalities (36.7% vs. 26.8%, p = 0.04), which was driven by aneuploidies (20.8% vs. 8.9%, p = 0.0006) in the FGR population. Early onset growth restriction was associated with a higher rate of genetic abnormalities (44.5% vs. 25.9%, p = 0.03). The rate of genetic abnormalities was significantly higher in the shunt category as compared to remainder of the cardiac anomalies (62.5% in shunt lesions vs. 24.7%, p < 0.00001). The rates of FGR (40.9% vs. 21.4%, p < 0.0001) and genetic abnormalities (52% vs. 20.4%, p < 0.0001) were significantly higher in the presence of extra-cardiac anomalies (ECA).

CONCLUSION

The presence of FGR in fetal CHD population was associated with underlying genetic abnormalities, specifically aneuploidies. Patients should be appropriately counseled regarding the higher likelihood of a genetic condition in the presence of FGR, early onset FGR, shunt lesions and ECA.

摘要

目的

确定胎儿生长受限（FGR）的存在是否与先天性心脏病（CHD）患者的遗传异常风险增加相关。

方法

这是一项回顾性队列研究，纳入了符合以下标准的妊娠：（i）产前诊断为 CHD，（ii）单胎活产，以及（iii）进行了产前或产后的基因检测。由临床遗传学家对遗传结果进行复查，以更新变异分类。根据胎龄（AGA）或胎儿生长受限（FGR）对胎儿生长进行分层。

结果

在符合研究标准的 445 例胎儿中，325 例（73.0%）为 AGA，120 例（27.0%）为 FGR。在 131 例（29.4%）妊娠中检测到遗传异常。FGR 组的遗传异常发生率更高（36.7% vs. 26.8%，p=0.04），这主要是由 FGR 组的非整倍体（20.8% vs. 8.9%，p=0.0006）引起的。早发性生长受限与遗传异常的发生率较高相关（44.5% vs. 25.9%，p=0.03）。与其他心脏异常相比，分流病变组的遗传异常发生率明显更高（分流病变组为 62.5%，其他心脏异常组为 24.7%，p<0.00001）。伴有心脏外异常（ECA）的胎儿生长受限（FGR）（40.9% vs. 21.4%，p<0.0001）和遗传异常（52% vs. 20.4%，p<0.0001）的发生率显著更高。