Fetal growth restriction: associated genetic etiology and pregnancy outcomes in a tertiary referral center

Meiying Cai; Na Lin; Linjuan Su; Xiaoqing Wu; Xiaorui Xie; Shiyi Xu; Xianguo Fu; Liangpu Xu; Hailong Huang

doi:10.1186/s12967-022-03373-z

Fetal growth restriction: associated genetic etiology and pregnancy outcomes in a tertiary referral center

J Transl Med. 2022 Apr 9;20(1):168. doi: 10.1186/s12967-022-03373-z.

Authors

Meiying Cai^#¹, Na Lin^#¹, Linjuan Su¹, Xiaoqing Wu¹, Xiaorui Xie¹, Shiyi Xu², Xianguo Fu³, Liangpu Xu⁴, Hailong Huang⁵

Affiliations

¹ Medical Genetic Diagnosis and Therapy Center, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fuzhou, China.
² Guangxi Medical University, Guangxi, China.
³ Department of Prenatal Diagnosis, Ningde Municipal Hospital, Ningde Normal University, Ningde, China.
⁴ Medical Genetic Diagnosis and Therapy Center, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fuzhou, China. xiliangpu@fjmu.edu.cn.
⁵ Medical Genetic Diagnosis and Therapy Center, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fuzhou, China. huanghailong@fjmu.edu.cn.

^# Contributed equally.

Abstract

Background: The etiology of fetal growth restriction (FGR) is complex and currently, there is a paucity of research about the genetic etiology of fetal growth restriction. We investigated the genetic associations and pregnancy outcomes in cases of fetal growth restriction.

Methods: A retrospective analysis of 210 pregnant women with fetal growth restriction was performed using karyotype analysis and single nucleotide polymorphism arrays (SNP-array). The differences in pathogenic copy number variation (CNV) detected by the two methods were compared. At the same time, the fetuses were divided into three groups: isolated FGR (n = 117), FGR with ultrasonographic soft markers (n = 48), and FGR with ultrasonographic structural anomalies (n = 45). Further, the differences in pathogenic copy number variations were compared among the groups.

Results: The total detection rate of pathogenic CNVs was 12.4% (26/210). Pathogenic copy number variation was detected in 14 cases (6.7%, 14/210) by karyotype analysis. Furthermore, 25 cases (11.9%, 25/210) with pathogenic CNVs were detected using the SNP-array evaluation method. The difference in the pathogenic CNV detection rate between the two methods was statistically significant. The result of the karyotype analysis and SNP-array evaluation was inconsistent for 13 cases with pathogenic CNV. The rate of detecting pathogenic CNVs in fetuses with isolated FGR, FGR combined with ultrasonographic soft markers, and FGR combined with ultrasonographic structural malformations was 6.0, 10.4, and 31.1%, respectively, with significant differences among the groups. During the follow-up, 35 pregnancies were terminated, two abortions occurred, and 13 cases were lost to follow-up. Of the 160 deliveries, nine fetuses had adverse pregnancy outcomes, and the remaining 151 had normal postnatal growth and developmental assessments.

Conclusions: Early diagnosis and timely genomic testing for fetal growth restriction can aid in its perinatal prognosis and subsequent intervention.

Keywords: Copy number variation; Fetal growth restriction; Karyotype analysis; SNP-array.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

DNA Copy Number Variations* / genetics
Female
Fetal Growth Retardation* / genetics
Humans
Pregnancy
Pregnancy Outcome
Prenatal Diagnosis / methods
Retrospective Studies
Tertiary Care Centers