Zhou Hang, Cheng Ken, Li Yingsi, Fu Fang, Li Ru, Zhang Yongling, Yang Xin, Jing Xiangyi, Li Fucheng, Han Jin, Pan Min, Zhen Li, Li Dongzhi, Liao Can
Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
School of Medicine, South China University of Technology, Guangzhou, China.
Front Genet. 2022 Apr 28;13:856522. doi: 10.3389/fgene.2022.856522. eCollection 2022.
To evaluate the utility of a chromosomal microarray (CMA) in fetuses with isolated fetal growth restriction (FGR) and explore risk factors for the prediction of chromosomal aberration and perinatal adverse outcomes. This study included 271 fetuses of estimated fetal weight less than the 3rd percentile without other structural malformation. Early-onset and late-onset FGR were defined as gestational weeks less than 32 weeks and more than 32 weeks respectively. These patients underwent quantitative fluorescent polymerase chain reaction (QF-PCR) and CMA as the first-line genetic detection strategy. Chromosomal anomalies were compared after stratified analysis by the early-onset and the late-onset FGR, including the absence or presence of ultrasound soft markers, abnormal amniotic fluid, abnormal umbilical Doppler, and gestational disorders. The follow-up time was within 1 year after birth. Logistic regression was used to seek risk predictors of chromosomal aberration and perinatal adverse outcomes for isolated FGR. The CMA identified clinically significant variants in 18/271 (6.6%) fetuses, and variants of unknown significance (VOUS) in 15/271 (5.5%) fetuses. Stratified analysis showed that there was a higher incidence of clinically significant variants in fetuses with the early-onset FGR compared with late-onset FGR (8.7%, 17/195 vs. 1.3%, 1/76, < 0.05). Regression analysis showed that early gestational age (GA) at diagnosis of FGR was the major risk factor for chromosomal aberration (OR = 0.846). By variable regression analysis, early GA at diagnosis and decreased estimated fetal weight (EFW) percentile of suspicion of FGR, asymmetrical FGR, abnormal amniotic fluid, and severe preeclampsia could all increase the risk of adverse outcomes of isolated FGR including intra-uterine fetal death (IUFD), termination of pregnancy (TOP), and preterm birth in pregnancies with FGR. This study emphasized the value of microarrays for unbalanced genomic variants in fetuses with isolated FGR, especially since the gestational age of nullipara was less than 32 weeks. Perinatal adverse outcomes of isolated FGR were influenced by multiple factors including GA and estimated fetal weight (EFW) percentile of suspicion of FGR, asymmetrical FGR, abnormal amniotic fluid, and severe preeclampsia.
评估染色体微阵列（CMA）在单纯性胎儿生长受限（FGR）胎儿中的应用价值，并探索预测染色体畸变和围产期不良结局的风险因素。本研究纳入了271例估计胎儿体重低于第3百分位数且无其他结构畸形的胎儿。早发型和晚发型FGR分别定义为孕周小于32周和大于32周。这些患者接受了定量荧光聚合酶链反应（QF-PCR）和CMA作为一线基因检测策略。通过早发型和晚发型FGR进行分层分析后比较染色体异常情况，包括是否存在超声软指标、羊水异常、脐动脉多普勒异常和妊娠疾病。随访时间为出生后1年内。采用逻辑回归分析寻找单纯性FGR染色体畸变和围产期不良结局的风险预测因素。CMA在18/271（6.6%）例胎儿中鉴定出临床显著变异，在15/271（5.5%）例胎儿中鉴定出意义未明的变异（VOUS）。分层分析显示，早发型FGR胎儿中临床显著变异的发生率高于晚发型FGR胎儿（8.7%，17/195 vs. 1.3%，1/76，<0.05）。回归分析表明，诊断FGR时的早期孕周（GA）是染色体畸变的主要危险因素（OR = 0.846）。通过变量回归分析，诊断时的早期GA、怀疑FGR时估计胎儿体重（EFW）百分位数降低、不对称性FGR、羊水异常和重度子痫前期均会增加单纯性FGR不良结局的风险，包括宫内胎儿死亡（IUFD）、终止妊娠（TOP）以及FGR妊娠中的早产。本研究强调了微阵列对于单纯性FGR胎儿不平衡基因组变异的价值，尤其是初产妇孕周小于32周的情况。单纯性FGR的围产期不良结局受多种因素影响，包括GA、怀疑FGR时的估计胎儿体重（EFW）百分位数、不对称性FGR、羊水异常和重度子痫前期。
