University of Utah Health, Salt Lake City, UT; Intermountain Healthcare, Salt Lake City, UT.
University of Utah Health, Salt Lake City, UT.
Am J Obstet Gynecol. 2023 May;228(5):579.e1-579.e11. doi: 10.1016/j.ajog.2022.11.1274. Epub 2022 Nov 8.
Fetal growth abnormalities are associated with a higher incidence of stillbirth, with small and large for gestational age infants incurring a 3 to 4- and 2 to 3-fold increased risk, respectively. Although clinical risk factors such as diabetes, hypertension, and placental insufficiency have been associated with fetal growth aberrations and stillbirth, the role of underlying genetic etiologies remains uncertain.
This study aimed to assess the relationship between abnormal copy number variants and fetal growth abnormalities in stillbirths using chromosomal microarray.
A secondary analysis utilizing a cohort study design of stillbirths from the Stillbirth Collaborative Research Network was performed. Exposure was defined as abnormal copy number variants including aneuploidies, pathogenic copy number variants, and variants of unknown clinical significance. The outcomes were small for gestational age and large for gestational age stillbirths, defined as a birthweight <10th percentile and greater than the 90th percentile for gestational age, respectively.
Among 393 stillbirths with chromosomal microarray and birthweight data, 16% had abnormal copy number variants. The small for gestational age outcome was more common among those with abnormal copy number variants than those with a normal microarray (29.5% vs 16.5%; P=.038). This finding was consistent after adjusting for clinically important variables. In the final model, only abnormal copy number variants and maternal age remained significantly associated with small for gestational age stillbirths, with an adjusted odds ratio of 2.22 (95% confidence interval, 1.12-4.18). Although large for gestational age stillbirths were more likely to have an abnormal microarray: 6.2% vs 3.3% (P=.275), with an odds ratio of 2.35 (95% confidence interval, 0.70-7.90), this finding did not reach statistical significance.
Genetic abnormalities are more common in the setting of small for gestational age stillborn fetuses. Abnormal copy number variants not detectable by traditional karyotype make up approximately 50% of the genetic abnormalities in this population.
胎儿生长异常与较高的死胎发生率相关，小于胎龄儿和大于胎龄儿的风险分别增加 3 至 4 倍和 2 至 3 倍。尽管临床危险因素，如糖尿病、高血压和胎盘功能不全与胎儿生长异常和死胎有关，但潜在遗传病因的作用仍不确定。
本研究旨在通过染色体微阵列评估异常拷贝数变异与死胎中胎儿生长异常的关系。
对来自死胎协作研究网络的死胎队列研究进行了二次分析。暴露定义为异常拷贝数变异，包括非整倍体、致病性拷贝数变异和临床意义不明的变异。结局为小于胎龄儿和大于胎龄儿的死胎，定义为出生体重小于胎龄第 10 百分位和大于胎龄第 90 百分位。
在 393 例具有染色体微阵列和出生体重数据的死胎中，16%存在异常拷贝数变异。异常拷贝数变异组的小于胎龄儿结局比正常微阵列组更常见（29.5%比 16.5%；P=.038）。在调整了重要临床变量后，这一发现仍然一致。在最终模型中，只有异常拷贝数变异和母亲年龄与小于胎龄儿死胎显著相关，调整后的比值比为 2.22（95%置信区间，1.12-4.18）。虽然大于胎龄儿死胎更可能有异常微阵列：6.2%比 3.3%（P=.275），比值比为 2.35（95%置信区间，0.70-7.90），但这一发现没有达到统计学意义。
在小于胎龄儿死胎中，遗传异常更为常见。无法通过传统核型检测到的异常拷贝数变异约占该人群遗传异常的 50%。
