Etiologic evaluation and pregnancy outcomes of fetal growth restriction (FGR) associated with structural malformations: experience from a tertiary referral center

Abstract

Abstract This study aimed to evaluate the etiology and pregnancy outcomes of fetuses underwent invasive prenatal diagnosis for fetal growth restriction (FGR) accompanied by structural malformations. Data from 130 pregnancies referred for prenatal diagnosis for FGR accompanied by structural malformations were obtained between July 2011 and July 2023. Traditional karyotyping were conducted for all the subjects. A total of 37 (28.5%) cases of chromosomal abnormalities were detected by karyotyping, including 30 cases of numerical anomalies and 7 cases of unbalanced structural anomalies. Trisomy 18 was the most common abnormalities, accounting for 51.4%, significantly higher than any other chromosomal abnormality. Early-onset and late-onset FGR accounted for 88.5% (115/130) and 11.5% (15/130) of the cohort, and their incidences of chromosomal abnormalities were 29.6% (34/115) and 20.0% (3/15), respectively (p > 0.05). The majority (74.6%, 97/130) of the cohort were affected by a single-system malformation, with chromosomal abnormalities found in 19.6% (19/97) of cases. While in pregnancies of structural malformations involving two and multiple systems, the frequencies were 56.5% (13/23), and 50.0% (5/10), respectively. Single nucleotide polymorphism array (SNP array) was performed in parallel for 65 of them, and it revealed additional 5 (7.7%) cases of copy number variants (CNVs) compared to karyotyping. Polymerase chain reaction (PCR) was used for detection of cytomegalovirus (CMV) DNA in 92 cases. All fetuses with FGR associated with two or more system malformations were either terminated or stillborn, irrespective of chromosomal aberrations. Conversely, 71.8% of pregnancies with a single-system malformation and normal genetic testing results resulted in live births. Additionally, two (2.2%) cases tested positive for CMV DNA, resulting in one termination and one case of serious developmental disorder after birth. Our study suggests that structural malformations associated with FGR are more inclined to affect a single system. When multiple systems are involved, the incidence of chromosomal abnormalities and termination rates are notably high. We strongly recommend utilizing CMA and CMV DNA examinations in cases that necessitate invasive prenatal diagnosis. These tests can provide valuable insights for etiological exploration and guidance in pregnancy management.