Comparison of Genetic Profiles of Neonates in Intensive Care Units Conceived With or Without Assisted Reproductive Technology

Abstract

ImportanceA growing number of children are conceived with assisted reproductive technology (ART). However, there is a lack of studies systematically analyzing the genetic landscape of live-born children conceived through ART who need intensive care in the neonatal period.ObjectiveTo investigate the incidence and type of molecular defects among neonates conceived through ART who are in intensive care units (NICUs) with suspected genetic conditions.Design, Setting, and ParticipantsThis was a cross-sectional study using data from the China Neonatal Genomes Project, a multicenter national neonatal genome data set managed by the Children’s Hospital of Fudan University. All participants were from level III and IV NICUs and included 535 neonates conceived through ART with suspected genetic conditions, with data collected between August 1, 2016, and December 31, 2021, and 1316 naturally conceived neonates with suspected genetic conditions in the same clinical settings, with data collected between August 1, 2016, and December 31, 2018. The data were analyzed between September 2021 and January 2023.ExposuresWhole-exome sequencing or target clinical exome sequencing with pathogenic or likely pathogenic single-nucleotide variant (SNV) and copy number variation (CNV) detection was performed for each individual.Main Outcomes and MeasuresThe primary outcome was the molecular diagnostic yield, mode of inheritance, spectrum of genetic events, and incidence of de novo variants.ResultsA total of 535 neonates conceived through ART (319 boys [59.6%]) and 1316 naturally conceived neonates (772 boys [58.7%]) were included. A genetic diagnosis was established for 54 patients conceived through ART (10.1%), including 34 patients with SNVs (63.0%) and 20 with CNVs (37.0%). In the non-ART group, 174 patients (13.2%) received a genetic diagnosis, including 120 patients with SNVs (69.0%) and 54 with CNVs (31.0%). The overall diagnostic yield was comparable between the ART group and the naturally conceived neonates (10.1% vs 13.2%; odds ratio [OR], 0.74; 95% CI, 0.53-1.02), as was the proportion of SNVs (63.0% vs 69.0%; OR, 0.68; 95% CI, 0.46-1.00) and CNVs (37.0% vs 31.0%; OR, 0.91; 95% CI, 0.54-1.53) detected by sequencing. Furthermore, the proportions of de novo variants in the ART group and the non-ART group were similar (75.9% [41 of 54] vs 64.4% [112 of 174]; OR, 0.89; 95% CI, 0.62-1.30).Conclusions and RelevanceThis cross-sectional study of neonates in NICUs suggests that the overall genetic diagnostic yield and the incidence of de novo variants were similar between live-born neonates conceived through ART and naturally conceived neonates in the same settings.

Whole-exome sequencing as the first-tier test for patients in neonatal intensive care unit: a Chinese single-center study

“…WES has become a primary clinical diagnostic tool for children suffering from developmental delays, intellectual disabilities, respiratory disease [ 10 , 19 ], and more. Recent discussions have highlighted its use in NICU settings and among neonatal populations in China, viewing it from various perspectives [ 2 , 9 , 12 , 13 ]. Despite these discussions, the potential of WES in diagnosing neonatal GDs remains underexplored.…”

“…Recent discussions have highlighted its use in NICU settings and among neonatal populations in China, viewing it from various perspectives [2,9,12,13]. Despite these discussions, the potential of WES in diagnosing neonatal GDs remains underexplored.…”

“…Additionally, a prospective study [ 11 ] showed that using whole-exome sequencing (WES) as a primary test in infants suspected of monogenic disorders could streamline the diagnostic process, offering a higher diagnostic yield than standard approaches. Recent research has also discussed the application of WES in NICU settings and among neonate populations in China from various perspectives [ 2 , 9 , 12 , 13 ], including the study of molecular defects in neonates conceived through assisted reproductive technology. Despite these advancements, the application of WES in diagnosing neonatal genetic diseases warrants further exploration.…”