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Observational Study
. 2022 Jan;181(1):359-367.
doi: 10.1007/s00431-021-04213-w. Epub 2021 Aug 4.

Congenital anomalies and genetic disorders in neonates and infants: a single-center observational cohort study

A Marouane  1 , R A C M Olde Keizer  2 , G W J Frederix  1   2 , L E L M Vissers  3 , W P de Boode  4 , W A G van Zelst-Stams  5
Affiliations
Observational Study

Congenital anomalies and genetic disorders in neonates and infants: a single-center observational cohort study

A Marouane et al. Eur J Pediatr. 2022 Jan.

Abstract

Neonates with genetic disorders or congenital anomalies (CA) contribute considerably to morbidity and mortality in neonatal intensive care units (NICUs). The objective of this study is to study the prevalence of genetic disorders in an academic level IV NICU. We retrospective collected and analyzed both clinical and genetic data of all 1444 infants admitted to the NICU of the Radboudumc (October 2013 to October 2015). Data were collected until infants reached at least 2 years of age. A total of 13% (194/1444) of the patients were genetically tested, and 32% (461/1444) had a CA. A total of 37% (72/194) had a laboratory-confirmed genetic diagnosis. In 53%, the diagnosis was made post-neonatally (median age = 209 days) using assays including exome sequencing. Exactly 63% (291/461) of the patients with CA, however, never received genetic testing, despite being clinically similar those who did.Conclusions: Genetic disorders were suspected in 13% of the cohort, but only confirmed in 5%. Most received their genetic diagnosis in the post-neonatal period. Extrapolation of the diagnostic yield suggests that up to 6% of our cohort may have remained genetically undiagnosed. Our data show the need to improve genetic care in the NICU for more inclusive, earlier, and faster genetic diagnosis to enable tailored management. What is Known: • Genetic disorders are suspected in many neonates but only genetically confirmed in a minority. • The presence of a genetic disorder can be easily missed and will often lead to a diagnostic odyssey requiring extensive evaluations, both clinically and genetically. What is New: • Different aspects of the clinical features and uptake of genetic test in a NICU cohort. • The need to improve genetic care in the NICU for more inclusive, earlier, and faster genetic diagnosis to enable tailored management.

Keywords: Diagnostic yield; Genetic diagnosis; NICU; Neonatal intensive care unit; Neonates.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart of the study
Fig. 2
Fig. 2
Percentage of all genetic tests per time period. QF-PCR quantitative fluorescent polymerase chain reaction
Fig. 3
Fig. 3
Relative frequencies for the occurrence of congenital anomalies in the total cohort in relation to genetic testing and its outcomes
Fig. 4
Fig. 4
Relative contribution of genetic assay establishing the conclusive genetic diagnosis in relation to moment of testing (panel A) and type of genetic alterations identified (panel B). Panel A UPD uniparental disomy. CNV copy number variant. SNV single-nucleotide variant. Panel B NIPT noninvasive prenatal testing. *Six abnormal NIPTs were confirmed with QF-PCR. QF-PCR quantitative fluorescent polymerase chain reaction. WES whole-exome sequencing
See this image and copyright information in PMC

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