Going Back in Time: Prenatal Presentations of Postnatal Genetic Diagnoses Made in a Neonatal Intensive Care Unit.

Objectives: Prenatal genetic diagnosis can impact care across the perinatal continuum; however, prenatal suspicion for genetic disorders may be complicated by incomplete knowledge of fetal rare-disease phenotypes. Here, we describe the prenatal presentations of a cohort of infants with rare genetic conditions who were diagnosed postnatally in a neonatal intensive care unit (NICU), to characterize prenatal presenting features and evaluate why the diagnosis was not identified prenatally.

Methods: Retrospective cohort study of infants born over a 7 year period (2017-2023) who were admitted to a Level IV NICU and received a postnatal genetic diagnosis prior to 1 year of age. We identified which of these infants had been imaged prenatally at our Maternal Fetal Care Center (MFCC) as an opportunity for prenatal genetic diagnosis. Clinical data were abstracted from the medical records.

Results: 51 cases met the inclusion criteria. Nine of the 51 infants were not strongly suspected to have a genetic syndrome prenatally when seen at the MFCC, as evidenced by lack of prenatal genetic consultation and lack of documented suspicion for a genetic etiology. These cases largely had absent or uncertain prenatal phenotypes. In most cases (42/51, 82.4%), prenatal diagnostic testing was not pursued even if offered. Overall, postnatal diagnoses, of which there was one dual diagnosis, were made by karyotype/FISH (11/52, 21.1%), microarray (8/52, 15.4%), gene panel/targeted testing (17/52, 32.7%), or exome sequencing (16/52, 30.8%).

Conclusions: Our data illustrate the challenges in fetal phenotyping and support a broad approach to prenatal testing to facilitate early genetic diagnosis, which may meaningfully impact postnatal care.