Retrospective identification of prenatal fetal anomalies associated with diagnostic neonatal genomic sequencing results

Abstract Objective To determine which types of fetal anomalies are associated with postnatal diagnoses of genetic diseases by genomic sequencing and to assess how prenatal genomic sequencing could affect clinical management. Method This was a secondary analysis of the second Newborn Sequencing in Genomic Medicine and Public Health study that compared fetal imaging results in critically ill infants who had actionable versus negative postnatal genomic sequencing results. Results Of 213 infants who received genomic sequencing, 80 had available prenatal ultrasounds. Twenty‐one (26%) of these were found to have genetic diseases by genomic sequencing. Fourteen (67%) of the 21 with genetic diseases had suspected anomalies prenatally, compared with 33 (56%) of 59 with negative results. Among fetuses with suspected anomalies, genetic diseases were 4.5 times more common in those with multiple anomalies and 6.7 times more common in those with anomalies of the extremities compared to those with negative results. Had the genetic diseases been diagnosed prenatally, clinical management would have been altered in 13 of 14. Conclusion Critically ill infants with diagnostic genomic sequencing were more likely to have multiple anomalies and anomalies of the extremities on fetal imaging. Among almost all infants with suspected fetal anomalies and diagnostic genomic sequencing results, prenatal diagnosis would have likely altered clinical management.