Utility of whole-genome sequencing for detection of newborn screening disorders in a population cohort of 1,696 neonates.

PURPOSE: To assess the potential of whole-genome sequencing (WGS) to replicate and augment results from conventional blood-based newborn screening (NBS). METHODS: Research-generated WGS data from an ancestrally diverse cohort of 1,696 infants and both parents of each infant were analyzed for variants in 163 genes involved in disorders included or under discussion for inclusion in US NBS programs. WGS results were compared with results from state NBS and related follow-up testing. RESULTS: NBS genes are generally well covered by WGS. There is a median of one (range: 0-6) database-annotated pathogenic variant in the NBS genes per infant. Results of WGS and NBS in detecting 28 state-screened disorders and four hemoglobin traits were concordant for 88.6% of true positives (n = 35) and 98.9% of true negatives (n = 45,757). Of the five infants affected with a state-screened disorder, WGS identified two whereas NBS detected four. WGS yielded fewer false positives than NBS (0.037 vs. 0.17%) but more results of uncertain significance (0.90 vs. 0.013%). CONCLUSION: WGS may help rule in and rule out NBS disorders, pinpoint molecular diagnoses, and detect conditions not amenable to current NBS assays.

Subtle adverse effects of late preterm birth: a cautionary note.

OBJECTIVE: Late preterm birth increases risk of perinatal health complications that typically resolve in the short term. Thus, early elective delivery is thought to have no long-term effects. Whether there is increased risk of adverse psychological outcomes that emerge in early childhood remains uncertain. METHOD: The authors compared intellectual, neuropsychological, and behavioral outcomes in 278 late preterm (35-36 weeks) and 192 term (37-41 weeks) participants at age 3 years recruited from a single center, using analysis of variance, analysis of covariance, and regression analyses. Late-preterm participants were further subgrouped by admission to the neonatal intensive care unit (NICU; n = 202) or a well-baby unit (n = 76). Analyses included 132 additional participants born at 34 weeks. RESULTS: Late preterm participants had lower general conceptual ability (GCA; i.e., IQ); lower verbal, nonverbal, spatial, visuomotor, and dexterity scores; and poorer adaptability than term participants (p < .01; -0.271 to -0.511 SDs). Gestational age was the most important predictor of these subtle outcomes, not neonatal medical variables; no differences were found between NICU admitted and nonadmitted late-preterm groups. A 1-week increase in gestational age resulted in a 1.941 increase in GCA (d = 0.127). CONCLUSION: Gestation is a developmental continuum best not interrupted during its natural course. Our data showing subtle but appreciable effects have important implications for obstetric practice and parental decision making regarding early elective delivery in the absence of maternal or fetal adverse indications.