Newborn screening for Duchenne muscular dystrophy: A two-year pilot study.

OBJECTIVE: Duchenne muscular dystrophy (DMD) is an X-linked disorder resulting in progressive muscle weakness and atrophy, cardiomyopathy, and in late stages, cardiorespiratory impairment, and death. As treatments for DMD have expanded, a DMD newborn screening (NBS) pilot study was conducted in New York State to evaluate the feasibility and benefit of NBS for DMD and to provide an early pre-symptomatic diagnosis. METHODS: At participating hospitals, newborns were recruited to the pilot study, and consent was obtained to screen the newborn for DMD. The first-tier screen measured creatine kinase-MM (CK-MM) in dried blood spot specimens submitted for routine NBS. Newborns with elevated CK-MM were referred for genetic counseling and genetic testing. The latter included deletion/duplication analysis and next-generation sequencing (NGS) of the DMD gene followed by NGS for a panel of neuromuscular conditions if no pathogenic variants were detected in the DMD gene. RESULTS: In the two-year pilot study, 36,781 newborns were screened with CK-MM. Forty-two newborns (25 male and 17 female) were screen positive and referred for genetic testing. Deletions or duplications in the DMD gene were detected in four male infants consistent with DMD or Becker muscular dystrophy. One female DMD carrier was identified. INTERPRETATION: This study demonstrated that the state NBS program infrastructure and screening technologies we used are feasible to perform NBS for DMD. With an increasing number of treatment options, the clinical utility of early identification for affected newborns and their families lends support for NBS for this severe disease.

Improving Recruitment for a Newborn Screening Pilot Study with Adaptations in Response to the COVID-19 Pandemic.

Seven months after the launch of a pilot study to screen newborns for Duchenne Muscular Dystrophy (DMD) in New York State, New York City became an epicenter of the coronavirus disease 2019 (COVID-19) pandemic. All in-person research activities were suspended at the study enrollment institutions of Northwell Health and NewYork-Presbyterian Hospitals, and study recruitment was transitioned to 100% remote. Pre-pandemic, all recruitment was in-person with research staff visiting the postpartum patients 1-2 days after delivery to obtain consent. With the onset of pandemic, the multilingual research staff shifted to calling new mothers while they were in the hospital or shortly after discharge, and consent was collected via emailed e-consent links. With return of study staff to the hospitals, a hybrid approach was implemented with in-person recruitment for babies delivered during the weekdays and remote recruitment for babies delivered on weekends and holidays, a cohort not recruited pre-pandemic. There was a drop in the proportion of eligible babies enrolled with the transition to fully remote recruitment from 64% to 38%. In addition, the proportion of babies enrolled after being approached dropped from 91% to 55%. With hybrid recruitment, the proportion of eligible babies enrolled (70%) and approached babies enrolled (84%) returned to pre-pandemic levels. Our experience adapting our study during the COVID-19 pandemic led us to develop new recruitment strategies that we continue to utilize. The lessons learned from this pilot study can serve to help other research studies adapt novel and effective recruitment methods.

c-KIT-Positive Fatal Diffuse Cutaneous Mastocytosis With Systemic Manifestations in a Neonate.

Diffuse cutaneous mastocytosis is a rare variant of mastocytosis in the neonatal period. We describe a case of c-KIT (DV) mutation-positive fatal diffuse cutaneous mastocytosis with systemic involvement of the gastrointestinal tract and associated malabsorption and hepatosplenomegaly associated with mast cell mediator release symptoms.

Implicit Physician Biases in Periviability Counseling.

OBJECTIVE: To assess whether neonatologists show implicit racial and/or socioeconomic biases and whether these are predictive of recommendations at extreme periviability. STUDY DESIGN: A nationwide survey using a clinical vignette of a woman in labor at 232/7 weeks of gestation asked physicians how likely they were to recommend intensive vs comfort care. Participants were randomized to 1 of 4 versions of the vignette in which racial and socioeconomic stimuli were varied, followed by 2 implicit association tests (IATs). RESULTS: IATs revealed implicit preferences favoring white (mean IAT score = 0.48, P < .001) and greater socioeconomic status (mean IAT score = 0.73, P < .001). Multivariable linear regression analysis showed that physicians with implicit bias toward greater socioeconomic status were more likely than those without bias to recommend comfort care when presented with a patient of high socioeconomic status (P = .037). No significant effect was seen for implicit racial bias. CONCLUSIONS: Building on previous demonstrations of unconscious racial and socioeconomic biases among physicians and their predictive validity, our results suggest that unconscious socioeconomic bias influences recommendations when counseling at the limits of viability. Physicians who display a negative socioeconomic bias are less likely to recommend resuscitation when counseling women of high socioeconomic status. The influence of implicit socioeconomic bias on recommendations at periviability may influence neonatal healthcare disparities and should be explored in future studies.