Browsing by Subject "Neonatal screening"

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    Identifying Sickle Cell Disease Beyond the Neonatal Period: A Case Series
    (2025-03-28) Gupta, Soumya; Slaughter, Mary; Li, Katherine; Harter, Michaela; Goubeaux, Derrick L.; Drayton Jackson, Meghan
    Background: Sickle Cell Disease (SCD) is an autosomal recessive chronic condition that causes hemolytic anemia and vaso-occlusive episodes that can present as dactylitis, pain, acute chest syndrome (ACS), and other complications. For early detection and intervention, newborn screening (NBS) for SCD is mandated in all 50 states. However, this screening is not readily available in many other areas of the world. Case Description : Three children who immigrated from countries outside the United States were diagnosed with SCD beyond the neonatal period. A 17-year-old female adopted from Kenya presented to the ER with dyspnea after starting oral contraceptives and was found to have a pulmonary embolism. Hemoglobin (Hgb) was 8.1 g/dl. She rapidly deteriorated and required intubation. Bronchoalveolar lavage revealed straw-colored fluid, a rare finding consistent with ACS. Electrophoresis confirmed HbSS. A 7-year-old male from the Dominican Republic presented with pneumonia and pain. Hgb was 8.4 g/dl. There was familial anemia, but he had not received work-up due to insufficient insurance coverage. Electrophoresis showed HbSS. A 7-year-old male from Nigeria presented to the ED after an episode of gross hematuria. His baseline Hgb was 10 g/dl, and his mother had SCD. Electrophoresis showed HbSS. Clinical Significance: Sickle cell disease is a multisystem disorder with complications that can lead to severe illness. Physicians must maintain high clinical suspicion for SCD in patients who did not receive NBS presenting with recurrent pain, severe infection, end organ damage, or anemia. Diagnosis is confirmed with hemoglobin electrophoresis. Conclusion: This case series highlights the need for heightened SCD awareness, particularly in those from areas without universal NBS. Providers must obtain relevant family history, recognize SCD’s diverse presentations, and work to reduce healthcare access barriers to ensure that patients receive timely diagnosis and care.
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    Rapid Whole-Genomic Sequencing and a Targeted Neonatal Gene Panel in Infants With a Suspected Genetic Disorder
    (American Medical Association, 2023) Maron, Jill L.; Kingsmore, Stephen; Gelb, Bruce D.; Vockley, Jerry; Wigby, Kristen; Bragg, Jennifer; Stroustrup, Annemarie; Poindexter, Brenda; Suhrie, Kristen; Kim, Jae H.; Diacovo, Thomas; Powell, Cynthia M.; Trembath, Andrea; Guidugli, Lucia; Ellsworth, Katarzyna A.; Reed, Dallas; Kurfiss, Anne; Breeze, Janis L.; Trinquart, Ludovic; Davis, Jonathan M.; Pediatrics, School of Medicine
    Importance: Genomic testing in infancy guides medical decisions and can improve health outcomes. However, it is unclear whether genomic sequencing or a targeted neonatal gene-sequencing test provides comparable molecular diagnostic yields and times to return of results. Objective: To compare outcomes of genomic sequencing with those of a targeted neonatal gene-sequencing test. Design, setting, and participants: The Genomic Medicine for Ill Neonates and Infants (GEMINI) study was a prospective, comparative, multicenter study of 400 hospitalized infants younger than 1 year of age (proband) and their parents, when available, suspected of having a genetic disorder. The study was conducted at 6 US hospitals from June 2019 to November 2021. Exposure: Enrolled participants underwent simultaneous testing with genomic sequencing and a targeted neonatal gene-sequencing test. Each laboratory performed an independent interpretation of variants guided by knowledge of the patient's phenotype and returned results to the clinical care team. Change in clinical management, therapies offered, and redirection of care was provided to families based on genetic findings from either platform. Main outcomes and measures: Primary end points were molecular diagnostic yield (participants with ≥1 pathogenic variant or variant of unknown significance), time to return of results, and clinical utility (changes in patient care). Results: A molecular diagnostic variant was identified in 51% of participants (n = 204; 297 variants identified with 134 being novel). Molecular diagnostic yield of genomic sequencing was 49% (95% CI, 44%-54%) vs 27% (95% CI, 23%-32%) with the targeted gene-sequencing test. Genomic sequencing did not report 19 variants found by the targeted neonatal gene-sequencing test; the targeted gene-sequencing test did not report 164 variants identified by genomic sequencing as diagnostic. Variants unidentified by the targeted genomic-sequencing test included structural variants longer than 1 kilobase (25.1%) and genes excluded from the test (24.6%) (McNemar odds ratio, 8.6 [95% CI, 5.4-14.7]). Variant interpretation by laboratories differed by 43%. Median time to return of results was 6.1 days for genomic sequencing and 4.2 days for the targeted genomic-sequencing test; for urgent cases (n = 107) the time was 3.3 days for genomic sequencing and 4.0 days for the targeted gene-sequencing test. Changes in clinical care affected 19% of participants, and 76% of clinicians viewed genomic testing as useful or very useful in clinical decision-making, irrespective of a diagnosis. Conclusions and relevance: The molecular diagnostic yield for genomic sequencing was higher than a targeted neonatal gene-sequencing test, but the time to return of routine results was slower. Interlaboratory variant interpretation contributes to differences in molecular diagnostic yield and may have important consequences for clinical management.
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    Real-world Associations of US Cystic Fibrosis Newborn Screening Programs With Nutritional and Pulmonary Outcomes
    (American Medical Association, 2022) Rosenfeld, Margaret; Ostrenga, Josh; Cromwell, Elizabeth A.; Margaret, Amalia; Szczesniak, Rhonda; Fink, Aliza; Schechter, Michael S.; Faro, Albert; Ren, Clement L.; Morgan, Wayne; Sanders, Don B.; Pediatrics, School of Medicine
    Importance: Newborn screening (NBS) for cystic fibrosis (CF) has been universal in the US since 2010, but its association with clinical outcomes is unclear. Objective: To describe the real-world effectiveness of NBS programs for CF in the US on outcomes up to age 10 years. Design, setting, and participants: This was a retrospective cohort study using CF Foundation Patient Registry data from January 1, 2000, to December 31, 2018. The staggered implementation of NBS programs by state was used to compare longitudinal outcomes among children in the same birth cohort born before vs after the implementation of NBS for CF in their state of birth. Participants included children with an established diagnosis of CF born between January 1, 2000, to December 31, 2018, in any of the 44 states that implemented NBS for CF between 2003 and 2010. Data were analyzed from October 5, 2020, to April 22, 2022. Exposures: Birth before vs after the implementation of NBS for CF in the state of birth. Main outcomes and measures: Longitudinal trajectory of height and weight percentiles from diagnosis, lung function (forced expiratory volume in 1 second, [FEV1] percent predicted) from age 6 years, and age at initial and chronic infection with Pseudomonas aeruginosa using linear mixed-effects and time-to-event models adjusting for birth cohort and potential confounders. Results: A total of 9571 participants (4713 female participants [49.2%]) were eligible for inclusion, with 4510 (47.1%) in the pre-NBS cohort. NBS was associated with higher weight and height percentiles in the first year of life (weight, 6.0; 95% CI, 3.1-8.4; height, 6.6; 95% CI, 3.8-9.3), but these differences decreased with age. There was no association between NBS and FEV1 at age 6 years, but the percent-predicted FEV1 did increase more rapidly with age in the post-NBS cohort. NBS was associated with older age at chronic P aeruginosa infection (hazard ratio, 0.69; 95% CI, 0.54-0.89) but not initial P aeruginosa infection (hazard ratio, 0.88; 95% CI, 0.77-1.01). Conclusions and relevance: NBS for CF in the US was associated with improved nutritional status up to age 10 years, a more rapid increase in lung function, and delayed chronic P aeruginosa infection. In the future, as highly effective modulator therapies become available for infants with CF, NBS will allow for presymptomatic initiation of these disease-modifying therapies before irreversible organ damage.