Neonatal Screening

ImportanceDetection of congenital cytomegalovirus (cCMV) infection has previously relied on targeted screening programs or clinical recognition; however, these approaches miss most cCMV-infected newborns and fail to identify those infants who are asymptomatic at birth but at risk for late-onset sensorineural hearing loss.ObjectiveTo determine the feasibility of using routinely collected newborn dried blood spots (DBS) in a population-based cCMV screen to identify infants at risk for hearing loss and describe outcomes of infants screened.Design, setting, and participantsThis diagnostic study of a population-based screening program in Ontario, Canada, took place from July 29, 2019, to July 31, 2023. All newborns with a DBS sample collected as part of routine care were screened using polymerase chain reaction (PCR) analysis for cCMV as a risk factor for hearing loss. Infants with positive DBS PCR results for cCMV were referred for confirmation of infection by urine PCR (the gold standard), as well as complete medical and audiologic assessments for sequelae of cCMV infection. Infants with possible or confirmed symptomatic cCMV were referred to pediatric infectious disease specialists for evaluation for potential treatment with valganciclovir.ExposureDetection of cCMV by polymerase chain reaction assay on a newborn DBS.Main outcomes and measuresNumber of infants with positive screening results successfully retrieved and confirmed to have cCMV and the timeliness of retrieval and symptomatic evaluation.ResultsOf 565 987 infants born in the screening period, 551 034 (97.4%) received cCMV screening on the DBS (45.7% female, 54.3% male). Of these infants, 689 (0.13%) screened positive for cCMV; 601 (87.2%) had cCMV infection confirmed and a complete assessment of sequelae of their congenital infection. Ninety-six infants with completed assessments (16.0%) were deemed to have cCMV symptoms, and 63 of these (65.6%) began valganciclovir treatment. Sensorineural hearing loss was confirmed in 34 of 96 infants (35.4%).Conclusions and relevanceThis program found acceptable and feasible implementation of a population-based screening program using routinely collected DBS samples, suggesting that it may serve as a template for jurisdictions considering universal cCMV screening. The program had a much lower than expected prevalence of cCMV-positive screens but still identified many children who would otherwise not have been diagnosed and who would benefit from ongoing audiologic surveillance.

BackgroundNewborn screening (NBS) for severe combined immunodeficiency (SCID), X-linked agammaglobulinemia (XLA), and spinal muscular atrophy (SMA) enables early diagnosis and intervention, significantly improving patient outcomes. Advances in real-time polymerase chain reaction (PCR) technology have been instrumental in facilitating their inclusion in NBS programs.MethodsWe employed multiplex real-time PCR to simultaneously detect T-cell receptor excision circles (TRECs), kappa-deleting recombination excision circles (KRECs), and the absence of the survival motor neuron (SMN) 1 gene in dried blood spots from 103,240 newborns in Zhejiang Province, China, between July 2021 and December 2022.ResultsOf all the samples, 122 were requested further evaluation. After flow cytometry evaluation and/or genetic diagnostics, we identified one patient with SCID, two patients with XLA, nine patients with SMA [one of whom also had Wiskott-Aldrich Syndrome (WAS)], and eight patients with other medical conditions. The positive predictive values (PPVs) of NBS for SCID, XLA, and SMA were 2.44%, 2.78%, and 100%, respectively. The estimated prevalence rates in the Chinese population were 1 in 103,240 for SCID, 1 in 51,620 for XLA, and 1 in 11,471 for SMA.ConclusionThis study represents the first large-scale screening in mainland China using a TREC/KREC/SMN1 multiplex assay, providing valuable epidemiological data. Our findings suggest that this multiplex assay is an effective screening method for SCID, XLA, and SMA, potentially supporting the universal implementation of NBS programs across China.

Sickle cell disease (SCD) is a worldwide genetic blood disorder. Roughly 400,000 babies are born with SCD each year worldwide. More than 75% of these births occur in sub-Saharan Africa. The establishment of sustainable newborn screening NBS programs is an excellent approach to improving the health of persons living with SCD. The need to set up such programs in Africa cannot be overemphasized. However, initial implementation does not guarantee sustainability. More than 500 children with sickle cell anaemia (SCA) die every day due to lack of access to early diagnosis and related treatment. We systematically highlighted suggestions proffered so far, for the sustainability of NBS in low income, high burden countries. We searched online databases, PubMed, and Google Scholar for literature on sustainability of newborn screening (NBS) published between 2012 and 2022. Articles were included if they reported as outcome; sustainability, government participation, scaling up and expansion of NBS, improved patient enrolment in the newborn screening programe. Articles not suggesting same were excluded. Data were extracted from published reports. Primary outcome was government participation and enhanced patient enrolment in the NBS programe. Thematic content analysis was applied using inductive and deductive codes. We came up with 9 major themes. This study is registered with PROSPERO with registration number as CRD42023381821. Literature search yielded 918 articles (including manual searching). After screening, nine (9) publications were suitable for data extraction and analysis. Two more articles were added by manual searching, making a total of eleven (11) articles. The most frequently addressed core elements of sustainability in these papers were complete integration of services into national health care systems for sustainability of NBS programs in Low-income high-burden countries, funding and engagement from government partners from the very beginning of program development should be prioritized. Screening should be tailored to the local context; using DBS on HemoTypeSC could be a game changer for scaling up and expanding the newborn screening program in Sub-Saharan Africa.

ImportanceCongenital cytomegalovirus (cCMV) is the most common nongenetic cause of sensorineural hearing loss in children and a cause of long-term neurological disabilities. In the absence of universal screening, cCMV disease in many newborns will go undiagnosed and untreated.ObjectiveTo determine the feasibility, screen-positive rate, and parental acceptance of newborn screening for cCMV using dried blood spot (DBS) specimens.Design, setting, and participantsIn this population-based diagnostic study, newborns whose DBS specimens were submitted to the New York State Newborn Screening Program from October 2, 2023, through September 30, 2024, for routine screening were also screened for CMV. Parents were given the option to opt out of receiving CMV results. Infectious disease specialists at designated medical centers performed follow-up of referred newborns. Of the 208 322 newborns whose specimens were submitted, 245 (0.1%) were opted out of the CMV screen by their parents; 22 families did so after CMV results were released.ExposureDBS screening of newborns.Main outcomes and measuresCMV was detected in DBS specimens from newborns using a quantitative polymerase chain reaction analysis. Appropriate follow-up and treatment were provided to referred newborns.ResultsOf the 208 099 newborns (48.6% female and 51.0% male; mean [SD] age at specimen collection, 3.5 [12.3] days [median, 1.0 days]) whose CMV results were reported, 529 had positive CMV screen results (0.3%). Following referral and initial diagnostic evaluation, 276 of the 529 newborns (52.2%) were diagnosed with cCMV (overall rate of 0.1%). Among the 276 newborns with cCMV, 68 (24.6%) had symptomatic cCMV disease, 197 (71.4%) had asymptomatic infection, and 11 (4.0%) had isolated sensorineural hearing loss. Additionally, 131 of the 529 referred newborns (24.8%) had likely acquired CMV postnatally, 17 (3.2%) had false-positive screen results, 43 (8.1%) had unknown CMV classification, and 62 (11.7%) were lost to follow-up or their parents declined follow-up. Of the 68 newborns with symptomatic cCMV disease, 48 (70.6%) were treated with antiviral medication.Conclusions and relevanceIn this diagnostic study, early identification of cCMV allowed newborns to be evaluated, which provided an opportunity for improved outcomes. Although the intent of the screening was to detect cCMV, a sizeable minority of cases identified had postnatally acquired CMV infections. Further studies that incorporate long-term data are needed to better understand the impact of cCMV identification among newborns with asymptomatic infection.