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Purpose Newborn genomic sequencing (nGS) has great potential to improve pediatric care. Parental interest and concerns about genomics are relatively unexplored. Understanding why parents decline research consent for nGS may reveal implementation barriers. Methods We evaluated parental interest in a randomized trial of nGS in well-baby and intensive care unit nursery settings. Interested families attended an informational enrollment session (ES) with a genetic counselor prior to consenting. Reason(s) for declining participation and sociodemographic associations were analyzed. Results Of 3860 eligible approached families, 10% attended ES, 67% of whom enrolled. Of 1760 families queried for decline reasons, 58% were uninterested in research. Among 499 families considering research, principal reasons for decline prior to ES included burdensome study logistics (48%), feeling overwhelmed postpartum (17%), and lack of interest/discomfort with genetic testing (17%). Decliners after ES more often cited concerns about privacy/insurability (41%) and uncertain/unfavorable results (23%). Conclusion Low interest in research and study logistics were major initial barriers to postpartum enrollment and are likely generic to many postpartum research efforts. Concerns over privacy and result implications were most commonly cited in decliners after ES. Understanding parental concerns around research nGS may inform future integration of nGS into newborn screening, predictive testing, and pediatric diagnostics.

Neonatal screening (NBS) was initiated in Europe during the 1960s with the screening for phenylketonuria. The panel of screened disorders (“conditions”) then gradually expanded, with a boost in the late 1990s with the introduction of tandem mass spectrometry (MS/MS), making it possible to screen for 40–50 conditions using a single blood spot. The most recent additions to screening programmes (screening for cystic fibrosis, severe combined immunodeficiency and spinal muscular atrophy) were assisted by or realised through the introduction of molecular technologies. For this survey, we collected data from 51 European countries. We report the developments between 2010 and 2020 and highlight the achievements reached with the progress made in this period. We also identify areas where further progress can be made, mainly by exchanging knowledge and learning from experiences in neighbouring countries. Between 2010 and 2020, most NBS programmes in geographical Europe matured considerably, both in terms of methodology (modernised) and with regard to the panel of conditions screened (expanded). These developments indicate that more collaboration in Europe through European organisations is gaining momentum. We can only accomplish the timely detection of newborn infants potentially suffering from one of the many rare diseases and take appropriate action by working together.

Background The greatest opportunity for lifelong impact of genomic sequencing is during the newborn period. The “BabySeq Project” is a randomized trial that explores the medical, behavioral, and economic impacts of integrating genomic sequencing into the care of healthy and sick newborns. Methods Families of newborns are enrolled from Boston Children’s Hospital and Brigham and Women’s Hospital nurseries, and half are randomized to receive genomic sequencing and a report that includes monogenic disease variants, recessive carrier variants for childhood onset or actionable disorders, and pharmacogenomic variants. All families participate in a disclosure session, which includes the return of results for those in the sequencing arm. Outcomes are collected through review of medical records and surveys of parents and health care providers and include the rationale for choice of genes and variants to report; what genomic data adds to the medical management of sick and healthy babies; and the medical, behavioral, and economic impacts of integrating genomic sequencing into the care of healthy and sick newborns. Discussion The BabySeq Project will provide empirical data about the risks, benefits and costs of newborn genomic sequencing and will inform policy decisions related to universal genomic screening of newborns. Trial registration The study is registered in ClinicalTrials.gov Identifier: NCT02422511 . Registration date: 10 April 2015.

In November, 2015, an epidemic of microcephaly was reported in Brazil, which was later attributed to congenital Zika virus infection. 7830 suspected cases had been reported to the Brazilian Ministry of Health by June 4, 2016, but little is known about their characteristics. We aimed to describe these newborn babies in terms of clinical findings, anthropometry, and survival. We reviewed all 1501 liveborn infants for whom investigation by medical teams at State level had been completed as of Feb 27, 2016, and classified suspected cases into five categories based on neuroimaging and laboratory results for Zika virus and other relevant infections. Definite cases had laboratory evidence of Zika virus infection; highly probable cases presented specific neuroimaging findings, and negative laboratory results for other congenital infections; moderately probable cases had specific imaging findings but other infections could not be ruled out; somewhat probable cases had imaging findings, but these were not reported in detail by the local teams; all other newborn babies were classified as discarded cases. Head circumference by gestational age was assessed with InterGrowth standards. First week mortality and history of rash were provided by the State medical teams. Between Nov 19, 2015, and Feb 27, 2015, investigations were completed for 1501 suspected cases reported to the Brazilian Ministry of Health, of whom 899 were discarded. Of the remainder 602 cases, 76 were definite, 54 highly probable, 181 moderately probable, and 291 somewhat probable of congenital Zika virus syndrome. Clinical, anthropometric, and survival differences were small among the four groups. Compared with these four groups, the 899 discarded cases had larger head circumferences (mean Z scores −1·54 vs −3·13, difference 1·58 [95% CI 1·45–1·72]); lower first-week mortality (14 per 1000 vs 51 per 1000; rate ratio 0·28 [95% CI 0·14–0·56]); and were less likely to have a history of rash during pregnancy (20·7% vs 61·4%, ratio 0·34 [95% CI 0·27–0·42]). Rashes in the third trimester of pregnancy were associated with brain abnormalities despite normal sized heads. One in five definite or probable cases presented head circumferences in the normal range (above −2 SD below the median of the InterGrowth standard) and for one third of definite and probable cases there was no history of a rash during pregnancy. The peak of the epidemic occurred in late November, 2015. Zika virus congenital syndrome is a new teratogenic disease. Because many definite or probable cases present normal head circumference values and their mothers do not report having a rash, screening criteria must be revised in order to detect all affected newborn babies. Brazilian Ministry of Health, Pan American Health Organization, and Wellcome Trust.

To update the congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency clinical practice guideline published by the Endocrine Society in 2010. The writing committee presents updated best practice guidelines for the clinical management of congenital adrenal hyperplasia based on published evidence and expert opinion with added considerations for patient safety, quality of life, cost, and utilization.

Background: In spinal muscular atrophy, clinical trial results indicated that disease-modifying treatments are highly effective when given prior to symptom onset, which has prompted newborn screening programs in growing number of countries. However, prognosis of those patients cannot be inferred from clinical trials conducted in presymptomatic individuals, as in some cases disease presents very early. Methods: we conducted a systematic review of articles published up to January 2023. Results: Among 35 patients with three SMN2 copies treated before 42 days of age and followed-up for at least 18 months, all but one achieved autonomous ambulation. Of 41 patients with two SMN2 copies, who were non-symptomatic at treatment initiation, all achieved a sitting position independently and 31 were able to walk. Of 16 patients with two SMN2 copies followed-up for at least 18 months who presented with symptoms at treatment onset, 3 achieved the walking milestone and all but one were able to sit without support. Conclusions: evaluation of data from 18 publications indicates that the results of early treatment depend on the number of SMN2 copies and the initial neurological status of the patient.

In this paper, we explore key aspects of the complex ethical and legal landscape surrounding consent in the context of incorporating genomic sequencing into existing newborn bloodspot screening programs. In particular, we consider the potential impact of genomic sequencing on the health rights of the child in relation to existing consent practices in newborn screening. We begin with an introduction to newborn screening programs and their population health goals. We then discuss public health ethics as a rationale underpinning newborn screening before turning to consent. We go on to describe seven current research projects on genomic sequencing in newborn screening and then introduce the ‘right of the asymptomatic at-risk child to be found’ as a useful concept to draw on when considering consent to newborn screening. We draw on this novel right to argue for the adoption of “appropriate consent” when it comes to certain uses of genomics in newborn screening. We contend that, for ‘virtual panels’ at least, appropriate consent proportionately balances the ongoing universality of newborn screening for important health conditions with an acknowledgement of the complex outcomes that bringing a complicated diagnostic technology into the screening domain will generate.

BackgroundSpinal muscular atrophy (SMA) is due to the homozygous absence of SMN1 in around 97% of patients, independent of the severity (classically ranked into types I–III). The high genetic homogeneity, coupled with the excellent results of presymptomatic treatments of patients with each of the three disease-modifying therapies available, makes SMA one of the golden candidates to genetic newborn screening (NBS) (SMA-NBS). The implementation of SMA in NBS national programmes occurring in some countries is an arising new issue that the scientific community has to address. We report here the results of the first Italian SMA-NBS project and provide some proposals for updating the current molecular diagnostic scenario.MethodsThe screening test was performed by an in-house-developed qPCR assay, amplifying SMN1 and SMN2. Molecular prognosis was assessed on fresh blood samples.ResultsWe found 15 patients/90885 newborns (incidence 1:6059) having the following SMN2 genotypes: 1 (one patient), 2 (eight patients), 2+c.859G>C variant (one patient), 3 (three patients), 4 (one patient) or 6 copies (one patient). Six patients (40%) showed signs suggestive of SMA at birth. We also discuss some unusual cases we found.ConclusionThe molecular diagnosis of SMA needs to adapt to the new era of the disease with specific guidelines and standard operating procedures. In detail, SMA diagnosis should be felt as a true medical urgency due to therapeutic implications; SMN2 copy assessment needs to be standardised; commercially available tests need to be improved for higher SMN2 copies determination; and the SMN2 splicing-modifier variants should be routinely tested in SMA-NBS.

This Consensus Statement covers recommendations for the diagnosis and management of patients with pseudohypoparathyroidism (PHP) and related disorders, which comprise metabolic disorders characterized by physical findings that variably include short bones, short stature, a stocky build, early-onset obesity and ectopic ossifications, as well as endocrine defects that often include resistance to parathyroid hormone (PTH) and TSH. The presentation and severity of PHP and its related disorders vary between affected individuals with considerable clinical and molecular overlap between the different types. A specific diagnosis is often delayed owing to lack of recognition of the syndrome and associated features. The participants in this Consensus Statement agreed that the diagnosis of PHP should be based on major criteria, including resistance to PTH, ectopic ossifications, brachydactyly and early-onset obesity. The clinical and laboratory diagnosis should be confirmed by a molecular genetic analysis. Patients should be screened at diagnosis and during follow-up for specific features, such as PTH resistance, TSH resistance, growth hormone deficiency, hypogonadism, skeletal deformities, oral health, weight gain, glucose intolerance or type 2 diabetes mellitus, and hypertension, as well as subcutaneous and/or deeper ectopic ossifications and neurocognitive impairment. Overall, a coordinated and multidisciplinary approach from infancy through adulthood, including a transition programme, should help us to improve the care of patients affected by these disorders.

ObjectiveTo evaluate England’s NHS newborn sickle cell screening programme performance in children up to the age of 5 years.DesignCohort of resident infants with sickle cell disease (SCD) born between 1 September 2010 and 31 August 2015 and followed until August 2016.Participants1317 infants with SCD were notified to the study from all centres in England and 1313 (99%) were followed up.InterventionsEarly enrolment in clinical follow-up, parental education and routine penicillin prophylaxis.Main outcome measuresAge seen by a specialist clinician, age at prescription of penicillin prophylaxis and mortality.ResultsAll but two resident cases of SCD were identified through screening; one baby was enrolled in care after prenatal diagnosis; one baby whose parents refused newborn screening presented symptomatically. There were 1054/1313 (80.3%, 95% CI 78% to 82.4%) SCD cases seen by a specialist by 3 months of age and 1273/1313 (97%, 95% CI 95.9% to 97.8%) by 6 months. The percentage seen by 3 months increased from 77% in 2010 to 85.4% in 2015. 1038/1292 (80.3%, 95% CI 78.1% to 82.5%) were prescribed penicillin by 3 months of age and 1257/1292 (97.3%, 95% CI 96.3% to 98.1%) by 6 months. There were three SCD deaths <5 years caused by invasive pneumococcal disease (IPD) sensitive to penicillin.ConclusionThe SCD screening programme is effective at detecting affected infants. Enrolment into specialist care is timely but below the programme standards. Mortality is reducing but adherence to antibiotic prophylaxis remains important for IPD serotypes not in the current vaccine schedule.