Implementation Of Universal Newborn Screening Research Articles

Newborn Screening for Congenital Cytomegalovirus

What Is the Issue? Congenital cytomegalovirus (cCMV) is estimated to affect between 0.2% and 2.4% of newborns worldwide, and may cause long-term effects, including hearing loss and neurodevelopmental disability. Newborn screening for cCMV can identify affected neonates and provide an opportunity for early treatment, which may reduce any long-term effects from infection. We wanted to know if universal newborn screening is a clinically effective and cost-effective intervention for identifying and managing cCMV. What Did We Do? We identified and summarized published literature comparing the clinical effectiveness and cost-effectiveness of universal newborn screening with either targeted newborn screening or no screening for congenital cytomegalovirus in neonates. We also identified and summarized published, evidence-based guidelines that make recommendations concerning the use of newborn screening for congenital cytomegalovirus to help inform decisions considering the use of this intervention. An information specialist searched for peer-reviewed and grey literature sources published between January 1, 2014, and March 19, 2024. The search was limited to English-language documents. One reviewer screened articles for eligibility based on predefined criteria, critically appraised the included studies, and narratively summarized the findings. What Did We Find? Evidence from 1 prospective cohort study in the US found that, compared to universal newborn screening for cCMV, targeted newborn screening failed to identify a significant proportion of neonates who developed hearing loss associated with infection. Three cost-effectiveness evaluations concluded that universal newborn screening for cCMV was cost-effective when compared to targeted newborn screening or no screening. None of these analyses were specific to the Canadian context. While 1 of 3 evidence-based guidelines identified by this review makes a recommendation favouring universal newborn screening for cCMV, 2 evidence-based guidelines recommend against the implementation of universal newborn screening for cCMV (including 1 from the Canadian context), generally citing a lack of sufficient clinical evidence. What Does This Mean? The included cost-effectiveness studies and evidence-based guidelines in this report emphasize that limited clinical evidence is currently available to inform decision-making concerning newborn screening for cCMV. Jurisdictions where universal newborn screening for cCMV has been implemented provide an opportunity for clinical research to support and inform future decision-making. The current limitation of available clinical data describing newborn screening for cCMV will require decision-makers to draw from a broader set of inputs and sources than those available from empirical studies.

Sickle Cell Disease Births and Social Vulnerability (2016-2020): A Report from the Sickle Cell Data Collection Program

Introduction Despite national implementation of universal newborn screening for sickle cell disease (SCD) since 2006, data on the prevalence of SCD births in the United States are scarce. Updated prevalence data by geographic location are needed to guide the allocation of resources and to connect newborns to comprehensive SCD care. The purposes of this study were to describe the 1) crude and race-adjusted SCD birth prevalence and 2) crude SCD birth prevalence by quartiles of the social vulnerability index (SVI, CDC, 2020) in 11 Sickle Cell Data Collection (SCDC) program states (Alabama, California, Colorado, Georgia, Indiana, Michigan, Minnesota, North Carolina, Tennessee, Virginia, and Wisconsin). Methods This retrospective cohort study used newborn screening (NBS) records from 2016 to 2020. Births were included if they were confirmed SCD births and the mother's county of residence at the time of birth was in an SCDC state. Mother's county and newborn's race, ethnicity, sex, date of birth, and genotype were extracted from NBS records or birth certificates, if available. Crude SCD birth prevalence per 10,000 was calculated by dividing the cumulative number of SCD births by the cumulative number of all live births from 2016 to 2020 and multiplying by 10,000. Race-adjusted SCD birth prevalence was calculated by dividing the cumulative number of Black SCD births by live non-Hispanic Black (NHB) births from 2016 to 2020 and multiplying by 10,000. Frequency of all births and NHB births were obtained from each state's health department. County characteristics were quantified by the SVI using the 2020 state-ranked CDC/ATSDR SVI datasets (CDC, 2020) and were matched to mother's county of residence at birth. SVI ranks counties on 16 social factors, including unemployment, minority status, and disability. Ranks were grouped into SVI quartiles: low (0 ≤ SVI ≤ 0.25), medium (0.25 < SVI ≤ 0.5), high (0.5 < SVI ≤ 0.75) and very high (0.75 < SVI ≤ 1.0) vulnerability. Crude SCD birth prevalence was calculated for each SVI quartile. Results From 2016 through 2020, there were 3,305 newborns with SCD across 11 SCDC states [ 49.6% male, 89.8% Black]. Georgia had the highest number of births (n=758) followed by North Carolina (n=435), California (n=419), and Alabama (n=386). The majority (57.0%) had Hb SS or Hb S Beta 0 thalassemia, 27.9% had Hb SC, and 9.6 % had Hb S Beta + thalassemia or other SCD type. The crude SCD birth prevalence ranged from 1.22 to 13.22 per 10,000 live births. The race-adjusted SCD birth prevalence for SCDC states was 28.55 per 10,000 or 1 in every 350 NHB births. Race-adjusted birth prevalence varied among states ranging from 19.53 to 34.11 per 10,000 NHB births (Table 1). Overall, the majority (67%) of mothers of newborns with SCD resided in high or very high social vulnerability counties (Figure 1). Except for Colorado, where the highest crude SCD birth prevalence was among mothers residing in medium social vulnerability counties, the remaining 10 SCDC states had the highest prevalence among mothers residing in high or very high social vulnerability counties. Limitations include using the mother's reported race for all births to calculate race-adjusted birth prevalence. Additionally, because of missing data on ethnicity for SCD births, we used all Black SCD births, rather than non-Hispanic Black SCD births, to calculate the race-adjusted SCD birth prevalence. Despite the limitations, the study provides crude and race-adjusted SCD birth prevalence data from 11 states in the South, Midwest, and Western United States, covering an estimated one third of the SCD population in the United States. Furthermore, providing the crude prevalence of SCD births by SVI quartile adds valuable information on county-level characteristics that might influence health outcomes for newborns with SCD. Conclusions The race-adjusted birth prevalence for SCD remains stable from previous estimates at 1 in every 350 BNH births. The finding that most mothers of newborns with SCD reside in high and very high social vulnerability counties at the time of birth underscores the importance of assessing social determinants of health (SDOH) that may impact health outcomes for newborns with SCD. Findings from this report can be used to guide state- and county-level programs that address SDOH for people with SCD and have implication for clinicians who must incorporate screening for SDOH in their practice and refer families to community resources as needed.

Implementation of Universal Newborn Screening for Severe Combined Immunodeficiency in Singapore While Continuing Routine Bacille-Calmette-Guerin Vaccination Given at Birth.

IntroductionSevere Combined Immunodeficiency (SCID) is generally fatal if untreated; it predisposes to severe infections, including disseminated Bacille-Calmette-Guerin (BCG) disease from BCG vaccination at birth. However, delaying BCG vaccination can be detrimental to the population in tuberculosis-endemic regions. Early diagnosis of SCID through newborn screening followed by pre-emptive treatment with anti-mycobacterial therapy may be an alternative strategy to delaying routine BCG vaccination. We report the results of the first year of newborn SCID screening in Singapore while continuing routine BCG vaccination at birth.MethodNewborn screening using a T-cell receptor excision circle (TREC) assay was performed in dried blood spots received between 10 October 2019 to 9 October 2020 using the Enlite Neonatal TREC kit. Patients with low TREC had lymphocyte subset analysis and full blood count performed to determine the severity of lymphopenia and likelihood of SCID to guide further management.ResultsOf the 35888 newborns screened in 1 year, no SCID cases were detected, while 13 cases of non-SCID T-cell lymphopenia (TCL) were picked up. Using a threshold for normal TREC to be >18 copies/μL, the retest rate was 0.1% and referral rate to immunologist was 0.04%. Initial low TREC correlated with low absolute lymphocyte counts (ALC), and subsequent normal ALC corresponded with increases in TREC, thus patients with normal first CD3+ T cell counts were considered to have transient idiopathic TCL instead of false positive results. 7/13 (54%) had secondary TCL (from sepsis, Trisomy 21 with hydrops and stoma losses or chylothorax, extreme prematurity, or partial DiGeorge Syndrome) and 6/13 (46%) had idiopathic TCL. No cases of SCID were diagnosed clinically in Singapore during this period and for 10 months after, indicating that no cases were missed by the screening program. 8/9 (89%) of term infants with abnormal TREC results received BCG vaccination within the first 6 days of life when TREC and ALC were low. No patients developed BCG complications after a median follow-up of 17 months.ConclusionNewborn screening for SCID can be implemented while continuing routine BCG vaccination at birth. Patients with transient TCL and no underlying primary immunodeficiency are able to tolerate BCG vaccination.

New Era of Curative Therapy for Spinal Muscular Atrophy in Children; Do We Need Implementation of Universal Newborn Screening for Spinal Muscular Atrophy?

New Era of Curative Therapy for Spinal Muscular Atrophy in Children; Do We Need Implementation of Universal Newborn Screening for Spinal Muscular Atrophy?

Effects of Diagnosis by Newborn Screening for Cystic Fibrosis on Weight and Length in the First Year of Life

Since the implementation of universal newborn screening (NBS) for cystic fibrosis (CF), the timing and magnitude of growth deficiency or its association with correlates of disease among infants with CF who underwent NBS has not been well described. To examine incremental weight gain, linear growth, and clinical features in the first year of life among infants with CF who underwent NBS. The Baby Observational and Nutrition Study (BONUS), a multicenter, longitudinal, observational cohort study, was conducted during regular CF clinic visits in the first 12 months of life at 28 US Cystic Fibrosis Foundation-accredited Care Centers from January 7, 2012, through May 31, 2015. Participants included 231 infants younger than 3.5 months who underwent NBS and had confirmed CF, with a gestational age of at least 35 weeks, birth weight of at least 2.5 kg, and toleration of full oral feeds. Of these, 222 infants (96.1%) had follow-up beyond 6 months of age and 215 (93.1%) completed 12 months of follow-up. Cystic fibrosis. Attained weight and length for age and World Health Organization normative z scores at ages 1 to 6 and 8, 10, and 12 months (defined a priori). Of the 231 infants enrolled, 110 infants (47.6%) were female and 121 (52.4%) were male, with a mean (SD) age of 2.58 (0.69) months. BONUS infants had lower than mean birth weights (mean z score, -0.15; 95% CI, -0.27 to -0.04) and higher birth lengths (mean z score, 0.44; 95% CI, 0.26 to 0.62). They achieved normal weight by 12 months, a significant improvement over a prescreening cohort of newborns with CF from 20 years before the contemporary cohort (mean z score increase, 0.57; 95% CI, 0.37-0.77). However, length was lower than the mean at 12 months (mean z score, -0.56; 95% CI, -0.70 to -0.42). Only 30 infants (13.6%) were at less than the 10th percentile of weight for age, whereas 53 (23.9%) were at less than the 10th percentile of length for age at more than half their visits. Male sex, pancreatic insufficiency, meconium ileus, histamine blocker use, and respiratory Pseudomonas aeruginosa infection were associated with lower weight or length during the first year. Insulinlike growth factor 1 levels were significantly lower among low-length infants. Persistently low-weight infants consumed significantly more calories, and weight and length z scores were negatively correlated with caloric intake. Since initiation of universal NBS for CF, significant improvement has occurred in nutritional status, with normalization of weight in the first year of life. However, length stunting remains common.

Morbidity and mortality among exclusively breastfed neonates with medium-chain acyl-CoA dehydrogenase deficiency

Despite greatly improved morbidity and mortality among infants with medium-chain acyl-CoA dehydrogenase deficiency (MCAD) since the implementation of universal newborn screening (NBS), a population of neonates still becomes ill before their positive screen results are available. Exclusive breastfeeding is a proposed risk factor in this group. Since initial studies of MCAD NBS, breastfeeding rates have increased substantially. In this study, we quantify the current risk of early decompensation in neonates with MCAD and identify factors associated with poor outcomes. We completed a retrospective analysis of neonates with MCAD referred to our center between 2010 and 2015. Of 46 infants with MCAD, 11 (23.9%) were symptomatic before the return of the NBS results. Four died or had cardiac arrest; the remaining seven had lethargy and hypoglycemia. All symptomatic patients were exclusively breastfed; only 40.6% of asymptomatic patients were exclusively breastfed. Breastfeeding rates increased from 45.5% in 2010-2011 to 64.7% in 2012-2013 and 87.5% in 2014-2015. Over these same periods, rates of early decompensation increased from 9.09% to 23.5% and 75%, respectively. Exclusively breastfed neonates with MCAD are at risk for early metabolic decompensation. As breastfeeding rates increase, close management of feeding difficulties is essential for all neonates awaiting NBS results.Genet Med 18 12, 1315-1319.

A Simple, Rapid, Low-Cost Test for the Diagnosis of Sickle Cell Disease Using a Paper-Based Hemoglobin Solubility Assay

Abstract 245▪▪This icon denotes a clinically relevant abstract Introduction:Sickle cell disease (SCD) is the most common inherited blood disorder caused by a mutation in the beta-globin chain of the hemoglobin (Hb) molecule. The result of this mutation, Hb S, polymerizes when deoxygenated, giving the red blood cells a characteristic, sickled shape. This polymerization causes in vivo vaso-occlusion and disrupts the vascular endothelium causing multi-organ complications in affected individuals. Nearly 70% of all affected births occur in Africa, where conservative estimates of SCD prevalence suggest a 10.68/1000 rate at birth (compared to 0.49/1000 in the U.S.). Although SCD causes significant morbidity and premature mortality, most affected persons born in the U.S. are able to survive into adulthood (primarily due to the implementation of universal newborn screening). In contrast, most affected individuals born in low-income countries die before the age of 5 years due to lack of early intervention. Current technology for diagnosing SCD relies on hemoglobin electrophoresis, isoelectric focusing or high performance liquid chromatography. This type of testing remains prohibitively expensive to low-income countries, where SCD is most prevalent and newborn screening is unavailable. Thus, many affected individuals are not diagnosed before severe complications or death can occur. The urgent need to develop a low-cost diagnostic test for SCD has been recently recognized as a priority by the World Health Organization. In this study, we describe the implementation of a paper-based hemoglobin solubility assay as a simple, low-cost and rapid test for definitive diagnosis of SCD. Materials and Methods:Normal human venous blood (Hb AA) was collected and compared to blood from patients with SCD (Hb SS) and SCT (Hb AS). To perform the test, a 20uL droplet of whole blood mixed with the components of the Hb solubility assay (SickleDex™, Streck) was deposited onto a paper-fluidic device fabricated using a previously published method. Polymerized deoxy-Hb S remained in the center of the blood stain entrapped by the paper substrate, while other forms of Hb remained soluble and were transported laterally to the periphery of the stain by capillary action. The resulting blood stain was digitized with a portable scanner and analyzed automatically. The red color intensity profiles were normalized by the total area under the curve to account for the differences in hematocrit among subjects. The SCD index was defined as the normalized color intensity 5 mm from the center of the blood stain. Data were presented as results of individual experiments and as mean ± SD. The values of the SCD index for samples from each Hb genotype were compared using a paired two-tailed t-test. Results:The entanglement of polymerized deoxy-Hb S by the fibers of the paper substrate resulted in the formation of a dark red spot in the center of the blood stain, while the wicking of the soluble forms of Hb from the center produced a pink ring on the periphery of the stain. The patterns of the blood stains produced on paper by normal (Hb AA), SCT (Hb AS) and SCD (Hb SS) samples were significantly different (Fig. A). The tight clustering of the normalized color intensity profiles for different subjects with the same Hb genotype enabled the use of the SCD index as a quantitative metric for distinguishing between the three types of samples (Fig. B). The difference between the SCD index measured for Hb AA, Hb AS and Hb SS samples was highly significant, with p<0.001 (Fig. C). Unlike the conventional, commercially available Hb solubility tests (e.g. SickleDex), the paper-based Hb solubility assay can conclusively differentiate between SCT and SCD samples using the characteristic blood stain patterns produced by each sample on the paper substrate. [Display omitted] Conclusions:This proof-of-concept study demonstrated the feasibility of using the paper-based Hb solubility assay as a simple, low-cost, point-of-care diagnostic test for SCD. The ability to diagnose SCD quickly and inexpensively will be particularly useful for universal SCD screening in resource-limited settings, such as Africa. This test will also be very useful in the emergency room setting in high-income countries to enable healthcare professionals to objectively confirm suspected SCD at the bedside. Disclosures:No relevant conflicts of interest to declare.

AMPLIFICATION FOR INFANTS

The recent implementation of universal newborn screening has created an urgent need for an expansion of audiologic and rehabilitative services for this population. The focus of this article is the provision of amplification for infants and young children. Specifically, this article provides (1) a brief review of the importance of early amplification, (2) a theoretical perspective on prescriptive fitting algorithms, (3) a broad overview of ``state-of-the-art'' hearing instrument selection, evaluation, fitting, and follow-up, (4) a discussion of outcome measures for this population, and (5) suggestions for future research needs.