Newborn Screening Studies Research Articles

Newborn screening follow-up in Bavaria: height and weight in paediatric patients with congenital adrenal hyperplasia.

Auxology is essential for monitoring congenital adrenal hyperplasia (CAH). Data from prospective studies of newborn screening (NBS) are scarce. Analysis of data extracted from a population-based prospective long-term follow-up survey study of children detected through NBS in Bavaria in 1999-2018. The study is based on standardized parent or patient questionnaires, supplemented by medical reports. Height, weight, and treatment dataof 146 children/adolescents with classical CAH were analyzed. The entire observation period up to the age of 18 years was completed by 55 patients. Standard Deviation Scores (SDS) for height/body-mass-index (BMI) at different ages and the deviation of the height SDS at age 18 years from the parental target-height SDS were calculated. Male and female patients with CAH showed different and altered growth patterns, resulting in a median [IQR] SDS deviation from target height of-0.81 [-1.05,-0.41] in males and-0.35 [-0.90, 0.02] in females. BMI-SDS values were significantly (p<0.05) increased in males aged 6-16 years and in females aged 2 and 8-12 years. The average total steroid dose was higher in males (p<0.001). For deviations from target height, significant associations were found with sex (p<0.05) and adherence (p<0.01), but not with mutation group or steroid-dose. For BMI, none of the parameters showed a significant correlation. Early treatment after NBS has helped to improve, but not to normalize, the development of height and weight in patients with CAH. Optimizing monitoring and treatment, preferably sex-specific, remains a challenge for clinical practice and research.

Inborn Errors of Immunity in Pediatric Intensive Care: Prevalence, Characteristics, and Prognosis.

Inborn errors of immunity (IEI) are a heterogeneous group of genetic diseases characterized by impaired immune system function. This prospective study aimed to determine the frequency, characteristics, and clinical course of IEI patients admitted to the pediatric intensive care unit (PICU) and identify mortality-related factors. Using a comprehensive immunological evaluation protocol, we screened 753 PICU admissions for potential IEIs during three years. Patients with pre-existing IEI diagnoses, chronic diseases, ongoing chronic medication regimens, other known comorbidities, trauma cases, post-surgical cases, and poisonings were excluded. Thirty-three patients were newly diagnosed with IEIs during or as a result of their PICU stay, representing an incidence of 4.39%. The most common disorders were immunodeficiencies with immune dysregulation (48.5%), followed by combined immunodeficiencies (24.2%). Severe viral infections (61%) and life-threatening infections (51.7%) were the most frequent warning signs. Only 31% of patients exhibited at least two Jeffrey Modell Foundation warning signs. The mortality rate was 58%, highlighting the need for early diagnosis and treatment. Newborn screening and family segregation studies are crucial to improving outcomes for IEI patients in intensive care settings.

Disparities in Congenital Cytomegalovirus (cCMV) Postpartum Newborn Screening Research Participation.

The objective of this study is to evaluate if racial and other demographic disparities exist between patients who enrolled or declined participation in a congenital cytomegalovirus (cCMV) newborn universal screening research study. We examined characteristics for patients approached over a 2-year period to participate in a cCMV newborn screening study. Maternal characteristics included age, race, ethnicity, preferred language, interpreter need, insurance type, and number of living children. Recruitment period was also examined (pre-pandemic January 1 to December 31, 2019, and during COVID-19 July 1, 2021 to June 30, 2022). Characteristics were compared for patients who enrolled in the study and those who declined participation using descriptive statistics and logistic regression. Of the study sample (n = 4156), 3148 (75.7%) patients enrolled and 1008 (24.3%) declined. Declined participation rates were 47.2% among non-Hispanic (NH) Black patients and 15.7% among NH White patients. In the final adjusted model, NH Black patients (OR 3.14, 95% CI 2.53-3.90), those with public insurance (OR 1.81, 95% CI 1.48-2.22), and those with four or more children (OR for 4 + children 1.45, 95% CI 1.11-1.90) were the most likely to decline research participation. NH Black and NH multiracial patients were among the most likely patient groups to decline study participation. These groups have previously been identified to be at increased risk for cCMV. This differential participation in cCMV research could result in underreported estimates of prevalence. Future cCMV research, including surveillance studies, should include documentation of differential participation to both address efforts to improve research participation and document and address potential bias in results.

Systematic Review of Newborn Screening Programmes for Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder causing the degeneration of motor neurons in the spinal cord. Recent studies suggest greater effectiveness of treatment in the presymptomatic stage. This systematic review synthesises findings from 37 studies (and 3 overviews) of newborn screening for SMA published up to November 2023 across 17 countries to understand the methodologies used; test accuracy performance; and timing, logistics and feasibility of screening. All studies screened for the homozygous deletion of SMN1 exon 7. Most (28 studies) used RT-PCR as the initial test on dried blood spots (DBSs), while nine studies also reported second-tier tests on DBSs for screen-positive cases. Babies testing positive on DBSs were referred for confirmatory testing via a range of methods. Observed SMA birth prevalence ranged from 1 in 4000 to 1 in 20,000. Most studies reported no false-negative or false-positive cases (therefore had a sensitivity and specificity of 100%). Five studies reported either one or two false-negative cases each (total of six cases; three compound heterozygotes and three due to system errors), although some false-negatives may have been missed due to lack of follow-up of negative results. Eleven studies reported false-positive cases, some being heterozygous carriers or potentially related to heparin use. Time to testing and treatment varied between studies. In conclusion, several countries have implemented newborn screening for SMA in the last 5 years using a variety of methods. Implementation considerations include processes for timely initial and confirmatory testing, partnerships between screening and neuromuscular centres, and timely treatment initiation.

Cranial Ultrasound Findings in Infants With Congenital Cytomegalovirus Infection in a Universal Newborn Screening Study in Minnesota.

Congenital cytomegalovirus (cCMV) is the most common infectious cause of neurodevelopmental deficits in US children. To inform patient management, it is important to define whether central nervous system (CNS) manifestations are present at birth. This study characterized neuroimaging findings in infants with cCMV identified by a universal screening study in Minnesota during February 2016-December 2022. Newborns with cCMV infection (confirmed by urine CMV polymerase chain reaction [PCR] testing, obtained following a positive screening saliva and/or dried blood spot result) underwent a diagnostic evaluation that included a cranial ultrasound (cUS) exam, laboratory studies, ophthalmological, and audiological evaluation. Neuroimaging findings and cCMV disease classification were interpreted based on international consensus guidelines. Among 87 newborns with confirmed cCMV, 76 underwent cUS. Of these, 53/76 (70%) had normal examinations, while 23/76 (30%) exhibited cUS findings: for 5 infants, these were clearly cCMV disease-defining, while for 18 infants, there were findings of uncertain significance. Magnetic resonance imaging (MRI) results (n = 10 infants) aligned with cUS cCMV disease-defining findings in 2 infants, while cCMV-specific abnormalities were noted by MRI in 2 of 6 infants with nondiagnostic/incidental cUS findings. Of 9 infants who had both cUS and MRI examination, the average time interval between studies was 220 days (range, 2-1061). Excluding infants with cCMV CNS disease-defining cUS abnormalities, incidental findings were observed more commonly in infants with clinical/laboratory features described in cCMV disease classification guidelines (9/13) than in newborns with completely asymptomatic infections (9/58; P < .0001). Among infants with cCMV identified in a universal screening study, the majority had a normal cUS. CNS disease-defining abnormalities were present in 7%, while 24% had findings of uncertain significance. We propose that many cUS findings are incidental, and not diagnostic of symptomatic cCMV infection. Although these findings may not be sufficient to define the presence of symptomatic cCMV disease involving the CNS, in our study they were more commonly observed in infants with other clinical and/or laboratory findings associated with symptomatic cCMV infection.

Cost-effectiveness of newborn screening for sickle cell disease: a systematic review protocol.

The purpose of this systematic review is to assess the cost-effectiveness of targeted/selective newborn screening compared with universal screening for sickle cell disease across various countries and settings. The incidence of sickle cell disease is a widespread and potentially fatal hematologic disorder that affects thousands of newborns worldwide. The cost of newborn screening creates a burden on households and the economy. Studies will be eligible for inclusion in the review if they focus on the cost-effectiveness of newborn screening for sickle cell disease, comparing targeted/selective screening with universal screening. A preliminary search of MEDLINE (PubMed) was undertaken using MeSH terms, such as sickle cell disease, newborn , and economic evaluations . Two reviewers will screen the titles, abstracts, and full text independently against the inclusion criteria. Disagreements will be resolved by discussion or with a third reviewer. To assess methodological quality, the JBI checklist for economic evaluation will be used. Data will be extracted by 2 reviewers using a modified JBI data extraction form. The JBI dominance ranking matrix for economic evaluations will be used to summarize and compare the results. Cost-effectiveness will be measured on the basis of cost per test/case detected, quality-adjusted life years gained, or disability-adjusted life years averted. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) assessment will be conducted to evaluate the certainty of economic evidence, such as use of resources and expenditures, and to incorporate the results into the decision-making process. PROSPERO CRD42017057963.

Comparative analysis of gene and disease selection in genomic newborn screening studies.

Genomic newborn screening (gNBS) is on the horizon given the decreasing costs of sequencing and the advanced understanding of the impact of genetic variants on health and diseases. Key to ongoing gNBS pilot studies is the selection of target diseases and associated genes to be included. In this study, we present a comprehensive analysis of seven published gene-disease lists from gNBS studies, evaluating gene-disease count, composition, group proportions, and ClinGen curations of individual disorders. Despite shared selection criteria, we observe substantial variation in total gene count (median 480, range 237-889) and disease group composition. An intersection was identified for 53 genes, primarily inherited metabolic diseases (83%, 44/53). Each study investigated a subset of exclusive gene-disease pairs, and the total number of exclusive gene-disease pairs was positively correlated with the total number of genes included per study. While most pairs receive "Definitive" or "Strong" ClinGen classifications, some are labeled as "Refuted" (n = 5) or "Disputed" (n = 28), particularly in genetic cardiac diseases. Importantly, 17%-48% of genes lack ClinGen curation. This study underscores the current absence of consensus recommendations for selection criteria for target diseases for gNBS resulting in diversity in proposed gene-disease pairs, their coupling with gene variations and the use of ClinGen curation. Our findings provide crucial insights into the selection of target diseases and accompanying gene variations for future gNBS program, emphasizing the necessity for ongoing collaboration and discussion about criteria harmonization for panel selection to ensure the screening's objectivity, integrity, and broad acceptance.

Neurobehavioral outcomes of neonatal asymptomatic congenital cytomegalovirus infection at 12-months

BackgroundCongenital cytomegalovirus (cCMV) is the most common congenital viral infection in the United States. Symptomatic infections can cause severe hearing loss and neurological disability, although ~ 90% of cCMV infections are asymptomatic at birth. Despite its prevalence, the long-term neurobehavioral risks of asymptomatic cCMV infections are not fully understood. The objective of this work was to evaluate for potential long-term neurobehavioral sequelae in infants with asymptomatic cCMV.MethodsInfants with cCMV were identified from a universal newborn cCMV screening study in a metropolitan area in the midwestern United States. Asymptomatic infants with cCMV were enrolled in a longitudinal neurodevelopmental study (N = 29). Age- and sex-matched healthy control infants (N = 193) were identified from the Baby Connectome Project (BCP), a longitudinal study of brain and behavioral development. The BCP sample supplemented an additional group of healthy control infants (N = 30), recruited from the same participant registry as the BCP specifically for comparison with infants with asymptomatic cCMV. Neurobehavioral assessments and parent questionnaires, including the Mullen Scales of Early Learning, the Repetitive Behavior Scales for Early Childhood (RBS-EC), and the Infant Toddler Social Emotional Assessment (ITSEA) were administered at 12 months of age. Neurobehavioral scores were compared between infants with asymptomatic cCMV and all identified healthy control infants.ResultsInfants with asymptomatic cCMV performed equivalently compared to healthy control infants on the neurobehavioral measures tested at 12 months of age.ConclusionsThese results indicate that at 12 months of age, infants with asymptomatic cCMV are not statistically different from controls in a number of neurobehavioral domains. Although follow-up is ongoing, these observations provide reassurance about neurobehavioral outcomes for infants with asymptomatic cCMV and inform the ongoing discussion around universal screening. Additional follow-up will be necessary to understand the longer-term outcomes of these children.

Prospective cohort study of genomic newborn screening: BabyScreen+ pilot study protocol

IntroductionNewborn bloodspot screening (NBS) is a highly successful public health programme that uses biochemical and other assays to screen for severe but treatable childhood-onset conditions. Introducing genomic sequencing into NBS...

Parent perspectives following newborn screening resulting in diagnoses of fragile X syndrome or fragile X premutation

BackgroundFragile X syndrome (FXS) is the most common inherited cause of intellectual disability. Early Check, a voluntary newborn screening study, screened 18,833 newborns for FXS over ∼3 years. Exploring parental attitudes and perspectives can provide insight to the potential future acceptability of public health screening. Methods and proceduresMothers of infants who received a screen positive result for FXS (n = 6) or fragile X premutation (FXPM; n = 18) were interviewed about their perceptions and experiences. Outcomes and resultsMothers of children with FXS described utility in receiving information about their child, particularly to monitor for potential developmental issues and intervene early; overall mothers did not regret participating. Mothers reported various reactions to receiving the FXS or FXPM results including (1) stress and worry; (2) guilt; (3) sadness and disappointment; (4) neutrality, relief, and acceptance; and (5) confusion and uncertainty. Conclusions and implicationsDespite initial reactions such as sadness, stress, and worry, mothers found value in learning of their child’s presymptomatic diagnosis of FXS, particularly the anticipated long-term benefits of early diagnosis to their child’s health and wellbeing. Our results indicate that professionals returning positive newborn screening results should anticipate and prepare for reactions such as parental shock, guilt, sadness, and uncertainty. Genetic counseling and psychosocial support are critical to supporting families.

A UK-based pre-pilot newborn screening study for metachromatic leukodytrosphy identified a late infantile case

A UK-based pre-pilot newborn screening study for metachromatic leukodytrosphy identified a late infantile case

ScreenPlus: A comprehensive, multi-disorder newborn screening program

The increasing availability of novel therapies highlights the importance of screening newborns for rare genetic disorders so that they may benefit from early therapy, when it is most likely to be effective. Pilot newborn screening (NBS) studies are a way to gather objective evidence about the feasibility and utility of screening, the accuracy of screening assays, and the incidence of disease. They are also an optimal way to evaluate the complex ethical, legal and social implications (ELSI) that accompany NBS expansion for disorders. ScreenPlus is a consented pilot NBS program that aims to enroll over 100,000 infants across New York City. The initial ScreenPlus panel includes 14 disorders and uses an analyte-based, multi-tiered screening platform in an effort to enhance screening accuracy. Infants who receive an abnormal result are referred to a ScreenPlus provider for confirmatory testing, management, and therapy as needed, along with longitudinal capture of outcome data. Participation in ScreenPlus requires parental consent, which is obtained in active and passive manners. Patient-facing documents are translated into the ten most common languages spoken at our nine pilot hospitals, all of which serve diverse communities. At the time of consent, parents are invited to receive a series of online surveys to capture their opinions about specific ELSI-related topics, such as NBS policy, residual dried blood spot retention, and the types of disorders that should be on NBS panels. ScreenPlus has developed a stakeholder-based, collective funding model that includes federal support in addition to funding from 14 advocacy and industry sponsors, all of which have a particular interest in NBS for at least one of the ScreenPlus disorders. Taken together, ScreenPlus is a model, multi-sponsored pilot NBS program that will provide critical data about NBS for a broad panel of disorders, while gathering key stakeholder opinions to help guide ethically sensitive decision-making about NBS expansion.

A pilot study of newborn screening for X-linked adrenoleukodystrophy based on liquid chromatography-tandem mass spectrometry method for detection of C26:0- lysophosphatidylcholine in dried blood spots: results from 43,653 newborns in a southern Chinese population

BackgroundX-linked adrenoleukodystrophy (X-ALD) is a rare X-linked disease caused by mutations of the ABCD1 gene. C26:0-lysophosphatidylcholine (C26:0-LPC) has been proved to be an accurate biomarker for X-ALD. This study aims to propose an effective method for screening of X-ALD and to evaluate the performance of the newborn screening (NBS) assay for X-ALD in Guangzhou. MethodsC26:0-LPC in dried blood spots (DBS) was extracted by methanol solution containing isotope-labelled internal standard (C26:0-d4-LPC) and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The sensitivity of the method was assessed in eight male X-ALD patients, two female carriers and 583 healthy controls. The method was conducted on 43,653 newborns. Next generation sequencing was performed on screen-positive samples. Plasma analysis of very long-chain fatty acids and genetic counselling were performed by way of follow-up. ResultsElevated C26:0-LPC were 100% sensitive for screening of X-ALD. Of 43,653 newborns, 32 (18 males, 14 females) screened positive. Of these, 14 (43.7%) were identified ABCD1 variants, including seven hemizygous males and seven heterozygous females, and two (6.3%) were diagnosed with other peroxisomal disorders. ConclusionThe LC-MS/MS method for screening of X-ALD can identify males, heterozygous females and other peroxisomal disorders. The incidence of X-ALD in Guangzhou is not low.

Newborn Screening with (C16 + C18:1)/C2 and C14/C3 for Carnitine Palmitoyltransferase II Deficiency throughout Japan Has Revealed C12/C0 as an Index of Higher Sensitivity and Specificity.

Carnitine palmitoyltransferase (CPT) II deficiency is a long-chain fatty acid oxidation disorder. It manifests as (1) a lethal neonatal form, (2) a hypoglycemic form, or (3) a myopathic form. The second form can cause sudden infant death and is more common among Japanese people than in other ethnic groups. Our study group had earlier used (C16 + C18:1)/C2 to conduct a pilot newborn screening (NBS) study, and found that the use of C14/C3 for screening yielded lower rates of false positivity; in 2018, as a result, nationwide NBS for CPT II deficiency started. In this study, we evaluated the utility of these ratios in 71 NBS-positive infants and found that the levels of both C14/C3 and (C16 + C18:1)/C2 in patients overlapped greatly with those of infants without the disease. Among the levels of acylcarnitines with various chain lengths (C18 to C2) and levels of free carnitine (C0) as well as their ratios of various patterns, C12/C0 appeared to be a promising index that could reduce false-positive results without missing true-positive cases detected by current indices. Although some cases of the myopathic form may go undetected even with C12/C0, its use will help prevent life-threatening onset of the hypoglycemic form of CPT II deficiency.

Long-term linguistic outcome in adults with congenital cytomegalovirus infection

Background Congenital cytomegalovirus (cCMV) is the most common prenatal infection and the main infectious cause of neurodevelopmental abnormalities in developed countries. Long-term neuropsychological outcome of cCMV infection is still not well understood. This is the first study that presents linguistic follow-up data performed on adults who were infected in utero. Method All individuals from a universal newborn CMV screening study in Sweden sampled from 1977 to 1985 were invited to participate in a follow-up study. 34/71 persons (48%) with cCMV and 22/46 controls (48%) were enrolled. Participants were between 34 and 43 years. Linguistic ability was evaluated with two-word fluency tasks (FAS letter fluency and verb fluency), and a qualitative analysis of the participants’ word retrieval strategies was conducted. Results No statistically significant group differences were found in the total number of retrieved words. When related to Swedish norm data, 43% of participants with cCMV infection, all asymptomatic at birth, had adequate results on both FAS and verb fluency tasks, compared to 86% of the controls. Education level was the most important factor for word fluency ability in both groups. Adults with cCMV infection and higher education levels used less effective retrieval strategies on FAS letter fluency than controls. Conclusion This study suggests that adults with cCMV infection may have deficits in the word retrieval process, even in the absence of known neurodevelopmental disorders. Long-term effects of cCMV infection may exist even in those with asymptomatic infection at birth.

Dried Blood Spots in Neonatal Studies: A Computational Analysis for the Role of the Hematocrit Effect.

Dried blood spot (DBS) microsampling is extensively employed in newborn screening (NBS) and neonatal studies. However, the impact of variable neonatal hematocrit (Ht) values on the results can be a source of analytical error, and the use of fixed Ht for calibration (Htcal) is not representative of all neonatal subpopulations. A computational approach based on neonatal demographics was developed and implemented in R® language to propose a strategy using correction factors to address the Ht effect in neonatal DBS partial-spot assays. A rational "tolerance level" was proposed for the Ht effect contribution to the total analytical error and a safe Ht range for neonatal samples, where the correction of concentrations can be omitted. Furthermore, an "alert zone" for a false positive or negative result in NBS was proposed, where the Ht effect has to be considered. Results point toward the use of Htcal values closely representative of populations under analysis and an acceptable level of percentage relative error can be attributed to the Ht effect, diminishing the probability of correction. Overall, the impact of the Ht effect on neonatal studies is important and future work may further investigate this parameter, correlated to other clinical variables potentially affecting results.

Pilot study of newborn screening for six lysosomal diseases in Brazil

Background: Lysosomal diseases (LDs) are progressive life-threatening disorders that are usually asymptomatic at birth. Specific treatments are available for several LDs, and early intervention improves patient's outcomes. Thus, these diseases benefit from newborn screening (NBS). We have performed a pilot study for six LDs in Brazil by tandem mass spectrometry. Methods: Dried blood spot (DBS) samples of unselected newborns were analyzed by the Neo-LSD™ kit (Perkin-Elmer) by MS/MS. Samples with low enzyme activity were submitted to the evaluation of specific biomarkers by ultra-performance liquid chromatography tandem-mass spectrometry as the second-tier, and were analyzed by a next-generation sequencing (NGS) multi-gene panel as the third-tier. All tests were performed in the same DBS sample. Results: In 20,066 newborns analyzed, 15 samples showed activity of one enzyme below the cutoff. Two newborns had biochemical and molecular results compatible with Fabry disease, and five newborns had biochemical results and pathogenic variants or variants of unknown significance (VUS) in GAA. Conclusions: This study indicates that the use of enzyme assay as the first-tier test gives an acceptably low number of positive results that requires second/third tier testing. The possibility to run all tests in a DBS sample makes this protocol applicable to large-scale NBS programs.

The Retrospective Study of Newborn Hearing Screening by Using Otoacoustic Emissions

The Retrospective Study of Newborn Hearing Screening by Using Otoacoustic Emissions

Use of a web-based portal to return normal individual research results in Early Check: Exploring user behaviors and attitudes.

Early Check is a voluntary, large-scale expanded newborn screening study in North Carolina that uses a self-directed web-based portal for return of normal individual research results (IRR). Little is known about participant perspectives in using web-based portals to receive IRR. This study explored user attitudes and behaviors within the Early Check portal using three methods: (1) a feedback survey available to the consenting parent of participating infants (typically mothers), (2) semi-structured interviews conducted with a subset of parents, and (3) Google Analytics. During an approximate 3-year period, 17 936 newborns received normal IRR and there were 27 812 visits to the portal. Most surveyed parents reported viewing their baby's results (86%, 1410/1639). Parents largely found the portal easy to use to get results, and helpful in understanding the results. However, 10% of parents said it was difficult to find enough information to understand their baby's results. In Early Check, providing normal IRR via the portal made a large-scale study practical, and was highly rated by most users. Return of normal IRR may be particularly amenable to web-based portals, as the consequences to participants from not viewing results are modest, and the interpretation of a normal result is relatively straightforward.

A multicenter prospective study of next-generation sequencing-based newborn screening for monogenic genetic diseases in China

BackgroundNewborn screening (NBS) is an important and successful public health program that helps improve the long-term clinical outcomes of newborns by providing early diagnosis and treatment of certain inborn diseases. The development of next-generation sequencing (NGS) technology provides new opportunities to expand current newborn screening methodologies.MethodsWe designed a a newborn genetic screening (NBGS) panel targeting 135 genes associated with 75 inborn disorders by multiplex PCR combined with NGS. With this panel, a large-scale, multicenter, prospective multidisease analysis was conducted on dried blood spot (DBS) profiles from 21,442 neonates nationwide.ResultsWe presented the positive detection rate and carrier frequency of diseases and related variants in different regions; and 168 (0.78%) positive cases were detected. Glucose-6-Phosphate Dehydrogenase deficiency (G6PDD) and phenylketonuria (PKU) had higher prevalence rates, which were significantly different in different regions. The positive detection of G6PD variants was quite common in south China, whereas PAH variants were most commonly identified in north China. In addition, NBGS identified 3 cases with DUOX2 variants and one with SLC25A13 variants, which were normal in conventional NBS, but were confirmed later as abnormal in repeated biochemical testing after recall. Eighty percent of high-frequency gene carriers and 60% of high-frequency variant carriers had obvious regional differences. On the premise that there was no significant difference in birth weight and gestational age, the biochemical indicators of SLC22A5 c.1400C > G and ACADSB c.1165A > G carriers were significantly different from those of non-carriers.ConclusionsWe demonstrated that NBGS is an effective strategy to identify neonates affected with treatable diseases as a supplement to current NBS methods. Our data also showed that the prevalence of diseases has significant regional characteristics, which provides a theoretical basis for screening diseases in different regions.