BACKGROUND: Fetal alcohol spectrum disorders (FASDs) are lifelong conditions that can occur in a person with prenatal alcohol exposure. Although studies using intensive, in-person assessments of children in selected communities have found higher estimates of children with FASDs than studies of healthcare claims data, claims-based studies provide more current information about individuals with recognized FASDs from diverse populations. We estimated the proportion of children with administratively reported FASDs in two large healthcare claims databases. METHODS: We analyzed Merative™ MarketScan® commercial and Medicaid claims databases, that include nationwide data from employer-sponsored health plans and from Medicaid programs in 8-10 states, respectively. For each database, we estimated the proportion of children aged 0-17 years with administratively reported FASDs, identified by one inpatient or two outpatient codes for prenatal alcohol exposure or fetal alcohol syndrome during the entire seven-year period from 2015 to 2021 and during each year. RESULTS: During 2015-2021, 1.2 per 10,000 commercially-insured and 6.1 per 10,000 Medicaid-insured children had an administratively reported FASD; estimates varied by sex, geography, and other available demographics. Among commercially-insured children, 0.5 per 10,000 in 2015 and 0.6 per 10,000 children in 2021 had an administratively reported FASD; among Medicaid-insured, 1.2 per 10,000 in 2015 and 2.1 per 10,000 children in 2021 had an administratively reported FASD. CONCLUSIONS: Although an underestimate of the true population of children with FASDs, patterns in administratively reported FASDs by demographics were consistent with previous studies. Healthcare claims studies can provide timely, ongoing information about children with recognized FASDs to complement in-persons studies.

OBJECTIVE: To examine the association between congenital cytomegalovirus (cCMV) and autism spectrum disorder (ASD) administrative diagnoses in US children. METHODS: Cohort study using 2014 to 2020 Medicaid claims data. We used diagnosis codes to identify cCMV (exposure), ASD (outcome), and covariates among children enrolled from birth through ≥4 to <7 years. Covariates include central nervous system (CNS) anomaly or injury diagnosis codes, including brain anomaly, microcephaly within 45 days of birth, cerebral palsy, epilepsy, or chorioretinitis. We used Cox proportional hazards regression models to estimate hazard ratios and 95% confidence intervals, overall and stratified by sex, birth weight and gestational age outcome (low birth weight or preterm birth), and presence of CNS anomaly or injury. RESULTS: Among 2 989 659 children, we identified 1044 (3.5 per 10 000) children with cCMV and 74 872 (25.0 per 1000) children with ASD. Of those with cCMV, 49% also had CNS anomaly or injury diagnosis codes. Children with cCMV were more likely to have ASD diagnoses (hazard ratio: 2.5; 95% confidence interval: 2.0-3.2, adjusting for birth year, sex, and region). This association differed by sex and absence of CNS anomaly or injury but not birth outcome. CONCLUSIONS: Children with (versus without) cCMV diagnoses in Medicaid claims data, most of whom likely had symptomatic cCMV, were more likely to have ASD diagnoses. Future research investigating ASD risk among cohorts identified through universal cCMV screening may help elucidate these observed associations.

BACKGROUND: Single-tier newborn screening (NBS) for CAH using 17-hydroxyprogesterone (17OHP) measured by fluoroimmunoassay (FIA) in samples collected at 24-48 hours produces a high false-positive rate (FPR). 2nd tier steroid testing can reduce the FPR and has been widely implemented. We investigated the accuracy of an alternative multi-tier CAH NBS protocol that incorporates molecular testing of the CYP21A2 gene and reduces the 1st tier 17OHP cutoff to minimize missed cases. METHODS: Created a Minnesota-specific CYP21A2 pathogenic variants panel; develop a rapid, high-throughput multiplex, allele-specific-primer-extension assay; perform 1-year retrospective analysis of Minnesota NBS results comparing metrics between a conventional steroid-based two-tier protocol and a molecular-based multi-tier NBS protocol, applied post-hoc. RESULTS: CYP21A2 gene sequencing of 103 Minnesota families resulted in a Minnesota-specific panel of 21 pathogenic variants. Centers for Disease Control and Prevention (CDC) created a molecular assay with 100% accuracy and reproducibility. Two-tier steroid-based screening of 68,659 live births during 2015 resulted in 2 false negatives (FNs), 91 FPs, and 1 true positive (TP). A three-tier protocol with a lower 1st-tier steroid cutoff, 2nd-tier 21-variant CYP21A2 panel and 3rd-tier CYP21A2 sequencing would have resulted in 0 FNs, 52 FPs and 3 TPs. CONCLUSIONS: Incorporation of molecular testing could improve the accuracy of CAH NBS, although some distinct challenges of molecular testing may need to be considered before implementation by NBS programs.

IMPORTANCE: Caring for children diagnosed with cancer may adversely affect the mental health (MH) of parents. OBJECTIVE: To characterize utilization of MH services among parents of children with vs without cancer using nationwide commercial claims data. DESIGN, SETTING, AND PARTICIPANTS: For this cross-sectional study, the Merative MarketScan Commercial Claims Database was used to identify continuously insured families of children treated for cancer (aged ≤21 years at diagnosis) during 2010 to 2018, compared with families who matched eligibility criteria but did not have a child with a cancer history. Parents were assessed from 18 months before to 12 months after their child's cancer diagnosis. Analyses were conducted from February 2022 to September 2023. EXPOSURES: Children's cancer diagnosis. MAIN OUTCOMES AND MEASURES: Outcomes included parents' MH-related visits during the first year following their child's cancer diagnosis. Logistic regressions compared outcomes between families of children with vs without cancer, adjusting for sociodemographic and clinical factors. RESULTS: This study included 4837 families of children with cancer (4210 mothers and 4016 fathers) and 24 185 families of children without cancer (21 444 mothers and 19 591 fathers) with continuous insurance enrollment. Most household leads were aged 35 to 54 years (3700 [76.5%] in families of children with cancer vs 17 812 [73.6%] in families of children without cancer) and resided in urban areas (4252 [87.9%] vs 21 156 [87.5%]). The probabilities of parents having anxiety-related visits (10.6% vs 7.0%), depression-related visits (8.4% vs 6.1%), and any MH-related visits (18.1% vs 13.3%) were higher in families of children with vs without cancer. Adjusted analyses showed absolute increases of 3.2 percentage points (95% CI, 2.3 to 4.0; 45.7% relative increase), 2.2 percentage points (95% CI, 1.4 to 3.0; 36.1% relative increase), and 4.2 percentage points (95% CI, 3.1 to 5.3; 31.3% relative increase) in the probabilities of 1 or both parents having anxiety-related visits, depression-related visits, and any MH-related visits, respectively, among families of children with vs without cancer. Such differences were greater in magnitude among mothers than fathers. CONCLUSIONS AND RELEVANCE: In this cohort study of privately insured parents, those caring for children with cancer had a higher likelihood of utilizing MH care than other parents. These findings underline the importance of interventions toward targeted counseling and support to better meet MH care needs among parents and caregivers of children with cancer.

As many as 5%–10% of infants with symptomatic congenital cytomegalovirus (cCMV) disease, or 0.4%–0.8% of all liveborn infants with cCMV infection, die in early infancy in high-income countries. However, estimates are uncertain due to several potential biases that can result from data limitations and study designs. First, infants with cCMV infections who die prior to diagnosis, which usually occurs at 1–4 weeks after birth, may be excluded from both the count of deaths and the denominator of cCMV births, resulting in left truncation and immortal time biases. These ‘biases’ are features of the data and do not reflect bias on the part of researchers, but understanding the potential existence of threats to validity can help with interpretation of findings. Left truncation of infant deaths occurring prior to diagnosis of cCMV can result in understatement of the burden of infant deaths due to cCMV. Conversely, overestimation of infant deaths associated with symptomatic cCMV may occur in clinical case series owing to greater representation of relatively severely affected infants owing to ascertainment and referral biases. In this review, we summarise the characteristics of 26 studies that reported estimates of cCMV-associated infant deaths, including potential biases or limitations to which those estimates may have been subject. We discuss study designs whose implementation might generate improved estimates of infant deaths attributable to cCMV. More complete estimates of the overall public health impact of cCMV could inform current and future screening, prevention, and vaccine research. © 2024 John Wiley & Sons Ltd.

BACKGROUND: The latest comprehensive diagnosis-specific estimates of hospital professional fees relative to facility fees are from 2004 to 2012. OBJECTIVE: Update professional fee ratio (PFR) estimates to improve cost analysis opportunities with hospital discharge data sources and compare them with previous PFR estimates. SUBJECTS: 2016-2020 MarketScan inpatient admissions and emergency department (ED) treat and release claims. MEASURES: PFR was calculated as total admission or ED visit payment divided by facility-only payment. This measure can be multiplied by hospital facility costs to yield a total cost estimate. RESEARCH DESIGN: Generalized linear regression models controlling for selected patient and service characteristics were used to calculate adjusted mean PFR per admission or ED visit by health payer type (commercial or Medicaid) and by selected diagnostic categories representing all clinical diagnoses (Major Diagnostic Category, Diagnostic Related Group, and Clinical Classification Software Revised). RESULTS: Mean 2016-2020 PFR was 1.224 for admissions with commercial payers (n = 6.7 million admissions) and 1.178 for Medicaid (n = 4.2 million), indicating professional payments on average increased total payments by 22.4% and 17.8%, respectively, above facility-only payments. This is a 9% and 3% decline in PFR, respectively, compared with 2004 estimates. PFR for ED visits during 2016-2020 was 1.283 for commercial payers (n = 22.2 million visits) and 1.415 for Medicaid (n = 17.7 million). This is a 12% and 5% decline in PFR, respectively, compared with 2004 estimates. CONCLUSIONS: Professional fees comprise a declining proportion of hospital-based care costs. Adjustments for professional fees are recommended when hospital facility-only financial data are used to estimate hospital care costs.

The economic impacts of health care treatments and services on individuals and their families are central to many decisions people make about the use of health care. However, without the high-quality data needed to generate evidence on the clinical effectiveness and economic impacts of an intervention, decision-makers are generally limited in their ability to make informed health care decisions that reflect patient values and preferences. The importance of evidence on economic impacts, including nonmedical costs and work-related impacts, was recognized in the reauthorization of the Patient-centered Outcomes Research Trust Fund,1 which added economic outcomes to the range of outcomes that should be considered as part of patient-centered outcomes research (PCOR).

Cytomegalovirus (CMV) is the most common infectious cause of congenital malformation and a leading cause of developmental disabilities such as sensorineural hearing loss (SNHL), motor and cognitive deficits. The significant disease burden from congenital CMV infection (cCMV) led the US National Institute of Medicine to rank CMV vaccine development as the highest priority. An average of 6.7/1000 live births are affected by cCMV, but the prevalence varies across and within countries. In contrast to other congenital infections such as rubella and toxoplasmosis, the prevalence of cCMV increases with CMV seroprevalence rates in the population. The true global burden of cCMV disease is likely underestimated because most infected infants (85-90 %) have asymptomatic infection and are not identified. However, about 7-11 % of those with asymptomatic infection will develop SNHL throughout early childhood. Although no licensed CMV vaccine exists, several candidate vaccines are in development, including one currently in phase 3 trials. Licensure of one or more vaccine candidates is feasible within the next five years. Various models of CMV vaccine strategies employing different target populations have shown to provide substantial benefit in reducing cCMV. Although CMV can cause end-organ disease with significant morbidity and mortality in immunocompromised individuals, the focus of this vaccine value profile (VVP) is on preventing or reducing the cCMV disease burden. This CMV VVP provides a high-level, comprehensive assessment of the currently available data to inform the potential public health, economic, and societal value of CMV vaccines. The CMV VVP was developed by a working group of subject matter experts from academia, public health groups, policy organizations, and non-profit organizations. All contributors have extensive expertise on various elements of the CMV VVP and have described the state of knowledge and identified the current gaps. The VVP was developed using only existing and publicly available information.

BACKGROUND: Dysfunction in the hypothalamic-pituitary-adrenal axis has been associated with depressive and anxiety disorders. Little is known about the risk for these disorders among individuals with congenital adrenal hyperplasia (CAH), a form of primary adrenal insufficiency. OBJECTIVE: We investigated the prevalence of depressive and anxiety disorders and antidepressant prescriptions in two large healthcare databases of insured children, adolescents, and young adults with CAH in the United States. METHODS: We conducted a retrospective cohort study using administrative data from October 2015 through December 2019 for individuals aged 4-25 years enrolled in employer-sponsored or Medicaid health plans. RESULTS: Adjusting for age, the prevalence of depressive disorders [adjusted prevalence ratio (aPR) = 1.7, 95% confidence interval (CI): 1.4-2.0, p<0.001], anxiety disorders [aPR = 1.7, 95% CI: 1.4-1.9, p<0.001], and filled antidepressant prescriptions [aPR = 1.7, 95% CI: 1.4-2.0, p<0.001] was higher among privately insured youth with CAH as compared to their non-CAH peers. Prevalence estimates were also higher among publicly insured youth with CAH for depressive disorders [aPR = 2.3, 95% CI: 1.9-2.9, p<0.001], anxiety disorders [aPR = 2.0, 95% CI: 1.6-2.5, p<0.001], and filled antidepressant prescriptions [aPR = 2.5, 95% CI: 1.9-3.1, p<0.001] as compared to their non-CAH peers. CONCLUSIONS: The elevated prevalence of depressive and anxiety disorders and antidepressant prescriptions among youth with CAH suggests that screening for symptoms of depression and anxiety among this population might be warranted.

Purpose To estimate health and economic outcomes associated with NBS for infantile-onset Pompe disease in the United States.Methods A decision analytic microsimulation model simulated health and economic outcomes of a birth cohort of 4 million children in the United States. Universal NBS and treatment was compared to clinical identification and treatment of infantile-onset Pompe disease. Main outcomes were projected cases identified, costs, quality adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) over the life course.Results Universal NBS for Pompe disease and confirmatory testing was estimated to cost an additional $26 million annually. Additional medication costs associated with earlier treatment initiation were $181 million; however, $8 million in medical care costs for other services were averted due to delayed disease progression. Infants with screened and treated infantile-onset Pompe disease experienced an average lifetime increase of 11.66 QALYs compared to clinical detection. The ICER was $408,000/QALY from the health care perspective and $379,000/QALY from a societal perspective. Results were sensitive to the cost of enzyme replacement therapy.Conclusions Newborn screening for Pompe disease results in substantial health gains for individuals with infantile-onset Pompe disease, but with additional costs.Competing Interest StatementThe authors have declared no competing interest.Funding StatementFinancial support for this study was provided by a grant from the Agency for Health Care Research and Quality, R01 HS020644. The funding agreement ensured the authors independence in designing the study, interpreting the data, writing, and publishing the report.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Not regulatedAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe manuscript and supplementary materials are designed to provide sufficient information for an interested reader to replicate the analysis. The statistical code is available by request from Dr. Prosser lisapros{at}umich.edu.

Guanidinoacetate methyltransferase (GAMT) deficiency is an autosomal recessive disorder of creatine biosynthesis due to pathogenic variants in the GAMT gene that lead to cerebral creatine deficiency and neurotoxic levels of guanidinoacetate. Untreated, GAMT deficiency is associated with hypotonia, significant intellectual disability, limited speech development, recurrent seizures, behavior problems, and involuntary movements. The birth prevalence of GAMT deficiency is likely between 0.5 and 2 per million live births. On the basis of small case series and sibling data, presymptomatic treatment with oral supplements of creatine, ornithine, and sodium benzoate, and a protein-restricted diet to reduce arginine intake, appear to substantially improve health and developmental outcomes. Without newborn screening, diagnosis typically happens after the development of significant impairment, when treatment has limited utility. GAMT deficiency newborn screening can be incorporated into the tandem-mass spectrometry screening that is already routinely used for newborn screening, with about 1 per 100 000 newborns screening positive. After a positive screen, diagnosis is established by finding an elevated guanidinoacetate concentration and low creatine concentration in the blood. Although GAMT deficiency is significantly more rare than other conditions included in newborn screening, the feasibility of screening, the low number of positive results, the relative ease of diagnosis, and the expected benefit of presymptomatic dietary therapy led to a recommendation from the Advisory Committee on Heritable Disorders in Newborns and Children to the Secretary of Health and Human Services that GAMT deficiency be added to the Recommended Uniform Screening Panel. This recommendation was accepted in January 2023.

Changing treatments and medical costs necessitate updates to hospitalization cost estimates for birth defects. The 2019 National Inpatient Sample was used to estimate the service delivery costs of hospitalizations among patients aged <65 years for whom one or more birth defects were documented as discharge diagnoses. In 2019, the estimated cost of these birth defect-associated hospitalizations in the United States was $22.2 billion. Birth defect-associated hospitalizations bore disproportionately high costs, constituting 4.1% of all hospitalizations among persons aged <65 years and 7.7% of related inpatient medical costs. Updating estimates of hospitalization costs provides information about health care resource use associated with birth defects and the financial impact of birth defects across the life span and illustrates the need to determine the continued health care needs of persons born with birth defects to ensure optimal health for all.

IMPORTANCE: Nearly 40% of US youth aged 2 to 19 years do not have a body mass index (BMI) in the healthy weight category. However, there are no recent estimates for BMI-associated expenditures using clinical or claims data. OBJECTIVE: To estimate medical expenditures among US youth across all BMI categories along with sex and age groups. DESIGN, SETTING, PARTICIPANTS: This cross-sectional study used IQVIA's ambulatory electronic medical records (AEMR) data set linked with IQVIA's PharMetrics Plus Claims database from January 2018 through December 2018. Analysis was performed from March 25, 2022, through June 20, 2022. It included a convenience sample of a geographically diverse patient population from AEMR and PharMetrics Plus. The study sample included privately insured individuals with a BMI measurement in 2018 and excluded patients with pregnancy-related visits. EXPOSURE: BMI categories. MAIN OUTCOMES AND MEASURES: Total medical expenditures were estimated using generalized linear model regression with γ distribution and log-link function. For out-of-pocket (OOP) expenditures, a 2-part model was used that included logistic regression to estimate the probability of positive expenditures followed by generalized linear model. Estimates were shown with and without accounting for sex, race and ethnicity, payer type, geographic region, age interacted with sex and BMI categories, and confounding conditions. RESULTS: The sample included 20 876 individuals aged 2 to 19 years; 104 066 were male (50.5%) and the median age was 12 years. Compared with those with healthy weight, total and OOP expenditures were higher for all other BMI categories. Differences in total expenditures were highest for those with severe obesity ($909; 95% CI, $600-$1218) followed by underweight ($671; 95% CI, $286-$1055) compared with healthy weight. Differences in OOP expenditures were highest for those with severe obesity ($121; 95% CI, $86-$155) followed by underweight ($117; 95% CI, $78-$157) compared with healthy weight. Having underweight was associated with higher total expenditures at ages 2 to 5 years and 6 to 11 years by $679 (95% CI, $228-$1129) and $1166 (95% CI, $632-$1700), respectively; having severe obesity was associated with higher total expenditures at ages 2 to 5 years, 6 to 11 years, and 12 to 17 years by $1035 (95% CI, $208-$1863), $821 (95% CI, $414-$1227), and $1088 (95% CI, $594-$1582), respectively. CONCLUSIONS AND RELEVANCE: The study team found medical expenditures to be higher for all BMI categories when compared with those with healthy weight. These findings may indicate potential economic value of interventions or treatments aimed at reducing BMI-associated health risks.

We read with interest the recent article by Kingsmore et al., who suggest that universal newborn rapid whole-genome sequencing is attractive for “comprehensive” newborn screening (NBS).1 Existing US NBS programs are based on mandated routine testing of newborns; evidence-based decision-making processes exist for this testing.2 Whether policy makers also consider routine rapid whole-genome sequencing of newborns to be warranted may depend on the resolution of a number of evidentiary, ethical, legal, social, and economic issues.3 Kingsmore et al. suggest that sequencing can complement existing public-health NBS programs but acknowledge the challenge of reconciling universal or near-universal genomic screening with informed parental consent and the allowable secondary use of genomic information.1

We appreciate the passion and commitment of Watchko and Maisels to the detection and treatment of neonatal hyperbilirubinemia (NBH) and jaundice. We understand their concern that our Viewpoint calls attention to evidence of a potential long-term harm of phototherapy: increased risk of epilepsy.1 Advocates often focus exclusively on benefits of screening and treatments. In contrast, it is the responsibility of policy makers to balance trade-offs between benefits and harms. Because the primary justification for screening and treatment for NBH is the prevention of kernicterus as a devastating long-term outcome, our Viewpoint focused on long-term health outcomes and did not attempt to catalog short-term harms or benefits of phototherapy.1 We realized that phototherapy is associated with a significantly lower need for exchange transfusions,2 which we considered a short-term benefit of treatment to reduce serum bilirubin levels.

Almut Winterstein and Amir Sarayani have three concerns regarding our article (May 2018). Their first concern is mortality (“likely while hospitalized”). Of the 199 patients enrolled twelve months before taking ivacaftor, 143 had twelve months of enrollment after treatment, and of the other 56, 1 died during a hospitalization in the twelve months after treatment. A twelve-month mortality rate of 1 in 199 (0.5 percent) patients is not surprising. In the Cystic Fibrosis Foundation’s Patient Registry, 10 of 1,779 (0.6 percent) patients who first took ivacaftor during 2012–15 died within twelve months (unpublished data).

The national EHDI 1-3-6 goals state that all infants should be screened for hearing loss before 1 month of age; with diagnostic testing before 3 months of age for those who do not pass screening; and early intervention (EI) services before 6 months of age for those with permanent hearing loss. This report updates previous summaries of progress on these goals by U.S. states and territories. Data are based on the Hearing Screening and Follow-up Survey (HSFS) conducted annually by the Centers for Disease Control and Prevention for the years 2006-2016. Trends were assessed using 3-year moving averages, with rates of newborns lost to follow-up or lost to documentation (LTF/D) also examined. During this period, the percentage of infants screened before one month increased from 85.1% to 95.3%, while the percentage receiving diagnostic testing before three months increased from 19.8% to 36.6%, and the percentage of infants identified with permanent hearing loss enrolled in early intervention (EI) before six months increased from 25.1% to 47.2%. Percentages of infants who ultimately received screening, diagnostic testing, and early intervention services - regardless of timing - were higher. During this period, LTF/D declined from 42.1% to 31.3% for diagnostic testing, and 39.4% to 20.3% for EI services. Diagnoses of hearing loss recorded increased from 0.9 to 1.7 per 1,000 infants screened, likely reflecting improved data.

In the article by Yoo and Grosse, entitled “The Cost Effectiveness of Screening Newborns | for Congenital Adrenal Hyperplasia” [Public Health Genomics 2009;12:67–72], the costeffectiveness results for newborn screening for congenital adrenal hyperplasia (CAH) do not | accurately reflect the assumptions stated in Table 1 of the article. Mr. Orban Holdgate | informed Dr. Grosse that the original cost-effectiveness model incorrectly applied the 80% | reduction in mortality among infants with the salt-wasting (SW) form of CAH with | screening to just a subset of infants with SW-CAH. | When the deterministic cost-effectiveness model was corrected for that error, the number of | deaths from SW-CAH in the screening scenario was 3.2 times less and the number of | averted deaths was 2.22 times greater. Consequently, the incremental cost-effectiveness ratio | (ICER) reported in the article, USD 292,000 per life-year (LY) saved, was greatly | overstated. A corrected estimate by Mr. Holdgate of the base-case ICER, assuming all | assumptions reported in the original article, is USD 128,000 per LY saved, in 2005. All | ICERs reported in the original Table 2 for the various sensitivity analyses should be | similarly adjusted downwards. The results for the probabilistic cost-effectiveness analysis | should be disregarded; Dr. Grosse was not able to replicate that analysis. | In qualitative terms, the original conclusion of Yoo and Grosse is not affected: newborn | screening for CAH would not be considered cost-effective using a threshold value of USD | 50,000 per LY saved. However, it might be considered cost-effective if a higher threshold | value were used. | The correct Table 2 reads as follows:

The Recommended Uniform Screening Panel (RUSP) is the list of conditions recommended by the US Secretary of Health and Human Services for inclusion in state newborn screening (NBS). During 2010-2022, seven conditions were added to the RUSP: severe combined immunodeficiency (SCID) (2010), critical congenital heart disease (CCHD) (2011), glycogen storage disease, type II (Pompe) (2015), mucopolysaccharidosis, type I (MPS I) (2016), X-linked adrenoleukodystrophy (X-ALD) (2016), spinal muscular atrophy (SMA) (2018), and mucopolysaccharidosis, type II (MPS II) (2022). The adoption of SCID and CCHD newborn screening by programs in all 50 states and three territories (Washington, D.C.; Guam; and Puerto Rico) took 8.6 and 6.8 years, respectively. As of December 2022, 37 programs screen for Pompe, 34 for MPS I, 32 for X-ALD, and 48 for SMA. The pace of implementation based on the average additional number of NBS programs per year was most rapid for SMA (11.3), followed by CCHD (7.8), SCID (6.2), MPS I (5.4), Pompe (4.9), and X-ALD (4.7).

Although we agree with Appelberg et al that newborn screening (NBS) for phenylketonuria (PKU) and congenital hypothyroidism (CH) is of great value,1 we disagree that such results in net cost-savings. Their contention relies on assumptions derived from cost-benefit studies published 4 decades ago.2,3 In 2005, a commentary in this journal challenged those arguments.4 We later reviewed the frequencies of intellectual disability among individuals with late-treated PKU and CH5,6; the latter review is the second reference cited in new CH clinical guidance.7 Our subsequent reviews of economic evaluations of NBS for PKU and CH pointed out that unrealistic assumptions about late-treated CH and PKU, like those made by Appelberg et al, result in overestimates of economic benefits.8, 9, 10

Prescription stimulant use, primarily for the treatment of attention-deficit/hyperactivity disorder (ADHD), has increased among adults in the United States during recent decades, while remaining stable or declining among children and adolescents (1,2). MarketScan commercial claims data were analyzed to describe trends in prescription stimulant fills before and during the COVID-19 pandemic (2016-2021) by calculating annual percentages of enrollees aged 5-64 years in employer-sponsored health plans who had one or more prescription stimulant fills overall and by sex and age group. Overall, the percentage of enrollees with one or more prescription stimulant fills increased from 3.6% in 2016 to 4.1% in 2021. The percentages of females aged 15-44 years and males aged 25-44 years with prescription stimulant fills increased by more than 10% during 2020-2021. Future evaluation could determine if policy and health system reimbursement changes enacted during the pandemic contributed to the increase in stimulant prescriptions. Stimulants can offer substantial benefits for persons with ADHD, but also pose potential harms, including adverse effects, medication interactions, diversion and misuse, and overdoses. Well-established clinical guidelines exist for ADHD care, but only for children and adolescents* (3); clinical practice guidelines for adult ADHD could help adults also receive accurate diagnoses and appropriate treatment.

Congenital cytomegalovirus (cCMV) infection is the leading nongenetic cause of sensorineural hearing loss (SNHL) in children.1 In the United States, cCMV occurs in an estimated 5 per 1000 live births.1 However, most cCMV infections remain undiagnosed. Newborns are usually tested for cCMV because of abnormal prenatal ultrasound findings, clinical suspicion at birth, maternal history of CMV infection during pregnancy, or referral from newborn hearing screening. Approximately 10% of infected infants present with clinical findings, such as purpura, petechiae, jaundice, hepatosplenomegaly, retinitis, or microcephaly, at birth.1 Up to 50% of symptomatic infants and 15% of asymptomatic infants present with SNHL either at birth or with delayed onset, which can be stable, fluctuating, or progressive.1

Lavelle et al1 have published an important modeling assessment of exome sequencing (ES) and genome sequencing (GS) in 2 types of pediatric patients. They concluded that first-line rapid GS (rGS) is likely to be cost-effective for diagnosing critically ill babies with suspected genetic disorders relative to the standard of diagnostic care, defined as including other types of genetic and laboratory tests, which is consistent with other studies.2,3 Lavelle et al1 also concluded that first-line rGS dominates (costs less and is at least as effective) alternative testing strategies, including first-line rapid ES (rES). We believe that it is premature to conclude that rGS dominates rES for 2 primary reasons. First, the relative difference between rES and rGS testing costs may be substantially greater than the 14% differential assumed in their model (ie, $10,320 [$3600] for trio rES vs $12,000 [$3000] for trio rGS based on 2019 laboratory prices).1 Second, the relative difference in diagnostic yield of rES and rGS may be less than the roughly 25% assumed in their model.1 Based on published estimates, rES in critically ill babies may be, at least in some settings, similar in effectiveness while costing substantially less than rGS.2

Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is an X-linked condition caused by pathogenic variants in the iduronate-2-sulfatase gene. The resulting reduced activity of the enzyme iduronate-2-sulfatase leads to accumulation of glycosaminoglycans that can progressively affect multiple organ systems and impair neurologic development. In 2006, the US Food and Drug Administration approved idursulfase for intravenous enzyme replacement therapy for MPS II. After the data suggesting that early treatment is beneficial became available, 2 states, Illinois and Missouri, implemented MPS II newborn screening. Following a recommendation of the Advisory Committee on Heritable Disorders in Newborns and Children in February 2022, in August 2022, the US Secretary of Health and Human Services added MPS II to the Recommended Uniform Screening Panel, a list of conditions recommended for newborn screening. MPS II was added to the Recommended Uniform Screening Panel after a systematic evidence review reported the accuracy of screening, the benefit of presymptomatic treatment compared with usual case detection, and the feasibility of implementing MPS II newborn screening. This manuscript summarizes the findings of the evidence review that informed the Advisory Committee's decision.

OBJECTIVE: To assess the association of body mass index (BMI) with inpatient care cost, duration, and acute complications among patients hospitalized for COVID-19 at 273 U.S. hospitals. METHODS: Children (2-17 years) and adults (≥18 years) hospitalized for COVID-19 during March 2020-July 2021 and measured BMI in a large electronic administrative healthcare database were included. We used generalized linear models to assess the association of BMI categories with the cost and duration of inpatient care. RESULTS: Among 108,986 adults and 409 children hospitalized for COVID-19, obesity prevalence was 53.4% and 45.0%, respectively. Among adults, overweight and obesity were associated with higher costs of care, and obesity was associated with longer hospital stays. Children with severe obesity had a higher cost of care, but not significantly longer hospital stays, compared to those with healthy weights. Children with severe obesity were 3.7 times (95% CI: 1.5 to 9.5) as likely to have invasive mechanical ventilation and 62% more likely to have an acute complication (95% CI, 39-90), compared to children with healthy weight. CONCLUSIONS: These findings show that patients with high BMIs experience significant healthcare burden during inpatient COVID-19 care. This article is protected by copyright. All rights reserved.

Among 342 US infants with congenital cytomegalovirus treated with antivirals, 114 (33%) received ganciclovir (with or without valganciclovir) and 228 (67%) received valganciclovir only, for a median of 8 and 171 days, starting at a median of 15 and 45 days of life, respectively, with neutropenia diagnosed in 25% and 17%.

From 20092015 to 20162019, the proportion of U.S. infants with congenital cytomegalovirus (cCMV) treated with valganciclovir roughly doubled for infants enrolled with employer-sponsored insurance (from 16% to 29%) and Medicaid (from 16% to 36%). The proportion treated with valganciclovir increased for all cCMV disease severity groups.

Cost-effectiveness analyses (CEAs) are often prepared to quantify the expected economic value of potential vaccination strategies. Estimated outcomes and costs of vaccination strategies depend on numerous data inputs or assumptions, including estimates of vaccine efficacy and disease incidence in the absence of vaccination. Limitations in epidemiologic data can meaningfully affect both CEA estimates and the interpretation of those results by groups involved in vaccination policy decisions. Developers of CEAs should be transparent with regard to the ambiguity and uncertainty associated with epidemiologic information that is incorporated into their models. We describe selected data-related challenges to conducting CEAs for vaccination strategies, including generalizability of estimates of vaccine effectiveness, duration and functional form of vaccine protection that can change over time, indirect (herd) protection, and serotype replacement. We illustrate how CEA estimates can be sensitive to variations in specific epidemiologic assumptions, with examples from CEAs conducted for the USA that assessed vaccinations against human papillomavirus and pneumococcal disease. These challenges are certainly not limited to these two case studies and may be relevant to other vaccines.

INTRODUCTION/AIMS: The multidisciplinary Duchenne muscular dystrophy (DMD) Care Considerations were developed to standardize care and improve outcomes. We provide cumulative cost estimates for selected key preventive (i.e., excluding new molecular therapies and acute care) elements of the care considerations in eight domains (neuromuscular, rehabilitation, respiratory, cardiac, orthopedic, gastrointestinal, endocrine, psychosocial management) independent of completeness of uptake or provision of non-preventive care. METHODS: We used de-identified insurance claims data from a large Midwestern commercial health insurer during 2018. We used Current Procedural Terminology and National Drug codes to extract unit costs for clinical encounters representing key preventive elements of the DMD Care Considerations. We projected per-patient cumulative costs from ages 5 to 25years for these elements by multiplying a schedule of recommended frequencies of preventive services by unit costs in 2018 US dollars. RESULTS: Assuming a diagnosis at age 5years, independent ambulation until age 11, and survival until age 25, we estimated 670 billable clinical events. The 20-year per-patient cumulative cost was $174,701 with prednisone ($2.3 million with deflazacort) and an expected total of $12,643 ($29,194) for out-of-pocket expenses associated with those events and medications. DISCUSSION: Standardized monitoring of disease progression and treatments may reduce overall costs of illness. Costs associated with these services would be needed to quantify potential savings. Our approach demonstrates a method to estimate costs associated with implementation of preventive care schedules.

BACKGROUND: In 2016, Zika virus (ZIKV) was recognized as a human teratogen. North Carolina (NC) had no local transmission of ZIKV but infants with relevant birth defects, including severe brain anomalies, microcephaly, and eye abnormalities, require specialized care and services, the costs of which have not yet been quantified. The objective of this study is to examine NC Medicaid healthcare expenditures for infants with defects potentially related to ZIKV compared to infants with no reported defects. METHODS: Data sources for this retrospective cohort study include NC birth certificates, Birth Defects Monitoring Program data, and Medicaid enrollment and paid claims files. Infants with relevant defects were identified and expenditure ratios were calculated to compare distributions of estimated expenditures during the first year of life for infants with relevant defects and infants with no reported defects. RESULTS: This analysis included 551 infants with relevant defects and 365,318 infants with no reported defects born 2011-2016. Mean total expenditure per infant with defects was $69,244 (median $30,544) for the first year. The ratio of these expenditures relative to infants with no reported defects was 14.5. Expenditures for infants with select brain anomalies were greater than those for infants with select eye abnormalities only. CONCLUSIONS: Infants with defects potentially related to ZIKV had substantially higher Medicaid expenditures than infants with no reported defects. These results may be informative in the event of a future outbreak and are a resource for program planning related to care for infants in NC.