Missed Cystic Fibrosis Newborn Screening Cases due to Immunoreactive Trypsinogen Levels below Program Cutoffs: A National Survey of Risk Factors.

Testing immunoreactive trypsinogen (IRT) is the first step in cystic fibrosis (CF) newborn screening. While high IRT is associated with CF, some cases are missed. This survey aimed to find factors associated with missed CF cases due to IRT levels below program cutoffs. Twenty-nine states responded to a U.S-wide survey and 13 supplied program-related data for low IRT false screen negative cases (CFFN) and CF true screen positive cases (CFTP) for analysis. Rates of missed CF cases and odds ratios were derived for each factor in CFFNs, and two CFFN subgroups, IRT above ("high") and below ("low") the CFFN median (39 ng/mL) compared to CFTPs for this entire sample set. Factors associated with "high" CFFN subgroup were Black race, higher IRT cutoff, fixed IRT cutoff, genotypes without two known CF-causing variants, and meconium ileus. Factors associated with "low" CFFN subgroup were older age at specimen collection, Saturday birth, hotter season of newborn dried blood spot collection, maximum ≥ 3 days laboratories could be closed, preterm birth, and formula feeding newborns. Lowering IRT cutoffs may reduce "high" IRT CFFNs. Addressing hospital and laboratory factors (like training staff in collection of blood spots, using insulated containers during transport and reducing consecutive days screening laboratories are closed) may reduce "low" IRT CFFNs.

Newborn tandem mass spectroscopy screening for adenosine deaminase deficiency.

BACKGROUND: Newborn screening (NBS) by means of T cell receptor excision circles (TREC) is now universal in the United States, Puerto Rico, and the Navajo Nation as a strategy to identify severe combined immunodeficiency (SCID) in newborns. Owing to the characteristics of adenosine deaminase (ADA) deficiency, a small but important number of cases can be missed by this screening. OBJECTIVE: To evaluate the results of the first year statewide NBS for ADA by means of dried blood spot NBS. METHODS: On October 7, 2019, the state of Michigan began screening newborn dried blood spots for ADA deficiency by means of the Neobase-2 tandem mass spectroscopy (TMS) kit. We report 1 known case of ADA deficiency in the 18 months before screening. We then reviewed the results of the first 2 years of TMS ADA screening in Michigan. RESULTS: There was 1 patient with ADA deficiency known to our centers in the 18 months before initiation of TMS ADA screening; this patient died of complications of their disease. In the first 2 years of TMS ADA NBS, 206,321 infants were screened, and 2 patients had positive ADA screen results. Both patients had ADA deficiency confirmed through biochemical and genetic testing. One patient identified also had a positive TREC screen and was confirmed to have ADA-SCID. CONCLUSION: In our first 2 years, TMS NBS for ADA deficiency identified 2 patients with ADA deficiency at negligible cost, including 1 patient who would not have been identified by TREC NBS. This report provides initial evidence of the value of specific NBS for ADA deficiency.

Use of Online Newborn Screening Educational Resources for the Education of Expectant Parents: An Improvement in Equity.

Educating parents about the newborn screening (NBS) process is critical in ensuring that families are aware of their child's NBS, which could contribute to better outcomes for the baby and experiences for the family. Successful education efforts result in expecting parents understanding the importance of NBS, feeling comfortable with the NBS process, and being aware of their choices after NBS is complete. Educating parents prenatally is challenging for many NBS programs for a variety of reasons. The COVID-19 pandemic added additional barriers to NBS programs' ability to educate parents prenatally about NBS. By initiating a department-wide partnership among other programs with a similar target audience, Michigan's NBS Program was able to host a virtual baby fair. Since the inaugural event, Michigan's NBS Program has hosted seven virtual fairs with 15 participating programs. A total of 692 participants registered for the baby fair and received a resource packet, over 157 participants joined one of the live presentations, and 211 have viewed the YouTube videos of recorded fairs. Virtual baby fairs are a cost-effective and convenient approach to education that could be implemented in any NBS program to educate parents prenatally about NBS.

Five cases of missed cystic fibrosis heterozygous mutations identified after a positive newborn screen on a sibling.

In Michigan (MI), NBS for CF was started in October 2007 using the IRT/DNA protocol. In 2016, a component of the Hologic molecular test kit used by the MI NBS lab was recalled (40 CF mutation 2nd tier test). This recall had a major impact on states using the Hologic test kits in their NBS programs. Michigan specimens were sent to another state's NBS Lab for 2nd tier testing using the Luminex 60 mutation test kit until the Luminex kit could be procured and validated in MI. In this report, we present five cases born during this time period. These cases were initially reported out as having normal NBS results for CF but had heterozygous F508 del (c.1521_1523delCTT) mutations later identified. Of the five cases, one was diagnosed with CF (Case1), one with CF related metabolic syndrome (CRMS), and the other three were carriers.

Current Practices for U.S. Newborn Screening of Pompe Disease and MPSI.

Two lysosomal storage disorders (LSDs), Pompe disease and Mucopolysaccharidosis type I (MPSI) were added to the Recommended Uniform Screening Panel (RUSP) for newborn screening (NBS) in 2015 and 2016, respectively. These conditions are being screened with variable practice in terms of primary and reflex analytes (either biochemical or molecular testing) as well as collection of short- and long-term follow-up elements. The goal of this study is to evaluate practices of state health departments in regards to screening methods and follow-up data collected. We conducted online surveys and phone questionnaires to determine each U.S. state's practices for screening and follow-up of positive newborn screens. We report the first snapshot of practices for NBS for the LSDs included on the RUSP. All 50 U.S. states responded to our survey. The majority of U.S. states are not currently screening for Pompe disease and MPSI as of March 2020, but this number will increase to 38 states in the coming 1-3 years based on survey results. Our survey identifies data elements used by state health departments for short-and long-term follow-up that could serve as the basis of common elements for larger, public health-based analyses of the benefits and efficacy of screening for Pompe disease and MPSI.

Performance of ICD-10-CM diagnosis codes for identifying children with Sickle Cell Anemia.

OBJECTIVE: To develop, test, and validate the performance of ICD-10-CM claims-based case definitions for identifying children with sickle cell anemia (SCA). DATA SOURCES: Medicaid administrative claims (2016) for children <18 years with potential SCA (any D57x diagnosis code) and newborn screening records from Michigan and New York State. STUDY DESIGN: This study is a secondary data analysis. DATA COLLECTION/EXTRACTION METHODS: Using specific SCA-related (D5700, D5701, and D5702) and nonspecific (D571) diagnosis codes, 23 SCA case definitions were applied to Michigan Medicaid claims (2016) to identify children with SCA. Measures of performance (sensitivity, specificity, area under the ROC curve) were calculated using newborn screening results as the gold standard. A parallel analysis was conducted using New York State Medicaid claims and newborn screening data. PRINCIPAL FINDINGS: In Michigan Medicaid, 1597 children had ≥1 D57x claim; 280 (18 percent) were diagnosed with SCA. Measures of performance varied, with sensitivities from 0.02 to 0.97 and specificities from 0.88 to 1.0. The case definition of ≥1 outpatient visit with a SCA-related or D571 code had the highest area under the ROC curve, with a sensitivity of 95 percent and specificity of 92 percent. The same definition also had the highest performance in New York Medicaid (n = 2454), with a sensitivity of 94 percent and specificity of 86 percent. CONCLUSIONS: Children with SCA can be accurately identified in administrative claims using this straightforward case definition. This methodology can be used to monitor trends and use of health services after transition to ICD-10-CM.

Hydrogen peroxide triggers an increase in cell surface expression of system xc- in cultured human glioma cells.

System xc- exchanges extracellular cystine for intracellular glutamate across the plasma membrane of many cell types. One of the physiological roles of System xc- is to provide cystine for synthesis of the antioxidant glutathione. Here we report that hydrogen peroxide (H2O2) triggers the translocation of System xc- to the plasma membrane within 10 min of the initial exposure. Specifically, we observed a three-fold increase in 35S-l-cystine uptake following a 10 min exposure to 0.3 mM H2O2. This effect was dose-dependent with an EC50 for H2O2 of 65 µM. We then used cell surface biotinylation analysis to test the hypothesis that the increase in activity is due to an increased number of transporters on the plasma membrane. We demonstrated that the amount of transporter protein, xCT, localized to the plasma membrane doubles within 10 min of H2O2 exposure as a result of an increase in its delivery rate and a reduction in its internalization rate. In addition, we demonstrated that H2O2 triggered a rapid decrease in total cellular glutathione which recovered within 2 h of the oxidative insult. The kinetics of glutathione recovery matched the time course for the recovery of xCT cell surface expression and System xc- activity following removal of the oxidative insult. Collectively, these results suggest that oxidants acutely modulate the activity of System xc- by increasing its cell surface expression, and that this process may serve as an important mechanism to increase de novo glutathione synthesis during periods of oxidative stress.

The financial and time burden associated with phenylketonuria treatment in the United States.

BACKGROUND: Phenylketonuria (PKU) imposes a substantial burden on people living with the condition and their families. However, little is known about the time cost and financial burden of having PKU or caring for a child with the condition. METHODS AND FINDINGS: Primary data were collected with a detailed cost and utilization survey. Primary outcomes included utilization and out-of-pocket costs of medical services, medical formula, and prescribed low-protein food consumption, as well as the time and perceived effort involved in following the PKU diet. Respondents were people living with PKU or parents of children with PKU identified through a state newborn screening program database. Secondary administrative claims data were also used to calculate mean total, insurer, and out-of-pocket payments in inpatient, outpatient (office visits, emergency room, and laboratory tests), and pharmacy settings for privately insured persons with PKU. Payments were calculated for sapropterin and for PKU formula.In primary data analysis (children n = 32, adults n = 52), annual out-of-pocket costs were highest for low-protein foods (child = $1651; adult = $967) compared with other categories of care. The time burden of PKU care was high; families reported spending more than 300 h per year shopping for and preparing special diet foods.In secondary data analysis, children 12-17 years old had the highest average medical expenditures ($54,147; n = 140) compared to children 0-11 years old ($19,057; n = 396) and adults 18 years and older ($40,705; n = 454). Medication costs were the largest contributor to medical costs, accounting for 61-81% of total costs across age groups. Sapropterin was the largest driver of medication costs, accounting for 85% of child medication costs and 92% of adult medication costs. CONCLUSION: Treatment for PKU incurs a substantial time and cost burden on persons with PKU and their families. Estimated medical expenditures using claims data varied by age group, but sapropterin represented the largest cost for PKU treatment from a payer perspective across age groups.

Evaluation of Pulse Oximetry Screening Rates Among the Midwife-Attended Out-of-Hospital Birth Community in Michigan.

INTRODUCTION: In Michigan, pulse oximetry screening rates for critical congenital heart defects (CCHDs) are assessed for birthing hospitals but have not been assessed for the midwife-attended births that occur in the out-of-hospital birth community. This analysis was conducted to determine pulse oximetry screening rates among the midwife-attended out-of-hospital birth community in Michigan overall, and among midwives provided with loaned pulse oximeters from the Michigan Department of Health and Human Services (MDHHS). METHODS: Records for midwife-attended out-of-hospital births between April 1, 2014, and December 31, 2016, were linked via probabilistic matching with newborn screening records. Pulse oximetry screening rates were calculated for the midwife-attended out-of-hospital birth population overall, by midwife, and stratified by receipt of loaned pulse oximeters from MDHHS. Births from midwives who attended 5 or more nonhospital births during the study period were included in this analysis. RESULTS: Of the 3410 midwife-attended out-of-hospital births, 20.8% (n = 710) reported as having received a pulse oximetry screening for CCHDs. For births attended by midwives who received pulse oximeters from MDHHS, 50.5% had pulse oximetry screening results reported, compared with 12.7% among births attended by midwives without a loaned pulse oximeter. Of the 78 total midwives, 18% (n = 14) reported pulse oximetry screening results on more than half of the births they attended. Of the 14 midwives who received a pulse oximeter from MDHHS, 50.0% (n = 7) reported screening results for more than half of all births they attended. DISCUSSION: Our findings indicate that CCHD screening rates are low among midwife-attended out-of-hospital birth community. Screening rates were higher among midwives who received a pulse oximeter from MDHHS, but fewer than half of the attended births had a reported pulse oximetry screening. Further discussions with the midwife-attended out-of-hospital birth community to better understand screening barriers may be beneficial.

Incidence, demographic characteristics, and geographic distribution of sickle cell trait and sickle cell anemia births in Michigan, 1997-2014.

BACKGROUND: This study describes the incidence, demographic characteristics, and geographic distribution of sickle cell anemia (SCA) and sickle cell trait births in Michigan. METHODS: Michigan newborn screening records and birth certificates (1997-2014) were used to identify sickle cell trait and SCA births, as well as demographic characteristics and mother's residential address. Incidence was calculated overall and by county. RESULTS: During the study period, there were 592 SCA births and 33,404 sickle cell trait births in Michigan. The majority of SCA (86.3%) and trait (80.2%) cases were among children who were black. Children with SCA were born in 23% of Michigan counties; children with trait were born in 93%. CONCLUSION: Compared to SCA, sickle cell trait births occur at 50-fold greater incidence and have a substantially expanded geographic distribution. Further research is necessary to understand the most appropriate and impactful use of resources to increase the proportion of families and adults that are aware of their sickle cell trait status.

Health outcomes and services in children with sickle cell trait, sickle cell anemia, and normal hemoglobin.

The health effects of sickle cell trait among children are unknown. We compared select health outcomes and health services utilization among children with sickle cell trait, sickle cell anemia (SCA), and normal hemoglobin. Newborn screening records were used to identify children with sickle cell trait and SCA born in Michigan (1997-2014) who were enrolled in Michigan Medicaid for ≥1 year from 2012 to 2014. Each select health outcome (acute otitis media, acute respiratory infections, fever, invasive pneumococcal disease, pneumonia and influenza, renal complications, spleen problems, stroke) was defined as ≥1 claim with a diagnosis code for the respective outcome within a study year. Health services utilization was summarized as counts of emergency department, inpatient, and outpatient encounters. The relationship between hemoglobin status and each health outcome or utilization was assessed by logistic or negative binomial regression with generalized estimating equations. The study population consisted of 18 257 children with sickle cell trait, 368 with SCA, and 74 523 with normal hemoglobin (227 188 total person-years). Compared with those with normal hemoglobin, children with sickle cell trait had lower odds of acute otitis media (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.84-0.91), acute respiratory infections (OR, 0.94; 95% CI, 0.92-0.97), pneumonia and influenza (OR, 0.93; 95% CI, 0.87-0.99), and outpatient visits (incidence rate ratio, 0.95; 95% CI, 0.93-0.97). Children with SCA had higher or nonsignificant odds of all outcomes and types of health services utilization. These results indicate that children with sickle cell trait may not be at additional health risk for these outcomes. However, additional case-control studies may be necessary to identify rare events.

Pneumococcal vaccination coverage among children with sickle cell anemia, sickle cell trait, and normal hemoglobin.

BACKGROUND: Children with sickle cell anemia and sickle cell trait are at an increased risk of invasive pneumococcal disease compared to children with normal hemoglobin. We assessed and compared pneumococcal vaccination status among these three groups. PROCEDURE: Children with sickle cell anemia and sickle cell trait were identified using Michigan newborn screening records (1997-2014); each child was matched to four children with normal hemoglobin based on age, Medicaid enrollment (at least 1 year from 2012-2014), race, and census tract. Vaccination records were obtained from the state's immunization system. Pneumococcal vaccine coverage (PCV7 or PCV13 depending on date of administration) was assessed at milestone ages of 3, 5, 7, and 16 months. The proportion of children with vaccine coverage at each milestone was calculated overall and compared among children with sickle cell anemia, sickle cell trait, and normal hemoglobin using chi-square tests. RESULTS: The study population consisted of 355 children with sickle cell anemia, 17,319 with sickle cell trait, and 70,757 with normal hemoglobin. The proportion of children with age-appropriate pneumococcal vaccination coverage was low at each milestone and generally decreased over time. Children with sickle cell anemia were more likely to be covered compared to children with sickle cell trait or normal hemoglobin. CONCLUSIONS: Despite higher pneumococcal vaccination coverage among children with sickle cell anemia, opportunities for improvement exist among all children. Targeted interventions will benefit from mechanisms to identify children with increased risks such as sickle cell anemia or trait to improve pneumococcal vaccination coverage among these groups.

Newborn Screening Collection and Delivery Processes in Michigan Birthing Hospitals: Strategies to Improve Timeliness.

Objectives This study aimed to determine which steps in the newborn screening collection and delivery processes contribute to delays and identify strategies to improve timeliness. Methods Data was analyzed from infants (N = 94,770) who underwent newborn screening at 83 hospitals in Michigan between April 2014 and March 2015. Linear mixed effects models estimated effects of hospital and newborn characteristics on times between steps in the process, whereas simulation explored how to improve timeliness through adjustments to schedules for the state laboratory and for specimen pickup from hospitals. Results Time from collection to receipt of arrival to the state laboratory varied greatly with collection timing (P < 0.001), with specimens collected on Friday or Saturday delayed an average of 9-12 h compared to other specimens. Simulation estimates shifting specimen pickup from 6 p.m. Sunday-Friday to 9 p.m. Sunday-Friday could lead to an additional 12.6% of specimens received by the Michigan laboratory within 60 h of birth. Conclusions for Practice The time between when a specimen is collected and received by the laboratory can be a significant bottleneck in the newborn screening process. Modifying hospital pickup schedules appears to be a simple way to improve timeliness.

Congenital Hypothyroidism 3-Year Follow-Up Project: Region 4 Midwest Genetics Collaborative Results.

To identify the 3-year follow-up management and education patterns of primary care clinicians and pediatric endocrinologists for children diagnosed with congenital hypothyroidism (CH) through newborn screening programs, the Region 4 Midwest Genetics Collaborative, made up of seven regional states (Illinois, Indiana, Kentucky, Michigan, Minnesota, Ohio, Wisconsin), performed a survey study of parents and physicians caring for children identified with CH. The clinicians and parents of 409 children with CH regionally identified in 2007 were invited to participate in a voluntary survey. Responses relating to treatment, monitoring practices, educational resources, genetic counseling, and services provided/received were collected from 214 clinicians and 77 parents. In total, 99% had undergone a confirmatory test following positive newborn screening and 55% had imaging at diagnosis, but only 50% were identified as having the etiology identified. Thyroid withdrawal challenge testing was the choice method for re-evaluating thyroid function, but the approach varied. Clinician and parent responses to education and genetic counseling also differed. Clinicians report face-to-face education as the most common method, with less than 50% providing handouts to patients. Only 14% of patients were referred to a genetics counselor. Of parents reporting on their educational experience, 86% received face-to-face education from a pediatric endocrinologist and 4% received education from a genetic counselor. Only 65%, however, were satisfied with their education. These survey data suggest a lack of a standardized approach to diagnosis, follow-up, education, and genetic counseling. This collaborative effort provides insight into developing three-year follow-up, education and genetic counseling guidelines for children diagnosed with CH.

Congenital Hypothyroidism Long-Term Follow-up Project: Navigating the Rough Waters of a Multi-Center, Multi-State Public Health Project.

The Region 4 Midwest Genetics Collaborative, made up of seven regional states (Illinois, Indiana, Kentucky, Michigan, Minnesota, Ohio, and Wisconsin), brought together pediatric endocrinologists, state laboratory experts, public health follow-up specialists, and parents of children with congenital hypothyroidism (CH) to identify the three-year follow-up management and education patterns of primary care clinicians and pediatric endocrinologists in the care of children diagnosed with CH by state newborn screening (NBS) programs. Among a number of challenges, each state had different NBS methods, data systems, public health laws, and institutional review board (IRB) requirements. Furthermore, the diagnosis of CH was complicated by the timing of the NBS sample, the gestational age, weight, and co-morbidities at delivery. There were 409 children with CH identified through NBS in 2007 in the seven state region. The clinician of record and the parents of these children were invited to participate in a voluntary survey. Approximately 64 % of clinician surveys were collected with responses to questions relating to treatment, monitoring practices, educational resources, genetic counseling, and services provided to children with confirmed CH and their families. Nearly one-quarter (24 %) of parents surveyed responded to questions relating to treatment, education, genetic counseling, resources, and services they received or would like to receive. De-identified data from six of the seven states were compiled for analysis, with one state being unable to obtain IRB approval within the study timeline. The data from this collaborative effort will improve state follow-up programs and aid in developing three-year follow-up guidelines for children diagnosed with CH. To aid in the facilitation of similar public health studies, this manuscript highlights the challenges faced, and focuses on the pathway to a successful multi-state public health endeavor.

Identifying sickle cell disease cases using administrative claims.

OBJECTIVE: To develop and test the accuracy of administrative claims method for identifying children with sickle cell disease (SCD) to enable quality of care assessments among children enrolled in Medicaid. METHODS: All administrative claims with an SCD diagnosis were obtained from Michigan Medicaid from 2008 to 2011 for children ≤18 years, representing 1828 individuals. All Medicaid claims were obtained for these children and classified into categories on the basis of SCD care; these classifications were used to develop 37 alternative case definitions for identifying children with SCD. Children with ≥1 SCD claim in 2010 or 2011 were identified as confirmed SCD or not SCD using the gold standard of Michigan newborn screening administrative records. Measures of performance were calculated for each case definition for eligible children in 2010. Further validation of the case definitions was performed among eligible children in 2011. RESULTS: In 2010, a total of 938 children met eligibility criteria and were linked to newborn screening records; 605 (59%) were confirmed SCD, and 333 (32%) were not SCD. Measures of performance varied among the 37 case definitions, and the 4 best case definitions on the basis of the sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve were validated among 924 children meeting eligibility criteria in 2011. The case definition of at least 3 SCD claims in any position identified children with SCD with the most accuracy, with an area under the ROC curve of 0.91 (95% confidence interval 0.89, 0.93). CONCLUSIONS: This definition can be used to facilitate a more accurate identification of children with SCD in future studies. Further investigation is necessary to determine whether this method translates to other populations besides Michigan Medicaid-insured children.

Improving the Rate of Sufficient Sweat Collected in Infants Referred for Sweat Testing in Michigan.

Objective. Sweat collected for testing should have quantity not sufficient (QNS) rate of ≤10% in babies ≤3 months of age. Michigan (MI) cystic fibrosis (CF) centers' QNS rates were 12% to 25% in 2009. This project was initiated to reduce sweat QNS rates in MI. Methods/Steps. (a) Each center's sweat testing procedures were reviewed by a consultant. (b) Each center received a report with recommendations to improve QNS rates. (c) Technicians visited other participating centers to observe their procedures. Results. A total of 778 infants were identified as positive via CF newborn screening over a 2-year period. The mean age at time of sweat test was 23.2 days (SD ± 13.0 days). The overall QNS percent decreased from 14.4% to 9.5% (P = .04) during the study. Conclusion. This project and teamwork approach led to a decrease of sweat test QNS rates, opportunities to solve a common problem, and improved quality of care.

From newborn screening to population health research: implementation of the Michigan BioTrust for health.

In June 2009, the Michigan Department of Community Health launched the Michigan BioTrust for Health to improve preservation and utility of residual dried blood spots from newborn screening (NBS) for biomedical research while maintaining public support and integrity of NBS. In this article, we chronicle implementation of the BioTrust and document its impact on NBS. Overall, the percentage of new parents who consent to possible future research use of their children's dried blood spots through the BioTrust has remained consistent with previous public opinion surveys. No significant increase in refusal of NBS has been observed despite increased publicity. There was, however, a slight increase in requests to destroy samples following completion of NBS, indicating readily accessible opt-out information. Given adequate training and cooperation of birthing hospital staff, as well as outreach education for parents and health-care providers, we conclude it is possible to implement a biobanking initiative without adversely impacting NBS.

Transient hypothyroidism at 3-year follow-up among cases of congenital hypothyroidism detected by newborn screening.

OBJECTIVE: To investigate the rate of transient thyroid deficiency and treatment compliance among cases with congenital hypothyroidism diagnosed and followed-up after age 3 years by newborn screening (NBS). STUDY DESIGN: Cases detected by Michigan NBS between October 1, 2003, and December 31, 2007, and followed-up after age 3 years were included. The χ(2) and Fisher exact tests were used to test differences among followed and lost cases. Logistic regression models were used to investigate predictors of treatment cessation. RESULTS: Roughly 45% of eligible cases were lost to follow-up, and disease state (transient or permanent congenital hypothyroidism) could not be determined for 12 cases (7.9%). Of the 72 followed cases, 34 (47%) were considered permanent congenital hypothyroidism based on thyroid imaging findings (n = 7) or an increase in medication dosage over time (n = 27). One-quarter of followed cases with congenital hypothyroidism were no longer being treated, and of these, just over 83% stopped treatment without medical supervision. Of 23 cases that underwent a medically supervised trial without thyroid hormone medication, treatment was reinstated in 20. Laboratory confirmation of euthyroidism was available for 6 of 18 cases clinically deemed transient. After adjustment, black race was the strongest predictor of treatment cessation (OR, 9.86; 95% CI, 1.82-53.31). Treatment cessation was also more common among low birth weight infants and those admitted to the neonatal intensive care unit at birth. CONCLUSION: We recommend that NBS programs include long-term follow-up through at least age 3 years to determine treatment compliance and disease permanence. Further research is needed to determine ideal follow-up program operations and reassessment methods for congenital hypothyroidism disease permanence. Guidelines that provide evidence-based reassessment methods would be beneficial for the healthcare providers of children with congenital hypothyroidism.

Screening for congenital hypothyroidism in newborns transferred to neonatal intensive care.

OBJECTIVE: To evaluate the effectiveness of four dried blood spot testing protocols used in newborn screening for congenital hypothyroidism (CH) among newborns transferred to the neonatal intensive care unit (NICU). DESIGN, SETTING AND PATIENTS: Michigan newborns transferred to the NICU from 1998 to 2011 and screened for CH are included in this population-based retrospective cohort study. MAIN OUTCOME MEASURES: Screening performance metrics are computed and logistic regression is used to test for differences in the likelihood of detection across four periods characterised by different testing protocols. RESULTS: Primary thyrotropin (TSH) plus retest at 30 days of life or discharge achieved the greatest detection rate (2.6: 1000 births screened). The odds of detection was also significantly greater in this period compared with the tandem thyroxine (T4) and TSH testing period and separately compared with TSH testing alone, adjusted for birth weight, sex and race (OR 1.5; CI 1.0 to 2.2; p=0.046, and OR 2.2; CI 1.5 to 3.4, respectively). Approximately half of the cases detected during primary TSH plus serial testing periods were identified by retest. CONCLUSIONS: Primary TSH testing programmes that do not incorporate serial screening may fail to identify approximately half of newborns with congenital thyroid hormone deficiency transferred to the NICU. Tandem T4 and TSH testing programmes also likely miss cases who otherwise would receive treatment if serial testing were conducted. Further research is necessary to determine the optimal newborn screening protocol for CH; strategies combining tandem T4 and TSH with serial testing conditional on birthweight may be useful.