Mary Kleyn

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.

Michigan BioTrust for Health: Public Support for Using Residual Dried Blood Spot Samples for Health Research

Purpose: Focus groups were utilized as a mechanism to solicit input from the public in developing the Michigan BioTrust for Health, a program of the Michigan Department of Community Health to improve storage conditions and promote use of residual newborn screening dried blood spots in health research. Methods: In 2008–2009, 10 diverse communities representative of the general public that might have special concerns as stakeholders in the BioTrust were identified, and 4 discussion questions were developed for use with a standard agenda. Focus group discussions were audio-recorded and transcribed by department staff. Qualitative conclusions resulting from the group discussions were compared with written, quantitative pre- and post-survey responses completed by individual participants. Results: Overall, there was considerable concurrence of opinion across the focus groups. Participants were generally positive about the BioTrust; a sentiment that held true across different demographic populations with over 85% of participants stating they would support use of residual dried blood spots in health research. Conclusion: The focus group process and findings played an important role for public health policy makers in affirming the importance of engaging and informing the public and led to concrete steps to foster community support.

Variation in immunoreactive trypsinogen concentrations among Michigan newborns and implications for cystic fibrosis newborn screening.

To investigate variation in immunoreactive trypsinogen (IRT) concentrations by race, sex, birth weight, and gestational age and their implications for the use of percentile‐based cutoffs for cystic fibrosis (CF) newborn screening (NBS) programs.

Predictors of insufficient sweat production during confirmatory testing for cystic fibrosis

Michigans Newborn Screening (NBS) Program began statewide screening for cystic fibrosis (CF) in October 2007. Confirmatory sweat testing is performed in infants having initial immunoreactive trypsinogen concentrations ≥99.8th percentile or ≥96th percentile and at least one CF mutation identified by DNA analysis. Some infants fail to produce a sufficient quantity of sweat (QNS—quantity not sufficient) to test for CF, meaning disease confirmation is delayed and sweat testing is later repeated. In this study, we evaluate predictors of QNS results. Information from the linked birth certificates and NBS diagnostic confirmation data were used. The study population was resident infants born in Michigan in 2008 who underwent a sweat test. Bivariate analyses revealed that preterm birth, low birth weight, CF care center, and race were significantly associated with QNS sweat testing results. Adjusted analyses indicated that preterm infants were 2.4 times more likely to have QNS results (95% CI 0.9, 6.4). When age at time of test, accounting for gestational age (gestational age at delivery plus postdelivery age of life = corrected age), was used in the multivariable model, infants <39 weeks were 7.4 times more likely to have QNS results (95% CI 2.5, 21.8). Waiting to sweat test until an infant is aged 39 weeks or more (corrected age) would likely reduce the rate of QNS results, thereby reducing the burden of repeat sweat testing on families and healthcare providers. Further research is necessary to understand the impact of potential delays in diagnosis/treatment relative to postponing sweat testing. Pediatr Pulmonol. 2011; 46:23–30.

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.

Newborn screening follow-up within the lifespan context: Michigan's experience.

Experience in using various data sources for surveillance systems and studies complements the growing knowledge base regarding requirements for newborn screening follow-up, which include integration with services other than clinical subspecialties. A proposed model for utilizing state resources to develop sickle cell disease surveillance across the lifespan is presented. This surveillance process should help evaluate the burden of sickle cell disease across the lifespan, and it could be used as a model for other hemoglobinopathies as well as other newborn screening disorders. Through the continued assessment and monitoring of prevalence, comorbidities, service utilization, cost, and patient outcomes, the newborn screening follow-up program will be able to inform public health policy.

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 childrens 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.

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.

Performance Metrics After Changes in Screening Protocol for Congenital Hypothyroidism

OBJECTIVE: To evaluate Michigan newborn screening for congenital hypothyroidism (CH) protocol changes. METHODS: This population-based study includes infants born and screened in Michigan (January 1, 1994–June 30, 2010). Screening performance is compared across 4 periods defined by the dried blood spot testing method: (1) thyroxine (T4) with backup thyrotropin, (2) tandem T4 and thyrotropin, (3) primary thyrotropin testing without serial testing, and (4) primary thyrotropin plus serial testing for births weighing <1800 g. Logistic regression is used to test for differences across periods. RESULTS: Thyrotropin testing exhibited greater specificity overall and greater likelihood of detection with serial testing relative to primary T4 testing. Tandem T4 and thyrotropin testing appeared more sensitive relative to other protocols, yet it produced significantly more false-positives, and detection may have been affected by overdiagnosis and misclassification. Central CH was no longer detected once T4 testing ceased. CONCLUSIONS: Primary thyrotropin plus serial testing for infants at risk for later rising thyrotropin outperformed other newborn screening strategies for classic CH, although 2 false-negatives occurred among normal birth weight infants admitted to the NICU during this testing period. Tandem T4 and thyrotropin screening outperformed other strategies for detection of both classic and central CH combined, although it is associated with increased operating costs. Additional research is necessary to weigh the benefits of increased sensitivity against additional program operating costs.

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

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.