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.

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.

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

OBJECTIVE: 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. PATIENTS AND METHODS: This cross-sectional population-based study of resident infants screened in Michigan investigates associations between demographic and perinatal variables and IRT concentrations after controlling for covariates. This study also analyzed how 96th and 99.8th IRT concentration percentiles values calculated by Michigan NBS vary by demographic and perinatal factors. Characteristics of infants having high (≥99.8th percentile) IRT concentrations and negative DNA tests are also explored. RESULTS: IRT mean concentrations and percentiles vary significantly by race, birth weight, gestational age, and to a lesser degree by sex. The greatest variation in mean IRT concentrations was observed among racial categories; black infants had an adjusted mean concentration of 36 ng/ml and Asian/Pacific Islander infants had a mean concentration of 25 ng/ml compared to an average concentration of 28 ng/ml in white infants and infants of other races. CONCLUSIONS: Variation in IRT concentrations resulted in the over-representation of certain groups referred for secondary testing, particularly referrals for sweat testing based on very high (≥99.8th percentile) concentrations alone, which is no longer recommended in Michigan. Further research may be warranted to evaluate initial IRT cutoffs used for CF NBS.

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.