Objective: This study was conducted to evaluate changes in newborn screening for congenital hypothyroidism operations in Michigan. Study Design & Participants: This population-based retrospective cohort analysis includes Michigan resident infants born and screened in Michigan from 1/1/1994 to 6/30/2010. Newborn screening laboratory and follow-up data managed by the Michigan Department of Community Health are used in this study. Methods: The primary exposure is the method of dried blood spot testing: 1) thyroxine (T4) with backup thyrotropin (TSH) testing, 2) tandem T4 and TSH testing; 3) primary TSH testing without serial testing; and 4) primary TSH testing plus serial testing for births weighing <1,800g. Outcomes of interest include screening performance metrics: detection rate, positive predictive value, false positive rate, sensitivity, and specificity. The proportion of cases later determined to have transient disease is also investigated among those detected since 10/1/2003 that were followed-up after age three years and underwent diagnostic re-evaluation. Logistic regression analysis is used to investigate: a) whether the detection and false positive rates changed significantly as dried blood spot testing methods changed, and b) to investigate predictors of transient CH among cases followed-up and re-evaluated after age three years. Results: T4 testing is as likely to detect CH as is primary TSH testing without serial testing. Primary TSH testing yields fewer false positive determinations. Primary TSH testing yields fewer false positive determinations. The addition of serial testing among infants born weighing < 1,800g to the primary TSH testing protocol significantly increased the detection rate; in this period, 14% of detected cases were identified by retest and three of five cases weighing <1,800g were detected by retest. Primary TSH screening is more susceptible to false negative screening determinations and is incapable of detecting the 1-3 cases of central hypothyroidism expected annually in Michigan. Tandem T4 and TSH testing increased the detection rate by 80% and 20% relative to primary T4 backup TSH and primary TSH plus serial testing approaches respectively; however, this approach increased the number of false positives by eight fold relative to primary TSH plus serial testing. At three year follow-up, one of four cases was no longer receiving thyroid hormone medication. One of five cases re-evaluated had stopped treatment without medical supervision. Discussion: Our results indicate that newborn screening programs should consider tandem T4 and TSH testing or primary TSH plus serial testing for infants at risk of later rising TSH for detecting congenital hypothyroidism; however, a benchmark balance between sensitivity and specificity is necessary to determine the optimal testing strategy. Further efforts are necessary to standardize the process of diagnosis and terminologies used to characterize cases across newborn screening programs to make comparisons between and within programs over time more meaningful; guidelines for newborn screening, pediatricians, and pediatric endocrinologists are necessary to support this effort. Our findings also indicate that long term follow-up should be conducted for all CH cases, not only those eligible for a trial off thyroid hormone supplements, to ensure treatment compliance in hopes of avoiding potential brain damage among cases. As diagnostics and the nomenclature of congenital hypothyroidism are standardized across newborn screening programs, cost-benefit analyses are necessary to support recommended program operations.
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