The Impact of Seasonal Changes on Thyroxine and Thyroid-Stimulating Hormone in Newborns.

Newborn screening for congenital hypothyroidism (CH) is performed by measuring the concentration of thyroxine (T4) and/or thyroid-stimulating hormone (TSH) in dried blood spots. Unfortunately, the levels of T4 and TSH vary due to multiple factors, and therefore the false-positive rate for the test is a challenge. We analyzed screening data from 2008 to 2017 to determine the effect of seasonal changes and manufacturer kit lot changes on T4 and TSH values and on numbers of infants referred. Over a 10-year period, we screened 2.4 million infants using commercially available fluoroimmunoassays to measure T4 and TSH concentrations in dried blood spots. During colder months, daily mean T4 and TSH values were higher and referral rates and false-positive rates were higher. However, there was no significant difference between the number of confirmed CH cases. Furthermore, in rare instances, we observed differences in T4 daily mean values during the 10-year period when manufacturer kit lot changes were made. Seasonal temperature variations influence measured T4 and TSH values and consequently lower the positive predictive value for CH testing in colder months. Newborn screening (NBS) programs should be aware that manufacturer kit lot changes may also influence T4 values.

Gender disparities in screening for congenital hypothyroidism using thyroxine as a primary screen.

OBJECTIVE: Newborn screening for congenital hypothyroidism (CH) is based on testing for the markers thyroxine (T4) and/or thyroid-stimulating hormone (TSH). Diagnosis of CH is complicated because many factors affect the levels of these hormones including infant birth weight, prematurity and age at specimen collection. We investigated whether the sex of the newborn affected the levels of T4 and TSH and consequently the outcome of newborn screening. DESIGN: In New York State, the Newborn Screening program initially tests all infants for T4 and any baby with a result in the lowest 10% is triaged for TSH screening. We analyzed data from 2008 to 2016 to determine mean and median T4 and TSH values and how these results correlate with the sex of infants who are reported as borderline, referred and confirmed with CH. METHODS: T4 and TSH concentrations in dried blood spots were measured using commercially available fluoroimmunoassays. RESULTS: From 2008 to 2016, of the 2.4 million specimens tested for thyroxine, 51.5% were from male and 48.5% were from female infants. Male infants constituted 60% of specimens triaged for TSH testing, 64.9% of repeat requests and 59.6% of referrals, but only 49% of confirmed CH cases. The mean and median T4 values were lower (a difference of approximately 0.8-1.1 µg/dL each year) and the median TSH values were higher in male compared to female infants. CONCLUSIONS: Natural differences in thyroid hormone levels in male and female infants leads to male infants being disproportionately represented in the false-positive category.

Newborn screening for congenital adrenal hyperplasia in New York State.

From 2007 to 2014 the New York State (NYS) Newborn Screening (NBS) program screened 2 million newborns for congenital adrenal hyperplasia (CAH). The data was analyzed to determine factors that affect 17α-hydroxyprogesterone levels and assist in developing algorithm changes that would improve the positive predictive value of the methodology being used. The concentration of 17-OHP in dried blood spots was measured using the AutoDELFIA Neonatal 17-OHP kit (Perkin Elmer, Turku, Finland). During the 8 year period of this study 2476 babies were referred, 105 babies were diagnosed with CAH (90 with the salt-wasting (SW), 8 with simple virilizing (SV), 5 with non-classical CAH, and 2 with another enzyme deficiency) and, 14 with possible CAH. Three false negative cases with SV-CAH were reported to the program. Of the total 108 known cases, 74 (69%) infants were detected by newborn screening in the absence of clinical information, or, known family history. The incidence of CAH in NYS is 1 in 18,170 with a ratio of SW to SV of 8.2:1. The incidence of CAH is lower in Black infants than in White, Hispanic and Asian infants. Despite a lower mean birth weight, female infants have a lower mean 17-OHP value than male infants and are under-represented in the referred category. As per other NBS programs the false positive rate is exacerbated by prematurity/low birth weight and by over-early specimen collection.

Screening for cystic fibrosis in New York State: considerations for algorithm improvements.

Newborn screening for cystic fibrosis (CF), a chronic progressive disease affecting mucus viscosity, has been beneficial in both improving life expectancy and the quality of life for individuals with CF. In New York State from 2007 to 2012 screening for CF involved measuring immunoreactive trypsinogen (IRT) levels in dried blood spots from newborns using the IMMUCHEM(™) Blood Spot Trypsin-MW ELISA kit. Any specimen in the top 5% IRT level underwent DNA analysis using the InPlex(®) CF Molecular Test. Of the 1.48 million newborns screened during the 6-year time period, 7631 babies were referred for follow-up. CF was confirmed in 251 cases, and 94 cases were diagnosed with CF transmembrane conductance regulated-related metabolic syndrome or possible CF. Nine reports of false negatives were made to the program. Variation in daily average IRT was observed depending on the season (4-6 ng/ml) and kit lot (<3 ng/ml), supporting the use of a floating cutoff. The screening method had a sensitivity of 96.5%, specificity of 99.6%, positive predictive value of 4.5%, and negative predictive value of 99.5%. CONCLUSION: Considerations for CF screening algorithms should include IRT variations resulting from age at specimen collection, sex, race/ethnicity, season, and manufacturer kit lots. WHAT IS KNOWN: Measuring IRT level in dried blood spots is the first-tier screen for CF. Current algorithms for CF screening lead to substantial false-positive referral rates. WHAT IS NEW: IRT values were affected by age of infant when specimen is collected, race/ethnicity and sex of infant, and changes in seasons and manufacturer kit lots The prevalence of CF in NYS is 1 in 4200 with the highest prevalence in White infants (1 in 2600) and the lowest in Black infants (1 in 15,400).