Transient versus Permanent Congenital Hypothyroidism after the Age of 3 Years in Infants Detected on the First versus Second Newborn Screening Test in Oregon, USA.

BACKGROUND/AIMS: The newborn screening (NBS) program in Oregon, USA, collects two routine specimens in all infants. The aim of our study was to determine the incidence of permanent versus transient congenital hypothyroidism (CH) in infants detected on the first versus second screening test. METHODS: Thyroid function was determined in infants after the age of 3 years diagnosed with CH and born in Oregon between 2005 and 2011. Permanent hypothyroidism was defined as a TSH rise >10 mIU/ml after the first year on treatment or a TSH rise >6 mIU/ml with temporary discontinuation of l-thyroxine after the age of 3 years. RESULTS: Of the cases detected on the first test, 72 of 87 (83%) were permanent and 15 of 87 (17%) were transient, while of the cases detected on the second test, 5 of 22 (23%) were permanent and 17 of 22 (77%) were transient (OR 16.3, p < 0.001). There was a female preponderance detected on the first screen versus a male preponderance on the second screen. Blood spot and serum thyroid function tests at diagnosis, before treatment, were not meaningfully different between the two groups. The mean l-thyroxine dose at the age of 3 years was greater on the first screen: 61.2 versus 36.6 µg/day. CONCLUSIONS: Infants detected on the second NBS specimen have a higher incidence of transient CH. © 2016 S. Karger AG, Basel.

Prevalence and distribution of the c.1436C→T sequence variant of carnitine palmitoyltransferase 1A among Alaska Native infants.

OBJECTIVES: To use genotype analysis to determine the prevalence of the c.1436C→T sequence variant in carnitine palmitoyltransferase 1A (CPT1A) among Alaskan infants, and evaluate the sensitivity of newborn screening by tandem mass spectrometry (MS/MS) to identify homozygous infants. STUDY DESIGN: We compared MS/MS and DNA analyses of 2409 newborn blood spots collected over 3 consecutive months. RESULTS: Of 2409 infants, 166 (6.9%) were homozygous for the variant, all but one of whom were of Alaska Native race. None of the homozygous infants was identified by MS/MS on the first newborn screen using a C0/C16 + C18 cutoff of 130. Among 633 Alaska Native infants, 165 (26.1%) were homozygous and 218 (34.4%) were heterozygous for the variant. The prevalence was highest in Alaska's northern/western regions (51.2% of 255 infants homozygous; allele frequency, 0.7). CONCLUSIONS: The CPT1A c.1436C→T variant is prevalent among some Alaska Native peoples, but newborn screening using current MS/MS cutoffs is not an effective means to identify homozygous infants. The clinical consequences of the partial CPT1A deficiency associated with this variant are unknown. If effects are substantial, revision of newborn screening, including Alaska-specific MS/MS cutoffs and confirmatory genotyping, may be needed.

Follow-up of newborns with elevated screening T4 concentrations.

OBJECTIVE: To determine the type and incidence of hyperthyroxinemic disorders detected by follow-up of infants with elevated screening total T4 (TT4) values. STUDY DESIGN: Infants born in Oregon with a screening TT4 measurement >3 SD above the mean were offered enrollment. Serum TT4, free T4, total T3, free T3, and thyroid-stimulating hormone concentrations were measured in study infants and their mothers. RESULTS: Over a 20-month period, 101 infants (51 boys) and their mothers enrolled in the study (of 241 eligible infants), from a total screening population of 80,884; 17 infants were identified with persistent hyperthyroxinemia (TT4 >16 microg/dL). Ten had thyroxine-binding globulin excess (1:8088), 5 had evidence for increased T4 binding but not thyroxine-binding globulin excess (1:16,177), and 2 had findings compatible with thyroid hormone resistance (1:40,442); the other 84 infants had transient hyperthyroxinemia. Sequence analysis revealed a point mutation in the thyroid hormone receptor-beta gene in one infant with thyroid hormone resistance; no mutation was identified in the other infant. CONCLUSIONS: Although neonatal Graves' disease occurs in approximately 1 in 25,000 newborn infants, we did not detect any case among 80,884 infants, most likely because their mothers were receiving antithyroid drugs. Although the other hyperthyroxinemic disorders in the aggregate occur frequently (1:4758) and may benefit from detection, in general they do not require treatment.