A Detailed Analysis of the Factors Influencing Neonatal TSH: Results From a 6-Year Congenital Hypothyroidism Screening Program

Abstract

Background: Neonatal thyrotropin (TSH) on dried blood spot (DBS), the most common screening strategy for primary congenital hypothyroidism (CH), is influenced by numerous factors that may hinder a true CH diagnosis. A second test can thus be performed to clarify the initial findings, although its application varies among screening programs. Objectives: The aim of this study was to evaluate the effect of maternal and neonatal factors on neonatal TSH levels and offer practical screening recommendations. Methods: We retrospectively analyzed screening data of 62,132 neonates born in Abruzzo, an Italian region considered mildly iodine deficient, between 2011 and 2016. We then performed a multiple linear regression to model the relationship between TSH (the dependent variable) and 13 independent variables extracted from blood collection cards. Results: Most neonates (53,551 of 62,132, 86%) had normal TSH and no clinical indications for a second screening. A minority (1,423, 2.3%) had elevated TSH in the initial DBS, which was confirmed in 97 cases (7%) on a second screen. The remaining neonates (6,594, 10.6%) had a normal initial TSH but underwent a second test in accordance with screening protocols, and were found to have delayed TSH elevation in 23 cases (0.4%). Those 120 newborns (97 + 23), considered highly suspicious for primary CH, were referred to a pediatrician for confirmatory testing and excluded from subsequent analysis of factors influencing TSH levels. Sex (β regression coefficient, β = 1.11 female to male, 95% CI 1.09, 1.12) and age at collection (β = 0.78 day 5 to days 2-3, 95% CI 0.74, 0.83) affected neonatal TSH, suggesting the utility of specific nomograms. In addition, prematurity (β = 0.85 term to preterm, 95% CI 0.80, 0.91), dopamine use (β = 0.71, 95% CI 0.62, 0.81), and birth weight (β = 1.40 normal vs. very low, 95% CI 1.05, 1.89) strongly influenced neonatal TSH. Conclusions: Neonatal TSH is influenced by several factors supporting the delineation of local sex-and age-adjusted TSH cutoffs, and the universal adoption of a second TSH test in neonates at risk of missed primary CH diagnosis.

Predictors of transient congenital primary hypothyroidism: data from the German registry for congenital hypothyroidism (AQUAPE “HypoDok”)

“…Treatment of mothers with iodine, anti-thyroid drugs or dopamine medication in neonates frequently causes TCH, because these drugs suppress thyroid function in the neonate temporarily [26,27]. In our study, in the TCH group, dopamine medication was more often used in the neonatal period as expected.…”

“…Therefore, age-dependent variations of serum TSH concentrations are expected to have a minor effect as in the vast majority of cases the confirmation of diagnosis was done within the first 14 days of age in both groups. Serum TSH concentrations may be further affected by daytime, gender [26] and specific assay modalities such as range and sensitivity [27].…”

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

“…Other theories put forward by researchers for elevated TSH during the winter are decreased maternal consumption of iodine-rich foods or lower maternal vitamin D during winter months and lower temperatures stimulating fetal pituitary to produce more TSH in the winter [ 33 , 34 , 35 ].…”

Predictors of Transient Congenital Primary Hypothyroidism: Data from the German Registry for Congenital Hypothyroidism (AQUAPE "HypoDok")

“…As neonatal screening is scheduled for a fixed period of time (1,21), age dependent variations of serum TSH concentrations are expected to have a minor effect. Serum TSH concentrations may be affected by daytime, gender (26) and specific assay modalities such as range and sensitivity (27).…”