medwireNews: Effective detection of newborn babies with congenital hypothyroidism (CH) requires a repeat screen with a lower thyroid-stimulating hormone (TSH) cutoff for at-risk infants, research suggests.

Antonella Olivieri (IRCCS San Raffaele Scientific Institute, Milan, Italy) and study co-authors looked at data from babies with CH who were detected through newborn screening in the Lombardy region of Italy between 2007 and 2014.

The first screen took place 49–120 hours after birth with a dried blood spot (b)TSH cutoff of 10 mU/L used – the team notes that the threshold varies even between different regions of Italy.

Babies with levels of 20 mU/L or higher were immediately referred, and those with levels of 10–20 mU/L underwent a second screen at age 7–9 days, as did those with lower levels but risk factors such as gestational age of less than 37 weeks, syndromes or malformations, use of steroids during pregnancy and maternal thyroid disease. The bTSH cutoff used at this second test was 5 mU/L.

Among 767,157 newborns screened, 842 were diagnosed with CH, including 273 (32.4%) who were negative at the first screen but positive at the second. Of the 119 of these babies who were seen at the researchers’ institute and therefore included in this study, 43.7% had bTSH values in the range of 5.0–9.9 mU/L at the second screening and 56.3% had values of 10.0 mU/L or higher.

The researchers note that only three of the 16 Italian screening laboratories reduce the bTSH threshold for the second screen, yet in their analysis nearly half of the babies identified at the second screen would have been missed had the 10.0 mU/L cutoff been used at both screens.

Babies identified with the reduced cutoff were more likely than those with bTSH levels of 10.0 mU/L or more to be born preterm (57.7 vs 23.9%), have a gestational age of less than 34 weeks (34.6 vs 6.0%), and to have been admitted to the neonatal intensive care unit (50.0 vs 17.9%) and to have a lower average birthweight after adjustment for gestational age (2185 vs 2920 g).

“These infants are therefore liable to be missed unless a second screen cut-off of 5 mU/L is used”, say Olivieri and colleagues.

Babies in the lower bTSH group were also more likely than those in the higher group to have mothers who were treated with glucocorticoids in pregnancy (11.5 vs 1.5%) or had maternal hypothyroidism and/or goitre (26.9 vs 10.4%).

However, the two groups were otherwise very similar. “Specifically, the frequency of thyroid dysgenesis and eutopic gland found in the Low bTSH Group was similar to that observed in the High bTSH Group, as well as the frequency of permanent and transient CH, and of persistent [hyperthyrotropinemia]”, writes the team.

Likewise, the proportion of babies with rare variants of CH candidate genes was similar regardless of whether bTSH was in the low or high category at the second screen.

There was also no significant difference between the low and higher bTSH level groups for rates of extra-thyroidal malformations or dysmorphic syndromes (21.2 and 16.4%, respectively) and multiple malformations (7.7 and 4.5%).

The researchers highlight the overall high rate of extra-thyroidal malformations among these babies, even those with transient CH, saying that “ours is the first study to show that not only severe but even mild forms of CH can be associated with extra-thyroidal malformations.”

Writing in The Journal of Clinical Endocrinology & Metabolism, Olivieri and team say that, taken together with previous research, “these findings strongly support both second screening and a low second screen cutoff”.

They believe this to be “particularly relevant in countries where the initial screening is obtained at 24–72 h of age, because early timing of the first screening necessitates higher TSH cutoffs to compensate for the physiologic postnatal TSH surge.”

By Eleanor McDermid

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J Clin Endocrinol Metab 2020; doi:10.1210/clinem/dgaa789