From the Journals

Initial screening not enough to catch all cases of preterm congenital hypothyroidism



Successive screenings to detect congenital hypothyroidism in preterm infants is key to identifying cases that would otherwise lead to permanent and decompensated hypothyroidism, reported Niamh McGrath, MD, of the department of pediatric endocrinology at Children’s University Hospital, Dublin, and her associates in the Journal of Pediatrics.

In a population-based prospective review of 898,424 records between 2004 and 2016, Dr. McGrath and her associates identified all preterm infants less than 33 weeks diagnosed with congenital hypothyroidism and receiving treatment with levothyroxine. Of the infants screened, just 53 were selected to participate in the study, including 26 who were diagnosed at the first thyroid-stimulating hormone (TSH) screening and 27 who had delayed TSH elevation.

Gestational age ranged from 23 to 33 weeks, median birth weight measured 1.2 kg, median serum TSH concentration at the time of diagnosis was 78.3 mU/L, and median free thyroxine concentration was 8.9 pmol/L.

For half of the infants ultimately diagnosed, congenital hypothyroidism was not detected during the initial newborn screening. The authors also noted that 25% of patients with delayed TSH elevation had been exposed to iodine while undergoing surgery for necrotizing enterocolitis; after age 28 days, four of these infants were found to have elevated TSH. They cautioned that while this finding emphasizes the need for close monitoring and repeat screening of infants who have been exposed to iodine for up to 1 month following exposure, they could not be certain that the iodine exposure was responsible for the transient hypothyroidism in these patients.

Dr. McGrath and her associates emphasized the importance of repeat TSH screening for all preterm infants, noting that standard protocol screenings conducted just once at age 2 weeks or 4 weeks are not sufficient to effectively identify all cases of congenital hypothyroidism in which TSH elevation is delayed. Instead, they recommended measuring TSH on days 3-5 and at 1 week, 2 weeks, 4 weeks, and term-corrected gestational age.

“Our data are consistent with studies showing a high incidence of delayed TSH rise, particularly in very-low-birth-weight infants,” the authors wrote. They speculated that delays in detecting primary congenital hypothyroidism could be caused by the suppression of TSH secretion as a result of “hypothalamic-pituitary immaturity, medication administration, and effects of serious neonatal illness.” In fact, had standard, recommended 2-week-only screening protocols been followed with their patient population, fully 48% of infants with delayed TSH elevation would have been overlooked; half of these patients were later found to have decompensated hypothyroidism.

Neurodevelopmental disability caused by congenital hypothyroidism, which affects roughly 1 in every 2,000-4,000 births, is increasingly being prevented with newborn screenings that identify the condition early, but the incidence of congenital hypothyroidism has increased considerably in the past 20 years. The authors attribute this increase to the gradual change in screening cutoff levels and the rise in number of preterm infants who are surviving.

The need for a second screening, as well as appropriate timing and optimal TSH cutoff, are “subjects of active debate,” the authors wrote. The latest European screening guidelines recommend second screenings for preterm and low-birth-weight infants at either 2 weeks of age or 2 weeks following preliminary screening. Although they make no recommendations regarding additional screenings, American Academy of Pediatrics guidelines, published in 2006, cite a “disproportionate incidence” of delayed increase in TSH and congenital hypothyroidism in infants with very low birth weight. Dr. McGrath and her associates speculated that not all screening programs have adopted repeat screening of preterm infants, perhaps because of the low yield results, “the transient nature of most cases” detected, as well as conflicting long-term data on neurodevelopmental outcomes.

Dr. McGrath receives funding from the Children’s Fund for Health. The authors declared no conflicts of interest.

SOURCE: McGrath N et al. J Pediatr. 2018 Oct 24. doi: 10.1016/j.jpeds.2018.09.044.

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