Delayed Thyrotropin Rise in Preterm Newborns: Value of Multiple Screening Samples and of a Detailed Clinical Characterization

Background: Newborn screening for congenital hypothyroidism (CH) has been implemented in high-income countries since the 1970s to prevent intellectual disability. A delayed thyrotropin (TSH) rise with a normal TSH on the first dry blood spot (DBS) sample, followed by an abnormal TSH on the subsequent DBS, is sometimes observed in preterm newborns. The incidence of permanent CH and the screening process in preterm newborns remain controversial. Our aim was to evaluate the incidence of transient and permanent CH and delayed TSH rise in preterm newborns. The utility of a multiple screening samples is discussed. Methods: We conducted a retrospective study on preterm newborns (<37 weeks of gestation) screened at the Newborn Screening Center of Université Libre de Bruxelles between January 2014 and December 2023. A literature review was performed to identify cases of permanent CH with delayed TSH rise in cohorts of preterm newborns. Results: Of the 3578 preterm newborns included in the study, 10 were diagnosed with CH (0.3%). The majority of CH cases were transient (6 out of 10 transient, one deceased and one under ongoing L-thyroxine, too young for weaning attempt). Six cases were detected at the first DBS, four at subsequent DBS. Only two cases were confirmed as permanent CH, yielding an incidence of 1 in 1789 for permanent CH in preterms (0.05%). One of the two had a delayed TSH rise. Genetic testing helped in establishing the diagnosis of permanent CH with gland in situ. Conclusions: Permanent CH appears to be rarer than transient CH among preterm newborns (1/1789 vs. 1/596). Transient CH may be suspected in case of iodine exposure or thyroid ultrasound showing an in situ gland with negative genetic testing and absent maternal blocking antibodies. In such cases, early L-thyroxine weaning may help avoid overtreatment. A delayed TSH rise leading to a false negative first DBS is not uncommon in preterm newborns with permanent CH. This justifies a second DBS in preterms. Given the retrospective nature of this study, these findings should be interpreted with caution, and further prospective research is warranted to confirm these observations.