Early diagnosis of congenital endocrinopathies with the introduction of expanded neonatal screening

Abstract

Background. Neonatal screening (NS) for congenital hypothyroidism (CH) and congenital adrenal hyperplasia (CAH) plays a pivotal role in the early medical care of children with these endocrine disorders and has been utilized globally for several decades. In Russia, screening for CH has been conducted since 1993, and for CAH since 2006. With the expansion of the list of diseases screened for in the neonatal period, the conditions for screening have been revised in 2023. Earlier timeframes for hormonal testing were introduced as diagnostic criteria for CH and CAH: on days 1–2 of life for full-term infants (instead of days 3–5) and on day 7 for preterm infants (instead of days 7–14). The physiological characteristics of dynamic hormonal changes in newborns during the first week of life can lead to an increase in false-positive results and a rise in erroneous diagnoses of CH and CAH.

Objective. To conduct a comparative analysis of neonatal screening results for CH and CAH in 2022 and 2023 among newborns born in Saint Petersburg, considering the changes in the timing of blood sampling for determining thyroid-stimulating hormone (TSH) in CH and 17-hydroxyprogesterone (17-OHP) in CAH, respectively.

Materials and methods. A retrospective single-center comparative study was conducted. Data on elevated results in the first dried blood spot during neonatal screening for CH and CAH in 2022 and 2023 were analyzed. For detailed statistical analysis, groups of newborns born at ≥37 weeks of gestation and weighing ≥2500 g were formed. A comparative statistical analysis of TSH and 17-OHP levels was performed based on the timing of dried blood spot collection for neonatal screening.

Results. In 2022, 51,203 newborns were screened, with elevated 17-OHP levels in the first dried blood spot detected in 213 cases (0.4%). In 2023, 51,306 newborns were screened, with deviations from the norm found in 1,373 cases (2.7%). A statistically significant difference in median 17-OHP levels was observed between 2022 and 2023, with higher values associated with earlier blood spot collection. Among full-term newborns weighing ≥2500 g in 2022 (n=44,875), the median 17-OHP level was 7.5 [5.6–9.9] nmol/L, compared to 12.4 [9.7–16.0] nmol/L in 2023 (n=46,360) (p <0.001). Similarly, a statistically significant difference in TSH levels was identified between 2022 and 2023, with higher values observed with earlier blood spot collection. Among full-term newborns weighing ≥2500 g in 2022 (n=44,870), the median TSH level was 2.0 [1.4–2.7] μIU/mL, compared to 3.9 [2.9–5.3] μIU/mL in 2023 (n=46,363) (p <0.001).

Conclusion. The increase in the number of false-positive results does not correlate with a significant rise in the expected number of patients with confirmed diagnoses. The rise in false-positive results in the first dried blood spot may be associated with earlier blood sampling in newborns. This complicates laboratory diagnostics and the establishment of an accurate diagnosis, highlighting the need for potential adjustments to the reference intervals for both 17-OHP and TSH.