Professor Dept OB/Gyn University of Wisconsin SMPH, United States
Background: The Wisconsin State Lab of Hygiene recently started extended screening for congenital adrenal hyperplasia (CAH) on newborn dried blood spots (DBS) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Newborns with elevated first tier 17-hydroxyprogesterone (17-OHP4) levels now receive second tier testing using LC-MS/MS that includes levels of cortisol and other steroid biosynthetic precursors. Although 17-OHP4 elevation in preterm infants is known to occur due to adrenal immaturity, DBS cortisol levels in this population is less well understood.
Objectives: This study examines the frequency and results of second tier CAH testing in extremely preterm infants.
Design/Methods: A retrospective chart review was done for 140 babies < 29 wks born between May 2021-June 2025 and examined DBS screening results for CAH. Since postnatal hydrocortisone can affect LC-MS/MS results, this chart review also determined if hydrocortisone was given at the time of the newborn screen. This study was done with IRB approval.
Results: Eight preterm infants (5.7%) had 17-OHP4 levels above the first tier cutoff leading to second tier testing. The first tier screening was abnormal at the 10-14 day DBS in all infants with three of the eight newborns also having abnormal DBS screening levels at other timepoints. None received exogenous hydrocortisone at the time of the newborn DBS or were diagnosed with congenital adrenal hyperplasia. Cortisol levels were available in four infants with second tier testing and ranged from 21 to 353 ng/ml. On chart review, none were SGA, 3 received hydrocortisone during hospitalization and none had hyperkalemia or hypotension at the time of DBS testing.
Conclusions: Extremely preterm babies have immature adrenal glands that lead to increased biosynthetic precursors such as 17-OHP4. LC-MS/MS assays in newborn screening labs offer a method to analyze cortisol and steroid precursors from small DBS volumes. Our studies show that some extremely preterm babies had elevation of both 17-OHP4 and cortisol levels, suggesting they may be trying to maintain high cortisol levels via continuous stimulation of an immature adrenal. Tracking both cortisol and steroid precursors may provide insights into adrenal immaturity and insufficiency in preterm infants. Future studies will examine clinical signs of adrenal insufficiency in preterm babies who receive second tier screening for CAH on the DBS.
