Postnatal Steroidogenic Remodeling in Small-for-Gestational-Age Male Infants During Minipuberty: A Longitudinal Cohort Study

Objectives: The objective of the study was to investigate postnatal steroidogenic remodeling in term male infants born small for gestational age (SGA) compared with appropriate-for-gestational-age (AGA) infants by evaluating serum product-to-precursor steroid ratios as indirect biochemical signatures of steroidogenic pathways during minipuberty. Methods: This prospective longitudinal cohort study included 51 healthy term male infants (27 AGA and 24 SGA), evaluated on postnatal day 3 and at approximately 2.5 months of age. Serum steroids were primarily quantified using liquid chromatography–tandem mass spectrometry, whereas dihydrotestosterone and gonadotropins were measured by electrochemiluminescence immunoassay. Five prespecified molar product-to-precursor ratios represented HSD3B2, HSD17B, SRD5A2, CYP11B1, and SULT2A1 pathway signatures. Between-group differences were assessed using Mann– Whitney U tests, applying a Bonferroni-adjusted significance threshold of p<0.01. Results: On day 3, HSD3B2 and SULT2A1 signatures were significantly higher in SGA infants. At 2.5 months, SGA infants demonstrated higher HSD17B (3.91 [3.45–5.32] vs. 1.35 [0.87–1.91]; p<0.001) and SULT2A1 (293 [243–591] vs. 243 [75–287]; p=0.001) signatures. Conversely, HSD3B2 was lower (0.66 [0.30–1.16] vs. 2.07 [1.11–2.93]; p<0.001). CYP11B1 was higher at the prespecified significance boundary (p=0.010). Testosterone concentrations and testicular volume remained comparable between groups. Conclusion: Term SGA male infants exhibited distinct serum steroidogenic pathway signatures during minipuberty despite comparable testosterone concentrations and testicular volume. These findings suggest altered postnatal steroid handling and warrant validation in larger longitudinal cohorts.