Post-natal steroid exposure in very low birthweight neonates and associations with acute kidney injury

J Perinatol. 2024 May 23. doi: 10.1038/s41372-024-02011-4.

Coleman, C. et al.

Reviewed by: Jaya Isaac


To test the association between post-natal steroid (PNS) exposure and the development of acute kidney injury (AKI) in very low birth weight (VLBW) neonates, defined as birthweight < 1500 grams. The authors’ hypothesized that as certain cases of AKI may be related to glucocorticoid-responsive circulatory collapse and relative adrenal insufficiency (AI) that receipt of PNS would be protective against AKI.

Study Design:

The study was a retrospective chart review of VLBW infants and with data collected on baseline demographic factors and on confounders for the development of AKI such as hypotension, caffeine exposure, patent ductus arteriosus, sepsis, mechanical ventilation, necrotizing enterocolitis, and nephrotoxic medication exposure. The exposure variable was the receipt of PNS and in those who had AKI, PNS exposure had to occur prior to the AKI event. The outcome variable was AKI as defined by the modified neonatal Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria.

The authors conducted both bivariate and multivariate generalized linear mixed modeling examining the association between PNS and AKI. A subgroup analysis was also conducted exclusively testing hydrocortisone exposure. 

Patient Characteristics: 

All neonates were born between January 1, 2018, and December 31, 2020, and admitted to the Medical University of South Carolina (MUSC). Infants were excluded if they had died/transitioned to palliative care within 48 hours of admission, had known congenital anomalies of the kidney and/or urinary tract, had lethal chromosomal anomalies, or had less than two serum creatinine values measured.


567 neonates were included in the final analysis. 97 neonates received PNS, and 70% of whom received hydrocortisone. 22.9% of the neonates had AKI and those who had AKI were more likely to have lower gestational age, birthweight, and Apgar scores, along with longer length of stay and increased mortality. 35 infants received PNS prior to their AKI. In multivariable analyses, PNS exposure was associated with an increased risk for AKI (aRR 1.72 95% CI 1.09 –2.72, p = 0.02). In the unadjusted secondary subgroup analysis, hydrocortisone exposure was associated with a protective effect against AKI. However, in multivariable analyses, hydrocortisone exposure did not have a significant effect on AKI development.


A novel finding from this study in the association of PNS with the development of AKI, which conflicted with the authors’ hypothesis. One supposition is that this may be because the neonates who received PNS may represent a group of sicker patients. Also, as there was a median of 12 days between PNS exposure and AKI, the authors also propose that the AKI may be due to iatrogenic AI, occurring during or after the steroid taper. As hydrocortisone seemed to be protective in unadjusted analyses, there may be a differing effect depending on the type of PNS exposure.

The fact that the results of this study contradicted the authors’ initial hypothesis indicate the complex relationship between PNS and AKI that requires further characterization. Special attention should be paid to the steroid type, dosing regimen, temporal association between PNS and AKI, and diagnosing neonates with iatrogenic AI after PNS use.