Presumed adrenal insufficiency in neonates treated with corticosteroids for the prevention of bronchopulmonary dysplasia

Josephsen, Justin B.; Hemmann, Brianna; Anderson, Connie D.; Hemmann, Brett M.; Buchanan, Paula; Williams, Howard L.; Lubsch, Lisa; Hillman, Noah H.

doi:10.1038/s41372-021-01251-y

Cited by 4 publications

(7 citation statements)

References 42 publications

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“…At DOL 11, we would expect to see a decrease in intubated patients in response to dexamethasone. Unfortunately, 40% of the budesonide exposed infants still required postnatal steroids, resulting in exposure to two strong corticosteroids early in life that could lead to late-onset adrenal insufficiency [20]. Previous analyses of neurological outcomes did not show negative effects of budesonide, similar to late dexamethasone use [2, 4, 17].…”

Section: Discussionmentioning

confidence: 99%

“…Our primary outcome was the incidence of presumed adrenal insufficiency, which was defined as the administration of hydrocortisone within the first 14 days of life (DOL) since serum cortisol levels are not a good predictor in preterm infants of adrenal function [21]. In the patients who received hydrocortisone, we evaluated for indicators of adrenal insufficiency: (1) hypotension (MAP/ GA <1), (2) hyperkalemia (K + >5.5), (3) hyponatremia (Na + <135), (4) decreased UOP (mL/kg/h) compared to the previous 24 h, and (5) oliguria (UOP <1 mL/kg/h) [20].…”

Section: Methodsmentioning

confidence: 99%

“…Data from the EMR (Epic) were extracted using Microsoft SQL server and verified by a chart review [3, 17, 20]. When placenta was available, histologic chorioamnionitis was defined as placental inflammation or funisitis.…”

Section: Methodsmentioning

confidence: 99%

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Early Physiological and Adrenal Effects of Budesonide Mixed with Surfactant in Large Observational Preterm Cohort Study

et al. 2022

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Background: The combination of surfactant and budesonide has been shown to decrease BPD rates and severity. Budesonide may be released systemically from lungs, and the effects on the immature adrenal glands are not known. Objective: The aim of this study was to determine if adrenal suppression rates are higher in preterm infants receiving budesonide with surfactant compared to surfactant alone. Methods: A retrospective chart review of 608 infants ≤1,250 g received intubation for surfactant therapy from 2013 through 2020. In August 2016, budesonide was added to surfactant for these infants. Indicators of adrenal suppression, including mean blood pressures, plasma electrolyte levels, hydrocortisone use, and the use of vasoactive medications, were analyzed for the first 14 days after birth. Respiratory variables, biochemical signs of adrenal insufficiency, and neonatal morbidities were analyzed. Results: There was no difference in hydrocortisone administration in the first 14 days between infants receiving budesonide with surfactant (n = 314) or surfactant alone (n = 294) (23% vs. 19%, p = 0.38). Budesonide exposed infants received hydrocortisone 3 days later than surfactant only infants (median DOL 5 vs. 2, p < 0.001). Infants receiving budesonide had higher blood pressures, required less dopamine (19% vs. 39%, p < 0.001) and dobutamine (2% vs. 6%, p = 0.02). Budesonide exposed infants were discharged home after a shorter NICU stay (85 days vs. 94 days, p = 0.02) and at a younger gestational age (39 vs. 40 weeks, p = 0.001). Conclusions: The use of surfactant and budesonide does not alter the rate of hydrocortisone use, but does delay the timing of treatment initiation and decreases the use of vasoactive medications.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Early Physiological and Adrenal Effects of Budesonide Mixed with Surfactant in Large Observational Preterm Cohort Study

et al. 2022

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“…Prenatal infection, mechanical ventilation, oxygen poisoning, antioxidant, patent ductus arteriosus (PDA) and postpartum infection can lead to BPD 2‐4 . Previous works indicate that systemic corticosteroids improve the respiratory function and accelerate exudation in preterm infants in a short term 5 . However, newborns treated with glucocorticoid have an increased risk of hypertension, hyperglycaemia and gastrointestinal complications, leading to a long‐term neurodevelopmental delay if glucocorticoid are administered within 4 days of birth 6 .…”

Section: Introductionmentioning

confidence: 99%

“… 2 , 3 , 4 Previous works indicate that systemic corticosteroids improve the respiratory function and accelerate exudation in preterm infants in a short term. 5 However, newborns treated with glucocorticoid have an increased risk of hypertension, hyperglycaemia and gastrointestinal complications, leading to a long‐term neurodevelopmental delay if glucocorticoid are administered within 4 days of birth. 6 At present, new approaches are needed to prevent BPD in premature infants.…”

Section: Introductionmentioning

confidence: 99%

Human breast milk‐derived exosomes through inhibiting AT II cell apoptosis to prevent bronchopulmonary dysplasia in rat lung

Zhou

Liu

et al. 2022

J Cellular Molecular Medi

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Human breast milk (HBM) effectively prevents and cures neonatal bronchopulmonary dysplasia (BPD). Exosomes are abundant in breast milk, but the function of HBM‐derived exosomes (HBM‐Exo) in BPD is still unclear. This study was to investigate the role and mechanism of HBM‐Exo in BPD. Overall lung tissue photography and H&E staining showed that HBM‐Exo improved the lung tissue structure collapse, alveolar structure disorder, alveolar septum width, alveolar number reduction and other injuries caused by high oxygen exposure. Immunohistochemical results showed that HBM‐Exo improved the inhibition of cell proliferation and increased apoptosis caused by hyperoxia. qPCR and Western blot results also showed that HBM‐Exo improved the expression of Type II alveolar epithelium (AT II) surface marker SPC. In vivo study, CCK8 and flow cytometry showed that HBM‐Exo improved the proliferation inhibition and apoptosis of AT II cells induced by hyperoxia, qPCR and immunofluorescence also showed that HBM‐Exo improved the down‐regulation of SPC. Further RNA‐Seq results in AT II cells showed that a total of 88 genes were significantly different between the hyperoxia and HBM‐Exo with hyperoxia groups, including 24 up‐regulated genes and 64 down‐regulated genes. KEGG pathway analysis showed the enrichment of IL‐17 signalling pathway was the most significant. Further rescue experiments showed that HBM‐Exo improved AT II cell damage induced by hyperoxia through inhibiting downstream of IL‐17 signalling pathway (FADD), which may be an important mechanism of HBM‐Exo in the prevention and treatment of BPD. This study may provide new approach in the treatment of BPD.

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

Coleman,

King,

Selewski

et al. 2024

J Perinatol

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Objective The relationship between adrenal insufficiency (AI), post-natal steroids (PNS) and neonatal acute kidney injury (AKI) remains understudied. We investigated associations between PNS and AKI in very low birthweight (VLBW) neonates, hypothesizing PNS is associated with reduced AKI. Study design We conducted a single-center retrospective review of VLBW infants comparing those with and without PNS exposure. Associations between PNS exposure and AKI were evaluated using generalized linear mixed-modeling adjusted for confounders. Result Of 567 neonates, 97 (17.1%) were exposed to PNS and 130 (22.9%) experienced AKI. Infants with PNS had lower gestational age, birthweight, Apgar scores, and experienced more AI versus those without PNS (all p < 0.05). PNS was associated with AKI (aRR 1.72, 95% CI 1.09–2.72) though hydrocortisone alone was not. Conclusion PNS exposure, but not hydrocortisone alone, is associated with increased AKI in VLBW neonates. Further analysis is needed to investigate the role of AI and AKI.

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Presumed adrenal insufficiency in neonates treated with corticosteroids for the prevention of bronchopulmonary dysplasia

Cited by 4 publications

References 42 publications

Early Physiological and Adrenal Effects of Budesonide Mixed with Surfactant in Large Observational Preterm Cohort Study

Early Physiological and Adrenal Effects of Budesonide Mixed with Surfactant in Large Observational Preterm Cohort Study

Human breast milk‐derived exosomes through inhibiting AT II cell apoptosis to prevent bronchopulmonary dysplasia in rat lung

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

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