ESPE Abstracts

Rationale: Bronchopulmonary dysplasia (BPD) is a major complication of preterm birth, which pathophysiology involves systematic inflammation. Preterm infants commonly suffer from relative adrenal insufficiency (RAI) in their first week of life, resulting in an insufficient production of cortisol inappropriate for the degree of inflammation. One of the major causes of RAI is immaturity of adrenal cortex enzymes, leading to an accumulation of cortisol precursors relative to cortisol. A low cortisol concentration, in the presence of excess cortisol precursor levels, likely results in reduced glucocorticoid receptor signaling, and consequently an imbalance between inflammation and anti-inflammation. We hypothesize that this phenomenon could contribute to the development of BPD.

Methods: Preterm infants born <30 weeks of gestation and admitted to the Neonatal Intensive Care Units of the Amsterdam UMC between October 2019 and March 2021, were included in this prospective observational study. Serum cortisol, 17-OH progesterone (17-OHP) and 11-deoxycortisol levels were measured in cord blood and blood obtained at postnatal days 3, 7, 14 and 28 by liquid chromatography-tandem mass spectrometry. Hormone levels measured after administration of postnatal corticosteroids were excluded. Non-parametric tests were used to compare hormone levels between infants with and without BPD. BPD diagnosis was defined as the need for >21% oxygen for at least 28 cumulative days, and the need for oxygen or respiratory support at 36 weeks postmenstrual age.

Results: Sixty-eight infants with a gestational age of 27±1.3 weeks were included for the analysis, of whom 21 (31%) developed BPD. Cortisol levels did not differ between the two groups, but 17-OHP and 11-deoxycortisol levels were significantly higher in the BPD group compared to the no BPD group at day 3 (17-OHP 16.6 [10.8-25.4] vs 9.4 [5.7-15.0] nmol/l, P-value 0.007; 11-deoxycortisol 6.9 [5.6-10.2] vs 5.1 [3.8-7.5] nmol/l, P-value 0.009) and day 7 (17-OHP 14.3 [10.0-23.2] vs 9.4 [6.1-14.1] nmol/l, P-value 0.015, in the BPD group and the no BPD group, respectively).

Conclusion: Compared to preterm infants without the diagnosis BPD, preterm infants with BPD had higher levels of cortisol precursors in their first week of life, but similar cortisol levels. These findings suggest that the development of BPD is accompanied by excess levels of cortisol precursors relative to cortisol, suggestive of a more active hypothalamus-pituitary-adrenal axis that could not fulfill the high cortisol demands in tissues. This biological profile is likely to predispose to more inflammation and BPD.