Benefit–risk ratio of hydrocortisone low in extremely preterm infants with low serum cortisol

Infants born extremely preterm with high serum levels of cortisol are more likely to suffer from severe intraventricular haemorrhage (IVH) and spontaneous intestinal perforation following hydrocortisone treatment, a recent study has shown.

Researchers conducted a secondary analysis of PREMILOC, a multicentre randomized controlled trial that enrolled infants delivered before 28 weeks of gestation. For the present analysis, data of baseline serum cortisol levels were retrieved for 325 neonates. Bronchopulmonary dysplasia (BPD)-free survival and adverse events were recorded and compared between the placebo (n=163) and hydrocortisone (n=145) groups.

Multivariate logistic regression analysis found that higher serum cortisol concentrations shortly after birth, expressed in z scores, significantly correlated with better BPD-free survival, but only in placebo-treated infants (adjusted odds ratio [aOR], 1.57, 95 percent confidence interval [CI], 1.08–2.27; p=0.02).

No such effect was reported for those treated with hydrocortisone (aOR, 1.02, 95 percent CI, 0.69–1.50; p=0.94).

In contrast, hydrocortisone treatment even magnified the risks of adverse events, leading to almost double the odds of grade 3–4 IVH (aOR, 1.82, 95 percent CI, 1.06–3.15; p=0.03) and a nearly fivefold increase in the likelihood of spontaneous intestinal perforation (aOR, 4.81, 95 percent CI, 1.34–17.22; p=0.02). These effects were absent in the placebo group.

“[W]e did not find a predictive value of baseline cortisol for BPD-free survival in infants treated with hydrocortisone born extremely preterm. However, we found high cortisol levels early after birth to be associated with a greater risk of severe IVH and spontaneous intestinal perforation in infants treated with hydrocortisone and, therefore, a lower benefit/risk ratio for the treatment,” the researchers said.

“[F]urther analysis to identify other baseline factors shortly after birth could improve our ability to identify the preterm infants who are most likely to benefit from hydrocortisone treatment,” they added.