Placental Findings and Effect of Prophylactic Hydrocortisone in Extremely Preterm Infants

Pediatrics. 2018 Feb;141(2):e20171788. doi: 10.1542/peds.2017-1788. Epub 2018 Jan 18.


Objectives: To investigate the relationship between histologic findings of the placenta and response to early postnatal hydrocortisone treatment used to prevent bronchopulmonary dysplasia (BPD) in extremely preterm infants.

Methods: In an exploratory analysis of the Early Low-Dose Hydrocortisone to Improve Survival Without Bronchopulmonary Dysplasia in Extremely Preterm Infants (PREMILOC) trial, detailed placental analyses were performed on the basis of standardized macroscopic and histologic examinations. Placental histology, categorized into 3 groups, was correlated to neonatal outcomes and response to hydrocortisone treatment.

Results: Of 523 randomly assigned patients, 457 placentas were analyzed. In total, 125 out of 457 (27%) placentas were classified as normal, 236 out of 457 (52%) placentas were classified as inflammatory, and 96 out of 457 (21%) placentas were classified as vascular. Placental inflammation was associated with a significant, increased rate of BPD-free survival at 36 weeks' postmenstrual age, independent of gestational age, treatment group, and sex (adjusted odds ratio: 1.72, 95% confidence interval [CI]: 1.05 to 2.82, P = .03). Regarding the response to treatment, the strongest benefit of hydrocortisone compared with placebo was found in infants born after placental vascular disease, with significantly more patients extubated at day 10 (risk difference: 0.32, 95% CI: 0.08 to 0.56, P = .004) and similar positive direction on survival without BPD (risk difference: 0.23, 95% CI: 0.00 to 0.46, P = .06). Adjusted to gestational age and treatment groups, placental inflammation was associated with significantly fewer patent ductus arteriosus ligation (adjusted hazard ratio: 0.58, 95% CI: 0.36 to 0.95, P = .03). Placental histology was not found to be associated with other adverse events related to preterm birth.

Conclusions: With these findings, we confirm that early low-dose hydrocortisone confers benefits in extremely preterm infants overall and we suggest there is a higher treatment effect in those born after placental vascular disease.

Trial registration: NCT00623740.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / administration & dosage*
  • Bronchopulmonary Dysplasia / prevention & control*
  • Double-Blind Method
  • Female
  • Humans
  • Hydrocortisone / administration & dosage*
  • Infant, Extremely Premature*
  • Infant, Newborn
  • Logistic Models
  • Male
  • Placenta / anatomy & histology
  • Placenta / blood supply
  • Placenta / pathology*
  • Postnatal Care
  • Pregnancy
  • Pregnancy Complications


  • Anti-Inflammatory Agents
  • Hydrocortisone

Associated data

  • EudraCT/2007-002041-20