Elsevier

The Journal of Pediatrics

Volume 192, January 2018, Pages 60-65.e1
The Journal of Pediatrics

Original Articles
A Time-Based Analysis of Inflammation in Infants at Risk of Bronchopulmonary Dysplasia

https://doi.org/10.1016/j.jpeds.2017.09.011Get rights and content

Objective

To precisely delineate the timing and contribution of inflammation to bronchopulmonary dysplasia (BPD) in preterm infants during the neonatal period.

Study design

Longitudinal study of blood inflammatory biomarkers (interleukin [IL]-6, IL-8, and granulocyte colony-stimulating factor) measured between birth and 42 days of age, at high temporal (daily) resolution, in infants born at or below 30 weeks of gestation. Cytokine predictors of BPD at 36 weeks postmenstrual age were adjusted for infant-specific and time-dependent factors, using hierarchical mixed effects regressions models.

Results

A total of 1518 data points were obtained in 62 infants (mean gestational age of 27 weeks). Infants who developed BPD later on presented increased inflammation after birth compared with infants without BPD. Inflammation was sustained, with gradual attenuation over 2 weeks (IL-8: OR: 6.5 [95% CI: 1.8-24]; granulocyte colony-stimulating factor: 3.3 [1.5-7.6]) and was higher in boys and in infants of lower birth weight. This inflammation preceded the clinical increased requirement in supplemental oxygen characteristic of BPD, and preceded the peak occurrence of neonatal sepsis or necrotizing enterocolitis.

Conclusions

Systemic inflammation occurs early in the neonatal period and precedes clinical symptoms in infants with BPD. These data provide a discrete vulnerability window period, supporting a role for targeted intensive care interventions during the early phase of BPD.

Section snippets

Methods

Preterm infants born at or below 30 weeks of gestation at the Children's and Women's Health Center of British Columbia (Vancouver, Canada) were eligible after admission to the neonatal intensive care unit, and recruited following written consent from their parent or legal guardian. The Children's and Women's Health Center is the only pediatric hospital in British Columbia and the main provincial tertiary care referral center. Exclusion criteria were an early anticipated demise (<72 hours) and

Results

During the study period, 154 infants were eligible and 65 were enrolled. Three infants died before 36 weeks of PMA and were, therefore, excluded from the analysis: 1 infant died of bacterial sepsis, 1 of necrotizing enterocolitis, and 1 from a severe intracranial hemorrhage. Thirty-two of the 62 infants (52%) in the study had BPD. Clinical characteristics were similar between infants with and without BPD, except for gestational age, birth weight, and use of postnatal corticosteroids (Table I).

Discussion

We conducted a detailed temporal analysis to precisely delineate when inflammation occurs in infants with BPD. Our data reveal that inflammation occurred shortly after birth and was sustained, with gradual attenuation over the early neonatal period. This inflammation preceded clinical symptoms of BPD, which directly supports a role of inflammation in the BPD lung insult. The analysis of markers of BPD at high temporal resolution provides a clearer representation of inflammation in relation to

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    Funded in part by the Molly Towell Perinatal Research Foundation and by the Canadian Institutes of Health Research (MOP-110938 to P.L.). P.L. received salary support from a BC Children's Hospital Investigator Grant Award and a Career Investigator Award from the Michael Smith Foundation for Health Research. The authors declare no conflicts of interest.

    Portions of this study published in abstract form at the Pediatric Academic Societies Meeting, April 25-28, 2015, San Diego, California.

    *

    Present address: Centre Hospitalier Mère-Enfant de l'Université Laval, Québec, Canada.

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