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Protective effect of chorioamnionitis on the development of bronchopulmonary dysplasia triggered by postnatal systemic inflammation in neonatal rats.

ABSTRACT: Prenatal or postnatal systemic inflammation can contribute to the development of bronchopulmonary dysplasia (BPD). We investigated whether prenatal intra-amniotic (i.a.) inflammation or early postnatal systemic inflammation can induce BPD in a rat model.One microgram of lipopolysaccharide (LPS) or vehicle was injected into the amniotic sacs 2 d before delivery (E20). After birth, 0.25 mg/kg of LPS or vehicle was injected into the peritoneum of pups on postnatal day (P)1, P3, and P5. On P7 and P14, peripheral blood (PB), bronchoalveolar lavage fluid (BALF), and lung tissue were obtained and analyzed.Postnatal i.p. injections of LPS significantly increased neutrophil counts in PB and BALF on P7 and P14. Similarly, proinflammatory cytokine and angiogenic factor transcript levels were increased in the lung by i.p. LPS on P7. Alveolar and pulmonary vascular development was markedly disrupted by i.p. LPS on P14. However, pretreatment with i.a. LPS significantly negated the detrimental effects of postnatal i.p. LPS on PB and BALF neutrophil counts and on lung proinflammatory cytokine expression and histopathological changes.Exposure to early postnatal systemic LPS induces BPD, an arrest in alveolarization, in neonatal rats. Preceding exposure to i.a. LPS protects the lungs against BPD triggered by postnatal systemic inflammation.

SUBMITTER: Choi CW

PROVIDER: S-EPMC4829878 | biostudies-other | 2016 Feb

REPOSITORIES: biostudies-other

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Project description:IMPORTANCE:Postnatally acquired cytomegalovirus (CMV) is typically benign in term infants but in very low-birth-weight (VLBW) infants can cause pneumonitis and sepsislike illness. Whether postnatal CMV infection results in long-term pulmonary sequelae in these infants is unknown. OBJECTIVE:To investigate the association between postnatal CMV infection and bronchopulmonary dysplasia (BPD) and mortality in a large multicenter cohort of VLBW infants. DESIGN, SETTING, AND PARTICIPANTS:Conducted between October 2014 and June 2015, this propensity-matched retrospective cohort study involved 101,111 hospitalized VLBW (<1500 g) infants at 348 neonatal intensive care units in the United States from 1997 to 2012. We matched infants with postnatal CMV infection 1:1 to comparison infants using propensity scores, and we used Poisson regression to examine the effect of postnatal CMV on the combined risk for death or BPD at 36 weeks' postmenstrual age. To describe features of postnatal CMV infection, we extracted clinical and laboratory data from 7 days before until 7 days after infants met criteria for postnatal CMV. EXPOSURES:Postnatal CMV infection was defined as a diagnosis of CMV or detection of CMV from blood, urine, cerebrospinal fluid, or respiratory secretions on or after day of life 21. Infants with a CMV diagnosis or virologic detection of CMV prior to day of life 21 were not considered to have postnatal infection. MAIN OUTCOMES AND MEASURES:The primary outcome was death or BPD at 36 weeks' postmenstrual age. RESULTS:Of 101,111 infants, 328 (0.3%) had postnatal CMV infection. We matched a comparison infant to 303 CMV-infected infants (92%) for a final cohort of 606 infants. The median gestational age and birth weight of this cohort were 25 weeks and 730 g, respectively. Postnatal CMV infection was associated with an increased risk for death or BPD at 36 weeks' postmenstrual age (risk ratio, 1.21; 95% CI, 1.10-1.32) and BPD (risk ratio, 1.33; 95% CI, 1.19-1.50). Changes in cardiorespiratory status associated with postnatal CMV infection included a new requirement for vasopressor medications (9%; n?=?29), intubation for mechanical ventilation (15%; n?=?49), a new oxygen requirement (28%; n?=?91), and death (1.2%; n?=?4). CONCLUSIONS AND RELEVANCE:In VLBW infants, postnatal CMV infection was associated with increased risk for BPD. Further studies are needed to determine the role of preventive measures against CMV in this population.

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Protective effect of chorioamnionitis on the development of bronchopulmonary dysplasia triggered by postnatal systemic inflammation in neonatal rats.

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