Background: Chorioamnionitis is a recognized risk factor of preterm delivery; however, controversy still persists concerning the relationship between maternal inflammation and neonatal morbidity and mortality. Objective: To determine the incidence of clinical chorioamnionitis and its relationship to morbidity and mortality among very-low-birth-weight (VLBW) infants. Methods: This was a retrospective analysis of prospectively collected data of VLBW neonates ≤32 weeks' gestational age (GA) admitted to collaborating units in the Spanish SEN1500 Network between January 2008 and December 2011. Clinical chorioamnionitis was defined by obstetricians based on clinical findings, and neonatal outcomes were compared between exposed and non-exposed infants by multivariate logistic regression analysis. Results: During the study period, 11,464 VLBW newborns were admitted to our units and 10,026 were ≤32 weeks' GA. Among them, 8,330 (83.1%) had complete data and were included. Of these, 1,480 (17.8%) were exposed to maternal clinical chorioamnionitis. The incidence was higher at lower GA and, after adjusting for confounding factors, exposed infants had higher risks of early-onset neonatal sepsis (EONS) (10.0 vs. 2.8%; aOR 3.102; 95% CI 2.306-4.173; p < 0.001) and necrotizing enterocolitis (NEC) (11.2 vs. 7.7%; aOR 1.300; 95% CI 1.021-1.655; p < 0.033), but lower risks of patent ductus arteriosus (PDA) (43.2 vs. 34.9%; aOR 0.831; 95% CI 0.711-0.971; p < 0.02) and late-onset bacterial sepsis (LONS) (36.6 vs. 32.5%; aOR 0.849; 95% CI 0.729-0.989; p < 0.035). There were no differences in mortality between the groups. Conclusions: The incidence of maternal clinical chorioamnionitis is inversely related to GA at delivery, and in VLBW infants ≤32 weeks' GA it is associated with higher risks of EONS and NEC, but lower risks of PDA and LONS. We did not found differences in survival.

Goldenberg RL, Hauth JC, Andrews WW: Intrauterine infection and preterm delivery. N Engl J Med 2000;342:1500-1507.
Hagberg H, Wennerholm UB, Savman K: Sequelae of chorioamnionitis. Curr Opin Infect Dis 2002;15:301-306.
Bracci R, Buonocore G: Chorioamnionitis: a risk factor for fetal and neonatal morbidity. Biol Neonate 2003;83:85-96.
Watterberg KL, Demers LM, Scott SM, Murphy S: Chorioamnionitis and early lung inflammation in infants in whom bronchopulmonary dysplasia develops. Pediatrics 1996;97:210-215.
Been JV, Zimmermann LJ: Histological chorioamnionitis and respiratory outcome in preterm infants. Arch Dis Child Fetal Neonatal Ed 2009;94:F218-F225.
Botet F, Figueras J, Carbonell-Estrany X, Arca G, and Castrillo Study Group: Effect of maternal clinical chorioamnionitis on neonatal morbidity in very-low birthweight infants: a case-control study. J Perinat Med 2010;38:269-273.
Thomas W, Speer CP: Chorioamnionitis: important risk factor or innocent bystander for neonatal outcome? Neonatology 2011;99:177-187.
Moro Serrano M, Fernández Pérez C, Figueras Alloy J, Pérez Rodríguez J, Coll E, Doménech Martínez E, Jiménez R, et al: SEN1500: design and implementation of a registry of infants weighing less than 1,500 g at birth in Spain (in Spanish). An Pediatr (Barc) 2008;68:181-188.
Gibbs RS, Duff P: Progress in pathogenesis and management of clinical intraamniotic infection. Am J Obstet Gynecol 1991;164:1317-1326.
Alexander JM, Gilstrap LC, Cox SM, McIntire DM, Leveno KJ: Clinical chorioamnionitis and the prognosis for very low birth weight infants. Obstet Gynecol 1998;91:725-729.
Ahn HM, Park EA, Cho SJ, Kim YJ, Park HS: The association of histological chorioamnionitis and antenatal steroids on neonatal outcome in preterm infants born at less than thirty-four weeks' gestation. Neonatology 2012;102:259-264.
Kramer BW, Kramer S, Ikegami M, Jobe AH: Injury, inflammation, and remodeling in fetal sheep lung after intra-amniotic endotoxin. Am J Physiol Lung Cell Mol Physiol 2002;283:L452-L459.
Kramer BW, Ladenburger A, Kunzmann S, Speer CP, Been JV, van Iwaarden JF, Zimmermann LJ, Gantert M, Garnier Y: Intravenous lipopolysaccharide-induced pulmonary maturation and structural changes in fetal sheep. Am J Obstet Gynecol 2009;200:195.e1-195.e10.
Been JV, Rours IG, Kornelisse RF, Jonkers F, de Krijger RR, Zimmermann LJ: Chorioamnionitis alters the response to surfactant in preterm infants. J Pediatr 2010;156:10-15.
Speer CP: Neonatal respiratory distress syndrome: an inflammatory disease? Neonatology 2011;99:316-319.
Soraisham AS, Singhal N, McMillan DD, Sauve RS, Lee SK; Canadian Neonatal Network: A multicenter study on the clinical outcome of chorioamnionitis in preterm infants. Am J Obstet Gynecol 2009;200:372.e1-372.e6.
Hamrick SE1, Hansmann G: Patent ductus arteriosus of the preterm infant. Pediatrics 2010;125:1020-1030.
Gonzalez A, Sosenko IR, Chandar J, Hummler H, Claure N, Bancalari E: Influence of infection on patent ductus arteriosus and chronic lung disease in premature infants weighing 1,000 grams or less. J Pediatr 1996;128:470-478.
Verma U, Tejani N, Klein S, Reale MR, Beneck D, Figueroa R, Visintainer P: Obstetric antecedents of intraventricular hemorrhage and periventricular leukomalacia in the low-birth-weight neonate. Am J Obstet Gynecol 1997;176:275-281.
Sarkar S, Kaplan C, Wiswell TE, Spitzer AR: Histological chorioamnionitis and the risk of early intraventricular hemorrhage in infants born ≤ 28 weeks gestation. J Perinatol 2005;25:749-752.
Wu YW, Colford JM: Chorioamnionitis as a risk factor for cerebral palsy. A meta-analysis. JAMA 2000;284:1417-1424.
Inder TE, Wells SJ, Mogridge NB, Spencer C, Volpe JJ: Defining the nature of the cerebral abnormalities in the premature infant: a qualitative magnetic resonance imaging study. J Pediatr 2003;143:171-179.
Schlapbach LJ, Aebischer M, Adams M, Natalucci G, Bonhoeffer J, Latzin P, Nelle M, Bucher HU, Latal B; Swiss Neonatal Network and Follow-Up Group: Impact of sepsis on neurodevelopmental outcome in a Swiss National Cohort of extremely premature infants. Pediatrics 2011;128:e348-e357.
Dempsey E, Chen MF, Kokottis T, Vallerand D, Usher R: Outcome of neonates less than 30 weeks' gestation with histologic chorioamnionitis. Am J Perinatol 2005;22:155-159.
Andrews WW, Goldenberg RL, Faye-Petersen O, Cliver S, Goepfert AR, Hauth JC: The Alabama Preterm Birth Study: polymorphonuclear and mononuclear cell placental infiltrations, other markers of inflammation, and outcomes in 23- to 32-week preterm newborn infants. Am J Obstet Gynecol 2006;195:803-808.
Strunk T, Doherty D, Jacques A, Simmer K, Richmond P, Kohan R, Charles A, Burgner D: Histologic chorioamnionitis is associated with reduced risk of late-onset sepsis in preterm infants. Pediatrics 2012;129:e134-e141.
Been JV, Lievense S, Zimmermann LJ, Kramer BW, Wolfs TG: Chorioamnionitis as a risk factor for necrotizing enterocolitis: a systematic review and meta-analysis. J Pediatr 2013;162:236-242.
Shah DK, Doyle LW, Anderson PJ, Bear M, Daley AJ, Hunt RW, Inder TE: Adverse neurodevelopment in preterm infants with postnatal sepsis or necrotizing enterocolitis is mediated by white matter abnormalities on magnetic resonance imaging at term. J Pediatr 2008;153:170-175.
Pappas A, Kendrick DE, Shankaran S, Stoll BJ, Bell EF, Laptook AR, Walsh MC, Das A, Hale EC, Newman NS, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network: Chorioamnionitis and early childhood outcomes among extremely low-gestational-age neonates. JAMA Pediatr 2014;168:137-147.
Been JV, Vanterpool SF, de Rooij JD, Rours GI, Kornelisse RF, van Dongen MC, van Gool CJ, de Krijger RR, Andriessen P, Zimmermann LJ, Kramer BW: A clinical prediction rule for histological chorioamnionitis in preterm newborns. PLoS One 2012;7:e46217.
Getahun D, Strickland D, Zeiger RS, Fassett MJ, Rhoads GG, Jacobsen SJ: Effect of chorioamnionitis on early childhood asthma. Arch Pediatr Adolesc Med 2010;164:187-192.
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