Background: Chorioamnionitis, a risk factor for preterm delivery, has been suggested to be associated with suboptimal neurological development in premature infants. Objective: To evaluate the association between chorioamnionitis and neurodevelopment in preterm infants at 5 years of age. Methods Very low birth weight and very low gestational age infants (n = 197) were recruited. Placental samples (n = 117) were evaluated for histological chorioamnionitis. Fetal histological chorioamnionitis was analyzed as a subgroup. The diagnosis of clinical chorioamnionitis was derived from medical records. Neurodevelopmental impairments were evaluated at 2 years of age, and cognitive development (n = 188) and neuropsychological performance (n = 193) were evaluated at 5 years of age. Results: There were no associations between histological or clinical chorioamnionitis and neurodevelopmental impairments at 2 years of age. Clinical chorioamnionitis and fetal histological chorioamnionitis were not associated with cognitive development or neuropsychological performance, but histological chorioamnionitis was associated with poorer cognitive outcome (regression coefficient = -7.22, 95% CI: -14.31 to -0.13) and weaker memory and learning functions (regression coefficient = -1.29, 95% CI: -2.40 to -0.18) at 5 years of age. Conclusion: Our study findings do not support clinical chorioamnionitis having a major independent role in the pathogenesis of neurodevelopmental problems in very preterm infants. Histological chorioamnionitis was associated with slightly less optimal performance at 5 years of age, but further studies are needed to verify the clinical significance of these findings.

1.
Goldenberg RL, Culhane JF, Iams JD, Romero R: Epidemiology and causes of preterm birth. Lancet 2008;371:75-84.
2.
Ylijoki M, Ekholm E, Haataja L, Lehtonen L; PIPARI Study Group: Is chorioamnionitis harmful for the brain of preterm infants? A clinical overview. Acta Obstet Gynecol Scand 2012;91:403-419.
3.
Soraisham AS, Trevenen C, Wood S, Singhal N, Sauve R: Histological chorioamnionitis and neurodevelopmental outcome in preterm infants. J Perinatol 2013;33:441-445.
4.
Andrews WW, Cliver SP, Biasini F, Peralta-Carcelen AM, Rector R, Alriksson-Schmidt AI, Faye-Petersen O, Carlo W, Goldenberg R, Hauth JC: Early preterm birth: association between in utero exposure to acute inflammation and severe neurodevelopmental disability at 6 years of age. Am J Obstet Gynecol 2008;198:466.e1-466.e11.
5.
Kent A, Lomas F, Hurrion E, Dahlstrom JE: Antenatal steroids may reduce adverse neurological outcome following chorioamnionitis: neurodevelopmental outcome and chorioamnionitis in premature infants. J Paediatr Child Health 2005;41:186-190.
6.
Redline RW, Minich N, Taylor HG, Hack M: Placental lesions as predictors of cerebral palsy and abnormal neurocognitive function at school age in extremely low birth weight infants (<1 kg). Pediatr Dev Pathol 2007;10:282-292.
7.
Miyazaki K, Furuhashi M, Ishikawa K, Tamakoshi K, Hayashi K, Kai A, Ishikawa H, Murabayashi N, Ikeda T, Kono Y, Kusuda S, Fujimura M: Impact of chorioamnionitis on short- and long-term outcomes in very low birth weight preterm infants: the Neonatal Research Network Japan. J Matern Fetal Neonatal Med 2015;8:1-7.
8.
Dammann O, Drescher J, Veelken N: Maternal fever at birth and non-verbal intelligence at age 9 years in preterm infants. Dev Med Child Neurol 2003;45:148-151.
9.
Versland LB, Sommerfelt K, Elgen I: Maternal signs of chorioamnionitis: persistent cognitive impairment in low-birthweight children. Acta Paediatr 2006;95:231-235.
10.
Hendson L, Russell L, Robertson CMT, Liang Y, Chen Y, Abdalla A, et al: Neonatal and neurodevelopmental outcomes of very low birth weight infants with histologic chorioamnionitis. J Pediatr 2011;158:397-402.
11.
van Vliet EO, de Kieviet JF, van der Voorn JP, Been JV, Oosterlaan J, van Elburg RM: Placental pathology and long-term neurodevelopment of very preterm infants. Am J Obstet Gynecol 2012;206:489.e1-7.
12.
Lahra MM, Jeffrey HE: A fetal response to chorioamnionitis is associated with early survival after preterm birth. Am J Obstet Gynecol 2004;190:147-151.
13.
Pappas A, Kendrick DE, Shankaran S, Stoll BJ, Bell EF, Laptook AR, Walsh MC, Das A, Hale EC, Newman NS, Higgins RD: Chorioamnionitis and early childhood outcomes among extremely low-gestational-age neonates. JAMA Pediatr 2014;168:137-147.
14.
Bek KM, Nielsen FR, Qvist I, Rasmussen PE, Tobiassen M: C-reactive protein (CRP) and pregnancy. An early indicator of chorioamnionitis. Eur J Obstet Gynecol Reprod Biol 1990;35:29-33.
15.
Saini S, Goel N, Sharma M, Arora B, Garg N: C-reactive protein as an indicator of sub-clinical infection in cases of premature rupture of membranes. Indian J Pathol Microbiol 2003;46:515-516.
16.
McElrath TF, Allred EN, Leviton A; Developmental Epidemiology Network Investigators: Prolonged latency after preterm premature rupture of membranes: an evaluation of histologic condition and intracranial ultrasonic abnormality in the neonate born at <28 weeks of gestation. Am J Obstet Gynecol 2003;189:794-798.
17.
Hansen AR, Collins MH, Genest D, Heller D, Schwarz S, Banagon P, et al: Very low birthweight infant's placenta and its relation to pregnancy and fetal characteristics. Pediatr Dev Pathol 2000;3:419-430.
18.
Redline RW: Placental inflammation. Semin Neonatol 2004;9:265-274.
19.
Reiman M, Kujari H, Maunu J, Parkkola R, Rikalainen H, Lapinleimu H, Lehtonen L, Haataja L; PIPARI Study Group: Does placental inflammation relate to brain lesions and volume in preterm infants? J Pediatr 2008;152:642-647.
20.
Redline RW, Wilson-Costello D, Borawski E, Fanaroff AA, Hack M: Placental lesions associated with neurologic impairment and cerebral palsy in very low-birth-weight infants. Arch Pathol Lab Med 1998;122:1091-1099.
21.
Haataja L, Mercuri E, Regev R, Cowan F, Rutherford M, Dubowitz V, Dubowitz L: Optimality score for the neurologic examination of the infant at 12 and 18 months of age. J Pediatr 1999;135:153-161
22.
Palisano R, Rosenbaum P, Walter S, Russell D, Wood E, Galuppi B: Development and reliability of a system to classify gross motor function in children with cerebral palsy. Dev Med Child Neurol 1997;39:214-223.
23.
Bayley N: Bayley Scales of Infant Development, ed 2. San Antonio, Psychological Corporation, 1993.
24.
Wechsler D: Wechslerin älykkyystestistö esikouluikäisille, käsikirja. Helsinki, Psykologien kustannus, 1995.
25.
Korkman M, Kirk U, Kemp SL: NEPSY II, ed 2. San Antonio, PsychCorp/Pearson Clinical Assessment, 2007.
26.
Korkman M, Kirk U, Kemp SL: NEPSY II. Helsinki, Psykologien kustannus, 2008.
27.
Lind A, Haataja L, Rautava L, Väliaho A, Lehtonen L, Lapinleimu H, et al: Relations between brain volumes, neuropsychological assessment and parental questionnaire in prematurely born children. Eur Child Adolesc Psychiatry 2010;19:407-417.
28.
Hardt NS, Kostenbauder M, Ogburn M, Behnke M, Resnick M, Cruz A: Influence of chorioamnionitis on long-term prognosis in low birth weight infants. Obstet Gynecol 1985;65:5-10.
29.
Nasef N, Shabaan AE, Schurr P, Iaboni D, Choudhury J, Church P, Dunn MS: Effect of clinical and histological chorioamnionitis on the outcome of preterm infants. Am J Perinatol 2013;30:59-68.
30.
Favrais G, van de Looij Y, Fleiss B, Ramanantsoa N, Bonnin P, Stoltenburg-Didinger G, Lacaud A, Saliba E, Dammann O, Gallego J, Sizonenko S, Hagberg H, Lelièvre V, Gressens P: Systemic inflammation disrupts the developmental program of white matter. Ann Neurol 2011;70:550-565.
31.
Been JV, Degraeuwe PL, Kramer BW, Zimmermann LJ: Antenatal steroids and neonatal outcome after chorioamnionitis: a meta-analysis. BJOG 2011;118:113-122.
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