Original article
Chorioamnionitis and cerebral palsy: Lessons from a patient registry

https://doi.org/10.1016/j.ejpn.2013.12.005Get rights and content

Abstract

Aim

The fetal neuroinflammatory response has been linked to the development of brain injury in newborns and subsequent neurologic impairment. We aimed to explore the maternal and child factors associated with histologic chorioamnionitis in cerebral palsy.

Methods

We conducted an observational study on a cohort of children with cerebral palsy who were identified from the Quebec Cerebral Palsy Registry. Placental pathology was reported prospectively. Maternal and child factors associated with histological chorioamnionitis were explored.

Results

Placental reports were available in 455 of 534 (85%) children with cerebral palsy, and of these 12% had histological signs of chorioamnionitis on reports. These children were more likely to have large placentas over 90th percentile for gestational age (53.7% versus 30.7%, p = 0.001) and were born significantly more prematurely (<32 weeks in 51.9% vs 24.1%, p = 0.007) than children without chorioamnionitis. A clinical sign of perinatal infection was reported in 61.1% of children with chorioamnionitis, however each clinical sign was seen in a minority of these children. Children with chorioamnionitis were more likely to have spastic diplegic cerebral palsy subtype (37% vs 19.2%, p = 0.003) and periventricular white matter injury on neuroimaging (52.9% vs 35.8%, p = 0.004). However no differences in neuroimaging or subtypes were seen when stratified by prematurity.

Discussion

Histological chorioamnionitis was a frequent pathological finding in children with cerebral palsy born prematurely, with larger placentas relative to gestation and birth weight. Future case control studies are needed to shed light on the role of inflammatory placental findings in pregnancy outcomes.

Introduction

Cerebral palsy (CP) is the most common cause of childhood motor disability, affecting 2 to 2.5 children per 1000 live births.1 CP is a permanent disorder of movement and posture that results in a non-progressive motor impairment and is often associated with epilepsy as well as deficits in sensation, perception, cognition, communication and behavior.2 The etiology of CP is multifactorial, relating to congenital or acquired disturbances to the brain during fetal or infant development.2 The harmful effects of prematurity and low birth weight on neurodevelopment are well described in the literature, and prematurity indeed is the best known risk factor for CP.3 Very preterm infants (under 32 weeks) account for 2% of all births, yet make up a quarter of all cases of CP.4 The prevalence of CP is inversely proportional to gestational age (GA), with a 60-fold higher risk of CP in children born at less than 28 weeks gestation compared to term infants.5 Not surprisingly, low birth weight has also been found to be strongly associated with CP, with a 70-fold increased risk of CP in extremely low birth weight infants (i.e. <1500 g) compared to normal birth weight infants.6

Chorioamnionitis and intrauterine exposure to maternal infection are risk factors for premature birth.7, 8 Although intrauterine infection appears to increase the risk of CP,5, 9, 10, 11, 12, 13 it is not clear if the effect is mediated solely through prematurity or through a neuroinflammatory response. A relationship between maternal infection during pregnancy and subsequent neurological sequelae in the newborn is not consistently demonstrated across all studies, especially when gestational age is adjusted for.14, 15, 16 An observational case–control study comparing infants born to mothers with and without chorioamnionitis concluded that adverse neurological outcome was not affected by chorioamnionitis once gestational age was controlled for.15 In a retrospective case–control study looking at placentas from very low birth weight infants with subsequent neurological impairment and placentas from matched controls, a similar prevalence of chorioamnionitis was found in both cases and controls.17 Another case–control study examining cases of infants exposed to chorioamnionitis and control infants and assessing neurodevelopment at two years of age found that chorioamnionitis had but a minor role in the development of later neurological impairment.18 The association between chorioamnionitis, periventricular white matter injury (PWMI) and later CP thus continues to be debated.19, 20

Our objective was to explore the maternal and child factors associated with chorioamnionitis in a cohort of children with CP.

Section snippets

Methods

We conducted an observational study on a cohort of children with CP who were identified from a large population-based CP Registry (Registre de la Paralyse Cérébrale de Québec (REPACQ)), which includes children with CP born between 1999 and 2010 from 6 of the 17 administrative health regions in Quebec, representing approximately half of the province's pediatric population. The diagnosis of CP was based on the consensus definition of CP as previously described.2 Children are registered in REPACQ

Results

Of the 534 children with CP registered in REPACQ, 455 (85.2%) had some placental pathology information available. Of these, 54 (11.9%) had histological chorioamnionitis documented, which was the most common placental pathology reported. Among children born prematurely (37 weeks gestation or less), chorioamnionitis was reported in 18.6% and in those born very prematurely (32 weeks gestation or less), chorioamnionitis was reported in 26.0%.

The maternal characteristics of the children in this

Discussion

Our study suggests that histologic chorioamnionitis is a frequent placental pathology finding in CP, seen in 12% of children in our cohort. This is in keeping with recent literature not only illustrating that chorioamnionitis is significantly associated with cerebral palsy (RR 1.9, 95% CI 1.5–2.5) and PWMI (RR 2.6, 95% CI 1.7–3.9)20 but that there can be up to an 80% increased risk of CP in patients with histological chorioamnionitis as compared to controls.26 Furthermore, in premature children

Conflict of interest

The authors have no conflict of interest to report.

Acknowledgment

The Registre de la Paralyse Cérébrale de Québec has been funded by the Réseau de recherche sur le développement, la santé et le bien-être de l'enfant des Fonds de Recherche en Santé du Québec and NeuroDevNet National Centre of Excellence. Neither funding sources were involved in the design, analysis or manuscript preparation of this study.

The Registre de la Paralyse Cérébrale de Québec consortium includes the following collaborators: Jean Mathieu, MD, Claude Desjardins, MD, Nicole Pigeon, MD,

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