Original articleChorioamnionitis and cerebral palsy: Lessons from a patient registry
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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Cited by (28)
Placental mediated mechanisms of perinatal brain injury: Evolving inflammation and exosomes
2022, Experimental NeurologyCitation Excerpt :The risk of developing cerebral palsy was associated with severe histologic chorioamnionitis and similarly increased with additional placental abnormalities (Redline & O'Riordan, 2000). Children with cerebral palsy were significantly associated with a history of histologic chorioamnionitis and were more likely to have spastic diplegic subtype as well as periventricular white matter injury (Shevell et al., 2014). Multiple meta-analyses show an increased risk in the development of CP in infants born to mothers with evidence of clinical and/or histologic chorioamnionitis (Ayubi et al., 2021; Shatrov et al., 2010; Shi et al., 2017a; Wu & Colford Jr., 2000).
The placenta
2019, Handbook of Clinical NeurologyThe Placenta in Neonatal Encephalopathy: A Case–Control Study
2018, Journal of PediatricsCitation Excerpt :Aberrant weights of babies or placentas have been noted in neonatal encephalopathy in previous studies, with the risk of cerebral palsy showing a similar increase in infants who were either heavier or lighter than a calculated optimum for gestational age and sex.18,34,35 Contrary to our expectation based on previous reports,13,20,22,23 we did not find an association of neonatal encephalopathy with maternal or neonatal signs of infection or inflammation. Abnormalities of the placenta have been reported for decades to be more common in babies born at term limp and poorly responsive than in those who were vigorous at birth.36-38
Preclinical chorioamnionitis dysregulates CXCL1/CXCR2 signaling throughout the placental-fetal-brain axis
2018, Experimental NeurologyCitation Excerpt :For a large proportion of infants with CNS injury associated with prematurity, the injury begins in utero with inflammation of the placenta and/or hypoxia-ischemia (HI) from placental insufficiency with resultant dysfunction in the placental-fetal-brain axis (Anblagan et al., 2016; Gopagondanahalli et al., 2016). Chorioamnionitis (CHORIO), or inflammation/infection of the placenta and surrounding membranes, has recently been recognized in a significant number of preterm and term infants with PBI (De Felice et al., 2001; Galinsky et al., 2013; Lee et al., 2013; Shevell et al., 2014; Soraisham et al., 2013; YW et al., 2003). CHORIO affects placental permeability and blood flow, disseminates HI and transmits inflammation to fetuses of all gestational ages (Dueck et al., 2009).