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Chorioamnionitis and risk of long-term neurodevelopmental disorders in offspring: a population-based cohort study - 20/07/22

Doi : 10.1016/j.ajog.2022.03.028 
Eleni Tsamantioti, MD, MMedSc a, , Sarka Lisonkova, MD, PhD b, c, Giulia Muraca, PhD a, b, Anne K. Örtqvist, MD, PhD a, d, Neda Razaz, PhD a
a Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden 
b Department of Obstetrics and Gynaecology, BC Women’s Hospital, Vancouver, Canada 
c School of Population and Public Health, The University of British Columbia, Vancouver, Canada 
d Department of Obstetrics and Gynecology, Visby County Hospital, Visby, Sweden 

Corresponding author: Eleni Tsamantioti, MD, MMedSc.

Abstract

Background

Evidence indicates that in utero exposure to chorioamnionitis might increase the risk of neurodevelopmental disorders in the offspring. However, findings on this topic have been inconsistent.

Objective

To examine the association between chorioamnionitis and neurodevelopmental disorders in offspring.

Study Design

This was a retrospective population-based cohort study in Sweden. A total of 2,228,280 singleton live births and stillbirths between 1998 and 2019 were included in our study population. Data on maternal characteristics and neurodevelopmental disorders in offspring were obtained by individual record-linkages of nationwide Swedish registries. Chorioamnionitis was identified using the National Medical Birth Register. Inpatient and outpatient diagnoses were obtained for cerebral palsy, autism, attention deficit hyperactivity disorder, epilepsy, and intellectual disability. Multivariable Cox proportional hazards regression was used to estimate the association between chorioamnionitis and each neurodevelopmental disorder with adjusted hazard ratios and 95% confidence intervals. A causal mediation analysis of the relationship between chorioamnionitis and neurodevelopmental disorders with preterm delivery (<37 weeks) was performed.

Results

A total of 5770 (0.26%) offspring were exposed to chorioamnionitis during pregnancy. During the study’s follow-up time there were 4752 (0.21%) cases of cerebral palsy, 17,897 (0.80 %) cases of epilepsy, 50,570 (2.27 %) cases of autism, 114,087 (5.12%) cases of attention deficit hyperactivity disorder, and 14,574 (0.65%) cases of intellectual disability. After adjusting for potential confounders, exposure to chorioamnionitis increased the hazard ratios of cerebral palsy (adjusted hazard ratio, 7.43; 95% confidence interval, 5.90–9.37), autism (adjusted hazard ratio, 1.43; 95% confidence interval, 1.21–1.68), attention deficit hyperactivity disorder (adjusted hazard ratio, 1.17; 95% confidence interval, 1.03–1.33), and intellectual disability (adjusted hazard ratio, 1.99; 95% confidence interval, 1.53–2.58), whereas chorioamnionitis was not significantly associated with higher rates of epilepsy in offspring. Mediation analysis revealed that these associations were mainly explained through preterm delivery; however, increased risk was also observed among term infants.

Conclusion

Chorioamnionitis increases the risk of neurodevelopmental disorders, particularly cerebral palsy, autism, attention deficit hyperactivity disorder, and intellectual disability. These associations were mainly mediated through preterm delivery. Efforts for timely identification and appropriate interventions to treat infections during pregnancy will have sustained benefits in reducing the burden of neurologic complications in children at the population level.

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Key words : attention deficit hyperactivity disorder, autism, cerebral palsy, chorioamnionitis, epilepsy, intellectual disability, intraamniotic inflammation, intraamniotic infection, neurodevelopmental disorders


Plan


 The authors report no conflict of interest.
 The study was approved by the Regional Ethical Review Board at Karolinska Institutet, Stockholm, Sweden (approval number 2020-01545).
 The lead author (E.T.) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
 The study was supported by grants by the Swedish Research Council for Health, Working Life and Welfare (grant number 4-2702/2019) and the Stockholm County Council, ALF Medicine (grant number 501143). Funders were not involved in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
 Cite this article as: Tsamantioti E, Lisonkova S, Muraca G, et al. Chorioamnionitis and risk of long-term neurodevelopmental disorders in offspring: a population-based cohort study. Am J Obstet Gynecol 2022;227:287.e1-17.


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Vol 227 - N° 2

P. 287.e1-287.e17 - août 2022 Retour au numéro
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