What is the neonatal mortality and morbidity of chorioamnionitis?

Updated: May 08, 2018
  • Author: Fayez M Bany-Mohammed, MD; Chief Editor: Ted Rosenkrantz, MD  more...
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In a study that evaluated the whole US population and linked infant birth and death certificate files for the year 2008, the neonatal mortality rate for infants exposed to chorioamnionitis was 1.40 per1000 live births (LB) versus 0.81 per 1000 LB for infants without chorioamnionitis, with an odds ratio (OR) of 1.72 and a 95% confidence interval (CI) 1.20-2.45. [69] The OR for neonatal death for infants with chorioamnionitis exposure who received antibiotics versus those who did not was 0.69 (95% CI = 0.21-2.26). [69]  In another study of infants born at 23-32 weeks' gestation with evidence of intrauterine infection and inflammation, the neonatal death rate was 9.9%-11.1%. [98]

Preterm infants born to mothers with chorioamnionitis have unfavorable short-term (meningitis and intraventricular hemorrhage and periventricular leukomalacia) and long-term (cerebral palsy and neurodevelopmental impairment) neurologic outcomes. [99, 100]  Cerebral palsy (CP) [101]  and cognitive impairment without CP [102]  have been linked to exposure to maternal chorioamnionitis. In particular, funisitis and the fetal inflammatory response syndrome have been associated with white matter brain injury or periventricular leukomalacia that is linked to activation of cytokine networks. [103, 104]  Interleukin (IL)-1beta, IL-6, IL-8, IL-17, IL-18, and tumor necrosis factor (TNF)-alpha are among the cytokines identified as agents related to the fetal inflammatory response syndrome (FIRS) that results in brain injury. [105, 106, 107] However, more recent systematic reviews suggest that the evidence for a causal or associative role of chorioamnionitis in CP is weak [108] and that improvements in neonatal intensive care may have attenuated the impact of chorioamnionitis on brain health outcomes. [109]

The relationship of chorioamnionitis and neonatal cardiopulmonary morbidity is conflicting. Different studies have evaluated the risk of respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), and childhood asthma after fetal exposure to chorioamnionitis. Although some studies showed chorioamnionitis to be associated with lower risk of RDS, [110, 111] other studies found an increased risk of RDS [111, 112] or no association after adjusting to other variables. [99]  Similar conflicting data exist for the link of chorioamnionitis and BPD; however, a 2017 French national prospective, population-based, cohort study that included 2513 live-born singletons delivered at 24-31 weeks of gestation and 1731 placentas concluded that histologic chorioamnionitis is not associated with BPD. [113]

Chorioamnionitis caused by Ureaplasma has been studied extensively [114] (including in animal models) and has been linked to congenital pneumonia, prolonged mechanical ventilation, and cytokine release in the neonatal lungs with subsequent development of BPD. [115] However, studies that looked at antibiotic therapy with erythromycin to reduce the incidence BPD when the neonatal lungs are colonized or infected with Ureaplasma have been disappointing. More recent studies with azithromycin are encouraging. [116, 117]

The link between fetal exposure to chorioamnionitis and the future development of childhood asthma was implied by a systematic review but there was much variation in the included studies with regard to the type of maternal infection, age of the children, and methods of exposure ascertainment that made the conclusion less certain. [118] Lastly, with regard to the association between chorioamnionitis and patent ductus arteriosus, two meta-analyses reached opposing conclusions about the association. [119, 120]

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