Maternal Infection During Pregnancy and Risk of Cerebral Palsy in Children: A Systematic Review and Meta-analysis

Abstract

Background and aim: The association between maternal infection during pregnancy and the risk of cerebral palsy has been previously reported. However, their results were relatively inconsistent. This systematic review and meta-analysis were carried out to investigate the association between maternal infection during pregnancy and the risk of cerebral palsy in children. Methods: PubMed, Scopus, and Web of Sciences databases were searched from inception to October 28, 2019. Heterogeneity was assessed using the I2 value. In case of substantial heterogeneity (I2 > 50%), a random effects model was applied, otherwise, a fixed effects model was used. The pooled associations were expressed as relative risks (RRs) and 95% confidence intervals (CIs). Publication bias and quality of studies included in the systematic review were checked using the Egger’s regression test and Newcastle-Ottawa Scale (NOS), respectively. Results: Thirty-seven studies were included in the systematic review. Among them, 21 studies were eligible for the meta-analysis. The pooled RR of cerebral palsy risk was 2.50 (95% CI 1.94, 3.21; I2 = 88.7%, P < .001) among children born to mothers who had any infection during pregnancy. The risk was increased to 2.85 (95% CI 1.96, 4.15; I2 = 75.9%, P < .001) when the mother was diagnosed with chorioamnionitis. Publication bias tests suggested no evidence of potential publication bias and 76% of the studies included in the meta-analysis were of high quality (NOS ≥ 6). Conclusion: This systematic review and meta-analysis provides evidence that maternal infection during pregnancy may be associated with an increased risk of cerebral palsy in children.

The association between maternal infection and intellectual disability in children: A systematic review and meta-analysis

“…Moreover, almost all subgroup analyses according to type of studies, publication year, and diagnostic criteria also indicated a positive association. These findings are in line with previous meta-analyses indicating that maternal infection is associated with increased risk of psychosis, cerebral palsy, and autism spectrum disorders [ 12 – 14 ].…”

Aetiology and Pathophysiology of Cerebral Palsy

“…There is a consensus in the literature that infections/inflammation via cytokinemediated injury to the immature brain are causally associated with CP (see Figure 2). Infection, inflammation and cytokines play a fundamental role in CP causation through their link with preterm labour (prematurity), placental pathology (chorioamnionitis, funisitis), congenital malformation, FGR, cerebral white matter injury (WMI) and perinatal asphyxia [29,[33][34][35][36][37]. Studies including recent meta-analyses have shown compelling evidence that maternal infections in pregnancy, intra-amniotic infection (chorioamnionitis), evidence of FIRS and neonatal infections are causally associated with CP [25,29,[35][36][37].…”

“…Infection, inflammation and cytokines play a fundamental role in CP causation through their link with preterm labour (prematurity), placental pathology (chorioamnionitis, funisitis), congenital malformation, FGR, cerebral white matter injury (WMI) and perinatal asphyxia [29,[33][34][35][36][37]. Studies including recent meta-analyses have shown compelling evidence that maternal infections in pregnancy, intra-amniotic infection (chorioamnionitis), evidence of FIRS and neonatal infections are causally associated with CP [25,29,[35][36][37]. Both transplacental TORCH infections (Toxoplasmosis, Others [syphilis, Epstein Barr virus, HIV, Zika virus], Rubella, Cytomegalovirus [CMV], Herpes virus), genitourinary infections (bacterial vaginosis, chlamydia, trichomonas, UTI) and neonatal infections (GBS-early onset sepsis, neonatal pneumonia, meningitis) have all been implicated in CP [37].…”

The use of stem cells in the treatment of cerebral palsy

“…It is believed that clinical chorioamnionitis increases the risk of CP in term (relative risk = 4.7) and preterm infants (relative risk = 1.9), due to inflammatory response to intrauterine infection that causes periventricular leukomalacia [2]. It is essential to remember the coexistence of GUI and preterm births as the risk factors of cerebral palsy, since pregnant women with maternal infections tend to have preterm labour (before 32 week's gestational age) [3].…”