Several different bodies of evidence support a link between infection and altered brain development. Maternal infections, such as influenza and human immunodeficiency virus, have been linked to the development of autism spectrum disorders, differences in cognitive test scores, and bipolar disorder; an association that has been shown in both epidemiologic and retrospective studies. Several viral, bacterial, and parasitic illnesses are associated with alterations in fetal brain structural anomalies including brain calcifications and hydrocephalus. The process of infection can activate inflammatory pathways causing the release of various proinflammatory biomarkers and histological changes consistent with an infectious intrauterine environment (chorioamnionitis) or umbilical cord (funisitis). Elevations in inflammatory cytokines are correlated with cerebral palsy, schizophrenias, and autism. Animal studies indicate that the balance of proinflammatory and anti-inflammatory cytokines is critical to the effect prenatal inflammation plays in neurodevelopment. Finally, chorioamnionitis is associated with cerebral palsy and other abnormal neurodevelopmental outcomes. In conclusion, a plethora of evidence supports, albeit with various degrees of certainty, the theory that maternal infection and inflammation that occur during critical periods of fetal development could theoretically alter brain structure and function in a time-sensitive manner.
Obstetricians and gynecologists, family physicians.
After completing this activity, the learner will be better able to demonstrate that human brain development occurs throughout the fetal period and can be altered by infection and inflammation in ways that are dependent on the nature and timing of the insults; discuss the various maternal infections that are associated with adverse neurological outcomes, including schizophrenia and autism; discuss the viral, parasitic, and bacterial infections that are associated with altered brain structure and anatomy in both human and animal models; and demonstrate that chorioamnionitis is associated with altered brain and neurological development.
*Resident, Obstetrics and Gynecology, †Fellow, Maternal Fetal Medicine, and ‡Associate Professor and Director, Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD
All authors and staff in a position to control the content of this CME activity and their spouses/life partners (if any) have disclosed that they have no financial relationships with, or financial interests in, any commercial organizations pertaining to this educational activity.
Correspondence requests to: Irina Burd, MD, PhD, Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Phipps 217, 600 N Wolfe St, Baltimore, MD. E-mail: email@example.com.