COVID-19 in pregnancy: implications for fetal brain development

Abstract

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy on the developing fetal brain is poorly understood. Other antenatal infections such as influenza have been associated with adverse neurodevelopmental outcomes in offspring. Although vertical transmission has been rarely observed in SARS-CoV-2 to date, given the potential for profound maternal immune activation, impact on the developing fetal brain is likely. Here we review evidence that SARS-CoV-2 and other viral infections during pregnancy can result in maternal, placental and fetal immune activation, and ultimately in offspring neurodevelopmental morbidity. Finally, we highlight the need for cellular models of fetal brain development to better understand potential short- and long-term impacts of maternal SARS-CoV-2 infection on the next generation.

Neurodevelopmental Outcomes at 1 Year in Infants of Mothers Who Tested Positive for SARS-CoV-2 During Pregnancy

“…However, the profound immune activation observed in a subset of infected individuals suggests that the developing fetal brain may be influenced by maternal and placental inflammation and altered cytokine expression during key developmental windows. 1 , 2 , 3 , 4 , 5 (For a review of how these mechanisms might apply to COVID-19, see Shook et al 1 ) Regardless of mechanism, epidemiologic studies demonstrate that maternal infection in pregnancy, including other viral infections such as influenza, is associated with adverse neurodevelopmental outcomes in offspring, including autism spectrum disorders, schizophrenia, cerebral palsy, cognitive dysfunction, bipolar disorder, and anxiety and depression. 6 , 7 , 8 , 9 Although the magnitude of these effects and strength of association varies, the consistency of such associations is difficult to ignore.…”

COVID-19 and pregnancy: clinical outcomes; mechanisms, and vaccine efficacy

“…115 Other preliminary studies have assessed different time periods following delivery, such as 3, 6, and 12 months, and also suggested that SARS-CoV-2 infection during pregnancy can have detrimental impacts on the brain development of the fetus. [116][117][118] Emerging data suggests the Delta variant of SARS-CoV-2 is increasingly associated with severe illness in young children. 119 A large multicenter investigation indicated that COVID-19 was associated with widespread, temporary brain impairment in children and adolescents hospitalized with the virus.…”

“…It is known that substantial neurodevelopmental impairment in offspring can be caused by the activation of the maternal immune system pathway, regardless of whether the infection was caused by a virus or bacteria. 118,121,122 Extreme cases with widespread neurological problems and mortality in children exposed to SARS-CoV-2 infection have been connected to elevated levels of inflammation. 120 Preliminary investigations have also shown that pregnant women infected with SARS-CoV-2 had highly elevated levels of proinflammatory cytokines such as IL-6, IFN-γ and IL-1β.…”

Long term implications of covid-19 in pregnancy

“…Beyond covid-19, this neglect had tragic consequences for women affected by the Zika and Ebola outbreaks. Intrauterine exposures to maternal covid-19 could reach 20 million a year globally, according to recent estimates 9. This, coupled with lessons from previous antenatal viral infections, means the possibility of long term neurological or neurodevelopmental harms from covid-19 warrant close attention.…”