Maternal nutrients and effects of gestational COVID-19 infection on fetal brain development

Abstract

Background & aims: Maternal gestational infection is a well-characterized risk factor for offsprings' development of mental disorders including schizophrenia, autism, and attention deficit disorder. The inflammatory response elicited by the infection is partly directed against the placenta and fetus and is the putative pathogenic mechanism for fetal brain developmental abnormalities. Fetal brain abnormalities are generally irreversible after birth and increase risk for later mental disorders. Maternal immune activation in animals models this pathophysiology. SARS-CoV-2 produces maternal inflammatory responses during pregnancy similar to previously studied common respiratory viruses. Method: Choline, folic acid, Vitamin D, and n-3 polyunsaturated fatty acids are among the nutrients that have been studied as possible mitigating factors for effects of maternal infection and inflammation on fetal development. Clinical and animal studies relevant to their use in pregnant women who have been infected are reviewed. Results: Higher maternal choline levels have positive effects on the development of brain function for infants of mothers who experienced viral infections in early pregnancy. No other nutrient has been studied in the context of viral inflammation. Vitamin D reduces pro-inflammatory cytokines in some, but not all, studies. Active folic acid metabolites decrease anti-inflammatory cytokines. N-3 polyunsaturated fatty acids have no effect. Conclusions: Vitamin D and folic acid are already supplemented in food additives and in prenatal vitamins. Despite recommendations by several public health agencies and medical societies, choline intake is often inadequate in early gestation when the brain is forming. A public health initiative for choline supplements during the pandemic could be helpful for women planning or already pregnant who also become exposed or infected with SARS-CoV-2.

Pharmacological Efficacy and Mechanism of Vitamin D in the Treatment of “Kidney-Brain” Disorders

“…Remarkably, as a nonclassical role beyond action on skeletal homeostasis, the pharmacological regulations of vitamin D on inflammation responses including neuroinflammation have been widely studied. An interesting review stated that vitamin D could partially produce positive effects on the development of brain function for infants of mothers who experienced viral infections in early pregnancy by reducing some pro-inflammatory cytokines [82]. Vitamin D might act as a strong immunosuppressant repressing cytokine release syndrome in COVID-19 via attenuating the production and secretion of crucial pro-inflammatory cytokines including NF-kB, IL-6, IL-1β, and TNF [83].…”

Deleterious effects of nervous system in the offspring following maternal SARS-CoV-2 infection during the COVID-19 pandemic

“…There is a study that reported that pregnant women during the influenza pandemics had a high incidence of psychiatric disorders in their offspring, including schizophrenia, autism spectrum disorder (ASD), and attention-deficit hyperactivity disorder (ADHD) [ 25 ]. Similar results have been obtained in animal experiments, where an animal model of maternal immune activation was constructed by administering polyinosinic- polycytidylic acid [Poly (I:C)] to pregnant mice, and it was found that exposure of mice on days 10–12 of embryonic life resulted in damage to the developing basal ganglia and offspring with defects in prepulse inhibition and latent inhibition that are similar to those found in ASD and schizophrenia individuals [ 26 ].…”

“…Based on previous experience with disease pandemics and experience with other respiratory viruses and animal models, increasing maternal choline levels and other nutrient levels may reduce the effects of infection on fetal brain development [ 25 ]. Choline supplementation may reduce the increase in fetal IL-6 levels caused by RNA virus stimulation and may decrease anxiety [ 62 ].…”

Congenital Infection Influence on Early Brain Development Through the Gut-Brain Axis

“…TORCH is a common acronym used to refer to a set of these infections: (T)oxoplasmosis, (O)ther agents such as syphilis and parvovirus B19, Rubella, (C)ytomegalovirus infection (CMV), and (H)erpes simplex virus (HSV) ( Macedo-da-Silva et al, 2020 ; Jaan and Rajnik, 2022 ). In addition, recent studies have been conducted to understand the effects of other viruses that cause congenital infection—such as Zika virus (ZIKV) and the novel SARS-CoV-2 coronavirus (virus causing COVID-19)—on fetal development ( Hoffman et al, 2021 ; Nunez et al, 2021 ). While the pathophysiology of the congenital infections has been investigated at length, recent developments in metabolomics and cellular physiology have begun to elucidate metabolic adaptations and derangements in the fetus that accompany these infections.…”