Deficient or Excess Folic Acid Supply During Pregnancy Alter Cortical Neurodevelopment in Mouse Offspring.

Folate is an essential micronutrient required for both cellular proliferation through de novo nucleotide synthesis and epigenetic regulation of gene expression through methylation. This dual requirement places a particular demand on folate availability during pregnancy when both rapid cell generation and programmed differentiation of maternal, extraembryonic, and embryonic/fetal tissues are required. Accordingly, prenatal neurodevelopment is particularly susceptible to folate deficiency, which can predispose to neural tube defects, or when effective transport into the brain is impaired, cerebral folate deficiency. Consequently, adequate folate consumption, in the form of folic acid (FA) fortification and supplement use, is widely recommended and has led to a substantial increase in the amount of FA intake during pregnancy in some populations. Here, we show that either maternal folate deficiency or FA excess in mice results in disruptions in folate metabolism of the offspring, suggesting diversion of the folate cycle from methylation to DNA synthesis. Paradoxically, either intervention causes comparable neurodevelopmental changes by delaying prenatal cerebral cortical neurogenesis in favor of late-born neurons. These cytoarchitectural and biochemical alterations are accompanied by behavioral abnormalities in FA test groups compared with controls. Our findings point to overlooked potential neurodevelopmental risks associated with excessively high levels of prenatal FA intake.

Prenatal folic acid and vitamin B12 imbalance alter neuronal morphology and synaptic density in the mouse neocortex.

Previous reports have provided evidence that insufficient or excessive maternal folic acid (FA) intake during pregnancy can alter neurodevelopment of the offspring by modulating prenatal neurogenesis. Furthermore, our earlier work in a mouse model confirmed long-term structural changes at the cellular level of either deficient or excessive FA supply by comparably reducing dendritic arborization of cortical projection neurons. Here, we report that excessive amounts of FA decrease arborization of deep layer projection neurons, but not upper layer neurons and that reduced complexity of deep layer neurons is not observed when folic acid is replaced by folinic acid, a stable reduced form of folate. In addition, deficiency of B12, a vitamin that critically regulates folate metabolism, causes even more marked decreases in neuronal arborization in both deep and upper layer neurons and particularly in combination with FA excess. Furthermore, both FA excess and B12 deficiency affect synaptic density and morphology. Our findings point to neurodevelopmental risks associated with insufficient amounts of prenatal B12, particularly in association with high levels of FA intake, suggesting that the neurodevelopmental program is sensitive to an imbalance in the status of these interacting micronutrients.

Side effects of messenger RNA vaccines and prior history of COVID-19, a cross-sectional study.

BACKGROUND: There are concerns regarding immunogenicity with coronavirus disease 2019 (COVID-19) mRNA vaccines among persons with prior history of COVID-19 (PHC). This study was to analyze the short-term side effects of mRNA vaccines among health care workers (HCWs) with and without PHC. METHODS: A cross-sectional study was performed using an independent online survey questionnaire that gathered responses from HCWs. RESULTS: Among 1,475 HCWs, 1268 (85.97%) completed the survey, 102/1268 (44/447 in Moderna group and 58/821 in Pfizer-BioNTech group) reported PHC during pre-vaccination period. Symptoms of flushing/P = .05, brain fogging/P= .005, vertigo/P= .041, numbness/P= .023, diarrhea/P= .047, hives/P= .028, itching/P= .028, swelling of lips/mouth/P= .001, shortness of breath/P= .022, and anxiety/P= .048 have greater occurrence among Pfizer-BioNtech group with PHC when compared to Pfizer-BioNtech group with no PHC. Symptoms of chills/P= .027, flushing/P= .045, tremor/P= .05, muscle spasm/P= .039, vomiting/P= .031, diarrhea/P= .015, and cough/P= .011 have higher occurrence among Moderna group with PHC when compared to Moderna group with no PHC. CONCLUSIONS: Few short-term side effects among mRNA vaccine recipients with PHC may have necessitated transient time-off from work. The PHC can be considered as a predictor for severity of side effects. While the vaccination program continues in the United States, a future COVID legislation that mandates vaccination among employees along with paid time off provision may help with higher compliance and acceptance.