Maternal influences on fetal brain development: The role of nutrition, infection and stress, and the potential for intergenerational consequences

Abstract

An optimal early life environment is crucial for ensuring ideal neurodevelopmental outcomes. Brain development consists of a finely tuned series of spatially and temporally constrained events, which may be affected by exposure to a sub-optimal intra-uterine environment. Evidence suggests brain development may be particularly vulnerable to factors such as maternal nutrition, infection and stress during pregnancy. In this review, we discuss how maternal factors such as these can affect brain development and outcome in offspring, and we also identify evidence which suggests that the outcome can, in many cases, be stratified by socio-economic status (SES), with individuals in lower brackets typically having a worse outcome. We consider the relevant epidemiological evidence and draw parallels to mechanisms suggested by preclinical work where appropriate. We also discuss possible transgenerational effects of these maternal factors and the potential mechanisms involved. We conclude that modifiable factors such as maternal nutrition, infection and stress are important contributors to atypical brain development and that SES also likely has a key role.

Association of Birth During the COVID-19 Pandemic With Neurodevelopmental Status at 6 Months in Infants With and Without In Utero Exposure to Maternal SARS-CoV-2 Infection

“…Similarly, early gestational exposure is most likely to be associated with adverse neurodevelopmental outcomes. [47][48][49] Given that only 25 maternal SARS-Cov-2 infections (8 imputed) in our sample occurred in the first trimester, our results provide limited power for detecting an association between infection at this early time point and neurodevelopment.…”

Birth during the COVID-19 pandemic, but not maternal SARS-CoV-2 infection during pregnancy, is associated with lower neurodevelopmental scores at 6-months

“…participants experienced an asymptomatic or mild SARS-CoV-2 infection, and therefore, infants exposed to significant MIA may not be represented in our data. Similarly, early gestational exposure is most likely to be associated with adverse neurodevelopmental outcomes [46][47][48] . Given that only 21 maternal SARS-Cov-2 infections (8 imputed) in our sample occurred in the first trimester, our results provide limited power for detecting the effects of infection at this early timepoint.…”

Fetal programming: could intrauterin life affect health status in adulthood?

“…Epidemiological studies have shown that there is a relationship between intrauterine environmental factors affecting fetal nutrition and the development of obesity and chronic diseases later in adult life [ 2 ]. The Developmental Origins of Health and Disease (DOHaD) hypothesis assumes that the prenatal period is a sensitive developmental period in which exposure to adverse environments as malnutrition, infection, or stress can have long-term or lasting effects on the health path of the offspring—this is termed “developmental programming” [ 7 ]. The “thrifty phenotype” hypothesis has been further developed to suggest that developmental programming is only one of a series of adaptations that occur in an external environment predicted during development.…”