Milestones of brain development in mammals are completed before birth, which provide the prerequisite for cognitive and intellectual performances of the offspring. Prenatal challenges, such as maternal stress experience or infections, have been linked to impaired cognitive development, poor intellectual performances as well as neurodevelopmental and psychiatric disorders in the offspring later in life. Fetal microglial cells may be the target of such challenges and could be functionally modified by maternal markers. Maternal markers can cross the placenta and reach the fetus, a phenomenon commonly referred to as “vertical transfer.” These maternal markers include hormones, such as glucocorticoids, and also maternal immune cells and cytokines, all of which can be altered in response to prenatal challenges. Whilst it is difficult to discriminate between the maternal or fetal origin of glucocorticoids and cytokines in the offspring, immune cells of maternal origin—although low in frequency—can be clearly set apart from offspring's cells in the fetal and adult brain. To date, insights into the functional role of these cells are limited, but it is emergingly recognized that these maternal microchimeric cells may affect fetal brain development, as well as post-natal cognitive performances and behavior. Moreover, the inheritance of vertically transferred cells across generations has been proposed, yielding to the presence of a microchiome in individuals. Hence, it will be one of the scientific challenges in the field of neuroimmunology to identify the functional role of maternal microchimeric cells as well as the brain microchiome. Maternal microchimeric cells, along with hormones and cytokines, may induce epigenetic changes in the fetal brain. Recent data underpin that brain development in response to prenatal stress challenges can be altered across several generations, independent of a genetic predisposition, supporting an epigenetic inheritance. We here discuss how fetal brain development and offspring's cognitive functions later in life is modulated in the turnstile of prenatal challenges by introducing novel and recently emerging pathway, involving maternal hormones and immune markers.

During mammalian pregnancy, immune cells are vertically transferred from mother to fetus. The functional role of these maternal microchimeric cells (MMc) in the offspring is mostly unknown. Here we show a mouse model in which MMc numbers are either normal or low, which enables functional assessment of MMc. We report a functional role of MMc in promoting fetal immune development. MMc induces preferential differentiation of hematopoietic stem cells in fetal bone marrow towards monocytes within the myeloid compartment. Neonatal mice with higher numbers of MMc and monocytes show enhanced resilience against cytomegalovirus infection. Similarly, higher numbers of MMc in human cord blood are linked to a lower number of respiratory infections during the first year of life. Our data highlight the importance of MMc in promoting fetal immune development, potentially averting the threats caused by early life exposure to pathogens.

BackgroundThe SARS-COVID-19 pandemic and its associated disease control restrictions have in multiple ways affected families with young children, who may be especially vulnerable to mental health problems. Studies report an increase in perinatal parental distress as well as symptoms of anxiety or depression in children during the pandemic. Currently, little is known about the impact of the pandemic on infants and their development. Infant regulatory problems (RPs) have been identified as early indicators of child socio-emotional development, strongly associated with maternal mental health and the early parent–infant interaction. Our study investigates whether early parenthood under COVID-19 is associated with more maternal depressive symptoms and with a perception of their infants as having more RPs regarding crying/fussing, sleeping, or eating, compared to mothers assessed before the pandemic.MethodsAs part of a longitudinal study, 65 women who had given birth during the first nationwide disease control restrictions in Northern Germany, were surveyed at 7 months postpartum and compared to 97 women assessed before the pandemic. RPs and on maternal depressive symptoms were assessed by maternal report. Number of previous children, infant negative emotionality, and perceived social support were assessed as control variables.ResultsCompared to the control cohort, infants born during the COVID-19 pandemic and those of mothers with higher depressive symptoms were perceived as having more sleeping and crying, but not more eating problems. Regression-based analyses showed no additional moderating effect of parenthood under COVID-19 on the association of depressive symptoms with RPs. Infant negative emotionality was positively, and number of previous children was negatively associated with RPs.LimitationsDue to the small sample size and cross-sectional assessment, the possibility for more complex multivariate analysis was limited. The use of parent-report questionnaires to assess infant RPs can support but not replace clinical diagnosis.ConclusionsThe pandemic conditions affecting everyday life may have a long-term influence on impaired infant self- and maternal co-regulation and on maternal mental health. This should be addressed in peripartum and pediatric care. Qualitative and longitudinal studies focusing on long-term parental and infant outcomes under ongoing pandemic conditions are encouraged.