The effects of experience of discrimination and acculturation during pregnancy on the developing offspring brain.

The experience of ethnic, racial, and structural inequalities is increasingly recognized as detrimental to health, and early studies suggest that its experience in pregnant mothers may affect the developing fetus. We characterized discrimination and acculturation experiences in a predominantly Hispanic sample of pregnant adolescent women and assessed their association with functional connectivity in their neonate's brain. We collected self-report measures of acculturation, discrimination, maternal distress (i.e., perceived stress, childhood trauma, and depressive symptoms), and socioeconomic status in 165 women. Then, we performed a data-driven clustering of acculturation, discrimination, perceived stress, depressive symptoms, trauma, and socioeconomic status variables during pregnancy to determine whether discrimination or acculturation clustered into distinct factors. Discrimination and acculturation styles loaded onto different factors from perceived stress, depressive symptoms, trauma, and socioeconomic status, suggesting that they were distinct from other factors in our sample. We associated these data-driven maternal phenotypes (discrimination and acculturation styles) with measures of resting-state functional MRI connectivity of the infant amygdala (n = 38). Higher maternal report of assimilation was associated with weaker connectivity between their neonate's amygdala and bilateral fusiform gyrus. Maternal experience of discrimination was associated with weaker connectivity between the amygdala and prefrontal cortex and stronger connectivity between the amygdala and fusiform of their neonate. Cautiously, the results may suggest a similarity to self-contained studies with adults, noting that the experience of discrimination and acculturation may influence amygdala circuitry across generations. Further prospective studies are essential that consider a more diverse population of minoritized individuals and with a comprehensive assessment of ethnic, racial, and structural factors.

Maternal prenatal immune activation associated with brain tissue microstructure and metabolite concentrations in newborn infants.

Importance: Few translational human studies have assessed the association of prenatal maternal immune activation with altered brain development and psychiatric risk in newborn offspring. Objective: To identify the effects of maternal immune activation during the 2nd and 3rd trimesters of pregnancy on newborn brain metabolite concentrations, tissue microstructure, and longitudinal motor development. Design: Prospective longitudinal cohort study conducted from 2012 - 2017. Setting: Columbia University Irving Medical Center and Weill Cornell Medical College. Participants: 76 nulliparous pregnant women, aged 14 to 19 years, were recruited in their 2nd trimester, and their children were followed through 14 months of age. Exposure: Maternal immune activation indexed by maternal interleukin-6 and C-reactive protein in the 2nd and 3rd trimesters of pregnancy. Main Outcomes and Measures: The main outcomes included (1) newborn metabolite concentrations, measured as N-acetylaspartate, creatine, and choline using Magnetic Resonance Spectroscopy; (2) newborn fractional anisotropy and mean diffusivity measured using Diffusion Tensor Imaging; and (3) indices of motor development assessed prenatally and postnatally at ages 4- and 14-months. Results: Maternal interleukin-6 and C-reactive protein levels in the 2nd or 3rd trimester were significantly positively associated with the N-acetylaspartate, creatine, and choline concentrations in the putamen, thalamus, insula, and anterior limb of the internal capsule. Maternal interleukin-6 was associated with fractional anisotropy in the putamen, insula, thalamus, precuneus, and caudate, and with mean diffusivity in the inferior parietal and middle temporal gyrus. C-reactive protein was associated with fractional anisotropy in the thalamus, insula, and putamen. Regional commonalities were found across imaging modalities, though the direction of the associations differed by immune marker. In addition, a significant positive association was observed between offspring motor development and both maternal interleukin-6 and C-reactive protein (in both trimesters) prenatally and 4- and 14-months of age. Conclusions and Relevance: Using a healthy sample, these findings demonstrate that levels of maternal immune activation in mid- to late pregnancy associate with tissue characteristics in newborn brain regions primarily supporting motor integration/coordination and behavioral regulation and may lead to alterations in motor development.

Utilizing maternal prenatal cognition as a predictor of newborn brain measures of intellectual development.

Identifying reliable indicators of cognitive functioning prior to age five has been challenging. Prior studies have shown that maternal cognition, as indexed by intellectual quotient (IQ) and years of education, predict child intelligence at school age. We examined whether maternal full scale IQ, education, and inhibitory control (index of executive function) are associated with newborn brain measures and toddler language outcomes to assess potential indicators of early cognition. We hypothesized that maternal indices of cognition would be associated with brain areas implicated in intelligence in school-age children and adults in the newborn period. Thirty-seven pregnant women and their newborns underwent an MRI scan. T2-weighted images and surface-based morphometric analysis were used to compute local brain volumes in newborn infants. Maternal cognition indices were associated with local brain volumes for infants in the anterior and posterior cingulate, occipital lobe, and pre/postcentral gyrus - regions associated with IQ, executive function, or sensori-motor functions in children and adults. Maternal education and executive function, but not maternal intelligence, were associated with toddler language scores at 12 and 24 months. Newborn brain volumes did not predict language scores. Overall, the pre/postcentral gyrus and occipital lobe may be unique indicators of early intellectual development in the newborn period. Given that maternal executive function as measured by inhibitory control has robust associations with the newborn brain and is objective, brief, and easy to administer, it may be a useful predictor of early developmental and cognitive capacity for young children.