Edward B. Quinn

Objectives: Maternal stress has long been associated with lower birthweight, which is associated with adverse health outcomes including many adult diseases. The underlying mechanisms remain elusive although changes in gene expression may play a role. Studies are only beginning to test how maternal stress impacts gene expression as reflected in the transcriptome.Materials and Methods: In a cohort of mothers and newborns in the eastern Democratic Republic of Congo (n = 93), we studied the effects of four maternal stress measures (chronic stress, war trauma, sexual trauma, and general trauma) on the transcriptomes of maternal venous blood, newborn venous blood, and placental tissues, and on newborn birthweight. Maternal stress was investigated as independent measures, principal components, and clusters identified through machine learning. The transcriptome was assayed using the ClariomD chip. Multiple regression models were used to test for associations between maternal stress measures, the transcriptome, and newborn birthweight.Results: None of the maternal stress measures showed an association with the expression of individual genes. In contrast, when testing global gene expression, war trauma was significantly associated with the placental transcriptome. War trauma was also significantly associated with birthweight in multiple models. Mediation analysis indicated that ~14% of the effect of war trauma on birthweight was mediated by a placental gene expression component.Discussion: Our results suggest that gene expression in the placenta, which represents the interface between mother and developing fetus, may partially mediate the negative impact of maternal stress on newborn birthweight.

The developing infant gut microbiome is highly sensitive to environmental exposures, enabling its evolution into an organ that supports the immune system, confers protection from infection, and facilitates optimal gut and central nervous system function. In this study, we focus on the impact of maternal psychosocial stress on the infant gut microbiome. Forty-seven mother–infant dyads were recruited at the HEAL Africa Hospital in Goma, Democratic Republic of Congo. Extensive medical, demographic, and psychosocial stress data were collected at birth, and infant stool samples were collected at six weeks, three months, and six months. A composite maternal psychosocial stress score was created, based on eight questionnaires to capture a diverse range of stress exposures. Full-length 16S rRNA gene sequences were generated. Infants of mothers with high composite stress scores showed lower levels of gut microbiome beta diversity at six weeks and three months, as well as higher levels of alpha diversity at six months compared to infants of low stress mothers. Longitudinal analyses showed that infants of high stress mothers had lower levels of health-promoting Lactobacillus gasseri and Bifidobacterium pseudocatenulatum at six weeks compared to infants of low stress mothers, but the differences largely disappeared by three to six months. Previous research has shown that L. gasseri can be used as a probiotic to reduce inflammation, stress, and fatigue, as well as to improve mental state, while B. pseudocatenulatum is important in modulating the gut–brain axis in early development and in preventing mood disorders. Our finding of reduced levels of these health-promoting bacteria in infants of high stress mothers suggests that the infant gut microbiome may help mediate the effect of maternal stress on infant health and development.

Objective: To test for effects of a problem-solving intervention for stroke caregivers on stroke survivor activities of daily living. Design: Two-arm parallel randomized clinical trial with repeated measures at 11 weeks and 19 weeks. Setting: Medical centers for US military Veterans. Subjects: Caregivers of stroke survivors. Intervention: A registered nurse guided caregivers in using problem-solving strategies emphasizing creative thinking, optimism, planning, and expert information to address challenges associated with caregiving. Caregivers in the intervention completed one telephone orientation session followed by eight online, asynchronous messaging center sessions. The messaging center sessions involved (a) education on the Resources and Education for Stroke Caregivers’ Understanding and Empowerment website ( https://www.stroke.cindrr.research.va.gov/en/ ), (b) supportive communication between the nurse and caregiver, (c) nurse and caregiver interactions to improve problem-solving, and (d) maintain adherence to discharge planning instructions. Main Outcome: The Barthel Index was used to measure activities of daily living. Results: 174 participants (standard care n = 88, intervention n = 86) were enrolled at baseline. There were no significant differences between groups at baseline. Change scores in activities of daily living between baseline and 11 weeks were significantly higher in the intervention group than the standard care group (group difference = 6.43, 95% confidence interval: 1.28, 11.58). Group differences in change scores between baseline and 19 weeks were not statistically significant (group difference = 3.89, 95% confidence interval: −3.58, 11.36). Conclusions: This web-based caregiver intervention improved stroke survivor activities of daily living by 11 weeks, but intervention effects were undetectable after 19 weeks.

The Developmental Origins of Health and Disease (DOHaD) hypothesis posits that early life adversity is associated with poor adult health outcomes. Epidemiological evidence has supported this framework by linking low birthweight with adult health and mortality, but the mechanisms remain unclear. Accelerated epigenetic aging may be a pathway to connect early life experiences with adult health outcomes, based on associations of accelerated epigenetic aging with increased morbidity and mortality. Sixty-seven mother-infant dyads were recruited in the eastern Democratic Republic of Congo. Birthweight data were collected at birth, and blood samples were collected at birth and follow-up visits up to age three. DNA methylation data were generated with the Illumina MethylationEPIC array and used to estimate epigenetic age. A multilevel model was used to test for associations between birthweight and epigenetic age acceleration. Chronological age was highly correlated with epigenetic age from birth to age three (r = 0.95, p < 2.2 x 10 ^-16). Variation in epigenetic age acceleration increased over time. Birthweight, dichotomized around 2500 grams, predicted epigenetic age acceleration over the first three years of life (b = -0.39, p = 0.005). Our longitudinal analysis provides the first evidence for accelerated epigenetic aging that emerges between birth and age three and associates with low birthweight. These results suggest that early life experiences, such as low birthweight, may shape the trajectory of epigenetic aging in early childhood. Furthermore, accelerated epigenetic aging may be a pathway that links low birthweight and poor adult health outcomes.