Butzin-Dozier Zachary, Mertens Andrew N, Tan Sophia T, Granger Douglas A, Pitchik Helen O, Il'yasova Dora, Tofail Fahmida, Rahman Md Ziaur, Spasojevic Ivan, Shalev Idan, Ali Shahjahan, Karim Mohammed Rabiul, Shahriar Sunny, Famida Syeda Luthfa, Shuman Gabrielle, Shoab Abul K, Akther Salma, Hossen Md Saheen, Mutsuddi Palash, Rahman Mahbubur, Unicomb Leanne, Das Kishor K, Yan Liying, Meyer Ann, Stewart Christine P, Hubbard Alan, Tabassum Naved Ruchira, Parvin Kausar, Mamun Md Mahfuz Al, Luby Stephen P, Colford John M, Fernald Lia C H, Lin Audrie
School of Public Health, University of California, Berkeley, Berkeley, CA USA.
Division of HIV, Infectious Diseases, and Global Medicine, University of California, San Francisco, San Francisco, CA, USA.
medRxiv. 2023 Sep 12:2023.09.12.23295429. doi: 10.1101/2023.09.12.23295429.
Hundreds of millions of children in low- and middle-income countries are exposed to chronic stressors, such as poverty, poor sanitation and hygiene, and sub-optimal nutrition. These stressors can have physiological consequences for children and may ultimately have detrimental effects on child development. This study explores associations between biological measures of chronic stress in early life and developmental outcomes in a large cohort of young children living in rural Bangladesh.
We assessed physiologic measures of stress in the first two years of life using measures of the hypothalamic-pituitary-adrenal (HPA) axis (salivary cortisol and glucocorticoid receptor gene methylation), the sympathetic-adrenal-medullary (SAM) system (salivary alpha-amylase, heart rate, and blood pressure), and oxidative status (F2-isoprostanes). We assessed child development in the first two years of life with the MacArthur-Bates Communicative Development Inventories (CDI), the WHO gross motor milestones, and the Extended Ages and Stages Questionnaire (EASQ). We compared development outcomes of children at the 75th and 25th percentiles of stress biomarker distributions while adjusting for potential confounders (hereafter referred to as contrasts) using generalized additive models, which are statistical models where the outcome is predicted by a potentially non-linear function of predictor variables.
We analyzed data from 684 children (49% female) at both 14 and 28 months of age; we included an additional 765 children at 28 months of age. We observed 135 primary contrasts of the differences in child development outcomes at the 75 and 25 percentiles of stress biomarkers, where we detected significant relationships in 5 out of 30 contrasts (17%) of HPA axis activity, 1 out of 30 contrasts (3%) of SAM activity, and 3 out of 75 contrasts (4%) of oxidative status. These findings revealed that measures of HPA axis activity were associated with poor development outcomes. We did not find consistent evidence that markers of SAM system activity or oxidative status were associated with developmental status.
Our observations reveal associations between the physiological evidence of stress in the HPA axis with developmental status in early childhood. These findings add to the existing evidence exploring the developmental consequences of early life stress.
