UC Santa Barbara

Among humans, female reproduction requires significant immune modulation. Invasive placentation results in exposure to fetal antigens and corresponding shifts in female immune function and disease susceptibility, which vary in magnitude in response to ecological conditions (e.g., pathogen exposure). By comparison, there have been very few studies on how time since delivery affects immune recovery or how variation in infant feeding behavior (e.g., breastfeeding, formula feeding, pumping) might moderate postpartum immune recovery. Of the few studies that have been conducted on postpartum women, most have come from post-industrial populations experiencing evolutionarily novel conditions (e.g., obesity, low pathogen exposure). Consequently, current understanding of sexual dimorphism in immune function, a phenomenon commonly observed in humans and other mammalian species, is skewed by absence of data from postpartum females as well as disproportionate sampling of populations experiencing environmental cues (e.g., obesity) that may exacerbate sex hormone production and amplify sex bias in immune function and disease risk. In this dissertation, I aim to address these gaps in knowledge via three distinct yet interconnected studies. I utilize pre-existing data from the Tsimane Health and Life History Project (THLHP) and the National Health and Nutrition Examination Survey (NHANES) to characterize and compare the effects of month since delivery on immune outcomes among Tsimane and USA women (two ecologically distinct populations) (Study 1) and compare the effects of sex and female reproductive phase on immune function across the lifespan in both the Tsimane and the USA (Study 2). Lastly, I investigate the impact of infant feeding behavior (e.g., at-the-nipple breastfeeding, pumping, other supplementation) on maternal immune function, health, and wellbeing among postpartum women in Seattle, Washington, USA using data I collected between October 2020 and July 2021 as part of the Seattle Postpartum Health Study (Study 3). My findings indicate that the postpartum period is a unique immunological state, with month of gestation and month since delivery exerting opposing effects on most immune markers. Observed differences between Tsimane and USA women point towards the role of environment in shaping immunological recovery and may specifically reflect differences in pathogen clearance requirements following pregnancy. My results also show that sex bias in immune status is comparatively attenuated among the Tsimane, indicating that ecological conditions in the USA (e.g., increased energetic budget) may exacerbate evolved mechanisms underlying sexual dimorphism in disease risk. Within each population, pregnancy was generally associated with increased sexual dimorphism while the postpartum period was often associated with attenuated sex bias, highlighting the underappreciated role of female reproductive phase in generating or dampening sex differences in immune function. Lastly, I provide evidence that both at-the-nipple breastfeeding and pumping confer benefits on postpartum maternal outcomes (e.g., fewer depressive symptoms, reduced inflammation) compared to reliance on formula/other forms of supplementation, but that heavy reliance on pumping is associated with increased symptoms of physical illness.