# Selection in utero and consequences for sex differences in adult mortality: a cohort approach > **NIH NIH R21** · UNIVERSITY OF CALIFORNIA-IRVINE · 2022 · $191,416 ## Abstract Project Summary (30 lines) Male cohort lifespan falls below female lifespan in all societies with reliable data. Although this male longevity deficit is well-described, less attention focuses on heightened male frailty in utero. Empirical work as well as strong theory indicates that the sex ratio at birth (i.e., M/F) gauges the strength of mortality selection in utero especially for males that ultimately survive to birth. We will test an innovative hypothesis which connects this frailty in utero to morbidity and mortality in older adulthood―specifically, whether males more than females born to the most selected birth cohorts show reduced morbidity and mortality rates at advanced ages. The “culled cohort” argument asserts that males born to low sex ratio cohorts live longer, on average, than expected because the frailest members of their group were culled in utero. Ecological analyses in industrial Europe find that males (but not females) born from the most culled cohorts (i.e., low sex ratio) exhibit lower than expected mortality rates at older ages. We intend to move beyond these ecological associations and test, using longitudinal, individual-level life history data from a high-fertility population whether the sex ratio at birth predicts sex differences in survival and morbidity (e.g., cardiovascular disease) beyond age 50. We will examine over 1.7 million males and females from the Utah Population Database (UPDB), born from 1850- 1940 and followed until the present (i.e., most cohorts will no longer have living members). The UPDB is one of the largest and highest quality individual-level life history databases in the world which may identify frail subgroups. Our aims will examine whether the hazard rate (≥50 years) of all-cause mortality, “biological” causes of mortality, and cause-specific morbidity varies for males more than females as a function of the cohort’s sex ratio. For all aims, we will (i.) examine males and females separately; and (ii.) test whether family and individual life-history characteristics (e.g., parental investments, SES), which may gauge phenotypic plasticity, attenuate or magnify any cohort effects of the sex ratio. All analyses will control for secular patterns in mortality, cohort attrition before age 50, shared family frailty, and other relevant confounders. We will also examine ambient stressors (e.g., Great Depression) as well as highly localized (e.g., drought at the county level) antecedents of selection in utero and later-life cohort mortality. Hypotheses will be tested with rarely combined but well-developed methods. Overall, our work is significant because it advances NIA’s research priority of “understanding sex and gender differences in health and disease at older ages.” Results will also inform the developmental origins field in that researchers measuring older-age responses (e.g., chronic disease) to ambient stressors during pregnancy may underestimate later-life adversity if they do not account for heter... ## Key facts - **NIH application ID:** 10492452 - **Project number:** 5R21AG067247-02 - **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE - **Principal Investigator:** Tim Allen Bruckner - **Activity code:** R21 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2022 - **Award amount:** $191,416 - **Award type:** 5 - **Project period:** 2021-09-30 → 2025-05-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10492452 ## Citation > US National Institutes of Health, RePORTER application 10492452, Selection in utero and consequences for sex differences in adult mortality: a cohort approach (5R21AG067247-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10492452. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*