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<p>Descendants of longevity-enriched sibships demonstrate a broad health and survival advantage throughout the life course. However, little is known about manifestations during very early life. Here we show a pattern of lower risk of adverse early-life outcomes in third-generation grandchildren (<i>N</i> = 5637) of Danish longevity-enriched sibships compared to the general population, including infant mortality (Hazard Ratio = 0.53, 95% CI [0.36, 0.77]) and a range of neonatal health indicators. These associations in fourth-generation great-grandchildren (<i>N</i> = 14,908) were attenuated and less consistent (e.g., infant mortality, Hazard Ratio = 0.90, [0.70, 1.17]). Dilatory patterns across successive generations were independent of stable advantages in select socioeconomic and behavioural indicators (e.g., parental education, income and maternal smoking), maternal and paternal lines of transmission, as well as secular trends in the background population. However, our socioeconomic and behavioral indicators were limited in both range and granularity. Our findings suggest that the familial aggregation of exceptional health and survival has early life developmental components.</p>

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Developmental origins of exceptional health and survival: a four-generation family cohort study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月9日

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  • Matthew Thomas Keys,
  • Søren Netra,
  • Dorthe Almind Pedersen,
  • Pernille Stemann Larsen,
  • Alexander Kulminski,
  • Mary F. Feitosa,
  • Mary Wojczynski,
  • Michael Province,
  • Kaare Christensen

摘要

Descendants of longevity-enriched sibships demonstrate a broad health and survival advantage throughout the life course. However, little is known about manifestations during very early life. Here we show a pattern of lower risk of adverse early-life outcomes in third-generation grandchildren (N = 5637) of Danish longevity-enriched sibships compared to the general population, including infant mortality (Hazard Ratio = 0.53, 95% CI [0.36, 0.77]) and a range of neonatal health indicators. These associations in fourth-generation great-grandchildren (N = 14,908) were attenuated and less consistent (e.g., infant mortality, Hazard Ratio = 0.90, [0.70, 1.17]). Dilatory patterns across successive generations were independent of stable advantages in select socioeconomic and behavioural indicators (e.g., parental education, income and maternal smoking), maternal and paternal lines of transmission, as well as secular trends in the background population. However, our socioeconomic and behavioral indicators were limited in both range and granularity. Our findings suggest that the familial aggregation of exceptional health and survival has early life developmental components.