长寿同胞的后代在整个生命历程中表现出广泛的健康和生存优势。然而,对生命早期的表现知之甚少。在这里,我们显示了与普通人群相比,丹麦长寿同胞的第三代孙子女(N=5637)的不良早期生活结果风险较低的模式。包括婴儿死亡率(危险比=0.53,95%CI[0.36,0.77])和一系列新生儿健康指标。第四代曾孙(N=14,908)的这些关联强烈减弱且不太一致(例如,婴儿死亡率,危险比=0.90,[0.70,1.17])。连续几代人的这些扩张模式独立于稳定的社会经济和行为优势(例如,父母教育和母亲吸烟),母系和父系的传播线,以及背景人口的长期趋势。我们的发现表明,特殊的健康和生存可能具有早期生命发育成分,并在其传播中涉及可遗传的遗传和/或表观遗传因素。
■先前的研究表明,在长寿家庭中,三代人都具有强大的健康和生存优势。然而,与家族长寿相关的生存优势可能比以前认为的更早地在生命中显现。
■我们进行了一项匹配的队列研究,比较了1973年至2018年间丹麦的第三代孙子女(n=5,637)和第四代曾孙女(n=14,908)与人口统计学匹配的出生(n=41,090)的早期健康轨迹。
■在孙辈的一系列不良早期生活结局中观察到较低的风险,包括婴儿死亡率(危险比(HR)=0.53,95%CI[0.36,0.77]),早产(赔率(OR)=0.82,[0.72,0.93]),小于胎龄(OR=0.83,[0.76,0.90])和新生儿呼吸系统疾病(OR=0.77,[0.67,0.88])。两代人在父母教育和母亲吸烟方面的相对优势相似。然而,在曾孙中观察到婴儿死亡率的下降幅度要小得多(HR=0.90,[0.70,1.17]),其他结局的获益也不太一致,尽管坚持社会经济和行为优势。最后,母性,和父系传播线在婴儿生存优势的传播中是等效的。
■长寿同胞的后代表现出广泛的健康优势,表现为围产期的早期。然而,这种影响在连续几代人中被强烈稀释。我们的发现表明,特殊的健康和生存可能具有早期发育成分,并在其特定传播中涉及可遗传的遗传和/或表观遗传因素。
■先前的研究表明,在长寿家庭中,三代人都具有强大的健康和生存优势。然而,与家族长寿相关的生存优势可能比以前认为的更早地在生命中显现。在我们对长寿同胞的第三代和第四代后代的研究中,我们观察到婴儿健康和生存方面的广泛优势体现在预防各种不良分娩结局方面.这些优势在第三代和第四代之间被强烈削弱,独立于其他稳定的社会经济和行为父母优势,以及母系和父系的传播线。我们的发现表明,异常健康和生存的家族聚集可能具有早期生命发育成分,并具有三角测量,以暗示可遗传的遗传和/或表观遗传因素在其传播中。
UNASSIGNED: Previous researched has demonstrated potent health and survival advantages across three-generations in longevity-enriched families. However, the survival advantage associated with familial longevity may manifest earlier in life than previously thought.
UNASSIGNED: We conducted a matched cohort study comparing early health trajectories in third-generation grandchildren (n = 5,637) and fourth-generation great-grandchildren (n = 14,908) of longevity-enriched sibships to demographically matched births (n = 41,090) in Denmark between 1973 and 2018.
UNASSIGNED: Lower risk was observed across a range of adverse early life outcomes in the grandchildren, including infant mortality (Hazard Ratio (HR) = 0.53, 95% CI [0.36, 0.77]), preterm birth (Odds Ratio (OR) = 0.82, [0.72, 0.93]), small for gestational age (OR = 0.83, [0.76, 0.90]) and neonatal respiratory disorders (OR = 0.77, [0.67, 0.88]). Relative advantages in parental education and maternal smoking were observed in both generations to a similar degree. However, a much smaller reduction in infant mortality was observed in the great-grandchildren (HR = 0.90, [0.70, 1.17]) and benefits across other outcomes were also less consistent, despite persisting socioeconomic and behavioural advantages. Lastly, maternal, and paternal lines of transmission were equipotent in the transmission of infant survival advantages.
UNASSIGNED: Descendants of longevity-enriched sibships exhibit a broad health advantage manifesting as early the perinatal period. However, this effect is strongly diluted over successive generations. Our findings suggest that exceptional health and survival may have early developmental components and implicate heritable genetic and or epigenetic factors in their specific transmission.