Centre for Fertility and Health, Norwegian Institute of Public Health, P.O. Box 222 Skøyen, Oslo, 0213, Norway.
Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
BMC Med. 2024 Nov 25;22(1):554. doi: 10.1186/s12916-024-03780-7.
Few studies have examined associations between maternal epigenetic age acceleration and adverse birth outcomes, and none have investigated paternal epigenetic age acceleration. Our objective was to assess the associations of parental (both maternal and paternal) epigenetic age acceleration in relation to birth outcomes.
Parental epigenetic age was estimated using seven established epigenetic clocks in 2198 mothers and 2193 fathers from the Norwegian Mother, Father, and Child Cohort Study (MoBa). Individual epigenetic age acceleration was then calculated as residuals from linear regressions of estimates from the epigenetic clocks on chronological age. Further, linear regression was used to analyze differences in continuous outcomes (gestational length and standardized birthweight), while logistic regression was used for binary outcomes (preterm birth, post-term birth, small-for-gestational age [SGA], large-for-gestational age [LGA], and pre-eclampsia), adjusting for chronological age, parity, educational level, smoking, and BMI.
Increasing maternal, but not paternal, epigenetic age acceleration was associated with decreased gestational length for five out of six clocks, with adjusted estimates ranging from a mean 0.51-day decrease (95% CI - 1.00, - 0.02; p-value 0.043) for the Horvath clock to a 0.80-day decrease (95% CI - 1.29, - 0.31; p-value 0.002) for the Levine clock. An association with increasing maternal epigenetic age acceleration according to the DunedinPACE clock was also seen with greater standardized birthweight [mean difference 0.08 (95% CI 0.04, 0.12; p-value < 0.001]. These results were also reflected in an increased risk of spontaneous preterm birth and LGA. No associations were observed with post-term birth, SGA, or pre-eclampsia.
Maternal, but not paternal, epigenetic age acceleration is associated with shorter pregnancies and an increased risk of spontaneous preterm birth. This may suggest that women's biological age acceleration, including factors such as metabolic and physiologic state, is an additional risk factor for preterm delivery, beyond chronological age.
很少有研究探讨母体表观遗传年龄加速与不良出生结局之间的关系，也没有研究过父系表观遗传年龄加速。我们的目的是评估父母（母亲和父亲）的表观遗传年龄加速与出生结局的关系。
在挪威母亲、父亲和儿童队列研究（MoBa）中，2198 名母亲和 2193 名父亲使用七种已建立的表观遗传时钟来估计父母的表观遗传年龄。然后，通过线性回归从表观遗传时钟的估计值中减去对年龄的残差来计算个体的表观遗传年龄加速。进一步，使用线性回归分析连续结局（ gestational length 和标准化出生体重）的差异，而使用逻辑回归分析二分类结局（早产、过期产、小于胎龄儿[SGA]、大于胎龄儿[LGA]和子痫前期），调整年龄、产次、教育程度、吸烟和 BMI。
在六种时钟中，有五种时钟显示母体表观遗传年龄加速与妊娠期缩短有关，经过调整的估计值范围从 Horvath 时钟的平均减少 0.51 天（95%CI-1.00，-0.02;p 值 0.043）到 Levine 时钟的 0.80 天减少（95%CI-1.29，-0.31;p 值 0.002）。DunedinPACE 时钟也显示母体表观遗传年龄加速与标准化出生体重增加有关[平均差异 0.08（95%CI 0.04，0.12;p 值<0.001]。这些结果也反映在自发性早产和 LGA 的风险增加上。与过期产、SGA 或子痫前期无关。
母体表观遗传年龄加速与妊娠时间缩短和自发性早产风险增加有关。这可能表明，女性的生物年龄加速，包括代谢和生理状态等因素，是除年龄以外早产的另一个危险因素。
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