Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan, United States.
Section of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
Am J Clin Nutr. 2024 Nov;120(5):1156-1164. doi: 10.1016/j.ajcnut.2024.07.003. Epub 2024 Oct 9.
Maternal obesity increases risk of infant mortality. Because obesity is highly inheritable, grandmaternal obesity could also play a role. However, it is unknown whether grandmaternal obesity is related to grandoffspring infant mortality risk.
We investigated the associations of grandmaternal early pregnancy body mass index [BMI (in kg/m)] and grandoffspring infant mortality risk.
Using Swedish nationwide registers, we estimated infant mortality hazard ratios (HRs) by levels of maternal grandmaternal early pregnancy BMI among 315,461 singleton live-born grandoffspring. We examined whether the association was mediated through maternal body size. In a subset of 164,095 grandsoffspring we evaluated the role of paternal grandmaternal BMI. To explore whether factors shared within families explained these associations, we studied the relations of maternal or paternal full sisters' BMI and infant mortality.
Maternal grandmaternal overweight or obesity (BMI ≥ 25.0) was associated with increased grandoffspring infant mortality risk. Compared with the population median BMI (21.7), estimated adjusted hazard ratios [HRs (95% confidence interval [CI])] of grandoffspring mortality for BMI 25.0 and 30.0 were, respectively, 1.60 (1.14, 2.23) and 1.61 (1.13, 2.27). Maternal high birth weight-for-gestational age and early pregnancy obesity (BMI ≥ 30.0) were also associated with increased infant mortality risk. The association between maternal grandmaternal overweight or obesity and grandoffspring infant mortality was mostly (62%) mediated through maternal overweight or obesity. Maternal sisters' BMI was unrelated to infant mortality. Paternal grandmaternal obesity was associated with increased infant mortality risk (HR [95% CI] for BMI 30.0 compared with 21.7: 1.65 [1.02, 2.67]); associations with paternal sisters' BMI were not statistically significant.
Maternal grandmaternal overweight or obesity is associated with increased risk of grandoffspring infant mortality; factors shared within families may not play a major role. The association is mediated through the maternal early pregnancy BMI. Whether the association with paternal grandmaternal BMI is explained by shared familial factors warrants future confirmation.
母体肥胖会增加婴儿死亡率。由于肥胖具有高度遗传性，祖母肥胖也可能起到一定作用。然而，尚不清楚祖母肥胖是否与孙代婴儿死亡率风险相关。
我们研究了祖母早孕时的体重指数（BMI，单位为 kg/m）与孙代婴儿死亡率风险之间的关系。
我们利用瑞典全国性登记处的数据，在 315461 例单胎活产孙代中，根据母亲的祖母早孕 BMI 水平估计了婴儿死亡率的危险比（HR）。我们研究了这种关联是否通过母体大小来介导。在 164095 例孙辈中，我们评估了祖父祖母 BMI 的作用。为了探究家族内共享的因素是否可以解释这些关联，我们研究了母亲或父亲全姐妹的 BMI 与婴儿死亡率的关系。
超重或肥胖的祖母（BMI≥25.0）与孙代婴儿死亡率风险增加相关。与人群中 BMI 的中位数（21.7）相比，BMI 为 25.0 和 30.0 的孙代死亡的校正后 HR（95%置信区间[CI]）分别为 1.60（1.14，2.23）和 1.61（1.13，2.27）。母亲巨大儿（出生体重与胎龄不符）和早孕肥胖（BMI≥30.0）也与婴儿死亡率风险增加相关。母亲的祖母超重或肥胖与孙代婴儿死亡率之间的关联主要（62%）通过母亲超重或肥胖来介导。母亲姐妹的 BMI 与婴儿死亡率无关。祖父的祖母肥胖与婴儿死亡率风险增加相关（与 BMI 21.7 相比，BMI 为 30.0 的 HR：1.65[1.02，2.67]）；与父亲姐妹的 BMI 没有统计学上的显著关联。
母亲的祖母超重或肥胖与孙代婴儿死亡率风险增加相关；家族内共享的因素可能不起主要作用。这种关联通过母亲早孕 BMI 来介导。祖父祖母 BMI 与孙代婴儿死亡率之间的关联是否可以通过家族内的共享因素来解释，尚有待未来的证实。
