Zhu Yiyang, Zhang Hao, Qi Jike, Liu Yuxin, Yan Yu, Wang Ting, Zeng Ping
Department of Biostatistics, School of Public Health, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China.
Center for Medical Statistics and Data Analysis, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China.
SSM Popul Health. 2023 Dec 23;25:101587. doi: 10.1016/j.ssmph.2023.101587. eCollection 2024 Mar.
Although extensive discussions on the influence of maternal educational attainment on offspring birthweight, the conclusion remains controversial, and it is challenging to comprehensively assess the causal association between them.
To estimate effect of maternal educational attainment on the birthweight of first child, we first conducted an individual-level analysis with UK Biobank participants of white ancestry ( = 208,162). We then implemented Mendelian randomization (MR) methods including inverse variance weighted (IVW) MR and multivariable MR to assess the causal relation between maternal education and maternal-specific birthweight. Finally, using the UK Biobank parent-offspring trio data ( = 618), we performed a polygenic score based MR to simultaneously adjust for confounding effects of fetal-specific birthweight and paternal educational attainment. We also conducted simulations for power evaluation and sensitivity analyses for horizontal pleiotropy of instruments.
We observed that birthweight of first child was positively influenced by maternal education, with 7 years of maternal education as the reference, adjusted effect = 44.8 (95%CIs 38.0-51.6, = 6.15 × 10), 54.9 (95%CIs 47.6-62.2, = 4.21 × 10), and 89.4 (95%CIs 82.1-96.7, = 4.28 × 10) for 10, 15 and 20 years of maternal educational attainment, respectively. A causal relation between maternal education and offspring birthweight was revealed by IVW MR (estimated effect = 0.074 for one standard deviation increase in maternal education years, 95%CIs 0.054-0.093, = 2.56 × 10) and by complementary MR methods. This connection was not substantially affected by paternal education or horizontal pleiotropy. Further, we found a positive but insignificant causal association (adjusted effect = 24.0, 95%CIs -150.1-198.1, = 0.787) between maternal education and offspring birthweight after simultaneously controlling for fetal genome and paternal education; this null causality was largely due to limited power of small sample sizes of parent-offspring trios.
This study offers supportive evidence for a causal association between maternal education and offspring birthweight, highlighting the significance of enhancing maternal education to prevent low birthweight.
尽管关于母亲教育程度对后代出生体重的影响已进行了广泛讨论，但结论仍存在争议，全面评估两者之间的因果关系具有挑战性。
为了估计母亲教育程度对第一个孩子出生体重的影响，我们首先对英国生物银行中白人血统的参与者（n = 208,162）进行了个体水平分析。然后，我们采用孟德尔随机化（MR）方法，包括逆方差加权（IVW）MR和多变量MR，以评估母亲教育程度与母亲特定出生体重之间的因果关系。最后，利用英国生物银行的亲子三联体数据（n = 618），我们进行了基于多基因评分的MR分析，以同时调整胎儿特定出生体重和父亲教育程度的混杂效应。我们还进行了功效评估模拟和对工具水平多效性的敏感性分析。
我们观察到，以母亲7年教育为参照，母亲教育程度对第一个孩子的出生体重有正向影响，母亲教育年限为10年、15年和20年时，调整后的效应分别为44.8（95%置信区间38.0 - 51.6，P = 6.15×10⁻⁶）、54.9（95%置信区间47.6 - 62.2，P = 4.21×10⁻⁶）和89.4（95%置信区间82.1 - 96.7，P = 4.28×10⁻⁶）。IVW MR（母亲教育年限每增加一个标准差，估计效应 = 0.074，95%置信区间0.054 - 0.093，P = 2.56×10⁻⁶）和其他补充MR方法揭示了母亲教育程度与后代出生体重之间的因果关系。这种联系不受父亲教育程度或水平多效性的实质性影响。此外，在同时控制胎儿基因组和父亲教育程度后，我们发现母亲教育程度与后代出生体重之间存在正向但不显著的因果关联（调整后的效应 = 24.0，95%置信区间 - 150.1 - 198.1，P = 0.787）；这种零因果关系主要是由于亲子三联体样本量小导致功效有限。
本研究为母亲教育程度与后代出生体重之间的因果关联提供了支持性证据，强调了提高母亲教育程度以预防低出生体重的重要性。
