School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK.
Harris Birthright Research Centre for Fetal Medicine, Fetal Medicine Research Institute, King's College Hospital, London, UK.
Am J Obstet Gynecol. 2020 Aug;223(2):246.e1-246.e10. doi: 10.1016/j.ajog.2020.01.054. Epub 2020 Feb 1.
Maternal obesity increases the risk for pregnancy complications and adverse neonatal outcome and has been associated with long-lasting adverse effects in the offspring, including increased body fat mass, insulin resistance, and increased risk for premature cardiovascular disease. Lifestyle interventions in pregnancy have produced no or modest effects in the reduction of adverse pregnancy outcomes in obese mothers. The Metformin in Obese Pregnant Women trial was associated with reduced adverse pregnancy outcomes and had no effect on birthweight. However, the long-term implications of metformin on the health of offspring remain unknown.
The purpose of this study was to assess whether prenatal exposure to metformin can improve the cardiovascular profile and body composition in the offspring of obese mothers.
In 151 children from the Metformin in Obese Pregnant Women trial, body composition, peripheral blood pressure, and arterial pulse wave velocity were measured. Central hemodynamics (central blood pressure and augmentation index) were estimated with the use of an oscillometric device. Left ventricular cardiac function and structure were assessed by echocardiography.
Children were 3.9±1.0 years old, and 77 of them had been exposed to metformin prenatally. There was no significant difference in peripheral blood pressure, arterial stiffness, and body composition apart from gluteal and tricep circumferences, which were lower in the metformin group (P<.05). The metformin group, compared with the placebo group, had lower central hemodynamics (mean adjusted decrease, -0.707 mm Hg for aortic systolic blood pressure, -1.65 mm Hg for aortic pulse pressure, and -2.68% for augmentation index; P<.05 for all) and lower left ventricular diastolic function (adjusted difference in left atrial area, -0.525 cm, in isovolumic relaxation time, -0.324 msec, and in pulmonary venous systolic wave, 2.97 cm/s; P<.05 for all). There were no significant differences in metabolic profile between the groups.
Children of obese mothers who were exposed prenatally to metformin, compared with those who were exposed to placebo, had lower central hemodynamic and cardiac diastolic indices. These results suggest that the administration of metformin in obese pregnant women potentially may have a beneficial cardiovascular effect for their offspring.
母体肥胖会增加妊娠并发症和不良新生儿结局的风险，并与后代的长期不良影响相关，包括体脂增加、胰岛素抵抗以及早发性心血管疾病风险增加。在肥胖母亲中，孕期生活方式干预对减少不良妊娠结局并没有产生影响或影响甚微。二甲双胍治疗肥胖孕妇试验与降低不良妊娠结局相关，且对出生体重没有影响。然而，二甲双胍对后代健康的长期影响仍不清楚。
本研究旨在评估孕期暴露于二甲双胍是否能改善肥胖母亲所生孩子的心血管特征和身体成分。
在二甲双胍治疗肥胖孕妇试验中的 151 名儿童中，测量了身体成分、外周血压和动脉脉搏波速度。使用振荡测量设备估计中心血液动力学（中心血压和增强指数）。通过超声心动图评估左心室心脏功能和结构。
儿童的年龄为 3.9±1.0 岁，其中 77 名儿童在孕期接受了二甲双胍治疗。除臀围和三头肌围较小外（P<.05），两组之间的外周血压、动脉僵硬度和身体成分无显著差异。与安慰剂组相比，二甲双胍组的中心血液动力学较低（主动脉收缩压平均校正下降 0.707mmHg，主动脉脉压下降 1.65mmHg，增强指数下降 2.68%；所有 P<.05），左心室舒张功能较低（左心房面积校正差异为 0.525cm，等容舒张时间校正差异为 0.324msec，肺静脉收缩波校正差异为 2.97cm/s；所有 P<.05）。两组之间的代谢特征无显著差异。
与接受安慰剂治疗的肥胖母亲所生孩子相比，孕期接受二甲双胍治疗的肥胖母亲所生孩子的中心血液动力学和心脏舒张指数较低。这些结果表明，在肥胖孕妇中使用二甲双胍可能对其后代有有益的心血管作用。
