Kadam Isma'il, Nebie Chauntelle, Dalloul Mudar, Saxena Anjana, Fordjour Lawrence, Hoepner Lori, Jiang Xinyin
PhD Program in Biochemistry, Graduate Center of the City University of New York, New York, NY 10016, USA; Department of Health and Nutrition Sciences, Brooklyn College of the City University of New York, Brooklyn, NY 11210, USA.
Department of Health and Nutrition Sciences, Brooklyn College of the City University of New York, Brooklyn, NY 11210, USA.
Clin Nutr. 2025 Sep;52:179-188. doi: 10.1016/j.clnu.2025.07.027. Epub 2025 Jul 31.
BACKGROUND & AIMS: Gestational diabetes mellitus (GDM) is associated with increased risks of fetal overgrowth, possibly due to the increased transport of macronutrients from the placenta to the GDM-exposed fetus. Maternal choline supplementation in obese mice normalizes placental fat and glucose transport and prevents fetal overgrowth. In this study, we aimed to determine the correlation of choline intake and metabolite status with fetal growth outcomes and placental macronutrient metabolism and transport in pregnancies with and without GDM.
In this prospective study, we recruited women with (n = 40) and without (n = 36) GDM at 25-33 weeks gestation and assessed their choline intake and blood choline metabolite concentrations. We also collected placenta and cord blood samples from a subset of participants (21 GDM and 26 non-GDM) at delivery to examine placental macronutrient metabolism and transport.
Our results demonstrated that a higher maternal choline intake was associated with lower placental mRNA expression of glucose transporter 3 (GLUT3) (β = -0.002, p = 0.012) in non-GDM pregnancies and leptin (LEP) (β = -0.02, p = 0.034) in GDM pregnancies, respectively. Both maternal blood (β = -77.97, p = 0.03) and placental (β = -0.38, p = 0.049) glycerophosphorylcholine (GPC) concentrations were negatively associated with infant birthweight regardless of GDM status. Maternal GPC concentrations were also negatively associated with placental triglyceride concentrations (β = -0.18, p = 0.017) and cord blood triglyceride (β = -11.1, p = 0.014) and free fatty acid (β = -39.6, p = 0.034) contents, while placental GPC concentrations were negatively associated with fatty acid transporter 1 (FATP1) mRNA expression (β = -1.38E-4, p = 0.036) in all participants. Lipidomics profiling demonstrated that maternal choline intake was negatively associated with concentrations of triglyceride species in the placenta regardless of GDM status.
In conclusion, maternal choline intakes demonstrated negative associations with placental macronutrient transporters and triglyceride contents. GPC concentrations seem to be a consistent indicator of reduced placental-fetal fat transport and eventually lower birth weight. These observations suggest the potential of using choline to alleviate GDM-related excess in transplacental fat transport and fetal overgrowth.
妊娠期糖尿病（GDM）与胎儿过度生长风险增加相关，这可能是由于从胎盘到暴露于GDM的胎儿的大量营养素转运增加所致。在肥胖小鼠中补充母体胆碱可使胎盘脂肪和葡萄糖转运正常化，并防止胎儿过度生长。在本研究中，我们旨在确定在有和没有GDM的妊娠中，胆碱摄入量和代谢物状态与胎儿生长结局以及胎盘大量营养素代谢和转运之间的相关性。
在这项前瞻性研究中，我们招募了妊娠25 - 33周的患有GDM（n = 40）和未患有GDM（n = 36）的女性，并评估了她们的胆碱摄入量和血液胆碱代谢物浓度。我们还在分娩时从一部分参与者（21例GDM和26例非GDM）中收集了胎盘和脐血样本，以检查胎盘大量营养素代谢和转运情况。
我们的结果表明，在非GDM妊娠中，较高的母体胆碱摄入量分别与葡萄糖转运蛋白3（GLUT3）的胎盘mRNA表达降低（β = -0.002，p = 0.012）相关，在GDM妊娠中与瘦素（LEP）的胎盘mRNA表达降低（β = -0.02，p = 0.034）相关。无论GDM状态如何，母体血液（β = -77.97，p = 0.03）和胎盘（β = -0.38，p = 0.049）甘油磷酸胆碱（GPC）浓度均与婴儿出生体重呈负相关。母体GPC浓度还与胎盘甘油三酯浓度（β = -0.18，p = 0.017）、脐血甘油三酯（β = -11.1，p = 0.014）和游离脂肪酸（β = -39.6，p = 0.034）含量呈负相关，而胎盘GPC浓度在所有参与者中与脂肪酸转运蛋白1（FATP1）的mRNA表达呈负相关（β = -1.38E - 4，p = 0.036）。脂质组学分析表明，无论GDM状态如何，母体胆碱摄入量与胎盘中甘油三酯种类的浓度呈负相关。
总之，母体胆碱摄入量与胎盘大量营养素转运蛋白和甘油三酯含量呈负相关。GPC浓度似乎是胎盘 - 胎儿脂肪转运减少以及最终出生体重降低的一致指标。这些观察结果表明，使用胆碱减轻与GDM相关的经胎盘脂肪转运过多和胎儿过度生长具有潜力。
