PDF(Pubmed)
Abstract：
Human milk is optimal for infant nutrition. However, many mothers cease breastfeeding because of low milk supply (LMS). It is difficult to identify mothers at risk for LMS because its biologic underpinnings are not fully understood. Previously, we demonstrated that milk micro-ribonucleic acids (miRNAs) may be related to LMS. Transforming growth factor beta (TGFβ) also plays an important role in mammary involution and may contribute to LMS. We performed a longitudinal cohort study of 139 breastfeeding mothers to test the hypothesis that milk levels of TGFβ would identify mothers with LMS. We explored whether TGFβ impacts the expression of LMS-related miRNAs in cultured human mammary epithelial cells (HMECs). LMS was defined by maternal report of inadequate milk production, and confirmed by age of formula introduction and infant weight trajectory. Levels of TGF-β1 and TGF-β2 were measured one month after delivery. There was a significant relationship between levels of TGF-β1 and LMS (X2 = 8.92, p = 0.003) on logistic regression analysis, while controlling for lactation stage (X2 = 1.28, p = 0.25), maternal pre-pregnancy body mass index (X2 = 0.038, p = 0.84), and previous breastfeeding experience (X2 = 7.43, p = 0.006). The model accounted for 16.8% of variance in the data (p = 0.005) and correctly predicted LMS for 84.6% of mothers (22/26; AUC = 0.72). Interactions between TGF-β1 and miR-22-3p displayed significant effect on LMS status (Z = 2.67, p = 0.008). Further, incubation of HMECs with TGF-β1 significantly reduced mammary cell number (t = -4.23, p = 0.003) and increased levels of miR-22-3p (t = 3.861, p = 0.008). Interactions between TGF-β1 and miR-22-3p may impact mammary function and milk levels of TGF-β1 could have clinical utility for identifying mothers with LMS. Such information could be used to provide early, targeted lactation support.
摘要：
母乳是婴儿营养的最佳选择。然而,许多母亲停止母乳喂养，因为牛奶供应不足（LMS）。很难确定有LMS风险的母亲，因为其生物学基础尚未完全了解。以前,我们证明牛奶微核糖核酸（miRNA）可能与LMS有关。转化生长因子β（TGFβ）在乳腺退化中起重要作用，并可能导致LMS。我们对139位母乳喂养的母亲进行了一项纵向队列研究，以检验以下假设：TGFβ的牛奶水平可以识别患有LMS的母亲。我们探讨了TGFβ是否影响培养的人乳腺上皮细胞（HMEC）中LMS相关miRNA的表达。LMS由产妇报告的牛奶产量不足定义，并通过配方奶粉的年龄和婴儿体重轨迹得到证实。分娩后1个月测量TGF-β1和TGF-β2的水平。在Logistic回归分析中，TGF-β1水平与LMS之间存在显着关系（X2=8.92，p=0.003）。在控制哺乳期的同时（X2=1.28，p=0.25），孕妇孕前体重指数（X2=0.038，p=0.84），和以前的母乳喂养经验（X2=7.43，p=0.006）。该模型占数据方差的16.8％（p=0.005），并正确预测了84.6％母亲的LMS（22/26；AUC=0.72）。TGF-β1和miR-22-3p之间的相互作用对LMS状态有显著影响(Z=2.67,p=0.008)。Further,HMEC与TGF-β1的孵育显着减少了乳腺细胞数量（t=-4.23，p=0.003），并增加了miR-22-3p的水平（t=3.861，p=0.008）。TGF-β1和miR-22-3p之间的相互作用可能会影响乳腺功能，而TGF-β1的乳汁水平可能对鉴定LMS母亲具有临床实用性。这些信息可以用来提供早期，有针对性的哺乳支持。
