Xing Y, Yu X, Zhu J, Chang Y M, You Y X, Chen Z K, Dou Y Q, Ma D F, Tong X M
Department of Pediatrics, Peking University Third Hospital, Beijing 100191, China.
Department of Social Medicine and Health Education,School of Public Health, Peking University, Beijing 100191,China.
Zhonghua Yu Fang Yi Xue Za Zhi. 2021 Sep 6;55(9):1067-1076. doi: 10.3760/cma.j.cn112150-20210513-00468.
To investigate the human milk oligosaccharides (HMOs) levels in breast milk of mothers delivering preterm infants and their effects on the early growth and development of infants. In this prospective cohort study, full-term and preterm newborns whose parents decided to breastfeed were recruited from Peking University Third Hospital between December 1, 2017 and November 30, 2018. The preterm infants were divided based on their gestational ages into extremely preterm (<28 weeks), very preterm (28-31 weeks) and moderate to late preterm (32-36 weeks) groups. Breast milk was collected from mothers at 7, 14, 28 and 120d postpartum. 368 breast milk samples were collected from 125 mothers in this study, including 54 mothers of full-term infants, 23 mothers of moderate to late preterm infants, 39 mothers of very preterm infants, and 9 mothers of extremely preterm infants. Ultra-performance liquid chromatography-mass spectrometer (UPLC-MS/MS) was used to determine the concentration of 2'-fucosyllactose (2'FL), 3-fucosyllactose (3FL), 3'-sialyllactose (3'SL), A-tetrasaccharide (P1), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), lacto-N-fucopentaose Ⅱ (LNFP-Ⅱ) and lacto-N-fucopentaose Ⅴ (LNFP-Ⅴ). Secretor status of mothers was defined as 2'-fucosyllactose (2'FL) concentration in colostrum and transitional milk greater than 200 μg/mL. Weight gain and the occurrence of allergic diseases of infants were collected at 120 d(4 months) postpartum. The chi-square test or the Fisher's exact test was used for the comparison of categorical data between groups; Kruskal-Wallis test and Wilcoxon rank sum test were used for comparison of continuous data between groups. Nemenyi test was used for multiple comparison. 79.2% (99/125) of the mothers were secretor. There were no statistical differences between groups in the secretor status of mothers (χ²=1.31,>0.05). The total concentration of HMOs peaked at 1-2 weeks postpartum. Compared to the preterm milk, the HMOs from the term milk was trending downwards at an earlier time. In the breast milk of secretor mothers on 28 d, total concentration of HMOs significant differed among the three groups of preterm milk and the term milk, with the median value of 4 587.09,4 615.25,5 277.44,5 476.03 μg/mL, respectively (Kruskal-Wallis χ²=8.1234,=0.044). When analyzed by the median weight gain of the infants (low high weight gain) at 4 months postpartum, 2'FL was significantly lower in the high weight gain group at 7 d (1 818.04 μg/mL 2 181.67 μg/mL, W=1 386,=0.018), while LNT & LNnT were significantly higher (1 182.36 μg/mL 1 053.62 μg/mL, W=816,=0.044). The level of 3FL at 120 d was significantly affected by presence of allergic disease in infants, breast milk from mothers of infants with allergic disease had lower 3FL than those from mothers of infants without allergic disease (256.17 μg/mL 286.18 μg/mL, W=564,=0.026). The overall profiles of HMOs in breast milk of mothers delivering preterm infants was basically the same as that of mothers delivering term infants; individual HMOs play a role in weight gain and the development of allergic diseases in preterm infants, but the mechanism is unclear and needs further study.
探讨早产产妇母乳中母乳低聚糖(HMOs)水平及其对婴儿早期生长发育的影响。在这项前瞻性队列研究中,2017年12月1日至2018年11月30日期间,从北京大学第三医院招募了父母决定进行母乳喂养的足月和早产新生儿。将早产儿根据胎龄分为极早产儿(<28周)、极早早产儿(28 - 31周)和中晚期早产儿(32 - 36周)组。在产后7、14、28和120天收集母亲的母乳。本研究从125名母亲中收集了368份母乳样本,包括54名足月婴儿的母亲、23名中晚期早产儿的母亲、39名极早早产儿的母亲和9名极早产儿的母亲。采用超高效液相色谱 - 质谱联用仪(UPLC - MS/MS)测定2'-岩藻糖基乳糖(2'FL)、3-岩藻糖基乳糖(3FL)、3'-唾液酸乳糖(3'SL)、A-四糖(P1)、乳糖 - N-四糖(LNT)、乳糖 - N-新四糖(LNnT)、乳糖 - N-岩藻五糖Ⅱ(LNFP - Ⅱ)和乳糖 - N-岩藻五糖Ⅴ(LNFP - Ⅴ)的浓度。母亲的分泌型状态定义为初乳和过渡乳中2'-岩藻糖基乳糖(2'FL)浓度大于200μg/mL。在产后120天(4个月)收集婴儿的体重增加情况和过敏性疾病的发生情况。采用卡方检验或Fisher精确检验比较组间分类数据;采用Kruskal - Wallis检验和Wilcoxon秩和检验比较组间连续数据。采用Nemenyi检验进行多重比较。79.2%(99/125)的母亲为分泌型。母亲的分泌型状态在组间无统计学差异(χ² = 1.31,P>0.05)。HMOs的总浓度在产后1 - 2周达到峰值。与早产母乳相比,足月母乳中的HMOs在更早的时间呈下降趋势。在产后28天分泌型母亲的母乳中,三组早产母乳和足月母乳中HMOs的总浓度存在显著差异,中位数分别为4587.09、4615.25、5277.44、5476.03μg/mL(Kruskal - Wallis χ² = 8.12.1234,P = 0.044)。当按产后4个月婴儿的中位数体重增加情况(低体重增加 高体重增加)进行分析时,高体重增加组在7天时2'FL显著较低(1818.04μg/mL对2181.67μg/mL,W = 1386,P = 0.018),而LNT和LNnT显著较高(1182.36μg/mL对1053.62μg/mL,W = 816,P = 0.044)。120天时3FL的水平受婴儿过敏性疾病的显著影响,患有过敏性疾病婴儿的母亲的母乳中3FL低于未患过敏性疾病婴儿的母亲(256.17μg/mL对286.18μg/mL,W = 564,P = 0.026)。早产产妇母乳中HMOs的总体概况与足月产妇母乳基本相同;个别HMOs在早产儿体重增加和过敏性疾病发生中起作用,但其机制尚不清楚,需要进一步研究。