Nantes Université, INRAE, UMR1280 PhAN, CRNH - Ouest, IMAD, 44000 Nantes, France; Department of Neonatalogy, Nantes University Hospital, 44000 Nantes, France; Centre D'investigation Clinique 0004, INSERM - Nantes University Hospital, 44000 Nantes, France.
Clinical Research Unit, Nestle Research, Société des Produits Nestlé S.A., Vers-chez-les-Blanc, 1000 Lausanne, Switzerland.
Clin Nutr. 2022 Sep;41(9):1896-1905. doi: 10.1016/j.clnu.2022.07.024. Epub 2022 Jul 21.
BACKGROUND & AIMS: The health benefit of human milk (HM) for preterm infant development is known but the role of human milk oligosaccharides (HMOs) contained in HM remains underexplored. We explored the relationship between exposure to HMOs contained in mother's milk and growth and neurodevelopment at 2-years corrected age in preterm infants.
Exclusively breastfed preterm infants born between 27 and 34 weeks of gestation were enrolled in a monocentric prospective observational study, LACTACOL. Samples of breast milk were collected once a week for 7 weeks after birth. HMOs and sialic acid were measured by liquid chromatography. Age and Stages questionnaire (ASQ) version 2 was used to assess 2-year neurodevelopmental outcome. We analyzed the relationship between HMO content and (i) infant neurodevelopment at 2-years, and (ii) growth outcome at discharge and at 2 years. A secondary analysis was performed among Secretor(+) Lewis(+) mothers. Only associations with a false discovery rate of 10% or less according to the Benjamini-Hochberg procedure were considered significant.
137 preterm infants (mean gestational age of 31.3 ± 1.7 weeks, mean birth weight of 1494 g ± 336 g) born to 117 mothers (mean age of 30.8 ± 5.0 years) were enrolled. Total HMOs and most individual HMOs and sialic acid concentrations decreased with advancing postnatal age, except for lacto-N-fucopentaose-III and 3-fucosyllactose, which increased. Total HMOs were positively correlated with neonatal length growth (adjusted p = 0.012). Neither total HMOs nor any individual HMO correlated with ASQ score in the overall cohort. However, lacto-N-fucopentaose-III (LNFP-III) was significantly associated with total ASQ score (adjusted p ≤ 0.015) among the 104 infants born to Secretor(+) Lewis(+) mothers.
In this exploratory study in very preterm infants, total HMOs and most individual HMOs, except LNFP-III, decreased with advancing postnatal age. Neither the concentration of total HMOs nor that of any individual HMO were associated with ASQ score at 2 years, except for LNFP-III in Secretor(+) Lewis(+) mothers.
人乳（HM）对早产儿发育的健康益处是已知的，但人乳中所含的人乳寡糖（HMOs）的作用仍未得到充分探索。我们探讨了早产儿母亲人乳中 HMOs 暴露与生长和 2 岁时神经发育的关系。
本单中心前瞻性观察研究纳入了胎龄 27 至 34 周的纯母乳喂养早产儿，命名为 LACTACOL。在出生后 7 周内，每周采集一次母乳样本。通过液相色谱法测量 HMO 和唾液酸。采用年龄和阶段问卷（ASQ）第 2 版评估 2 岁时的神经发育结局。我们分析了 HMO 含量与（i）婴儿 2 岁时的神经发育，和（ii）出院时和 2 岁时的生长结局之间的关系。在 Secretor(+) Lewis(+)母亲中进行了二次分析。只有根据 Benjamini-Hochberg 程序错误发现率为 10%或更低的关联才被认为具有统计学意义。
共纳入 117 名母亲（平均年龄 30.8 ± 5.0 岁）所生的 137 名早产儿（平均胎龄 31.3 ± 1.7 周，平均出生体重 1494 ± 336 g）。总 HMOs 以及大多数 HMOs 和唾液酸的浓度随着出生后年龄的增加而降低，除了乳-N-岩藻糖五糖-III 和 3-岩藻糖基乳糖，它们的浓度随着出生后年龄的增加而增加。总 HMOs 与新生儿长度生长呈正相关（调整后 p=0.012）。在整个队列中，总 HMOs 或任何单个 HMO 均与 ASQ 评分无相关性。然而，乳-N-岩藻糖五糖-III（LNFP-III）与 104 名 Secretor(+) Lewis(+) 母亲所生婴儿的总 ASQ 评分显著相关（调整后 p ≤ 0.015）。
在这项针对极早产儿的探索性研究中，总 HMOs 和大多数 HMOs（除 LNFP-III 外）随着出生后年龄的增加而降低。总 HMOs 浓度和任何单个 HMOs 浓度均与 2 岁时的 ASQ 评分无关，除了 Secretor(+) Lewis(+) 母亲中的 LNFP-III 与总 ASQ 评分有关。
