Alberto Hurtado Faculty of Medicine, Cayetano Heredia Peruvian University, Lima, Peru.
Department of Pediatrics, and Larsson-Rosenquist Foundation Mother-Milk-Infant Center of Research Excellence, University of California San Diego, La Jolla, CA, USA.
Am J Clin Nutr. 2020 Jul 1;112(1):106-112. doi: 10.1093/ajcn/nqaa102.
Oligosaccharides are the third most abundant component in human milk. They are a potential protective agent against neonatal sepsis.
We aimed to explore the association between human milk oligosaccharides (HMOs) and late-onset sepsis in very-low-birth-weight infants, and to describe the composition and characteristics of HMOs in Peruvian mothers of these infants.
This is a secondary data analysis of a randomized clinical trial. We conducted a retrospective cohort study of mothers and their very-low-birth-weight (<1500 g) infants with ≥1 milk sample and follow-up data for >30 d. HMOs were measured by high performance liquid chromatography (HPLC). We used factor analysis and the Mantel-Cox test to explore the association between HMOs and late-onset neonatal sepsis.
We included 153 mother-infant pairs and 208 milk samples. Overall, the frequency of the secretor phenotype was 93%. Secretors and nonsecretors were defined by the presence and near-absence of α1-2-fucosylated HMOs, respectively. The most abundant oligosaccharides were 2'-fucosyllactose, lacto-N-fucopentaose (LNFP) I, and difucosyllacto-N-tetraose in secretors and lacto-N-tetraose and LNFP II in nonsecretors. Secretors had higher amounts of total oligosaccharides than nonsecretors (11.45 g/L; IQR: 0.773 g/L compared with 8.04 g/L; IQR: 0.449 g/L). Mature milk samples were more diverse in terms of HMOs than colostrum (Simpson's Reciprocal Diversity Index). We found an association of factor 3 in colostrum with a reduced risk of late-onset sepsis (HR: 0.63; 95% CI: 0.41, 0.97). Fucosyl-disialyllacto-N-hexose (FDSLNH) was the only oligosaccharide correlated to factor 3.
These findings suggest that concentrations of different HMOs vary from one individual to another according to their lactation period and secretor status. We also found that FDSLNH might protect infants with very low birth weight from late-onset neonatal sepsis. Confirming this association could prove 1 more mechanism by which human milk protects infants against infections and open the door to clinical applications of HMOs.This trial was registered at clinicaltrials.gov as NCT01525316.
低聚糖是母乳中第三丰富的成分。它们是预防新生儿败血症的潜在保护剂。
本研究旨在探讨极低出生体重儿（VLBW）母乳低聚糖（HMOs）与晚发性败血症之间的关系，并描述秘鲁此类婴儿母亲的 HMO 组成和特征。
这是一项随机临床试验的二次数据分析。我们对有≥1 次母乳样本和＞30 d 随访数据的母亲及其 VLBW（＜1500 g）婴儿进行了回顾性队列研究。采用高效液相色谱法（HPLC）检测 HMOs。我们使用因子分析和 Mantel-Cox 检验来探讨 HMOs 与晚发性新生儿败血症之间的关系。
我们纳入了 153 对母婴和 208 份母乳样本。总体而言，分泌型表型的频率为 93%。分泌型和非分泌型是根据是否存在和几乎不存在α1-2-岩藻糖基化 HMOs 来定义的。最丰富的低聚糖分别为 2'-岩藻糖基乳糖、乳-N-岩藻五糖（LNFP）I 和二岩藻糖基乳糖-N-四糖，在分泌型中；乳-N-四糖和 LNFP II 在非分泌型中。与非分泌型相比，分泌型的总低聚糖含量更高（11.45 g/L；IQR：0.773 g/L 比 8.04 g/L；IQR：0.449 g/L）。成熟母乳样本在 HMO 方面比初乳更具多样性（HMO 辛普森倒数多样性指数）。我们发现，初乳中因子 3 与晚发性败血症风险降低相关（HR：0.63；95%CI：0.41，0.97）。岩藻糖基二唾液酸乳糖-N-六糖（FDSLNH）是唯一与因子 3 相关的低聚糖。
这些发现表明，根据泌乳期和分泌状态的不同，不同 HMOs 的浓度在个体之间存在差异。我们还发现，FDSLNH 可能保护极低出生体重儿免受晚发性新生儿败血症的影响。证实这种关联可以证明人乳保护婴儿免受感染的另一种机制，并为 HMOs 的临床应用开辟道路。该试验在 clinicaltrials.gov 上注册为 NCT01525316。
