Breast Milk Lipidome Is Associated with Early Growth Trajectory in Preterm Infants

Abstract

Human milk is recommended for feeding preterm infants. The current pilot study aims to determine whether breast-milk lipidome had any impact on the early growth-pattern of preterm infants fed their own mother's milk. A prospective-monocentric-observational birth-cohort was established, enrolling 138 preterm infants, who received their own mother's breast-milk throughout hospital stay. All infants were ranked according to the change in weight Z-score between birth and hospital discharge. Then, we selected infants who experienced "slower" (n = 15, -1.54 ± 0.42 Z-score) or "faster" (n = 11, -0.48 ± 0.19 Z-score) growth; as expected, although groups did not differ regarding gestational age, birth weight Z-score was lower in the "faster-growth" group (0.56 ± 0.72 vs. -1.59 ± 0.96). Liquid chromatography-mass spectrometry lipidomic signatures combined with multivariate analyses made it possible to identify breast-milk lipid species that allowed clear-cut discrimination between groups. Validation of the selected biomarkers was performed using multidimensional statistical, false-discovery-rate and ROC (Receiver Operating Characteristic) tools. Breast-milk associated with faster growth contained more medium-chain saturated fatty acid and sphingomyelin, dihomo-γ-linolenic acid (DGLA)-containing phosphethanolamine, and less oleic acid-containing triglyceride and DGLA-oxylipin. The ability of such biomarkers to predict early-growth was validated in presence of confounding clinical factors but remains to be ascertained in larger cohort studies.

Keywords: breast milk lipidome; growth trajectory; preterm infant.

Figure 1

Flowchart of infants enrolled in the ancillary study of the mono-centric prospective population-based LACTACOL. (ClinicalTrials.gov Identifier: NCT01493063, acronyme for “Impact of Breast Milk on the Neurodevelopment of Preterm Newborns").

Figure 2

Statistical workflow applied on breast-milk Liquid Chromatography–High-Resolution-Mass Spectrometry profiles obtained in positive and negative ionization mode.

Figure 3

Multi-group PLS-DA score plots based on the LC-ESI⁺-HRMS profiles (3451 features, 118 milks) obtained on human preterm milk. Representation of the individuals: milk provided to preterm infants who experienced “faster” (orange) or “slower” (blue) growth from Week 2 to Week 7 of lactation. MB-PLS-DA score plots: ○ Week 2; ∆ Week 3; + Week 4; × Week 5; ◊ Week 6; ∇ Week 7.

Figure 4

AoV-PLS and LDA models, based on the LC-ESI⁺-HRMS profiles of human preterm milk, on the factor weight Z-score (discharge-birth): AoV-PLS score plot with 45% of variance (R2Y = 38%) on: components 1–2 (a); and LDA (built on 10 components of AoV-PLS) with a p-value = 0) (b). Breast milk provided to preterm infants who experienced “faster” (green) or “slower” (red) growth and to twin infants with discordant growth rate, one with high growth rate and one with low growth rate, (blue).

Figure 5

Scatter plot and ROC plot analysis using lipids biomarkers abundance (SM (d18:0/12:0), TG (18:0/18:1/18:1), PE (O-18:0/20:5), PE (20:3/22:6), MCSAT and one deoxy-dimethyl-PGE2) in breast milk provided to preterm infants who experienced “faster” (black triangle, F group) versus “slower” (white triangle, S group) growth during hospital stay. Scatter plot (median): from w2 to w4 of lactation period; ROC plot: over the entire W2–W4 lactation period. ▲ Faster growth group (F); Δ slower growth group (S).