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Breast milk lipidome as a predictive component of postnatal growth trajectory in preterm infants. 

Marie-Cécile Alexandre-Gouabau, Thomas Moyon, Véronique  Cariou, Jean-Philippe Antignac, ElMostafa Qannari, Mikaël Croyal, Mohamed Molamine, Yann Guitton, Agnès David-Sochard, Hélène Billard, Arnaud Legrand, Cécile Boscher_, Dominique Darmaun, Clair-Yves Boquien_,  Jean-Christophe Rozé.

Early nutrition of preterm infants (7% of babies in France) is of utmost importance since early growth impacts not only brain development but also the risk of adult chronic diseases. Human milk, recommended for feeding preterm infants, is a highly complex mixture. The potential health benefits of human milk lipid species composition on infancy growth has still received little attention, merely limited to few trials, in term infants or in studies comparing breastfed and formula-fed infants.

The relationships between mass spectrometry-based lipidomics phenotyping of human breast milk and preterm babies’ growth during their hospitalization was investigated in an observational, prospective mono-centric cohort, LACTACOL. Maternal milk lipidomic signatures were performed in two groups of 13 infants (gestational age: 30.6 ± 1.5 weeks, birth weight: 1.42 ± 0.29 kg), focusing on the bottom and top deciles for the difference of weight Z-score between discharge and birth. Lipidomics data were extracted, using the workflow4metabolomics Galaxy platform, combined to normalization of batch effects by fitting regression models to quality control samples. Factor growth effect, encompassing time and mother, was assessed by an in-home multivariate statistical analysis, AoV-PLS combined to linear discriminant analysis, in the scope of biomarkers selection. The predictive ability of these biomarkers on the postnatal weight growth trajectory of the preterm infants was evaluated by multiple linear regression method, taking into account confounding factors such as infants’ birth weight, gestational age, total parenteral feeding and mother’s body mass index. Several relevant lipids biomarkers were annotated using online database searches on LIPID-Maps and an in-house reference databank.

Several fatty acids, triacylglycerol and phospholipid species were identified as predictive biomarkers to evaluate the early growth rate of breast-fed preterm infants, leading to a comprehensive view of the mechanisms by which early gestational age impacts human milk composition and consequently trajectory growth’s infants.