The Effect of Gestational and Lactational Age on the Human Milk Metabolome

Abstract

Human milk is the ideal nutrition source for healthy infants during the first six months of life and a detailed characterisation of the composition of milk from mothers that deliver prematurely (<37 weeks gestation), and of how human milk changes during lactation, would benefit our understanding of the nutritional requirements of premature infants. Individual milk samples from mothers delivering prematurely and at term were collected. The human milk metabolome, established by nuclear magnetic resonance (NMR) spectroscopy, was influenced by gestational and lactation age. Metabolite profiling identified that levels of valine, leucine, betaine, and creatinine were increased in colostrum from term mothers compared with mature milk, while those of glutamate, caprylate, and caprate were increased in mature term milk compared with colostrum. Levels of oligosaccharides, citrate, and creatinine were increased in pre-term colostrum, while those of caprylate, caprate, valine, leucine, glutamate, and pantothenate increased with time postpartum. There were differences between pre-term and full-term milk in the levels of carnitine, caprylate, caprate, pantothenate, urea, lactose, oligosaccharides, citrate, phosphocholine, choline, and formate. These findings suggest that the metabolome of pre-term milk changes within 5–7 weeks postpartum to resemble that of term milk, independent of time of gestation at pre-mature delivery.

Clinical Metabolomics in Neonatology: From Metabolites to Diseases

“…Thus, the finding of both betaine and choline and its derivatives in colostrum of preterm neonates in the study of Sundekilde et al [36], as well as the discovery of an increase of glycerophosphocholine in the first 3 months of lactation highlighted by Andreas et al [37], support the hypothesis of the importance of these 2 metabolites for the survival and growth of preterm neonates. In a recent study by Marincola et al [4] an age-dependent modification of the urine metabolome was observed in term neonates, mainly characterized by similar temporal trends of choline and betaine.…”

Breastmilk Metabolomics: Bridging the Gap between Maternal Nutrition and Infant Health Outcomes

“…With most compounds having hydrogen, ¹H-NMR provides a robust approach in the detection and identification of various metabolites (Savorani et al, 2013), thus several BM metabolomic studies have employed this technique (Smilowitz et al, 2013;Praticò et al, 2016;Longini et al, 2014;Sundekilde et al, 2016;Wu et al, 2016). Unlike MS-based techniques, NMR is nondestructive allowing preservation of metabolites for multiple analysis (Ryan et al, 2013).…”

“…One of the strengths of NMR-based metabolomics is that it can provide structural and quantitative information on the metabolite which facilitates identification of unknown metabolites, a major hurdle in metabolomics (Brennan, 2016). A major drawback of NMR-based techniques is the lack of sensitivity making detection of low abundance metabolites difficult (Brennan, 2016;Sundekilde et al, 2016).…”

“…Using ¹H-NMR spectroscopy, Sundekilde et al (2016) identified differences in BM metabolite profiles in women of different gestational and lactational ages. The levels of valine, leucine, betaine, and creatinine were found to be elevated in colostrum from term mothers compared with mature milk.…”

Impacto da implementação da Iniciativa Hospital Amigo da Criança para Unidades Neonatais - IHAC-Neo na prevalência do aleitamento materno exclusivo em prematuros e nas práticas assistenciais

“…Além disso, existem diferenças específicas e significativas entre o leite das mães de prematuros e de bebês a termo (GROSS et al, 1980;BOBINSKI et al, 2013;SUNDEKILDE et al, 2016). A produção de leite materno é altamente sensível às necessidades específicas do filho RN (GROSS et al, 1980;BOBINSKI et al, 2013), sugerindo que a composição do leite materno pode ser fortemente moldada pela idade gestacional e peso do neonato (BOBINSKI et al, 2013).…”