Detection of Vitamin D Metabolites in Breast Milk: Perspectives and challenges for measurement by Liquid Chromatography Tandem-Mass Spectrometry

Breast milk is an emerging matrix for vitamin D assessment of breastfed infants and their mothers. It is considered a more reliable indicator of infant intake than the assessment of maternal circulating vitamin D. With the improved sensitivity of mass spectrometry-based technologies, this method principle has been the recent mainstay for the quantitation of various vitamin D metabolites in breast milk for population-based clinical trials. There are still several areas across the total testing process (pre-analytical, analytical and post-analytical) to be defined and harmonised to translate breast milk vitamin D measurement by liquid chromatography-tandem mass spectrometry (LC-MS/MS) from population-based research to routine clinical use and public health applications. Pre-analytically, the determination of the best form of vitamin D to measure in breast milk requires more evidence. Analytically, standardisation of the methods to allow for comparability of results is required. Post analytically, breast milk vitamin D decision limits are needed to turn the individual numerical outputs into clinically meaningful results. This review aims to synthesise the current evidence and utility of measurement of breast milk vitamin D by LC-MS/MS and to lead a future discussion on best practices to allow for its clinical utility beyond its current research-based use.