The mothers, infants, and lactation quality (MILQ) study: A multi-center collaboration

Authors: Allen, Lindsay - A; HAMPEL, DANIELA - University Of California, Davis; Shahab-Ferdows, Setti; ANDERSSON, MARIA - University Hospital Zurich; BARROS, ERICA - Universidade Federal Do Rio De Janeiro; DOEL, ANDREW - King'S College; ERIKSEN, KAMILLA - University Of Copenhagen; CHRISTENSEN, SOPHIE HILARIO - University Of Copenhagen; ISLAM, MUNIRUL - International Centre For Diarrhoeal Disease Research; KAC, GILBERTO - Universidade Federal Do Rio Grande Do Norte (UFRN); KEYA, FARHANA - International Centre For Diarrhoeal Disease Research; MICHAELSEN, KIM - University Of Copenhagen; MUCCI, DANIELA - Universidade Federal Do Rio De Janeiro; NJIE, FANTA - London School Of Hygiene & Tropical Medicine; PEERSON, JANET - Eg Consulting (SELF-EMPLOYED); MOORE, SOPHIE - King'S College

Submitted to: Current Developments in Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/7/2021
Publication Date: 9/20/2021
Citation: Allen, L.H., Hampel, D., Shahab-Ferdows, S., Andersson, M., Barros, E., Doel, A., Eriksen, K.G., Christensen, S., Islam, M., Kac, G., Keya, F.K., Michaelsen, K., Mucci, D., Njie, F., Peerson, J., Moore, S.E. 2021. The mothers, infants, and lactation quality (MILQ) study: A multi-center collaboration. Current Developments in Nutrition. 5(10). Article nzab116. https://doi.org/10.1093/cdn/nzab116.
DOI: https://doi.org/10.1093/cdn/nzab116

Interpretive Summary: Exclusive breastfeeding (EBF) is recommended by the World Health Organization (WHO) for infants’ first 6 months of life. Besides being the sole recommended nutrient source during this time, human milk is a crucial provider of nutrients for the next ˜200 days. However, there is little valid information on the actual nutrient concentrations, especially in the case of micronutrients (MN), due to sample collection and analytical limitations. No valid Reference Values (RVs) are available for the concentrations of nutrients in milk across lactation. Consequently, it is likely that inaccurate estimates of milk MN concentrations have been used to set recommendations for nutrient intakes of infants, young children, and lactating women. Further, we lack benchmarks against which to evaluate human milk quality (i.e. adequacy of nutrient content), or the need for, or effects of, nutrient interventions on milk MN. In this multi-center collaborative study, RVs will be established for human milk nutrients across the first 8.5 months of lactation. Well-nourished, unsupplemented lactating women in Bangladesh, Brazil, Denmark, and The Gambia (n = 250 per site) are recruited during the third trimester of pregnancy. Milk, blood, saliva, urine, and stool samples from mothers and infants are collected at three time periods (1-3.49, 3.5-5.99, 6.0-8.49 months of lactation) in an identical way across all sites. EBF is required for the first time period, predominantly breastfeeding (PBF) for the second and some breastfeeding for the third. At all three time periods, milk analyses include macronutrients, fat- and water-soluble vitamins, trace elements and other minerals, iodine, metabolomics, amino acids, human milk oligosaccharides, and bioactive peptides. Further, we measure breast milk volumes; maternal and infant diets, anthropometry, and morbidity; infant development; and at some sites, the maternal genome and the infant and maternal microbiome. We will present RVs as a range between the 5th (lowest) percentile and 95th (highest) percentile of values from the combined data across countries. Clinical trials.gov registration number: NCT03254329

Technical Abstract: Background: Exclusive breastfeeding (EBF) is the feeding practice recommended by the World Health Organization (WHO) for infants’ first 6 months of life. Besides being the sole recommended nutrient source during this time, human milk is a crucial provider of nutrients for the next ˜200 days. However, there is little valid information on the actual nutrient concentrations, especially in the case of micronutrients (MN), due to sample collection and analytical limitations. No valid Reference Values (RVs) are available for the concentrations of nutrients in milk across lactation. Consequently, it is likely that inaccurate estimates of milk MN concentrations have been used to set recommendations for nutrient intakes of infants, young children, and lactating women. Further, there are no RV benchmarks against which to evaluate human milk quality (i.e. adequacy of nutrient content), or the need for, or effects of, nutrient interventions on milk MN. Methods: In this multi-center collaborative study, RVs will be established for human milk nutrients across the first 8.5 months of lactation. Well-nourished, unsupplemented lactating women in Bangladesh, Brazil, Denmark, and The Gambia (n = 250 per site) are recruited during the third trimester of pregnancy. Milk, blood, saliva, urine, and stool samples from mothers and infants are collected at three time periods (1-3.49, 3.5-5.99, 6.0-8.49 months of lactation) in a systematic, identical way across all country sites. EBF is required for the first time period, predominantly breastfeeding (PBF) for the second and some breastfeeding for the third. At all three time periods, milk analyses include macronutrients, fat- and water-soluble vitamins, trace elements and other minerals, iodine, metabolomics, amino acids, human milk oligosaccharides, and bioactive peptides. Further, we measure breast milk volumes; maternal and infant diets, anthropometry, and morbidity; infant development; and at some sites, the maternal genome and the infant and maternal microbiome. Results: RVs will be constructed in a similar way to the WHO Child Growth Standards and the Intergrowth-21st Project. Clinical trials.gov registration number: NCT03254329