Location: Obesity and Metabolism Research
Project Number: 2032-51000-005-04-A
Project Type: Cooperative Agreement
Start Date: Nov 18, 2016
End Date: Jan 31, 2020
Breast milk is recommended as the sole source of nutrients for infants during the first 180 days postpartum and as an important source for the next ˜200 days, but we lack valid information on the nutrient content of human milk, and especially on its micronutrient (MN) content, and there are no Reference Values (RVs). Consequently we are basing recommended nutrient intakes of infants, young children and lactating women on many unvalidated and incorrect estimates of milk MN concentrations and have no benchmarks against which to evaluate breast milk quality in different populations, or the need for or effects of nutrient interventions on breast milk micronutrients. The limited existing evidence suggests that many vitamins and some minerals may be low in the milk of undernourished women. The overall objective of this research is to develop RVs for micronutrients in human milk, based on the range of nutrient concentrations in samples that we will obtain from well-nourished but unsupplemented lactating women in four countries. Maternal plasma will also be collected to verify the adequacy of maternal micronutrient status and to describe the relationships between maternal status and milk micronutrient concentrations. Infant plasma will be analyzed to determine the effects of breast milk micronutrient concentrations on infant status. These objectives will be facilitated by our recent validation of methods for milk micronutrient analysis, and our ability to measure several vitamins simultaneously by mass spectrometry.
Colostrum, and breast milk samples at 1-3.4, 3.5 to 5.9, and 6-8.9 mo. of lactation, will be collected from well-nourished mothers, age 18 to 40 y, in a systematic, identical way in four countries. The four sites are Copenhagen, Denmark; Mirpur, Dhaka, Bangladesh; Bakau, The Gambia; and Rio de Janeiro, Brazil. Criteria for selection of these field sites are: mothers are healthy and well-nourished but not consuming mineral-vitamin supplements during the third trimester of pregnancy or during lactation, or consuming substantial amounts of food highly fortified with micronutrients. (Folic acid-iron supplements or fortification are permitted). “Well-nourished” population groups will be identified during the pilot phase of the study, using existing data and collecting new information in a relevant subsample: dietary data to estimate prevalence of inadequate intakes of specific and total micronutrients; assessment of anemia (Hemocue); a locally-validated food frequency questionnaire (usual consumption of animal source foods + a dietary diversity score); birth weights in normal range and a low prevalence of stunting. Exclusive breastfeeding must be common through 4 mo. postpartum and breastfeeding typically continue to 9 mo. postpartum. An absolute requirement is ability to recruit 250 mother-infant dyads who are exclusively breastfed at 1 to 3.4 mo. postpartum and predominantly breastfeeding at 3.5 to 5.9 mo., based on WHO definitions. This requires enrollment of 500 mothers at delivery assuming 50% exclusive breastfeeding at 4 mo. Since many mothers will not be exclusively breastfeeding after 6 mo., the 6-9 mo. milk and serum samples can be collected from a cross-sectional sample of participants including those who became ineligible. The last participants will be enrolled 10-12 mo. after the start of the study and fieldwork completed in 2 y. An additional 1.5 y will be needed to complete sample and data analyses and construct the RVs. With the samples obtained the ARS WHNRC in Davis will analyze: (a) milk, serum and urine macronutrients and micronutrients to construct RVs for global application and assess micronutrient status, (b) human milk oligosaccharides (HMOs) and proteins, and (c) metabolomics to measure free amino acids and other metabolites in infant serum. Colostrum and fecal samples will be collected and stored for later analyses. Data on concentrations of micronutrients and other bioactives in human milk will be expressed as centiles of the distributions of each nutrient e.g. 5th, 25th, 50th, 75th, 95th. Future exploratory analyses will also assess the relationships between milk nutrient concentrations and other collected information, including milk volume, child growth, child developmental milestones, maternal plasma values, and infant plasma values.