Establishing Global Reference Values for Human Milk

NCT03254329 | Unknown

• 1 other identifier: MILQ
• Study Type: observational
• Target: 2,000
• Locations: 4 countries
• Sites: 4

Brief Summary

The primary purpose of the proposed research is to establish Reference Values (RVs) for micronutrients (MN) and macronutrients in human milk. The investigators' research to date has revealed highly variable milk MN concentrations among populations, and very low values in some low income countries (LICs) likely caused by poor maternal status and/or diet but RVs are needed to interpret these values. During the past year the investigators conducted a review of human milk nutrient composition, and formed a Technical Advisory Group (TAG) which developed the current proposal. Here, the investigators are conducting a longitudinal project on well-nourished women and infants. The Mothers, Infants and Lactation Quality (MILQ) study is a multi-center cohort project, investigating breast milk nutrient composition in well-nourished women across the first 8.5 months of lactation in four different populations. The countries involved are Denmark, Brazil, Bangladesh and The Gambia. Exclusive breastfeeding is an eligibility criterion up until the second post-partum study visit (between 1 - 3.4 months postpartum), with the exception of the first week after delivery. Other data collected on mothers and infants, including maternal and infant nutrient intake and status, morbidity, milk volume, and infant development, will inform interpretation and support application of the results. While the priority is to develop RVs for MN, other analyses will include human milk oligosaccharides (HMOs) and proteins, and free amino acids (FAA) in infant plasma. Thus, with the samples obtained the investigators will perform (a) laboratory analyses of milk, plasma and urine nutrients to construct RVs for global application, (b) analyses of HMOs and proteins in milk, and (c) metabolomic analysis of FAA and other metabolites in infant plasma. By request of the Bill and Melinda Gates Foundation (BMGF), colostrum and fecal microbiota samples will also be collected and stored for later analyses.

Conditions

Human Milk Nutrient Reference Values

Keywords

human milk; micronutrients; lactation; milk volume; milk composition; reference values

Outcome Measures

Primary Outcomes (1)

• Change in vitamin and mineral concentrations in human breast milk

  To establish reference values, the vitamin and mineral concentrations will be measured in milk of well-nourished women

  Breast milk samples collected 1-3.4, 3.5-5.9, and 6-8.5 months postpartum

Secondary Outcomes (27)

• Variation in other constituents of human breast milk

  Breast milk samples collected at 1-3.4, 3.5-5.9, and 6-8.5 months postpartum

• Micronutrient status of mothers and infants

  Blood and urine samples surveyed at 1-3.4, 3.5-5.9, and 6-8.5 months postpartum

• Milk volume

  1-3.4, 3.5-5.9, and 6-8.5 months postpartum

• Maternal and infant iodine status

  1-3.4, 3.5-5.9, and 6-8.5 months postpartum

• Milk iodine

  1-3.4, 3.5-5.9, and 6-8.5 months postpartum

Study Arms (4)

Bangladesh

Assessment of human milk nutrient composition. Approximately 500 women and their infants recruited, 250 dyads completing study

Other: Assessment of human milk nutrient composition

Brazil

Assessment of human milk nutrient composition. Approximately 500 women and their infants recruited, 250 dyads completing study

Other: Assessment of human milk nutrient composition

Denmark

Assessment of human milk nutrient composition. Approximately 500 women and their infants recruited, 250 dyads completing study

Other: Assessment of human milk nutrient composition

The Gambia

Assessment of human milk nutrient composition. Approximately 500 women and their infants recruited, 250 dyads completing study

Other: Assessment of human milk nutrient composition

Interventions

Assessment of human milk nutrient composition OTHER

Observational study to measure nutrients in human milk during lactation and their relationship to maternal and infant nutritional status.

Bangladesh; Brazil; Denmark; The Gambia

Eligibility Criteria

• Age: 18 Years - 40 Years
• Gender Eligibility Details: Pregnant and lactating women
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Well-nourished pregnant women in the third trimester of pregnancy at recruitment, then lactating with their infant from 1-8.5 months postpartum.

You may qualify if:

• No vitamin-mineral supplements during third trimester of pregnancy or during lactation except for iron + folic acid, also vitamin D and Ca in Denmark.
• Low habitual intake of highly-fortified foods (iodized salt excepted).
• No relevant past or current medical problems including gestational diabetes or pre-eclampsia.
• Singleton delivery, not preterm.
• BMI ≥18.5 to \<30.0 kg/m2, height ≥150 cm.
• Mid-upper arm circumference (MUAC) ≥23 and ≤33 cm in pregnancy
• Consuming a nutritionally adequate diet i.e. not vegan or macrobiotic, ≥5 food groups/d each ≥15g. At screening this information will be collected with a locally-appropriate and validated food frequency questionnaire.
• Non-anemic in pregnancy (Hb \>100 g/L)
• Alcohol intake ≤5 units (50 mL pure alcohol)/week.
• Non-smoker.
• Birth weight 2500-4200 g, 37-42 weeks of gestation.
• No congenital malformations that interfere with feeding or growth and development.

You may not qualify if:

• Cessation of or non-exclusive breastfeeding.
• Serious maternal illness.
• Infant length-for-age, weight-for-age or weight-for-length \< -2 Z.
• Cessation of breastfeeding.
• Serious maternal illness.
• Infant length-for-age, weight-for-age or weight-for-length \< -2 Z.

Sponsors & Collaborators

• USDA, Western Human Nutrition Research Center: lead
• University of Copenhagen: collaborator
• Medical Research Council Unit, The Gambia: collaborator
• International Centre for Diarrhoeal Disease Research, Bangladesh: collaborator
• Universidade Federal do Rio de Janeiro: collaborator
• Bill and Melinda Gates Foundation: collaborator

Study Sites (4)

International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b)

Dhaka, 1212, Bangladesh

RECRUITING

Federal University of Rio de Janeiro

Rio de Janeiro, RJ21941-590, Brazil

RECRUITING

University of Copenhagen

Copenhagen, Frederiksberg, 1958, Denmark

RECRUITING

Medical Research Council Gambia

Bakau, Kombo Saint Mary's, The Gambia

RECRUITING

Related Publications (3)

• Christensen SH, Rom AL, Greve T, Lewis JI, Frokiaer H, Allen LH, Molgaard C, Renault KM, Michaelsen KF. Maternal inflammatory, lipid and metabolic markers and associations with birth and breastfeeding outcomes. Front Nutr. 2023 Sep 4;10:1223753. doi: 10.3389/fnut.2023.1223753. eCollection 2023.

  PMID: 37731394 DERIVED

• Christensen SH, Lewis JI, Larnkjaer A, Frokiaer H, Allen LH, Molgaard C, Michaelsen KF. Associations between maternal adiposity and appetite-regulating hormones in human milk are mediated through maternal circulating concentrations and might affect infant outcomes. Front Nutr. 2022 Nov 4;9:1025439. doi: 10.3389/fnut.2022.1025439. eCollection 2022.

  PMID: 36407523 DERIVED

• Allen LH, Hampel D, Shahab-Ferdows S, Andersson M, Barros E, Doel AM, Eriksen KG, Christensen SH, Islam M, Kac G, Keya FK, Michaelsen KF, de Barros Mucci D, Njie F, Peerson JM, Moore SE. The Mothers, Infants, and Lactation Quality (MILQ) Study: A Multi-Center Collaboration. Curr Dev Nutr. 2021 Sep 20;5(10):nzab116. doi: 10.1093/cdn/nzab116. eCollection 2021 Oct.

  PMID: 34712893 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Breast milk, blood, saliva, urine and feces

MeSH Terms

Conditions

Breast Feeding

Condition Hierarchy (Ancestors)

Feeding Behavior; Behavior

Study Officials

• Lindsay H Allen, PhD

  USDA/WHNRC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lindsay H Allen, PhD

CONTACT

530 752 5268; lindsay.allen@ars.usda.gov

Setareh Shahab-Ferdows, PhD

CONTACT

530 752 9540; setti.shahab-ferdows@ARS.USDA.GOV

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: PROSPECTIVE
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2017
• First Posted: August 18, 2017
• Study Start: September 1, 2017
• Primary Completion: November 30, 2021
• Study Completion: November 30, 2021
• Last Updated: July 7, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1); DK (1); TH (1); BA (1)