- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03254329
Establishing Global Reference Values for Human Milk (MILQ)
Establishing Global Reference Values for Human Milk Composition in a Multi-Center Collaborative Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The investigators will collect breast milk samples at four visits, at 2-3 days after birth (colostrum) and at 1-3.4, 3.5-5.9, and 6-8.5 months of lactation from well-nourished mothers age ≥18 to ≤40 years, in a systematic, identical way in four countries. The four sites are: Copenhagen, Denmark; Banjul, The Gambia; Rio de Janeiro, Brazil; and Mirpur, Dhaka, Bangladesh. The most important site selection criteria were that multiple micronutrient supplements are not consumed after week 28 of pregnancy; maternal diet is adequate but consumption of highly fortified foods is limited; and exclusive breastfeeding is 60% at 4 months.
In order to have 250 women and infants per site complete the study at 8.5 months, approximately 500 women will be recruited during the third trimester of pregnancy. This should allow for mothers and infants not meeting study eligibility criteria in pregnancy or early lactation, and drop-outs from the study. Recruitment during pregnancy will increase the opportunity to locate and recruit women since recruitment in the immediate post-delivery period will be difficult. It will also enable the women to be counselled on the importance of exclusive breastfeeding (EBF). Colostrum will be collected at 2-3 days postpartum for future analysis. The first collection of mature milk will occur between 1 and 3.4 months postpartum, when maternal and infant blood samples will also be collected on all participants. At the final two visits, in addition to milk collection, blood will be taken from all mothers but only half of the infants each time, primarily for the assessment of micronutrient status.
A requirement is that infants must be EBF in the 1-3.4 month period, and breastfed (BF) in the second and third period. Longitudinal measurements on the same mother after the BF period are not necessary for statistical reasons, as the investigators are not creating RVs for change in milk composition. The investigators expect that due to attrition and cessation of BF, the sample size will need to be augmented in later months; the alternative would have been to recruit and measure many more women in earlier stages in order to have an adequate sample size in the 7-8.5 month interval, which would be a much less efficient approach. Therefore after 6 months, if women are not breastfeeding, additional lactating women will be recruited from the group that was not EBF in the 3.4 month period, or from the local health center or community.
At all three points of mature milk collection the investigators will measure breast milk volume; diet, anthropometry and morbidity of the mother and infant; and infant development at 3.5-5.9 and 6 to 8.5 months; and will collect infant fecal samples for future analyses of the microbiome. Milk volume will be measured at three sites using the International Atomic Energy Agency's protocol that requires dosing the mother with deuterated water and collecting maternal and infant saliva urine samples at 0, 1, 2, 3, 4, 13 and 14 days after the dose. In Denmark breast milk volume will be measured by 24 hour infant weighing.
Most of the laboratory analyses will be conducted at the United States Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center (WHNRC) in Davis, California. Other analyses will be performed in the Department of Chemistry at University of California, Davis (HMOs and other bioactive compounds in milk), and the Swiss Federal Institute of Technology in Zurich (iodine status). RVs will be constructed following the methods and principles developed for the World Health Organization (WHO) Child Growth Standards and the Intergrowth-21st Project.
An add-on study "Evaluation of maternal insulin resistance, metabolic and inflammatory biomarkers for prediction of successful initiation and duration of breastfeeding" is being conducted at the Danish site and was approved by The Regional Committee on Health Research Ethics with (H-17015174).
The aims of the add-on study are to evaluate if maternal metabolic and inflammatory biomarkers can predict successful initiation and duration of breastfeeding in a population of healthy non-obese Danish women, to evaluate the impact of maternal inflammatory biomarkers during pregnancy on the offspring's growth and risk factors for later disease, and to relate the impact of maternal metabolic and inflammatory biomarkers during pregnancy on breastfeeding behavior and on the offspring's growth and risk factors for later disease in this population to corresponding outcomes in an established cohort of infants born of obese mothers.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Lindsay H Allen, PhD
- Phone Number: 530 752 5268
- Email: lindsay.allen@ars.usda.gov
Study Contact Backup
- Name: Setareh Shahab-Ferdows, PhD
- Phone Number: 530 752 9540
- Email: setti.shahab-ferdows@ARS.USDA.GOV
Study Locations
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Dhaka, Bangladesh, 1212
- Recruiting
- International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b)
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Contact:
- Md. Munirul Islam, MD, PhD
- Phone Number: 2352 +880 2 9827001-10
- Email: mislam@icddrb.org
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Principal Investigator:
- Munir Islam, Ph.D.
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Rio de Janeiro, Brazil, RJ21941-590
- Recruiting
- Federal University of Rio de Janeiro
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Contact:
- Gilberto Kac, MD, PhD
- Email: Gilberto.Kac@gmail.com
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Contact:
- Erica Barros
- Email: ericabarros86@gmail.com
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Frederiksberg
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Copenhagen, Frederiksberg, Denmark, 1958
- Recruiting
- University of Copenhagen
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Contact:
- Kim F Michaelsen, MD, PhD
- Phone Number: +45 35 33 22 21
- Email: kfm@nexs.ku.dk
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Contact:
- Kamilla G Eriksen, PhD
- Phone Number: +45 35 32 61 76
- Email: kge@nexs.ku.dk
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Kombo Saint Mary's
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Bakau, Kombo Saint Mary's, Gambia
- Recruiting
- Medical Research Council Gambia
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Contact:
- Sophie Moore, PhD
- Email: sophie.moore@kcl.ac.uk
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Contact:
- Andrew Doel
- Phone Number: +44 758081041
- Email: andrew.doel@kcl.ac.uk
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria for Mother
- 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.
Inclusion Criteria for Infant
- Birth weight 2500-4200 g, 37-42 weeks of gestation.
- No congenital malformations that interfere with feeding or growth and development.
Exclusion Criteria at 1 to 3.4 Months Postpartum
- Cessation of or non-exclusive breastfeeding.
- Serious maternal illness.
- Infant length-for-age, weight-for-age or weight-for-length < -2 Z.
Exclusion criteria 3.5 to 8.5 months postpartum
- Cessation of breastfeeding.
- Serious maternal illness.
- Infant length-for-age, weight-for-age or weight-for-length < -2 Z.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Bangladesh
Assessment of human milk nutrient composition.
Approximately 500 women and their infants recruited, 250 dyads completing study
|
Observational study to measure nutrients in human milk during lactation and their relationship to maternal and infant nutritional status.
|
Brazil
Assessment of human milk nutrient composition.
Approximately 500 women and their infants recruited, 250 dyads completing study
|
Observational study to measure nutrients in human milk during lactation and their relationship to maternal and infant nutritional status.
|
Denmark
Assessment of human milk nutrient composition.
Approximately 500 women and their infants recruited, 250 dyads completing study
|
Observational study to measure nutrients in human milk during lactation and their relationship to maternal and infant nutritional status.
|
The Gambia
Assessment of human milk nutrient composition.
Approximately 500 women and their infants recruited, 250 dyads completing study
|
Observational study to measure nutrients in human milk during lactation and their relationship to maternal and infant nutritional status.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in vitamin and mineral concentrations in human breast milk
Time Frame: Breast milk samples collected 1-3.4, 3.5-5.9, and 6-8.5 months postpartum
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To establish reference values, the vitamin and mineral concentrations will be measured in milk of well-nourished women
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Breast milk samples collected 1-3.4, 3.5-5.9, and 6-8.5 months postpartum
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Variation in other constituents of human breast milk
Time Frame: Breast milk samples collected at 1-3.4, 3.5-5.9, and 6-8.5 months postpartum
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Macronutrients, and human milk oligosaccharides and proteins will be analyzed
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Breast milk samples collected at 1-3.4, 3.5-5.9, and 6-8.5 months postpartum
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Micronutrient status of mothers and infants
Time Frame: Blood and urine samples surveyed at 1-3.4, 3.5-5.9, and 6-8.5 months postpartum
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Vitamin and mineral status of mothers and infants will be assessed in blood and urine
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Blood and urine samples surveyed at 1-3.4, 3.5-5.9, and 6-8.5 months postpartum
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Milk volume
Time Frame: 1-3.4, 3.5-5.9, and 6-8.5 months postpartum
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Measurements of usual daily milk volume using deuterated water or, in Denmark, 24 hour infant weighing
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1-3.4, 3.5-5.9, and 6-8.5 months postpartum
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Maternal and infant iodine status
Time Frame: 1-3.4, 3.5-5.9, and 6-8.5 months postpartum
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Urinary iodine; thyroid stimulating hormone, thyroglobulin and thyroxine in dried blood spots
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1-3.4, 3.5-5.9, and 6-8.5 months postpartum
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Milk iodine
Time Frame: 1-3.4, 3.5-5.9, and 6-8.5 months postpartum
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Milk iodine
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1-3.4, 3.5-5.9, and 6-8.5 months postpartum
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Maternal nutrient intake during pregnancy
Time Frame: Measured during gestational week 35-37
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Assessment of dietary intake by two days 24-hour recall in Denmark and Brazil
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Measured during gestational week 35-37
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Maternal nutrient intake
Time Frame: 1-3.4, 3.5-5.9, and 6-8.5 months postpartum
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Assessment of dietary intake by two days 24-hour recall
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1-3.4, 3.5-5.9, and 6-8.5 months postpartum
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Infant nutrient intake
Time Frame: 1-3.4, 3.5-5.9, and 6-8.5 months
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Assessment of dietary intake by two days 24-hour recall of the infant's diet
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1-3.4, 3.5-5.9, and 6-8.5 months
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Infant dietary habits
Time Frame: 1-3.4, 3.5-5.9, and 6-8.5 months
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Assessment of dietary intake by diet habits questionnaire
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1-3.4, 3.5-5.9, and 6-8.5 months
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Maternal weight
Time Frame: 1-3.4, 3.5-5.9, and 6-8.5 months postpartum
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Measure of weight in kilograms (kg)
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1-3.4, 3.5-5.9, and 6-8.5 months postpartum
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Infant weight
Time Frame: 1-3.4, 3.5-5.9, and 6-8.5 months
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Measure of weight in grams (g) or kilograms (kg)
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1-3.4, 3.5-5.9, and 6-8.5 months
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Maternal height
Time Frame: 1-3.4, 3.5-5.9, and 6-8.5 months postpartum
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measured in centimeters (cm)
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1-3.4, 3.5-5.9, and 6-8.5 months postpartum
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Infant length
Time Frame: 1-3.4, 3.5-5.9, and 6-8.5 months
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measured in cm
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1-3.4, 3.5-5.9, and 6-8.5 months
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Maternal body mass index
Time Frame: 1-3.4, 3.5-5.9, and 6-8.5 months postpartum
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Maternal weight and height will be combined to determine body mass index (kg/m2)
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1-3.4, 3.5-5.9, and 6-8.5 months postpartum
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Infant growth
Time Frame: 1-3.4, 3.5-5.9, and 6-8.5 months postpartum
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Infant weight and length will be aggregated to determine infant growth status
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1-3.4, 3.5-5.9, and 6-8.5 months postpartum
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Maternal body composition
Time Frame: 1-3.4, 3.5-5.9, and 6-8.5 months postpartum
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Assessment of body composition by bioimpedance in Denmark, The Gambia, and Brazil only.
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1-3.4, 3.5-5.9, and 6-8.5 months postpartum
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Infant body composition
Time Frame: 1-3.4, 3.5-5.9, and 6-8.5 months
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Assessment of body composition by Air Displacement Plethysmography, in The Gambia, and by bioimpedance in Denmark and Brazil.
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1-3.4, 3.5-5.9, and 6-8.5 months
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Infant morbidity
Time Frame: 1-3.4, 3.5-5.9, and 6-8.5 months
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Data collected from mothers on infant health
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1-3.4, 3.5-5.9, and 6-8.5 months
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Infant development
Time Frame: 6-8.5 months
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Ages and Stages questionnaire
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6-8.5 months
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Infant motor development
Time Frame: 3.5-5.9 and 6-8.5 months
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Infant motor development measured using a World Health Organization (WHO) assessment of motor milestones
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3.5-5.9 and 6-8.5 months
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Change in infant microbiome
Time Frame: 1-3.4, 3.5-5.9, and 6-8.5 months
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DNA analyses of infant gut bacteria derived from fecal samples
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1-3.4, 3.5-5.9, and 6-8.5 months
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Change in maternal microbiome
Time Frame: Collected at gestational week 28-40, and 1-3.4, 3.5-5.9, and 6-8.5 months postpartum
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DNA analyses of maternal gut bacteria derived from fecal samples in The Gambia and Brazil only
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Collected at gestational week 28-40, and 1-3.4, 3.5-5.9, and 6-8.5 months postpartum
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Maternal Glucose Tolerance
Time Frame: Measured once at gestational week 28-30
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In Denmark only, an Oral Glucose Tolerance Test will be performed.
Fasting blood sugar (BS), and BS at 1 and 2 hours after glucose beverage.
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Measured once at gestational week 28-30
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Maternal Hemoglobin A1c (HbA1c)
Time Frame: Measured once at gestational week 28-30
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In Denmark only, maternal Hemoglobin A1c will be measured in whole blood
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Measured once at gestational week 28-30
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Maternal markers of insulin sensitivity
Time Frame: Measured once at gestational week 28-30
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In Denmark only, a serum sample will be collected and stored for measurement of insulin (mU/l), c-peptide (pmol/l), and leptin (ng/l)
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Measured once at gestational week 28-30
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Maternal lipid panel
Time Frame: Measured once at gestational week 28-30
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In Denmark only, a serum sample will be collected and stored for measurement of a lipid profile including Total Cholesterol, High Density Lipoprotein-cholesterol, Low Density Lipoprotein-cholesterol, Very Low Density Lipoprotein-cholesterol, and Triglycerides in mmol/l).
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Measured once at gestational week 28-30
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Maternal inflammatory markers
Time Frame: Measured once at gestational week 28-30
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In Denmark only, a serum sample will be collected and stored for measurement of high sensitivity C-reactive protein (mg/l).
|
Measured once at gestational week 28-30
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Lindsay H Allen, PhD, USDA/WHNRC
Publications and helpful links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- MILQ
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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