D
Revised Search Criteria
TABLE D-1 Specified Inclusion and Related Exclusion Criteria for Milk Composition Reports
| Inclusion Criteria | Related Exclusion Criteria |
|---|---|
| Healthy Study Population | |
| Adult women (≥ 18 years old) | Not adult women |
| Mother generally healthy: e.g., not suffering from acute or chronic illness that might influence milk composition and/or production; living in a high- or middle-income country during the study;a include obese women unless they have comorbidities | Mother not healthy: e.g., suffering from acute or chronic illness that might influence milk composition and/or production; living in a low-income country during the study |
| Full-term singleton infant (defined as ≥ 37 weeks gestation length) | Preterm, twins |
| Infant generally healthy | Infant not healthy |
| Infant/child ≤ 12 months old | Infant/child > 12 months old |
| Nutrients of Interest Included | |
| Milk nutrients of interest: vitamins A, C, D, E, K, thiamin, riboflavin, niacin, B6, folate, B12, pantothenic acid, biotin, choline, copper, fluorides, iodine, iron, magnesium, manganese, molybdenum, chromium, calcium, phosphorus, sodium, selenium, zinc, potassium, chlorides, total milk protein, lactose, total milk fat, fatty acids (linoleic, alpha linolenic, eicosapentaenoic, docosahexaenoic acids) | No nutrients of interest; this would include such things as human milk oligosaccharide; milk protein fractions (e.g., whey proteins, caseins); fatty acid classes that do not include triglycerides (e.g., phospholipids, cholesteryl esters, free fatty acids) |
| No oligosaccharides | Contains only data on human milk oligosaccharides |
| Publication Appropriate | |
| Published on or after 1980 (revised date)b | Published before 1980 (revised date) |
| Peer-reviewed, primary data | Non-peer-reviewed editorial, commentary, or abstract from conference; review or meta-analysis (no original data) |
| Study Design and Methods | |
| Sample size ≥10 | Sample size <10 |
| Reported values include a measure of central tendency (mean or median) and a measure of variance (SE, SD, 95% CI, or IQR); values reported in text or tabular form | Reported values do not include a measure of central tendency and variance; values only reported graphically |
| Study participants not consuming maternal vitamin/mineral supplements or galactagogues, except for OTC prenatal vitamins or general vitamin/mineral usage | Women taking supplements or galactagogues (that would not be considered OTC prenatal vitamins or general vitamin/mineral usage) as part of intervention study |
| Eligible study design: RCT, observational prospective cohort study | Ineligible study design: case study, inadequate control group, donor or pooled milk |
| Adequate milk collection and storage methods used for outcome of interest: e.g., complete breast expression for total lipids | Inadequate milk collection and storage methods used for outcome of interest: e.g., not complete breast expression for total lipids |
| Adequate analysis methods used for outcome of interest: e.g., milk protein values adjusted for nonprotein nitrogen. | Inadequate analysis methods used for outcome of interest: e.g., milk protein values not adjusted for nonprotein nitrogen |
| Adequate units of measure in reported values of nutrients and/or classes of nutrients: e.g., absolute values (mg/mL milk) for lipids | Inadequate units of measure in reported values of nutrients and/or classes of nutrients: e.g., relative amounts of fatty acids based on only identified fatty acids (%wt:wt) |
NOTE: CI = confidence interval; IQR = interquartile range; mg = milligram; mL = milliliter; OTC = over-the-counter; RCT = randomized, double-blind, placebo-controlled trial; SD = standard deviation; SE = standard error; wt:wt = weight:weight.
a The committee made the decision to go beyond the United States and Canada to accept data from countries that were ranked high-income or high middle-income by the World Bank. The committee used its own judgment to decide whether to exclude reports from high middle-income countries that would have not been in this classification when the investigation was done. The committee chose to use these two groups of countries as they helped it to distinguish environments that might produce results for milk volume and composition that would be similar to those obtained among contemporary American women.
b Original search date was 1970.
TABLE D-2 Specified Inclusion and Related Exclusion Criteria for Milk Volume Reports
| Inclusion Criteria | Related Exclusion Criteria |
|---|---|
| Healthy Study Population | |
| Adult women (≥ 18 years old) | Not adult women |
| Mother generally healthy: e.g., not suffering from acute or chronic illness that might influence milk production; no mention of lactation insufficiency or difficulty; living in a high- or middle-income country during the study; include obese women unless they have comorbidities | Mother not healthy: e.g., suffering from acute or chronic illness that might influence milk production; lactation insufficiency or difficulty; living in a low-income country during the study |
| Full-term, singleton infant (defined as ≥ 37 weeks gestation length) | Preterm, twins, etc. |
| Infant generally healthy | Infant not healthy |
| Infant/child ≤ 6 months old | Infant/child > 6 months old |
| Exclusive breastfeeding | Nonexclusive breastfeeding |
| Outcome of Interest | |
| Milk consumption over a period of ≥ 24 hours | Milk consumption over a period of < 24 hours; milk output/synthesis rather than consumption measured |
| Publication | |
| Published on or after 1980 (revised date) | Published before 1980 (revised date) |
| Peer-reviewed, primary data | Non-peer-reviewed editorial, commentary, or abstract from conference; review or meta-analysis (no original data) |
| Study Design and Methods | |
| Sample size ≥10 | Sample size <10 |
| Reported values include a measure of central tendency (mean or median) and a measure of variance (SE, SD, 95% CI, or IQR); values reported in text or tabular form | Reported values do not include a measure of central tendency and variance; values only reported graphically |
| Study participants not consuming galactagogues (to our knowledge) | Women taking galactagogues as part of intervention study |
| Eligible study design: RCT, observational prospective cohort study | Ineligible study design: case study, inadequate control group |
| Adequate method used:a 24-hour infant test-weighing; deuterium dilution (note that the committee is not excluding studies that did not correct for insensible water loss) | Inadequate method used: weighing mother rather than infant; not directly measuring milk intake during night |
| Adequate units of measure in reported values of milk intake: e.g., mL/24 hour | Inadequate units of measure in reported values of milk intake: e.g., mL/kg/24 hour, mL/kg, mL/24 hour/breast, mL/feed |
NOTE: CI = confidence interval; IQR = interquartile range; kg = kilogram; mL = milligram; RCT = randomized, double-blind, placebo-controlled trial; SD = standard deviation; SE = standard error.
a To measure milk volume, infant intake is assessed, not maternal weight change or total production which can be higher because infants leave milk in the breast. Weighing the infant before and after a feed underestimates the volume consumed because of insensible water loss (sweat that has evaporated and exhaled water). Because very few reports corrected for these losses and often without having estimated the amount lost, the committee did not use correction for insensible water loss as an exclusion criterion.
TABLE D-3 Analytical Methods for Sampling and Analysis of Human Milk Relevant to the Specified Inclusion and Exclusion Criteria
| Nutrient | Sampling | Analysis | Reference(s) |
|---|---|---|---|
| Total fat | Full-breast expression;a 24-hour collection or weighted combined aliquots of fore- and hindmilk from one breast at each pumping over 24 hours; standardize by time of day, collection mode, collection breast and time since last feed/expression | Solvent extraction (Folch method or HPLC); creamatocrit is “not accurate for database development” | Committee opinion; Jensen et al., 1985; Leghi et al., 2020; Wu et al., 2018 |
| Fatty acids | See total fat | To determine the amount in milk both total fat and the amount of the fatty acid (as wt%) are required | Committee opinion; Jensen et al., 1985; Leghi et al., 2020 |
| Total protein | Fore-, mid- or hindmilk are adequate; standardized by time of day, collection mode, collection breast, and time since last feed/expression | Kjeldahl with correction for nonprotein nitrogen by acid precipitation | Atkinson et al., 1980; Leghi et al., 2020; Wu et al., 2018 |
| Lactose | Fore-, mid- or hindmilk are adequate; standardized by time of day, collection mode, collection breast, and time since last feed/expression | “LC-MS or HPLC are superior to enzymatic methods”; Miris analyzer reports lower values (excluded by committee opinion) | Leghi et al., 2020; Sprenger et al., 2017; Wu et al., 2018 |
| Vitamin A | As for total fat (presumably); no circadian variability | HPLC (coupled with UV, fluorescence, and MS detection) has been the dominant method | Hampel et al., 2017, 2018 |
| Vitamin D | As for total fat (presumably) | “HPLC and CPBA or LC-MS/MS should be applied” | Hampel et al., 2018 |
| Vitamin E | As for total fat (presumably); no circadian variability | “HPLC coupled with fluorescence or UV detection is a well-studied and suitable technique for quantifying vitamin E; LC-MS/MS is a valid alternative” | Hampel et al., 2017, 2018 |
| Vitamin K | As for total fat (presumably) | “HPLC-FLD is the preferred method; alternatively, LC-MS/MS provides the needed sensitivity” | Hampel et al., 2018 |
| Thiamin | Morning and evening sample combined; avoid fasting or soon after supplement ingestion; afternoon and evening samples are preferred | Thiochrome method; recent methods use chromatographic separation before fluorescence detection; among the microbiological assays, “only L. viridescens provides results comparable to the thiochrome assay” | Hampel and Allen, 2016; Hampel et al., 2017, 2018 |
| Riboflavin | See thiamin; afternoon and evening samples are preferred | Microbiological approaches are susceptible to error; Preferred: HPLC separation followed by fluorescence detection (current infant AI is based on UV detection and fluorometric measurements after HPLC separation) | Hampel et al., 2017, 2018 |
| Niacin | See thiamin; afternoon and evening samples are preferred | A microbiological assay with L. arabinosus “continues to be a suitable choice;” LC-MS/MS can also be used | Hampel et al., 2017, 2018 |
| Vitamin B6 | See thiamin; afternoon and evening samples are preferred | Usually assessed with LC-based methods of Saccharomyces uvarum; HPLC methods provide “a more robust and rapid approach” | Hampel et al., 2017, 2018 |
| Vitamin B12 | See thiamin; afternoon and evening samples are preferred | L. leichmanii has been used in the past but may overestimate the vitamin; preferred method is competitive chemiluminescence enzyme immunoassays | Hampel et al., 2017, 2018 |
| Folate | See thiamin | Method of choice: microbiological assay with L. casei | Hampel et al., 2018 |
| Pantothenic acid | See thiamin | “The majority of analyses have been conducted via microbiological assays, but chromographic separation followed by UV or MS/MS detection may be beneficial” | Hampel et al., 2018 |
| Biotin | See thiamin | Microbiological assays (L. arabinosus and L. plantarum) are commonly used; novel LC-MS/MS are being developed | Hampel et al., 2018 |
| Choline | Unknown | “LC-MS/MS provides validated results with only minimal sample preparation without possible radiation exposure;” older methods include RIA and GC-MS analysis | Hampel et al., 2018 |
| Vitamin C | See thiamin | “HPLC methods should be used;” note that the current AI is based on colorimetric assays | Hampel et al., 2018 |
| Iron | Use trace-element free supplies | “Both AAS and inductively coupled argon plasma spectroscopy are suitable” | Hampel et al., 2018 |
| Copper | Use trace-element free supplies | “AAS, ICP-AES, and ICP-MS are valid approaches” | Hampel et al., 2018 |
| Zinc | Use trace-element free supplies | Same as for copper | Hampel et al., 2018 |
| Iodine | Use trace-element free supplies | “ICP-MS is the preferred approach;” older studies used colorimetric approaches and have some analytic bias; iodide is analyzed differently | Hampel et al., 2018 |
| Selenium | Use trace-element free supplies | AAS (less sample handling and no radiation step compared to other methods) | Hampel et al., 2018 |
| Flouride(s) | Unknown | Fluoride-specific electrode | D. Hampel (personal communication) |
| Magnesium | Unknown | ICP-MS | Method used by Daniels et al., 2019 |
| Molybdenum | Use trace-element free supplies | ICP-MS (based on official analysis method for infant formula) | AOAC, 2011 |
| Chromium | Use trace-element free supplies | ICP-MS (based on official analysis method for infant formula) | AOAC, 2011 |
| Calcium | Unknown | ICP-MS | Method used by Daniels et al., 2019 |
| Phosphorus | Unknown | ICP-MS | Method used by Daniels et al., 2019 |
| Sodium | Unknown | ICP-MS flame atomic emission spectrometry; ICP-MS is a branch of AAS Flame photometry (aka flame atomic emission spectrometry) is another branch of AAS that is acceptable for metal ions (Na, K) | Method used by Daniels et al., 2019 |
| Chloride(s) | Unknown | Chloridometer or colorimetric titration by chloride counter; potentiometric method | D. Hampel (pers. comm.); Wack et al., 1997 |
| Potassium | Unknown | ICP-MS is a branch of AAS Flame photometry (aka flame atomic emission spectrometry) is another branch of AAS that is acceptable for metal ions (Na, K) | Method used by Daniels et al., 2019 |
NOTE: AAS = atomic absorption spectrometry; AI = Adequate Intake; CPBA = competitive protein-binding assay; GC-MS = gas chromatography–mass spectrometry; HPLC = high-performance liquid chromatography; HPLC-FLD = high-performance liquid chromatography with fluorescence detection; ICP-AES = inductively coupled plasma-atomic emission spectrometry; ICP-MS = inductively coupled plasma–mass spectrometry; LC-MS/MS = liquid chromatography-tandem mass spectrometry; MS = mass spectrometry; MS/MS = tandem mass spectrometry; RIA = radioimmunoassay; UV = ultraviolet; wt = weight.
a A number of authors claimed that fatty acids do not change within a feed and used this as their rationale for not using a complete breast expression as their sample. However, the fatty acids are part of the lipid component of milk, which varies throughout the feed. If the proportion of fatty acids is the only objective, less than a full expression may be sufficient. For estimating an infant’s needs, however, the total amount of a fatty acid actually delivered is required. Total fatty acid is the product of the total lipid in the entire feed with the proportion of the fatty acid.
REFERENCES
AOAC (Association of Official Analytical Chemists). 2011. AOAC official method 2011.19. Chromium, selenium, and molybdenum in infant formula and adult nutritional products. Inductively coupled plasma-mass spectrometry. First action 2011. http://stakeholder.aoac.org/SPIFAN/2011.19.pdf (accessed June 29, 2020).
Atkinson, S. A., I. C. Radde, G. W. Chance, M. H. Bryan, and G. H. Anderson. 1980. Macro-mineral content of milk obtained during early lactation from mothers of premature infants. Early Human Development 4(1):5-14.
Daniels, L., R. S. Gibson, A. Diana, J. J. Haszard, S. Rahmannia, D. E. Luftimas, D. Hampel, S. Shahab-Ferdows, M. Reid, L. Melo, Y. Lamers, L. H. Allen, and L. A. Houghton. 2019. Micronutrient intakes of lactating mothers and their association with breast milk concentrations and micronutrient adequacy of exclusively breastfed Indonesian infants. American Journal of Clinical Nutrition 110(2):391-400.
Hampel, D., and L. H. Allen. 2016. Analyzing B-vitamins in human milk: Methodological approaches. Critical Reviews in Food Science and Nutrition 56(3):494-511.
Hampel, D., S. Shahab-Ferdows, M. M. Islam, J. M. Peerson, and L. H. Allen. 2017. Vitamin concentrations in human milk vary with time within feed, circadian rhythm, and single-dose supplementation. Journal of Nutrition 147(4):603-611.
Hampel, D., D. K. Dror, and L. H. Allen. 2018. Micronutrients in human milk: Analytical methods. Advanced Nutrition 9(Suppl 1):313S-331S.
Jensen, R. G., L. Wood, M. T. Clandinin, and R. M. Clark. 1985. Methods for the sampling and analysis of human milk lipids. In Human lactation: Milk components and methodologies, edited by R. G. Jensen and M. C. Neville. New York: Plenum Press.
Sprenger, N., L. Y. Lee, C. A. De Castro, P. Steenhout, and S. K. Thakkar. 2017. Longitudinal change of selected human milk oligosaccharides and association to infants' growth, an observatory, single center, longitudinal cohort study. PLoS One 12(2):e0171814.
Wack, R. P., E. L. Lien, D. Taft, and J. D. Roscelli. 1997. Electrolyte composition of human breast milk beyond the early postpartum period. Nutrition 13(9):774-777.
Wu, X., R. T. Jackson, S. A. Khan, J. Ahuja, and P. R. Pehrsson. 2018. Human milk nutrient composition in the United States: Current knowledge, challenges, and research needs. Current Developments in Nutrition 2(7):nzy025.
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