Comparison of Nutrient Content Between Preterm and Term Human Milk: a Systematic Review and Meta-analysis

August 19, 2026 updated by: Li Cai, PhD, Sun Yat-sen University
The purpose of this study is to thoroughly evaluate nutrient disparities between preterm and term human milk.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Preterm birth (gestational age of less than 37 weeks) is a major global health issue, associated with a high burden of mortality and long-term morbidity. Achieving optimal nutrition is critical for improving outcomes in this vulnerable population. However, the specific nutritional requirements for supporting postnatal growth akin to intrauterine rates are exceptionally high. While human milk is the recommended foundation of nutrition, its unfortified use may not meet these demands, and common alternatives like preterm formula present a balance of potential benefits and risks. Crucially, formulating effective nutritional strategies hinges on a precise understanding of the composition of preterm human milk itself. Existing evidence on this composition, especially regarding micronutrients and their influencing factors, is inconsistent and incomplete. Prior reviews have largely focused on macronutrients, leaving a gap in the synthesized evidence regarding micronutrient levels and their key determinants. Therefore, we performed this systematic review and meta-analysis to quantitatively compare the nutrient profile of preterm and term human milk and to evaluate the influence of factors such as lactation stage on these differences.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
102

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China
        • Sun Yat-sen University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Probability Sample

Study Population

Among these studies, most of them were performed in Europe. The sample size ranged from 10 to 2,633, with a median sample size of 49. All studies provided comparative data from mothers who delivered preterm and term infants, with gestational age consistently categorized as preterm (<37 weeks) and term (≥37 weeks). The stage of lactation at sample collection (including colostrum, transitional, and mature milk) was reported in most studies.

Description

Inclusion Criteria:

  • Studies needed to be population-based observational designs and report nutrient composition data for both preterm and term human milk. They must clearly define gestational age (preterm: 25-36 weeks; term: 37-42 weeks) and examine at least one comparable nutrient in both groups, such as energy, macronutrients (such as protein, fat, lactose), and/or micronutrients (including minerals like calcium and phosphorus, and vitamins such as vitamin D). We included articles published in Chinese or English only.

Exclusion Criteria:

  • Studies were excluded if they focused solely on mothers with specific medical conditions (such as malnutrition, mastitis, or diabetes), if they involved nutrient supplementation as an intervention, or if they were published in languages other than Chinese or English.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
lactating mothers or mothers providing human milk
Other: observational study
This study is a systematic review and meta-analysis. No intervention is administered to participants. Data regarding human milk composition are extracted and synthesized from previously published observational studies.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Energy content in human milk
Time Frame: Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
The energy content in human milk. Data will be extracted from included observational studies and expressed as mean ± standard deviation for comparison between preterm and term groups.
Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
Concentration of Protein in human milk
Time Frame: Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
The concentration of protein in human milk. Data will be extracted from included observational studies and expressed as mean ± standard deviation for comparison between preterm and term groups.
Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
Concentration of Fat in human milk
Time Frame: Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
The concentration of fat in human milk. Data will be extracted from included observational studies and expressed as mean ± standard deviation for comparison between preterm and term groups.
Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
Concentration of Lactose in human milk
Time Frame: Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
The concentration of lactose in human milk. Data will be extracted from included observational studies and expressed as mean ± standard deviation for comparison between preterm and term groups.
Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Concentration of IgA in human milk
Time Frame: Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
The concentration of IgA in human milk. Data will be extracted from included observational studies and expressed as mean ± standard deviation for comparison between preterm and term groups.
Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
Concentration of Total nitrogen in human milk
Time Frame: Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
The concentration of total nitrogen in human milk. Data will be extracted from included observational studies and expressed as mean ± standard deviation for comparison between preterm and term groups.
Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
Concentration of Lysozyme in human milk
Time Frame: Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
The concentration of lysozyme in human milk. Data will be extracted from included observational studies and expressed as mean ± standard deviation for comparison between preterm and term groups.
Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
Concentration of Lactoferrin in human milk
Time Frame: Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
The concentration of lactoferrin in human milk. Data will be extracted from included observational studies and expressed as mean ± standard deviation for comparison between preterm and term groups.
Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
Concentration of Lactalbumin in human milk
Time Frame: Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
The concentration of lactalbumin in human milk. Data will be extracted from included observational studies and expressed as mean ± standard deviation for comparison between preterm and term groups.
Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
Concentration of Albumin in human milk
Time Frame: Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
The concentration of albumin in human milk. Data will be extracted from included observational studies and expressed as mean ± standard deviation for comparison between preterm and term groups.
Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
Concentration of Sodium in human milk
Time Frame: Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
The concentration of sodium in human milk. Data will be extracted from included observational studies and expressed as mean ± standard deviation for comparison between preterm and term groups.
Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
Concentration of Potassium in human milk
Time Frame: Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
The concentration of potassium in human milk. Data will be extracted from included observational studies and expressed as mean ± standard deviation for comparison between preterm and term groups.
Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
Concentration of Calcium in human milk
Time Frame: Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
The concentration of calcium in human milk. Data will be extracted from included observational studies and expressed as mean ± standard deviation for comparison between preterm and term groups.
Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
Concentration of Magnesium in human milk
Time Frame: Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
The concentration of magnesium in human milk. Data will be extracted from included observational studies and expressed as mean ± standard deviation for comparison between preterm and term groups.
Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
Concentration of Phosphorus in human milk
Time Frame: Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
The concentration of phosphorus in human milk. Data will be extracted from included observational studies and expressed as mean ± standard deviation for comparison between preterm and term groups.
Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
Concentration of Zinc in human milk
Time Frame: Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
The concentration of zinc in human milk. Data will be extracted from included observational studies and expressed as mean ± standard deviation for comparison between preterm and term groups.
Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
Concentration of Copper in human milk
Time Frame: Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
The concentration of copper in human milk. Data will be extracted from included observational studies and expressed as mean ± standard deviation for comparison between preterm and term groups.
Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
Concentration of Iron in human milk
Time Frame: Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
The concentration of iron in human milk. Data will be extracted from included observational studies and expressed as mean ± standard deviation for comparison between preterm and term groups.
Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
Concentration of Iodine in human milk
Time Frame: Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
The concentration of iodine in human milk. Data will be extracted from included observational studies and expressed as mean ± standard deviation for comparison between preterm and term groups.
Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
Concentration of Selenium in human milk
Time Frame: Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
The concentration of selenium in human milk. Data will be extracted from included observational studies and expressed as mean ± standard deviation for comparison between preterm and term groups.
Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
Concentration of Manganese in human milk
Time Frame: Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
The concentration of manganese in human milk. Data will be extracted from included observational studies and expressed as mean ± standard deviation for comparison between preterm and term groups.
Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
Concentration of Molybdenum in human milk
Time Frame: Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
The concentration of molybdenum in human milk. Data will be extracted from included observational studies and expressed as mean ± standard deviation for comparison between preterm and term groups.
Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
Concentration of Vitamin E in human milk
Time Frame: Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
The concentration of vitamin E in human milk. Data will be extracted from included observational studies and expressed as mean ± standard deviation for comparison between preterm and term groups.
Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
Concentration of Vitamin A in human milk
Time Frame: Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
The concentration of vitamin A in human milk. Data will be extracted from included observational studies and expressed as mean ± standard deviation for comparison between preterm and term groups.
Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
Concentration of Vitamin B6 in human milk
Time Frame: Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.
The concentration of vitamin B6 in human milk. Data will be extracted from included observational studies and expressed as mean ± standard deviation for comparison between preterm and term groups.
Human milk samples are collected during the defined lactation periods. Specifically, colostrum is defined as samples collected within 3-5 days postpartum, transitional milk within 7-14 days postpartum, and mature milk at ≥15 days postpartum.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sun Yat-sen University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 6, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 8, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 12, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 3, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 3, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 10, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 20, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 19, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HMP

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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