Three-part Advances in Nutrition systematic review finds there’s still much we don’t know

The World Health Organization (WHO) recommends exclusive breastfeeding for the first six months and continued breastfeeding as a component of an infant’s diet up until at least two years of age.  The favorable growth and development outcomes observed in infants who are breastfed according to WHO guidelines can be attributed in part to the array of nutritional and non-nutritional components of human milk.  On the other hand, suboptimal breastfeeding, especially in the first six months of life, may result in as many as 1.4 million child deaths annually and account for an estimated 10% of the total burden of childhood diseases globally.

Despite a marked increase in human milk research in recent decades, major gaps still remain in our understanding of how human milk components influence childhood growth and development.  However, as technology improves, there has been an increasing push to expand the breadth and scope of current research, moving beyond individual nutrient analysis in order to investigate diverse human milk components and their combined associated clinical outcomes among children.

“Human Milk Composition and Child Growth and Body Composition in the First 2 Years: A Systematic Review,” published in Advances in Nutrition, explores the current evidence to help us better understand the link between human milk components and growth and body composition over the course of the first two years of life.  Due to the large number of research studies in this area, results have been organized into three manuscripts dedicated to (1) human milk macronutrients, (2) human milk micronutrients, and (3) human milk biologically active (bioactive) components.

This Supplement is free to view.  Readers can access all three articles regardless of subscription status.

Authors involved in this three-part review are part of the International Milk Composition Consortium funded by the Bill & Melinda Gates Foundation and directed by Dr. Meghan Azad, Tier 2 Canada Research Chair in Early Nutrition and the Developmental Origins of Health and Disease.  The International Milk Composition Consortium was established in 2020 to bring together maternal-child health and human milk researchers with statistical experts in order to develop an effective, harmonized approach to human milk research and analysis.  Among the authors are Dr. Meredith Brockway and ASN members Lindsay H. Allen, Daniela Hampel, and Sarah M. Reyes.

Below is a brief summary of the key findings from each of the three manuscripts:

Human Milk Macronutrients and Child Growth and Body Composition in the First 2 Years: A Systematic Review

Macronutrients in human milk have been well studied.  Nonetheless, their relationship to growth and body composition in early life is still not well understood.  In response, the authors of this review systematically searched the scientific literature, leading them to 57 studies exploring the relationship between human milk macronutrients and infant growth and body composition gathered from 5,979 mother-infant dyads.  In general, the authors found that “digestible carbohydrates were positively associated with infant weight outcomes.”  Moreover, “protein was positively associated with infant length, but no associations were reported for infant weight.”  Interestingly, “human fat was not consistently associated with any infant growth metrics.”  The authors did note that their ability to reach strong conclusions was limited by differences in study design as well as insufficient reporting of results.  Moving forward, the authors urge researchers to “accurately record and account for breastfeeding exclusivity; use consistent sampling protocols that account for the temporal variation in human milk macronutrients; and use reliable, sensitive and accurate techniques for human milk macronutrient analysis.”

Human Milk Micronutrients and Child Growth and Body Composition in the First 2 Years: A Systematic Review

Micronutrients play a critical role in the growth and development of children.  Although it is well documented that deficiency in some micronutrients, such as zinc, iron, and vitamin A, may result in poor childhood growth, knowledge about the specific relationships between human milk micronutrients and infant and child growth is incomplete.  In particular, “this systematic review reveals that little is known about how individual human milk micronutrients influence infant and young child anthropometrics.”  The authors noted that data were sparse for many micronutrients.  Moreover, despite the WHO recommendation to breastfeed for at least two years or longer, most studies focused on the first six months of life.  Nonetheless, the authors did observe that “current evidence suggests a positive correlation between infant growth and human milk concentrations of iodine, manganese, calcium, and zinc.”  The authors, however, cautioned that even these relationships “remain largely unclear due to sparse data, small sample sizes, and methodological limitations of existing studies.”

Human Milk Bioactive Components and Child Growth and Body Composition in the First 2 Years: A Systematic Review

Non-nutritive human milk bioactives, including hormones, human milk oligosaccharides and immunomodulatory components, can have a prolonged impact on an infant’s microbiome, immune function, and growth and development.  While infant formula can potentially deliver the nutrients found in human milk, it does not replace many of the critical non-nutritive human milk bioactives.  The largest body of evidence among these human milk bioactive components shows an inverse relationship between concentrations of the hormones leptin and adiponectin with infant growth, although not all studies were in agreement.  Overall, however, this systematic review “revealed inconsistent associations between human milk bioactive components and infant body composition in the first 2 years.”  Moreover, it “highlighted inconsistent data collection methods and identified many knowledge gaps for future research.”  The authors believe that “future research should ideally capture human milk intake, use biologically relevant anthropometrics, and integrate components across categories, embracing a systems biology approach to better understand how human milk components work independently and synergistically to influence infant growth.”


We invite you to explore this three-part systematic review in its entirety to gain a deeper understanding of the relationship between human milk components and childhood growth and development.  Moreover, the authors can point you to areas where more research is needed to improve infant and child health.