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

Abstract

Among exclusively breastfed infants, human milk (HM) provides complete nutrition in the first mo of life and remains an important energy source as long as breastfeeding continues. Consisting of digestible carbohydrates, proteins, and amino acids, as well as fats and fatty acids, macronutrients in human milk have been well studied; however, many aspects related to their relationship to growth in early life are still not well understood. We systematically searched Medline, EMBASE, the Cochrane Library, Scopus, and Web of Science to synthesize evidence published between 1980 and 2022 on HM components and anthropometry through 2 y of age among term-born healthy infants. From 9992 abstracts screened, 57 articles reporting observations from 5979 dyads were included and categorized based on their reporting of HM macronutrients and infant growth. There was substantial heterogeneity in anthropometric outcome measurement, milk collection timelines, and HM sampling strategies; thus, meta-analysis was not possible. In general, digestible carbohydrates were positively associated with infant weight outcomes. Protein was positively associated with infant length, but no associations were reported for infant weight. Finally, HM fat was not consistently associated with any infant growth metrics, though various associations were reported in single studies. Fatty acid intakes were generally positively associated with head circumference, except for docosahexaenoic acid. Our synthesis of the literature was limited by differences in milk collection strategies, heterogeneity in anthropometric outcomes and analytical methodologies, and by insufficient reporting of results. Moving forward, HM researchers should accurately record and account for breastfeeding exclusivity, use consistent sampling protocols that account for the temporal variation in HM macronutrients, and use reliable, sensitive, and accurate techniques for HM macronutrient analysis.

Keywords: amino acids; anthropometry; body composition; breastfeeding; breastmilk; carbohydrates; fat; fatty acids; glucose; growth; human milk; infant; lactation; lactose; macronutrients; protein.

FIGURE 1

Systematic review of associations between human milk macronutrients and infant growth in the first 2 y: PRISMA flow diagram. Irrelevant articles did not meet inclusion criteria, such as ill or preterm infants or articles that only examine formula intake. Reasons for study exclusion were recorded in the order listed in the figure. Though some studies had more than one reason for exclusion, each study was only counted once (e.g., if a study reported no human milk analytes of interest and was not in English, it was recorded as the former). Macronutrient studies are reported in the current paper; Micronutrient and Bioactive studies are reported separately [5,108].

FIGURE 2

Summary of quality assessments of included articles. Association of human milk bioactives and infant growth in the first 2 y Quality scores awarded based on the number of points assigned according to criteria in Supplemental Table S1. Detailed numeric scores are presented in Supplemental Table S2. HM, human milk. ∗Indicates that data were collected directly from authors and no quality assessment of an article was conducted.

FIGURE 3

Mean directions of associations between Concentrations of Human Milk Carbohydrates and infant growth in the first 2 y. Significant associations between carbohydrates and infant anthropometrics reflect results as reported by individual study authors (e.g., using human milk concentrations as the predictor variable, see Table 1). Value in cells indicate the number of studies examining each comparison. Red squares indicate mean positive associations, blue squares indicate mean inverse associations, white squares indicate a mean association of 0, and black squares indicate that association was not assessed. Abbreviations: Δ Weight – weight gain; Δ BMI – BMI gain; WFL - weight for length; Δ WLZ – gain in weight-for-length Z-Score; WFA – weight for age; Δ WAZ – gain in weight-for-age Z-Score; LFA - length for age; Δ LAZ – gain in length-for-age Z-Score; FFM - fat free mass; FFMI – fat free mass index; FMI - fat mass index; ABD – abdominal; Sub Q - subcutaneous.

FIGURE 4

Mean directions of associations between Concentrations of Human Milk Protein and Amino Acids and infant growth in the first 2 y. Significant associations between proteins and infant anthropometrics reflect results as reported by individual study authors (e.g., using human milk concentrations as the predictor variable, see Table 1). Value in cells indicate the number of studies examining each comparison. Red squares indicate mean positive associations, blue squares indicate mean inverse associations, white squares indicate a mean association of 0, and black squares indicate that association was not assessed. ∗Indicates that equal numbers of positive and negative associations were observed, resulting in a gradient of zero (0). Abbreviations: Δ Weight – weight gain; Δ Length – length gain; Δ BMI Z-Score – gain in BMI Z-Score; Δ HCA Z-Score – gain in head circumference-for-age Z-Score; WFL - weight for length; Δ WLZ – gain in weight-for-length Z-Score; WFA - Weight for age; Δ WAZ – gain in weight-for-age Z-Score; LFA - length for age; Δ LAZ – gain in length-for-age Z-Score; FFMI – fat free mass index; FFM - fat free mass; FMI - fat mass index.

FIGURE 5

Mean directions of associations between Concentrations of Human Milk Fat and Fatty Acids and infant growth in the first 2 y. Significant associations between immunomodulators and infant anthropometrics reflect results as reported by individual study authors (e.g., using human milk concentrations as the predictor variable, see Table 1). Value in cells indicate the number of studies examining each comparison. Red squares indicate mean positive associations, blue squares indicate mean inverse associations, white squares indicate a mean association of 0, and black squares indicate that association was not assessed. ∗Indicates that equal numbers of positive and negative associations were observed, resulting in a gradient of zero (0). ∼ Indicates contradictory results within the same study at different time points. Abbreviations: Δ Weight – weight gain; Δ Length – length gain; Δ BMI – gain in BMI; HCA Z-Score – gain in head circumference-for-age Z-Score; Δ HC – gain in head circumference; WFL - weight for length; Δ WLZ – gain in weight-for-length Z-Score; WFA - Weight for age; Δ WAZ – gain in weight-for-age Z-Score; LFA - length for age; Δ LAZ – gain in length-for-age Z-Score; FMI - fat mass index; Δ Skinfold – gain in skinfold; Abd Sub Q – abdominal subcutaneous.