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

Abstract

Human milk (HM) provides a plethora of nutritional and non-nutritional compounds that support infant development. For many compounds, concentrations vary substantially among mothers and across lactation, and their impact on infant growth is poorly 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 infants. Outcomes included weight-for-length, length-for-age, weight-for-age, body mass index (in kg/m²)-for-age, and growth velocity. From 9992 abstracts screened, 144 articles were included and categorized based on their reporting of HM micronutrients, macronutrients, or bioactive components. Micronutrients (vitamins and minerals) are reported here, based on 28 articles involving 2526 mother-infant dyads. Studies varied markedly in their designs, sampling times, geographic and socioeconomic settings, reporting practices, and the HM analytes and infant anthropometrics measured. Meta-analysis was not possible because data were sparse for most micronutrients. The most-studied minerals were zinc (15 articles, 1423 dyads) and calcium (7 articles, 714 dyads). HM iodine, manganese, calcium, and zinc concentrations were positively associated with several outcomes (each in ≥2 studies), whereas magnesium (in a single study) was negatively associated with linear growth during early lactation. However, few studies measured HM intake, adjusted for confounders, provided adequate information about complementary and formula feeding, or adequately described HM collection protocols. Only 4 studies (17%) had high overall quality scores. The biological functions of individual HM micronutrients are likely influenced by other HM components; yet, only 1 study analyzed data from multiple micronutrients simultaneously, and few addressed other HM components. Thus, available evidence on this topic is largely inconclusive and fails to address the complex composition of HM. High-quality research employing chronobiology and systems biology approaches is required to understand how HM components work independently and together to influence infant growth and to identify new avenues for future maternal, newborn, or infant nutritional interventions.

Keywords: anthropometry; body composition; calcium; growth; human milk; infant; lactation; micronutrients; stunting; zinc.

FIGURE 1

Systematic review of associations between human milk micronutrients and infant growth in the first 2 y: PRISMA flow diagram. Reasons for study exclusion were recorded in the order listed in the figure. Though some studies had >1 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). Micronutrient studies are reported in the current paper; Macronutrient and Non-nutritive Bioactive studies are reported separately.

FIGURE 2

Association of human milk micronutrients and infant growth in the first 2 y: Summary of quality assessments of included articles. Asterisks denote companion articles from the same study. Quality scores are awarded based on the number of points assigned according to the criteria in Supplementary Table 1. Detailed numeric scores are presented in Supplementary Table 2.

FIGURE 3

Association of human milk (HM) micronutrients and infant growth in the first 2 y: Summary of data collection and study time points (A) and anthropometric outcome measurements (B) for all included articles, highlighting zinc as an example. (A) Text color reflects that studies reported HM micronutrients as either estimated intakes (blue text) or concentrations (black text). Asterisks denote companion articles from the same study. The width of rectangles reflects the time postpartum measurements were taken. Narrow rectangles reflect that all measurements occurred approximately at the same time postpartum for all dyads. Wide rectangles reflect that the timing of measurements varied across dyads. (B) Zinc is highlighted here because it had the most evidence available, but even so, data were too sparse to conduct a meta-analysis. Whether HM zinc was measured and data were extractable is denoted as follows: yes (green circle); yes but not extractable (striped yellow circle); no (red circle).

FIGURE 4

Association of human milk (HM) micronutrients and infant growth in the first 2 y: Summary results of all included articles. Associations between HM micronutrients and infant anthropometrics reflect results as reported by study authors (e.g., using HM concentrations or estimated intakes as the predictor variable, see Table 1). Red squares indicate positive associations, blue squares indicate an inverse association, white squares indicate no pooled association and black squares indicate association was not examined in any studies. The number in each square indicates the number of studies examining the association. Breastfeeding exclusivity was difficult to determine in most studies; thus, results summarize data from all included studies and may include infants with varying diets (see Supplementary Table 2). Multiple∗ indicates multiple micronutrients analyzed in multivariate models. B6, vitamin B-6; B12, vitamin B-12; HAZ, height-for-age z-score; HCA-Z, head circumference-for-age z-score; LAZ, length-for-age z-score; Pro-A, provitamin A/β-carotene; WAZ, weight-for-age z-score; WFLZ, weight-for-length z-score; WHZ, weight-for-height z-score; WLZ, weight-for-length z-score; ∗Supplemented group only; ± Association lost after adjustment for covariates; ∼ Body Composition for vitamin A = arc, the sin of the square root of (weight/height²-A) - authors also referred to this as BMI; for zinc = skinfold thickness.