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

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.

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

Human milk (HM) contains macronutrients, micronutrients, and a multitude of other bioactive factors, which can have a long-term impact on infant growth and development. We systematically searched MEDLINE, EMBASE, 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. From 9992 abstracts screened, 141 articles were included and categorized based on their reporting of HM micronutrients, macronutrients, or bioactive components. Bioactives including hormones, HM oligosaccharides (HMOs), and immunomodulatory components are reported here, based on 75 articles from 69 unique studies reporting observations from 9980 dyads. Research designs, milk collection strategies, sampling times, geographic and socioeconomic settings, reporting practices, and outcomes varied considerably. Meta-analyses were not possible because data collection times and reporting were inconsistent among the studies included. Few measured infant HM intake, adjusted for confounders, precisely captured breastfeeding exclusivity, or adequately described HM collection protocols. Only 5 studies (6%) had high overall quality scores. Hormones were the most extensively examined bioactive with 46 articles (n = 6773 dyads), compared with 13 (n = 2640 dyads) for HMOs and 12 (n = 1422 dyads) for immunomodulatory components. Two studies conducted untargeted metabolomics. Leptin and adiponectin demonstrated inverse associations with infant growth, although several studies found no associations. No consistent associations were found between individual HMOs and infant growth outcomes. Among immunomodulatory components in HM, IL-6 demonstrated inverse relationships with infant growth. Current research on HM bioactives is largely inconclusive and is insufficient to address the complex composition of HM. Future research should ideally capture HM intake, use biologically relevant anthropometrics, and integrate components across categories, embracing a systems biology approach to better understand how HM components work independently and synergistically to influence infant growth.

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

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.

Oils Rich in α-Linolenic Acid or Docosahexaenoic Acid Have Distinct Effects on Plasma Oxylipin and Adiponectin Concentrations and on Monocyte Bioenergetics in Women with Obesity.

BACKGROUND: Omega-3 fatty acids, including DHA and α-linolenic acid (ALA), are proposed to improve metabolic health by reducing obesity-associated inflammation. Their effects are mediated in part by conversion to oxylipins. ALA is relatively understudied, and direct comparisons to other omega-3 fatty acids are limited. OBJECTIVES: We compared the effects of equal doses of ALA and DHA on plasma oxylipins and markers of metabolic health in women with obesity. METHODS: We carried out a randomized, double-blind, crossover clinical trial where women aged 20-51 with a BMI of 30-51 kg/m2 were supplemented with 4 g/day of ALA or DHA for 4 weeks in the form of ALA-rich flaxseed oil or DHA-rich fish oil. The primary outcome, the plasma oxylipin profile, was assessed at Days 0 and 28 of each phase by HPLC-MS/MS. Plasma fatty acids, inflammatory markers, and the monocyte glucose metabolism were key secondary outcomes. Data were analyzed using a mixed model. RESULTS: Compared to the baseline visit, there were higher plasma levels of nearly all oxylipins derived from DHA (3.8-fold overall; P < 0.001) and EPA (2.7-fold overall; P < 0.05) after 28 days of fish-oil supplementation, while there were no changes to oxylipins after flaxseed-oil supplementation. Neither supplement altered plasma cytokines; however, adiponectin was increased (1.1-fold; P < 0.05) at the end of the fish-oil phase. Compared to the baseline visit, 28 days of flaxseed-oil supplementation reduced ATP-linked oxygen consumption (0.75-fold; P < 0.05) and increased spare respiratory capacity (1.4-fold; P < 0.05) in monocytes, and countered the shift in oxygen consumption induced by LPS. CONCLUSIONS: Flaxseed oil and fish oil each had unique effects on metabolic parameters in women with obesity. The supplementation regimens were insufficient to reduce inflammatory markers but adequate to elicit increases in omega-3 oxylipins and adiponectin in response to fish oil and to alter monocyte bioenergetics in response to flaxseed oil. This trial was registered at clinicaltrials.gov as NCT03583281.