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.

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.

Health and nutrition claims for infant formula: international cross sectional survey.

OBJECTIVES: To review available health and nutrition claims for infant formula products in multiple countries and to evaluate the validity of the evidence used for substantiation of claims. DESIGN: International cross sectional survey. SETTING: Public facing and healthcare professional facing company owned or company managed formula industry websites providing information about products marketed for healthy infants delivered at full term in 15 countries: Australia, Canada, Germany, India, Italy, Japan, Nigeria, Norway, Pakistan, Russia, Saudi Arabia, South Africa, Spain, the United Kingdom, and the United States in 2020-22. MAIN OUTCOME MEASURES: Number and type of claims made for each product and ingredient. References cited were reviewed and risk of bias was assessed for registered clinical trials using the Cochrane risk of bias tool, and for systematic reviews using the Risk Of Bias in Systematic reviews tool. RESULTS: 757 infant formula products were identified, each with a median of two claims (range from 1 (Australia) to 4 (US)), and 31 types of claims across all products. Of 608 products with ≥1 claims, the most common claim types were "helps/supports development of brain and/or eyes and/or nervous system" (323 (53%) products, 13 ingredients), "strengthens/supports a healthy immune system" (239 (39%) products, 12 ingredients), and "helps/supports growth and development" (224 (37%) products, 20 ingredients). 41 groups of ingredients were associated with ≥1claims, but many claims were made without reference to a specific ingredient (307 (50%) products). The most common groups of ingredients cited in claims were long chain polyunsaturated fatty acids (278 (46%) products, 9 different claims); prebiotics, probiotics, or synbiotics (225 (37%) products, 19 claims); and hydrolysed protein (120 (20%) products, 9 claims). 161/608 (26%) products with ≥1 claims provided a scientific reference to support the claim-266 unique references were cited for 24 different claim types for 161 products. The reference types most frequently cited were clinical trials (50%, 134/266) and reviews (20%, 52/266). 28% (38/134) of referenced clinical trials were registered, 14% (19/134) prospectively. 58 claims referred to 32 registered clinical trials, of which 51 claims (27 trials) related to a randomised comparison. 46 of 51 claims (90%) referenced registered clinical trial outcomes at high risk of bias, and all cited systematic reviews and pooled analyses, carried a high risk of bias. CONCLUSIONS: Most infant formula products had at least one health and nutrition claim. Multiple ingredients were claimed to achieve similar health or nutrition effects, multiple claims were made for the same ingredient type, most products did not provide scientific references to support claims, and referenced claims were not supported by robust clinical trial evidence.

Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.

A review of the disruption of breastfeeding supports in response to the COVID-19 pandemic in five Western countries and applications for clinical practice.

BACKGROUND: The COVID-19 pandemic has significantly altered how breastfeeding support is provided, resulting in mixed breastfeeding outcomes and experiences for mothers. The World Health Organization has consistently supported breastfeeding from the beginning of the pandemic. However, recommendations from obstetrical and gynaecological societies within individual countries have varied in their alignment with this guidance, resulting in inconsistent recommendations. It is unknown how breastfeeding guidelines, maternal breastfeeding experiences, and breastfeeding initiation and duration compared across five Western countries. The current study is comprised of two parts, each with a different objective. Part One objective: to review pandemic-related changes in professional society guidelines on breastfeeding support in Australia, New Zealand, Canada, the United Kingdom, and the United States; and Part Two objective: to conduct a narrative review to summarize the evidence of how the pandemic has changed breastfeeding initiation, duration, and mothers' breastfeeding experiences during the pandemic in these five countries and provide recommendations for clinical lactation support. METHODS: We searched for indicators that are impactful on breastfeeding outcomes: skin-to-skin contact, rooming in, direct breastfeeding and breast washing, in the five countries mentioned above and compared these to the recommendations from the World Health Organization. Next, we conducted a narrative review of the literature from these five countries to explore how the pandemic altered breastfeeding outcomes and used this information to provide suggestions for clinical practice moving forward. RESULTS: Recommendations on the four practices above differed by country and were not always in alignment with the World Health Organization recommendations. Mother-infant separation after birth in the United States was associated with a lower prevalence of breastfeeding initiation and duration. While some mothers reported positive breastfeeding experiences during the pandemic, many mothers indicated negative experiences related to decreased social and professional support. CONCLUSIONS: The pandemic can inform practice recommendations and can be viewed as an opportunity to permanently modify existing methods to support breastfeeding families. The use of virtual care increased during the pandemic and should continue with specific considerations for prioritizing in-person care. This will help to provide more timely and accessible support for breastfeeding mothers.