The contributions of parental lactation on offspring development: It's not udder nonsense!

The Developmental Origins of Health and Disease (DOHaD) hypothesis describes how maternal stress exposures experienced during critical periods of perinatal life are linked to altered developmental trajectories in offspring. Perinatal stress also induces changes in lactogenesis, milk volume, maternal care, and the nutritive and non-nutritive components of milk, affecting short and long-term developmental outcomes in offspring. For instance, selective early life stressors shape the contents of milk, including macro/micronutrients, immune components, microbiota, enzymes, hormones, milk-derived extracellular vesicles, and milk microRNAs. In this review, we highlight the contributions of parental lactation to offspring development by examining changes in the composition of breast milk in response to three well-characterized maternal stressors: nutritive stress, immune stress, and psychological stress. We discuss recent findings in human, animal, and in vitro models, their clinical relevance, study limitations, and potential therapeutic significance to improving human health and infant survival. We also discuss the benefits of enrichment methods and support tools that can be used to improve milk quality and volume as well as related developmental outcomes in offspring. Lastly, we use evidence-based primary literature to convey that even though select maternal stressors may modulate lactation biology (by influencing milk composition) depending on the severity and length of exposure, exclusive and/or prolonged milk feeding may attenuate the negative in utero effects of early life stressors and promote healthy developmental trajectories. Overall, scientific evidence supports lactation to be protective against nutritive and immune stressors, but the benefits of lactation in response to psychological stressors need further investigation.

Prepregnancy Body Mass Index Is Associated with Time-Dependent Changes in Secretory Activation Measures During the First 7 Days Postpartum in Breast Pump-dependent Mothers of Premature Infants.

Background: Little is known about the biology of secretory activation (SA) in overweight and obese (OW/OB) mothers who are breast pump dependent with a premature infant in the neonatal intensive care unit. Objective: To compare time-dependent changes in daily pumped milk volume, maternal milk sodium (Na) concentration, and Na-to-potassium (K) ratios (Na:K) in the first 14 days postpartum in breast pump-dependent mothers with prepregnancy body mass index (BMI) <27 and BMI ≥27 kg/m2. Design/Methods: This secondary analysis for 39 subjects, 44% (n = 17) with prepregnancy BMI <27 and 56% (n = 22) with BMI ≥27, included transformed data of outcome measures, chi-square, t-tests, and growth curve models. Results: For days 1-7, daily pumped milk volume increased significantly more rapidly for mothers with BMI <27 (65.82 mL/d) versus BMI ≥27 (33.08 mL/d), but the daily rate of change in pumped milk volume during days 8-14 was not statistically different. Daily milk Na concentration decreased significantly faster in BMI <27 (-3.93 mM/d) versus BMI ≥27 (-2.00 mM/day) during days 1-7, but was not significantly different for days 8-14. No statistical differences were noted for Na:K ratio for either time period. Conclusion: These data add biologic evidence to previous research, suggesting delayed or impaired SA in OW/OB mothers, and suggest that the window of opportunity for research and clinical interventions is days 1-7 postpartum in this population.

lncRNA NORAD is consistently detected in breastmilk exosomes and its expression is downregulated in mothers of preterm infants.

Breast milk is the ideal food for infants and undoubtedly has immediate and long­term benefits. Breast milk contains extracellular vesicles (EVs) i.e., exosomes secreted by maternal breast cells. Exosomes carry genetic material, such as long non­coding RNAs (lncRNAs), which possibly participate in cell­to­cell communications, as they are known to regulate critical gene pathways. The aim of the present study was to screen human breastmilk exosomes for their lncRNA cargo and to examine exosomal lncRNA levels associated with milk obtained from mothers that gave birth at term or prematurely (<37 weeks of gestation). Samples were collected at 3 weeks postpartum from 20 healthy, breastfeeding mothers; 10 mothers had given birth at full­term and 10 mothers preterm. Exosomal RNA was extracted from all samples and the expression of 88 distinct lncRNAs was determined using reverse transcription­quantitative PCR. A total of 13 lncRNAs were detected in ≥85% of the samples, while 31 were detected in ≥50% of the samples. Differential expression analysis of the lncRNAs between the two groups revealed ≥2­fold differences, with generally higher lncRNA concentrations found in the milk of the mothers that gave birth at term compared with those that gave birth preterm. Among these, the non­coding RNA activated at DNA damage (NORAD) was prominently detected in both groups, and its expression was significantly downregulated in the breast milk exosomes of mothers who delivered preterm. On the whole, the present study demonstrates that breast milk lncRNAs may be important factors of normal early human development. Collectively, the presence of lncRNAs in human breast milk may explain the consistent inability of researchers to fully 'humanize' animal milk.

Controversia actual sobre el papel crítico de los ácidos grasos poliinsaturados de cadena larga, araquidónico (ARA) y docosahexaenoico (DHA), en el lactante / Controversy about the critical role of long-chain polyunsaturated fatty acids, arachidonic acid (ARA) and docosahexaenoic acid (DHA), during infancy

Los ácidos grasos poliinsaturados de cadena larga (AGPI-CL) son críticos para el crecimiento y desarrollo infantil, en particular los ácidos araquidónico (ARA, C20:4n-6) y docosahexaenoico (DHA, C22:6n-3). El ARA y el DHA son componentes de los fosfolípidos de las membranas celulares y desempeñan importantes funciones en la división, diferenciación y señalización celular, siendo el DHA el ácido graso de la serie n-3 predominante en el cerebro y la retina en desarrollo. Durante el tercer trimestre de la gestación, los AGPI-CL aumentan de forma sustancial en la circulación fetal, observándose un proceso de “biomagnificación” en el cerebro fetal. Además, los AGPI-CL son precursores de los eicosanoides y metabolitos implicados en la modulación de la intensidad y duración de la respuesta inmunitaria. La síntesis de AGPI-CL implica un complejo proceso de desaturación y elongación desde los precursores principales, el ácido linoleico (18:3 n-6) (LA) (serie n-6) y el ácido α-linolénico (20:3 n-3) (LNA) (serie n-3), por los cuales compiten las enzimas desaturasas (FADS) y elongasas (ELOVL). Es importante indicar que en los primeros meses de vida, como consecuencia de la baja actividad enzimática, la síntesis de AGPI-CL a partir de LA y LNA es reducida, especialmente en los niños con variaciones en los genes que codifican las FADS y ELOVL involucradas en la síntesis de AGPI-CL y que, por tanto, son incapaces de cubrir por sí mismos sus necesidades de ARA y DHA. Los homocigotos para el haplotipo A de las FADS (97 % de la población latinoamericana) muestran niveles de ARA y DHA de tan solo un 43 % y un 24 %, respectivamente, inferiores a los de los individuos con haplotipo D (más frecuente en Europa, África y Asia). (AU)

Long-chain polyunsaturated fatty acids (LC-PUFAs) are critical for infant growth and development, particularly arachidonic acid (ARA, C20:4n-6) and docosahexaenoic acid (DHA, C22:6n-3). ARA and DHA are components of cell membrane phospholipids and play an important role in cell division, differentiation, and signaling; and DHA is the n-3 fatty acid predominant in the developing brain and retina. During the third trimester of pregnancy, LC-PUFAs increase substantially in fetal circulation, and a “biomagnification” process in the fetal brain is observed. Moreover, LC-PUFAs are precursors of eicosanoids and metabolites, which modulate the intensity and duration of the immune response.LC-PUFA synthesis implies complex desaturation and elongation processes on their principal precursors, linoleic acid (LA) (18:3 n-6) (series n-6) and α-linolenic acid (LNA) (20:3 n-3) (series n-3), where fatty acid desaturases (FADS) and elongases (ELOVL) are competing. It is important to notice that during the first months of life, as a consequence of low enzymatic activity, LC-PUFA synthesis from LA and LNA is reduced, especially in those infants carrying variations in the FADS and ELOVL genes, which are involved in LC-PUFA synthesis, and so they are unable to supply their own DHA and ARA needs. Homozygote infants for FADS haplotype A (97 % of the Latinoamerican population) show low levels of ARA (only 43 %) and DHA (only 24 %) when compared to those carrying haplotype D (more prevalent in Europe, Africa and Asia). (AU)

[Controversy about the critical role of long-chain polyunsaturated fatty acids, arachidonic acid (ARA) and docosahexaenoic acid (DHA), during infancy]. / Controversia actual sobre el papel crítico de los ácidos grasos poliinsaturados de cadena larga, araquidónico (ARA) y docosahexaenoico (DHA), en el lactante.

INTRODUCTION: Long-chain polyunsaturated fatty acids (LC-PUFAs) are critical for infant growth and development, particularly arachidonic acid (ARA, C20:4n-6) and docosahexaenoic acid (DHA, C22:6n-3). ARA and DHA are components of cell membrane phospholipids and play an important role in cell division, differentiation, and signaling; and DHA is the n-3 fatty acid predominant in the developing brain and retina. During the third trimester of pregnancy, LC-PUFAs increase substantially in fetal circulation, and a "biomagnification" process in the fetal brain is observed. Moreover, LC-PUFAs are precursors of eicosanoids and metabolites, which modulate the intensity and duration of the immune response. LC-PUFA synthesis implies complex desaturation and elongation processes on their principal precursors, linoleic acid (LA) (18:3 n-6) (series n-6) and α-linolenic acid (LNA) (20:3 n-3) (series n-3), where fatty acid desaturases (FADS) and elongases (ELOVL) are competing. It is important to notice that during the first months of life, as a consequence of low enzymatic activity, LC-PUFA synthesis from LA and LNA is reduced, especially in those infants carrying variations in the FADS and ELOVL genes, which are involved in LC-PUFA synthesis, and so they are unable to supply their own DHA and ARA needs. Homozygote infants for FADS haplotype A (97 % of the Latinoamerican population) show low levels of ARA (only 43 %) and DHA (only 24 %) when compared to those carrying haplotype D (more prevalent in Europe, Africa and Asia). Human milk is the only source of LA, LNA, ARA, and DHA for the neonate and infant till complementary feeding (CF) is introduced. Infants fed with infant formulas must receive enough amounts of LA, LNA, ARA, and DHA to cover their nutritional requirements. The new guidelines by the European Food Safety Authority (EFSA) (2016) recommend that infant formulas and follow-on formulas must contain 20-50 mg of DHA/100 kcal (0.5-1 % of total fatty acids, which is higher than in human milk and the majority of infant formulas in the market), and it is not necessary to add ARA. This new regulation, which is already applicable since February 2020, has resulted in profound controversy because there is no scientific evidence about its appropriateness and safety for healthy children. Then, different international expert groups have revised the research already published about the effects of ARA and DHA addition to infant formulas, and discussed different emerging questions from this European directive. The expert group led from the University of Granada (Spain) recommends the addition of ARA in similar or higher concentrations than those of DHA, at least equal to those present in human milk (0.3 % of total fatty acids), although preferably 0.5 % and up to around 0.64 % of total fatty acids, since new studies confirm the optimal intake of ARA and DHA during the different developmental stages. This recommendation could be of particular importance for infants carrying the haplotype A of FADS.

INTRODUCCIÓN: Los ácidos grasos poliinsaturados de cadena larga (AGPI-CL) son críticos para el crecimiento y desarrollo infantil, en particular los ácidos araquidónico (ARA, C20:4n-6) y docosahexaenoico (DHA, C22:6n-3). El ARA y el DHA son componentes de los fosfolípidos de las membranas celulares y desempeñan importantes funciones en la división, diferenciación y señalización celular, siendo el DHA el ácido graso de la serie n-3 predominante en el cerebro y la retina en desarrollo. Durante el tercer trimestre de la gestación, los AGPI-CL aumentan de forma sustancial en la circulación fetal, observándose un proceso de "biomagnificación" en el cerebro fetal. Además, los AGPI-CL son precursores de los eicosanoides y metabolitos implicados en la modulación de la intensidad y duración de la respuesta inmunitaria. La síntesis de AGPI-CL implica un complejo proceso de desaturación y elongación desde los precursores principales, el ácido linoleico (18:3 n-6) (LA) (serie n-6) y el ácido α-linolénico (20:3 n-3) (LNA) (serie n-3), por los cuales compiten las enzimas desaturasas (FADS) y elongasas (ELOVL). Es importante indicar que en los primeros meses de vida, como consecuencia de la baja actividad enzimática, la síntesis de AGPI-CL a partir de LA y LNA es reducida, especialmente en los niños con variaciones en los genes que codifican las FADS y ELOVL involucradas en la síntesis de AGPI-CL y que, por tanto, son incapaces de cubrir por sí mismos sus necesidades de ARA y DHA. Los homocigotos para el haplotipo A de las FADS (97 % de la población latinoamericana) muestran niveles de ARA y DHA de tan solo un 43 % y un 24 %, respectivamente, inferiores a los de los individuos con haplotipo D (más frecuente en Europa, África y Asia). La leche humana constituye la única fuente de LA, LNA, ARA y DHA para el recién nacido y el lactante hasta la introducción de la alimentación complementaria (AC). Los niños alimentados con fórmulas infantiles deben recibir las cantidades de LA, LNA, ARA y DHA suficientes para cubrir los requerimientos nutricionales. La nueva normativa de la Autoridad Europea de Seguridad Alimentaria (EFSA) (2016) indica que las fórmulas infantiles de inicio y continuación deben contener entre 20 y 50 mg de DHA/100 kcal (0,5-1 % del total de ácidos grasos: más elevado que en la leche humana y en la mayoría de fórmulas infantiles comercializadas) sin la necesidad de incluir también ARA. Esta nueva regulación, que está vigente desde febrero de 2020, ha despertado una gran controversia, al no existir evidencia científica acerca de su pertinencia y seguridad para los niños sanos. Por ello, diferentes grupos de expertos internacionales han revisado la investigación publicada acerca del ARA y el DHA, y discutido diferentes cuestiones emergentes a partir de esta nueva directiva Europea. El grupo de expertos, liderado desde la Universidad de Granada (España), recomienda la adición de ARA en concentraciones iguales o mayores que las de DHA, alcanzando al menos el contenido presente en la leche humana (0,3 % del total de ácidos grasos), aunque preferiblemente un 0,5 % y hasta alrededor del 0,64 % del total de AG, hasta que nuevos estudios confirmen la ingesta óptima de ARA y DHA durante las distintas etapas del desarrollo. Esta recomendación podría ser de especial importancia para los niños portadores del haplotipo A de las FADS.

Human Breast Milk Composition and Function in Human Health: From Nutritional Components to Microbiome and MicroRNAs.

Human breast milk (HBM) is not only an indispensable source of nutrients for early human growth and development, supplying components that support infant growth and development, but also contains various essential immunologic components with anti-infectious activities and critical roles in the formation of immunity. It is also known that HBM contains its own unique microbiome, including beneficial, commensal, and potentially probiotic bacteria, that can contribute to infant gut colonization. In addition, HBM-derived extracellular vesicles, exosomes, and microRNA are attracting increasing interest for their potential to transfer to the infant and their role in infant development. In this article, we examine some of the various constituents in HBM and review the evidence supporting their associated health effects and their potential applications in human health.

Use and experiences of galactagogues while breastfeeding among Australian women.

BACKGROUND: Galactagogues are substances thought to increase breast milk production, however evidence to support their efficacy and safety remain limited. We undertook a survey among Australian women to examine patterns of use of galactagogues and perceptions regarding their safety and effectiveness. METHODS: An online, cross-sectional survey was distributed between September and December 2019 via national breastfeeding and preterm birth support organisations, and networks of several research institutions in Australia. Women were eligible to participate if they lived in Australia and were currently/previously breastfeeding. The survey included questions about galactagogue use (including duration and timing), side effects and perceived effectiveness (on a scale of 1 [Not at all effective] to 5 [Extremely effective]). RESULTS: Among 1876 respondents, 1120 (60%) reported using one or more galactagogues. Women were 31.5 ± 4.8 years (mean ± standard deviation) at their most recent birth. Sixty-five percent of women were currently breastfeeding at the time of the survey. The most commonly reported galactagogues included lactation cookies (47%), brewer's yeast (32%), fenugreek (22%) and domperidone (19%). The mean duration of use for each galactagogue ranged from 2 to 20 weeks. Approximately 1 in 6 women reported commencing galactagogues within the first week postpartum. Most women reported receiving recommendations to use herbal/dietary galactagogues from the internet (38%) or friends (25%), whereas pharmaceutical galactagogues were most commonly prescribed by General Practitioners (72%). The perceived effectiveness varied greatly across galactagogues. Perceived effectiveness was highest for domperidone (mean rating of 3.3 compared with 2.0 to 3.0 among other galactagogues). Over 23% of domperidone users reported experiencing multiple side effects, compared to an average of 3% of women taking herbal galactagogues. CONCLUSIONS: This survey demonstrates that galactagogues use is common in Australia. Further research is needed to generate robust evidence about galactagogues' efficacy and safety to support evidence-based strategies and improve breastfeeding outcomes.

Rates and time trends in the consumption of breastmilk, formula, and animal milk by children younger than 2 years from 2000 to 2019: analysis of 113 countries.

BACKGROUND: Previous analyses of trends in feeding indicators of children younger than 2 years have been limited to low-income and middle-income countries. We aimed to assess time trends in the consumption of different types of milk (breastmilk, formula, and animal milk) by children younger than 2 years from 2000 to 2019 at a global level. METHODS: In this time-series analysis, we combined cross-sectional data from 487 nationally representative surveys from low-income and middle-income countries and information from high-income countries to estimate seven infant and young child feeding indicators in up to 113 countries. Multilevel linear models were used in pooled analyses to estimate annual changes in feeding practices from 2000 to 2019 for country income groups and world regions. FINDINGS: For the absolute average annual changes, we found significant gains in any breastfeeding at age 6 months in high-income countries (1·29 percentage points [PPs] per year [95% CI 1·12 to 1·45]; p<0·0001) and at age 1 year in high-income countries (1·14 PPs per year [0·99 to 1·28]; p<0·0001) and upper-middle-income countries (0·53 PPs per year [0·23 to 0·82]; p<0·0001). We also found a small reduction in low-income countries for any breastfeeding at age 6 months (-0·07 PPs per year [-0·11 to -0·03]; p<0·0001) and age 1 year (-0·13 PPs per year [-0·18 to -0·09]; p<0·0001). Data on exclusive breastfeeding and consumption of formula and animal milk were only available for low-income and middle-income countries, where exclusive breastfeeding in the first 6 months of life increased by 0·70 PPs per year (0·51-0·88; p<0·0001) to reach 48·6% (41·9-55·2) in 2019. Exclusive breastfeeding increased in all world regions except for the Middle East and north Africa. Formula consumption in the first 6 months of life increased in upper-middle-income countries and in east Asia and the Pacific, Latin America and the Caribbean, the Middle East and north Africa, and eastern Europe and central Asia, whereas the rates remained below 8% in sub-Saharan Africa and south Asia. Animal milk consumption by children younger than 6 months decreased significantly (-0·41 PPs per year [-0·51 to -0·31]; p<0·0001) in low-income and middle-income countries. INTERPRETATION: We found some increases in exclusive and any breastfeeding at age 6 months in various regions and income groups, while formula consumption increased in upper-middle-income countries. To achieve the global target of 70% exclusive breastfeeding by 2030, however, rates of improvement will need to be accelerated. FUNDING: Bill & Melinda Gates Foundation, through WHO.

The need to study human milk as a biological system.

Critical advancement is needed in the study of human milk as a biological system that intersects and interacts with myriad internal (maternal biology) and external (diet, environment, infections) factors and its plethora of influences on the developing infant. Human-milk composition and its resulting biological function is more than the sum of its parts. Our failure to fully understand this biology in a large part contributes to why the duration of exclusive breastfeeding remains an unsettled science (if not policy). Our current understanding of human-milk composition and its individual components and their functions fails to fully recognize the importance of the chronobiology and systems biology of human milk in the context of milk synthesis, optimal timing and duration of feeding, and period of lactation. The overly simplistic, but common, approach to analyzing single, mostly nutritive components of human milk is insufficient to understand the contribution of either individual components or the matrix within which they exist to both maternal and child health. There is a need for a shift in the conceptual approach to studying human milk to improve strategies and interventions to support better lactation, breastfeeding, and the full range of infant feeding practices, particularly for women and infants living in undernourished and infectious environments. Recent technological advances have led to a rising movement towards advancing the science of human-milk biology. Herein, we describe the rationale and critical need for unveiling the multifunctionality of the various nutritional, nonnutritional, immune, and biological signaling pathways of the components in human milk that drive system development and maturation, growth, and development in the very early postnatal period of life. We provide a vision and conceptual framework for a research strategy and agenda to change the field of human-milk biology with implications for global policy, innovation, and interventions.

The Gut‒Breast Axis: Programming Health for Life.

The gut is a pivotal organ in health and disease. The events that take place in the gut during early life contribute to the programming, shaping and tuning of distant organs, having lifelong consequences. In this context, the maternal gut plays a quintessence in programming the mammary gland to face the nutritional, microbiological, immunological, and neuroendocrine requirements of the growing infant. Subsequently, human colostrum and milk provides the infant with an impressive array of nutrients and bioactive components, including microbes, immune cells, and stem cells. Therefore, the axis linking the maternal gut, the breast, and the infant gut seems crucial for a correct infant growth and development. The aim of this article is not to perform a systematic review of the human milk components but to provide an insight of their extremely complex interactions, which render human milk a unique functional food and explain why this biological fluid still truly remains as a scientific enigma.

Maternal aryl hydrocarbon receptor activation protects newborns against necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a disease of premature infants characterized by acute intestinal necrosis. Current dogma suggests that NEC develops in response to post-natal dietary and bacterial factors, and so a potential role for in utero factors in NEC remains unexplored. We now show that during pregnancy, administration of a diet rich in the aryl hydrocarbon receptor (AHR) ligand indole-3-carbinole (I3C), or of breast milk, activates AHR and prevents NEC in newborn mice by reducing Toll-like receptor 4 (TLR4) signaling in the newborn gut. Protection from NEC requires activation of AHR in the intestinal epithelium which is reduced in mouse and human NEC, and is independent of leukocyte activation. Finally, we identify an AHR ligand ("A18") that limits TLR4 signaling in mouse and human intestine, and prevents NEC in mice when administered during pregnancy. In summary, AHR signaling is critical in NEC development, and maternally-delivered, AHR-based therapies may alleviate NEC.

Breast Milk for Term and Preterm Infants-Own Mother's Milk or Donor Milk?

Hormones are important biological regulators, controlling development and physiological processes throughout life. We investigated pituitary hormones such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) and total protein levels during the first 6 months of lactation. Breast milk samples were collected every fourth week of lactation from mothers who gave birth to preterm (n = 14) or term (n = 16) infants. Donor milk is suggested when own mother's milk is not available; therefore, we collected breast milk samples before and after Holder pasteurization (HoP) from the Breast Milk Collection Center of Pécs, Hungary. Three infant formulas prepared in the Neonatal Intensive Care Unit of the University of Pécs were tested at three different time points. Our aim was to examine the hormone content of own mother's milk and donor milk. There were no significant changes over time in the concentrations of any hormone. Preterm milk had higher PRL (28.2 ± 2.5 vs 19.3 ± 2.3 ng/mL) and LH (36.3 ± 8.8 vs 15.9 ± 4.1 mIU/L) concentrations than term milk during the first 6 months of lactation. Total protein and FSH concentrations did not differ between preterm and term breast milk. Holder pasteurization decreased the PRL concentration (30.4 ± 1.8 vs 14.4 ± 0.6 ng/mL) and did not affect gonadotropin levels of donor milk. Infant formulas have higher total protein content than breast milk but do not contain detectable levels of pituitary hormones. Differences were detected in the content of pituitary hormones produced for preterm and term infants. Divergence between feeding options offers opportunities for improvement of nutritional guidelines for both hospital and home feeding practices.

Human Milk Hormone Intake in the First Month of Life and Physical Growth Outcomes in Preterm Infants.

CONTEXT: Human milk contains hormones that regulate metabolism. Extrauterine growth restriction remains common among preterm infants, but the effect of ingesting milk hormones on preterm infant growth is poorly understood. OBJECTIVE: To quantify associations of longitudinal exposure to leptin, adiponectin, and insulin in milk with physical growth of preterm infants. DESIGN/METHODS: In 50 preterm neonates (median gestational age 29.4 weeks), we sampled maternal milk on day-of-life 7, 14, 21, and 28 and measured hormone levels in whole milk by ELISA. Milk leptin levels were available for a subset of 18 infants. We calculated milk hormone doses by multiplying the hormone level by the milk volume ingested on each day and estimated the area under the curve (AUC) to reflect longitudinal exposure. We analyzed associations of milk hormone exposure with growth outcomes in generalized estimated equations. MAIN OUTCOME MEASURES: Weight gain velocity and z-scores in weight, length, head circumference, and body mass index at 36 weeks' postmenstrual age (PMA). RESULTS: Higher leptin intake was associated with greater weight gain (2.17g/kg/day [95% CI, 1.31, 3.02]) and weight z-score at 36 weeks' PMA (0.30 [0.08, 0.53] higher z-score per tertile). Higher adiponectin intake was associated with greater length z-score (0.41 [0.13, 0.69]), however, this association was nullified after adjustment of protein and calorie intake. Higher adiponectin was associated with smaller head circumference z-score (-0.36 [-0.64, -0.07]). Insulin was not associated with growth outcomes. CONCLUSIONS: Milk leptin and adiponectin exposures may affect growth of preterm infants. The long-term effects of milk hormones warrant further investigation.

The "weanling's dilemma" revisited: Evolving bodies of evidence and the problem of infant paleodietary interpretation.

Breastfeeding is known to be a powerful mediator of maternal and childhood health, with impacts throughout the life course. Paleodietary studies of the past 30 years have accordingly taken an enduring interest in the health and diet of young children as a potential indicator of population fertility, subsistence, and mortality patterns. While progress has been made in recent decades toward acknowledging the agency of children, many paleodietary reconstructions have failed to incorporate developments in cognate disciplines revealing synergistic dynamics between maternal and offspring biology. Paleodietary interpretation has relied heavily on the "weanling's dilemma," in which infants are thought to face a bleak choice between loss of immunity or malnutrition. Using a review of immunological and epidemiological evidence for the dynamic and supportive role that breastfeeding plays throughout the complementary feeding period, this article offers context and nuance for understanding past feeding transitions. We suggest that future interpretative frameworks for infant paleodietary and bioarchaeological research should include a broad knowledge base that keeps pace with relevant developments outside of those disciplines.

Estado nutricional de la madre lactante y la cantidad de leche producida en una población que asiste a una sala amiga de la lactancia en Bogotá, Colombia / Nutritional status of the nursing mother and the amount of milk produced in a population attending a breastfeeding friendly room in Bogotá, Colombia

INTRODUCCIÓN: La cantidad de leche durante los primeros días es un factor determinante para la lactancia. El exceso de peso estaría asociado a una baja producción, pero no existe evidencia concluyente sobre la asociación entre el estado nutricional de la madre y la cantidad de leche. OBJETIVO: Evaluar el estado nutricional pregestacional, gestacional y postparto inmediato de la madre lactante y la cantidad de leche producida, en una población que asiste a la sala amiga de lactancia del Hospital Universitario Mayor-Méderi entre septiembre y noviembre de 2019. MÉTODOS: Estudio descriptivo prospectivo con madres que asistieron a la sala de lactancia del Hospital Universitario Mayor-Méderi entre septiembre y noviembre de 2019. Las variables (sociodemográficas, obstétricas, nutricionales) se determinaron por cuestionarios e historia clínica, el volumen de leche se cuantificó al día 1 y con intervalos de tres días la medida 2, 3 y 4. Se realizaron análisis descriptivos e inferenciales. RESULTADOS: El estudio fue terminado por 33 mujeres con 27,6±4,7 años. El 69,7% (n=23) presentaron IMC pregestacional normal, durante el embarazo 33,3% (n=11) IMC adecuado y 30,3% (n=10) sobrepeso, el peso retenido después del parto fue 8,1±6,5 Kg. Se encontró una correlación negativa estadísticamente significativa entre el peso retenido y la cantidad de leche (-0,4636 p = 0,0075 para la primera medición y -0,3656 p = 0,0396 para la segunda). No se encontraron diferencias significativas en otras variables. DISCUSIÓN: Para esta población de 33 mujeres que asistieron a la sala de lactancia del Hospital Universitario Mayor-Méderi, entre menor era el peso retenido en el postparto inmediato mayor cantidad de leche producida, al inicio del estudio. CONCLUSIÓN: La retención del peso postparto se asoció negativamente con la cantidad de leche producida. Se requieren estudios con una muestra superior para verificar las asociaciones encontradas

INTRODUCTION: The amount of milk during the first days isa determining factor for breastfeeding. Excess weight would be associated with low production, but there is no conclusiveevidence on the association between the mother's nutritional status and the amount of milk. OBJECTIVE: To evaluate the pregestational, gestational and immediate postpartum nutritional status of the nursing mother and the amount of milk produced, in a population that attends the lactation friendly room of the Mayor-Méderi University Hospital between September and November 2019. METHODS: Study Prospective descriptive study with mothers who attended the lactation room of the Hospital Universitario Mayor-Méderi between September and November 2019. The variables (sociodemographic, obstetric, nutritional) were determined by questionnaires and clinical history, the volume of milk was quantified per day 1 and measurements 2, 3 and 4 with three-day intervals. Descriptive and inferential analyzes were carried out. RESULTS: The study was completed by 33 women with 27.6± 4.7 years. 69.7% (n = 23) had normal pre-pregnancy BMI, during pregnancy 33.3% (n = 11) adequate BMI and 30.3%(n = 10) were overweight, the weight retained after delivery was 8, 1 ± 6.5 Kg. A statistically significant negative correlation was found between the retained weight and the amount of milk (-0.4636 p = 0.0075 for the first measurement and -0.3656 p = 0.0396 for the second). No significant differences were found in other variables. DISCUSSION: For this population of 33 women who attended the lactation room of the Hospital Universitario Mayor-Méderi, the lower the weight retained in the immediate post-partum period, the greater the quantity of milk produced at the beginning of the study. CONCLUSION: Postpartum weight retention was negatively associated with the amount of milk produced. Studies with a larger sample are required to verify the associations found

The Protective and Long-Lasting Effects of Human Milk Oligosaccharides on Cognition in Mammals.

Over the last few years, research indicated that Human Milk Oligosaccharides (HMOs) may serve to enhance cognition during development. HMOs hereby provide an exciting avenue in the understanding of the molecular mechanisms that contribute to cognitive development. Therefore, this review aims to summarize the reported observations regarding the effects of HMOs on memory and cognition in rats, mice and piglets. Our main findings illustrate that the administration of fucosylated (single or combined with Lacto-N-neoTetraose (LNnT) and other oligosaccharides) and sialylated HMOs results in marked improvements in spatial memory and an accelerated learning rate in operant tasks. Such beneficial effects of HMOs on cognition already become apparent during infancy, especially when the behavioural tasks are cognitively more demanding. When animals age, its effects become increasingly more apparent in simpler tasks as well. Furthermore, the combination of HMOs with other oligosaccharides yields different effects on memory performance as opposed to single HMO administration. In addition, an enhanced hippocampal long-term potentiation (LTP) response both at a young and at a mature age are reported as well. These results point towards the possibility that HMOs administered either in singular or combination forms have long-lasting, beneficial effects on memory and cognition in mammals.

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2'-Fucosyllactose promotes Bifidobacterium bifidum DNG6 adhesion to Caco-2 cells.

Adhesion to the intestinal mucosa is the prerequisite for bifidobacteria to colonize and exert biological functions, whereas the choice of carbon source affects the ability of bifidobacteria to adhere to and interact with intestinal epithelial cells. However, knowledge about the relationship between human milk oligosaccharide consumption by bifidobacteria and its adhesion is still limited. In this study, we aim to investigate the effect of 2'-fucosyllactose (2'-FL) as the carbon source on the growth and adhesion properties of Bifidobacterium bifidum DNG6, and make comparisons with galactooligosaccharides and glucose. We found that the growth and adhesion properties of B. bifidum DNG6 grown in different carbon sources were varied. The 2'-FL as a carbon source improves the adhesion ability of B. bifidum DNG6. The expression of adhesion-associated genes was significantly higher in B. bifidum DNG6 grown in 2'-FL after incubation with Caco-2 cells compared with that in galactooligosaccharides and glucose. Our results indicated that 2'-FL may promote B. bifidum DNG6 adhesion to Caco-2 cells through high expression of genes encoding adhesion proteins. The findings of this study contribute to a better understanding of the involvement of human milk oligosaccharides in the adhesion of bifidobacteria and further support the potential application of 2'-FL as a prebiotic in infant nutritional supplements.