Article

Dynamics of human milk nutrient composition of women from Singapore with a special focus on lipids

Authors:
  • Nestle Research Center, Nestec Ltd., Lausanne
  • Nestle Research Center
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Abstract

A recent report suggested that human milk (HM) composition not only changes with lactation stages but also vary according to gender of the offspring. In spite of available literature, the dynamic changes of HM composition still remain to be completely explored and characterized. Progress in analytical technologies together with quantitative sampling of HM allows for a better quantification of HM nutrients and thereby providing a deeper understanding of the dynamics of HM secretion. To characterize and quantify HM nutrients based on appropriate for analyses sampling procedures and advanced analytical methodologies. We conducted an observatory, single center, longitudinal trial with HM collection at 30, 60, and 120 days postpartum from 50 mothers (singleton-deliveries of 25 male and 25 female infants). HM samples were analyzed for lipid, lactose, energy density, fatty acids, phospholipids, and gangliosides. Longitudinal analyses of the datasets have been carried out using linear mixed models. HM for male infants compared to females at 120 days, were higher for energy content and lipids by 24 and 39%, respectively. Similarly, other bioactive lipids such as linoleic acid, phospholipids and gangliosides were also significantly different based on the gender of the infant. Significant stage-based differences were observed for total lipids, energy density, phospholipids, and gangliosides. Such difference in HM composition may stem from different energy needs to cope up for individual growth and development. Collectively, the current observations affirm that HM secretion, especially the lipid composition, is a very dynamic and personalized biological process. Am. J. Hum. Biol., 2013. © 2013 Wiley Periodicals, Inc.

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... It is also worth noting that factors other than diet and geographical location may affect the profile of FA in milk. LA, for example, was shown to be consistently more highly expressed in HM secreted for male infants (37% increase) compared to female (65). The effect of gestational age on FA profile has been reviewed and linked to changes in DHA concentration (increase in premature milk) in some studies (66) but not in others (28). ...
... Table 2 provides a summary of studies on the variation of HM phospholipid species across lactation. SM was found to be the most abundant phospholipid (27.4-43.4% of total phospholipid) from analysis using Phosphorus-31 nuclear magnetic resonance ( 31 P NMR), Thin-layer chromatography (TCL) (43.3 ± 2.6%) (82,88) and by High-performance liquid chromatography with evaporative light-scattering detection (HPLC-ELSD) (23,65,84), with the exception of Giuffrida et al. (58) who reported PC as the most abundant phospholipid using ELSD. HM phospholipids analyses using liquid chromatography-mass spectrometry generally conclude that the major phospholipid is PE (7,89). ...
... An improved HPLC-MS method was developed by Fong et al. (108), reporting the content and number and a large number of ganglioside structures in different food matrixes. In 2013-2014, this method was used to report that the total content of gangliosides in HM of Singaporean and Chinese mothers 30-120 days after delivery was 4.6-5.6 and 9.1-10.7 mg/L, respectively (65,103). In 2015, Ma et al. reported the content of HM in mothers from South China within 8 months after delivery as 13.1-22.9 ...
Article
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There has been a growing interest in understanding how the relative levels of human milk fat globule (MFG) components change over the course of lactation, how they differ between populations, and implications of these changes for the health of the infant. In this article, we describe studies published over the last 30 years which have investigated components of the MFG in term milk, focusing on changes over the course of lactation and highlighting infant and maternal factors that may influence these changes. We then consider how the potential health benefits of some of the milk fat globule membrane (MFGM) components and derived ingredients relate to compositional and functional aspects and how these change throughout lactation. The results show that the concentrations of phospholipids, gangliosides, cholesterol, fatty acids and proteins vary throughout lactation, and such changes are likely to reflect the changing requirements of the growing infant. There is a lack of consistent trends for changes in phospholipids and gangliosides across lactation which may reflect different methodological approaches. Other factors such as maternal diet and geographical location have been shown to influence human MFGM composition. The majority of research on the health benefits of MFGM have been conducted using MFGM ingredients derived from bovine milk, and using animal models which have clearly demonstrated the role of the MFGM in supporting cognitive and immune health of infants at different stages of growth and development.
... Foremilk and hindmilk are known to differ in lipid concentration [18,19] and PUFA concentration [20] but only few data on the composition of HM FA on full expressed breast milk are available, i.e., from women living in Asia [21,22]. ...
... Mean pre-pregnancy maternal weight was 61.71 kg (SD: 8.11), and based on ppBMI, 229 women were NW (79%) and 61 women were OW (21%). The mean (SD) height and ppBMI were 164.82 (6.13) and 22.71 (2.67), respectively. ...
... The general pattern of the FA composition of HM observed in this study (compositions of short-, medium-, and odd-chain saturated, as well as of MUFAs and PUFAs) agreed with what was previously reported in different countries [14]. Oleic acid was the most abundant FA (35-38%) followed by palmitic acid (22-25%) ( Table 2) in agreement with previous works [21,22,[34][35][36][37][38][39]. LA composition (12-14%) was comparable to that reported in HM from European women [13,[38][39][40][41], and relatively lower than what reported in milk of Chinese and South American population [13,[35][36][37]42], traditionally consuming vegetable oils rich in LA, such as soybean and sunflower oils [42,43]. ...
Article
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Purpose Human milk (HM) composition is influenced by factors, like maternal diet and body stores, among other factors. For evaluating the influence of maternal fatty acid (FA) status on milk FA composition, the correlation between FA content in HM and in maternal plasma, erythrocytes, and adipose tissue was investigated. Methods 223 European women who delivered at term, provided HM samples over first four months of lactation. Venous blood and adipose tissue (only from mothers who consented and underwent a C-section delivery) were sampled at delivery. FAs were assessed in plasma, erythrocytes, adipose tissue, and HM. Evolution of HM FAs over lactation and correlations between FA content in milk and tissues and between mother’s blood and cord blood were established. Results During lactation, arachidonic acid (ARA) and docosahexaenoic acid (DHA) significantly decreased, while linoleic acid (LA), alpha-linolenic acid (ALA), and eicosapentaenoic acid (EPA) remained stable. Positive correlations were observed between HM and adipose tissue for palmitic, stearic, oleic, and polyunsaturated fatty acids (PUFAs). Correlations were found between milk and plasma for oleic, LA, ARA, ALA, DHA, monounsaturated fatty acids (MUFAs), and PUFAs. No correlation was observed between erythrocytes and HM FAs. LA and ALA were more concentrated in maternal blood than in infant blood, contrary to ARA and DHA, supporting that biomagnification of LCPUFAs may have occurred during pregnancy. Conclusions These data show that maternal adipose tissue rather than erythrocytes may serve as reservoir of PUFAs and LCPUFAs for human milk. Plasma also supplies PUFAs and LCPUFAs to maternal milk. If both, adipose tissue and plasma PUFAs, are reflection of dietary intake, it is necessary to provide PUFAs and LCPUFAs during pregnancy or even before conception and lactation to ensure availability for mothers and enough supply for the infant via HM.
... So far, PL concentrations in mature HM samples have been studied in various countries and regions [10][11][12][13][14], providing information on PE (5.2-9.9 mg/100 mL), PI (0.7-4.0 mg/100 mL), PS (0.8-4.3 mg/100 mL), PC (2.6-6.0 mg/100 mL), and SM (6.8-10.3 mg/100 mL). ...
... mg/100 mL). In addition, studies on the factors affecting PL concentration in HM, such as lactation stages, gestational ages, and sex of the infant, have also been conducted [10][11][12][13]15]. Among these factors, the lactation period appears to be the most significant. ...
... As for the contents of PLs in Korean HM, SM was the most abundant PL, with a mean content of 5.11 mg/100 g HM, followed by PC (2.26 mg/100 g) and PE (2.00 mg/100 g) ( Table 1). The finding that SM was the most abundant PL in mature HM was in agreement with the literature [10][11][12][13][14][15][25][26][27], wherein a concentration range of 6.8-10.3 mg/100 mL was reported, accounting for 30.8%-43.3% of total PLs. ...
Article
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Fat globule size and phospholipid (PL) content in human milk (HM) were investigated. HM was classified into three groups depending on fat content (A < B < C). PL content (mg/100 g HM) was significantly higher in the C group (p < 0.05), indicating its positive relationship with HM fat content. When the PL content was normalized (mg/g fat), that of group A was significantly higher (p < 0.05) and fat droplet size in group C was slightly larger, suggesting that HM fat content is affected by fat droplet numbers to a larger extent than by fat droplet size. A correlation between PC and SM content in HM was observed regardless of fat content, while correlation between PE and either PC or SM increased in the order of C > B > A, hence the composition and content of PL species in HM varied according to its fat content.
... Circadian variability Lipids and lipolytic enzymes in HM peak at mid-day Evidence probable (150,214,215,(225)(226)(227)(228)(229)(230)(231)(232)(233)(234)(235)(236)(237)(238)(239) (186). The same study revealed lipids such as linoleic acid, phospholipids and gangliosides were increased in HM of male infants in later lactation, potentially based on the higher energy requirement of a male infant (186). Interestingly, in resource poor setting, HM for female infants was richer in lipids, while in a resource sufficient setting, the milk for male infants was richer suggesting that infant sex and maternal socioeconomic status showed an interaction and should be studied further (187). ...
... Additionally, a higher concentration of total proteins has been observed in colostrum and transitional compared with mature milk (190). In contrast, lipids are present at higher concentration in mature milk (186,196). In next section we review the different aspects of changes across lactation as reported in the literature. ...
... The energy content of HM showed an initial decrease followed by an increase over the course of lactation, which was directly related to the HM lipid content (186,196). With respect to carbohydrates, several studies showed that lactose concentrations remained constant throughout lactation (186,195,197), however, there is also some evidence to the contrary, indicating an increase in HM lactose from 56 to 69 g/l over the first 4 months of lactation (198). ...
Article
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Human milk (HM) is dynamic and shows a high inter- and intra-individual variability. To characterize HM with precision, it is necessary to understand the factors that modulate its composition. The objective of this narrative review is to summarize the maternal, infant and methodological factors that affect HM composition. We searched SCOPUS and PubMed databases for articles related to factors that are known to or could potentially influence HM composition and volume across lactation periods. Our comprehensive review encompasses various maternal-, infant-related, and methodological factors that modulate aspects of HM composition including macro- and micronutrients, vitamins and minerals, as well as volume. The most profound changes were observed in HM lipids and lipophiles. Evidence exists for many of the infant-related factors known to affect the nutritive and non-nutritive components of HM (e.g., birth weight, gestational age, infant age/stage of lactation). In contrast, less is known with respect to maternal factors; where there is either limited research or conflicting evidence (e.g., maternal lifestyle, obstetric history, medical conditions), except for the mother's diet, for which there is a relatively well-established understanding. Equally, although many of the methodological factors (e.g., HM sampling, handling and analytics) are known to impact HM composition, few studies have investigated this as a primary outcome, making it an important area of future research in HM. Here we propose a systematic capture of numerous maternal- and infant-related characteristics to facilitate associative comparisons of HM data within and across studies. Additionally, it would be prudent to standardize the methodological aspects known to affect HM composition in analytics, not only for HM lipids and lipophiles, but also for those nutrients whose variability is yet less well-understood. Defining the factors determining HM composition with accuracy will open perspectives for maternal intervention to optimize milk composition for specific needs of infants.
... Infant formulas are regularly improved by incorporating new nutrients in the effort to mimic breast milk composition and to aid formula fed infants in having similar overall growth and development to that of breastfed infants. The incorporation of milk polar lipids in formula is gaining interest due to their presence in breast milk [3], their bioactive properties and ability to support human health [4,5], and their potential role in brain development [6]. Examples of polar lipids include glycolipids, sphingolipids, and phospholipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine [7]. ...
... Lastly, no differences due to early-life dietary treatment were detected for MWF developmental patterns (Table 4). 3 Parameter estimations for each outcome were computed for maximum absolute (i.e., plateau) value (a), onset of initial developmental increase (b), and overall rate of development (g). ...
... Abbreviations: CONT, control diet; FA, fractional anisotropy; ROI, region of interest; SEM, standard error of the mean; TEST, test diet. 2 p-values derived from a two-sample t-test comparing pigs provided different early-life dietary interventions.3 Parameter estimations for each outcome were computed for maximum absolute (i.e., plateau) value (a), onset of initial developmental increase (b), and overall rate of development (g). ...
Article
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Polar lipids, which are found in human milk, serve essential functions within biological membranes, hence their importance in brain development and cognition. Therefore, we aimed to evaluate the longitudinal effects on brain macrostructural and microstructural development and recognition memory of early-life polar lipid supplementation using the translational pig model. Twenty-eight intact (i.e., not castrated) male pigs were provided either a control diet (n = 14) or the control diet supplemented with polar lipids (n = 14) from postnatal day 2 until postnatal week 4. After postnatal week 4, all animals were provided the same nutritionally-adequate diets until postnatal week 24. Pigs underwent magnetic resonance imaging at 8 longitudinal time-points to model brain macrostructural and microstructural developmental trajectories. The novel object recognition task was implemented at postnatal weeks 4 and 8 to evaluate recognition memory. Subtle differences were observed between groups in hippocampal absolute brain volumes and fractional anisotropy, and no differences in myelin water fraction developmental patterns were noted. Behavioral outcomes did not differ in recognition memory, and only minimal differences were observed in exploratory behaviors. Our findings suggest that early-life dietary supplementation of polar lipids has limited effect on brain developmental patterns, object recognition memory, and exploratory behaviors.
... There are recent studies that report the changes in HMOs [27][28][29][30], PLs [31][32][33], and GAs [32][33][34][35] across lactation for various population cohorts; however, to our knowledge, there is no specific study reported for the UAE or other Middle Eastern populations. In this study, the HMO, PL, and GA concentrations in transitional (5-15 days) and mature milk (at 6 months post-partum) were measured in a cross section of UAE mothers' breast milk samples, collected from a wider mother-infant study cohort (MISC) [36]. ...
... There are recent studies that report the changes in HMOs [27][28][29][30], PLs [31][32][33], and GAs [32][33][34][35] across lactation for various population cohorts; however, to our knowledge, there is no specific study reported for the UAE or other Middle Eastern populations. In this study, the HMO, PL, and GA concentrations in transitional (5-15 days) and mature milk (at 6 months post-partum) were measured in a cross section of UAE mothers' breast milk samples, collected from a wider mother-infant study cohort (MISC) [36]. ...
... Various factors such as diet, geography, ethnicity, milk collection time, and genetics have been implicated to have a significant influence on the HMO, PL, and GA composition in HM, but most of the data obtained to date indicate that the stage of lactation is perhaps the primary factor that has the greatest influence on HM composition [27][28][29]39]. There are several recent studies reporting the composition of HM, trying to gain a better understanding of the changes in the HMOs and complex lipids (PLs and GAs) through lactation of different geographical population cohorts [28,31,32,34,35,39,40]. However, this is the first study that looks at the transitional and mature milk from UAE mothers, helping to address geographical variation in HMOs, PLs, and GAs. ...
Article
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Human milk oligosaccharides (HMOs), phospholipids (PLs), and gangliosides (GAs) are components of human breast milk that play important roles in the development of the rapidly growing infant. The differences in these components in human milk from the United Arab Emirates (UAE) were studied in a cross-sectional trial. High-performance liquid chromatography‒mass spectrometry was used to determine HMO, PL, and GA concentrations in transitional (5–15 days) and mature (at 6 months post-partum) breast milk of mothers of the United Arab Emirates (UAE). The results showed that the average HMO (12 species), PL (7 species), and GA (2 species) concentrations quantified in the UAE mothers’ transitional milk samples were (in mg/L) 8204 ± 2389, 269 ± 89, and 21.18 ± 11.46, respectively, while in mature milk, the respective concentrations were (in mg/L) 3905 ± 1466, 220 ± 85, and 20.18 ± 9.75. The individual HMO concentrations measured in this study were all significantly higher in transitional milk than in mature milk, except for 3 fucosyllactose, which was higher in mature milk. In this study, secretor and non-secretor phenotype mothers showed no significant difference in the total HMO concentration. For the PL and GA components, changes in the individual PL and GA species distribution was observed between transitional milk and mature milk. However, the changes were within the ranges found in human milk from other regions.
... mg/100 mL (3.05-5.11 mg/g of milk fat), comprising about 1% of all lipids [40,[61][62][63][64][65][66][67][68][69][70][71][72][73]. SM is generally considered as the predominant phospholipid in human milk fat, accounting for 29.00-45.50% ...
... W.Wei, et al. Progress in Lipid Research 74 (2019)[69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86] ...
... Reproduced from[150,176].W.Wei, et al. Progress in Lipid Research 74 (2019)[69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86] ...
Article
The first commercial infant formula, invented in 1867, contained lipids mainly from cow’s milk. We now know that human milk fat differs from the milk fat of other mammals and even more from vegetable oils. Human milk fat is one of the most complex natural lipid mixtures with a unique fatty acid composition, distribution, and numerous complex lipids. Therefore, to mimic human milk fat, human milk fat substitutes (HMFSs) have been produced through the enzymatic/chemical modification of natural lipids. Researchers have become increasingly interested in use of HMFSs as functional lipids due to their nutritional effects on the growth and development of formula-fed infants. This paper discusses the history and recent advances in HMFSs. A comprehensive summary of the composition of human milk fat (fatty acids, sn-2 fatty acids, triacylglycerols, and complex lipids) and its structure (human milk fat globules), as well as the changes during the lactation period. Nutritional bases, preparation methods, and applications of HMFSs (long-chain polyunsaturated fatty acids, sn-2 palmitate, medium-chain triacylglycerols, and milk fat globule membrane supplements) have been reviewed. Legislation relating to the fat fraction of infant formulae are also presented in this paper.
... GM1, GM3, and GD3 are three types of gangliosides in human milk that bind pathogens without causing inflammatory reactions [212]. A study by Thakkar et al. (2013) demonstrated that the concentration of gangliosides in human milk was significantly higher at 120 days postpartum in male infants [213]. ...
... GM1, GM3, and GD3 are three types of gangliosides in human milk that bind pathogens without causing inflammatory reactions [212]. A study by Thakkar et al. (2013) demonstrated that the concentration of gangliosides in human milk was significantly higher at 120 days postpartum in male infants [213]. ...
Article
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Maternal obesity is associated with metabolic changes in mothers and higher risk of obesity in the offspring. Obesity in breastfeeding mothers appears to influence human milk production as well as the quality of human milk. Maternal obesity is associated with alteration of immunological factors concentrations in the human milk, such as C-reactive protein (CRP), leptin, IL-6, insulin, TNF-Alpha, ghrelin, adiponectin, and obestatin. Human milk is considered a first choice for infant nutrition due to the complete profile of macro nutrients, micro nutrients, and immunological properties. It is essential to understand how maternal obesity influences immunological properties of human milk because alterations could impact the nutrition status and health of the infant. This review summarizes the literature regarding the impact of maternal obesity on the concentration of particular immunological properties in the human milk.
... The average content of phospholipids in human milk ranges from 9.8 to 47.4 mg/100 mL (104), and it is estimated that a 4-wk-old breastfed infant has a daily intake of 140 mg phospholipids/d (105), calculated based on a polar lipid concentration of 23.8 mg phospholipids/ 100 mL milk [mature milk from women in Singapore (106)] and consumption of 600 mL human milk at age 4 wk (107). Table 1 summarizes the range of polar lipid content in human milk and reports the most abundant phospholipids in human milk fat are usually SM and PC (expressed as percentages of total phospholipid content) (104,106,(108)(109)(110)(111)(112)(113)(114)(115)(116). Glycosphingolipids are present in low amounts, with cerebrosides the most abundant (0.28 mg/100 mL; 74% of the neutral glycosphingolipids), followed by lactosyl, Gb3 and Gb4, and lower amounts of gangliosides, mostly GM3 and GD3 (96,100,106,110,(117)(118)(119)(120)(121)(122)(123)(124)(125)(126). ...
... Table 1 summarizes the range of polar lipid content in human milk and reports the most abundant phospholipids in human milk fat are usually SM and PC (expressed as percentages of total phospholipid content) (104,106,(108)(109)(110)(111)(112)(113)(114)(115)(116). Glycosphingolipids are present in low amounts, with cerebrosides the most abundant (0.28 mg/100 mL; 74% of the neutral glycosphingolipids), followed by lactosyl, Gb3 and Gb4, and lower amounts of gangliosides, mostly GM3 and GD3 (96,100,106,110,(117)(118)(119)(120)(121)(122)(123)(124)(125)(126). Polar lipid concentrations and proportions vary greatly, depending on the method of milk expression or analysis and the lactation period, with increased GM3 and decreased GD3 concentrations over lactation time (122). ...
Article
Polar lipids are amphiphilic lipids with a hydrophilic head and a hydrophobic tail. Polar lipids mainly include phospholipids and sphingolipids. They are structural components of neural tissues, with the peak rate of accretion overlapping with neurodevelopmental milestones. The critical role of polar lipids in cognitive development is thought to be mediated through the regulation of signal transduction, myelination, and synaptic plasticity. Animal products (egg, meat, and dairy) are the major dietary sources of polar lipids for children and adults, whereas human milk and infant formula provide polar lipids to infants. Due to the differences observed in both concentration and proportion of polar lipids in human milk, the estimated daily intake in infants encompasses a wide range. In addition, health authorities define neither intake recommendations nor guidelines for polar lipid intake. However, adequate intake is defined for 2 nutrients that are elements of these polar lipids, namely choline and DHA. To date, limited studies exist on the brain bioavailability of dietary polar lipids via either placental transfer or the blood-brain barrier. Nevertheless, due to their role in pre- and postnatal development of the brain, there is a growing interest for the use of gangliosides, which are sphingolipids, as a dietary supplement for pregnant/lactating mothers or infants. In line with this, supplementing gangliosides and phospholipids in wild-type animals and healthy infants does suggest some positive effects on cognitive performance. Whether there is indeed added benefit of supplementing polar lipids in pregnant/lactating mothers or infants requires more clinical research. In this article, we report findings of a review of the state-of-the-art evidence on polar lipid supplementation and cognitive development. Dietary sources, recommended intake, and brain bioavailability of polar lipids are also discussed.
... However, evidence for systematic sex-biased favoring males has been equivocal [13][14][15][16][17]. Post-natal, sex-biased nursing care has been investigated as a possible reason for sex-biased milk production in several mammalians, including humans. Several studies reported evidence of sexbiased milk synthesis in different species but drawing definitive conclusions from these studies has been difficult for several reasons [11,12,[18][19][20][21][22][23][24][25][26][27][28][29][30]. ...
... Also, cows seem to favor living bull offspring over unborn bull offspring, but unborn bull offspring over living heifer offspring [33]. The magnitude of sex bias milk production, when observed in other species, seems to be stronger among first parity females [11,26,27,30,59]. The fetal sex effect may be disguised in multiparous females because of the cumulative effects of sequential gestations with fetuses of different sexes on the mammary gland architecture [1]. ...
Chapter
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The main source of incomes in a dairy farm is milk sales, and any factor altering the production affects the farmers' income significantly. According to the Trivers-Willard hypothesis, if the cows' systems are generally good and offer competitive conditions, they produce more milk for bull calves. They also suggest that cows in a worse condition or of a genetically diverging strain invest more milk in heifer calves. The existence of a sex-bias in cows' milk production remains controversial even if it would open new insights on the economic impacts of using sex-sorted semen to enhance farm productivity. Sex-biased milk production in cows can vary, favoring one sex or the other and, sometimes, none. It seems to favor females in intensive production systems, while in other less intensive systems, this effect seems to disappear. This chapter intends to address available evidence on the sex-biased cows' milk production and discuss why further research forecasting this issue is needed, including other cattle populations and correlating the investment strategy with an animal welfare index. Besides, other factors, such as different housing and feedings, can impact the calf-sex milk production bias through pathways still to be understood.
... In 2010, Powe et al. observed an increase in energy value of 25% for male infants of well-fed American women [42]. In a study conducted in Singapore, Thakkar et al. found similar differences in term newborns (energy + 24% and fat + 39% for boys), with a lipid profile that also varied by gender [43]. More recently, in a term delivering population of mothers living in Seoul, Hahn also observed an increased energy density in HM for male infants, related to a higher carbohydrates content. ...
Article
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Background: Mother's own milk is the optimal source of nutrients and provides numerous health advantages for mothers and infants. As they have supplementary nutritional needs, very preterm infants may require fortification of human milk (HM). Addressing HM composition and variations is essential to optimize HM fortification strategies for these vulnerable infants. Aims: To analyze and compare macronutrient composition in HM of mothers lactating very preterm (PT) (28 0/7 to 32 6/7 weeks of gestational age, GA) and term (T) infants (37 0/7 to 41 6/7 weeks of GA) over time, both at similar postnatal and postmenstrual ages, and to investigate other potential factors of variations. Methods: Milk samples from 27 mothers of the PT infants and 34 mothers of the T infants were collected longitudinally at 12 points in time during four months for the PT HM and eight points in time during two months for the T HM. Macronutrient composition (proteins, fat, and lactose) and energy were measured using a mid-infrared milk analyzer, corrected by bicinchoninic acid (BCA) assay for total protein content. Results: Analysis of 500 HM samples revealed large inter- and intra-subject variations in both groups. Proteins decreased from birth to four months in the PT and the T HM without significant differences at any postnatal time point, while it was lower around term equivalent age in PT HM. Lactose content remained stable and comparable over time. The PT HM contained significantly more fat and tended to be more caloric in the first two weeks of lactation, while the T HM revealed higher fat and higher energy content later during lactation (three to eight weeks). In both groups, male gender was associated with more fat and energy content. The gender association was stronger in the PT group, and it remained significant after adjustments. Conclusion: Longitudinal measurements of macronutrients compositions of the PT and the T HM showed only small differences at similar postnatal stages in our population. However, numerous differences exist at similar postmenstrual ages. Male gender seems to be associated with a higher content in fat, especially in the PT HM. This study provides original information on macronutrient composition and variations of HM, which is important to consider for the optimization of nutrition and growth of PT infants.
... It has been demonstrated that human mothers make different milk depending upon whether the mother's baby is a boy or girl. For example, it was reported that mothers with sons provided milk with more energy (Powe etal, 2010) and fats (Thakkar et al, 2013) than those with daughters. In our previous study (Musallam et al, 2017), we reported that mothers with boys produced breast milk with higher value of viscosity and higher contents of protein and lactose than mothers with daughters. ...
Article
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Human milk is a complex fluid, which contains a number of constituents such as fats, proteins and vitamins, in addition to other compounds. These nutrients are needed for infant protection against infections and diseases. This study was undertaken to evaluate some physicochemical properties and biochemical constituents content of human milk samples (based on the gender of the breast feeding infant). This includes acidity, density and viscosity, as well as lactose, protein, calcium and magnesium contents. Results showed that the highest value of viscosity as well as the highest percentages of protein and acidity were recorded for human breast milk for a boy (2.212 cP, 1.237% and 0.02% respectively) while close values for density and other biochemical contents were recorded for both types of samples. However, only the change in viscosity was found to be significant (p˂0.05). Variations in some properties of human milk depending on the infant' sex could be of benefit for developing infant formula taking infant’s gender into consideration.
... g/100 mL and þ0.35-1.53 g/100 mL 40,41 ), with the remainder showing no differences between infant sex. 5,42 In consideration of total lipid intake, there is also conflicting evidence whether milk intake is different between male and female infants. ...
Article
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Human milk lipids are among the many nutrients delivered to the infant, providing >50% of the infant’s calorie intake. These lipids are highly complex and variable, and bioactive, contributing to infant growth, development, and health. The lipid concentration of milk samples is often measured in human cohorts; however, few studies measure infant intake of milk. Intake is important because it considers the variability of both lipid concentration and infants’ consumed volume of milk. Measurement of infants’ lipid intake in exclusively breastfeeding infants requires 3 main considerations: human milk sampling protocol (ie, the collection of representative samples); measurement of the infant milk intake, because volume varies widely between infants; and appropriate analytical laboratory methods. The purpose of this review was to provide an overview of existing methodology and demonstrate the importance of measuring infants’ lipid intake to understand the impact that human milk lipids have on infant outcomes.
... These data support the hypothesis that preterm infants may have sex-specific nutritional requirements in the neonatal period. Such an hypothesis is supported by evidence from animal, 26 and human, [27][28][29] studies that maternal breastmilk composition differs by offspring sex, providing higher concentrations of lipid and energy to boys. There is also evidence that supplementation of enteral feeds after preterm birth leads to sex-specific differences in growth and neurodevelopmental outcomes, with preterm boys who receive supplemented feeds showing bigger changes in short-and long-term growth, 11,30 and improvements in verbal and overall IQ scores, 31 compared to girls. ...
Article
Although early nutrition is associated with neurodevelopmental outcome at 2 years’ corrected age in children born very preterm, it is not clear if these associations are different in girls and boys. Retrospective cohort study of infants born <30 weeks’ gestational age or <1500 g birth weight in Auckland, NZ. Macronutrient, energy and fluid volumes per kg per day were calculated from daily nutritional intakes and averaged over days 1−7 (week 1) and 1−28 (month 1). Primary outcome was survival without neurodevelopmental impairment at 2 years corrected age. More girls (215/478) survived without neurodevelopmental impairment at 2 years (82% vs. 72%, P = 0.02). Overall, survival without neurodevelopmental impairment was positively associated with more energy, fat, and enteral feeds in week 1, and more energy and enteral feeds in month 1 (P = 0.005−0.03), but all with sex interactions (P = 0.008−0.02). In girls but not boys, survival without neurodevelopmental impairment was positively associated with week 1 total intakes of fat (OR(95% CI) for highest vs. lowest intake quartile 62.6(6.6–1618.1), P < 0.001), energy (22.9(2.6–542.0), P = 0.03) and enteral feeds (1.9 × 10⁹(9.5–not estimable), P < 0.001). Higher early fat and enteral feed intakes are associated with improved outcome in girls, but not boys. Future research should determine sex-specific neonatal nutritional requirements.
... These results are consistent with study conducted in Singapore. Thakkar et al. [40] reported that HM for male infants compared to females at 120 days postpartum was higher in energy and fat by 24% and 39%, respectively. ...
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The present study investigates the influence of selected infant and maternal factors on the energy and macronutrient composition of mature human milk (HM). The study enrolled 77 mothers at 4–8 weeks postpartum. Each mother provided 1 sample of HM. Each extracted HM sample was formed by mixing four subsamples of HM, each of which were obtained in one predefined 6-h periods of the day. Among maternal factors, the analysis included: anthropometric data before and after pregnancy; weight gain in pregnancy; body composition, assessed using the Maltron BioScan 920-II to analyze bioimpedance; and dietary intake, assessed with three-day dietary records. Among the neonatal factors, birth weight and length, number of daily feedings and type of delivery were included. The composition of HM, including energy content, protein, fat and carbohydrate concentrations, was analyzed using the Miris human milk analyzer. Pearson’s and Spearman’s correlation coefficients and multivariable logistic regression models were used to analyze the association between the selected maternal and infant factors and HM milk composition. It was found that total protein content of HM was correlated with pre-pregnancy BMI (Spearman rho = 0.238; p = 0.037), current lean body mass (Spearman rho = −0.293, p = 0.01) and total water content (Spearman rho = −0.315, p = 0.005). Carbohydrates were the only macronutrients whose composition was significantly affected by the infant factors. It was reported that higher carbohydrate content was associated with male sex (OR = 4.52, p = 0.049). Our results show that maternal and infant factors, especially maternal pre-pregnancy and current nutritional status and infant sex, interact and affect HM composition, suggesting that macronutrient and energy content in HM may be determined in pregnancy and may have unique compositional profile for every mother–infant dyad.
... HM cortisol was correlated with maternal BMI and height, but not HM cortisone, suggesting a more complex relationship between HM glucocorticoids and maternal adiposity. The composition of HM is influenced by the complex interplay between maternal, infant and diverse environmental factors (10); and also varies depending upon the stages of lactation (34)(35)(36). In the current study, it was demonstrated that cortisol, cortisone and their ratio did not significantly change over the first 12 months of lactation. ...
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Human milk (HM) is a complex and dynamic biological fluid, which contains appreciable concentrations of the glucocorticoids, cortisol and cortisone. Experimental studies in non-human primates suggest the HM glucocorticoids' impact on infant growth and body composition. In this current study, analysis is made of the relationships between HM glucocorticoid concentrations and the infant growth and development over the first year of life. HM was collected by lactating healthy women (n = 18), using a standardized protocol, at 2, 5, 9, and 12 months after childbirth. Cortisol and cortisone concentrations in the HM were measured using liquid chromatography mass spectrometry. Infant weight, length and head circumference were measured by standard protocols and percentage fat mass (% FM) determined by whole body bioimpedance. Cortisol and cortisone concentrations were unaltered over the analyzed lactation period (2–12 months), and were altered by infant sex. Although, HM cortisol was positively associated with infant percentage fat mass (% FM) (p = 0.008) and cortisone positively associated with infant head circumference (p = 0.01). For the first 12 months of life, the concentration of HM glucocorticoids levels was positively associated with infant adiposity (%FM) and head circumference. This preliminary evidence provides insight to a possible relationship between ingested HM glucocorticoids and infant body composition. Further studies are required to determine the mechanisms regulating HM glucocorticoids.
... Increasing awareness of the roles that GAs play in human neurological development, immune system regulation and protection against enteric pathogens [4,7,8,9,10,11], particularly during the early stages of life, has recently led to a number of studies looking at the GA content in human milk and over lactation [12,13,24,25]. Although there is limited information on the dietary GA intake for infants, using the breast milk consumption data presented by Gurnida et al. [17] for the exclusively breast-fed Indonesian infant and the average GA levels in mature breast milk (18.5 mg/L [13]), the estimated daily TGA intake for Indonesian infants during the first 6 months ranged from 13.7 to 16.5 mg/day, compared with 3.8-4.9 ...
... Many HM components vary based on the infant's gestational age, week of life, birth order and even gender. 1,2 Immunologic factors are influenced by infant illness, and some HM hormones have been found to have diurnal changes in concentration. 3,4 The long-term benefits of HM are promising for all infants, and these benefits likely remain through adulthood. ...
Article
This review highlights clinical outcomes of human milk from infancy through adulthood. Human milk outcomes of both preterm and term infants, including critically ill term infants (such as infants with congenital heart disease and those requiring therapeutic hypothermia) are summarized. Several human milk diets are identified to reduce the risk of specific diseases. Emerging research of newly discovered components of human milk are also reviewed. Human milk has significant effects on the gut microbiome, somatic growth, and neurocognitive outcomes. Continued research promises to improve donor human milk and donor milk derived products to achieve better outcomes for infants who do not receive their own mother's milk. The promotion of human milk is well-founded on evidence from the previous half century.
... However, the lactation stage was not specifically distinguished in the MING study [25] and the MISC cohort study [29]. Other possible explanations for the U-shape trajectory were the dramatic upregulation in the expression of genes associated with lipid metabolism and milk FA production in the initiation of human lactation [30], and the increased de novo synthesis in the mammary gland with the establishment of lactation [31,32]. ...
Article
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Phospholipids are pivotal polar lipids in human milk and essential for infants’ growth and development, especially in the brain and cognitive development. Its content and composition are affected by multiple factors and there exist discrepancies in different studies. In this study, we determined five major phospholipids classes (phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, phosphatidylcholine, and sphingomyelin) in 2270 human milk samples collected from 0 to 400 days postpartum in six regions of China. The high-performance liquid chromatography coupled with an evaporative light scattering detector (HPLC-ELSD) was performed to quantify the phospholipids. Total phospholipid median (IQR) content was in a range between 170.38 ± 96.52 mg/L to 195.69 ± 81.80 mg/L during lactation and was higher concentrated in colostrum milk and later stage of lactation (after 200 days postpartum) compared with that in the samples collected between 10 to 45 days postpartum. Variations in five major sub-class phospholipids content were also observed across lactation stages (phosphatidylethanolamine: 52.61 ± 29.05 to 59.95 ± 41.74 mg/L; phosphatidylinositol: 17.65 ± 10.68 to 20.38 ± 8.55 mg/L; phosphatidylserine: 15.98 ± 9.02 to 22.77 ± 11.17 mg/L; phosphatidylcholine: 34.13 ± 25.33 to 48.64 ± 19.73 mg/L; sphingomyelin: 41.35 ± 20.31 to 54.79 ± 35.26 mg/L). Phosphatidylethanolamine (29.18–32.52%), phosphatidylcholine (19.90–25.04%) and sphingomyelin (22.39–29.17%) were the dominant sub-class phospholipids in Chinese breast milk during the whole lactation period. These results updated phospholipids data in Chinese human milk and could provide evidence for better development of secure and effective human milk surrogates for infants without access to breast milk.
... An important factor that was not taken into consideration in the present study is the impact of offspring sex on milk composition, due to difficulties in controlling for this in our large litter bearing animal model. Indeed, several epidemiological and experimental (with smaller litter bearing animals) studies have well demonstrated differences in milk composition between male and female infants [59,60]; demonstrating that infant sex has a significant impact on milk quality. This highlights the need for well-controlled human and animal studies to identify alterations in milk composition between infant sexes in several different pregnancy complications. ...
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The in utero and early postnatal environments play essential roles in offspring growth and development. Standardizing or reducing pup litter size can independently compromise long-term health likely due to altered milk quality, thus limiting translational potential. This study investigated the effect reducing litter size has on milk quality and offspring outcomes. On gestation day 18, dams underwent sham or bilateral uterine vessel ligation surgery to generate dams with normal (Control) and altered (Restricted) milk quality/composition. At birth, pups were cross-fostered onto separate dams with either an unadjusted or reduced litter size. Plasma parathyroid hormone-related protein was increased in Reduced litter pups, whereas ionic calcium and total body calcium were decreased. These data suggest Reduced litter pups have dysregulated calcium homeostasis in early postnatal life, which may impair bone mineralization decreasing adult bone bending strength. Dams suckling Reduced litter pups had increased milk long-chain monounsaturated fatty acid and omega-3 docosahexaenoic acid. Reduced litter pups suckled by Normal milk quality/composition dams had increased milk omega-6 linoleic and arachidonic acids. Reduced litter male adult offspring had elevated blood pressure. This study highlights care must be taken when interpreting data from research that alters litter size as it may mask subtle cardiometabolic health effects.
... This difference was found sufficient to explain the growth rate difference between male and female offspring [23]. Furthermore, Thakkar et al. [24] reported that both breast milk energy and lipid composition were higher when nursing sons compared to daughters. These findings explain the general weight differences between breastfed male and female offspring observed in our study (figure 1c) and align to animal studies of polygynous species such as wallabies (Macropus eugenii) [25], sheep (Ovis aries) [26], apes (Macaca mulata) [20,27] and deer (Cervus elaphus hispanicus, Dama dama) [28]. ...
Article
Animal studies have shown that maternal resource allocation can be sex-biased in order to maximize reproductive success, yet this basic concept has not been investigated in humans. In this study, we explored relationships between maternal factors, offspring sex and prenatal and postnatal weight gain. Sex-specific regression models not only indicated that maternal ethnicity impacted male ( n = 2456) and female ( n = 1871) childrens postnatal weight gain differently but also that parity and mode of feeding influenced weight velocity of female ( β ± s.e. = −0.31 ± 0.11 kg, p = 0.005; β ± s.e. = −0.37 ± 0.11 kg, p < 0.001) but not male offspring. Collectively, our findings imply that maternal resource allocation to consecutive offspring increases after a male firstborn. The absence of this finding in formula fed children suggests that this observation could be mediated by breast milk. Our results warrant further mechanistic and epidemiological studies to elucidate the role of breastfeeding on the programming of infant growth as well as of metabolic and cardiovascular diseases, with potential implications for tailoring infant formulae according to sex and birth order.
... After 2009, the improved HPLC-MS method was used to detect gangliosides in animal food, and the absolute content was obtained directly, which promoted the development of gangliosides detection. In 2013, this method was used to report that the content of ganglioside in breast milk of Singapore mothers within 30-120 days after delivery was 4.6-5.6 mg/L [22]. In 2014, Giuffrida et. ...
Article
Objective: To study the ganglioside intake of lactating mothers and its effect on the breast milk and infants. Methods: The related information of mothers and infants was obtained by questionnaire survey, including the recipe, family information, and so on. The content of gangliosides in the mothers' food and breast milk was tested by HPLC-MS. The intake of gangliosides for infants was recorded and calculated. Then the dynamic changes of the content of gangliosides in breast milk and the impact on the development of infants were evaluated. Results: GD3 was rich in milk and dairy products. The average intake of gangliosides for lactating mothers was 6.33 mg/day, of which GM3 was 3.02 mg/day and GD3 was 1.51 mg/day. The main food sources of gangliosides were meat (46.6%), eggs (26.6%), and dairy products (18.9%). The average content of gangliosides in breast milk was 9.58 mg/L. The content in 0-7 days after delivery (15.95 mg/L) was the highest, and then gradually decreased with time, getting the lowest in 6 months after delivery (6.47 mg/L). GM3 and GD3 were the two main types in breast milk. The average milk intake of infants under 6 months gradually increased from 570 mL to 1367 mL, and the daily intake of gangliosides was relatively stable, with a median of 6.4 mg. There was no significant relationship between the intake of gangliosides and physical development in infants. Conclusion: This study is the first to report the dietary ganglioside intake of Chinese city mothers. This study is also the first to indirectly infer the demand of infant ganglioside by detecting the components of breast milk. It will accumulate basic data for improving the diet of Chinese mothers and the recommended amount of infant nutrients.
... Conventional data suggests that FA in HM may be modified by the maternal dietary or nutritional supplement intake but not the quantity or concentration of total lipids [13]. The concentration of HM lipids increases with advancing stages of lactation [14][15][16]. In fact, HM composition may be impacted by a multitude of factors ranging from maternal to infant parameters and even including the physiological and behavioral aspects observed in the mother-infant dyad. ...
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We longitudinally compared fatty acids (FA) from human milk (HM) of mothers delivering term and preterm infants. HM was collected for 4 months postpartum at 12 time points for preterm and for 2 months postpartum at 8 time points for term group. Samples were collected from the first feed of the morning, and single breast was fully expressed. FA were analyzed by gas chromatography coupled with flame ionization detector. Oleic, palmitic and linoleic acids were the most abundant FA across lactation and in both groups. Preterm colostrum contained significantly (p < 0.05) higher 8:0, 10:0, 12:0, sum medium chain fatty acids (MCFA), 18:3 n-3 FA compared to term counterparts. Preterm mature milk contained significantly higher 12:0, 14:0, 18:2 n-6, sum saturated fatty acids (SFA), and sum MCFA. We did not observe any significant differences between the preterm and term groups for docosahexaenoic acid, arachidonic acid and eicosapentaenoic acid at any stage of lactation. Overall, preterm milk was higher for SFA with a major contribution from MCFA and higher in 18:2 n-6. These observational differences needs to be studied further for their implications on preterm developmental outcomes and on fortification strategies of either mothers’ own milk or donor human milk.
... Total lipids in HM were analyzed by mid-infrared spectroscopy (HMA, Miris AB, Uppsala, Sweden) as previously reported (15). Total protein content in HM was measured using the colorimetric bicinchoninic acid (BCA) method according to the manufacturer's protocol of BCA assay kit (Thermo Fisher Scientific, Waltham, MA, United States). ...
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Background The effect of the mode of neonatal delivery (cesarean or vaginal) on the nutrient composition of human milk (HM) has rarely been studied. Given the increasing prevalence of cesarean section (C-section) globally, understanding the impact of C-section vs. vaginal delivery on the nutrient composition of HM is fundamental when HM is the preferred source of infant food during the first 4 postnatal months.Objective This study aimed to evaluate the association between mode of delivery and nutrient composition of HM in the first 4 months of life.DesignMilk samples were obtained from 317 healthy lactating mothers as part of an exploratory analyses within a multicenter European longitudinal cohort (ATLAS cohort) to study the HM composition, and its potential association with the mode of delivery. We employed traditional mixed models to study individual nutrient associations adjusted for mother’s country, infant birth weight, parity, and gestational age, and complemented it, for the first time, with a multidimensional data analyses approach (non-negative tensor factorization, NTF) to examine holistically how patterns of multiple nutrients and changes over time are associated with the delivery mode.ResultsOver the first 4 months, nutrient profiles in the milk of mothers who delivered vaginally (n = 237) showed significantly higher levels of palmitoleic acid (16:1n-7), stearic acid (18:0), oleic acid (18:1n-9), arachidic acid (20:0), alpha-linolenic acid (18:3n-3), eicosapentaenoic acid (20:5n-3), docosahexenoic acid (22:6n-3), erucic acid (22:1n-9), monounsaturated fatty acids (MUFA)%, calcium, and phosphorus, whereas the ratios of arachidonic acid/docosahexaenoic acid (ARA/DHA) and n-6/n-3, as well as polyunsaturated fatty acids (PUFA)% were higher in milk from women who had C-sections, in the unadjusted analyses (p < 0.05 for all), but did not retain significance when adjusted for confounders in the mixed models. Using a complementary multidimension data analyses approach (NTF), we show few similar patterns wherein a group of mothers with a high density of C-sections showed increased values for PUFA%, n-6/n-3, and ARA/DHA ratios, but decreased values of MUFA%, 20:1n-9, iodine, and fucosyl-sialyl-lacto-N-tetraose 2 during the first 4 months of lactation.Conclusion Our data provide preliminary insights on differences in concentrations of several HM nutrients (predominantly fatty acids) among women who delivered via C-section. Although these effects tend to disappear after adjustment for confounders, given the similar patterns observed using two different data analytical approaches, these preliminary findings warrant further confirmation and additional insight on the biological and clinical effects related to such differences early in life.
... It has been hypothesised that inappropriate placental transport of FAs would be compensated for after birth, with higher levels of FAs in HM [33]. There are approximately 170 types of FAs in HM, and their composition depends on many factors, including genetics, length of gestation, and the diet of the woman during both pregnancy and lactation [34,35]. The socioeconomic status of the mothers is correlated with their income, education, and lifestyle, which may in turn determine their dietary choices [36]. ...
Article
Objectives: Human milk (HM) is a complex fluid that meets the nutritional needs of infants. Its composition idrfs associated with environmental, maternal, and foetal variables. It provides nutrients and bioactive substances, including cytokines, immunoglobulins, and constituents with antioxidative properties. Boys are reportedly more susceptible to oxidative stress. This study aimed to determine the relationship between infant sex and the antioxidants vitamins C and E, and the fatty acid (FA) profile of HM. Results of this investigation may infer sex differences for the composition of infant formulas. Methods: Thirty days after delivery, a sample of HM was collected from 152 healthy, non-smoking mothers of full-term new-borns (77 males) born in good clinical condition. After FAs were extracted from the fat component, they were converted into methyl esters and separated using high-performance gas chromatography. Tocopherol content was determined using a method described in a previous study. Vitamin C content was determined using reversed-phase high-performance liquid chromatography with ultraviolet detection, as described in the same study. Results: The study groups (male versus female offspring) did not differ in terms of vitamin and FA content in HM. The only difference found was in gondoic acid 20:1 (n-9), with a higher concentration in the HM of mothers with female offspring (mean 0.63 ± 0.18 versus 0.59 ± 0.15 g/100 g FA; p < 0.047). Conclusions: Despite the acknowledged differences in the composition of HM associated with infant sex and the increased oxidative stress in males, antioxidant content did not appear to differ according to infant sex. These results suggest that there is no need for the antioxidant content of infant formulas to be sex specific.
... The composition of BM is highly variable and can be affected by lactation stage, 16,17 stage of a feed (fore-versus hind-milk), 18 circadian rhythm, 19,20 maternal diet, nutritional supplementation and medical conditions, 17,21,22 maternal anthropometry, parity, socioeconomic status, 23,24 and infant sex, 17,25 although the strength of the evidence for maternal and infant factors is less strong. Length of gestation also influences the composition of BM 16 with mothers of preterm infants producing BM in the first 12-16 postnatal weeks with higher energy and protein content, 16 lower lactose, 26 and a different profile of fatty acids (FA), especially medium-chain FAs (MCFAs), 27 compared to BM produced by mothers of full-term (FT) infants. ...
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Background Volatile compounds in breastmilk (BM) likely influence flavor learning and, through the cephalic phase response, metabolism, and digestion. Little is known about the volatile compounds present in preterm BM. We investigated whether maternal or infant characteristics are associated with the profile of volatile compounds in preterm BM. Methods Using solid-phase microextraction coupled with gas chromatography/mass spectrometry, we analyzed volatile compounds in 400 BM samples collected from 170 mothers of preterm infants. Results Forty volatile compounds were detected, mostly fatty acids and their esters (FA and FAe), volatile organic compounds (VOCs), aldehydes, terpenoids, alcohols, and ketones. The relative concentration of most FA and FAe increased with advancing lactation and were lower in BM of most socially deprived mothers and those with gestational diabetes ( p < 0.05), but medium-chain FAs were higher in colostrum compared to transitional BM ( p < 0.001). Infant sex, gestational age, and size at birth were not associated with the profile of volatile compounds in preterm BM. Conclusions Sensory-active volatile FA and FAe are the major contributors to the smell of preterm BM. The associations between lactation stage, maternal characteristics, and volatile compounds, and whether differences in volatile compounds may affect feeding behavior or metabolism, requires further research. Impact Sensory-active volatile FAs are major contributors to the smell of preterm BM and are influenced by the lactation stage and maternal characteristics. Longitudinal analysis of volatile compounds in preterm BM found that FAs increased with advancing lactation. Colostrum had a higher concentration of medium-chain FAs compared to transitional BM and the concentration of these is associated with socioeconomic status, gestational diabetes, and ethnicity.
... Lipids in human milk provide almost half of the caloric intake of infants [4]. The total lipid content is relatively stable and crucial in fulfilling nutritional needs, although the lipid composition in human milk changes over the course of lactation [5,6]. Lipids in human milk are present as lipid droplets with a volume-based mode diameter of 3-5 µm and are enveloped by a tri-layered membrane mainly consisting of phospholipids, membranespecific proteins and cholesterol [7][8][9]. ...
Article
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Lipids are essential for healthy infant growth and development. The structural complexity of lipids in human milk is not present in infant milk formula (IF). A concept IF was developed mimicking more closely the structure and composition of human milk fat globules. The current study evaluates whether a concept IF with large, milk phospholipid-coated lipid droplets (mode diameter 3 to 5 μm) is equivalent to standard IF with regard to growth adequacy and safety in healthy, term Asian infants. In this randomized, double-blind, controlled trial, infants were randomized after parents decided to introduce formula. Infants received a standard IF with (Control) or without the specific prebiotic mixture scGOS/lcFOS (9:1 ratio; Control w/o prebiotics), or a Concept IF with large, milk phospholipid-coated lipid droplets and the prebiotic mixture. A group of 67 breastfed infants served as a reference. As a priori defined, only those infants who were fully intervention formula-fed ≤28 days of age were included in the equivalence analysis (Control n = 29; Control w/o prebiotics n = 28; Concept n = 35, per-protocol population). Primary outcome was daily weight gain during the first four months of life, with the difference between the Concept and Control as the key comparison of interest. Additionally, adverse events, growth and tolerance parameters were evaluated. Equivalence of daily weight gain was demonstrated between the Concept and Control group after additional correction for ethnicity and birthweight (difference in estimated means of 0.1 g/d, 90%CI [−2.30, 2.47]; equivalence margin +/− 3 g/d). No clinically relevant group differences were observed in secondary growth outcomes, tolerance outcomes or number, severity or relatedness of adverse events. This study corroborates that an infant formula with large, milk phospholipid-coated lipid droplets supports adequate growth and is well tolerated and safe for use in healthy infants.
Article
This brief report is derived from a postgraduate project that aims to assay the influence of maternal and perinatal factors on the composition of human milk. Such research shows that the gender of the newborn can influence this composition.
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Early-life adversity (ELA) is a major risk factor for developing later-life mental and metabolic disorders. However, if and to what extent ELA contributes to the comorbidity and sex-dependent prevalence/presentation of these disorders remains unclear. We here comprehensively review and integrate human and rodent ELA (pre- and postnatal) studies examining mental or metabolic health in both sexes and discuss the role of the placenta and maternal milk, key in transferring maternal effects to the offspring. We conclude that ELA impacts mental and metabolic health with sex-specific presentations that depend on timing of exposure, and that human and rodent studies largely converge in their findings. ELA is more often reported to impact cognitive and externalizing domains in males, internalizing behaviors in both sexes and concerning the metabolic dimension, adiposity in females and insulin sensitivity in males. Thus, ELA seems to be involved in the origin of the comorbidity and sex-specific prevalence/presentation of some of the most common disorders in our society. Therefore, ELA-induced disease states deserve specific preventive and intervention strategies.
Article
Sexual dimorphism of the fetus manifests itself even during pregnancy. Preterm births are more common in pregnancies with male fetuses. Intrauterine and postnatal growth nomograms are sex-specific. The human milk composition in term infants appears to be sex-specific. Early nutrition has sex-specific effects and neurodevelopmental outcomes. A large same-sex twin study suggests that a mother’s own milk (MOM) provides sex-specific growth advantages probably related to the calibration of a mother’s milk based on her newborn’s sex. Formula composition does not vary with infant sex, which may be one reason why body composition data favors the use of MOM over formula. However, given the lack of data on this subject, we need more detailed information on how the sex-specific micronutrients in MOM influence infant well-being. We also need more information to ascertain the sex differences in infants’ macronutrient requirements, such as whether preterm females have higher fat requirements and preterm males have higher protein requirements for optimal growth and neurodevelopmental outcomes. This information may also influence milk banking and the use of donor human milk (DBM). Further research may help us determine if we should provide sex-specific DBM to those preterm infants who cannot get their MOM.
Article
The unique geographical characteristics and food culture of Tibet can affect the nutrition of human milk lipids. But little has been done in the comparison of the lipids between Tibet and other areas. This study gives in-depth analysis of the species, concentration and composition of lipid subclasses at the molecular level of the Tibetan human milk. There were averagely 132 ± 30 species of lipids, among which triglycerides (TAGs), phosphatidylethanolamine (PE) and sphingomyelin (SM) accounted for 79.78% of the total species number in the Tibetan human milk samples. The contents of TAG, SM, phosphatidylcholine (PC), and PE in the Tibetan human milk were 85.84%, 17.79%, 25.94% and 55.81% of those in the comparative human milk of China, respectively. The contents of TAGs and diglycerides (DAGs) with PUFAs in Tibetan human milk were significantly lower than those in the comparative group. However, the content and percentage of TAGs and DAGs with odd-chain saturated fatty acids were both higher in the Tibetan human milk than those in the comparative human milk. In total, 18 molecular species of lipids were downregulated and 5 ones were upregulated in the Tibetan human milk compared with those in the comparative human milk of China. The profile of lipids in the Tibetan human milk at the molecular level provided the scientific basis for maternal diet and supplemented the Chinese human milk lipids database.
Article
Background: If the mother and infant cannot meet after birth, it is recommended to express milk and give it to the infant. There was evidence indicating that there might be decrease in essential nutrient values in human milk content depending on the expression technique in literature. The goal of this systematic review was to investigate the effect of human milk expression techniques on the macronutrient milk content and establish an evidence base for future studies. Methods: Studies investigating the effect of human milk expression techniques on milk content were reviewed without year limitations. A literature review was conducted in six electronic databases (MEDLINE, Web of Science, PubMed, ScienceDirect, CINAHL and Cochrane) until 30 May 2021, using the keywords of breast milk expression techniques, milk content and breast milk pumping. Results: From 258 articles initially screened, we included 6 articles in the systematic review. The fat, protein and lactose content of human milk was analyzed in the studies reviewed. It was concluded that there was no significant effect on the protein (9.7-9.8 g/dl and 2.1-2.1 g/dl, respectively) and lactose (6.50-6.53% and 6.1-6.1 g/dl, respectively) content of milk. However, the fat (58.30, 48.81g/l; 2.6-2.2 g/dl) content was affected. Conclusions: This study investigated the effect of milk expression techniques on the macronutrient content of human milk, and it was concluded that there was no significant effect on the protein and carbohydrate content of milk. However, the fat content was affected. Limitation of this study is that some factors that might affect the content of human milk were not standardized sufficiently in the included studies.
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Urodzenie syna, w porównaniu do urodzenia córki, w odmienny sposób wpływa na zdrowie i fizjologię matki. W trakcie ciąży synowie są większym obciążeniem energetycznym i immunologicznym dla organizmu kobiety. Matki będące w ciąży z chłopcami częściej chorują na cukrzycę i nadciśnienie ciążowe oraz częściej poddawane są cesarskiemu cięciu. Kobiety będące w ciąży z córkami częściej cierpią na nudności, wymioty i większe zaburzenia funkcji poznawczych. Dla synów matki produkują bardziej wartościowe mleko. Niektóre różnice w konsekwencjach urodzenia synów lub córek obserwowane są dopiero w późniejszym wieku. Urodzenie dużej liczby synów może negatywnie odbijać się na ogólnym zdrowiu matek w późniejszym wieku, co może w konsekwencji zwiększać ryzyko zgonu. Natomiast urodzenie samych córek zwiększa ryzyko wystąpienia nowotworu jajnika. Nie jest możliwe jednoznaczne rozstrzygnięcie, czy rodzenie córek jest dla matek bardziej korzystne od rodzenia synów. Jednak aby w pełni zrozumieć konsekwencje reprodukcji dla zdrowia i fizjologii kobiet, niezbędne jest uwzględnianie płci urodzonych dzieci.
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Background Children with intestinal failure (IF) receiving long-term parenteral nutrition (PN) have altered body composition (BC), but data on BC changes from start of PN onwards are lacking. Objectives We aimed to assess growth and BC in infants after neonatal intestinal surgery necessitating PN and at risk of IF, and to explore associations with clinical parameters. Methods A prospective cohort study in infants after intestinal surgery. IF was defined as PN dependency for >60 d. SD scores (SDS) for anthropometry were calculated until 6-mo corrected age. In a subgroup, fat mass (FM) and fat-free mass (FFM) were measured with air-displacement plethysmography at 2- and 6-mo corrected age. SDS for length-adjusted FM index and FFM index were calculated. Associations between cumulative amount of PN and BC parameters were analyzed with linear mixed-effect models. Results Ninety-five neonates were included (54% male, 35% born <32 wk) and 39 infants (41%) had IF. Studied infants had compromised anthropometric parameters during follow-up. At 6-mo corrected age, they remained smaller (median weight-for-age SDS –0.9 [IQR –1.5, 0.1], P < 0.001) than the normal population. In 57 infants, 93 BC measurements were performed. FM index SDS was lower than in healthy infants at 2- and 6-mo corrected age (–0.9 [–1.6, –0.3], P < 0.001 and –0.7 [–1.3, 0.1], P = 0.001, respectively), but FFM index SDS did not differ. A higher cumulative amount of PN predicted a higher FM index in female infants but lower FM index in male infants. Conclusions In this cohort of infants receiving PN after intestinal surgery, compromised anthropometrics, decreased FM, and adequate FFM were observed during the first 6 mo. Male and female infants seemed to respond differently to PN when it comes to FM index. Continuing growth monitoring after the age of 6 mo is strongly recommended, and further research should explore the benefit of incorporating ongoing BC monitoring during follow-up.
Chapter
Virtually all living cells produce and secrete extracellular vesicles into the extracellular space. Among the various classes of extracellular vesicles, exosomes (~100 nm diameter) are of particular interest because of their unique role in cell-to-cell communication. This type of communication is facilitated by the transfer of regulatory cargos such as microRNAs from donor cells to adjacent or distant recipient cells. Evidence suggests that exosomes and their microRNA cargos are derived not only from endogenous synthesis but may also be absorbed in the gastrointestinal tract from milk, and microRNAs in milk exosomes alter gene expression in recipient cells. Studies of exosomes and microRNA cargos in human milk and infant nutrition are just beginning to emerge. Preliminary evidence, discussed in this chapter, suggests that exosomes found in milk and consumed from the diet accumulate primarily in the brain and liver in mice and change microbial communities in the murine rectum. In addition, consumption of a diet depleted of milk-borne exosomes and their microRNA cargos causes a loss in spatial learning and memory, alters purine metabolism, and might impair immune function compared with exosomes and microRNA-sufficient controls in murine models. Much remains to be discovered about milk-borne exosomes and their biological functions.
Chapter
Human milk contains myriad bioactive lipids, many originating from the milk fat globule membrane. The mean ganglioside, cholesterol, and phospholipid concentrations range (per 100 mL) from 3.015.0 μg total lipid-bound sialic acid to 12.1–21.4 mg, to 16.0–36.0 mg, respectively. When measured, there are several other minor sterols found in milk. Sampling procedures, time postpartum, preterm birth, and analytical methodology all influence, to varying degrees, the estimated content of these lipids. Despite being in small and somewhat variable amounts in a mothers’ milk, these bioactive lipids likely contribute to the optimal development of her infant. The objective of this chapter is to review and summarize the published literature on what is known (and in many cases not known) about the content of these minor lipids in human milk across lactation and the methodologies used to quantify them.
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The composition of human milk is the result of the evolution of mammals over millions of years. Among the most important components of milk are fatty acids. Approximately 85% are saturated and monounsaturated fatty acids – the rest are polyunsaturated one. Their role is to provide energy and immunity and to serve as buildings blocks, as well as assisting the hormonal system and the metabolism of fats, carbohydrates and proteins. The structural differences between fatty acids determine their biodiversity and give them particular physiological importance. Correct development of the nervous system, retina and other structures depend on an adequate supply of both these fatty acids during intrauterine development and in the newborn and infant stages. The fats present in milk form milk fat globules – structures that do not appear in milk formula prepared using vegetable oils. Apart from the mother’s diet, other sources of fatty acids are endogenous biosynthesis in the mammary gland and the fat deposits from which the fatty acids are released. Evolution of the mother’s body has also created adaptive mechanisms that adjust the amount of fatty acids in milk to the state of health and needs of the child. These mechanisms go some way to creating a buffer with regard to dietary shortages experienced by pregnant/breastfeeding women, and optimalise the composition of milk fatty acids depending on the age of the pregnant woman, the birth weight of the infant and the efficiency of the placenta during pregnancy.
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Using gas chromatography and HPLC–MS/MS, 28 fatty acids and 74 molecular species of phospholipid were identified in 90 mature (96–180 days) human milk samples from three regions of China (Zhengzhou, Wuhan and Harbin). There were obvious differences in the content of some phospholipid fatty acids from three regions. The differences in fatty acid composition of human milk phospholipids in different individuals were mainly reflected in the contents of unsaturated fatty acids. The molecular species with the highest content of glycerophospholipids in human milk samples tested were 36:2. The molecular species of sphingomyelin in human milk from the three regions differed greatly, but the glycerophospholipid composition did not differ significantly. Compared with glycerophospholipid, the contents of molecular species in human milk sphingomyelin from different individuals had a higher coefficient of variation (33.14%).
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Concentrations of five phospholipid (PL) classes and their respective molecular species were determined in mature milk samples from a cohort of Chinese mothers over an eight month lactational period. Although changes were not statistically significant, average total PL concentrations increased over the mature milk period from a one month low of 193 mg L⁻¹ to a high of 246 mg L⁻¹ at eight months lactation. Phosphatidyl ethanolamine (37% of total PLs) was the most abundant phospholipid class throughout the mature milk period, followed by sphingomyelin (32%), phosphatidyl choline (22%), phosphatidyl serine (4%) and phosphatidyl inositol (3%). The molecular species 36:2 was identified as the most abundant for the glycerophospholipids, ranging from 37% to 64% of the total molecular species intensities, and lactational changes in this molecular species dominated the overall lactational changes in proportions of molecular species. At 20.6%, the molecular species d40:1 was the major sphingomyelin molecular species identified.
Article
Gangliosides (GA) are glycosphingolipids containing sialic acid, existing in various sources, such as dairy products, eggs, brains and other tissues. The monosialoganglioside GM3 is the major GA species in mature human milk, while the disialoganglioside GD3 is the most abundant species in bovine milk and human colostrum. Recently, GA have attracted substantial attention due to their positive influences in several biological actions, for instance pathogen binding, neural development and immune system activation. Consequently, this review aimed to summarise the structure, biosynthesis, analysis and identification of these functional biomolecules. Furthermore, the nutritional, functional and therapeutic attributes of GA are highlighted. Glycosphingolipids represent 0.6% of milk fat, and they are restricted in the milk fat globule membrane. Gangliosides have positive influences in biological processes, for instance pathogen binding, neural development and immune system activation.
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A concept infant formula (IF) was developed with physical properties of lipid droplets mimicking more closely those in human milk. This paper describes the unique design of a randomised controlled trial evaluating the impact of the concept IF on infant growth and body composition development whilst applying a cohort-like recruitment approach that fully supports breastfeeding practices of the study population. Subjects entered the study between birth and 1 months of age, and whenever parents decided to introduce formula were randomised to one of three study formulas; the concept IF comprising large lipid droplets coated by milk phospholipids and containing a specific mixture of prebiotics, a standard IF with the specific prebiotic mixture or a standard IF without the prebiotic mixture. The primary objective was to evaluate the impact of the concept IF on growth and body composition outcomes during the first year of life with a follow-up at 2, 3, 4 and 5 years of age. In addition, stool, saliva and buccal smear samples and parameters assessing safety, gastrointestinal tolerance and cognitive outcomes were collected. The applied cohort-like enrolment approach is distinctly different from standard clinical safety or efficacy studies and may provide valuable insights on trial design for the evaluation of IF while carefully considering breastfeeding practices.
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Milk polar lipids provide choline, ethanolamine, and polyunsaturated fatty acids, which are needed for the growth and plasticity of the tissues in a suckling child. They may also inhibit cholesterol absorption by interacting with cholesterol during micelle formation. They may also have beneficial luminal, mucosal, and metabolic effects in both the neonate and the adult. The milk fat globule membrane contains large proportions of sphingomyelin (SM), phosphatidylcholine (PC), and phosphatidylethanolamine (PE), and some phosphatidylserine (PS), phosphatidylinositol (PI), and glycosphingolipids. Large-scale technical procedures are available for the enrichment of milk fat globule membrane (MFGM) in milk replacement formulations and food additives. Pancreatic phospholipase A2 (PLA2) and mucosal phospholipase B digest glycero-phospholipids in the adult. In the neonate, where these enzymes may be poorly expressed, pancreatic lipase-related protein 2 probably has a more important role. Mucosal alkaline SM-ase and ceramidase catalyze the digestion of SM in both the neonate and the adult. In the mucosa, the sphingosine is converted into sphingosine-1-phosphate, which is both an intermediate in the conversion to palmitic acid and a signaling molecule. This reaction sequence also generates ethanolamine. Here, we summarize the pathways by which digestion and absorption may be linked to the biological effects of milk polar lipids. In addition to the inhibition of cholesterol absorption and the generation of lipid signals in the gut, the utilization of absorbed choline and ethanolamine for mucosal and hepatic phospholipid synthesis and the acylation of absorbed lyso-PC with polyunsaturated fatty acids to chylomicron and mucosal phospholipids are important.
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Boys born preterm are recognised to be at higher risk of adverse outcomes than girls born preterm. Despite advances in neonatal intensive care and overall improvements in neonatal morbidity and mortality, boys born preterm continue to show worse short- and long-term outcomes than girls. Preterm birth presents a nutritional crisis during a critical developmental period, with postnatal undernutrition and growth-faltering common complications of neonatal intensive care. Furthermore, this preterm period corresponds to that of rapid in utero brain growth and development, and the developmental window relating to foetal programming of adult non-communicable diseases, the prevalence of which are associated both with preterm birth and sex. There is increasing evidence to show that from foetal life, boys and girls have different responses to maternal nutrition, that maternal breastmilk composition differs based on foetal sex and that early neonatal nutritional interventions affect boys and girls differently. This narrative review examines the evidence that sex is an important moderator of the outcomes of preterm nutrition intervention, and describes what further knowledge is required before providing nutrition intervention for infants born preterm based on their sex. This review examines the increasing evidence that boys and girls respond differently to nutritional stressors before birth, that maternal breastmilk composition differs by foetal sex and that nutritional interventions have different responses based on infant sex. Boys and girls born preterm are given standard nutritional support which does not take infant sex into account, and few studies of neonatal nutrition consider infant sex as a potential mediator of outcomes. By optimising early nutrition for boys and girls born preterm, we may improve outcomes for both sexes. We propose future studies of neonatal nutritional interventions should consider infant sex.
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Background: To evaluate the potential factors associated with the nutritional composition of human milk of puerperal women. Methods: cross-sectional study, conducted between March 2016 and August 2017, with 107 women, selected in a Tertiary Health Care Tertiary Health Facility of the Unified Health System (SUS) in the Municipality of Rio de Janeiro. Data were collected two months after delivery. The dependent variable of the study was the nutritional composition of human milk. We divided the independent variables into hierarchical levels: distal (age, schooling, parity and pregestational nutritional status), intermediate (number of prenatal visits and gestational weight gain) and proximal (alcohol consumption, smoking, diabetes mellitus and hypertension). For data analysis, we applied the multiple linear regression, centered on the hierarchical model. Only the variables associated with the nutritional composition of breast milk remained in the final model at a 5% level of significance. Results: The nutritional composition of human milk yielded by women with pregestational overweight, smokers and hypertensive had higher amounts of lipids and energy. Conversely, women with gestational weight gain below the recommended had lower amounts of these components. Conclusion: The evaluation of factors associated with the nutritional composition of human milk is extremely important to assist post-partum care practices. In this study, we observed that lipid and energy contents were associated to pregestational nutritional status, gestational weight gain, smoking and hypertension.
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Background: Lack of robust estimates of human-milk nutrient composition and influential maternal factors, such as body composition, are barriers to informing nutrition policies and programs. Objective: The objective was to understand the relation between maternal BMI and human-milk energy, fat, and/or total protein. Methods: Four electronic databases (MEDLINE, Embase, CINAHL, and Web of Science) were searched. Outcomes assessed were human-milk energy (kcal/L), fat (g/L), and total protein (g/L) from mothers 1 to 6 mo postpartum. Studies with data on maternal BMI or weight and height that quantified human-milk energy, fat, or protein between 1 and 6 mo postpartum were eligible. Random-effects meta-regression weighted by the inverse of the study-level SE was completed for each of the 3 outcomes. The certainty of evidence for each outcome was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Results: A total of 11,373 titles and abstracts were identified, and after full-text screening, 69 articles of 66 studies were included. Meta-regression results showed a positive association between maternal BMI and human-milk fat (β: 0.56 g/L; 95% CI: 0.034, 1.1; P = 0.04; I2 = 93.7%, n = 63 datapoints). There was no significant association between maternal BMI and human-milk energy (β: 3.9 kcal/L; 95% CI: -1.6, 9.5; P = 0.16, I2 = 93.3%, n = 40 datapoints) or total protein (β: 0.13 g/L; 95% CI: -0.16, 0.41; P = 0.37, I2 = 99.1%, n = 40 datapoints). The certainty of evidence for human-milk energy was low and the certainty of evidence for fat and total protein was very low. Conclusions: Meta-regression analysis of available literature suggested an association between maternal BMI and human-milk fat between 1 and 6 mo postpartum. Future studies are needed to confirm the relation between maternal BMI; variation in human-milk energy, fat, and protein content; and the implications for child growth and development. This review is registered with International Prospective Register of Systematic Reviews (PROSPERO 2018 CRD42018098808) at https://www.crd.york.ac.uk/prospero/.
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The rapid growth of infant brains places an exceptionally high demand on the supply of nutrients from the diet, particularly for preterm in-fants. Sialic acid (Sia) is an essential component of brain gangliosides and the polysialic acid (polySia) chains that modify neural cell adhe-sion molecules (NCAM). Sia levels are high in human breast milk, predominately as N-acetylneuraminic acid (Neu5Ac). In contrast, in-fant formulas contain a low level of Sia consisting of both Neu5Ac and N-glycolylneuraminic acid (Neu5Gc). Neu5Gc is implicated in some human inflammatory diseases. Brain gangliosides and polysia-lylated NCAM play crucial roles in cell-to-cell interactions, neuronal outgrowth, modifying synaptic connectivity, and memory formation. In piglets, a diet rich in Sia increases the level of brain Sia and the expres-sion of two learning-related genes and enhances learning and memory. The purpose of this review is to summarize the evidence showing the importance of dietary Sia as an essential nutrient for brain development and cognition.
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The WHO has developed new growth curves based on breast-fed infants. Recommendations for energy intake have been adopted based on measurements of total energy expenditure. Data on human milk (HM) intake are needed to estimate the energy intake from this food source. However, objective HM data from around the world have not been available, because these measurements are difficult to obtain. Stable isotope methods have been developed to provide objective measurements over a 14-d period. A pooled analysis of 1115 data points of HM intake, obtained using the dose to the mother deuterium oxide turnover method, was undertaken in infants aged 0-24 mo from 12 countries across 5 continents. A hierarchical model was needed to estimate mean HM intake and its variance within and between countries given the complexity of the data. The overall mean HM intake was 0.78 (95% CI = 0.72, 0.84) kg/d, and the age-specific estimates indicated that intake increased over the first 3-4 mo and remained above 0.80 kg/d until 6-7 mo. The variability of intake increased in late infancy. Boys consumed 0.05 kg/d more than girls (P < 0.01). HM intake was strongly, inversely associated with non-HM water intake [r = -0.448 (95% CI -0.511 to -0.385); P < 0.0001]. These objective isotope values of HM intake improve our understanding of the magnitude and variability of HM intake within and across populations and help to estimate nutrient intakes in breast-fed infants.
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Lactation, an important characteristic of mammalian reproduction, has evolved by exploiting a diversity of strategies across mammals. Comparative genomics and transcriptomics experiments have now allowed a more in-depth analysis of the molecular evolution of lactation. Milk cell and mammary gland genomic studies have started to reveal conserved milk proteins and other components of the lactation system of monotreme, marsupial, and eutherian lineages. These analyses confirm the ancient origin of the lactation system and provide useful insight into the function of specific milk proteins in the control of lactation. These studies also illuminate the role of milk in the regulation of growth and development of the young beyond simple nutritive aspects.
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The presence of mammary glands is the defining morphological feature of mammals. The recent assembly of the bovine genome and a report in Genome Biology that links the milk and lactation data of bovine and other mammalian genomes will help biologists investigate this economically and medically important feature.
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Factors associated with concentrations of energy-yielding nutrients in human milk were examined at 3, 6, 9, and 12 mo postpartum in the DARLING (Davis Area Research on Lactation, Infant Nutrition and Growth) Study. Samples were obtained by complete expression of alternate breasts over 24 h. Milk energy density was highly correlated with lipid concentration; both were positively related to maternal percent of ideal body weight (%IBW) at 6, 9, and 12 mo and negatively related to milk volume at 3 mo and to parity at 12 mo. Milk protein concentration was negatively related to milk volume at 6 and 9 mo and positively related to nursing frequency at 6 mo and %IBW at 9 mo. Milk lactose concentration was positively related to milk volume at 6 and 9 mo and to continued amenorrhea at 9 mo. In a subsample who completed dietary records, protein intake was positively associated with lipid concentration after 16 wk postpartum but not before. These findings suggest that milk composition is more sensitive to maternal factors such as body composition, diet, and parity during later lactation than during the first few months.
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Patterns of infant feeding, basal prolactin concentrations, and ovarian activity were studied longitudinally in 27 breast-feeding mothers from delivery until first ovulation. Suckling frequency (6.1 feeds/day) and suckling duration (122 mins/day) reached peak values four weeks post partum and remained relatively constant until the introduction of supplementary food at a mean of 16 weeks post partum. There were subsequently sharp declines in both the frequency and duration of suckling, both of which correlated closely with basal prolactin concentrations. None of the 27 mothers ovulated during unsupplemented breast-feeding, but within 16 weeks of introducing supplements ovarian follicular development had returned in 20 and ovulation in 14 mothers. The mothers who ovulated within 16 weeks of giving supplements had reduced frequency and duration of suckling more quickly and weaned more abruptly than those who continued to suppress ovulation. These data suggest that the introduction of supplementary food may exert an important and hitherto unrecognised effect on the timing of first ovulation by reducing the frequency and duration of suckling episodes.
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Mice carrying either a deletion of the murine alpha-lactalbumin (alpha-lac) gene (null allele) or its replacement by the human alpha-lac gene (humanized allele) have been generated by gene targeting. Homozygous null females are alpha-lac-deficient, produce reduced amounts of thickened milk containing little or no lactose, and cannot sustain their offspring. This provides definitive evidence that alpha-lac is required for lactose synthesis and that lactose is important for milk production. Females homozygous for the humanized allele lactate normally, indicating that human alpha-lac can replace murine alpha-lac. Mouse and human alpha-lac expression was compared in mice heterozygous for the humanized allele. The human gene expressed approximately 15-fold greater mRNA and approximately 14-fold greater protein than the mouse, indicating that the major determinants of human alpha-lac expression are close to, or within, the human gene and that the mouse locus does not exert a negative influence on alpha-lac expression. Variations in alpha-lac expression levels in nondeficient mice did not affect milk lactose concentration, but the volume of milk increased slightly in mice homozygous for the humanized allele. These variations demonstrated that alpha-lac expression in mice is gene dosage dependent.
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The substrate demands of lactation must be met by increased dietary intake or by mobilization of nutrients from tissues. The capacity of animals to rely on stored nutrients depends to a large extent on body size; large animals have greater stores, relative to the demands of lactation, than do small animals. The substrate demands of lactation depend on the composition and amount of milk produced. Animals that fast or feed little during lactation are expected to produce milks low in sugar but high in fat, in order to minimize needs for gluconeogenesis while sustaining energy transfers to the young. The patterns of nutrient transfer are reviewed for four taxonomic groups that fast during part of or throughout lactation: sea lions and fur seals (Carnivora: Otariidae), bears (Carnivora: Ursidae), true seals (Carnivora: Phocidae) and baleen whales (Cetacea: Mysticeti). All these groups produce low-sugar high-fat milks, although the length of lactation, rate of milk production and growth of the young are variable. Milk protein concentrations also tend to be low, if considered in relation to milk energy content. Maternal reserves are heavily exploited for milk production in these taxa. The amounts of lipid transferred to the young represent about one-fifth to one-third of maternal lipid stores; the relative amount of the gross energy of the body transferred in the milk is similar. Some seals and bears also transfer up to 16-18 % of the maternal body protein via milk. Reliance on maternal reserves has allowed some large mammals to give birth and lactate at sites and times far removed from food resources.
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Differences in the growth pattern of breastfed (BF) and formula-fed (FF) infants are well-recognized and have been attributed to differences in nutrient intake. However, the impact of qualitative and quantitative differences in nutrient intake on the body composition of BF and FF infants has been unclear. Furthermore, it is unknown whether putative differences in body composition persist beyond weaning. Prospective cohort study. Repeated anthropometric and body composition measurements were performed on 40 BF and 36 FF infants at 0.5, 3, 6, 9, 12, 18, and 24 months of age. A multicomponent body composition model based on total body water by deuterium dilution, total body potassium by whole body counting, and bone mineral content by dual-energy x-ray absorptiometry was used to estimate fat-free mass (FFM) and fat mass (FM). Independent measurements of FFM and FM were made using total body electrical conductivity and dual-energy x-ray absorptiometry. By design, infants were either exclusively BF or FF from birth to 4 months of age; thereafter, the feeding mode was at the discretion of the parents. Infant food intake was measured at 3, 6, 12, and 24 months of age using 3-day weighed-intake records. Data were analyzed by repeated measures analysis of variance. Weight velocity was higher in FF than BF infants age 3 to 6 months, and higher in FF than BF girls 6 to 9 months of age. Adjusted for gender and baseline values, BF infants had lower total body water at 3 months, lower total body potassium at 3 to 24 months, and lower bone mineral content at 12 months. The multicomponent model indicated that FFM was lower in BF than FF infants at 3 months, and FM and %FM were higher in BF than FF infants at 3 and 6 months (boys only). Total body electric conductivity confirmed lower FFM in BF than FF infants at 3 months, as well as at 6 and 9 months; FM and %FM were higher in BF than FF at 3 and 6 months, and 9 months (boys only). Intakes of energy, protein, fat, and carbohydrate were lower in BF than FF infants at 3 and 6 months, and were positively correlated with weight gain and FFM gain, but not FM gain. No differences in nutrient intakes were observed at 12 or 24 months. Infant feeding mode is associated with differences in body composition in early infancy which do not persist into the second year of life.
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Human milk provided by healthy and well-nourished mothers is believed to cover the infant's nutrient requirements during the first half year of life. It is composed of a mixture of nutritive components as well as other bioactive factors with relevant physiologic effects in the neonate infant. Human milk composition has a dynamic nature and varies with time postpartum, during a nursing, and with the mother's diet and certain diseases. The changes of human milk composition with time of lactation seem to match the changing needs of the growing infant over time. Human milk proteins are a source of peptides, amino acids, and nitrogen for the infant, but also in the protein fraction reside other properties of human milk that may benefit the breastfeeding infant. Specific whey proteins are involved in the development of the immune response (immunoglobulins), whereas others participate in the nonimmunologic defense (lactoferrin). In addition, human milk contains a complex mixture of oligosaccharides that are present only in minute amounts in other mammal's milk. They may act as inhibitors of bacterial adhesion to epithelial surfaces, and thus play an important role in preventing infectious diseases in the newborn infant. Oligosaccharides may also promote the development of a so-called bifidus flora. In the next years, future research will lead to improved characterization of human milk components and elucidation of their individual mechanisms of action, which will increase our knowledge about the properties of human milk and the benefits of breastfeeding for the infant.
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Breastfeeding and human milk are the normative standards for infant feeding and nutrition. Given the documented short-and long-term medical and neurodevelopmental advantages of breastfeeding, infant nutrition should be considered a public health issue and not only a lifestyle choice. The American Academy of Pediatrics reaffirms its recommendation of exclusive breastfeeding for about 6 months, followed by continued breastfeeding as complementary foods are introduced, with continuation of breastfeeding for 1 year or longer as mutually desired by mother and infant. Medical contraindications to breastfeeding are rare. Infant growth should be monitored with the World Health Organization (WHO) Growth Curve Standards to avoid mislabeling infants as underweight or failing to thrive. Hospital routines to encourage and support the initiation and sustaining of exclusive breastfeeding should be based on the American Academy of Pediatrics-endorsed WHO/UNICEF "Ten Steps to Successful Breastfeeding." National strategies supported by the US Surgeon General's Call to Action, the Centers for Disease Control and Prevention, and The Joint Commission are involved to facilitate breastfeeding practices in US hospitals and communities. Pediatricians play a critical role in their practices and communities as advocates of breastfeeding and thus should be knowledgeable about the health risks of not breastfeeding, the economic benefits to society of breastfeeding, and the techniques for managing and supporting the breastfeeding dyad. The "Business Case for Breastfeeding" details how mothers can maintain lactation in the workplace and the benefits to employers who facilitate this practice. Pediatrics 2012; 129:e827-e841
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Background: Smoking during pregnancy is associated with disturbed cardio-respiratory control of the infant and is a major risk factor for sudden infant death syndrome (SIDS). Although it is not known whether the harmful effects of smoking are caused by nicotine or other toxic substances in tobacco smoke, nicotine replacement therapy (NRT) during pregnancy is often regarded as being safer than smoking.
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Human milk provides the key nutrients necessary for the infants' growth and development. The fatty acid composition of human milk has been extensively studied over the last 20 years and the results obtained by analyzing the fatty acid profile followed by lipid extraction and expressing data as g per 100g of fatty acids. The main drawback is that normalizing data set does not give any information on the amount of fatty acid mother's milk and therefore the level of intake by the infant. The objective of the present study was to develop and validate a direct method to analyze the fatty acid content in liquid human milk samples. Hydrochloric acid in a solution of methanol was selected as the catalyst and methyl undecanoate (11:0) as the internal standard together with tritridecanoin (13:0 TAG) to monitor transesterification performance. The separation of fatty acid methyl esters (FAME) was performed using a 100m highly polar capillary column and a certified calibration mixture used to calculate experimental response factors. The method is suitable to quantify fatty acids in human milk from a 250μL sample and allow expression of the data in mg of fatty acids per deciliter of human milk as well as weight % of fatty acids. The method has been validated and show a good repeatability [CV(r)<15% and CV(r)<20% for the concentrations close to the LOQ] and a good intermediate reproducibility [CV(iR)<15% and CV(iR)<20% for the concentrations close to the LOQ]. The method was applied to analyze human milk samples obtained from 50 mothers 4 weeks post partum and the data are provided in absolute and relative quantity. These results show that the inter-individual variability of the fatty acid content in human milk is of prime importance and such information cannot be captured with normalized data sets.
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This article reviews risks of illness or exposures to breastfed infants. Galactosemia in an infant is a contraindication to breastfeeding. There are no medical conditions in the mother that are contraindications, although diagnostic procedures, treatment, or illness can interfere. Restrictive diets or malnutrition are not contraindications but are opportunities to provide nutritional counseling. Environmental toxic exposures within the United States are uncommon; breastfeeding is not usually contraindicated. In any concerning situation, an assessment and discussion of risks and benefits for the mother-infant dyad (breastfed or formula fed) is indicated. Coordinated medical care and lactation assistance can facilitate successful breastfeeding.
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This article provides an overview of the composition of human milk, its variation, and its clinical relevance. The composition of human milk is the biological norm for infant nutrition. Human milk also contains many hundreds to thousands of distinct bioactive molecules that protect against infection and inflammation and contribute to immune maturation, organ development, and healthy microbial colonization. Some of these molecules (eg, lactoferrin) are being investigated as novel therapeutic agents. Human milk changes in composition from colostrum to late lactation, within feeds, by gestational age, diurnally, and between mothers. Feeding infants with expressed human milk is increasing.
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Human milk is a complex and variable fluid of increasing interest to human biologists who study nutrition and health. The collection and analysis of human milk poses many practical and ethical challenges to field workers, who must balance both appropriate methodology with the needs of participating mothers and infants and logistical challenges to collection and analysis. In this review, we address various collection methods, volume measurements, and ethical considerations and make recommendations for field researchers. We also review frequently used methods for the analysis of fat, protein, sugars/lactose, and specific biomarkers in human milk. Finally, we address new technologies in human milk research, the MIRIS Human Milk Analyzer and dried milk spots, which will improve the ability of human biologists and anthropologists to study human milk in field settings. © 2012 Wiley Periodicals, Inc.
Article
The immune activation that occurs with infection diverts energy from growth and can contribute to poor nutritional outcomes in developing infants and children. This study investigates the association between salivary immunoglobulin A (IgA) levels and growth outcomes among Ariaal infants of northern Kenya. The Ariaal are a group of settled northern Kenyan pastoralists who are under considerable nutritional stress. Two hundred and thirty-nine breastfeeding Ariaal infants were recruited into the study and underwent anthropometric measurement and saliva collection, with mothers providing individual and household characteristics for them via questionnaire. Infant saliva samples were analyzed with an ELISA for IgA in the United States. Infant anthropometric measurements were converted to height-for-age z-scores (HAZ) using the WHO Child Growth Standards. Based on multivariate models performed in SAS 9.2 two main results emerge: 1) low HAZ, an indicator of chronic undernutrition, was significantly associated with higher IgA concentration (β = -0.12, P = 0.050) and 2) boys had significantly higher IgA levels than girls (β = 0.25, P = 0.039). Although there was not a significant interactive effect between HAZ and sex, the two variables confound each other, with boys having significantly lower HAZ values than girls do. In addition, maternal breastmilk IgA was significantly associated with infant salivary IgA, indicating that maternal effects play a role in infant IgA development. Future research will unravel the three-way association between sex, stunting, and immune function in the Ariaal community.
Article
In the emergence of diverse animal life forms, food is the most insistent and pervasive of environmental pressures. As the life sciences begin to understand organisms in genomic detail, evolutionary perspectives provide compelling insights into the results of these dynamic interactions between food and consumer. Such an evolutionary perspective is particularly needed today in the face of unprecedented capabilities to alter the food supply. What should we change? Answering this question for food production, safety and sustainability will require a much more detailed understanding of the complex interplay between humans and their food. Many organisms that we grow, produce, process and consume as foods naturally evolved adaptations in part to avoid being eaten. Crop breeding and processing have been the tools to convert overtly toxic and antinutritious commodities into foods that are safe to eat. Now the challenge is to enhance the nutritional quality and thereby contribute to improving human health. We posit that the Rosetta stone of food and nourishment is mammalian lactation and 'mother's milk'. The milk that a mammalian mother produces for her young is a complete and comprehensive diet. Moreover, the capacity of the mammary gland as a remarkable bioreactor to synthesise milk, and the infant to utilise milk, reflects 200 million years of symbiotic co-evolution between producer and consumer. Here we present emerging transdisciplinary research 'decoding' mother's milk from humans and other mammals. We further discuss how insights from mother's milk have important implications for food science and human health.
Article
Data on sex differences in mortality, morbidity, growth under conditions of environmental stress, and growth responses to environmental improvement are reviewed to test the hypothesis that males are less buffered than females against the environment during growth and development. The hypothesis predicts that males should be more affected by environmental stress, and the strongest support for this is found in studies of the prenatal period. Under stressful conditions, males have higher late fetal mortality than females, and their fetal growth generally has been found to be more retarded. Investigations of postnatal responses to environmental stress have yielded much less consistent results, in large part because of the fact that male children are given preferential treatment in many societies. Results of studies of differences between the sexes in their response to environmental improvement are contradictory. During the prenatal peroid males seem to show a greater response to nutritional supplementation, while postnatal catch-up growth is usually greater in females. Similarly, some investigations report larger secular trends in males, while others have found larger increases in females. These contradictory findings can be reconciled with the hypothesis of greater male environmental sensitivity, but they illustrate the need to obtain more specific information on the environment to which males and females are subject before the hypothesis can be tested adequately.
Article
The Trivers-Willard hypothesis predicts the unequal parental investment between daughters and sons, depending on maternal condition and offspring reproductive potential. Specifically, in polygynous populations where males have higher reproductive variance than females, it predicts that mothers in good condition will invest more in sons, whereas mothers in poor condition will invest more in daughters. Previous studies testing this hypothesis focused on behavioral investment, whereas few examined biological investment. This study investigates the Trivers-Willard hypothesis on both behavioral and biological parental investment by examining breastfeeding frequencies and breast milk fat concentrations. Data from exclusively breastfeeding mothers in Northern Kenya were used to test hypotheses: Economically sufficient mothers will breastfeed sons more frequently than daughters, whereas poor mothers will breastfeed daughters more frequently than sons, and economically sufficient mothers will produce breast milk with higher fat concentration for sons than daughters, whereas poor mothers will produce breast milk with higher fat concentration for daughters than sons. Linear regression models were applied, using breastfeeding frequency or log-transformed milk fat as the dependent variable, and offspring's sex (son = 1/daughter = 0), socioeconomic status (higher = 1/lower = 0), and the sex-wealth interaction as the predictors, controlling for covariates. Our results only supported the milk fat hypothesis: infant's sex and socioeconomic status interacted (P = 0.014, n = 72) in their relation with milk fat concentration. The model estimated that economically sufficient mothers produced richer milk for sons than daughters (2.8 vs. 0.6 gm/dl) while poor mothers produced richer milk for daughters than sons (2.6 vs. 2.3 gm/dl). Further research on milk constituents in relation to offspring's sex is warranted.
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The energy requirements of the brain are very high, and tight regulatory mechanisms operate to ensure adequate spatial and temporal delivery of energy substrates in register with neuronal activity. Astrocytes-a type of glial cell-have emerged as active players in brain energy delivery, production, utilization, and storage. Our understanding of neuroenergetics is rapidly evolving from a "neurocentric" view to a more integrated picture involving an intense cooperativity between astrocytes and neurons. This review focuses on the cellular aspects of brain energy metabolism, with a particular emphasis on the metabolic interactions between neurons and astrocytes.
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The human baby is born extremely immature, with its major organs and immune system not fully developed. for its survival, the infant depends on an extraordinarily well-adapted evolutionary strategy shared by all mammals: breastfeeding. But what does milk contain that makes it so essential for the newborn and how does it provide immunity, nutrition, and a source for optimal growth? Human milk is a very complex living fluid which comprises proteins, carbohydrates, lipids, cells and other biologically important components. These milk components interact synergistically with each other and their environment (the infant's gut) at a biomolecular level with the final result being that breastmilk feeds and protects the newborn. This article summarises the key characteristics of breastmilk proteins and describes their functions as critical molecules conferring human milk with its diverse bioactive properties. Also presented are some of the factors which hav an influence on the quantity and quality of breastmilk proteins.
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Lipids are a complex group of biomolecules whose precise functions remain poorly understood. As a result of this poor understanding, it is difficult to make mechanistically based recommendations for appropriate dietary intakes. It is equally difficult to develop methods that are capable of diagnosing functional impairments because of insufficiencies or excesses in particular fatty acids. Lipids are abundant building blocks of cellular membranes, supply components for lipid particle assembly and substrates for metabolic fuel, and provide a precursor pool for an astonishingly diverse range of signalling molecules. In each of these broad functions, the functional consequences of different structures of fatty acids are not fully understood. According to research on membrane functions through early evolution, docosahexaenoic acid provides two biophysical properties to membranes - accelerating the lateral motion of lipids and proteins within the plane of the membrane and simultaneously slowing the rate of diffusion/leakage of charged species across the plane of the membrane. The range of fatty acid structures used as substrates for assembly of either lipoproteins or milk fat globules is broad, yet the functional consequences of differences are not known. Different lipids signal into a remarkable range of biological processes. Saturated and monounsaturated fatty acids are becoming recognized as signal molecules in their own right. The complex composition of human milk lipids implies that diets with a diversity of fatty acids in complex lipid forms and structures is more beneficial than a narrow range of any particular group of fatty acids.
Article
This study examines sex differences in vulnerability among children experiencing rapid culture change that may reflect distinct microecologies driven by differential parental investment and/or sex-specific life history strategies. Apparent female growth canalization may be a life history strategy favoring growth over maintenance but also may reflect sex-differentiated selection for resilience based on unequal treatment during early life. Stature, weight, and serum measures of C-reactive protein (CRP, an inflammation marker) and Epstein-Barr Virus antibodies (EBV, a humoral immune response marker) were collected longitudinally among children/adolescents ages 5-20 years (N = 65), 5-9 years after sustained contact in a fringe highland hunter-horticulturalist group from the Schrader Range in Papua New Guinea exhibiting male preference and sex-biased survival. It was hypothesized that girls would exhibit canalization, with better nutritional status than boys; lower maintenance investment would yield lower female immune activation; and because of differential survivorship, females would appear increasingly canalized as early conditions for girls worsened relative to boys. Girls had greater arm circumference z-scores than boys, less frequent stunting, and lower CRP despite high pathogen load. Average nutritional status for girls improved over time as the sex ratio became increasingly male biased and the condition of female infants reportedly worsened. Both canalization and survivorship effects were found. Although a life history perspective on female canalization can help explain developmental outcomes in populations undergoing rapid culture change amid adversity, possible sex differences in the strength of survivorship effects that select for resiliency should not be ignored.
Article
Infant body composition is affected by maternal obesity, which results in increased % body fat in the infant. With the rapidly increasing incidence of obesity, it is important that normative data are available for infant body composition that is not affected by this trend in maternal obesity. This study assessed body composition in infants born at term to women with a BMI between 18.5 and 25. Infant % body fat, fat mass (FM), and fat free mass (FFM) were assessed at birth, 6 wk, 3 mo, and 4.5 mo of age by air displacement plethysmography, using the PEA POD body composition system. The effects of age, gender, GA, and feeding mode on these parameters were assessed. The % body fat doubled between birth and 6 wk of age and then increased at a slower rate. FFM was higher in male infants at all ages, whereas % body fat was higher in female infants at 4.5 mo. There was a trend to increased % fat and decreased FFM in breastfed (BF) infants. The study provides unique data regarding changes in infant body composition and growth in infants born to women in the healthy weight range.
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Human milk oligosaccharides (HMO) are complex glycans that are present at very high concentrations in human milk but not in infant formula. The significant energy expended by mothers to make these complex glycans suggests they must be important. How do maternal HMOs benefit the breast-fed infant? How are HMOs synthesized in the human mammary gland? How can we provide formula-fed infants with HMOs or HMO-like glycans? This article reviews current knowledge and open questions on the biosynthesis and functions of HMOs.
Article
Early development of the percentage of fat and muscle is rarely considered, but is important because excessive fat is related to the development of diabetes and other morbidities later in life. In pediatric medicine, there are few to no data comparing sex differences in body composition in the first months of life despite the fact that males are typically longer and weigh more than girls at birth. The purpose of this study was to determine whether observed sex differences in body composition at birth persist through the first 6 months of life. Methods: Participants were healthy, full-term, male and female newborns. Children throughout the Oklahoma City, Oklahoma, metropolitan area were enrolled. The inclusion criteria were: mothers aged 18 to 45 years at the time of delivery; a term pregnancy lasting >or=37 weeks of gestation (determined by mother's physician); weight adequate for gestational age; and a hospital stay for the infant of <3 days following delivery. The exclusion criteria were: maternal tobacco use or alcohol consumption (>1 drink per week) during pregnancy; gestational diabetes; preeclampsia; and infants with presumed or known congenital birth defects. Baseline assessment at birth included length and weight. Newborns had their body composition (percent fat [%fat], total fat, and fat-free mass) determined at approximately 1 month of age using whole body plethysmography. Mothers were invited to have their children take part in a 5-month extension that conducted additional body composition measurements at 3 and 6 months of age. Sixty-four girls (mean [SD] age at time of testing, 20.9 [7.9] days; birth weight, 3500 [388] g; birth length, 49.9 [2.4] cm; white race, 73.4%) and 53 boys (mean age at time of testing, 20.2 [7.3] days; birth weight, 3353 [413] g; birth length, 51.0 [2.4] cm; white race, 69.8%) were assessed and included in the study. At birth, girls were significantly shorter and weighed more than boys (both, P < 0.05). At ~1 month of age, body composition revealed that girls had significantly greater %fat (15.1% vs 12.7%; P < 0.05) and less fat-free mass (3182 [303] vs 3454 [361] g; P < 0.001) than did boys. At 3 months of age, girls continued to have significantly less fat-free mass (4379 [347] vs 4787 [310] g; P < 0.01) than did boys; however, by 6 months of age, no significant sex difference was observed in any body composition variable studied. In this small sample of healthy, full-term newborns, at ~1 month of age, statistically significant differences in %fat and fat-free mass existed between girls and boys; however, by 6 months of age, these differences no longer existed.
Article
During human evolutionary history, and for many around the world, breast milk is the primary source of nutritional energy for infants. Variation in breast milk quality might logically have important effects on infant health, growth, and development, yet the sources of this variation remain largely unelucidated. We quantified nutrient and energy content of breast milk from 25 healthy, well-nourished Massachusetts mothers with infants aged 2-5 months. We examined several potential sources of variation in milk quality, particularly feeding patterns, infant sex, and maternal breast growth during pregnancy. After controlling for time since last feeding, a known correlate of milk composition, we found that mothers of male infants produced milk that had 25% greater energy content than mothers of female infants (P < 0.001). Change in maternal bra cup size during pregnancy was associated with 16.17 kcal/100 ml greater energy content of milk (P = 0.009), but was not significant after taking infant sex into account. Greater nutritional investment in sons may account for the greater observed growth rates in male compared to female infants.