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1.
Thiamine dose response in human milk with supplementation among lactating women in Cambodia: study protocol for a double-blind, four-parallel arm randomised controlled trial.
Whitfield, KC, Kroeun, H, Green, T, Wieringa, FT, Borath, M, Sophonneary, P, Measelle, JR, Baldwin, D, Yelland, LN, Leemaqz, S, et al
BMJ open. 2019;(7):e029255
Abstract
INTRODUCTION Thiamine (vitamin B1) deficiency remains a concern in Cambodia where women with low thiamine intake produce thiamine-poor milk, putting their breastfed infants at risk of impaired cognitive development and potentially fatal infantile beriberi. Thiamine fortification of salt is a potentially low-cost, passive means of combating thiamine deficiency; however, both the dose of thiamine required to optimise milk thiamine concentrations as well as usual salt intake of lactating women are unknown. METHODS AND ANALYSIS In this community-based randomised controlled trial, 320 lactating women from Kampong Thom, Cambodia will be randomised to one of four groups to consume one capsule daily containing 0, 1.2, 2.4 or 10 mg thiamine as thiamine hydrochloride, between 2 and 24 weeks postnatal. The primary objective is to estimate the dose where additional maternal intake of thiamine no longer meaningfully increases infant thiamine diphosphate concentrations 24 weeks postnatally. At 2, 12 and 24 weeks, we will collect sociodemographic, nutrition and health information, a battery of cognitive assessments, maternal (2 and 24 weeks) and infant (24 weeks only) venous blood samples (biomarkers: ThDP and transketolase activity) and human milk samples (also at 4 weeks; biomarker: milk thiamine concentrations). All participants and their families will consume study-provided salt ad libitum throughout the trial, and we will measure salt disappearance each fortnight. Repeat weighed salt intakes and urinary sodium concentrations will be measured among a subset of 100 participants. Parameters of Emax dose-response curves will be estimated using non-linear least squares models with both 'intention to treat' and a secondary 'per-protocol' (capsule compliance ≥80%) analyses. ETHICS AND DISSEMINATION Ethical approval was obtained in Cambodia (National Ethics Committee for Health Research 112/250NECHR), Canada (Mount Saint Vincent University Research Ethics Board 2017-141) and the USA (University of Oregon Institutional Review Board 07052018.008). Results will be shared with participants' communities, as well as relevant government and scientific stakeholders via presentations, academic manuscripts and consultations. TRIAL REGISTRATION NUMBER NCT03616288.
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2.
Protective factors in mature human milk: a look into the proteome and peptidome of adolescent mothers' breast milk.
Campanhon, IB, da Silva, MRS, de Magalhães, MTQ, Zingali, RB, Bezerra, FF, Torres, AG
The British journal of nutrition. 2019;(12):1377-1385
Abstract
The characterisation of proteome and peptidome of adolescent mothers' breast milk brings important information to both mother's and infant's health; however, it has not been investigated. Bioactive peptides derived from milk proteins have numerous functions. The bioactivity of breast milk peptides includes anti-inflammatory and antimicrobial activities and regulation of gastrointestinal function. We aimed to characterise the proteome and peptidome of mature breast milk of adolescent mothers and investigate whether it is affected by lactational period. We used a combination of electrophoretic and nano-scale LC-quadrupole time-of-flight MS/MS (nLC-Q-TOF-MS/MS) techniques and bioinformatics to explore the proteome of human skimmed milk expressed by lactating adolescents in two groups according to postpartum period (up to 3 and over 5 weeks postpartum). This is the first study that analysed the proteome of adolescent mothers' breast milk produced during two periods of lactation using 1D-electrophoresis combined with nLC-Q-TOF-MS/MS analysis. Our results showed that the protein composition of adolescent milk varies independently of lactation stage and showed high inter-individual variation. A total of 424 proteins were identified in skimmed milk, of which 137 proteins were common to both groups. Most of the peptides found in adolescents' breast milk were not derived from major proteins in milk. Association maps showed several interactions between groups of peptides that pointed to the relevance of breast milk peptides to neonatal defensive system.
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3.
Differences in energy expenditure in human donor milk versus formula milk in preterm newborns: A crossover study.
Soares, FVM, Abranches, AD, Méio, MDBB, Gomes, SC, Villela, LD, Moreira, MEL
Nutrition (Burbank, Los Angeles County, Calif.). 2019;:1-4
Abstract
OBJECTIVE The aim of this study was to compare the ratio between energy expenditure and caloric density in human donor milk versus formula milk in preterm newborn infants. METHODS This was a crossover, randomized clinical trial with 29 preterm newborn infants receiving full diet. The infants were randomly assigned to receive either human milk or formula milk alternating, after a 24-h period. Energy expenditure was evaluated by indirect calorimetry. Total calorie and macronutrient values in the human milk were calculated individually with infrared technique; energy expenditure/caloric density ratio was calculated. RESULTS Human donor milk energy expenditure/caloric density ratio was significantly greater than in formula milk at all time points. The total mean was 1.04 ± 0.27 for the human milk and 0.81 ± 0.11 for the formula. However, when we analyzed a subgroup of newborns that received human donor milk with >60 kcal/100 mL, there was no statistical difference (P = 0.36). The mean calorie values were 58.9 kcal/100 mL (human donor milk) and 81.4 kcal/100 mL (formula milk). CONCLUSION Formula milk produced a better metabolic response than human donor milk. Human donor milk with higher caloric content showed no difference from formula, so the use of human donor milk with more caloric density should be reinforced.
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4.
Human milk protein vs. formula protein and their use in preterm infants.
Gianni, ML, Roggero, P, Mosca, F
Current opinion in clinical nutrition and metabolic care. 2019;(1):76-81
Abstract
PURPOSE OF REVIEW We review the current available evidence on the metabolic fate of human milk proteins and their potential clinical implications for growth and body composition development vs. those of formula proteins in preterm infants. RECENT FINDINGS The decreased content of human milk protein in preterm mothers throughout lactation might contribute to the reduced growth reported in exclusively human milk-fed infants compared with that of formula-fed infants. Recent studies have demonstrated that preterm infants are capable of degrading human milk proteins regardless of their degree of prematurity or postnatal age, with limited contribution from milk proteases to protein digestion. The nitrogen balance of fortified human milk-fed preterm infants is higher than that of formula-fed preterm infants. Moreover, the growth of human milk-fed preterm infants appears to be accompanied by fat-free mass deposition. SUMMARY Provided that adequate protein and energy intakes are delivered, human milk enhances protein use rather than oxidation as well as promotes tissue growth, leading to preferential fat-free mass deposition and contributing to the recovery of the body composition in preterm infants. Human milk feeding should be supported and promoted for all preterm mother-infant pairs.
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5.
[Non-caloric sweeteners in pregnancy and lactation].
Cavagnari, BM
Revista espanola de salud publica. 2019
Abstract
Many pregnancies have a weight gain that is higher than recommended, situation that carries several risks for the mother and her child. As a strategy to achieve a lower weight gain, the replacement of sugar-sweetened foods and beverages by those with non-caloric sweeteners could be a choice for pregnant or puerperal mothers. The objective of this article is to review the available evidence regarding the use of non-caloric sweeteners during pregnancy and lactation. Pregnancy is not a period to lose weight, so it would not be advisable to perform hypocaloric diets. However, to achieve an adequate weight gain during pregnancy, many women choose to consume food and beverages with non-caloric sweeteners. During pregnancy, the consumption of cyclamate, saccharin and crude stevia leaf should be avoided, as well as that of stevia infusions or extracts of the whole leaf. Regarding the rest of the approved non-caloric sweeteners, their consumption during pregnancy and lactation is considered to be safe, as long as they are consumed in moderation, adhering to their admissible daily intake levels. Aspartame does not reach breast milk. While saccharin, sucralose, and acesulfame-K are detectable in breast milk, their concentration is several orders of magnitude below their admissible daily intake levels.
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Production of HMOs using microbial hosts - from cell engineering to large scale production.
Bych, K, Mikš, MH, Johanson, T, Hederos, MJ, Vigsnæs, LK, Becker, P
Current opinion in biotechnology. 2019;:130-137
Abstract
Human Milk Oligosaccharides (HMOs) constitute an important, highly abundant part of mothers' milk delivering many health benefits to the neonate. Until recently, limited availability of HMOs has prevented their use in infant nutrition and impeded research into their biological effects. The shift from chemical synthesis to biotechnological manufacturing has made them accessible in quantities and at prices that are within reach for commercial applications, including infant formula. It accelerated the studies in the field of pre-clinical and clinical HMO biology. This review gives a short overview of HMO manufacturing from the design and optimization of the microbial cell factory and the production of HMOs in the industrial fermentation process to the purification in the downstream process necessary to obtain a final product. Moreover, the transition from chemistry to biotechnology and the current regulatory landscape and commercialization progress are briefly reviewed.
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7.
[Medications in breastfeeding: what evidence is there?].
Raminelli, M, Hahn, SR
Ciencia & saude coletiva. 2019;(2):573-587
Abstract
Breastfeeding plays a fundamental role in the benefits for the health of the newborn child and the nursing mother. The use of medications during breastfeeding is a relevant issue, by virtue of the frequent need for pharmacological treatment in the postpartum period. The scope of this article was to conduct a review of the literature regarding the efficacy and safety of medications used during the breastfeeding period. A search was conducted in the PubMed (National Library of Medicine), ScienceDirect and Biblioteca Virtual em Saúde (BVS) databases for articles published in Portuguese, English and Spanish in the period from 1981 to 2016. This review discusses the risk of the use of medications during lactation and the effects that they may have on the breastfed infant. Few medications are contraindicated and others require care due the risk of adverse effects on breastfed infants or in the suppression of breast milk volume. Therefore, the dissemination of updated information for the health professional to adequately assess the risks and the benefits of the use of medications during breastfeeding is of vital importance, thereby contributing to avoid early weaning.
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8.
Antiretroviral Drug Concentrations in Breastmilk, Maternal HIV Viral Load, and HIV Transmission to the Infant: Results From the BAN Study.
Davis, NL, Corbett, A, Kaullen, J, Nelson, JAE, Chasela, CS, Sichali, D, Hudgens, MG, Miller, WC, Jamieson, DJ, Kourtis, AP
Journal of acquired immune deficiency syndromes (1999). 2019;(4):467-473
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Abstract
BACKGROUND Concentration of antiretroviral (ARV) drug found in plasma, and amounts of drug excreted into breastmilk, may affect HIV viral load and potentially perinatal HIV transmission. METHODS In this cohort study with 2-phase sampling, we included mothers randomized to postpartum maternal ARVs or daily infant nevirapine during 28 weeks of breastfeeding in the Breastfeeding, Antiretrovirals, and Nutrition study. Among these, we included all mothers who transmitted HIV to their infants between 2 and 28 weeks and 15% of mothers who did not (n = 27 and 227, respectively). Spearman correlation coefficients (r) were used to assess the correlation between maternal plasma and breastmilk ARV concentration. Associations between the median effective drug concentration (EC50) and detectable maternal viral load (plasma: >40 copies per milliliter, breastmilk: >56 copies per milliliter) were assessed using mixed-effects models. Cox models were used to estimate the association between maternal or infant plasma drug concentration and breastmilk HIV transmission from 2 to 28 weeks. RESULTS All ARV compounds exhibited substantial correlations between maternal plasma and breastmilk concentrations (r: 0.85-0.98, P-value <0.0001). Having plasma drug concentration above the EC50 was associated with lower odds of having detectable HIV RNA [maternal plasma odds ratio (OR) 0.64, 95% confidence interval (CI): 0.45 to 0.91; breastmilk OR 0.22, 95% CI: 0.14 to 0.35] and a reduced rate of breastmilk HIV transmission (hazard ratio 0.40, 95% CI: 0.18 to 0.93). Having breastmilk drug concentration above the EC50 was also associated with lower odds of having detectable maternal HIV RNA (plasma OR 0.62, 95% CI: 0.45 to 0.85; breastmilk OR 0.42, 95% CI: 0.29 to 0.59). CONCLUSIONS Ensuring adequate drug concentration is important for viral suppression and preventing breastmilk HIV transmission.
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Effect of preeclampsia on human milk cytokine levels.
Freitas, NA, Santiago, LTC, Kurokawa, CS, Meira Junior, JD, Corrente, JE, Rugolo, LMSS
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2019;(13):2209-2213
Abstract
INTRODUCTION Preeclampsia (PE) is a systemic inflammatory disease, and its effect on human milk immune components is poorly understood. OBJECTIVE To investigate whether PE affects human milk cytokine levels. METHODS This was a prospective observational study involving mothers diagnosed with PE and with singleton pregnancy with no fetal malformation. The following cases were excluded: diabetes, chorioamnionitis, use of illicit drugs and alcohol, mastitis and congenital infection. In total, 228 mothers were studied and divided into two groups matched by gestational age: PE (n = 114) and normotensive (control, n = 114). Colostrum was collected from 24-72 hours postpartum, and mature milk was collected at the end of the first month. Cytokines (IL-1β, IL-6, IL-8, IL-10, IL-12, and TNF-α) were measured using flow cytometry. A generalized linear model with a gamma distribution was used to analyze the differences between groups versus time interaction. RESULTS The mean gestational age was 36 weeks. Increased IL-1 and IL-6 levels and reduced IL-12 levels in the colostrum were detected in PE, while in the mature milk, the IL-6 and IL-8 levels were lower than those of the control group. CONCLUSIONS PE is associated with increased levels of inflammatory cytokines in colostrum and decreased levels in mature milk.
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Immunonutrition for Preterm Infants.
Walsh, V, McGuire, W
Neonatology. 2019;(4):398-405
Abstract
Care and outcomes for very preterm infants continue to improve, but important causes of mortality and acute and long-term morbidity associated with prolonged hospitalisation remain. Necrotising enterocolitis (NEC) and late-onset infection have emerged as the major causes of death beyond the early neonatal period and of neurodisability in very preterm infants. Although the pathogenesis of these conditions is incompletely understood, it appears to be related to the content and mode of delivery of the enteral diet, particularly the impact of immunonutrients from human breast milk on the microbial and metabolic balance within the immature intestine. Evidence exists to support investment in measures to help mothers to express breast milk as the primary source of nutrition for their very preterm infants. In the absence of maternal milk, pasteurised donor breast milk provides protection against NEC, but its nutritive adequacy is not clear and its cost-effectiveness is uncertain. Supplementation with individual immunonutrients, including immunoglobulins and lactoferrin, has not been shown to be effective in preventing NEC or infection in randomised controlled trials. The evidence base for prebiotics and probiotics is stronger, but concerns exist about the choice, safety and availability of formulations. Other strategies - including avoidance of drugs such as gastric acid suppressants that compromise innate immunity, as well as evidence-based progressive feeding strategies that reduce exposure to invasive interventions - are emerging as key components of care packages to reduce the burden of NEC, infection and associated growth and developmental faltering for very preterm infants.