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Changes in HMO Concentrations throughout Lactation: Influencing Factors, Health Effects and Opportunities.
Thum, C, Wall, CR, Weiss, GA, Wang, W, Szeto, IM-Y, Day, L
Nutrients. 2021;(7)
Abstract
Human milk oligosaccharides (HMOs) are important functional biomolecules in human breast milk. Understanding the factors influencing differences in HMO composition and changes in their concentration over lactation can help to design feeding strategies that are well-adapted to infant's needs. This review summarises the total and individual concentration of HMOs from data published from 1999 to 2019. Studies show that the HMO concentrations are highest in colostrum (average 9-22 g/L), followed by slightly lower concentrations in transitional milk (average 8-19 g/L), with a gradual decline in mature milk as lactation progresses, from 6-15 g/L in breast milk collected within one month of birth, to 4-6 g/L after 6 months. Significant differences in HMO composition have been described between countries. Different HMOs were shown to be predominant over the course of lactation, e.g., 3-fucosyllactose increased over lactation, whereas 2'-fucosyllactose decreased. Recent clinical studies on infant formula supplemented with 2'-fucosyllactose in combination with other oligosaccharides showed its limited beneficial effect on infant health.
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Resolving Human Lactation Heterogeneity Using Single Milk-Derived Cells, a Resource at the Ready.
Martin Carli, JF, Trahan, GD, Rudolph, MC
Journal of mammary gland biology and neoplasia. 2021;(1):3-8
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Single cell RNA sequencing (scRNAseq) of human milk-derived cells (HMDCs) makes highly detailed analyses of the biology of human lactation possible. We explore this powerful application as an exciting tool to inspect the cellular composition of human milk. We point out some important challenges unique to this approach and highlight the importance of collaborations between biologists and well-trained bioinformaticians to utilize these data to their maximum potential. We extend this focus by discussing the first two such studies that describe HMDCs via scRNAseq and a variety of important questions in the field that warrant attention through further research. The stage is set to apply scRNAseq in human lactation biology, potentially leading to new insights regarding the molecular and cellular diversity of human secretory mammary epithelial cells.
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Pharmacotherapy for depression and bipolar disorder during lactation: A framework to aid decision making.
Sprague, J, Wisner, KL, Bogen, DL
Seminars in perinatology. 2020;(3):151224
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OBJECTIVE Breastmilk is recommended as the exclusive source of nutrition for infants younger than 6 months due to the numerous health benefits for both infants and mothers. Although many women are prescribed medications during pregnancy and postpartum, limited data are available to assist women in weighing the benefits compared to the risks of peripartum medication use. The goals of this paper are to discuss the importance of breastmilk for the health of both the mother and infant, evaluate the impact of medication use on women's infant feeding choice, describe the transfer of drugs to breastmilk and infants, and provide a framework for clinicians to support evidence-based counseling for women treated for mood disorders. RECOMMENDATIONS We recommend early pregnancy counseling to discuss the benefits and risks of medications during breastfeeding. The Surgeon General's Call to Action (2011) highlights the short and long-term negative health effects of not providing breastmilk. Integrating recommendations from the pediatric and obstetric teams allows patients to make decisions based on evidence and reach their infant feeding goals. Databases containing summaries of research findings and pharmacologic properties of the drug of interest are an essential resource for clinicians.
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Early-Life Effects of Vitamin D: A Focus on Pregnancy and Lactation.
Wagner, CL, Hollis, BW
Annals of nutrition & metabolism. 2020;:16-28
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Vitamin D is an endocrine regulator of calcium and bone metabolism. Yet, its effects include other systems, such as innate and adaptive immunity. Unique to pregnancy, circulating 1,25-dihydroxyvitamin D (1,25[OH]2D) increases early on to concentrations that are 2-3 times prepregnant values. At no other time during the lifecycle is the conversion of 25-hydroxyvitamin D (25[OH]D) to 1,25(OH)2D directly related and optimized at ≥100 nmol/L. Vitamin D deficiency appears to affect pregnancy outcomes, yet randomized controlled trials of vitamin D supplementation achieve mixed results depending on when supplementation is initiated during pregnancy, the dose and dosing interval, and the degree of deficiency at the onset of pregnancy. Analysis of trials on an intention-to-treat basis as opposed to the use of 25(OH)D as the intermediary biomarker of vitamin D metabolism yields differing results, with treatment effects often noted only in the most deficient women. Immediately after delivery, maternal circulating 1,25(OH)2D concentrations return to prepregnancy baseline, at a time when a breastfeeding woman has increased demands of calcium, beyond what was needed during the last trimester of pregnancy, making one question why 1,25(OH)2D increases so significantly during pregnancy. Is it to serve as an immune modulator? The vitamin D content of mother's milk is directly related to maternal vitamin D status, and if a woman was deficient during pregnancy, her milk will be deficient unless she is taking higher doses of vitamin D. Because of this relative "deficiency," there is a recommendation that all breastfed infants receive 400 IU vitamin D3/day starting a few days after birth. The alternative - maternal supplementation with 6,400 IU vitamin D3/day, effective in safely raising maternal circulating vitamin D, that of her breast milk, and effective in achieving sufficiency in her recipient breastfeeding infant - remains a viable option. Additional research is needed to understand vitamin D's influence on pregnancy health and the effect of maternal supplementation on breast milk's immune signaling.
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Human milk fatty acid profile across lactational stages after term and preterm delivery: A pooled data analysis.
Floris, LM, Stahl, B, Abrahamse-Berkeveld, M, Teller, IC
Prostaglandins, leukotrienes, and essential fatty acids. 2020;:102023
Abstract
BACKGROUND Lipids in human milk (HM) provide the majority of energy for developing infants, as well as crucial essential fatty acids (FA). The FA composition of HM is highly variable and influenced by multiple factors. We sought to increase understanding of the variation in HMFA profiles and their development over the course of lactation, and after term and preterm delivery, using a pooled data analysis. OBJECTIVE To review the literature and perform a pooled data analysis to qualitatively describe an extensive FA profile (36 FAs) in term and preterm colostrum, transitional - and mature milk up to 60 days postpartum. DESIGN A Medline search was conducted for HMFA profile data following term or preterm delivery. The search was confined to English language papers published between January 1980 and August 2018. Studies reporting original data, extensive FA profiles in HM from healthy mothers were included. Weighted least squares (WLS) means were calculated from the pooled data using random or fixed effect models. RESULTS Our pooled data analysis included data from 55 studies worldwide, for a total of 4374 term milk samples and 1017 preterm milk samples, providing WLS means for 36 FAs. Patterns in both term and preterm milk were apparent throughout lactation for some FAs: The most abundant FAs (palmitic, linoleic and oleic acid) remained stable over time, whereas several long-chain polyunsaturated FAs (including ARA and DHA) seemed to decrease and short- and medium-chain FAs increased over time. CONCLUSIONS High heterogeneity between individual studies was observed for the reported levels of some FAs, whereas other FAs were remarkably consistent between studies. Our pooled data suggests that specific FA categories fluctuate according to distinct patterns over the course of lactation; many of these patterns are comparable between term and preterm milk.
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What Evidence Do We Have for Pharmaceutical Galactagogues in the Treatment of Lactation Insufficiency?-A Narrative Review.
Grzeskowiak, LE, Wlodek, ME, Geddes, DT
Nutrients. 2019;(5)
Abstract
Inadequate breast milk supply is a frequently reported reason for early discontinuation of breastfeeding and represents a critical opportunity for intervening to improve breastfeeding outcomes. For women who continue to experience insufficient milk supply despite the utilisation of non-pharmacological lactation support strategies, pharmacological intervention with medications used to augment lactation, commonly referred to as galactagogues, is common. Galactagogues exert their pharmacological effects through altering the complex hormonal milieu regulating lactation, particularly prolactin and oxytocin. This narrative review provides an appraisal of the existing evidence regarding the efficacy and safety of pharmaceutical treatments for lactation insufficiency to guide their use in clinical practice. The greatest body of evidence surrounds the use of domperidone, with studies demonstrating moderate short-term improvements in breast milk supply. Evidence regarding the efficacy and safety of metoclopramide is less robust, but given that it shares the same mechanism of action as domperidone it may represent a potential treatment alternative where domperidone is unsuitable. Data on remaining interventions such as oxytocin, prolactin and metformin is too limited to support their use in clinical practice. The review provides an overview of key evidence gaps and areas of future research, including the impacts of pharmaceutical galactagogues on breast milk composition and understanding factors contributing to individual treatment response to pharmaceutical galactagogues.
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A Review of Bioactive Factors in Human Breastmilk: A Focus on Prematurity.
Gila-Diaz, A, Arribas, SM, Algara, A, Martín-Cabrejas, MA, López de Pablo, ÁL, Sáenz de Pipaón, M, Ramiro-Cortijo, D
Nutrients. 2019;(6)
Abstract
Preterm birth is an increasing worldwide problem. Prematurity is the second most common cause of death in children under 5 years of age. It is associated with a higher risk of several pathologies in the perinatal period and adulthood. Maternal milk, a complex fluid with several bioactive factors, is the best option for the newborn. Its dynamic composition is influenced by diverse factors such as maternal age, lactation period, and health status. The aim of the present review is to summarize the current knowledge regarding some bioactive factors present in breastmilk, namely antioxidants, growth factors, adipokines, and cytokines, paying specific attention to prematurity. The revised literature reveals that the highest levels of these bioactive factors are found in the colostrum and they decrease along the lactation period; bioactive factors are found in higher levels in preterm as compared to full-term milk, they are lacking in formula milk, and decreased in donated milk. However, there are still some gaps and inconclusive data, and further research in this field is needed. Given the fact that many preterm mothers are unable to complete breastfeeding, new information could be important to develop infant supplements that best match preterm human milk.
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The Functional Power of the Human Milk Proteome.
Zhu, J, Dingess, KA
Nutrients. 2019;(8)
Abstract
Human milk is the most complete and ideal form of nutrition for the developing infant. The composition of human milk consistently changes throughout lactation to meet the changing functional needs of the infant. The human milk proteome is an essential milk component consisting of proteins, including enzymes/proteases, glycoproteins, and endogenous peptides. These compounds may contribute to the healthy development in a synergistic way by affecting growth, maturation of the immune system, from innate to adaptive immunity, and the gut. A comprehensive overview of the human milk proteome, covering all of its components, is lacking, even though numerous analyses of human milk proteins have been reported. Such data could substantially aid in our understanding of the functionality of each constituent of the proteome. This review will highlight each of the aforementioned components of human milk and emphasize the functionality of the proteome throughout lactation, including nutrient delivery and enhanced bioavailability of nutrients for growth, cognitive development, immune defense, and gut maturation.
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Cabergoline: a review of its use in the inhibition of lactation for women living with HIV.
Tulloch, KJ, Dodin, P, Tremblay-Racine, F, Elwood, C, Money, D, Boucoiran, I
Journal of the International AIDS Society. 2019;(6):e25322
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INTRODUCTION In developed countries, breastfeeding is not recommended for women living with human immunodeficiency virus (WLWH). However, lactation symptoms can be distressing for women who choose not to breastfeed. There is currently no universal guideline on the most appropriate options for prevention or reduction of lactation symptoms amongst WLWH. This review describes the evidence base for using cabergoline, a dopaminergic agonist, for the post-partum inhibition of lactation for WLWH. METHODS A scoping review of post-partum pharmaceutical lactation inhibition specific for WLWH was conducted using searches in PubMed, Medline Ovid, EBM Reviews Ovid, Embase, Web of Science and Scopus until 2019. A narrative review of cabergoline pharmacologic properties, therapeutic efficacy, tolerability data and drug interaction data relevant to lactation inhibition was then conducted. RESULTS AND DISCUSSION Among 1366 articles, the scoping review identified 13 relevant publications. Eight guidelines providing guidance regarding lactation inhibition for WLWH and two surveys of medical practice on this topic in UK have been published. Three studies have evaluated the use of pharmaceutical agents in WLWH. Two of these studies evaluated cabergoline and reported it to be an effective method of lactation inhibition in this population. The third study evaluated ethinyl estradiol and bromocriptine use and showed poor efficacy. Cabergoline is a long-acting dopamine D2 agonist and ergot derivative that inhibits prolactin secretion and suppresses physiologic lactation when given as a single oral dose of 1 mg after delivery. Cabergoline is at least as effective as bromocriptine for lactation inhibition with success rates between 78% and 100%. Transient, mild to moderate adverse events to cabergoline are described in clinical trials. Few drug interactions exist as cabergoline is neither a substrate nor an inducer/inhibitor of hepatic cytochrome P450 isoenzymes. There are no reported clinically significant drug-drug interactions between cabergoline and any antiretroviral medications including protease inhibitors. CONCLUSIONS Cabergoline is a safe and effective pharmacologic option for the prevention of physiological lactation and associated physical symptoms in non-breastfeeding women. Future studies should focus on its safety, efficacy and acceptability among WLWH.
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Lactation ketoacidosis: case presentation and literature review.
Al Alawi, AM, Falhammar, H
BMJ case reports. 2018
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A 35-year-old woman presented to the emergency department with a 2 days history of malaise and headache. She was breastfeeding her 5-month old infant and had recently started an altered diet based on reducing carbohydrate amount. Moreover, she had also started exercising 2 weeks prior to her illness. Initial blood tests revealed high anion gap metabolic acidosis and hypoglycaemia (pH 7.13 (normal 7.30-7.40), bicarbonate 9.4 mmol/L (normal 21.0-28.0), anion gap 22.6 mmol/L (normal 8-12), glucose 2.9 mmol/L (normal fasting 3.9-5.8) and ketones 6.4 mmol/L (normal <0.6)). The patient was treated with intravenous dextrose and showed complete resolution of ketoacidosis and hypoglycaemia within 48 hours. She was discharged home and remained well with a balanced diet. After excluding all other the causes of hypoglycaemia and ketoacidosis, the diagnosis of lactation ketoacidosis was made and it was considered triggered by altered diet, exercise and skipping meals. All 11 cases of lactation ketoacidosis which has previously been published are reviewed as well.