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Titres and neutralising capacity of SARS-CoV-2-specific antibodies in human milk: a systematic review.
Low, JM, Low, YW, Zhong, Y, Lee, CYC, Chan, M, Ng, NBH, Amin, Z, Ng, YPM
Archives of disease in childhood. Fetal and neonatal edition. 2022;(2):174-180
Abstract
OBJECTIVE Synthesise evidence on production of SARS-CoV-2 antibodies in human milk of individuals who had COVID-19, and antibodies' ability to neutralise SARS-CoV-2 infectivity. DESIGN A systematic review of studies published from 1 December 2019 to 16 February 2021 without study design restrictions. SETTING Data were sourced from PubMed, MEDLINE, Embase, CNKI, CINAHL and WHO COVID-19 database. Search was also performed through reviewing references of selected articles, Google Scholar and preprint servers. Studies that tested human milk for antibodies to SARS-CoV-2 were included. PATIENTS Individuals with COVID-19 infection and human milk tested for anti-SARS-CoV-2 neutralising antibodies. MAIN OUTCOME MEASURES The presence of neutralising antibodies in milk samples provided by individuals with COVID-19 infection. RESULTS Individual participant data from 161 persons (14 studies) were extracted and re-pooled. Milk from 133 (82.6%) individuals demonstrated the presence of anti-SARS-CoV-2 immunoglobulin A (IgA), IgM and/or IgG. Illness severity data were available in 146 individuals; 5 (3.4%) had severe disease, 128 (87.7%) had mild disease, while 13 (8.9%) were asymptomatic. Presence of neutralising antibodies in milk from 20 (41.7%) of 48 individuals neutralised SARS-CoV-2 infectivity in vitro. Neutralising capacity of antibodies was lost after Holder pasteurisation but preserved after high-pressure pasteurisation. CONCLUSION Human milk of lactating individuals after COVID-19 infection contains anti-SARS-CoV-2-specific IgG, IgM and/or IgA, even after mild or asymptomatic infection. Current evidence demonstrates that these antibodies can neutralise SARS-CoV-2 virus in vitro. Holder pasteurisation deactivates SARS-CoV-2-specific IgA, while high-pressure pasteurisation preserves the SARS-CoV-2-specific IgA function.
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Efficacy of Wang Nam Yen herbal tea on human milk production: A randomized controlled trial.
Saejueng, K, Nopsopon, T, Wuttikonsammakit, P, Khumbun, W, Pongpirul, K
PloS one. 2022;(1):e0247637
Abstract
BACKGROUND Insufficient milk production is a common problem affecting breastfeeding women, in particular following Cesarean delivery. Wang Nam Yen herbal tea is a promising traditional Thai medicine used by postpartum women to stimulate milk production, as an alternative to pharmaceutical galactagogues. We aimed to compare the efficacy of Wang Nam Yen herbal tea, domperidone, and placebo, in increasing milk production in mothers who underwent Cesarean delivery. METHODS Women who underwent uncomplicated cesarean delivery at Sunpasitthiprasong Hospital were randomized into three groups. The participants received the treatments daily for three consecutive days. The primary outcome was breast milk volume at 72 hours after delivery. Secondary outcomes were pregnancy and neonatal outcomes, adverse events, and participant satisfaction. RESULTS Of the 1,450 pregnant women that underwent cesarean delivery, 120 women were enrolled. Their mean age and gestational ages were 28.7 years and 38.4 weeks, respectively. Breast milk volume at 72 hours postpartum was significantly different among the three groups (p = 0.030). The post hoc Bonferroni correction indicated a significant difference in breast milk volume between Wang Nam Yen herbal tea group and placebo control group (p = 0.007) while there was no difference between Wang Nam Yen herbal tea group and domperidone group (p = 0.806) and between domperidone group and placebo control group (p = 0.018). There was no difference in pregnancy and neonatal outcomes, adverse events, and participant satisfaction among the three groups. CONCLUSION Wang Nam Yen herbal tea was effective in augmenting breast milk production at 72 hours postpartum in mothers following cesarean delivery, and there was no evidence that herbal tea and domperidone differed in terms of augmenting breast milk production. TRIAL REGISTRATION The study was approved by the institutional review board of Sunpasitthiprasong Hospital (No.061/2559) and was registered TCTR20170811003 with the Thai Clinical Trial Registry.
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Oropharyngeal administration of mother's own milk influences levels of salivary sIgA in preterm infants fed by gastric tube.
Chen, LL, Liu, J, Mu, XH, Zhang, XY, Yang, CZ, Xiong, XY, Wang, MQ
Scientific reports. 2022;(1):2233
Abstract
The aim of the present study was to explore the effect of oropharyngeal mother's milk administration on salivary secretory immunoglobulin A (sIgA) levels in preterm infants fed by gastric tube. Infants (n = 130) with birth weight < 1500 g were randomly allocated into two groups which both received breast milk for enteral nutrition. The experimental group (n = 65) accepted oropharyngeal mother's milk administration before gastric tube feeding for 14 days after birth. The control group (n = 65) accepted oropharyngeal 0.9% normal saline administration. Saliva concentration of sIgA were assessed at the 2 h, 7th and 14th day after birth. The level of salivary sIgA in experimental group were significantly higher than those in control group on the 7th day after birth (p < 0.05), but there were no differences in salivary sIgA levels on the 14th day between the two groups. The results of quantile regression analysis showed that oropharyngeal mother's milk administration, delivery mode and gestational age had significant effects on the increase of sIgA. SIgA in experimental group and the total number of intervention had a significant positive correlation (p < 0.05). Oropharyngeal mother's milk administration can improve salivary sIgA levels of preterm infants.
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Functional Antibodies Against SARS-CoV-2 Receptor Binding Domain Variants with Mutations N501Y or E484K in Human Milk from COVID-19-Vaccinated, -Recovered, and -Unvaccinated Women.
Demers-Mathieu, V, Hakansson, AP, Hall, S, Lavangnananda, S, Fels, S, Medo, E
Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine. 2022;(2):163-172
Abstract
Background: New variants are evolving in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and receptor binding domain (RBD) mutations have been associated with a higher capacity to evade neutralizing antibodies (NAbs). We aimed at determining the impact of COVID-19 vaccine and infection on human milk antibody titers and activity against the RBD mutations from SARS-CoV-2 variants of concern. Materials and Methods: Milk samples were collected from 19 COVID-19 vaccinated women, 10 women who had a positive COVID-19 PCR test, and 13 unvaccinated women. The titers and NAbs of secretory IgA (SIgA)/IgA, secretory IgM (IgM)/IgM, and IgG against SARS-CoV-2 RBD with mutations N501Y or E484K were measured by using ELISA and a surrogate virus neutralization assay. Results: The titers of human milk IgG against N501Y were higher in the COVID-19 vaccine group than in the no-vaccine group but comparable with the COVID-19 PCR group. Other antibody titers did not differ between the three groups. The titers of SIgA/IgA were higher than those of SIgM/IgM and IgG in all three groups. The titers of SIgM/IgM and the inhibition of NAbs were higher against the mutation E484K than N501Y. Milk NAb did not differ between the three groups, but the inhibition of NAb against binding of the two mutant RBD proteins to their receptor was higher in the COVID-19 vaccine and PCR groups than in milk from prepandemic women. Conclusions: COVID-19 vaccination and exposure of mothers to SARS-CoV-2 influenced the titers and NAbs in breast milk against the variants of concern.
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Antihistamine use during breastfeeding with focus on breast milk transfer and safety in humans: A systematic literature review.
Ngo, E, Spigset, O, Lupattelli, A, Panchaud, A, Annaert, P, Allegaert, K, Nordeng, H
Basic & clinical pharmacology & toxicology. 2022;(1):171-181
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Abstract
Current data on use of antihistamines during breastfeeding and risks to the breastfed infant are insufficient. The aim of this systematic review was to provide an overview of studies measuring the levels of antihistamines in human breast milk, estimating the exposure for breastfed infants and/or reporting possible adverse effects on the breastfed infant. An additional aim was to review the antihistamine product labels available in the European Union (EU) and the United States. We searched seven online databases and identified seven human lactation studies that included 25 mother-infant pairs covering cetirizine, clemastine, ebastine, epinastine, loratadine, terfenadine and triprolidine. In addition, one study investigated the impact of chlorpheniramine or promethazine on prolactin levels among 17 women, and one study investigated possible adverse drug reactions in 85 breastfed infants exposed to various antihistamines. The relative infant dose was below 5% for all antihistamines, ranging from 0.3% for terfenadine to 4.5% for clemastine. Most product labels of the 10 antihistamines with available information in both the EU and the United States reported lack of evidence and recommended to avoid use during breastfeeding. The knowledge gap on antihistamines and lactation is extensive, and further human studies are warranted to ensure optimal treatment of breastfeeding women with allergy.
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The Diverse Antimicrobial Activities of Human Milk Oligosaccharides against Group B Streptococcus.
Moore, RE, Townsend, SD, Gaddy, JA
Chembiochem : a European journal of chemical biology. 2022;(3):e202100423
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Abstract
Streptococcus agalactiae or Group B Streptococcus (GBS) is a Gram-positive bacterial pathobiont that is the etiological cause of severe perinatal infections. GBS can colonize the vagina of pregnant patients and invade tissues causing ascending infections of the gravid reproductive tract that lead to adverse outcomes including preterm birth, neonatal sepsis, and maternal or fetal demise. Additionally, transmission of GBS during labor or breastfeeding can also cause invasive infections of neonates and infants. However, human milk has also been shown to have protective effects against infection; a characteristic that is likely derived from antimicrobial and immunomodulatory properties of molecules that comprise human milk. Recent evidence suggests that human milk oligosaccharides (HMOs), short-chain sugars that comprise 8-20 % of breast milk, have antimicrobial and anti-biofilm activity against GBS and other bacterial pathogens. Additionally, HMOs have been shown to potentiate the activity of antibiotics against GBS. This review presents the most recent published work that studies the interaction between HMOs and GBS.
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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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COVID-19 mRNA Vaccination in Lactation: Assessment of Adverse Events and Vaccine Related Antibodies in Mother-Infant Dyads.
Golan, Y, Prahl, M, Cassidy, AG, Gay, C, Wu, AHB, Jigmeddagva, U, Lin, CY, Gonzalez, VJ, Basilio, E, Chidboy, MA, et al
Frontiers in immunology. 2021;:777103
Abstract
BACKGROUND Data regarding symptoms in the lactating mother-infant dyad and their immune response to COVID-19 mRNA vaccination during lactation are needed to inform vaccination guidelines. METHODS From a prospective cohort of 50 lactating individuals who received mRNA-based vaccines for COVID-19 (mRNA-1273 and BNT162b2), blood and milk samples were collected prior to first vaccination dose, immediately prior to 2nd dose, and 4-10 weeks after 2nd dose. Symptoms in mother and infant were assessed by detailed questionnaires. Anti-SARS-CoV-2 antibody levels in blood and milk were measured by Pylon 3D automated immunoassay and ELISA. In addition, vaccine-related PEGylated proteins in milk were measured by ELISA. Blood samples were collected from a subset of infants whose mothers received the vaccine during lactation (4-15 weeks after mothers' 2nd dose). RESULTS No severe maternal or infant adverse events were reported in this cohort. Two mothers and two infants were diagnosed with COVID-19 during the study period before achieving full immune response. PEGylated proteins were not found at significant levels in milk after vaccination. After vaccination, levels of anti-SARS-CoV-2 IgG and IgM significantly increased in maternal plasma and there was significant transfer of anti-SARS-CoV-2-Receptor Binding Domain (anti-RBD) IgA and IgG antibodies to milk. Milk IgA levels after the 2nd dose were negatively associated with infant age. Anti-SARS-CoV-2 IgG antibodies were not detected in the plasma of infants whose mothers were vaccinated during lactation. CONCLUSIONS COVID-19 mRNA vaccines generate robust immune responses in plasma and milk of lactating individuals without severe adverse events reported.
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Using Nature to Nurture: Breast Milk Analysis and Fortification to Improve Growth and Neurodevelopmental Outcomes in Preterm Infants.
Ottolini, KM, Schulz, EV, Limperopoulos, C, Andescavage, N
Nutrients. 2021;(12)
Abstract
Premature infants are born prior to a critical window of rapid placental nutrient transfer and fetal growth-particularly brain development-that occurs during the third trimester of pregnancy. Subsequently, a large proportion of preterm neonates experience extrauterine growth failure and associated neurodevelopmental impairments. Human milk (maternal or donor breast milk) is the recommended source of enteral nutrition for preterm infants, but requires additional fortification of macronutrient, micronutrient, and energy content to meet the nutritional demands of the preterm infant in attempts at replicating in utero nutrient accretion and growth rates. Traditional standardized fortification practices that add a fixed amount of multicomponent fortifier based on assumed breast milk composition do not take into account the considerable variations in breast milk content or individual neonatal metabolism. Emerging methods of individualized fortification-including targeted and adjusted fortification-show promise in improving postnatal growth and neurodevelopmental outcomes in preterm infants.
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Centering human milk composition as normal human biological variation.
Quinn, EA
American journal of human biology : the official journal of the Human Biology Council. 2021;(1):e23564
Abstract
OBJECTIVES Human biological variation in the phenotype is the cornerstone of modern human biology, evolutionary anthropology, and related studies of human evolution. Minimal dialogue, however, has considered human milk to be part of this phenotypic variation. This may reflect researcher bias-mental models oriented around commercial infant formula and homogenized cow's milk, both of which present milk composition as static. A general lack of research outside primarily Western, well-nourished populations has also contributed to this underestimation of biological variation. METHODS This review analyzes published research on breast milk composition, developmental metabolic programming, and maternal body composition to articulate the ways in which population-based studies of human milk outside the United Sates are necessary to better understanding biological variation in human milk phenotypes. RESULTS This review discusses some of the common issues in current research on the biological variation in human milk composition and argues that anthropological inquiries that frame milk as part of an adaptive phenotype are necessary to better understand the biological significance of human milk composition in the production of human biological variation. CONCLUSIONS Biological anthropology is uniquely positioned to investigate biological variation in human milk, using evolutionary theory, cutting edge biology, and anthropologically informed perspectives that challenge the biomedical framing of lactation and often act to privilege well nourished, primarily western populations and formula feeding as normatives for infant feeding research.