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1.
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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2.
COVID-19 mRNA vaccine and antibody response in lactating women: a prospective cohort study.
Charepe, N, Gonçalves, J, Juliano, AM, Lopes, DG, Canhão, H, Soares, H, Serrano, EF
BMC pregnancy and childbirth. 2021;(1):632
Abstract
BACKGROUND Immunological protection via breastfeeding is well known. The immunological profile of human milk changes during lactation. No clinical trials have been conducted in lactating women with the newest mRNA vaccines against SARS- CoV-2. A Few studies have shown the presence of antibodies in breastmilk after vaccination. The aim of this work is to study possible antibodies transfer via breastmilk and also the immunological characteristics of lactating women compared to non-lactating women, after using the BNT162b2 Pfizer vaccine. METHODS This is a prospective cohort study with a convenience homogenous sample of 24 healthcare workers (14 lactating and 10 non-lactating women) enrolled at the time of COVID-19 vaccination. Clinical data was registered in a questionnaire. Titers of SARS-CoV-2 spike IgG, IgA and IgM were quantified in post vaccination blood and human milk. Antibody quantification was performed by an in-house ELISA to SARS-CoV-2 trimeric spike protein. RESULTS All women showed immunity after vaccination with positive antibodies for IgM, IgA and IgG antibodies. The dominant serum antibody response was IgG. Modest levels of antibodies in breastmilk of lactating mothers were observed in this study, especially IgG in 42.9%. There was a moderate association between higher titers of IgG and a longer duration of breastfeeding (R= 0.55, p=0.041). CONCLUSIONS Evidence of antibody transfer in human milk after COVID-19 vaccination is scarce. The presence of antibodies in human milk is reported, but immunization through breastfeeding is still to be established.
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Human Milk Oligosaccharide Profile Variation Throughout Postpartum in Healthy Women in a Brazilian Cohort.
Ferreira, AL, Alves, R, Figueiredo, A, Alves-Santos, N, Freitas-Costa, N, Batalha, M, Yonemitsu, C, Manivong, N, Furst, A, Bode, L, et al
Nutrients. 2020;(3)
Abstract
Human milk oligosaccharide (HMO) composition varies throughout lactation and can be influenced by maternal characteristics. This study describes HMO variation up to three months postpartum and explores the influences of maternal sociodemographic and anthropometric characteristics in a Brazilian prospective cohort. We followed 101 subjects from 28-35 gestational weeks (baseline) and throughout lactation at 2-8 (visit 1), 28-50 (visit 2) and 88-119 days postpartum (visit 3). Milk samples were collected at visits 1, 2 and 3, and 19 HMOs were quantified usinghigh-performance liquid chromatography with fluorescence detection (HPLC-FL). Friedman post-hoc test, Spearman rank correlation for maternal characteristics and HMOs and non-negative matrix factorization (NMF) were used to define the HMO profile. Most women were secretors (89.1%) and presented high proportion of 2'-fucosyllactose (2ꞌFL) at all three sample times, while lacto-N-tetraose (LNT, 2-8 days) and lacto-N-fucopentaose II (LNFPII, 28-50 and 88-119 days) were the most abundant HMOs in non-secretor women. Over the course of lactation, total HMO weight concentrations (g/L) decreased, but total HMO molar concentrations (mmol/L) increased, highlighting differential changes in HMO composition over time. In addition, maternal pre-pregnancy body mass index (BMI) and parity influence the HMO composition in healthy women in this Brazilian cohort.
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Temporal Changes in Breast Milk Fatty Acids Contents: A Case Study of Malay Breastfeeding Women.
Khor, GL, Tan, SS, Stoutjesdijk, E, Ng, KWT, Khouw, I, Bragt, M, Schaafsma, A, Dijck-Brouwer, DAJ, Muskiet, FAJ
Nutrients. 2020;(1)
Abstract
The composition of human breast milk changes in the first two months of life, adapting itself to the evolving needs of the growing new-born. Lipids in milk are a source of energy, essential fatty acids (FA), fat-soluble vitamins, and vital bioactive components. Information on breast milk FA of Malaysian lactating women is scarce. Based on convenience sampling, a total of 20 Malay breastfeeding women who fulfilled the inclusion criteria were recruited. Breast milk was collected three times from each subject at consecutive intervals of 2-3 weeks apart. A total of 60 breast milk samples were collected and classified into "transitional milk" (n = 8), "early milk" (n = 26) and "mature milk" (n = 26). All milk samples were air freighted to University of Groningen, Netherlands for analysis. The dominant breast milk FA were oleic acid, constituting 33% of total fatty acids, followed by palmitic acid (26%). Both these FA and the essential FA, linoleic acid (10%) and alpha-linolenic acid (0.4%), showed no significant changes from transitional to mature milk. Breast milk ratio of n-6:n-3 polyunsaturated fatty acids (PUFA) was comparatively high, exceeding 10 throughout the lactation period, suggesting a healthier balance of PUFA intake is needed in pregnancy and at postpartum.
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A single-arm study to evaluate the transfer of drospirenone to breast milk after reaching steady state, following oral administration of 4 mg drospirenone in healthy lactating female volunteers.
Melka, D, Kask, K, Colli, E, Regidor, PA
Women's health (London, England). 2020;:1745506520957192
Abstract
OBJECTIVE The primary objective of this trial was to assess the transfer of drospirenone to breast milk after daily administration of an oral test preparation containing 4 mg of drospirenone at the steady state. The secondary objective of the trial was to assess safety based on clinical and laboratory measurements and reporting of adverse events and/or adverse drug reactions. PATIENTS AND METHODS This was an open label, non-comparative single-center study. Drospirenone 4 mg per day was the first postpartum contraceptive for the study participants who were no longer breastfeeding yet were still lactating. It was administered for 7 days to achieve steady-state concentration. All participants were volunteers who planned to use oral contraceptives as their family planning method in the future. RESULTS Twelve volunteers completed the trial according to the protocol, and the samples of all 12 study completers were analyzed. The average concentration-time curve of drospirenone in plasma 24 h after the administration of the last dose (area under the curve (0-24 h)) was 635.33 ng h/mL and 120 h after the single repeated dose administration (area under the curve (0-120 h)) was 1180.57 ng h/mL, respectively. The average Cmax was 48.64 ng/mL.The average concentration-time curve of drospirenone in milk 24 h after the administration of the last dose (area under the curve (0-24 h)) was 134.35 ng h/mL and 120 h after the single repeated dose administration (area under the curve (0-120 h)) was 227.17 ng h/mL, respectively. The average Cmax was 10.34 ng/mL. CONCLUSION On average, 18.13% of plasma drospirenone made it to breast milk and the highest concentration of drospirenone in breast milk was 17.55% of that in plasma. The total quantity of drospirenone passing to breast milk is on average 4478 ng during a 24-h period representing 0.11% of the maternal daily dose. Thus, at the recommended doses, no effects on breastfed newborns/infants are anticipated with drospirenone 4 mg.
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Longer-term breastfeeding outcomes associated with domperidone use for lactation differs according to maternal weight.
Grzeskowiak, LE, Amir, LH, Smithers, LG
European journal of clinical pharmacology. 2018;(8):1071-1075
Abstract
PURPOSE To examine differences in longer-term breastfeeding outcomes among mothers of preterm infants according to domperidone exposure status, as well as examine the potential for effect modification according to maternal weight. METHODS Retrospective cohort study of 198 mothers of very preterm infants (born ≤ 30 weeks' gestation) who initiated breastfeeding and whose infants survived until hospital discharge. Data on domperidone use were obtained from hospital pharmacy records, with the primary outcome defined as continuation of breastfeeding at infant discharge from the Neonatal Unit. The relationship between domperidone exposure and breastfeeding status was investigated using multivariable regression analysis, adjusting for potential confounders. Additional pre-determined analyses were undertaken following stratification according to maternal weight to investigate the presence of effect modification. RESULTS No overall difference was observed in the proportion of mothers continuing to breastfeed at the time of infant discharge from the Neonatal Unit according to whether or not they received domperidone (aRR 0.99; 0.86-1.13). Notably, effect modification was observed according to maternal weight, with use of domperidone associated with a reduced likelihood of breastfeeding at discharge among women ≥ 70 kg (aRR 0.72; 0.54-0.97), but not among those < 70 kg (aRR 1.16; 0.92-1.46). CONCLUSIONS Despite experiencing low milk supply, longer-term breastfeeding outcomes were similar between women who did and did not use domperidone. Differences in domperidone effectiveness according to maternal weight have important implications for clinical practice given the increasing prevalence of overweight/obesity in reproductive-age women and their higher risk of low milk supply, highlighting the importance of further research in this area.
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13C-labeled oligosaccharides in breastfed infants' urine: individual-, structure- and time-dependent differences in the excretion.
Dotz, V, Rudloff, S, Blank, D, Lochnit, G, Geyer, R, Kunz, C
Glycobiology. 2014;(2):185-94
Abstract
Human milk oligosaccharides (HMOs) have been paid much attention due to their beneficial effects observed in vitro, e.g., prebiotic, anti-infective and anti-inflammatory properties. However, in vivo investigations with regard to HMO metabolism and functions are rare. The few data available indicate that HMOs are absorbed to a low extent and excreted via urine without noteworthy modifications, whereas the major proportion reaches infant's colon undigested. Via intrinsic (13)C-labeling of HMOs during their biosynthesis in the mammary gland of 10 lactating women, we were able to follow the fate of (13)C-labeled oligosaccharides (OSs) from their secretion in milk to the excretion in the urine of their breastfed infants. To a certain extent, we could therefore discriminate between original HMOs and non-labeled OSs derived from degradation of HMOs or endogenous glycoconjugates. By means of our novel, rapid, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based approach, we found a homogeneous time pattern of isotopomer enrichment in milk among all subjects and between single OS species. In contrast, the time curves from infants' urine varied strongly between individuals and OS species, though the overall MALDI-TOF MS profile resembled those of the mothers' milk. Our data suggest that neutral HMOs might be processed and/or utilized differentially after or upon absorption from the gut, as deduced from their structure-dependent variation in the extent of tracer enrichment and in the retention times in infant's organism. This sheds new light on the role of HMOs within infant's body, beyond the intestine and its microbiota alone.
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Urinary metabolomic fingerprinting after consumption of a probiotic strain in women with mastitis.
Vázquez-Fresno, R, Llorach, R, Marinic, J, Tulipani, S, Garcia-Aloy, M, Espinosa-Martos, I, Jiménez, E, Rodríguez, JM, Andres-Lacueva, C
Pharmacological research. 2014;:160-5
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Abstract
Infectious mastitis is a common condition among lactating women, with staphylococci and streptococci being the main aetiological agents. In this context, some lactobacilli strains isolated from breast milk appear to be particularly effective for treating mastitis and, therefore, constitute an attractive alternative to antibiotherapy. A (1)H NMR-based metabolomic approach was applied to detect metabolomic differences after consuming a probiotic strain (Lactobacillus salivarius PS2) in women with mastitis. 24h urine of women with lactational mastitis was collected at baseline and after 21 days of probiotic (PB) administration. Multivariate analysis (OSC-PLS-DA and hierarchical clustering) showed metabolome differences after PB treatment. The discriminant metabolites detected at baseline were lactose, and ibuprofen and acetaminophen (two pharmacological drugs commonly used for mastitis pain), while, after PB intake, creatine and the gut microbial co-metabolites hippurate and TMAO were detected. In addition, a voluntary desertion of the pharmacological drugs ibuprofen and acetaminophen was observed after probiotic administration. The application of NMR-based metabolomics enabled the identification of the overall effects of probiotic consumption among women suffering from mastitis and highlighted the potential of this approach in evaluating the outcomes of probiotics consumption. To our knowledge, this is the first time that this approach has been applied in women with mastitis during lactation.
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In vivo assessment of number of milk duct orifices in lactating women and association with parameters in the mother and the infant.
Jütte, J, Hohoff, A, Sauerland, C, Wiechmann, D, Stamm, T
BMC pregnancy and childbirth. 2014;:124
Abstract
BACKGROUND In vitro and in vivo analyses differ between the number of milk ducts found in the lactating breast, and there is a lack of knowledge as to whether or not external factors in the mother or the child affect the number of ductal orifices. The aim of this study was to determine the number of milk duct orifices in vivo and to investigate the possible influence of variable parameters in mother and infant. STUDY DESIGN Prospective clinical trial. In 98 breastfeeding women we investigated the nipple surface in order to identify the number of milk duct orifices using Marmet's manual milk expression technique. In addition mothers were interviewed on different parameters of birth and breastfeeding. RESULTS Every nipple had 3.90 ± 1.48 milk duct orifices on average. There was no significant difference between left and right breasts. The use of a breast pump in addition to breastfeeding did not have any effect on the number of ductal orifices. Multiparous women exhibited more ductal orifices (8.5 ± 3.0) as compared to primipara (7.1 ± 2.7). Boys were associated with significantly more ductal orifices in their mother's right breast (4.2 ± 1.7) than girls (3.5 ± 1.4). Furthermore boys were breastfed for longer per session. A shorter birth height of males correlated with more ductal orifices in left nipples. Fluid intake of mothers was associated with a higher number of ductal orifices. Restless infant behavior could not be explained by less milk duct orifices. Pain in the breast during breastfeeding did not have an influence on ductal orifices either. Psychological criteria, such as duration of maternity leave and total intended breastfeeding period, did not affect the number of orifices in the papilla mammaria of breasts during lactation. CONCLUSION For the first time an in vivo investigation of the number of ductal orifices in lactating women was conducted non-invasively and associations with variables in the mother and the child, birth parameters in infants, and breastfeeding parameters in mothers and children were assessed. We conclude that the number of activated ductal orifices on the surface of the nipple is primarily associated with functional aspects.
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Excretion of moxidectin into breast milk and pharmacokinetics in healthy lactating women.
Korth-Bradley, JM, Parks, V, Chalon, S, Gourley, I, Matschke, K, Gossart, S, Bryson, P, Fleckenstein, L
Antimicrobial agents and chemotherapy. 2011;(11):5200-4
Abstract
Moxidectin, registered worldwide as a veterinary antiparasitic agent, is currently under development for humans for the treatment of onchocerciasis in collaboration with the World Health Organization. The objective of this study was to assess the pharmacokinetics of moxidectin in healthy lactating women, including the excretion into breast milk. Twelve women, ages 23 to 38 years, weighing 54 to 79 kg, all more than 5 months postpartum, were enrolled, following their plan to wean their infants and provision of informed consent. A single 8-mg, open-label dose was administered orally after consumption of a standard breakfast. Complete milk collection was done for approximately 28 days, and plasma samples were collected for 90 days. Moxidectin concentrations were measured by high-performance liquid chromatography (HPLC) with fluorescence detection, with a validated range of 0.08 to 120 ng/ml. Noncompartmental pharmacokinetic methods were used to find the following results: peak concentration in plasma (C(max)), 87 ± 25 ng/ml; time to C(max) (t(max)), 4.18 ± 1.59 h; terminal-phase elimination half-life (t(1/2)), 832 ± 321 h; total area under the concentration-time curve (AUC), 4,046 ± 1,796 ng · h/ml; apparent oral dose clearance (CL/F), 2.35 ± 1.07 l/h; ratio of CL/F to the terminal-phase disposition rate constant, λ(z) (Vλ(z)/F), 2,526 ± 772 liters; percentage of maternal dose excreted in milk, 0.701 ± 0.299%; absolute amount excreted in milk, 0.056 ± 0.024 mg; relative infant dose, 8.73 ± 3.17% of maternal dose assuming complete absorption; clearance in milk (CL(milk)), 0.016 ± 0.009 liter/h. Nine of 12 subjects reported adverse events, all of which were considered treatment emergent but not drug related and were mostly reported during the long outpatient period 8 to 90 days after dose administration. The most frequently reported adverse events were headache and nausea (n = 4), oropharyngeal pain (n = 2), rhinitis, viral pharyngitis, and viral upper respiratory tract infection (n = 2).