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1.
Heliyon ; 9(8): e19218, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37654447

RESUMO

Background: Moderate exercise results in a significant increase in serum and salivary immunoglobulins. Maternal physical activity might therefore also be a factor influencing antibody levels in human milk. This study aims to determine the influence of physical activity on SARS-CoV-2-specific Immunoglobulin A (IgA) in human milk and Immunoglobulin G (IgG) in serum. Methods: In this prospective cross-sectional cohort study, all lactating women in the Netherlands were eligible to participate. SARS-CoV-2-specific IgA in human milk and IgG in serum were determined using an enzyme-linked immunosorbent assay (ELISA). Data on performed physical activity was collected using the Short Questionnaire to Assess Health enhancing physical activity (SQUASH), which includes intensity and duration of the performed activity. Findings: In total, 356 out of 2312 lactating women tested positive for SARS-CoV-2-specific antibodies in serum. Of them, 323 filled in the questionnaire and were included in the analysis. An association between the activity score and SARS-CoV-2-specific antibodies in human milk (B = 1·035, 95·0% CI = 1·019 to 1·052, p = 0·042) and serum (B = 1·019, 95·0% CI = 1·009 to 1·029, p = 0·048) was demonstrated. No association was found between the duration of physical activity and SARS-CoV-2-specific antibodies in human milk or serum. Interpretation: Our findings suggest that physical activity is beneficial for the levels of SARS-CoV-2-specific antibodies in human milk and serum, with the intensity of the physical activity being the most important contributor to this relationship. A higher level of antibodies in human milk might provide better immunological protection for infants against COVID-19.

2.
Front Nutr ; 10: 1165764, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37743929

RESUMO

Background: Maternal stress in the postpartum period affects not only the mother but also her newborn child, who is at increased risk of developing metabolic and mental disorders later in life. The mechanisms by which stress is transmitted to the infant are not yet fully understood. Human milk (HM) is a potential candidate as maternal stress affects various components of HM, e.g., fat and immunoglobulin concentrations. To date, it is unknown whether maternal stress also affects the amino acids (AAs) in HM, even though this nutrient is of extreme importance to child health and development. This study aimed to investigate whether and how maternal stress is associated with the AA composition of HM. Methods: In this observational cohort study (Amsterdam, The Netherlands), lactating women were recruited in two study groups: a high-stress (HS) group; women whose child was hospitalized (n = 24), and a control (CTL) group; women who gave birth to a healthy child (n = 73). HM was collected three times a day, on postpartum days 10, 17, and 24. Perceived psychological stress was measured using validated questionnaires, while biological stress measures were based on hair, saliva, and HM cortisol concentrations. HM protein-bound and free AAs were analyzed by liquid chromatography and compared between groups. Results: Maternal perceived stress scores were higher in the HS group (p < 0.01). The concentrations of protein-bound AAs in HM were higher in the HS group compared to the CTL group (p = 0.028) and were positively associated with HM cortisol concentrations (p = 0.024). The concentrations of free AAs did not differ between study groups and were unrelated to cortisol concentrations. Conclusion: Findings from this prospective cohort study suggest that maternal stress in the postpartum period is associated with an altered human milk amino acid composition, which could play a role in the transmission of maternal stress effects to her child. The physiological implications of these stress-induced changes for infant development await future research.

3.
Front Nutr ; 10: 1107768, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37599690

RESUMO

Background: The maternal diet greatly influences the nutritional composition of human milk. With the rise of vegan diets by lactating mothers, there are concerns about the nutritional adequacy of their milk. Two important nutrients, vitamin B2 and carnitine, are mostly ingested via animal products. Objective: We investigated the influence of a vegan diet on the vitamin B2 and carnitine concentrations in milk and serum of lactating women. Methods: In this case-control study, 25 lactating mothers following an exclusive vegan diet were comparted to 25 healthy lactating mothers with an omnivorous diet without use of supplements. High-performance liquid chromatography and liquid chromatography-tandem mass spectrometry were used to measure vitamin B2 and carnitine concentrations, respectively. A linear regression model was used to determine differences in human milk and serum concentrations between study groups. Results: Vitamin B2 concentrations in human milk and serum did not differ between study groups. While the human milk free carnitine (C0) and acetyl carnitine (C2) concentrations did not differ between study groups, serum carnitine concentrations were lower in participants following a vegan diet than in omnivorous women (p < 0.0001). Conclusion: A maternal vegan diet did not affect human milk concentration of vitamin B2 and carnitine. Breastfed infants of mothers following an exclusive vegan diet therefore are likely not at increased risk of developing a vitamin B2 or carnitine deficiency.

4.
Pediatr Res ; 94(5): 1804-1809, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37355738

RESUMO

BACKGROUND: Systemic inflammation plays a key role in the development of bronchopulmonary dysplasia (BPD). Cortisol is known to dampen inflammation. However, adrenal function following preterm birth is characterized by insufficient cortisol levels for the degree of inflammation, and a relative abundancy of cortisol precursors. We investigated whether this pattern could contribute to the development of BPD in preterm infants born <30 weeks of gestation. METHODS: Cortisol, cortisone, 17-OH progesterone (17-OHP) and 11-deoxycortisol were measured in serum obtained at postnatal days 1, 3, 7, 14 and 28, using liquid-chromatography-tandem-mass-spectrometry. The presence of BPD was ascertained at 36 weeks postmenstrual age. RESULTS: Sixty-five infants were included for analysis, of whom 32 (49%) developed BPD. Preterm infants developing BPD, as compared to those without BPD, had higher levels of 17-OHP, 11-deoxycortisol and cortisone relative to cortisol in their first week of life, but not at birth or beyond day 7. CONCLUSION: Preterm infants developing BPD had higher levels of cortisol precursors and cortisone relative to cortisol in their first week of life than infants without BPD. These findings suggest that BPD is preceded by an activated hypothalamus-pituitary-adrenal axis that could not meet the high cortisol demands, which may predispose to inflammation and BPD. IMPACT: Relative adrenal insufficiency is common in the first weeks after preterm birth, resulting in insufficient cortisol production for the degree of inflammation and a relative abundance of cortisol precursors; Whether this pattern contributes to the development of bronchopulmonary dysplasia (BPD) is not fully elucidated, since most studies focused on cortisol levels; Preterm infants developing BPD had higher levels of cortisol precursors and cortisone relative to cortisol in the first week of life, suggestive of a hypothalamus-pituitary-adrenal-axis activation during BPD development which cannot meet the high cortisol demands in tissues; This glucocorticoid pattern is likely to dispose to inflammation and BPD.


Assuntos
Displasia Broncopulmonar , Cortisona , Nascimento Prematuro , Lactente , Feminino , Recém-Nascido , Humanos , Glucocorticoides , Recém-Nascido Prematuro , Hidrocortisona , Cortodoxona , Inflamação
5.
Int J Infect Dis ; 130: 126-135, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36868302

RESUMO

OBJECTIVES: Preventive measures against COVID-19 are essential for pregnant women. Pregnant women are particularly vulnerable to emerging infectious pathogens due to alterations in their physiology. We aimed to determine the optimum timing of vaccination to protect pregnant women and their neonates from COVID-19. METHODS: A prospective observational longitudinal cohort study in pregnant women who received COVID-19 vaccination. We collected blood samples to evaluate levels of antispike, receptor binding domain and nucleocapsid antibodies against SARS-CoV-2 before vaccination and 15 days after the first and second vaccination. We determined the neutralizing antibodies from mother-infant dyads in maternal and umbilical cord blood at birth. If available, immunoglobulin A was measured in human milk. RESULTS: We included 178 pregnant women. Median antispike immunoglobulin G levels increased significantly from 1.8 to 5431 binding antibody units/ml and receptor binding domain from 6 to 4466 binding antibody units/ml. Virus neutralization showed similar results between different weeks of gestation at vaccination (P >0.3). CONCLUSION: We advise vaccination in the early second trimester of pregnancy for the optimum balance between the maternal antibody response and placental antibody transfer to the neonate.


Assuntos
COVID-19 , SARS-CoV-2 , Gravidez , Recém-Nascido , Lactente , Feminino , Humanos , Formação de Anticorpos , Vacinas contra COVID-19 , Estudos Longitudinais , Segundo Trimestre da Gravidez , COVID-19/prevenção & controle , Placenta , Anticorpos Antivirais , Vacinação , Mães
6.
Commun Biol ; 6(1): 100, 2023 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-36697496

RESUMO

Human milk contains SARS-CoV-2-specific antibodies after COVID-19 vaccination. These milk antibodies decrease several months post-vaccination. Whether booster immunization restores human milk antibody levels, potentially offering prolonged passive immunity for the infant, remains unknown. In this prospective follow-up study, we investigated the longitudinal SARS-CoV-2-specific antibody response in human milk of 26 lactating women who received a COVID-19 booster dose of an mRNA-based vaccine. Moreover, we evaluated whether the booster-induced human milk antibody response differs for participants who received a similar or different vaccine type in their primary vaccination series. All participants (100%) who received a homologous booster vaccination showed SARS-CoV-2-specific immunoglobulin A (IgA) and immunoglobulin G (IgG) in their milk. Heterologous booster vaccination resulted in milk conversion for 9 (69%) and 13 (100%) participants for IgA and IgG respectively. Findings of this study indicate that both homologous and heterologous boosting schedules have the potential to enhance SARS-CoV-2-specific IgA and IgG in human milk.


Assuntos
COVID-19 , Leite Humano , Lactente , Humanos , Feminino , SARS-CoV-2 , Formação de Anticorpos , Vacinas contra COVID-19 , Seguimentos , Lactação , Estudos Prospectivos , COVID-19/prevenção & controle , Anticorpos Antivirais , Imunoglobulina G , Imunoglobulina A
7.
Cell Mol Immunol ; 20(1): 26-37, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36447030

RESUMO

The most abundant immunoglobulin present in the human body is IgA. It has the highest concentrations at the mucosal lining and in biofluids such as milk and is the second most abundant class of antibodies in serum. We assessed the structural diversity and clonal repertoire of IgA1-containing molecular assemblies longitudinally in human serum and milk from three donors using a mass spectrometry-based approach. IgA-containing molecules purified from serum or milk were assessed by the release and subsequent analysis of their Fab fragments. Our data revealed that serum IgA1 consists of two distinct structural populations, namely monomeric IgA1 (∼80%) and dimeric joining (J-) chain coupled IgA1 (∼20%). Also, we confirmed that IgA1 in milk is present solely as secretory (S)IgA, consisting of two (∼50%), three (∼33%) or four (∼17%) IgA1 molecules assembled with a J-chain and secretory component (SC). Interestingly, the serum and milk IgA1-Fab repertoires were distinct between monomeric, and J-chain coupled dimeric IgA1. The serum dimeric J-chain coupled IgA1 repertoire contained several abundant clones also observed in the milk IgA1 repertoire. The latter repertoire had little to no overlap with the serum monomeric IgA1 repertoire. This suggests that human IgA1s have (at least) two distinct origins; one of these produces dimeric J-chain coupled IgA1 molecules, shared in human serum and milk, and another produces monomeric IgA1 ending up exclusively in serum.


Assuntos
Imunoglobulina A , Leite Humano , Humanos , Fragmentos Fab das Imunoglobulinas
8.
Front Nutr ; 10: 1305086, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38288064

RESUMO

Introduction: Upon vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) humans will start to produce antibodies targeting virus specific antigens that will end up in circulation. In lactating women such antibodies will also end up in breastmilk, primarily in the form of secretory immunoglobulin A1 (SIgA1), the most abundant immunoglobulin (Ig) in human milk. Here we set out to investigate the SIgA1 clonal repertoire response to repeated SARS-CoV-2 vaccination, using a LC-MS fragment antigen-binding (Fab) clonal profiling approach. Methods: We analyzed the breastmilk of six donors from a larger cohort of 109 lactating mothers who received one of three commonly used SARS-CoV-2 vaccines. We quantitatively monitored the SIgA1 Fab clonal profile over 16 timepoints, from just prior to the first vaccination until 15 days after the second vaccination. Results: In all donors, we detected a population of 89-191 vaccine induced clones. These populations were unique to each donor and heterogeneous with respect to individual clonal concentrations, total clonal titer, and population size. The vaccine induced clones were dominated by persistent clones (68%) which came up after the first vaccination and were retained or reoccurred after the second vaccination. However, we also observe transient SIgA1 clones (16%) which dissipated before the second vaccination, and vaccine induced clones which uniquely emerged only after the second vaccination (16%). These distinct populations were observed in all analyzed donors, regardless of the administered vaccine. Discussion: Our findings suggest that while individual donors have highly unique human milk SIgA1 clonal profiles and a highly personalized SIgA1 response to SARS-CoV-2 vaccination, there are also commonalities in vaccine induced responses.

9.
Life Sci Alliance ; 5(12)2022 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-35926873

RESUMO

Human milk is important for antimicrobial defense in infants and has well demonstrated antiviral activity. We evaluated the protective ability of human milk against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a human fetal intestinal cell culture model. We found that, in this model, human milk blocks SARS-CoV-2 replication, irrespective of the presence of SARS-CoV-2 spike-specific antibodies. Complete inhibition of both enveloped Middle East respiratory syndrome coronavirus and human respiratory syncytial virus infections was also observed, whereas no inhibition of non-enveloped enterovirus A71 infection was seen. Transcriptome analysis after 24 h of the intestinal monolayers treated with human milk showed large transcriptomic changes from human milk treatment, and subsequent analysis suggested that <i>ATP1A1</i> down-regulation by milk might be of importance. Inhibition of ATP1A1 blocked SARS-CoV-2 infection in our intestinal model, whereas no effect on EV-A71 infection was seen. Our data indicate that human milk has potent antiviral activity against particular (enveloped) viruses by potentially blocking the ATP1A1-mediated endocytic process.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , Antivirais/farmacologia , Humanos , Leite Humano
10.
Front Nutr ; 9: 923501, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35845768

RESUMO

Importance: SARS-CoV-2-specific antibodies in human milk might protect the breastfed infant against COVID-19. One of the factors that may influence human milk antibodies is psychological stress, which is suggested to be increased in lactating women during the COVID-19 pandemic. Objective: To determine whether psychological stress is increased in lactating women during the COVID-19 pandemic, and if maternal stress is associated with the level of SARS-CoV-2-specific antibodies in human milk. Design: Population-based prospective cohort study. Setting: Data collection took place in the Netherlands between October 2020 and February 2021. Participants: Lactating women living in the Netherlands were eligible to participate in this study. In total, 2310 women were included. Exposures: Stress exposure during the COVID-19 pandemic was determined using the Perceived Stress Scale (PSS) questionnaire and maternal lifetime stress was determined by the Life Stressor Checklist - revised (LSC-r) questionnaire. Main Outcomes and Measures: Stress experience during the COVID-19 pandemic was compared with a pre-pandemic cohort. SARS-CoV-2-specific antibodies in human milk were measured using an Enzyme-Linked Immunosorbent Assay (ELISA) with the Spike protein of SARS-CoV-2. The association between maternal stress and human milk antibodies was determined using a multiple regression model. Results: The PSS score of lactating mothers was not increased during the pandemic compared to the PSS score in the prepandemic cohort. Six hundred ninety-one participants had SARS-CoV-2-specific antibodies and were included in the regression models to assess the association between maternal stress and human milk antibodies. No association was found between PSS scores and human milk antibodies. In contrast, the LSC-r score was negatively associated with SARS-CoV-2-specific IgA in human milk (ß = 0.98, 95% CI: 0.96-0.997, p = 0.03). Conclusions and Relevance: Our results suggest that lactating women in the Netherlands did not experience higher stress levels during the COVID-19 pandemic. Breastfed infants of mothers with high chronic stress levels receive lower amounts of antibodies through human milk, which possibly makes them more vulnerable to respiratory infections. This emphasizes the importance of psychological wellbeing during lactation.

11.
Metabolites ; 12(6)2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35736407

RESUMO

Variation in metabolite levels reflects individual differences in genetic and environmental factors. Here, we investigated the role of these factors in urinary metabolomics data in children. We examined the effects of sex and age on 86 metabolites, as measured on three metabolomics platforms that target amines, organic acids, and steroid hormones. Next, we estimated their heritability in a twin cohort of 1300 twins (age range: 5.7-12.9 years). We observed associations between age and 50 metabolites and between sex and 21 metabolites. The monozygotic (MZ) and dizygotic (DZ) correlations for the urinary metabolites indicated a role for non-additive genetic factors for 50 amines, 13 organic acids, and 6 steroids. The average broad-sense heritability for these amines, organic acids, and steroids was 0.49 (range: 0.25-0.64), 0.50 (range: 0.33-0.62), and 0.64 (range: 0.43-0.81), respectively. For 6 amines, 7 organic acids, and 4 steroids the twin correlations indicated a role for shared environmental factors and the average narrow-sense heritability was 0.50 (range: 0.37-0.68), 0.50 (range; 0.23-0.61), and 0.47 (range: 0.32-0.70) for these amines, organic acids, and steroids. We conclude that urinary metabolites in children have substantial heritability, with similar estimates for amines and organic acids, and higher estimates for steroid hormones.

12.
Microbiol Spectr ; 10(4): e0040522, 2022 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-35762813

RESUMO

Infants may develop severe viral respiratory tract infections because their immune system is still developing in the first months after birth. Human milk provides passive humoral immunity during the first months of life. During the COVID-19 pandemic, circulation of common respiratory viruses was virtually absent due to the preventative measures resulting in reduced maternal exposure. Therefore, we hypothesized that this might result in lower antibody levels in human milk during the pandemic and, subsequently, decreased protection of infants against viral respiratory tract infections. We assessed antibody levels against respiratory syncytial virus (RSV), Influenza virus, and several seasonal coronaviruses in different periods of the COVID-19 pandemic in serum and human milk using a Luminex assay. IgG levels against RSV, Influenza, HCoV-OC43, HCoV-HKU1, and HCoV-NL63 in human milk were reduced with a factor of 1.7 (P < 0.001), 2.2 (P < 0.01), 2.6 (P < 0.05), 1.4 (P < 0.01), and 2.1 (P < 0.001), respectively, since the introduction of the COVID-19 restrictions. Furthermore, we observed that human milk of mothers that experienced COVID-19 contained increased levels of IgG and IgA binding to other respiratory viruses. Passive immunity via human milk against common respiratory viruses was reduced during the COVID-19 pandemic, which may have consequences for the protection of breastfed infants against respiratory infections. IMPORTANCE Passive immunity derived from antibodies in human milk is important for protecting young infants against invading viruses. During the COVID-19 pandemic, circulation of common respiratory viruses was virtually absent due to preventative measures. In this study, we observed a decrease in human milk antibody levels against common respiratory viruses several months into the COVID-19 pandemic. This waning of antibody levels might partially explain the previously observed surge of hospitalizations of infants, mostly due to RSV, when preventative hygiene measures were lifted. Knowledge of the association between preventative measures, antibody levels in human milk and subsequent passive immunity in infants might help predict infant hospital admissions and thereby enables anticipation to prevent capacity issues. Additionally, it is important in the consideration for strategies for future lockdowns to best prevent possible consequences for vulnerable infants.


Assuntos
COVID-19 , Infecções Respiratórias , Vírus , Anticorpos Antivirais , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Feminino , Humanos , Imunoglobulina G , Lactente , Leite Humano , Pandemias , Vírus Sinciciais Respiratórios , Infecções Respiratórias/epidemiologia
13.
J Hum Lact ; 38(3): 401-406, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35726498

RESUMO

BACKGROUND: SARS-CoV-2-specific antibodies are secreted into human milk after women are vaccinated against COVID-19, which might protect the breastfed infant. Due to several reports of severe side-effects of the Oxford-AstraZeneca ChAdOx1 (AZD1222) vaccine against COVID-19, some lactating women followed a heterologous vaccination schedule consisting of the first dose of AZD1222 and a second dose of an mRNA-based vaccine. However, it is unclear whether this generates a significant SARS-CoV-2-specific antibody response in human milk. MAIN ISSUE: To quantify the SARS-CoV-2-specific antibody response in human milk of two lactating women receiving a heterologous vaccination schedules: AZD1222 and mRNA-based vaccine (Pfizer-BioNTech [BNT162b2] and Moderna [mRNA-1273]). MANAGEMENT: Both participants collected 16 samples of human milk longitudinally. SARS-CoV-2-specific Immunoglobulin A was measured using an enzyme-linked immunosorbent assay. CONCLUSION: Based on our results, it could be suggested that heterologous vaccination with AZD1222 and an mRNA-based vaccine can elicit a significant SARS-CoV-2 specific IgA response in human milk.


Assuntos
COVID-19 , Vacinas Virais , Anticorpos Antivirais , Formação de Anticorpos , Vacina BNT162 , Aleitamento Materno , COVID-19/prevenção & controle , Vacinas contra COVID-19 , ChAdOx1 nCoV-19 , Feminino , Humanos , Lactação , Leite Humano , RNA Mensageiro , SARS-CoV-2 , Vacinas Virais/farmacologia
14.
Viruses ; 14(5)2022 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-35632607

RESUMO

Anelloviruses (AVs) are found in the vast majority of the human population and are most probably part of a healthy virome. These viruses infect humans in the early stage of life, however, the characteristics of the first colonizing AVs are still unknown. We screened a collection of 107 blood samples from children between 0.4 and 64.8 months of age for the presence of three AV genera: the Alpha-, Beta- and Gammatorquevirus. The youngest child that was positive for AV was 1.2 months old, and a peak in prevalence (100% of samples positive) was reached between the twelfth and eighteenth months of life. Intriguingly, the beta- and gammatorqueviruses were detected most at the early stage of life (up to 12 months), whereas alphatorqueviruses, the most common AVs in adults, increased in prevalence in children older than 12 months. To determine whether that order of colonization may be related to oral transmission and unequal presence of AV genera in breast milk, we examined 63 breast milk samples. Thirty-two percent of the breast milk samples were positive in a qPCR detecting beta- and gammatorqueviruses, while alphatorqueviruses were detected in 10% of the samples, and this difference was significant (p = 0.00654). In conclusion, we show that beta- and gammatorqueviruses colonize humans in the first months of life and that breastfeeding could play a role in AV transmission.


Assuntos
Anelloviridae , Adulto , Anelloviridae/genética , Aleitamento Materno , Criança , Feminino , Humanos , Lactente , Leite Humano , Prevalência , Viroma
15.
EClinicalMedicine ; 47: 101393, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35465077

RESUMO

Background: Vaccination of lactating women against COVID-19 may protect not only themselves but also their breastfed infant through human milk. Therefore, it is important to gain insight into the human milk antibody response after immunization with the various vaccines that are currently widely used. The aim of this study is to determine and compare the antibody response in human milk following vaccination with mRNA- and vector-based vaccines up to over two months post-vaccination. Methods: This prospective cohort study was conducted in the Netherlands between January 06, 2021 and July 31, 2021. Participants were recruited through social media. Human milk samples were collected longitudinally during a period of 70 days from women receiving one of the four different severe acute respiratory coronavirus 2 (SARS-CoV-2) vaccines: Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273), Oxford/AstraZeneca (AZD1222) and Johnson&Johnson (Ad26.COV2.S). SARS-CoV-2-specific antibodies were measured using an enzyme-linked immunosorbent assay. The area under the curve (AUC) of the Immunoglobulins A (IgA) and G (IgG) antibody response was determined over 15 and 70 days following the first vaccination and compared between the different vaccines. Findings: This study enrolled 134 vaccinated lactating women of whom 97 participated the entire study period. In total, 1887 human milk samples were provided. The human milk antibody response differed between SARS-CoV-2 vaccines over the study period. The mean AUC of SARS-CoV-2-specific IgA, but not IgG, in human milk over 15 days was higher after vaccination with an mRNA-based vaccine than a vector-based vaccine (AUC with respect to ground [AUCg] ± the standard error of the mean [SEM] for IgA was 6·09 ± 0·89 in the BNT162b2 group, 7·48 ± 1·03 in the mRNA-1273 group, 4·17 ± 0·73 in the AZD1222 group, and 5·71 ± 0·70 in the Ad26.COV2.S group). Over a period of 70 days, the mean AUCg of both IgA and IgG was higher after vaccination with an mRNA-based vaccine than a vector-based vaccine (AUCg ± SEM for IgA was 38·77 ± 6·51 in the BNT162b2 group, 50·13 ± 7·41 in the mRNA-1273 group, 24·12 ± 5·47 in the AZD1222 group, and 28·15 ± 6·69 in the Ad26.COV2.S group; AUCg ± SEM for IgG was 40·43 ± 2·67 in the BNT162b2 group, 37·01 ± 2·38 in the mRNA-1273 group, 16·04 ± 5·09 in the AZD1222 group, and 10·44 ± 2·50 in the Ad26.COV2.S group). Interpretation: Overall, maternal vaccination during lactation with an mRNA-based vaccine resulted in higher SARS-CoV-2 antibody responses in human milk compared to vector-based vaccines. Therefore, vaccination with mRNA-based vaccines, preferably with the mRNA-1273 vaccine, might not only provide better immunological protection for the mother but also for her breastfed infant. Funding: Stichting Steun Emma Kinderziekenhuis and the Amsterdam Infection and Immunity Institute (grant 24175).

17.
Front Mol Biosci ; 9: 858856, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35274008

RESUMO

The Alpha-1-Antitrypsin (A1AT) protein is an important protease inhibitor highly abundant in human serum and other body fluids. Additional to functioning as a protease inhibitor, A1AT is an important acute phase protein. Here, we set out to compare the proteoform profiles of A1AT purified from the human serum and milk of eight healthy donors to determine the origin of human milk A1AT. Following affinity purification, size-exclusion chromatography coupled to native mass spectrometry was used to monitor individual proteoform profiles comparing inter- and intra-donor profiles. The A1AT intra-donor proteoform profiles were found to be highly identical between serum and milk, while they were highly distinct between donors, even when comparing only serum or milk samples. The observed inter-donor proteoform variability was due to differences in the abundances of different N-glycoforms, mainly due to branching, fucosylation, and the relative abundance of N-terminally processed A1AT fragments. From our data we conclude that nearly all A1AT in serum and milk is synthesized by a common source, i.e. the liver, and then secreted into the circulation and enters the mammary gland via diffusion or transport. Thereby, proteoform profile changes, as seen upon infection and/or inflammation in the blood will be reflected in the milk, which may then be transferred to the breastfed infant.

18.
Vaccines (Basel) ; 9(12)2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34960222

RESUMO

SARS-CoV-2-specific antibodies are secreted into human milk of infected or vaccinated lactating women and might provide protection to the breastfed infant against COVID-19. Differences in antibody response after these types of exposure are unknown. In this longitudinal cohort study, we compared the antibody response in human milk following SARS-CoV-2 vaccination or infection. We analyzed 448 human milk samples of 28 lactating women vaccinated with the SARS-CoV-2 vaccine BNT162b2 as well as 82 human milk samples of 18 lactating women with a prior SARS-CoV-2 infection. The levels of SARS-CoV-2-specific IgA in human milk were determined over a period of 70 days both after vaccination and infection. The amount of SARS-CoV-2-specific IgA in human milk was similar after SARS-CoV-2 vaccination and infection. After infection, the variability in IgA levels was higher than after vaccination. Two participants with detectable IgA prior to vaccination were analyzed separately and showed higher IgA levels following vaccination compared to both groups. In conclusion, breastfed infants of mothers who have been vaccinated with the BNT162b2 vaccine receive human milk with similar amounts of SARS-CoV-2-specific antibodies compared to infants of previously infected mothers.

19.
Antioxidants (Basel) ; 10(11)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34829608

RESUMO

High rates of oxidative stress are common in preterm born infants and have short- and long-term consequences. The antioxidant properties of human milk limits the consequences of excessive oxidative damage. However, as the mother's own milk it is not always available, donor milk may be provided as the best alternative. Donor milk needs to be pasteurized before use to ensure safety. Although pasteurization is necessary for safety reasons, it may affect the activity and concentration of several biological factors, including antioxidants. This literature review describes the effect of different pasteurization methods on antioxidant properties of human milk and aims to provide evidence to guide donor milk banks in choosing the best pasteurization method from an antioxidant perspective. The current literature suggests that Holder pasteurization reduces the antioxidant properties of human milk. Alternative pasteurization methods seem promising as less reduction is observed in several studies.

20.
J Hum Lact ; 37(3): 485-491, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34308720

RESUMO

BACKGROUND: Human milk contains antibodies against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) following Coronavirus Disease 2019 (COVID-19). These antibodies may serve as protection against COVID-19 in infants. However, the evolution of these human milk antibodies over time is unclear. RESEARCH AIM: To elucidate the evolution of immunoglobulin A (IgA) against SARS-CoV-2 in human milk after a SARS-CoV-2 infection. METHODS: This longitudinal follow-up study included lactating mothers (N = 24) who had participated in the COVID MILK study. To assess the evolution of SARS-CoV-2 antibodies, serum and human milk samples were collected 14-143 days after the onset of clinical symptoms related to COVID-19. Enzyme-Linked ImmunoSorbent Assay was used to detect antibodies against the ectodomain of the SARS-CoV-2 spike protein. RESULTS: SARS-CoV-2 antibodies remain present up to 5 months (143 days) in human milk after onset of COVID-19 symptoms. Overall, SARS-CoV-2 IgA in human milk seems to gradually decrease over time. CONCLUSION: Human milk from SARS-CoV-2 convalescent lactating mothers contains specific IgA antibodies against SARS-CoV-2 spike protein up to at least 5 months post-infection. Passive viral immunity can be transferred via human milk and may serve as protection for infants against COVID-19.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , Aleitamento Materno , Feminino , Seguimentos , Humanos , Lactente , Lactação , Leite Humano , Glicoproteína da Espícula de Coronavírus
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