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This research study investigates the intricate relationship among COVID-19, maternal and infant health, and breastfeeding practices, with a specific focus on assessing the transfer of nirmatrelvir and ritonavir into human milk. Our aim is to provide critical insights to those managing COVID-19 treatment in lactating individuals. The InfantRisk Center Human Milk Biorepository contained human milk and corresponding health information for eight mother-infant dyads exposed to standard doses of maternal nirmatrelvir with ritonavir (300 mg nirmatrelvir and 100 mg ritonavir taken orally twice daily for 5 days). The primary outcomes measured were drug levels in milk using liquid chromatography-mass spectrometry and reporting the tolerance of the breastfed infant. Nirmatrelvir with ritonavir was measurable in all participants at a mean concentration of 33.48 ng/mL (ritonavir) and 729 ng/mL (nirmatrelvir). The estimated infant dose via milk was 0.0024 mg/kg/12 h (ritonavir) and 0.054 mg/kg/12 h (nirmatrelvir). The estimated relative infant dose was 0.19% (ritonavir) and 1.43% (nirmatrelvir) well under the standard 10% safety threshold. Among the eight infants exposed in this study, there were no reported adverse events. Nirmatrelvir with ritonavir is the recommended treatment for ambulatory COVID-19 patients with mild-to-moderate COVID-19 infection at high risk for progression to severe disease. Although its use is recommended in lactating women, there are no previous studies on the transfer of nirmatrelvir into human milk. The study findings endorse the current approach of nirmatrelvir/ritonavir use in lactating women and encourage healthcare providers to consider prescribing this treatment irrespective of lactation status when indicated., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

Respiratory syncytial virus (RSV) is a major global pathogen, causing lower respiratory tract disease in at-risk populations including young children. Antibodies form a crucial layer of protection from RSV disease, particularly in immunologically naïve infants. Such antibodies are derived from the mother via transplacental transfer and breast milk, but may be particularly low in high-risk infants such as those born preterm. Maternally derived antibodies can now be supplemented by the administration of anti-RSV monoclonal antibodies, while a rising wave of maternal and paediatric vaccine strategies are approaching. The implementation of these prophylactics may profoundly decrease the healthcare burden of RSV. In this article, we review the role of antibody-mediated immunity in protecting children from RSV. We focus on maternally derived antibodies as the main source of protection against RSV and study factors that influence the scale of this transfer. The role of passive and active prophylactic approaches in protecting infants against RSV are discussed and knowledge gaps in our understanding of antibody-mediated protection against RSV are identified., Competing Interests: Conflict of interest: A. Moureau is an employee of Sanofi and owns Sanofi stock as an employee. C. Vernhes was an employee of Sanofi at the time the work was performed, owns Sanofi stock as a former employee and is currently employed by the trade association Vaccines Europe. P.J.M. Openshaw reports consulting fees from GSK, Moderna, Janssen, Seqirus, Pfizer, Sanofi, AstraZeneca, and Icosavax; honoraria for lectures from GSK, Moderna, Seqirus, Sanofi, and AstraZeneca; participation on a Data Safety Monitoring Board for Sanofi; board membership for the Science Media Centre and a role as governor for Sidcot School. R.S. Thwaites reports consulting fees from AOBiome, Gossamer Bio, Indalo Therapeutics, and PrEP Biopharm; and honoraria for lectures from AstraZeneca and GSK. All other authors report no conflicts of interest., (Copyright ©The authors 2024.)

Purpose of Review: Although there are multiple benefits of mother's own milk feeding for very-low birth weight, low gestation infants, those born to cytomegalovirus (CMV)-seropositive mothers are at risk for acquiring postnatal CMV infection. This review will describe the risk and consequences of postnatal CMV infection among very preterm infants., Recent Findings: Postnatal CMV may manifest as clinically silent infection or as mild to severe and occasionally fatal disease. The risk of disease is balanced by the health benefits of human milk feeding to preterm infants. Postnatal CMV infection has been associated with increased risks of multiple preterm morbidities such as bronchopulmonary dysplasia, necrotizing enterocolitis and neurodevelopmental impairment, but current evidence is limited by the selection bias inherent to reporting in case series and retrospective cohort studies., Summary: Knowledge gaps exist regarding the risk-benefit balance of pasteurization to inactivate CMV in fresh breast milk, as well as the optimal dosing, duration and efficacy of treating infected infants with antiviral medications. Multicenter, prospective studies are urgently needed to accurately determine the true burden that postnatal CMV infection presents to very preterm infants. Such studies will inform the need for preventive strategies and treatment guidance., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Children born to women with HIV but who do not become HIV infected experience increased morbidity and mortality compared with children born to women without HIV. The basis of this increased vulnerability is unknown. The microbiome, specifically the infant gut microbiome, likely plays an important role in infant immune development. The human milk microbiome is thought to have an important role in the development of the infant gut and therefore, if perturbed, may contribute to this increased vulnerability. We investigated the effects of HIV and its therapies on the milk microbiome and possible changes in the milk microbiome before or after infant HIV infection., Results: Seven-hundred fifty-six human milk samples were selected from three separate studies conducted over a 15-year period to investigate the role of HIV and its therapies on the human milk microbiome. Our data reveal that the milk microbiome is modulated by parity (R 2  = 0.006, p = 0.041), region/country (R 2  = 0.014, p = 0.007), and duration of lactation (R 2  = 0.027-0.038, all p < 0.001). There is no evidence, however, using 16S rRNA V4 amplicon sequencing, that the human milk microbiome is altered by HIV infection (R 2  = 0.003, p = 0.896), by combination antiretroviral therapy (R 2  = 0.0009, p = 0.909), by advanced maternal disease (R 2  = 0.003, p = 0.263), or in cases of infant infection either through isolated early mucosal (R 2  = 0.003, p = 0.197) or early mucosal and breast milk transmission (R 2  = 0.002, p = 0.587)., Conclusions: The milk microbiome varies by stage of lactation, by parity, and by region; however, we found no evidence that the human milk microbiome is altered by maternal HIV infection, disease severity, or antiretroviral therapy. Additionally, we found no association between the milk microbiome and transmission of HIV to the infant. Investigations including higher resolution microbiome approaches or into other potential mechanisms to understand why the approximately one million children born annually to women with HIV escape infection, but do not escape harm, are urgently needed. Video Abstract., (© 2024. The Author(s).)

At the beginning of the pandemic, SARS-CoV-2 infection represented a great medical burden worldwide, as targeted and effective therapeutic options were lacking. This resulted in the revival of existing molecules and the increasing popularity of over-the-counter nutritional supplements. Among the latter, lactoferrin has been investigated as an adjuvant in COVID-19 therapy with conflicting results, mainly depending on different study designs. Considering that lactoferrin is one of the main components of human breast milk with anti-microbial and anti-inflammatory activity, it is conceivable that such bioactive molecule could be effective in supporting anti-SARS-CoV-2 infection therapy, especially in infants and pregnant women, two subpopulations that have been poorly evaluated in the existing clinical trials. This narrative review is intended to offer insight into the existing literature on lactoferrin's biological functions and protective effects against COVID-19, with a special focus on pregnant women and their infants.

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus found in human breast milk that is frequently transmitted from HCMV-seropositive mothers to their infants during the postnatal period. Despite extensive research, the mechanisms underlying HCMV transmission from breast milk and the anatomical location at which virus transfer takes place remain unclear. Breast milk contains many uniquely differentiated macrophages that undergo specific morphological and functional modifications in the mammary gland during lactation. Although the existence of permissive HCMV infection in differentiated macrophages has been well-described, the role of breast milk in this process remains unknown. Herein, we report that exposure of isolated peripheral blood monocytes to breast milk induces their differentiation into macrophages that exhibit an M2 phenotype (CD14 high CD163 high CD68 high CD206 high ) and promotes a productive and sustained HCMV infection. We also found that breast milk triggers macrophage proliferation and thus sustains a unique population of proliferating, long-lived, and HCMV-susceptible macrophages that are capable of ongoing production of infectious virions. These results suggest a mechanism that explains chronic HCMV shedding into the breast milk of postpartum seropositive mothers. We also found that HCMV virions released from breast milk-induced macrophages generate a productive infection in primary infant tonsil epithelial cells. Collectively, our results suggest that breast milk may facilitate HCMV transmission from mother to infant via the oropharyngeal mucosa., Importance: While human cytomegalovirus (HCMV) is frequently detected in the breast milk of HCMV-seropositive women and is often transmitted to infants via breastfeeding, the mechanisms by which this transmission occurs remain unclear. In this study, we modeled HCMV transmission at the oropharyngeal mucosa. We treated human monocytes with breast milk to mimic the lactating mammary gland microenvironment. We found that monocytes differentiated into macrophages with an M2 phenotype, which were highly permissive for HCMV. We also discovered that breast milk induces macrophage proliferation. Thus, exposure to breast milk increased the number of HCMV-susceptible macrophages and supported high levels of infectious HCMV. We found that HCMV virions released from breast milk-induced macrophages could infect primary infant tonsil epithelial cells. Collectively, these findings reveal the dual role of breast milk that induces the differentiation and proliferation of macrophages in the mammary gland and thus facilitates mother-to-child HCMV transmission at the oropharyngeal mucosa., Competing Interests: The authors declare no conflict of interest.

Breastfeeding provides infection protection for several pathogens but not for noroviruses. Mechanisms explaining this discrepancy have been unclear. In this issue of Cell Host & Microbe, Peiper et al. demonstrate that while breastmilk protects mice from intestinal damage, it promotes neonatal murine norovirus infection due to maternal-derived bile acids. 1 ., Competing Interests: Declaration of interests J.K.P. is on the advisory board of Cell Host & Microbe., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The pathogenic outcome of enteric virus infections is governed by a complex interplay between the virus, intestinal microbiota, and host immune factors, with metabolites serving as a key mediator. Noroviruses bind bile acid metabolites, which are produced by the host and then modified by commensal bacteria. Paradoxically, bile acids can have both proviral and antiviral roles during norovirus infections. Working in an infant mouse model of norovirus infection, we demonstrate that microbiota and their bile acid metabolites protect from norovirus diarrhea, whereas host bile acids promote disease. We also find that maternal bile acid metabolism determines the susceptibility of newborn mice to norovirus diarrhea during breastfeeding. Finally, targeting maternal and neonatal bile acid metabolism can protect newborn mice from norovirus disease. In summary, neonatal metabolic immaturity and breastmilk bile acids are central determinants of heightened newborn vulnerability to norovirus disease., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To compare the presence of neutralizing antibodies against SARS-CoV-2 found in the breast milk and blood of vaccinated lactating women with those not vaccinated., Data Source: The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under CRD42021287554 and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Cohort, case-control, and cross-sectional studies that evaluated antibodies against SARS-CoV-2 in the milk and blood of vaccinated mothers and had as control group unvaccinated mothers were eligible. Health Sciences Descriptors (DeCs), Medical Subject Headings (MeSH) and Emtree descriptors were used for the Virtual Health Library (VHL), Medical Literature Analysis and Retrieval System Online (Medline/Pubmed), and Embase databases, respectively. In the Web of Science and Scopus, the strategy was adapted. No restrictions on the publication period and language were set., Data Synthesis: The search identified 233 records, of which 128 duplicates and 101 papers that did not meet the inclusion criteria were excluded. Hence, four cohort studies were eligible. Nursing mothers vaccinated with the Pfizer-BioNTech and Moderna vaccines showed antibodies against SARS-CoV-2 in their blood and breast milk., Conclusions: Vaccinated lactating women had higher levels of immunoglobulin G (IgG) and A (IgA) in serum and breast milk than unvaccinated women.

Combined antiretroviral therapy has significantly reduced perinatal human immunodeficiency virus (HIV) transmission risk through breastfeeding, prompting shifts in clinical guidance to support breastfeeding for women with HIV who have sustained viral suppression. This review examines the current evidence on HIV transmission via breast milk, including risk factors, mechanisms, and risk reduction strategies to inform patient-centered and evidence-driven clinical care., Competing Interests: Disclosure All authors declare no financial conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Human cytomegalovirus (CMV) is a highly prevalent herpesvirus that is often transmitted to the neonate via breast milk. Postnatal CMV transmission can have negative health consequences for preterm and immunocompromised infants, but any effects on healthy term infants are thought to be benign. Furthermore, the impact of CMV on the composition of the hundreds of bioactive factors in human milk has not been tested. Here, we utilize a cohort of exclusively breastfeeding full-term mother-infant pairs to test for differences in the milk transcriptome and metabolome associated with CMV, and the impact of CMV in breast milk on the infant gut microbiome and infant growth. We find upregulation of the indoleamine 2,3-dioxygenase (IDO) tryptophan-to-kynurenine metabolic pathway in CMV+ milk samples, and that CMV+ milk is associated with decreased Bifidobacterium in the infant gut. Our data indicate two opposing CMV-associated effects on infant growth; with kynurenine positively correlated, and CMV viral load negatively correlated, with infant weight-for-length at 1 month of age. These results suggest CMV transmission, CMV-related changes in milk composition, or both may be modulators of full-term infant development., (© 2024. The Author(s).)

Introduction: Human cytomegalovirus (HCMV) is the most common viral infection seen in newborns. The major route of transmission for acquired human cytomegalovirus infection is breast milk from mothers who are HCMV seropositive to the infants. Thus, a rapid, economical, and simple method to perform HCMV test in breast milk is crucial and necessary for preventing acquired HCMV infection, especially in underdeveloped regions with limited laboratory resources., Methods: In this study, an effective technique for the detection of HCMV was constructed by combining multienzyme isothermal rapid amplification (MIRA) and lateral flow chromatography strip (LFD). Primers for the conserved HCMV sequence UL83 were utilized for MIRA-LFD testing., Results: Our results showed that the entire MIRA reaction could be completed in 12 minutes at 37°C, and LFD outcomes could be observed visibly after 10 minutes. The detection sensitivity of this method reached 50 copy/μl. Samples of breast milk were examined to compare MIRA-LFD and conventional qPCR. The accuracy of MIRA-LFD was 100%., Discussion: The straightforward, rapid, economic features of the test can provide the significant advantages for the prevention of breast milk-acquired cytomegalovirus infection, particularly in resource-limited locations with high seroprevalence of cytomegalovirus., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Guo, Sun, Li, Liu, Chen, Wang, Wang, Li, Yao, Li and Pan.)

Given that HIV can be transmitted through breastfeeding, historically, breastfeeding among women with HIV in the US and other resource-rich settings was discouraged. Formula feeding was the mandated feeding option out of concern for breast-milk transmission of HIV, which occurred in 16-24% of cases pre-antiretroviral therapy (pre-ART) use. In January 2023, the US Department of Health and Human Services' Perinatal Guidelines were revised to support shared decision-making for infant feeding choices. Updated clinical trials' data from resource-limited settings suggest the actual breastmilk HIV transmission rate in the context of maternal ART or neonatal postexposure prophylaxis is 0.3-1%. High-income countries are reporting more people with HIV breastfeeding their infants without cases of HIV transmission. We present the reasons for fully embracing breast-/chestfeeding as a viable, safe infant feeding option for HIV-exposed infants in high-income settings, while acknowledging unanswered questions and the need to continually craft more nuanced clinical guidance., Competing Interests: Potential conflicts of interest. A. A. has served as a member of a scientific advisory board (Gilead, Merck, ViiV), as site investigator under a clinical research contract managed through Johns Hopkins (Gilead, Merck), and as Principal Investigator of an investigator-initiated study with funds to the university (Gilead). A. A. also reports grant funds to their institution from the National Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute on Minority Health and Health Disparities (NIMHD), National Institute of Mental Health (NIMH), and the Health Resources and Services Administration (HRSA); payment for expert testimony to the author for medicolegal work; and roles as Board chair of the HIV Medicine Association and Advocates for youth. A. A. is a member of the Department of Health and Human Services (DHHS) Adolescent and Adult Antiretroviral Treatment Guidelines Panel. A. P. is a member of the US DHHS Perinatal HIV Guidelines. A. P. reports grants or contracts from NIH-K23; royalties or licenses from UptoDate as coauthor for the cervicitis chapter; and payment or honoraria from Cepheid (funds to the author for a presentation at the Infectious Diseases Society for Obstetrics and Gynecology 2023 meeting). Both authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

To breast feed or not has long been a difficult question for women with human immunodeficiency virus (HIV) in high-income countries, as undetectable HIV in maternal plasma does not translate to zero risk of transmission while breastfeeding, and clean water and formula are readily available. Recent, and more permissive, changes in US and other high-income-country guidelines regarding breastfeeding underscore this issue and acknowledge the information gaps that are essential for informed maternal choice and provider management. These include lack of guidance as to routine monitoring of mothers during lactation, type and length of prophylaxis for infants, and lack of data on factors associated with increased breast-milk viral load and risk of transmission. Ancillary to data are the education and staffing needs for providers participating in the management of breastfeeding individuals. Future studies of breast-milk transmission will need to evaluate these gaps so that we can move transmission to zero., Competing Interests: Potential conflicts of interest. S.N. reports support as International Maternal Pediatrics Adolescent AIDS Clinical Trial (IMPAACT) Network PI; National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Mental Health (NIMH), and Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). G.A. reports grants or contracts as IMPAACT Network LC PI ; NIAID, NIMH, and NICHD for MSM and Substances Cohort at UCLA Linking Infections Noting Effects, Scientific Advisor & Repository Director NIDA; ACTG LC Network PI; NIAID, NIMH, and NICHD for UCLA-CDU CFAR Core Director NIAID; Trial of Human Oligosaccharide-based Synbiotics for HIV Exposed Uninfected NICHD Investigator for ATN Scientific Leadership Group, NICHD; Effects of Human Milk Oligosaccharides and Gut Microbiome on Growth and Morbidity in HIV-Exposed Uninfected Infants MPI NICHD for The Impact of COVID-19 Pandemic on Severe Mental Illness Investigator, Investigator, NIMH. Both authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study highlights the importance of human milk in providing anti-severe acute respiratory syndrome coronavirus 2 immunity to newborns. The highest protective activity of human milk against COVID-19 was found in colostrum from infected mothers. Neutralizing activity was associated with high levels of specific IgA. Depletion of IgA, but not IgG, from milk samples completely abolished the ability of human milk to neutralize severe acute respiratory syndrome coronavirus 2., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Limited data are available regarding the balance of risks and benefits from human milk and/or breastfeeding during and following maternal infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., Objective: To investigate whether SARS-CoV-2 can be detected in milk and on the breast after maternal coronavirus disease 2019 (COVID-19) diagnosis; and characterize concentrations of milk immunoglobulin (Ig) A specific to the SARS-CoV-2 spike glycoprotein receptor binding domain (RBD) during the 2 months after onset of symptoms or positive diagnostic test., Methods: Using a longitudinal study design, we collected milk and breast skin swabs one to seven times from 64 lactating women with COVID-19 over a 2-month period, beginning as early as the week of diagnosis. Milk and breast swabs were analyzed for SARS-CoV-2 RNA, and milk was tested for anti-RBD IgA., Results: SARS-CoV-2 was not detected in any milk sample or on 71% of breast swabs. Twenty-seven out of 29 (93%) breast swabs collected after breast washing tested negative for SARS-CoV-2. Detection of SARS-CoV-2 on the breast was associated with maternal coughing and other household COVID-19. Most (75%; 95% CI, 70-79%; n=316) milk samples contained anti-RBD IgA, and concentrations increased ( P =.02) during the first two weeks following onset of COVID-19 symptoms or positive test. Milk-borne anti-RBD IgA persisted for at least two months in 77% of women., Conclusion: Milk produced by women with COVID-19 does not contain SARS-CoV-2 and is likely a lasting source of passive immunity via anti-RBD IgA. These results support recommendations encouraging lactating women to continue breastfeeding during and after COVID-19 illness., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pace, Williams, Järvinen, Meehan, Martin, Ley, Barbosa-Leiker, Andres, Yeruva, Belfort, Caffé, Navarrete, Lackey, Pace, Gogel, Fehrenkamp, Klein, Young, Rosen-Carole, Diaz, Gaw, Flaherman, McGuire, McGuire and Seppo.)

Despite the significant progress that has been made to eliminate vertical HIV infection, more than 150,000 children were infected with HIV in 2019, emphasizing the continued need for sustainable HIV treatment strategies and ideally a cure for children. Mother-to-child-transmission (MTCT) remains the most important route of pediatric HIV acquisition and, in absence of prevention measures, transmission rates range from 15% to 45% via three distinct routes: in utero , intrapartum, and in the postnatal period through breastfeeding. The exact mechanisms and biological basis of these different routes of transmission are not yet fully understood. Some infants escape infection despite significant virus exposure, while others do not, suggesting possible maternal or fetal immune protective factors including the presence of HIV-specific antibodies. Here we summarize the unique aspects of HIV MTCT including the immunopathogenesis of the different routes of transmission, and how transmission in the antenatal or postnatal periods may affect early life immune responses and HIV persistence. A more refined understanding of the complex interaction between viral, maternal, and fetal/infant factors may enhance the pursuit of strategies to achieve an HIV cure for pediatric populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Amin, Powers, Bricker and Chahroudi.)

Competing Interests: Competing interests: All authors have read and understood BMJ policy on declaration of interests and have no interests to declare. The article was funded by the South African Medical Research Council. The content is the sole responsibility of the authors and does not necessarily represent the official views of the organisations and funders.

Cytomegalovirus (CMV) infections acquired by very-low-birthweight (VLBW) infants are incompletely characterized. To examine CMV transmission in VLBW infants, we evaluated maternal DNAlactia, infant DNAemia, and presence of clinical disease in a blinded study in VLBW infants in our newborn intensive care unit (NICU). To examine these issues, 200 VLBW infants were enrolled in a surveillance study, with weekly breast milk and infant whole blood samples collected, as available. Virologic (breast milk and infant whole blood real time PCR) and immunologic (IgG, IgM, and IgG avidity) correlates were evaluated. A chart review examined whether infants had symptoms compatible with CMV disease. DNAlactia was identified in 65/150 (43%) of lactating mothers. Nine CMV infections were identified in 9/75 CMV-exposed infants (12% of exposed infants). A higher median breast milk viral load (DNAlactia) correlated with an increased likelihood of DNAemia ( p = 0.05). Despite potential symptoms compatible with CMV infection, clinicians had not considered the diagnosis of CMV in 6/9 cases (66%). All of these infants had chronic lung disease at discharge. There was no correlation between IgG antibody titer or IgG avidity index and the likelihood of transmission or CMV disease. In conclusion, in VLBW infants receiving milk from seropositive mothers, CMV infections are commonly acquired, and are frequently unrecognized. Future studies are needed to determine whether routine surveillance for CMV of either breast milk or infant plasma is beneficial in preventing or recognizing infection.

Objective: To systematically review and meta-analyse the rate of SARS-CoV-2 genome identification and the presence of SARS-CoV-2 antibodies in breastmilk of mothers with COVID-19., Design: A systematic review of studies published between January 2019 and October 2020 without study design or language restrictions., Setting: Data sourced from Ovid Embase Classic+Embase, PubMed, Web of Science, Scopus, relevant bibliographies and the John Hopkins University COVID-19 database., Patients: Mothers with confirmed COVID-19 and breastmilk tested for SARS-CoV-2 by RT-PCR or for anti-SARS-CoV-2 antibodies., Main Outcome Measures: Presence of SARS-CoV-2 genome and antibodies in breastmilk., Results: We included 50 articles. Twelve out of 183 women from 48 studies were positive for SARS-CoV-2 genome in their breastmilk (pooled proportion 5% (95% CI 2% to 15%; I 2 =48%)). Six infants (50%) of these 12 mothers tested positive for SARS-CoV-2, with one requiring respiratory support. Sixty-one out of 89 women from 10 studies had anti-SARS-CoV-2 antibody in their breastmilk (pooled proportion 83% (95% CI 32% to 98%; I 2 =88%)). The predominant antibody detected was IgA., Conclusions: SARS-CoV-2 genome presence in breastmilk is uncommon and is associated with mild symptoms in infants. Anti-SARS-CoV-2 antibodies may be a more common finding. Considering the low proportion of SARS-CoV-2 genome detected in breastmilk and its lower virulence, mothers with COVID-19 should be supported to breastfeed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: There are limited published data on the transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from mothers to newborns through breastfeeding or from breast milk. The World Health Organization released guidelines encouraging mothers with suspected or confirmed COVID-19 to breastfeed as the benefits of breastfeeding outweighs the possible risk of transmission. The objective of this study was to determine if SARS-CoV-2 was present in the breast milk of lactating mothers who had a positive SARS-CoV-2 nasopharyngeal swab test prior to delivery, and the clinical outcomes for their newborns., Study Design: This was a single-center, observational, prospective cohort study. Maternal-newborn dyads that delivered at New York University Langone Hospital Brooklyn with confirmed maternal SARS-CoV-2 positive screen test at the time of admission were recruited for the study. Breast milk samples were collected during postpartum hospitalization and tested for the presence of SARS-CoV-2 genes N1 and N2 by two-step reverse transcription polymerase chain reaction. Additionally, the clinical characteristics of the maternal newborn dyad, results of nasopharyngeal SARS-CoV-2 testing, and neonatal follow-up data were collected., Results: A total of 19 mothers were included in the study and their infants who were all fed breast milk. Breast milk samples from 18 mothers tested negative for SARS-CoV-2, and 1 was positive for SARS-CoV-2 RNA. The infant who ingested the breast milk that tested positive had a negative nasopharyngeal test for SARS-CoV-2, and had a benign clinical course. There was no evidence of significant clinical infection during the hospital stay or from outpatient neonatal follow-up data for all the infants included in this study., Conclusion: In a small cohort of SARS-CoV-2 positive lactating mothers giving birth at our institution, most of their breast milk samples (95%) contained no detectable virus, and there was no evidence of COVID-19 infection in their breast milk-fed neonates., Key Points: · Breast milk may rarely contain detectable SARS-CoV-2 RNA and was not detected in asymptomatic mothers.. · Breast milk with detectable SARS-CoV-2 RNA from a symptomatic mother had no clinical significance for her infant.. · Breast feeding with appropriate infection control instructions appears to be safe in mother with COVID infection.., Competing Interests: None declared., (Thieme. All rights reserved.)

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus that was declared a Public Health Emergency of International Concern by the World Health Organization (WHO). One major problem faced is whether breastfeeding by mothers infected with the virus is safe. The objective of this work is to study the impact that the SARS-CoV-2 virus can have on breastfeeding, and whether the virus or antibodies can be transmitted from mother to child through milk. We carried out a systematic review of studies focusing on the impact of SARS-CoV-2 on breastfeeding by mothers infected with the virus. The bibliographic search was done through Medline (Pubmed), MedlinePlus and Google Scholar. From 292 records, the title and summary of each were examined according to the criteria, and whether they meet the selection criteria was also analysed. A total of 30 articles are included, of which 26 deal with the study of RNA virus in breastmilk and its involvement in breastfeeding and four on the study of SARS-CoV-2 antibodies in milk. Most studies have been conducted in China. Breastfeeding by mothers infected with SARS-CoV-2 is highly recommended for infants, if the health of the mother and the infant allow for it. Direct breastfeeding and maintaining appropriate protective measures should be encouraged. Should the mother's health condition not permit direct breastfeeding, infants should be fed with pumped breastmilk or donor milk.

Objective: Very low birth weight preterm infants are at risk for life-threatening infections in the NICU. Breast milk protects against infections but carries the risk of infection by cytomegalovirus (CMV) shed in mother's milk. Lactoferrin is a breast milk and saliva protein with potent neutralizing activity against CMV., Study Design: VLBW, maternal breast milk fed infants in the NICU and their lactating mothers were enrolled and followed for 3 months/discharge. Breast milk and infant saliva samples were collected biweekly. Maternal CMV status was determined on breast milk. CMV was measured using quantitative polymerase chain reaction and lactoferrin by enzyme-linked immunosorbent assay., Results: In an in vitro neutralization assay, the IC 90 of purified human lactoferrin against CMV was 2.08 ng/mL. Bovine lactoferrins were more potent, IC 90 s > 10-fold higher. Lactoferrin was detected in all breast milk (median: 3.3 × 10 6  ng/mL) and saliva (median: 84.4 ng/swab) samples. Median CMV load in breast milk was 893 copies/mL. There was no correlation between breast milk lactoferrin concentration and CMV load. Five infants acquired postnatal CMV. There was no difference in saliva or breast milk lactoferrin concentration for mother-infant pairs and postnatal CMV acquisition., Conclusion: Lactoferrin neutralizes CMV in vitro, but concentrations in breast milk and saliva are likely too low for effective neutralization in vivo., Competing Interests: S.R.P is a consultant for Merck, Pfizer, Moderna, and Sanofi vaccine programs and has a sponsored program with Moderna. No other disclosures were reported., (Thieme. All rights reserved.)

Most viruses use several entry sites and modes of transmission to infect their host (parenteral, sexual, respiratory, oro-fecal, transplacental, transcutaneous, etc.). Some of them are known to be essentially transmitted via arthropod bites (mosquitoes, ticks, phlebotomes, sandflies, etc.), and are thus named arthropod-borne viruses, or arboviruses. During the last decades, several arboviruses have emerged or re-emerged in different countries in the form of notable outbreaks, resulting in a growing interest from scientific and medical communities as well as an increase in epidemiological studies. These studies have highlighted the existence of other modes of transmission. Among them, mother-to-child transmission (MTCT) during breastfeeding was highlighted for the vaccine strain of yellow fever virus (YFV) and Zika virus (ZIKV), and suggested for other arboviruses such as Chikungunya virus (CHIKV), dengue virus (DENV), and West Nile virus (WNV). In this review, we summarize all epidemiological and clinical clues that suggest the existence of breastfeeding as a neglected route for MTCT of arboviruses and we decipher some of the mechanisms that chronologically occur during MTCT via breastfeeding by focusing on ZIKV transmission process.

Background: Since last year, COVID-19, the disease caused by the novel Sars-Cov-2 virus, has been globally spread to all the world. COVID-19 infection among pregnant women has been described. However, transplacental transmission of Sars-Cov-2 virus from infected mother to the newborn is not yet established. The appropriate management of infants born to mothers with confirmed or suspected COVID-19 and the start of early breastfeeding are being debated., Case Presentation: We report a case of the joint management of a healthy neonate with his mother tested positive for Covid-19 before the delivery and throughout neonatal follow-up. The infection transmission from the mother to her baby is not described, even after a long period of contact between them and breastfeeding., Conclusion: It may consider an appropriate practice to keep mother and her newborn infant together in order to facilitate their contact and to encourage breastfeeding, although integration with infection prevention measures is needed.

The human milk (HM) microbiota is a significant source of microbes that colonize the infant gut early in life. The aim of this study was to compare transient and mature HM virome compositions, and also possible changes related to the mode of delivery, gestational age, and weight for gestational age. Overall, in the 81 samples analyzed in this study, reads matching bacteriophages accounted for 79.5% (mainly Podoviridae, Myoviridae, and Siphoviridae ) of the reads, far more abundant than those classified as eukaryotic viruses (20.5%, mainly Herpesviridae ). In the whole study group of transient human milk, the most abundant families were Podoviridae and Myoviridae . In mature human milk, Podoviridae decreased, and Siphoviridae became the most abundant family. Bacteriophages were predominant in transient HM samples (98.4% in the normal spontaneous vaginal delivery group, 92.1% in the premature group, 89.9% in the C-section group, and 68.3% in the large for gestational age group), except in the small for gestational age group (only ~45% bacteriophages in transient HM samples). Bacteriophages were also predominant in mature HM; however, they were lower in mature HM than in transient HM (71.7% in the normal spontaneous vaginal delivery group, 60.8% in the C-section group, 56% in the premature group, and 80.6% in the large for gestational age group). Bacteriophages still represented 45% of mature HM in the small for gestational age group. In the transient HM of the normal spontaneous vaginal delivery group, the most abundant family was Podoviridae ; however, in mature HM, Podoviridae became less prominent than Siphoviridae . Myoviridae was predominant in both transient and mature HM in the premature group (all C-section), and Podoviridae was predominant in transient HM, while Siphoviridae and Herpesviridae were predominant in mature HM. In the small for gestational age group, the most abundant taxa in transient HM were the family Herpesviridae and a species of the genus Roseolovirus . Bacteriophages constituted the major component of the HM virome, and we showed changes regarding the lactation period, preterm birth, delivery mode, and birth weight. Early in life, the HM virome may influence the composition of an infant's gut microbiome, which could have short- and long-term health implications. Further longitudinal mother-newborn pair studies are required to understand the effects of these variations on the composition of the HM and the infant gut virome.

Introduction: In addition to hand washing and wearing masks, social distancing and reducing exposure time to <15 minutes are the most effective measures against the spread of COVID-19. Unfortunately, three of these guidelines are very difficult, if not impossible, for nursing babies: they cannot wear masks, stay six feet away from the lactating breasts, nor consistently finish within 15 minutes while nursing. We report a case of a nursing mother with SARS-CoV-2 infection, documenting changes of immune cells and cytokines in breast milk with and without the infection. Case Description: With Institutional Review Board (IRB) approval, we obtained expressed breast milk samples from a lactating mother before and during SARS-CoV-2 infection as documented by reverse transcription-PCR. Using flow cytometry analysis, we measured the immune cell profiles and expression of cytokines such as interferon alpha (IFNα) in milk leukocytes before and during infection. Results: There was an eightfold increase in IFNα+ milk leukocytes, from 1% before SARS-CoV-2 infection to 8% when actively infected. The milk macrophages showed the highest increase in IFNα expression. Both T and B lymphocytes showed mild increase. Innate lymphoid cells, neutrophils, and natural killer cells showed no increase in IFNα expression and the dendritic cells actually showed a reduction. Conclusion: We document the presence and high expression of IFNα in the breast milk macrophages of a lactating mother with confirmed COVID-19, compared with her milk before the infection.

Introduction: During the Coronavirus Disease 2019 global pandemic, maternal and newborn wellbeing has received much attention. Detailed reports of infected women breastfeeding their infants are uncommon. Due to incomplete information available, full data about those infants' outcomes are lacking, and evidence of infectivity through breastfeeding has not been documented., Main Issue: Here, we report about a mother who breastfed her infant until she was confirmed with the SARS-Cov-2 infection. After follow-up, we have confirmed that the infant, who was breastfed by the infected mother, was not infected., Methods: A 33-year-old woman gave birth to a full-term male infant on November 8, 2019. Since birth, she had been exclusively breastfeeding the baby until she was confirmed with the SARS-Cov-2 infection on February 8, 2020. She was hospitalized, isolated from her baby, and stopped breastfeeding. Even though she remained asymptomatic, her milk was expressed using a breast pump and discarded. The mother's milk sample was collected on February 9, 2020, and the result of the nucleic acid test for COVID-19 was negative. Her infant was asymptomatic and remained virus negative. Her laboratory findings and chest Computed Tomography imaging was normal. She was treated according to the national protocol with aerosolized interferon α2β, lopinavir/ritonavir and ribavirin. Her serum SARS-CoV-2 specific antibodies(IgG and IgM) tested positive when discharged. She returned to breastfeeding after discharge., Conclusion: Our findings suggest that breastfeeding may be less of a risk than anticipated. Additional research is needed to explore this possibility.

Although the COVID‑19 epidemic has lasted for months, it has not yet been successfully controlled, and little is known about neonatal COVID‑19. Therefore, literature search was conducted for references in PubMed, Science Direct, ProQuest, Web of Science and China National Knowledge Infrastructure for detailed case reports on neonatal COVID‑19 published as of July 15, 2020, to facilitate the clinical treatment, epidemic prevention and control of neonatal COVID‑19. Forty nonoverlapping case reports focusing mainly on the demographic characteristics, transmission modes, clinical features, treatments and prognosis of neonatal COVID‑19, including 3 in Chinese and 37 in English, were available.

The main route of mother-to-child transmission (MTCT) of human T cell leukemia virus type 1 is vertical transmission via breastfeeding. Although the most reliable method for preventing MCTC is exclusive formula feeding (ExFF), short-term breastfeeding (STBF) or frozen-thawed breast milk feeding (FTBMF) has been offered as an alternative method if breastfeeding is strongly desired. The aim of this review was to clarify the pooled risk ratio of MCTC of STBF and FTBMF compared with ExFF. This study was registered with PROSPERO (number 42018087317). A literature search of PubMed, CINAHL, the Cochrane Database, EMBASE, and Japanese databases through September 2018 identified 1979 articles, 10 of which met the inclusion criteria. Finally, 11 articles, including these 10 studies and the report of a recent Japanese national cohort study, were included in the meta-analysis. The pooled relative risks of STBF ≤3 months, STBF ≤6 months, and FTBMF compared with ExFF were 0.72 (95% confidence interval (CI): 0.30-1.77; p = 0.48), 2.91 (95% CI: 1.69-5.03; p = 0.0001), and 1.14 (95% CI: 0.20-6.50; p = 0.88), respectively. This meta-analysis showed no statistical difference in the risk of MTCT between STBF ≤3 months and ExFF, but the risk of MTCT significantly increased in STBF ≤6 months.

Defining immune responses that protect humans against diverse HIV strains has been elusive. Studying correlates of protection from mother-to-child transmission provides a benchmark for HIV vaccine protection because passively transferred HIV antibodies are present during infant exposure to HIV through breast milk. A previous study by our group illustrated that passively acquired antibody-dependent cellular cytotoxicity (ADCC) activity is associated with improved infant survival whereas neutralization is not. Here, we show, in another cohort and with two effector measures, that passively acquired ADCC antibodies correlate with infant survival. In combined analyses of data from both cohorts, there are highly statistically significant associations between higher infant survival and passively acquired ADCC levels (p = 0.029) as well as dimeric FcγRIIa (p = 0.002) or dimeric FcγRIIIa binding (p < 0.001). These results suggest that natural killer (NK) cell- and monocyte antibody-mediated effector functions may contribute to the observed survival benefit and support a role of pre-existing ADCC-mediating antibodies in clinical outcome., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

The rate of mother-to-child transmission (MTCT) of HIV from breastfeeding is increasing relative to other causes of MTCT. Early effective preconception and antenatal antiretroviral therapy (ART) reduces intrauterine and intrapartum MTCT, whereas maternal post-partum HIV acquisition, untreated maternal HIV, and suboptimal postnatal maternal ART adherence increase the risk of MTCT through breastfeeding. Although the absolute number of cases of MTCT acquired through breastfeeding is decreasing, the rate of decrease is less than the decrease in intrauterine and intrapartum MTCT. Unless current strategies are universally applied, they might not be sufficient to eliminate MTCT due to breastfeeding. Urgent action is needed to evaluate and implement additional preventive biomedical strategies in high HIV prevalence and incidence settings to eliminate MTCT from breastfeeding. Preventive strategies include: pre-exposure prophylaxis in breastfeeding women who have an increased risk of acquiring HIV; postnatal reinforcement strategies, such as maternal retesting for HIV, maternal care reinforcement, and prophylaxis in infants exposed to HIV via breastmilk; and active (vaccine) or passive immunoprophylaxis with long-acting broadly neutralising antibodies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: We performed a systematic review and meta-analysis to evaluate the incidence of breast milk-acquired cytomegalovirus (CMV) infection in preterm infants born to CMV-seropositive mothers., Methods: PubMed, Embase, and Cochrane Library databases were searched using the terms: ("breast feeding" or "breast milk" or "human milk" or "breast") and ("HCMV" or "cytomegalovirus") and ("infant, extremely premature" or "premature birth" or "newborn" or "neonate" or "low birth weight" or "very low birth weight" or "premature" or "preterm infant"). Studies that had information on CMV status and breast feeding were included in the meta-analysis., Results: A total of 2,502 newborns from 19 studies were included in this meta-analysis. The rate of postnatally acquired CMV infection among breastfed infants with CMV-seropositive mothers was 16.5% (95% confidence interval [CI], 0.10-0.26; P < 0.001). The infection rate was 26% with fresh breast milk, 8% with a combined diet of fresh and freeze-thawed breast milk, and 11% with freeze-thawed breast milk. Among cases where the CMV status of breast milk was determined, CMV shedding into breast milk occurred in 80.5% (95% CI, 0.71-0.87; P < 0.001) of CMV seropositive mothers. The breast milk-acquired CMV infection rate among infants fed CMV-positive breast milk was 20.7% (95% CI, 0.14-0.30; P < 0.001)., Conclusion: This meta-analysis examined the rate of breast milk-acquired CMV infections in preterm infants with CMV-seropositive mothers; the CMV infection rate was higher in preterm infants fed fresh breast milk. Until further data are available, we cautiously suggest the use of freeze-thawed breast milk, rather than fresh breast milk, for preterm infants or very low birth weight infants., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

COVID-19 pandemic since the end of 2019 spreads worldwide, counting millions of victims. The viral invasion, systemic inflammation, and consequent organ failure are the gravest features of coronavirus disease 2019 (COVID-19), and they are associated with a high mortality rate. The aim of this study is to evaluate the role of breast milk in the COVID-19 pandemic, analyzing its antiviral, anti-inflammatory, and immunoregulatory effects due to its bioactive components, so numerous and important for the protection of infants. The study tried to demonstrate that all the components of human milk are capable of performing functions on all the pathogenic events recognized and described in COVID-19 disease. Those human milk factors are well-tolerated and practically free of side effects, so breast milk should become a research topic to discover therapies even in this epidemic. In the first part, the mechanisms of protection and defense of the breast milk elements will be delineated; in the second section, it will describe the human milk effects in viral infections and it will be hypothesized how the known mechanisms could act in COVID infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Quitadamo, Comegna and Cristalli.)

To help inform global guidelines on infant feeding, this systematic review synthesizes evidence related to the presence of the Ebola virus (EBOV) in breast milk and its potential risk of viral transmission to the infant when breastfeeding. We relied on a comprehensive search strategy to identify studies including women with suspected, probable, or confirmed EBOV infection, intending to breastfeed or give breast milk to an infant. Our search identified 10,454 records, and after deduplication and screening, we assessed 148 full texts. We included eight studies reporting on 10 breastfeeding mothers and their children (one mother with twins), who provided breast milk samples for assessment. EBOV was detected via RT-PCR or viral culture in seven out of ten breast milk samples. Four out of the five-breastfed infants with EBOV-positive breast milk were found positive for EBOV infection, and all of these EBOV-positive infants died. Since previous reports have detected EBOV in tears, saliva, sweat, and contaminated surfaces, with the current evidence, it is not possible to conclude with certainty that breast milk was the main route of EBOV transmission., (© 2020 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of New York Academy of Sciences.)

Objectives: Infectious Zika viral particles were detected in human milk; however, whether they can be transmitted via breastfeeding remains unknown, so our objective was to clarify this., Methods: Here, in a natural breastfeeding model, wild-type (C57Bl/6; WT) or interferon α/β (IFNα/β) receptor-deficient (A129; KO) murine dams on day 1 post-delivery were infected with Zika virus (ZIKV) intraperitoneally, and the neonates were suckled. In a novel artificial feeding model, WT suckling mice at 1 day old were fed with ZIKV alone or ZIKV and human breast milk mixtures. Thereafter, the virus distribution, clinical progression and neuropathology in the WT or KO neonates were characterized to evaluate the risk of ZIKV transmission through breast milk., Results: In natural breastfeeding, viral RNAs (8/8) and infectious viral particles (7/8) were extensively present in the mammary glands of KO dams. All tested KO neonates (5/5), and none of WT neonates (0/9), were infected with ZIKV. In artificial feeding, 100% of the WT neonates (two groups, 12/12 and 16/16) were infected and developed some signs of neurodegeneration. ZIKV tended to seed and accumulate in the lungs and were subsequently disseminated to other tissues in both 16 naturally suckled and 19 artificially fed infected neonates. As human breast milk was mixed with ZIKV and fed to WT neonates, 45% individuals (9/20) were infected; in the infected neonates, the viral spread to the brain was delayed, and the clinical outcomes were alleviated., Conclusions: These results demonstrated that suckling mice can be infected with ZIKV through suckling, and breast milk has potential antiviral activity, inhibiting ZIKV infection., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the clinical course and impact of coronavirus disease 2019 (COVID-19) infection on pregnant women., Methods: A prospective cohort study was conducted on pregnant women with confirmed COVID-19 infection. Demographic features, clinical characteristics, and perinatal outcomes were prospectively evaluated., Results: Of the 533 cases, 161 (30.2%) had co-morbidities and 165 (30.9%) were asymptomatic. Cough (n = 178, 33.4%) and myalgia (n = 168, 31.5%) were the leading symptoms. In total, 261 patients (48.9%) received COVID-19 therapy, 509 (95.5%) had mild disease, 7 (1.3%) were admitted to the intensive care unit (ICU), and invasive mechanical ventilation was necessary in 2 (0.4%) patients. Maternal mortality was observed in 2 (0.4%) cases. Of the patients, 297 (55.7%) were hospitalized, 39 (7.3%) had suspicious radiologic imaging findings, 66 (12.4) had pregnancy complications (preterm delivery [n =22, 4.1%] and miscarriage [n =12, 2.2%] were the most common pregnancy complications), 131 births occurred, and the cesarean section rate was 66.4%. All neonates were negative for COVID-19. The rate of admission to the neonatal ICU was 9.9%. One specimen of breast milk was positive for the infection., Conclusion: The course of COVID-19 was mild in the majority of cases. However, increased rates of pregnancy complications and cesarean delivery were observed., (© 2020 International Federation of Gynecology and Obstetrics.)

Human cytomegalovirus (HCMV) is a ubiquitous pathogen that is potentially pathogenic in immunosuppressed individuals and pregnant females during primary infection. The HCMV envelope glycoprotein B (gB) facilitates viral entry into all cell types and induces a potent immune response. AD-2 epitope is a highly conserved linear neutralizing epitope of gB and a critical target for antibodies; however, only 50% of sero-positive individuals make IgG antibodies to this site and IgA responses have not been fully investigated. This study aimed to compare IgG and IgA responses against gB and the AD-2 epitope in naturally exposed individuals and those receiving a recombinant gB/MF59 adjuvant vaccine. Thus, vaccination of sero-positive individuals improved pre-existing gB-specific IgA and IgG levels and induced de novo gB-specific IgA and IgG responses in sero-negative recipients. Pre-existing AD-2 IgG and IgA responses were boosted with vaccination, but de novo AD-2 responses were not detected. Naturally exposed individuals had dominant IgG responses towards gB and AD-2 compared with weaker and variable IgA responses, although a significant IgA binding response to AD-2 was observed within human breastmilk samples. All antibodies binding AD-2 contained kappa light chains, whereas balanced kappa/lambda light chain usage was found for those binding to gB. V region-matched AD-2-specific recombinant IgG and IgA bound both to gB and to AD-2 and neutralized HCMV infection in vitro. Overall, these results indicate that although human IgG responses dominate, IgA class antibodies against AD-2 are a significant component of human milk, which may function to protect neonates from HCMV., (© 2020 The Authors. Immunology published by John Wiley & Sons Ltd.)

Purpose of Review: Breastfeeding is beneficial to both the newborn and the mother. During the COVID-19 pandemic, concerns have been raised on whether the SARS-CoV-2 virus could be transmitted from COVID-19 positive mother to the newborn through breastmilk. The purpose of this review is to examine the available evidence on the risks of transmission of infection from COVID-19 mothers to their newborns through breastfeeding., Recent Findings: Data is very limited in this regard, with only a few smaller case series, and case reports have been published so far. In most of the studies, breastmilk samples from COVID-19 mothers tested negative for the virus. In the case reports where the virus was detected in breastmilk and the infants were diagnosed with COVID-19, it remained unclear whether the disease was transmitted through breastmilk or direct contact or through delivery. Another hypothesis is that the viral antibodies could pass to the newborn passively through breastmilk of COVID-19 positive mothers and give immunity to the child, but data is minimal. Based on the currently available limited evidence and recognizing the benefits of breastfeeding, it may be concluded that if the health of the mother and her newborn allows, direct breastfeeding or extracted breastmilk should be encouraged by the healthcare providers after a careful discussion of the risks of vertical transmission to the mother and her family. Preventive measures should be taken by COVID-19 mothers to prevent droplet transmission of infection to the infants while breastfeeding.

Breastfeeding is recommended for all neonates due to a known variety of beneficial effects, but infants can be infected by cell-associated bacteria and viruses from breast milk, such as cytomegalovirus (CMV). The majority of CMV-seropositive breastfeeding women have a viral, self-restricted reactivation, can shed the virus in the milk for about 12 weeks after delivery, and can transmit the infection to their offspring. Post-natal CMV-infected term infants are mainly asymptomatic, while very low birth weight (VLBW, <1500 g) and extremely low birth weight (ELBW, <1000 g) infants may present with severe disease, short-term sequelae ranging from abnormalities in laboratory indexes to sepsis-like syndrome, and long-term sequelae such as developmental problems. Thus, the use of thermally treated maternal milk for VLBW/ELBW infants may be indicated to prevent/reduce the risk of CMV transmission. Different techniques, with varying efficacy in eradicating CMV and maintaining the activity of biological compounds in milk are available: long/short pasteurization, freeze-thawing, the use of microwaves, and ultraviolet-C irradiation. In our NICU, the use of maternal raw milk is always strongly recommended for term/preterm infants, but to reduce risk of CMV transmission, freeze-thawing mother's own milk is used in neonates with GA ≤ 30 weeks or/and weight ≤ 1000 g, usually regardless of serological maternal condition, as CMV screening is not routinely offered to pregnant women and the milk of seroimmune mothers is not evaluated for CMV reactivation, as its rate is similar to seroprevalence. Over the last 4 years, we had 10 VLBW/ELBW newborns in our NICU with late-onset sepsis and negative cultures. In these cases, the research of CMV DNA in neonatal urine or saliva, for the diagnosis of post-natal symptomatic infection (once congenital transmission has been excluded) may be useful and not invasive. The take-home message we would like to share is that acquired CMV infection should be considered in VLBW/ELBW infants breastfed by seropositive mothers and presenting severe symptoms-particularly sepsis with negative cultures. This could allow pediatricians to make better-quality diagnoses, perform supportive therapy, provide antiviral treatment if needed, or establish a "pre-emptive" therapy for these high-risk neonates.

Whether mother-to-infant SARS-CoV-2 transmission can occur during breastfeeding and, if so, whether the benefits of breastfeeding outweigh this risk during maternal COVID-19 illness remain important questions. Using RT-qPCR, we did not detect SARS-CoV-2 RNA in any milk sample ( n  = 37) collected from 18 women following COVID-19 diagnosis. Although we detected evidence of viral RNA on 8 out of 70 breast skin swabs, only one was considered a conclusive positive result. In contrast, 76% of the milk samples collected from women with COVID-19 contained SARS-CoV-2-specific IgA, and 80% had SARS-CoV-2-specific IgG. In addition, 62% of the milk samples were able to neutralize SARS-CoV-2 infectivity in vitro , whereas milk samples collected prior to the COVID-19 pandemic were unable to do so. Taken together, our data do not support mother-to-infant transmission of SARS-CoV-2 via milk. Importantly, milk produced by infected mothers is a beneficial source of anti-SARS-CoV-2 IgA and IgG and neutralizes SARS-CoV-2 activity. These results support recommendations to continue breastfeeding during mild-to-moderate maternal COVID-19 illness. IMPORTANCE Results from prior studies assaying human milk for the presence of SARS-CoV-2, the causative virus of COVID-19, have suggested milk may act as a potential vehicle for mother-to-child transmission. Most previous studies are limited because they followed only a few participants, were cross-sectional, and/or failed to report how milk was collected and/or analyzed. As such, considerable uncertainty remains regarding whether human milk is capable of transmitting SARS-CoV-2 from mother to child. Here, we report that repeated milk samples collected from 18 women following COVID-19 diagnosis did not contain SARS-CoV-2 RNA; however, risk of transmission via breast skin should be further evaluated. Importantly, we found that milk produced by infected mothers is a source of anti-SARS-CoV-2 IgA and IgG and neutralizes SARS-CoV-2 activity. These results support recommendations to continue breastfeeding during mild-to-moderate maternal COVID-19 illness as milk likely provides specific immunologic benefits to infants., (Copyright © 2021 Pace et al.)

In Brazil prevention of mother to child HIV transmission guidelines recommend formula feeding. This qualitative study, carried out in a public clinic (CEADIPE/UNIFESP), aimed at exploring experiences of breastfeeding avoidance of women living with HIV living in São Paulo. Individual interviews were carried out with the support of a semi-structured questionnaire. Data was analyzed in a thematic approach with the support of AtlasTi ® . During the months of January-February 2010, 25 women were interviewed, including women with ( n  = 12) and without previous breastfeeding experience ( n  = 13). Major themes identified were: Non-breastfeeding as a trigger for stigmatization, Non-breastfeeding, guilt and coping, Attitudes around non-breastfeeding for women with and without previous breastfeeding experience, and Women's support through non-breastfeeding. In conclusion women interviewed faced challenges related to HIV diagnosis, which got entangled with difficulties with breastfeeding avoidance. Different patterns of reaction and coping could be identified, regardless of mothers' previous breastfeeding experiences. Health systems were key in providing women living with HIV with tailored services and the necessary support.

Background: The Coronavirus Disease 2019 (COVID-19) is a novel disease which has been having a worldwide affect since December 2019. Evidence regarding the effects of SARS-CoV-2 during pregnancy is conflicting. The presence of SARS-CoV-2 has been demonstrated in biological samples during pregnancy (placenta, umbilical cord or amniotic fluid); however, maternal and fetal effects of the virus are not well known., Methods: Descriptive, multicentre, longitudinal, observational study in eight tertiary care hospitals throughout Spain, that are referral centres for pregnant women with COVID-19. All pregnant women with positive SARS-CoV-2 real-time reverse transcriptase polymerase chain reaction during their pregnancy or 14 days preconception and newborns born to mothers infected with SARS-CoV-2 will be included. They will continue to be followed up until 4 weeks after delivery. The aim of the study is to investigate both the effect of COVID-19 on the pregnancy, and the effect of the pregnancy status with the evolution of the SARS-CoV-2 disease. Other samples (faeces, urine, serum, amniotic fluid, cord and peripheral blood, placenta and breastmilk) will be collected in order to analyse whether or not there is a risk of vertical transmission and to describe the behaviour of the virus in other fluids. Neonates will be followed until 6 months after delivery to establish the rate of neonatal transmission. We aim to include 150 pregnant women and their babies. Ethics approval will be obtained from all the participating centres., Discussion: There is little information known about COVID-19 and its unknown effects on pregnancy. This study will collect a large number of samples in pregnant women which will allow us to demonstrate the behaviour of the virus in pregnancy and postpartum in a representative cohort of the Spanish population.

We systematically searched regional and international databases and screened 1658 non-duplicate records describing women with suspected or confirmed ZIKV infection, intending to breastfeed or give breast milk to an infant to examine the potential of mother-to-child transmission of Zika virus (ZIKV) through breast milk or breastfeeding-related practices. Fourteen studies met our inclusion criteria and inform this analysis. These studies reported on 97 mother-children pairs who provided breast milk for ZIKV assessment. Seventeen breast milk samples from different women were found positive for ZIKV via RT-PCR, and ZIKV replication was found in cell cultures from five out of seven breast milk samples from different women. Only three out of six infants who had ZIKV infection were breastfed, no evidence of clinical complications was found to be associated with ZIKV RNA in breast milk. This review updates our previous report by including 12 new articles, in which we found no evidence of ZIKV mother-to-child transmission through breast milk intake or breastfeeding. As the certainty of the present evidence is low, additional studies are still warranted to determine if ZIKV can be transmitted through breastfeeding.

Zika virus (ZIKV) has been detected in blood, urine, semen, cerebral spinal fluid, saliva, amniotic fluid, and breast milk. In most ZIKV infected individuals, the virus is detected in the blood to one week after the onset of symptoms and has been found to persist longer in urine and semen. To better understand virus dynamics, a prospective cohort study was conducted in Brazil to assess the presence and duration of ZIKV and related markers (viral RNA, antibodies, T cell response, and innate immunity) in blood, semen, saliva, urine, vaginal secretions/menstrual blood, rectal swab and sweat. The objective of the current manuscript is to describe the cohort, including an overview of the collected data and a description of the baseline characteristics of the participants. Men and women ≥ 18 years with acute illness and their symptomatic and asymptomatic household contacts with positive reverse transcriptase-polymerase chain reaction test for ZIKV in blood and/or urine were included. All participants were followed up for 12 months. From July 2017 to June 2019, a total of 786 participants (284 men, 502 women) were screened. Of these, 260 (33.1%) were enrolled in the study; index cases: 64 men (24.6%), 162 (62.3%) women; household contacts: 12 men (4.6%), 22 (8.5%) women. There was a statistically significant difference in age and sex between enrolled and not enrolled participants (p<0.005). Baseline sociodemographic and medical data were collected at enrollment from all participants. The median and interquartile range (IQR) age was 35 (IQR; 25.3, 43) for men and 36.5 years (IQR; 28, 47) for women. Following rash, which was one of the inclusion criteria for index cases, the most reported symptoms in the enrollment visit since the onset of the disease were fever, itching, arthralgia with or without edema, non-purulent conjunctivitis, headache, and myalgia. Ten hospitalizations were reported by eight patients (two patients were hospitalized twice) during follow up, after a median of 108 days following symptom onset (range 7 to 266 days) and with a median of 1.5 days (range 1 to 20 days) of hospital stay. A total of 4,137 visits were performed, 223 (85.8%) participants have attended all visits and 37 (14.2%) patients were discontinued., Competing Interests: The authors have declared that no competing interests exist.

In addition to providing life-giving nutrients and other substances to the breastfed infant, human milk can also represent a vehicle of pathogen transfer. As such, when an infectious disease outbreak, epidemic, or pandemic occurs-particularly when it is associated with a novel pathogen-the question will naturally arise as to whether the pathogen can be transmitted through breastfeeding. Until high-quality data are generated to answer this question, abandonment of breastfeeding due to uncertainty can result. The COVID-19 pandemic, which was in full swing at the time this document was written, is an excellent example of this scenario. During these times of uncertainty, it is critical for investigators conducting research to assess the possible transmission of pathogens through milk, whether by transfer through the mammary gland or contamination from respiratory droplets, skin, breast pumps, and milk containers, and/or close contact between mother and infant. To promote the most rigorous science, it is critical to outline optimal methods for milk collection, handling, storage, and analysis in these situations, and investigators should openly share their methods in published materials. Otherwise, the risks of inconsistent test results from preanalytical and analytical variation, false positives, and false negatives are unacceptably high and the ability to provide public health guidance poor. In this study, we provide "best practices" for collecting human milk samples for COVID-19 research with the intention that this will also be a useful guide for future pandemics.

The coronavirus disease 2019 (COVID-19) pandemic has affected all dimensions of health care, including exclusive breastfeeding assurance and its promotion. The risk of contagion and the consequences of the pandemic have raised concerns among future mothers or in those who are already breastfeeding due to the risk of possible transmission of the virus through breast milk, although active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not yet been detected in breast milk. The fear of contagion has favored mother-child isolation policies. So far, there is no evidence of vertical transmission, and the risk of horizontal transmission in the infant is similar to that of the general population. In infants with COVID-19, breastfeeding can even favorably change the clinical course of the disease., (Copyright: © 2021 Permanyer.)

Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.