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"Meehan, Courtney L."
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Characterization of SARS-CoV-2 RNA, Antibodies, and Neutralizing Capacity in Milk Produced by Women with COVID-19
by
Belfort, Mandy B.
,
Meehan, Courtney L.
,
Fitzgerald, Theresa
in
Adult
,
Antibodies
,
Antibodies, Neutralizing - metabolism
2021
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. 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.
Journal Article
Breastfeeding patterns are associated with human milk microbiome composition: The Mother-Infant Microbiomes, Behavior, and Ecology Study (MIMBES)
by
Pace, Ryan M.
,
Meehan, Courtney L.
,
Holdsworth, Elizabeth A.
in
Abundance
,
Achromobacter
,
Analysis
2023
The human milk microbiome (HMM) is hypothesized to be seeded by multiple factors, including the infant oral microbiome during breastfeeding. However, it is not known whether breastfeeding patterns (e.g., frequency or total time) impact the composition of the HMM. As part of the Mother-Infant Microbiomes, Behavior, and Ecology Study (MIMBES), we analyzed data from naturalistic observations of 46 mother-infant dyads living in the US Pacific Northwest and analyzed milk produced by the mothers for its bacterial diversity and composition. DNA was extracted from milk and the V1-V3 region of the 16S rRNA gene was amplified and sequenced. We hypothesized that number of breastfeeding bouts (breastfeeding sessions separated by >30 seconds) and total time breastfeeding would be associated with HMM α-diversity (richness, diversity, or evenness) and differential abundance of HMM bacterial genera. Multiple linear regression was used to examine associations between HMM α-diversity and the number of breastfeeding bouts or total time breastfeeding and selected covariates (infant age, maternal work outside the home, frequency of allomother physical contact with the infant, non-household caregiving network). HMM richness was inversely associated with number of breastfeeding bouts and frequency of allomother physical contact, but not total time breastfeeding. Infants’ non-household caregiving network was positively associated with HMM evenness. In two ANCOM-BC analyses, abundances of 5 of the 35 most abundant genera were differentially associated with frequency of breastfeeding bouts ( Bifidobacterium , Micrococcus , Pedobacter , Acidocella , Achromobacter ); 5 genera ( Bifidobacterium , Agreia , Pedobacter , Rugamonas , Stenotrophomonas ) were associated with total time breastfeeding. These results indicate that breastfeeding patterns and infant caregiving ecology may play a role in influencing HMM composition. Future research is needed to identify whether these relationships are consistent in other populations and if they are associated with variation in the infant’s gastrointestinal (including oral) microbiome.
Journal Article
SARS‐CoV‐2 and human milk: What is the evidence?
by
Pace, Ryan M.
,
Meehan, Courtney L.
,
Raiten, Daniel J.
in
Adult
,
Antibodies, Viral - analysis
,
Babies
2020
The novel coronavirus SARS‐CoV‐2 has emerged as one of the most compelling and concerning public health challenges of our time. To address the myriad issues generated by this pandemic, an interdisciplinary breadth of research, clinical and public health communities has rapidly engaged to collectively find answers and solutions. One area of active inquiry is understanding the mode(s) of SARS‐CoV‐2 transmission. Although respiratory droplets are a known mechanism of transmission, other mechanisms are likely. Of particular importance to global health is the possibility of vertical transmission from infected mothers to infants through breastfeeding or consumption of human milk. However, there is limited published literature related to vertical transmission of any human coronaviruses (including SARS‐CoV‐2) via human milk and/or breastfeeding. Results of the literature search reported here (finalized on 17 April 2020) revealed a single study providing some evidence of vertical transmission of human coronavirus 229E; a single study evaluating presence of SARS‐CoV in human milk (it was negative); and no published data on MERS‐CoV and human milk. We identified 13 studies reporting human milk tested for SARS‐CoV‐2; one study (a non‐peer‐reviewed preprint) detected the virus in one milk sample, and another study detected SARS‐CoV‐2 specific IgG in milk. Importantly, none of the studies on coronaviruses and human milk report validation of their collection and analytical methods for use in human milk. These reports are evaluated here, and their implications related to the possibility of vertical transmission of coronaviruses (in particular, SARS‐CoV‐2) during breastfeeding are discussed.
Journal Article
What’s Normal? Immune Profiling of Human Milk from Healthy Women Living in Different Geographical and Socioeconomic Settings
2017
Human milk provides a very wide range of nutrients and bioactive components, including immune factors, human milk oligosaccharides, and a commensal microbiota. These factors are essential for interconnected processes including immunity programming and the development of a normal infant gastrointestinal microbiome. Newborn immune protection mostly relies on maternal immune factors provided through milk. However, studies dealing with an in-depth profiling of the different immune compounds present in human milk and with the assessment of their natural variation in healthy women from different populations are scarce. In this context, the objective of this work was the detection and quantification of a wide array of immune compounds, including innate immunity factors (IL1β, IL6, IL12, INFγ, TNFα), acquired immunity factors (IL2, IL4, IL10, IL13, IL17), chemokines (IL8, Groα, MCP1, MIP1β), growth factors [IL5, IL7, epidermal growth factor (EGF), granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, TGFβ2], and immunoglobulins (IgA, IgG, IgM), in milk produced by healthy women of different ethnicities living in different geographic, dietary, socioeconomic, and environmental settings. Among the analyzed factors, IgA, IgG, IgM, EGF, TGFβ2, IL7, IL8, Groα, and MIP1β were detected in all or most of the samples collected in each population and, therefore, this specific set of compounds might be considered as the \"core\" soluble immune factors in milk produced by healthy women worldwide. This approach may help define which immune factors are (or are not) common in milk produced by women living in various conditions, and to identify host, lifestyle, and environmental factors that affect the immunological composition of this complex biological fluid.
www.ClinicalTrials.gov, identifier NCT02670278.
Journal Article
Prevalence and duration of SARS-CoV-2 fecal shedding in breastfeeding dyads following maternal COVID-19 diagnosis
by
Martin, Melanie A.
,
Barbosa-Leiker, Celestina
,
Meehan, Courtney L.
in
Asymptomatic
,
Babies
,
Breast feeding
2024
There is a paucity of data on the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in feces of lactating women with coronavirus disease 2019 (COVID-19) and their breastfed infants as well as associations between fecal shedding and symptomatology.
We examined whether and to what extent SARS-CoV-2 is detectable in the feces of lactating women and their breastfed infants following maternal COVID-19 diagnosis.
This was a longitudinal study carried out from April 2020 to December 2021 involving 57 breastfeeding maternal-infant dyads: 33 dyads were enrolled within 7 d of maternal COVID-19 diagnosis, and 24 healthy dyads served as controls. Maternal/infant fecal samples were collected by participants, and surveys were administered via telephone over an 8-wk period. Feces were analyzed for SARS-CoV-2 RNA.
Signs/symptoms related to ears, eyes, nose, and throat (EENT); general fatigue/malaise; and cardiopulmonary signs/symptoms were commonly reported among mothers with COVID-19. In infants of mothers with COVID-19, EENT, immunologic, and cardiopulmonary signs/symptoms were most common, but prevalence did not differ from that of infants of control mothers. SARS-CoV-2 RNA was detected in feces of 7 (25%) women with COVID-19 and 10 (30%) of their infants. Duration of fecal shedding ranged from 1-4 wk for both mothers and infants. SARS-CoV-2 RNA was sparsely detected in feces of healthy dyads, with only one mother's and two infants' fecal samples testing positive. There was no relationship between frequencies of maternal and infant SARS-CoV-2 fecal shedding (
=0.36), although presence of maternal or infant fever was related to increased likelihood (7-9 times greater,
≤0.04) of fecal shedding in infants of mothers with COVID-19.
Journal Article
Variation in Human Milk Composition Is Related to Differences in Milk and Infant Fecal Microbial Communities
2021
Previously published data from our group and others demonstrate that human milk oligosaccharide (HMOs), as well as milk and infant fecal microbial profiles, vary by geography. However, little is known about the geographical variation of other milk-borne factors, such as lactose and protein, as well as the associations among these factors and microbial community structures in milk and infant feces. Here, we characterized and contrasted concentrations of milk-borne lactose, protein, and HMOs, and examined their associations with milk and infant fecal microbiomes in samples collected in 11 geographically diverse sites. Although geographical site was strongly associated with milk and infant fecal microbiomes, both sample types assorted into a smaller number of community state types based on shared microbial profiles. Similar to HMOs, concentrations of lactose and protein also varied by geography. Concentrations of HMOs, lactose, and protein were associated with differences in the microbial community structures of milk and infant feces and in the abundance of specific taxa. Taken together, these data suggest that the composition of human milk, even when produced by relatively healthy women, differs based on geographical boundaries and that concentrations of HMOs, lactose, and protein in milk are related to variation in milk and infant fecal microbial communities.
Journal Article
SARS-CoV-2 specific antibody trajectories in mothers and infants over two months following maternal infection
by
Martin, Melanie A.
,
Barbosa-Leiker, Celestina
,
Meehan, Courtney L.
in
Adolescent
,
Adult
,
Age groups
2022
Infants exposed to caregivers infected with SARS-CoV-2 may have heightened infection risks relative to older children due to their more intensive care and feeding needs. However, there has been limited research on COVID-19 outcomes in exposed infants beyond the neonatal period. Between June 2020 – March 2021, we conducted interviews and collected capillary dried blood spots from 46 SARS-CoV-2 infected mothers and their infants (aged 1-36 months) for up to two months following maternal infection onset (COVID+ group, 87% breastfeeding). Comparative data were also collected from 26 breastfeeding mothers with no known SARS-CoV-2 infection or exposures (breastfeeding control group), and 11 mothers who tested SARS-CoV-2 negative after experiencing symptoms or close contact exposure (COVID- group, 73% breastfeeding). Dried blood spots were assayed for anti-SARS-CoV-2 S-RBD IgG and IgA positivity and anti-SARS-CoV-2 S1 + S2 IgG concentrations. Within the COVID+ group, the mean probability of seropositivity among infant samples was lower than that of corresponding maternal samples (0.54 and 0.87, respectively, for IgG; 0.33 and 0.85, respectively, for IgA), with likelihood of infant infection positively associated with the number of maternal symptoms and other household infections reported. COVID+ mothers reported a lower incidence of COVID-19 symptoms among their infants as compared to themselves and other household adults, and infants had similar PCR positivity rates as other household children. No samples returned by COVID- mothers or their infants tested antibody positive. Among the breastfeeding control group, 44% of mothers but none of their infants tested antibody positive in at least one sample. Results support previous research demonstrating minimal risks to infants following maternal COVID-19 infection, including for breastfeeding infants.
Journal Article
Multipathogen Analysis of IgA and IgG Antigen Specificity for Selected Pathogens in Milk Produced by Women From Diverse Geographical Regions: The INSPIRE Study
by
Gindola, Debela
,
Otoo, Gloria E.
,
Meehan, Courtney L.
in
Antibodies
,
Antibody Specificity - immunology
,
Antigens
2021
Breastfeeding provides defense against infectious disease during early life. The mechanisms underlying this protection are complex but likely include the vast array of immune cells and components, such as immunoglobulins, in milk. Simply characterizing the concentrations of these bioactives, however, provides only limited information regarding their potential relationships with disease risk in the recipient infant. Rather, understanding pathogen and antigen specificity profiles of milk-borne immunoglobulins might lead to a more complete understanding of how maternal immunity impacts infant health and wellbeing. Milk produced by women living in 11 geographically dispersed populations was applied to a protein microarray containing antigens from 16 pathogens, including diarrheagenic E. coli , Shigella spp. , Salmonella enterica serovar Typhi, Staphylococcus aureus , Streptococcus pneumoniae, Mycobacterium tuberculosis and other pathogens of global health concern, and specific IgA and IgG binding was measured. Our analysis identified novel disease-specific antigen responses and suggests that some IgA and IgG responses vary substantially within and among populations. Patterns of antibody reactivity analyzed by principal component analysis and differential reactivity analysis were associated with either lower-to-middle-income countries (LMICs) or high-income countries (HICs). Antibody levels were generally higher in LMICs than HICs, particularly for Shigella and diarrheagenic E. coli antigens, although sets of S. aureus , S. pneumoniae , and some M. tuberculosis antigens were more reactive in HICs. Differential responses were typically specific to canonical immunodominant antigens, but a set of nondifferential but highly reactive antibodies were specific to antigens possibly universally recognized by antibodies in human milk. This approach provides a promising means to understand how breastfeeding and human milk protect (or do not protect) infants from environmentally relevant pathogens. Furthermore, this approach might lead to interventions to boost population-specific immunity in at-risk breastfeeding mothers and their infants.
Journal Article
Cannabis use, decision making, and perceptions of risk among breastfeeding individuals: the Lactation and Cannabis (LAC) Study
by
Barbosa-Leiker, Celestina
,
Gang, David R.
,
Meehan, Courtney L.
in
Babies
,
Breastfeeding
,
Breastfeeding & lactation
2024
Objective
Our primary objective was to understand breastfeeding individuals’ decisions to use cannabis. Specifically, we investigated reasons for cannabis use, experiences with healthcare providers regarding use, and potential concerns about cannabis use.
Methods
We collected survey data from twenty breastfeeding participants from Washington and Oregon who used cannabis at least once weekly. We documented individuals’ cannabis use and analyzed factors associated with their decisions to use cannabis during lactation. Qualitative description was used to assess responses to an open-ended question about potential concerns.
Results
Fifty-five percent of participants (
n
= 11) reported using cannabis to treat or manage health conditions, mostly related to mental health. Eighty percent of participants (
n
= 16) reported very few or no concerns about using cannabis while breastfeeding, although participants who used cannabis for medical purposes had significantly more concerns. Most participants (
n
= 18, 90%) reported receiving either no or unhelpful advice from healthcare providers. Four themes arose through qualitative analysis, indicating that breastfeeding individuals are: 1) identifying research gaps and collecting evidence; 2) monitoring their child’s health and development; 3) monitoring and titrating their cannabis use; and 4) comparing risks between cannabis and other controlled substances.
Conclusions
Breastfeeding individuals reported cannabis for medical and non-medical reasons and few had concerns about cannabis use during breastfeeding. Breastfeeding individuals reported using a variety of strategies and resources in their assessment of risk or lack thereof when deciding to use cannabis. Most participants reported receiving no helpful guidance from healthcare providers.
Journal Article