You are on page 1of 2

Letters

RESEARCH LETTER Methods | This cohort study included 11 healthy lactating indi-
viduals who received either the Moderna mRNA-1273 vac-
Detection of Messenger RNA COVID-19 Vaccines cine (n = 5) or the Pfizer BNT162b2 vaccine (n = 6) within
in Human Breast Milk 6 months after delivery (Table 1). Participants were asked to
Vaccination is a cornerstone in fighting the COVID-19 pan- collect and immediately freeze EBM samples at home until
demic. However, the initial messenger RNA (mRNA) vaccine transported to the laboratory. Samples of EBM were collected
clinical trials excluded several vulnerable groups, including before vaccination (control) and for 5 days postvaccination.
young children and lactating individuals. 1 The US Food A total of 131 EBM samples were collected 1 hour to 5 days af-
and Drug Administration de- ter vaccine administration. Extracellular vesicles (EVs) were
ferred the decision to autho- isolated in EBM using sequential centrifugation, and the EV
Supplemental content
rize COVID-19 mRNA vac- concentrations were determined by ZetaView (Analytik)
cines for infants younger than 6 months until more data are (eMethods in the Supplement). The presence of COVID-19
available because of the potential priming of the children’s im- vaccine mRNA in different milk fractions (whole EBM, fat,
mune responses that may alter their immunity.2 The Centers cells, and supernatant EVs) was assayed using 2-step quanti-
for Disease Control and Prevention recommends offering the tative reverse transcriptase–polymerase chain reaction. The
COVID-19 mRNA vaccines to breastfeeding individuals,3 al- vaccine detection limit was 1 pg/mL of EBM (eMethods in the
though the possible passage of vaccine mRNAs in breast milk Supplement).
resulting in infants’ exposure at younger than 6 months was
not investigated. This study investigated whether the COVID-19 Results | Of 11 lactating individuals enrolled, trace amounts of
vaccine mRNA can be detected in the expressed breast milk BNT162b2 and mRNA-1273 COVID-19 mRNA vaccines were de-
(EBM) of lactating individuals receiving the vaccination within tected in 7 samples from 5 different participants at various
6 months after delivery. times up to 45 hours postvaccination (Table 2). The mean (SD)

Table 1. Demographic and Clinical Information About Breast Milk Samples Collected From 11 Lactating Individuals
After Receiving an mRNA COVID-19 Vaccine
Participant Maternal Race and Mode of d Gestational age Vaccine timing
No. age, y ethnicity elivery at birth, wk after delivery, wk Vaccine typea
1 33 White Vaginal 26 10 mRNA-1273
2 33 White Vaginal 39 25 BNT162b2
3 35 White Vaginal 37 9 BNT162b2
4b 34 Asian Cesarean 39 18 BNT162b2
5 37 White Cesarean 39 7 mRNA-1273
6b 37 White Vaginal 32 6 mRNA-1273
7b 22 White Vaginal 38 24 BNT162b2
8b 35 White Cesarean 39 4 BNT162b2
9 38 Black Vaginal 39 20 BNT162b2
10b 34 White Cesarean 39 7 mRNA-1273
11 35 White Cesarean 26 5 mRNA-1273
Abbreviation: mRNA, messenger RNA. Pfizer-BioNTech.
a b
mRNA-1273 was manufactured by Moderna and BNT162b2 by Participants who had detectable vaccine mRNA in their breast milk.

Table 2. Detection of Vaccine RNA in Whole Expressed Breast Milk and Extracellular Vesicles in 5 Patients
at Various Time Points Postvaccination
Concentration of vaccine Concentration of
Participant Time points of vaccine mRNA detected in vaccine mRNA detected
No. Vaccine type mRNA detection in EBM whole milka in EBM EVsa Abbreviation: EBM, expressed breast
4 BNT162b2 27-hb Sample Not detected 14.01 pg/mL milk; EVs, extracellular vesicles;
mRNA, messenger RNA.
6 mRNA-1273 27-h and 42-hb Samples 11.7 pg/mL 16.78 pg/mL a
Units for concentration are
7 BNT162b2 37-hb Sample Not detected 4.69 pg/mL picogram of mRNA per milliliter
8 BNT162b2 1-h and 3-hb Samples 1.3 pg/mL 6.77 pg/mL of whole milk equivalent.
b
Sample used for vaccine mRNA
10 mRNA-1273 45-hb Sample 2.5 pg/mL 2.13 pg/mL
concentration detection.

jamapediatrics.com (Reprinted) JAMA Pediatrics Published online September 26, 2022 E1

© 2022 American Medical Association. All rights reserved.


Letters

yield of EVs isolated from EBM was 9.110 (5.010) particles/mL, Research Laboratory, NYU Long Island School of Medicine, Mineola, New York
and the mean (SD) particle size was 110.0 (3.0) nm. The vac- (Lin, Manzano De Mejia, Botros, Gurzenda).

cine mRNA appears in higher concentrations in the EVs than Accepted for Publication: July 25, 2022.
in whole milk (Table 2). No vaccine mRNA was detected in pre- Published Online: September 26, 2022. doi:10.1001/jamapediatrics.2022.3581
vaccination or postvaccination EBM samples beyond 48 hours Corresponding Author: Nazeeh Hanna, MD, Division of Neonatology,
of collection. Also, no COVID-19 vaccine mRNA was detected Department of Pediatrics, NYU Langone Hospital–Long Island, NYU Long Island
School of Medicine, 259 First St, Mineola, NY 11501 (nazeehhanna@gmail.com).
in the EBM fat fraction or the EBM cell pellets.
Author Contributions: Dr Hanna had full access to all of the data in the study
and takes responsibility for the integrity of the data and the accuracy of the
Discussion | The sporadic presence and trace quantities of data analysis.
COVID-19 vaccine mRNA detected in EBM suggest that breast- Concept and design: All authors.
feeding after COVID-19 mRNA vaccination is safe, particu- Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Hanna, Heffes-Doon, Lin, Nayak.
larly beyond 48 hours after vaccination. These data demon- Critical revision of the manuscript for important intellectual content: All authors.
strate for the first time to our knowledge the biodistribution Statistical analysis: Hanna, Lin.
of COVID-19 vaccine mRNA to mammary cells and the poten- Obtained funding: Hanna.
Administrative, technical, or material support: Hanna, Lin, Manzano De Mejia,
tial ability of tissue EVs to package the vaccine mRNA that can
Botros, Gurzenda, Nayak.
be transported to distant cells. Little has been reported on lipid Supervision: Hanna.
nanoparticle biodistribution and localization in human tis- Conflict of Interest Disclosures: Dr Hanna reported grants from the National
sues after COVID-19 mRNA vaccination. In rats, up to 3 days Institute of Child Health and Human Development, National Institute of
following intramuscular administration, low vaccine mRNA Environmental Health Sciences, American Lung Association, March of Dimes,
New York State Department of Health, and Robert Wood Johnson Foundation.
levels were detected in the heart, lung, testis, and brain tis-
No other disclosures were reported.
sues, indicating tissue biodistribution.4 We speculate that,
Funding/Support: All financial and material support for this work was provided
following the vaccine administration, lipid nanoparticles con- by the Department of Pediatrics, NYU Langone Hospital–Long Island, New York
taining the vaccine mRNA are carried to mammary glands via University Long Island School of Medicine.
hematogenous and/or lymphatic routes.5,6 Furthermore, Role of the Funder/Sponsor: The supporting organization had a role in the
we speculate that vaccine mRNA released into mammary cell design and conduct of the study; collection, management, analysis, and
interpretation of the data; preparation, review, or approval of the manuscript;
cytosol can be recruited into developing EVs that are later se-
and decision to submit the manuscript for publication.
creted in EBM.
Additional Contributions: We acknowledge the participants who volunteered
The limitations of this study include the relatively small for this study. We are thankful to Christie Clauss, PharmD (Department of
sample size and the lack of functional studies demonstrating Pharmacy, NYU Langone Hospital–Long Island), for voluntarily providing
whether detected vaccine mRNA is translationally active. Also, unused vaccines for this study and for her critical revision of the manuscript.
We are also thankful to the following individuals for their voluntary help in
we did not test the possible cumulative vaccine mRNA expo- recruitment: Regina Cafferty, RN (Department of Pediatrics, NYU Langone
sure after frequent breastfeeding in infants. We believe it is safe Hospital–Long Island), and Elisabeth Sulger, MD, and Hollisa Rosa, MD
to breastfeed after maternal COVID-19 vaccination. However, (Department of Obstetrics and Gynecology, NYU Langone Hospital–Long
Island). None of these individuals received compensation for their contribution.
caution is warranted about breastfeeding children younger than
6 months in the first 48 hours after maternal vaccination un- 1. Van Spall HGC. Exclusion of pregnant and lactating women from COVID-19
vaccine trials: a missed opportunity. Eur Heart J. 2021;42(28):2724-2726.
til more safety studies are conducted. In addition, the poten- doi:10.1093/eurheartj/ehab103
tial interference of COVID-19 vaccine mRNA with the im- 2. US Food and Drug Administration. Coronavirus (COVID-19) update: FDA
mune response to multiple routine vaccines given to infants authorizes Moderna and Pfizer-BioNTech COVID-19 vaccines for children down
during the first 6 months of age needs to be considered. It is to 6 months of age. Released June 17, 2022. https://www.fda.gov/news-events/
press-announcements/coronavirus-covid-19-update-fda-authorizes-moderna-
critical that lactating individuals be included in future vacci-
and-pfizer-biontech-covid-19-vaccines-children
nation trials to better evaluate the effect of mRNA vaccines on
3. Centers for Disease Control and Prevention. COVID-19 vaccines while
lactation outcomes. pregnant or breastfeeding. Accessed March 8, 2021. https://www.cdc.gov/
coronavirus/2019-ncov/vaccines/recommendations/pregnancy.html.
Nazeeh Hanna, MD 4. European Medicines Agency. Assessment report: COVID-19 vaccine
Ari Heffes-Doon, MD Moderna. Published March 11, 2021. http://www.ema.europa.eu/en/documents/
Xinhua Lin, PhD assessment-report/spikevax-previously-covid-19-vaccine-moderna-epar-public-
assessment-report_en.pdf.
Claudia Manzano De Mejia, MD
5. Pardi N, Tuyishime S, Muramatsu H, et al. Expression kinetics of
Bishoy Botros, BS
nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various
Ellen Gurzenda, BS routes. J Control Release. 2015;217:345-351. doi:10.1016/j.jconrel.2015.08.007
Amrita Nayak, MD 6. Bansal S, Perincheri S, Fleming T, et al. Cutting edge: circulating exosomes
with COVID spike protein are induced by BNT162b2 (Pfizer-BioNTech)
Author Affiliations: Division of Neonatology, Department of Pediatrics, vaccination prior to development of antibodies: a novel mechanism for
NYU Langone Hospital–Long Island, NYU Long Island School of Medicine, immune activation by mRNA vaccines. J Immunol. 2021;207(10):2405-2410.
Mineola, New York (Hanna, Heffes-Doon, Nayak); Women and Children’s doi:10.4049/jimmunol.2100637

E2 JAMA Pediatrics Published online September 26, 2022 (Reprinted) jamapediatrics.com

© 2022 American Medical Association. All rights reserved.

You might also like