Safety and Efficacy of Coronavirus Disease 2019 (COVID-19) mRNA Vaccines During Lactation : Obstetrics & Gynecology

Secondary Logo

Journal Logo

Narrative Review

Safety and Efficacy of Coronavirus Disease 2019 (COVID-19) mRNA Vaccines During Lactation

Shook, Lydia L. MD; Edlow, Andrea G. MD, MSc

Author Information
Obstetrics & Gynecology ():10.1097/AOG.0000000000005093, January 10, 2023. | DOI: 10.1097/AOG.0000000000005093
  • Free
  • PAP

Nearly 2 years have elapsed since coronavirus disease 2019 (COVID-19) mRNA vaccines initially became available to the public, during which time knowledge about the safety and efficacy of COVID-19 vaccination in pregnancy and lactation has grown substantially. It is well-established that COVID-19 mRNA vaccines are highly immunogenic in pregnant and lactating people1–3 and provide excellent protection against severe COVID-19 in these high-risk groups, as they do in the general adult population.4–6 Receipt of a booster shot generates similar immune responses in pregnant and lactating individuals compared with nonpregnant individuals, including against the Omicron variant, and is well-tolerated.7–9 The Centers for Disease Control and Prevention and multiple professional organizations, including the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine, have consistently recommended vaccination with COVID-19 mRNA vaccines for people who are pregnant or breastfeeding and have recommended adherence to recommended booster dosing schedules, including with the bivalent COVID-19 vaccine booster.10–12

Although the COVID-19 vaccination rate in pregnant populations initially lagged that in age-matched groups,13,14 with critical disparities in vaccine coverage noted in racial and ethnic minority groups,15 71% of currently pregnant individuals in the United States have completed a primary COVID-19 vaccine series as of December 17, 2022,16 and many have received booster doses.17,18 Although serious illness and death from COVID-19 still occurs, with pregnancy being an important risk factor for severe disease,19 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the Omicron-dominant period resulted in less severe disease compared with the Delta and pre-Delta epochs in pregnant individuals.20 This reduced risk of severe–critical disease is attributable not only to differences in strain virulence but also to higher vaccination rates in pregnant people.

Although the benefits of COVID-19 vaccination during pregnancy are clear, some individuals who are unvaccinated or due for a booster and hesitant about receiving an mRNA vaccine during pregnancy may consider deferring vaccination to the postpartum period. A pressing question for these individuals has become, what is the optimal time to receive a COVID-19 vaccine that maximizes benefit and minimizes risk to both members of the mother–infant dyad? The recent article from Hanna et al in JAMA Pediatrics21 reporting transient detection of small levels of vaccine-derived mRNA in human breast milk presents an opportunity to review the safety and efficacy of COVID-19 vaccination during lactation. In this review, we aim to 1) briefly summarize the data on the safety and reactogenicity of COVID-19 vaccines during lactation to date, 2) contextualize the findings of the Hanna et al study with what is known about mRNA vaccine components in breast milk, and 3) discuss the efficacy of COVID-19 vaccines in providing immune protection for the breastfeeding infant. Key points are summarized in Box 1.

Box 1.

Key Points

  • • COVID-19 mRNA vaccination is recommended for lactating individuals (CDC, ACOG).
  • • Staying up to date on booster doses, including the bivalent COVID-19 booster, is recommended for lactating individuals (CDC, ACOG).
  • • There is no evidence that breast milk from lactating individuals who have received a COVID-19 mRNA vaccine can cause harm to breastfeeding infants.
  • • The breast milk of vaccinated individuals contains SARS-CoV-2–specific antibodies and T cells that may benefit the breastfeeding infant's developing immune system.
  • • How much protection a vaccinated mother's breast milk affords the breastfeeding infant against COVID-19 or severe COVID-19 illness or both, and how long that protection lasts, is not known.
  • • Transfer of SARS-CoV-2–specific antibodies from mother to infant is highest when vaccination occurs during pregnancy compared with lactation, because the breastfeeding infant receives both long-lasting antibodies through the placenta and breast-milk antibodies through breast milk.

COVID-19, coronavirus disease 2019; CDC, Centers for Disease Control and Prevention; ACOG, American College of Obstetricians and Gynecologists; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.


Although pregnant and lactating individuals were excluded from initial COVID-19 vaccine trials,13,22 at this point in the pandemic, numerous studies including thousands of lactating individuals receiving mRNA vaccines and their breastfed infants have been reported in the literature; a comprehensive summary of the literature is publicly available on the LactMed database.23 A search of the National Institutes of Health/National Library of Medicine's Drugs and Lactation Database (LactMed) conducted in November 2022 revealed no reports in the peer-reviewed literature of serious adverse events in either the breastfeeding recipient of COVID-19 mRNA vaccines or the breastfed infant. Side effects are similar in lactating individuals receiving a primary mRNA vaccine series compared with nonlactating individuals, with postvaccination symptoms more common after the second dose.1,24–26 Rates of local or systemic postvaccination symptoms ranged from 56% to 85% among lactating study participants, with pain at the injection site being the most commonly reported postvaccine symptom.24–27 In a large study of more than 4,400 lactating vaccine recipients, the Moderna (mRNA-1273) vaccine was consistently more reactogenic than the Pfizer–BioNTech (BNT162b2) vaccine24; in a smaller study of only 86 patients, the Oxford/Astra-Zeneca (ChAdOx1 nCoV-19) vaccine was associated with more postvaccination symptoms than either of the mRNA vaccines.28

No serious adverse events have been reported in breastfeeding infants whose mothers received a COVID-19 mRNA vaccine. In an early prospective study of 84 lactating COVID-19 vaccine recipients, four reported fever in their breastfeeding infants; however, in all cases, fever occurred more than 7 days after maternal vaccination, and all infants had symptoms of upper respiratory tract infections, which were thought to be the etiology of the fevers.27 Most subsequent studies reporting outcomes of breastfed infants have been survey-based, which lack a nonvaccinated control group with which to compare and contextualize the responses and are subject to some recall bias. Regardless, these studies report low rates of observed effects in infants, with the most frequent events including changes in sleep or behavior (either increased sleepiness or irritability) and gastrointestinal symptoms, with a range of 1–31% of mothers reporting at least one symptom in these studies.9,24,25,29,30

Data are conflicting regarding effect on milk supply after receipt of the COVID-19 mRNA vaccines. In a study including more than 4,400 lactating individuals receiving COVID-19 vaccines, 4% of recipients reported a transient increase in milk supply.24 However, the same study reported a transient decrease in milk supply in the days after receipt of a COVID-19 vaccine in 6% of recipients, and other studies have also reported a transient decrease in milk supply in 6–8% of vaccine recipients, with supply returning to normal within 3 days of vaccination.24,25,31 Transient changes in milk color have also been reported.25,31 Available data suggest that lactational concerns may be less frequent after booster doses: in a follow-up survey study of more than 10,000 lactating individuals, 96% of individuals reported no lactational concerns after vaccination, with 1.2% reporting any issue with their breastfed infant and 3.5% reporting decreased milk supply.9 In summary, although transient effects on milk supply or infant behavior or both have been reported after maternal vaccination, the lack of serious side effects in either mother or infant across numerous studies is reassuring.


The COVID-19 mRNA vaccines deliver lipid nanoparticles that encapsulate mRNA, encoding the SARS-CoV-2 spike protein to the vaccine recipient's cells. Once taken up by the host cell, the mRNA is released and translated into the SARS-CoV-2 spike protein, which is then processed into peptides that get displayed on the cell surface for immune recognition.32 Vaccine mRNA has been detected in the plasma of vaccine recipients in low levels in the days after vaccination,33 so there exists a theoretical possibility that mRNA from the maternal circulation could be excreted intact into breast milk.

To date, four studies have investigated levels of BNT162b2 or mRNA-1273 mRNA in the breast milk of vaccine recipients.21,34–36 In a small study of 14 lactating health care workers in Singapore receiving the BNT162b2 vaccine, 4 out of 40 breast-milk samples collected within a week of vaccination had detectable levels of vaccine mRNA at low levels (highest concentration of BNT162b2 mRNA was 2 ng/mL, which translates to 0.667% of the original vaccine dose per 100 mL of human milk given to the infant).35 A second study of 35 lactating health care workers, also in Singapore, receiving the BNT162b2 vaccine detected mRNA (median 70 pg/mL) in 5 of 309 breast-milk samples collected within 1 week of vaccination; all positive samples were collected within 3 days.36 None of five breastfeeding infants recruited had detectable mRNA in their serum. In a small study of seven individuals who received a COVID-19 mRNA vaccine during lactation in the United States, breast milk was collected 8–48 hours after vaccination, and milk supernatant, fat layer, and cells were tested for vaccine mRNA.34 Using highly sensitive assays with a lower limit of detection of 0.195 picograms/mL for the BNT162b2 vaccine and 1.5 picograms/mL for the mRNA-1273 vaccine, none of the 13 samples had detectable vaccine mRNA.

In a recently published study by Hanna et al,21 breast milk from 11 lactating vaccine recipients was collected up to 5 days after vaccination and analyzed for the presence of vaccine mRNA in both whole breast milk and in extracellular vesicles (EVs) isolated from breast-milk supernatant. Extracellular vesicles are particles released from cells that have a phospholipid bilayer and can carry biologically important molecules, including nucleic acids and proteins, in body fluids.37 The authors report that 5 of 11 samples had detectable vaccine mRNA in breast milk at levels ranging from 1.3 to 16.8 pg/mL, with mRNA being detectable at timepoints ranging from 1 hour to 45 hours postvaccination. No breast-milk samples had detectable mRNA after 45 hours. Two of five positive samples had detectable vaccine mRNA in EVs only. To put these amounts in perspective, even at the highest detected concentration of vaccine mRNA in EVs (16 pg/mL), a 100-mL breast-milk sample would contain at most 0.002% of the amount of mRNA in the mRNA-1273 vaccine.

The study of milk-derived EVs is still relatively nascent. Because human milk EVs have been found to contain various types of RNA,37,38 it is not surprising that vaccine mRNA would be detected in a greater proportion of breast-milk samples when isolated breast-milk EVs are examined. Evidence is limited, however, as to whether EVs can survive the infant's highly acidic gastric environment or enzymatic digestion of the small intestine. Although a small in vitro study suggests that such survival is possible, and perhaps key to the potential biological relevance of breast-milk EVs to the infant,39 there is no direct in vivo evidence that breast-milk EVs can traverse the mucous layer of the intestine and enter the infant blood stream intact.37 Naked mRNA is highly unstable, subject to rapid degradation by RNases, and poorly taken up by cells in the absence of encapsulation.40–43 Although small quantities of vaccine mRNA in breast milk may minutely augment the substantial natural EV–RNA cargo, they are unlikely to have biological effects if released. Although small quantities of mRNA may be transiently detectable in breast milk after maternal vaccination, there are no data to suggest harm to the breastfeeding infant.


Pregnant and lactating individuals mount immunologic responses to the COVID-19 mRNA vaccines that are comparable with those of nonpregnant reproductive-aged females.1,44 Receiving a primary COVID-19 mRNA vaccination series during pregnancy protects the vaccinated mother from serious illness and protects the fetus and neonate by lowering the risk of COVID-19–associated preterm birth.14,45 Vaccination during pregnancy also provides the infant with protection against COVID-19 hospitalization in the first 6 months of life by transplacental transfer of durable vaccine-derived anti–SARS-CoV-2 immunoglobulin (Ig) G, in addition to breast-milk transfer of vaccine-derived IgA, IgM, and IgG if the infant is breastfed (Fig. 1A).3,46–48 Receiving a COVID-19 vaccine during pregnancy does not increase the risk of side effects, miscarriage, preterm birth, or fetal growth restriction49–51 and may in fact protect against stillbirth.6

Fig. 1.:
Coronavirus disease 2019 (COVID-19) vaccine–induced breast-milk antibodies. A. Maternal COVID-19 vaccination has been demonstrated to be associated with generation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific immune globulin (Ig) G, M, and A, with neutralizing capabilities. In addition, COVID-19 vaccination has been demonstrated to generate SARS-CoV-2–specific T cells that are detectable in human breast milk. B. Breast-milk antibodies serve diverse functions in the neonatal gut, including neutralizing pathogens, promoting antigen tolerance, and maintaining a healthy gut microbiome through selection of favorable commensal bacteria. Created with

Vaccination during pregnancy has clear benefits for the vaccinated individual and the infant, regardless of breastfeeding status. Despite these benefits, some pregnant individuals remain hesitant about vaccination during pregnancy and choose to pursue vaccination in the postpartum and lactational period, which is still beneficial because it offers protection for the postpartum individual as well as protection for the infant if breastfed. In addition, some individuals who were vaccinated before, during, or after pregnancy have become eligible for a booster dose while lactating. To aid with COVID-19 vaccine decision making in lactating individuals, a conversation about any risks associated with vaccination should be balanced with a discussion of the potential benefits breastfeeding provides for SARS-CoV-2–specific and overall newborn immunity.

Human breast milk plays an important, multifaceted role in providing immune protection to the breastfeeding infant.52 Although multiple biologically active components of human breast milk provide nonspecific immune defenses, maternal Igs transferred in breast milk to the lactating infant are key to supporting antigen-specific immunity.53 Secretory IgA is the most abundant Ig isotype in human breast milk, although secretory IgM and IgG are also present in breast milk and play important roles in both immune tolerance and defense against pathogens.52 By populating and coating the infant’s mucosal surfaces, secretory IgA provides barrier immunity by neutralizing pathogens (Fig. 1A)54 and supports the development and maintenance of a healthy gut microbiome through selection of useful commensal bacteria (Fig. 1B).55 Although the roles of breast-milk–derived secretory IgM and IgG are less well understood, IgG has been shown to protect against pathogenic bacteria in the gut as well as respiratory viruses such as respiratory syncytial virus,56,57 particularly in preterm infants who have altered gut permeability.58

Multiple studies have demonstrated the presence of SARS-CoV-2–specific IgA and IgG in human breast milk in the weeks after primary maternal COVID-19 mRNA vaccination during pregnancy and lactation.59 In one large study of 98 breastfeeding mRNA vaccine recipients, SARS-CoV-2–specific IgA was detected in 89% of samples and IgG in all samples collected 14 days after the second vaccine dose.60 Studies across multiple cohorts and vaccine platforms consistently demonstrate the presence of SARS-CoV-2–specific IgA and IgG in breast milk, with breast-milk antibody levels correlating with levels in maternal blood.59,61,62

The capability of breast milk from vaccinated, lactating individuals to neutralize SARS-CoV-2, including variants of concern, has been demonstrated in multiple studies.62–64 Although SARS-CoV-2–specific IgA and IgG levels decrease over time in breast milk, levels of both IgA and IgG remain elevated up to 6 months after vaccination.65,66 In a small study of 10 lactating participants who received an mRNA booster shot, boosting significantly improved antibody levels and breast-milk neutralizing capability in vitro, from 12% to 66% inhibition of SARS-CoV-2.67 Although the neutralizing SARS-CoV-2–specific antibodies in breast milk likely confer some level of protection to the breastfeeding infant, the degree and durability of infant protection that maternal breast-milk antibodies provide is not known. However, these data support the ability of maternal mRNA COVID-19 vaccination to generate significant levels of SARS-CoV-2–specific functional antibodies in breast milk, which may be boosted by vaccination during lactation.

SARS-CoV-2–specific antibodies detected in the breast milk of breastfeeding vaccine recipients are transferred to the mucosal surfaces of the breastfeeding infant, and limited evidence suggests that they may be capable of transiting beyond the infant's mouth and upper respiratory tract into the lower gastrointestinal tract. Breast-milk–derived SARS-CoV-2–specific antibodies have been detected in significant amounts in the breastfeeding infants' saliva and stool,64,65,68 and studies performed in vitro support the capability of breast-milk–derived anti–SARS-CoV-2 IgG and secretory IgA to resist degradation in the infant gut.69,70 Importantly, however, anti–SARS-CoV-2 antibodies have not been detected in the blood of infants whose mothers were vaccinated during lactation only,29,68 suggesting that maternally derived antibodies from breast milk likely do not cross the gut mucosal barrier in detectable quantities. This stands in contrast to antibodies that are transplacentally transferred from mothers vaccinated during pregnancy, which are detectable in the infant's circulation for up to 6 months in the majority of cases.46 Primary vaccination during pregnancy likely affords more long-lasting infant protection than breastfeeding alone, given that IgG can be transferred to the newborn circulation only by transplacental transfer and not by breast milk.

Although the breast milk of vaccinated mothers likely confers antibody-mediated neutralization of SARS-CoV-2 that lasts only hours to days after cessation of breastfeeding, there is increasing evidence that breast-milk antibodies play a more complex role in neonatal protection than simple neutralization of pathogens at the mucosal surface. Breast-milk antibodies may serve a more durable immune function in the neonate and infant by helping to establish and maintain the gut microbiome and training the immune system to “tolerate” antigens at the mucosal surface (Fig. 1B).52 In addition, whether intact immune cells, which could provide longer-lasting immunity against SARS-CoV-2, can transfer to the breastfed infant is an open question.

The presence of SARS-CoV-2–reactive CD4+ T cells in breast milk has been demonstrated after maternal vaccination (Fig. 1A),71 with expansion of spike-specific T cell receptors in breast milk observed after a COVID-19 mRNA booster.72 High levels of mucosal-homing markers in breast-milk T cells suggest that these cells may be derived from a T cell population residing in the breast tissue itself that is modulated by maternal vaccination.72 In addition, recent evidence suggests that breast-milk–derived maternal cells may be able to traffic across the infant gut mucosa and take up residence in infant tissues.73 Breast-milk immunity is likely far more complex than simple antibody persistence on infant mucosal surfaces, and the durability of breast-milk–transferred cellular immunity to the infant as well as breast-milk education of the infant gut microbiome are key areas for future study.52,74,75 Longitudinal studies of breastfed infants born to vaccinated mothers are needed to better understand the potential short-and long-term protective benefits conferred by breastfeeding.


A key area for future study is the extent to which enhanced protection of the neonate is afforded by the combination of transplacentally transferred maternal IgG and breast-milk–acquired IgA, IgM, and IgG. As more individuals are entering pregnancy vaccinated, it is increasingly important to understand how receipt of a COVID-19 vaccine during lactation complements the transplacental transfer of SARS-CoV-2–specific immunity from prior vaccination. Several studies have demonstrated population of the breastfeeding newborn's gut with protective and functional (eg, capable of activation of neutrophil phagocytosis) vaccine-induced SARS-CoV-2–specific antibodies,64,65,68,76 but the extent to which this protection can be augmented by a booster dose during lactation remains unknown. In addition, whether intranasal COVID-19 vaccines, which target induction of mucosal immunity against SARS-CoV-2 and are currently in development,77 might enhance breast-milk immunity will be important to assess; some evidence has shown enhanced breast-milk immunity after intranasal influenza vaccination compared with the intramuscular vaccine.78

Without any evidence of harm to mothers or infants after COVID-19 vaccine administration during lactation, recommendations to avoid vaccination while breastfeeding or to withhold breast milk from the infant for any period of time after vaccination are inappropriate. Although misinformation about the safety of COVID-19 mRNA vaccines in reproduction continues to affect the public's perception of vaccine safety,79,80 the benefits of COVID-19 vaccination for the mother–infant dyad are clear, whether during pregnancy or lactation, and far outweigh any potential theoretical risks. Pregnant individuals desiring to optimize infant protection against COVID-19 should be encouraged to vaccinate during pregnancy rather than deferring vaccination until after delivery. As COVID-19 variants become increasingly transmissible over time, pregnant and lactating individuals should be encouraged to stay on schedule with mRNA booster doses, because this remains an important strategy for protecting both members of the breastfeeding pair from COVID-19 illness.


1. Gray KJ, Bordt EA, Atyeo C, Deriso E, Akinwunmi B, Young N, , et al. Coronavirus disease 2019 vaccine response in pregnant and lactating women: a cohort study. Am J Obstet Gynecol 2021;225:303.e1–17. doi: 10.1016/j.ajog.2021.03.023.
2. Beharier O, Plitman Mayo R, Raz T, Nahum Sacks K, Schreiber L, Suissa-Cohen Y, , et al. Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA COVID-19 vaccine. J Clin Invest 2021;131:e150319. doi:10.1172/JCI150319
3. Prabhu M, Murphy EA, Sukhu AC, Yee J, Singh S, Eng D, , et al. Antibody response to coronavirus disease 2019 (COVID-19) messenger RNA vaccination in pregnant women and transplacental passage into cord blood. Obstet Gynecol 2021;138:278–80. doi:10.1097/AOG.0000000000004438
4. Goldshtein I, Nevo D, Steinberg DM, Rotem RS, Gorfine M, Chodick G, , et al. Association between BNT162b2 vaccination and incidence of SARS-CoV-2 infection in pregnant women. JAMA 2021;326:728–35. doi: 10.1001/jama.2021.11035
5. Dagan N, Barda N, Biron-Shental T, Makov-Assif M, Key C, Kohane IS, , et al. Effectiveness of the BNT162b2 mRNA COVID-19 vaccine in pregnancy. Nat Med 2021;27:1693–5. doi: 10.1038/s41591-021-01490-8
6. Prasad S, Kalafat E, Blakeway H, Townsend R, O'Brien P, Morris E, Draycott T, , et al. Systematic review and meta-analysis of the effectiveness and perinatal outcomes of COVID-19 vaccination in pregnancy. Nat Commun 2022;13:2414. doi: 10.1038/s41467-022-30052-w
7. Atyeo C, Shook LL, Nziza N, Deriso EA, Muir C, Baez AM, , et al. COVID-19 booster dose induces robust antibody response in pregnant, lactating, and nonpregnant women. Am J Obstet Gynecol 2023;228:68.e1–12. doi:10.1016/j.ajog.2022.07.014
8. Yang YJ, Murphy EA, Singh S, Sukhu AC, Wolfe I, Adurty S, , et al. Association of gestational age at coronavirus disease 2019 (COVID-19) vaccination, history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and a vaccine booster dose with maternal and umbilical cord antibody levels at delivery. Obstet Gynecol 2021;139:373–80. doi:10.1097/AOG.0000000000004693
9. Kachikis A, Englund JA, Covelli I, Frank Y, Haghighi C, Singleton M, , et al. Analysis of vaccine reactions after COVID-19 vaccine booster doses among pregnant and lactating individuals. JAMA Netw Open 2022;5:e2230495. doi:10.1001/jamanetworkopen.2022.30495
10. Centers for Disease Control and Prevention. COVID-19 vaccines while pregnant or breastfeeding. Accessed February 28, 2022.
11. American College of Obstetricians and Gynecologists. Practice advisory. COVID-19 vaccination considerations for obstetric–gynecologic care. Accessed September 3, 2021.
12. American College of Obstetricians and Gynecologists. ACOG and SMFM recommend COVID-19 vaccination for pregnant individuals. Accessed August 13, 2021.
13. Shook LL, Kishkovich TP, Edlow AG. Countering COVID-19 vaccine hesitancy in pregnancy: the “4 Cs”. Am J Perinatol 2021;39:1048–54. doi:10.1055/a-1673-5546
14. Stock SJ, Carruthers J, Calvert C, Denny C, Donaghy J, Goulding A, , et al. SARS-CoV-2 infection and COVID-19 vaccination rates in pregnant women in Scotland [published erratum appears in Nat Med 2022 Feb 4]. Nat Med 2022;28:504–12. doi:10.1038/s41591-021-01666-2
15. Kriss JL, Hung MC, Srivastav A, Black CL, Lindley MC, Lee JT, , et al. COVID-19 vaccination coverage, by race and ethnicity - national immunization survey adult COVID module, United States, December 2020-November 2021. MMWR Morb Mortal Wkly Rep 2022;71:757–63. doi:10.15585/mmwr.mm7123a2
16. Centers for Disease Control and Prevention. COVID-19 vaccination among pregnant people aged 18-49 years overall, by race/ethnicity, and date reported to CDC - vaccine Safety Datalink,* United States. Accessed November 28, 2022.
17. Centers for Disease Control and Prevention. Stay up to date with COVID-19 vaccines including boosters. Accessed January 2, 2023.
18. Razzaghi H, Meghani M, Crane B, Ellington S, Naleway AL, Irving SA, , et al. Receipt of COVID-19 booster dose among fully vaccinated pregnant individuals aged 18 to 49 years by key demographics. JAMA 2022;327:2351–4. doi:10.1001/jama.2022.6834
19. Zambrano LD, Ellington S, Strid P, Galang RR, Oduyebo T, Tong VT, , et al. Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status - United States, January 22-October 3, 2020. MMWR Morb Mortal Wkly Rep 2020;69:1641–7. doi:10.15585/mmwr.mm6944e3
20. Adhikari EH, MacDonald L, SoRelle JA, Morse J, Pruszynski J, Spong CY. COVID-19 cases and disease severity in pregnancy and neonatal positivity associated with Delta (B.1.617.2) and Omicron (B.1.1.529) variant predominance. JAMA 2022;327:1500–2. doi:10.1001/jama.2022.4356
21. Hanna N, Heffes-Doon A, Lin X, Manzano De Mejia C, Botros B, Gurzenda E, , et al. Detection of messenger RNA COVID-19 vaccines in human breast milk [published erratum appears in JAMA Pediatr 2022;176:1154]. JAMA Pediatr 2022;176:1268–70. doi:10.1001/jamapediatrics.2022.3581
22. Shook LL, Fallah PN, Silberman JN, Edlow AG. COVID-19 vaccination in pregnancy and lactation: current research and gaps in understanding. Front Cell Infect Microbiol 2021;11:735394. doi: 10.3389/fcimb.2021.735394
23. COVID-19 vaccines. In: Drugs and Lactation Database (LactMed). National Library of Medicine; 2020.
24. McLaurin-Jiang S, Garner CD, Krutsch K, Hale TW. Maternal and Child symptoms following COVID-19 vaccination among breastfeeding mothers. Breastfeed Med 2021;16:702–9. doi: 10.1089/bfm.2021.0079
25. Bertrand K, Honerkamp-Smith G, Chambers CD. Maternal and child outcomes reported by breastfeeding women following messenger RNA COVID-19 vaccination. Breastfeed Med 2021;16:697–701. doi: 10.1089/bfm.2021.0169
26. Fu W, Sivajohan B, McClymont E, Albert A, Elwood C, Ogilvie G, , et al. Systematic review of the safety, immunogenicity, and effectiveness of COVID-19 vaccines in pregnant and lactating individuals and their infants. Int J Gynecol Obstet 2022;156:406–17. doi: 10.1002/ijgo.14008
27. Perl SH, Uzan-Yulzari A, Klainer H, Asiskovich L, Youngster M, Rinott E, , et al. SARS-CoV-2-specific antibodies in breast milk after COVID-19 vaccination of breastfeeding women. JAMA 2021;325:2013–4. doi:10.1001/jama.2021.5782
28. Selma-Royo M, Bäuerl C, Mena-Tudela D, Aguilar-Camprubí L, Pérez-Cano FJ, Parra-Llorca A, , et al. Anti-SARS-CoV-2 IgA and IgG in human milk after vaccination is dependent on vaccine type and previous SARS-CoV-2 exposure: a longitudinal study. Genome Med 2022;14:42. doi: 10.1186/s13073-022-01043-9
29. Golan Y, Prahl M, Cassidy AG, Gay C, Wu AHB, Jigmeddagva U, , et al. COVID-19 mRNA vaccination in lactation: assessment of adverse events and vaccine related antibodies in mother-infant dyads. Front Immunol 2021;12:777103. doi: 10.3389/fimmu.2021.777103
30. Romero Ramírez DS, Suárez Hernández MI, Fernández Vilar AM, Rivero Falero M, Reyes Millán B, González Carretero P, , et al. Evaluation of adverse effects in nursing mothers and their infants after COVID-19 mRNA vaccination. Breastfeed Med 2022;17:412–21. doi: 10.1089/bfm.2021.0256
31. Jacob-Chow B, Vasundhara KL, Cheang HK, Lee LY, Low JM, Amin Z. Reactogenicity of mRNA- and non-mRNA-based COVID-19 vaccines among lactating mother and Child dyads. Vaccines (Basel) 2022;10:1094. doi: 10.3390/vaccines10071094
32. Le TK, Paris C, Khan KS, Robson F, Ng WL, Rocchi P. Nucleic acid-based technologies targeting coronaviruses. Trends Biochem Sci 2021;46:351–65. doi: 10.1016/j.tibs.2020.11.010
33. Fertig TE, Chitoiu L, Marta DS, Ionescu VS, Cismasiu VB, Radu E, , et al. Vaccine mRNA can be detected in blood at 15 days post-vaccination. Biomedicines 2022;10:1538. doi: 10.3390/biomedicines10071538
34. Golan Y, Prahl M, Cassidy A, Lin CY, Ahituv N, Flaherman VJ, , et al. Evaluation of messenger RNA from COVID-19 BTN162b2 and mRNA-1273 vaccines in human milk. JAMA Pediatr 2021;175:1069–71. doi:10.1001/jamapediatrics.2021.1929
35. Low JM, Gu Y, Ng MSF, Amin Z, Lee LY, Ng YPM, , et al. Codominant IgG and IgA expression with minimal vaccine mRNA in milk of BNT162b2 vaccinees. NPJ Vaccin 2021;6:105. doi:10.1038/s41541-021-00370-z
36. Yeo KT, Chia WN, Tan CW, Ong C, Yeo JG, Zhang J, , et al. Neutralizing activity and SARS-CoV-2 vaccine mRNA persistence in serum and breastmilk after BNT162b2 vaccination in lactating women. Front Immunol 2021;12:783975. doi:10.3389/fimmu.2021.783975
37. Hu Y, Thaler J, Nieuwland R. Extracellular vesicles in human milk. Pharmaceuticals 2021;14:1050. doi:10.3390/ph14101050
38. Chutipongtanate S, Morrow AL, Newburg DS. Human milk extracellular vesicles: a biological system with clinical implications. Cells 2022;11:2345. doi:10.3390/cells11152345
39. Liao Y, Du X, Li J, Lönnerdal B. Human milk exosomes and their microRNAs survive digestion in vitro and are taken up by human intestinal cells. Mol Nutr Food Res 2017;61:1700082. doi:10.1002/mnfr.201700082
40. Kowalski PS, Rudra A, Miao L, Anderson DG. Delivering the messenger: advances in technologies for therapeutic mRNA delivery. Mol Ther 2019;27:710–28. doi:10.1016/j.ymthe.2019.02.012
41. Pardi N, Hogan MJ, Porter FW, Weissman D. mRNA vaccines - a new era in vaccinology. Nat Rev Drug Discov 2018;17:261–79. doi:10.1038/nrd.2017.243
42. Tsui NBY, Ng EKO, Lo YD. Stability of endogenous and added RNA in blood specimens, serum, and plasma. Clin Chem 2002;48:1647–53. doi:10.1093/clinchem/48.10.1647
43. Kauffman KJ, Webber MJ, Anderson DG. Materials for non-viral intracellular delivery of messenger RNA therapeutics. J Controlled Release 2016;240:227–34. doi:10.1016/j.jconrel.2015.12.032
44. Atyeo CG, Shook LL, Brigida S, De Guzman RM, Demidkin S, Muir C, , et al. Maternal immune response and placental antibody transfer after COVID-19 vaccination across trimester and platforms. Nat Commun 2022;13:3571. doi:10.1038/s41467-022-31169-8
45. Theiler RN, Wick M, Mehta R, Weaver AL, Virk A, Swift M. Pregnancy and birth outcomes after SARS-CoV-2 vaccination in pregnancy. Am J Obstet Gynecol MFM 2021;3:100467. doi:10.1016/j.ajogmf.2021.100467
46. Shook LL, Atyeo CG, Yonker LM, Fasano A, Gray KJ, Alter G, , et al. Durability of anti-spike antibodies in infants after maternal COVID-19 vaccination or natural infection. JAMA 2022;327:1087–9. doi:10.1001/jama.2022.1206
47. Burns MD, Muir C, Atyeo C, Davis JP, Demidkin S, Akinwunmi B, , et al. Relationship between anti-spike antibodies and risk of SARS-CoV-2 infection in infants born to COVID-19 vaccinated mothers. Vaccines (Basel) 2022;10:1696. doi:10.3390/vaccines10101696
48. Halasa NB, Olson SM, Staat MA, et al. Maternal vaccination and risk of hospitalization for covid-19 among infants. N Engl J Med 2022;387:109–19. doi:10.1056/nejmoa2204399
49. Shimabukuro TT, Kim SY, Myers TR, Moro PL, Oduyebo T, Panagiotakopoulos L, , et al. Preliminary findings of mRNA covid-19 vaccine safety in pregnant persons [published erratum appears in N Engl J Med 2021;385:1536. N Engl J Med 2021;384:2273–82. doi:10.1056/NEJMoa2104983
50. Zauche LH, Wallace B, Smoots AN, Olson CK, Oduyebo T, Kim SY, , et al. Receipt of mRNA covid-19 vaccines and risk of spontaneous abortion. New Engl J Med 385:1533–5. doi:10.1056/NEJMc2113891
51. Lipkind HS, Vazquez-Benitez G, DeSilva M, Vesco KK, Ackerman-Banks C, Zhu J, , et al. Receipt of COVID-19 vaccine during pregnancy and preterm or small-for-gestational-age at birth - eight integrated health care organizations, United States, December 15, 2020-July 22, 2021. MMWR Morb Mortal Wkly Rep 2022;71:26–30. doi:10.15585/mmwr.mm7101e1
52. Atyeo C, Alter G. The multifaceted roles of breast milk antibodies. Cell 2021;184:1486–99. doi:10.1016/j.cell.2021.02.031
53. Andreas NJ, Kampmann B, Mehring Le-Doare K. Human breast milk: a review on its composition and bioactivity. Early Hum Develop 2015;91:629–35. doi:10.1016/j.earlhumdev.2015.08.013
54. Brandtzaeg P. Induction of secretory immunity and memory at mucosal surfaces. Vaccine 2007;25:5467–84. doi:10.1016/j.vaccine.2006.12.001
55. Rogier EW, Frantz AL, Bruno MEC, Wedlund L, Cohen DA, Stromberg AJ, , et al. Secretory antibodies in breast milk promote long-term intestinal homeostasis by regulating the gut microbiota and host gene expression. Proc Natl Acad Sci U S A 2014;111:3074–9. doi:10.1073/pnas.1315792111
56. Zheng W, Zhao W, Wu M, Song X, Caro F, Sun X, , et al. Microbiota-targeted maternal antibodies protect neonates from enteric infection. Nature 2020;577:543–8. doi:10.1038/s41586-019-1898-4
57. Mazur NI, Horsley NM, Englund JA, Nederend M, Magaret A, Kumar A, , et al. Breast milk prefusion F immunoglobulin G as a correlate of protection against respiratory syncytial virus acute respiratory illness. J Infect Dis 2019;219:59–67. doi:10.1093/infdis/jiy477
58. Gregory KE, Walker WA. Immunologic factors in human milk and disease prevention in the preterm infant. Curr Pediatr Rep 2013;1:222–8. doi:10.1007/s40124-013-0028-2
59. Muyldermans J, De Weerdt L, De Brabandere L, Maertens K, Tommelein E. The effects of COVID-19 vaccination on lactating women: a systematic review of the literature. Front Immunol 2022;13:852928. doi:10.3389/fimmu.2022.852928
60. Romero Ramírez DS, Lara Pérez MM, Carretero Pérez M, Suárez Hernández MI, Martín Pulido S, Pera Villacampa L, , et al. SARS-CoV-2 antibodies in breast milk after vaccination. Pediatrics 2021;148:e2021052286. doi:10.1542/peds.2021-052286
61. Juncker HG, Mulleners SJ, Ruhé EJM, Coenen ERM, Bakker S, van Doesburg M, , et al. Comparing the human milk antibody response after vaccination with four COVID-19 vaccines: a prospective, longitudinal cohort study in the Netherlands. EClinicalMedicine 2022;47:101393. doi:10.1016/j.eclinm.2022.101393
62. Rosenberg-Friedman M, Kigel A, Bahar Y, Werbner M, Alter J, Yogev Y, , et al. BNT162b2 mRNA vaccine elicited antibody response in blood and milk of breastfeeding women. Nat Commun 2021;12:6222. doi:10.1038/s41467-021-26507-1
63. Collier ARY, McMahan K, Yu J, Tostanoski LH, Aguayo R, Ansel J, , et al. Immunogenicity of COVID-19 mRNA vaccines in pregnant and lactating women. JAMA 2021;325:2370–80. doi:10.1001/jama.2021.7563
64. Narayanaswamy V, Pentecost BT, Schoen CN, Alfandari D, Schneider SS, Baker R, , et al. Neutralizing antibodies and cytokines in breast milk after coronavirus disease 2019 (COVID-19) mRNA vaccination. Obstet Gynecol 2022;139:181–91. doi:10.1097/aog.0000000000004661
65. Stafford L, Valcarce V, Henry M, Neu J, Parker L, Martina M, , et al. Detection of SARS-CoV-2 IgA and IgG in human milk and breastfeeding infant stool 6 months after maternal COVID-19 vaccination [preprint]. Res Sq 2022 Aug 19. doi:10.21203/
66. Perez SE, Luna Centeno LD, Cheng WA, Cheng WA, Marentes Ruiz CJ, Lee Y, , et al. Human milk SARS-CoV-2 antibodies up to 6 months after vaccination. Pediatrics 2022;149:e2021054260. doi:10.1542/peds.2021-054260
67. Bender JM, Lee Y, Cheng WA, Marentes Ruiz CJ, Pannaraj PS. Coronavirus disease 2019 vaccine booster effects are seen in human milk antibody response. Front Nutr 2022;9:898849. doi:10.3389/fnut.2022.898849
68. Schwartz A, Nir O, Toussia-Cohen S, Leibovich L, Strauss T, Asraf K, , et al. Presence of SARS-CoV-2 antibodies in lactating women and their infants following BNT162b2 messenger RNA vaccine. Am J Obstet Gynecol 2021;225:577–9. doi:10.1016/j.ajog.2021.07.016
69. Pieri M, Maniori MA, Shahabian L, Kanaan E, Paphiti-Demetriou I, Pipis S, , et al. Survival of vaccine-induced human milk SARS-CoV-2 IgG, IgA and SIgA immunoglobulins across simulated human infant gastrointestinal digestion. Nutrients 2022;14:3368. doi:10.3390/nu14163368
70. Calvo-Lerma J, Bueno-Llamoga P, Bäuerl C, Cortés-Macias E, Selma-Royo M, Pérez-Cano F, , et al. Persistence of anti SARS-CoV-2 antibodies in breast milk from infected and vaccinated women after in vitro-simulated gastrointestinal digestion. Nutrients 2022;14:2117. doi:10.3390/nu14102117
71. Gonçalves J, Juliano AM, Charepe N, Alenquer M, Athayde D, Ferreira F, , et al. Secretory IgA and T cells targeting SARS-CoV-2 spike protein are transferred to the breastmilk upon mRNA vaccination. Cell Rep Med 2021;2:100468. doi:10.1016/j.xcrm.2021.100468
72. Armistead B, Jiang Y, Carlson M, Ford ES, Jani S, Houck J, , et al. Spike-specific T cells are enriched in breastmilk following SARS-CoV-2 mRNA vaccination [preprint]. medRxiv 2022 Sep 28. doi:10.1101/2021.12.03.21267036
73. Molès JP, Tuaillon E, Kankasa C, Bedin AS, Nagot N, Marchant A, et al. Breastfeeding-related maternal microchimerism [letter]. Nat Rev Immunol 2017;17:729. doi:10.1038/nri.2017.115
74. Darby MG, Chetty A, Mrjden D, Rolot M, Smith K, Mackowiak C, , et al. Pre-conception maternal helminth infection transfers via nursing long-lasting cellular immunity against helminths to offspring. Sci Adv 2019;5:eaav3058. doi:10.1126/sciadv.aav3058
75. Camacho-Morales A, Caba M, García-Juárez M, Caba-Flores MD, Viveros-Contreras R, Martínez-Valenzuela C. Breastfeeding contributes to physiological immune programming in the newborn. Front Pediatr 2021;9:744104. doi:10.3389/fped.2021.744104
76. Atyeo C, DeRiso EA, Davis C, Bordt EA, De Guzman RM, Shook LL, , et al. COVID-19 mRNA vaccines drive differential antibody Fc-functional profiles in pregnant, lactating, and non-pregnant women. Sci Transl Med 2021;13:eabi8631. doi:10.1126/scitranslmed.abi8631
77. Waltz E. How nasal-spray vaccines could change the pandemic. Nature 2022;609:240–2. doi:10.1038/d41586-022-02824-3
78. Pannaraj PS, da Costa-Martins AG, Cerini C, Li F, Wong SS, Singh Y, , et al. Molecular alterations in human milk in simulated maternal nasal mucosal infection with live attenuated influenza vaccination. Mucosal Immunol 2022;15:1040–7. doi:10.1038/s41385-022-00537-4
79. Abbasi J. Widespread misinformation about infertility continues to create COVID-19 vaccine hesitancy. JAMA 2022;327:1013–5. doi:10.1001/jama.2022.2404
80. KFF. Misinformation about COVID-19 vaccines and pregnancy is widespread, including among women who are pregnant or planning to get pregnant. Accessed November 7, 2022.

Supplemental Digital Content

© 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.