Next Article in Journal
Acute Antibody-Mediated Rejection in Liver Transplant Recipients with Autoimmune Liver Disease: A Clinical and Pathologic Study of 4 Cases
Next Article in Special Issue
Impacts of the COVID-19 Pandemic on Anxiety and Depressive Symptoms in Pregnant Women and Related Perinatal Outcomes
Previous Article in Journal
Urine-Based Detection of Biomarkers Indicative of Chronic Kidney Disease in a Patient Cohort from Ghana
Previous Article in Special Issue
Comparison of Maternal–Fetal Outcomes among Unvaccinated and Vaccinated Pregnant Women with COVID-19
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:

COVID-19 Vaccines during Pregnancy and Breastfeeding: A Systematic Review

Department of Obstetrics and Gynaecology, La Fe University and Polytechnic Hospital, Avenida Fernando Abril Martorell 106, 46026 Valencia, Spain
Author to whom correspondence should be addressed.
J. Pers. Med. 2023, 13(1), 40;
Received: 6 December 2022 / Revised: 18 December 2022 / Accepted: 23 December 2022 / Published: 25 December 2022


Background: Pregnant and breastfeeding women received unclear recommendations regarding COVID-19 vaccination at the beginning of the pandemic, as they were not included in the initial clinical trials. This systematic review aims to provide an update regarding COVID-19 vaccines during pregnancy and breastfeeding. Methods: The systematic review was carried out through a literature search in Medline/Pubmed. Studies were selected if they included information regarding COVID-19 vaccination during pregnancy and breastfeeding. The PRISMA guidelines for systematic reviews were followed. Results: A total of 33 studies were included. The main adverse effect is pain at the injection site, as in the general population. Adverse effects are more frequent after the second dose, being slightly more frequent after the Moderna vaccine. COVID-19 vaccination reduces the risk of severe COVID-19 in pregnant women. Additionally, COVID-19 vaccination induces artificial active immunogenicity in the mother and natural passive immunogenicity in the child. Breastmilk straddles both immediate antibody-mediated and long-lived cellular-mediated immune protection. Regarding neonatal benefits, vaccination is associated with a larger and more stable Immunoglobulin G response, while COVID-19 Infection is associated with a rapid and long-lasting Immunoglobulin A response. Conclusions: COVID-19 vaccines are not only suggested but strongly recommended for pregnant and breastfeeding populations to protect mothers and newborns.

1. Introduction

Pregnancy is a stressful situation for the human body. The pregnant woman undergoes well-known physiological changes in her respiratory and cardiovascular systems [1,2]. Pregnancy is associated to a procoagulant and proinflammatory state [3,4]. Moreover, the maternal immune system has to achieve an immune tolerance toward the fetus [3], which entails a decrease in responses to viral infections [3]. All of these features make pregnant women, particularly those with chronic diseases, susceptible to severe COVID-19 disease [5,6].
Pregnant women develop a more severe COVID-19 disease compared to non-pregnant patients [7]. In addition, pregnant patients with SARS-CoV-2 infection experience a higher rate of preterm birth, cesarean birth, and stillbirth compared to non-infected pregnant women [8,9]. Moreover, COVID-19 during pregnancy has been associated with preeclampsia [10,11], especially among nulliparous women [11].
The best strategy to fight against infections is immunization through vaccination [7]. This becomes even more efficient in pregnant and lactating women, achieving double immunization with a single administration: active artificial for the mother and passive natural for the fetus [12].
Nonetheless, pregnant and lactating women received unclear recommendations regarding COVID-19 vaccination at the beginning of the pandemic, because they were not included in the first clinical trials. Accordingly, the acceptance of the COVID-19 vaccine in the pregnant and lactating populations has been reported to be limited [13,14,15,16]. This systematic review aims to analyze the growing body of evidence regarding the safety, efficacy, and immunogenicity of SARS-CoV-2 vaccination during pregnancy and lactation.

2. Materials and Methods

This systematic review was carried out according to PRISMA guidelines [17,18]. The search guidelines used were MEDLINE/ PUBMED. The search terms used were “COVID-19 vaccines AND pregnancy” and “COVID-19 vaccines AND breastfeeding”. ZOTERO was used to arrange articles and eliminate duplicates. The literature search was performed, and all published studies from the 1 December 2019 to the 5 December 2022 were initially selected.
Inclusion criteria were studies regarding COVID-19 vaccines and pregnant and/or breastfeeding women as well as quantitative studies. Articles regarding pregnant women were included regardless of the week of gestation. Studies concerning breastfeeding women were also included, irrespective of the age of the children. The exclusion criteria were review articles, non-human studies, and studies with less than 10 participants. There were no language restrictions.
A second researcher double-checked that the selected abstracts met the criteria. Disagreements were resolved by discussion and consensus. Data were then collected by reading the articles that were finally included.

3. Results

Combined database searches yielded 1893 articles, as shown in Figure 1. A total of 33 studies were ultimately included. The PRISMA flow chart shown in Figure 1 reveals the search process for the systematic review.
Study characteristics are described in Table 1. The vast majority of studies had a cohort design. Three studies used a cross-sectional design [19,20,21], and two used a case-control design [22,23].
Regarding the comparison of vaccines, most studies compare vaccines made by messenger ribonucleic acid (mRNA) technology: Pfizer (BNT162b2) and Moderna (mRNA-1273). However, four studies included the AstraZeneca vaccine (ChAdOx1-S) [20,24,25,26], a Brazilian study included the CoronaVac (Biotech) vaccine [27], and one study included the Janssen (Johnson & Johnson) (NCT04505722) vaccine [23].
Table 1. Characteristics of the studies included in the systematic review.
Table 1. Characteristics of the studies included in the systematic review.
AuthorPopulationNStudy DesignVaccine TypeNo DoseCountryDate of Publication
Atyeo [28] Pregnant, breastfeeding and non-pregnant.131Observational cohortPfizer or Moderna2USA10/2021
Bertrand [29]Breastfeeding vaccinated180Observational cohortPfizer or Moderna1 or 2USA08/2021
Calil [27] Breastfeeding vaccinated20Observational cohortCoronaVac (Biotech)2Brazil06/2021
Charepe [30]Breastfeeding and not24Observational cohortPfizer2Portugal09/2021
Collier [31]Pregnant and breastfeeding vaccinated
unvaccinated infected
131Observational cohortPfizer or ModernaDoes not specifyUSA03/2021
Esteve-Palau [32]Breastfeeding vaccinated33Observational cohortPfizer2Spain08/2021
Rosenberg-Friedman [33]Breastfeeding vaccinated10Observational cohortPfizer2Israel03/2021
Golan [34]Breastfeeding vaccinated50Observational cohortPfizer or Moderna 2USA11/2021
Gonçalves [35]Breastfeeding, vaccinated23Observational cohortPfizer or
Gray [36]Pregnant, breastfeeding and non-pregnant.131Observational cohortPfizer or Moderna1 or 2USA09/2021
Guida [37]Breastfeeding, vaccinated10Observational cohortPfizer2Italy07/2021
Jakuszko [38]Breastfeeding vaccinated and not vaccinated60Observational cohortPfizer2Poland06/2021
Juncker [39]Breastfeeding vaccinated26Observational cohortPfizer2Netherlands08/2021
Kachikis [40]Pregnant, breastfeeding and planning pregnancy vaccinated.17,525Observational cohortPfizer or Moderna1 or 2 USA08/2021
Kadali [19]Pregnant vaccinated38Cross-sectionalPfizer or Moderna1 or 2USA10/2021
Lechosa-Muñiz [20]Breastfeeding vaccinated110Cross-SectionalPfizer, Moderna, or AstraZeneca 1 or 2Spain08/2021
Low [41]Breastfeeding, vaccinated or unvaccinated or infected25Observational cohortPfizer2Singapore08/2021
McLaurin-Jiang [21]Breastfeeding vaccinated4455Cross-sectionalPfizer or Moderna1 or 2USA06/2021
Mithal [42]Pregnant vaccinated27Observational cohortPfizer or Moderna1 or 2USA08/2021
Montalti [43]Breastfeeding and pregnant600Observational cohortPfizer2Italy08/2021
Olearo [44]Breastfeeding, vaccinated or not, having had de infection or not21Observational cohortPfizer1 or 2Germany09/2022
Perez [45]Pregnant or breastfeeding vaccinated30Observational cohortPfizer or Moderna1USA02/2022
Perl [46]Breastfeeding vaccinated84Observational cohortPfizer2Israel04/2021
Pietrasanta [47]Breastfeeding vaccinated and their babies24Observational cohortPfizer2Italy06/2022
Prabhu [48]Pregnant vaccinated122Observational cohortPfizer or Moderna1 or 2USA04/2021
Rottenstreich [49]Pregnant vaccinated20Observational cohortPfizer2Israel04/2021
Scrimin [50]Breastfeeding vaccinated, infected or not42Observational cohortPfizer, Moderna, or AstraZeneca 1 or 2Italy01/2022
Selma-Royo [25]Breastfeeding vaccinated vs Breastfeeding not vaccinated86Observational cohortPfizer, Moderna, or AstraZeneca 2Spain04/2021
Shanes [22]Pregnant vaccinated and unvaccinated200Case controlNot mentionedNot mentionedUSA08/2021
Shimabukuro [51]Pregnant vaccinated35,691Observational cohortPfizer or Moderna1 or 2USA04/2021
Theiler [23]Pregnant vaccinated vs not vaccinated2002Case- controlPfizer, Janssen, or Moderna1 or 2USA11/2021
Young [17]Breastfeeding vaccinated or infected77Observational cohortModerna or Pfizer2USA11/2021
Martínez-Varea [26]Pregnant infected vaccinated or not487Observational cohortPfizer, Moderna, or AstraZeneca2Spain12/2022

3.1. Safety

A total of 9 articles have been found that discussed the side effects of vaccination [19,20,21,22,23,29,40,43,51]. Most of them detected no [22] or minor side effects. In the largest prospective cohort (17,525 patients), the main side effects were pain at the injection site (92%) and fatigue (30% and 70% after the second dose) [40]. These side effects were similar to the general population [19]. Among lactating women, decreased milk supply <24 h was described in 7%, with few or no subsequent repercussions, and 2% presented interrupted breastfeeding [40]. Other side effects were general malaise (18.2% of the women), adenopathy (18.2%), headache (9.1%), fever (6.4%), and nausea (0.9%). No side effects were described in 34.5% of the women (20).
Slightly more adverse effects and decreased milk supply have been reported with the Moderna vaccine [29]. A Spanish study administered the AstraZeneca vaccine to 18.2% of the 110 patients. The most frequent side effects of the AstraZeneca vaccine were general malaise and lymphadenopathy [20].
Several studies agree about more adverse effects after the second dose, such as fatigue, nausea/vomiting, headache, or arthralgia/myalgia [21,23,29,43]. Nonetheless, all of them are considered minor adverse effects.
Adverse obstetrical outcomes were not described in association with COVID-19 vaccines [51]. The abortion rate was similar to that of the general population [51].
On the other hand, the presence of mARN vaccines in some milk samples (maximum 2 ng/mL) [41] were reported, which does not damage the newborn [41].

3.2. Efficacy

A recently published study among 487 pregnant women with SARS-CoV-2 infection showed that vaccinated patients had an 80% lower risk for developing pneumonia and hospital admission due to COVID-19 than unvaccinated patients. Moreover, vaccinated pregnant patients with COVID-19 were associated to a lower composite adverse maternal outcome and requirement of antibiotics, corticosteroids, and oxygen therapy compared to unvaccinated patients [26]. Furthermore, no severe COVID-19 was found among pregnant patients vaccinated with at least two doses [26]. Theiler et al. studied a cohort of 2002 pregnant women in which the unvaccinated patients underwent a higher incidence of COVID-19 compared with the vaccinated patients [23].

3.3. Immunogenicity

Most of the studies focus their aim on the humoral response, quantifying the immunoglobulin isotypes. Several authors have studied immunoglobulin A (IgA). An Italian study analyzes the immunity of breastfed babies by mothers vaccinated during lactation [47]. Only the IgA1 isotype was found in milk, and the study was unable to demonstrate significant mucosal IgA2. The authors did not find a significant amount of antibodies in babies’ buccal swabs or feces [47]. Thus, they conclude that vaccination induces a strong Immunoglobulin G (IgG) humoral response in maternal serum and is lower in breast milk (10–150 times fewer immunoglobulins in milk than in maternal serum) [47].
Golan et al. did not find IgA in milk in 25% of the mothers. Additionally, 83% of them had children older than 5.5 months. The authors conclude that there is less IgA in the mother’s milk of older babies [34]. Another study found no relationship between IgA and the age of the newborn [35].
If vaccination and natural infection are compared, the presence and dynamics of antibodies are different. A study that included 2312 women concluded that IgA was detectable in milk 10 months after the infection [39]. In a lactating vaccinated population, the authors describe a biphasic IgA response. It rises a week after the first dose and a week after the second dose, reaching 85% positivity, but decreases quickly [39]. Perl et al. showed that 86.1% of the samples were positive for IgA a week after the second dose, this value reducing to 65.7% of samples a week later [46]. Scrimin et al. showed the absence of IgA in serum and breast milk 20 days after the second vaccine dose [50]. However, a Brazilian study observed IgA rises from 2 weeks post-vaccination and peaks at 5–6 weeks [27]. Nonetheless, only 20 patients were included in this study [27]. Young et al. showed IgA increases in human milk only after the first dose, reducing after the second dose [17]. These data were confirmed by other studies [36].
Some studies also analyze the dynamics of IgG. Scrimin and Esteve-Palau et al. showed long-lasting IgG in both serum and breast milk after the second vaccine. IgG was detected four weeks [32,50] and even six months after vaccination, gradually decreasing its efficacy [45]. Perl et al. detected IgG antibodies in 97% of samples 5–6 weeks after the first dose [46]. Jakusszko et al. described that the IgG response was strongest seven days after the second vaccine dose [38]. Gray et al. also showed an increase in IgG in serum and milk after the second dose [36], and a Portuguese study concluded that the main response to vaccination was IgG-mediated [30].
A prospective cohort of 86 breastfeeding women, vaccinated or not, described similar IgG quantification in patients who were infected and recovered from COVID-19 disease after the first vaccine dose compared to patients vaccinated after the second dose without suffering the infection [25].
Regarding the relationship between milk and serum antibody levels, Golan et al. observed a positive relation measured 4–10 weeks after the second dose. However, levels were similar after the first dose [34]. Friedman et al. described that antibody response is rapid and highly synchronized between breastmilk and serum, reaching stabilization 14 days after the second dose [33]. Moreover, in 84% of the cases, IgG was detected in serum longer than in breast milk [24]. An Italian cohort did not find a correlation between serum and milk [37].
The ratio IgG-IgA has also been quantified [25,41]. Low et al. described that the amount of IgA and IgG reached its maximum at 3–7 days after the second dose. However, IgG is more stable and is even detected 4–6 weeks after vaccination [41].
Apart from A and G, other isotypes of immunoglobulin have been studied. Previous studies agree with Golan et al. who concluded that high levels of immunoglobulin M (IgM) and IgG are found in the serum of vaccinated mothers. IgG is multiplied by 6 with the second vaccine dose (which doesn’t occur with IgM) [34]. The function of IgG was not modified after pasteurization but it inactivated isotypes M and A [45].
In a Spanish cohort of 86 patients, 32 were vaccinated with AstraZeneca. Authors describe that the presence and persistence of specific antibodies against SARS-CoV-2 in breast milk depended on the type of vaccine, with this being stronger for the mRNA vaccines than the AstraZeneca one [25].
A more efficient passive immunity has also been described in vaccinated women (starting 16 days after the first dose) [48] than in women who recovered from COVID-19 infection. This finding was also described by Olearo et al., who compared infected lactating women who were vaccinated and not vaccinated. The transfer of antibodies to breast milk was significantly higher in women who recovered from COVID-19 and were vaccinated during lactation versus recovered unvaccinated women [44]. Even though the efficacy of passive immunity for the COVID-19 vaccine has been proven, it is weaker than passive immunity induced by other classical vaccines, such as the flu and whooping cough [49].
Atyeo et al. analyzed a cohort of 131 women to compare their response to vaccination. They observed that the titre of antibodies was similar. Nonetheless, the junction to the Fc receptor and the function of the antibody was induced later after the first vaccine in pregnant and lactating populations, compared to not pregnant and not lactating individuals [28]. This catches up after the second dose [28].
There is a stronger transfer of antibodies to the newborn if early vaccination occurs during pregnancy. A latency of weeks was described for vaccine response [42]. This latency was also observed for milk donors [42] as well as infected unvaccinated patients [26].

4. Discussion

In this systematic review of vaccination during pregnancy and breastfeeding, it was found that vaccination is safe for pregnant and breastfeeding women. The main adverse effects were pain at the injection site and fatigue. These women are not more susceptible to adverse effects than the general population [19]. Adverse effects, such as fatigue, headache, and myalgia, are more frequent after the second dose and are slightly more frequent after the Moderna vaccine [21,23,29,43].
Furthermore, the vaccine does not lead to adverse obstetrics outcomes [40,51]. Evidence refutes the alarm raised by preliminary studies, which warned of an 82% risk of spontaneous abortion [52].
The studies about the vaccine’s efficacy agree that vaccination in pregnant women reduces the risk of severe infection in this population [23,26], who are more susceptible to developing severe COVID-19 disease [5,6,9,11]. Vaccination also reduces the risk of developing pneumonia, hospital admission, and the requirement for antibiotics, corticosteroids, and oxygen therapy [26].
The humoral response to COVID-19 vaccination has been widely studied [17,25,30,32,33,34,36,38,39,41,46,47,50]. Recent studies focus on clarifying the mother–child transmission of the cellular response [31,35]. Following mRNA vaccination, immune transfer into breast milk occurs through a combination of spike-reactive secretory antibodies (SIgA) secreted by mammary mucosa-associated lymphoid tissue (MALT) (90% of the total Ig), IgG, T cells, and bioactive factors such as lactoferrin, oligosaccharides, and cytokines [50]. These lines of defense could create synergies by conferring both immediate (SIgA) and long-lasting (T cell) immunity [35]. T-lymphocytes survive and seed in the newborn’s respiratory and gastrointestinal tracts. Memory T cells are long-lived. Therefore, the protection transferred by milk can be present in the baby even after stopping breastfeeding [35]. In addition, a longer-lived memory B cell response has been observed in lactating women [35]. Therefore, breastmilk straddles an immediate antibody-mediated and long-lived cellular-mediated immune protection [31,35].
According to Pietrasanta et al., vaccination induces a stronger immune response in maternal serum than in milk because IgA was not found in infants’ mucosae [47]. This finding has a physiological reason, as IgA2 is the only one resistant to protease. When authors conclude that the immune response in milk is weaker, they could be underestimating natural passive immunity because the cellular response is not analyzed [47]. Regarding the evolution of IgA and the age of the newborn, there are contradictory conclusions: from none [35] to a negative relationship [34].
The vast majority of studies are consistent about immunoglobulin dynamics in response to vaccination and infection [25,30,32,33,34,38,41,45,46,50]. The presence and dynamics of antibodies are different. IgA levels was detectable in women’s serum seven days post vaccination. They decrease two weeks after vaccination, being undetectable twenty days after vaccination [39,46,50]. However, IgG could be detected four weeks after vaccination [32,46,50]. Therefore, vaccination is associated with a larger and more stable IgG response (IgA decreases faster than IgG), while infection is associated with a rapid and long-lasting IgA response [17,25,30,36]. The vaccination response is optimal using mRNA vaccines [25]. IgG is more stable [25,41] and is the only isotype not inactivated by pasteurization [45].
A Spanish study concluded that artificial active immunogenicity acquired after vaccination is similar to natural active immunogenicity developed after infection [25]. However, a more efficient passive immunity in vaccinated women [48] than in women who recovered from COVID-19 infection has also been described. Furthermore, passive immunity for the COVID-19 vaccine is weaker than passive immunity induced by other classical vaccines such as the flu and whooping cough [49].
A similar quantitative but lower efficacy immune response to the vaccine in pregnant and breastfeeding women has been described compared to the general population [28]. The immune response is equalized after the second dose [28]. Thus, pregnant and lactating women should be encouraged to complete the vaccination schedule. Moreover, it is optimal to do it as soon as possible to compensate for the immune response latency [28,42].
Most studies found a positive relation between milk and serum antibody levels [33,34,50], with the exception of the Italian cohort [37]. These contradictory data could be explained because the latter study only included ten patients in the cohort [37].
The findings of this review are consistent with the results of existing systematic reviews on this topic [53,54]. However, these reviews were limited by their inclusion of fewer studies written before publication. COVID-19 has posed a challenge to researchers and clinicians, who have had to update daily in the face of the significant growth of scientific literature at an unprecedented speed.
Several weaknesses in the underlying literature were identified. The sample size of most of the studies was not a randomized sample from the general population. The Healthy volunteer bias could also have been committed. Furthermore, there were many healthcare workers, as they were the first young population to be vaccinated. However, working in healthcare was not associated with an increased vaccine acceptance [13,14,15,16]. Interestingly, white and Asian pregnant individuals were more likely to accept vaccination [13].
The strengths of this study include a comprehensive search strategy and the inclusion of a large and updated number of studies regarding COVID-19 vaccination during pregnancy and breastfeeding. However, the heterogeneity of the data reported in the literature prevented the authors from performing a meta-analysis. Future studies are needed to investigate COVID-19 vaccines and their long-term consequences. Additionally, research concerning immunogenicity with a larger number of patients is required.

5. Conclusions

This systematic review has shown the safety of COVID-19 vaccination during pregnancy and breastfeeding. The minor side effects were pain at the injection site and fatigue. This study also proves the efficacy of vaccination, given that it reduces the risk of severe COVID-19 in pregnant women.
Passive immunity, both in terms of cellular and humoral immune response, for the COVID-19 vaccine has been proven. The vaccination response is optimal using mRNA vaccines. Vaccination is associated with a larger and more stable IgG response and infection with a rapid and long-lasting IgA response.
Thus, COVID-19 vaccination is not only suggested but strongly recommended for pregnant and breastfeeding populations to protect mothers and newborns.

Author Contributions

A.M.-V. and B.N. performed the work’s conceptualization, methodology, and design. A.M.-V. supervised the research work. B.N. and A.M.-V. wrote the original draft. All authors have read and agreed to the published version of the manuscript.


This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Patient consent was waived due to the retrospective nature of this review study.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.


Messenger ribonucleic acidmARN
Immunoglobulin A, G, MIgA, IgG, IgM


  1. Ouzounian, J.G.; Elkayam, U. Physiologic changes during normal pregnancy and delivery. Cardiol. Clin. 2012, 30, 317–329. [Google Scholar] [CrossRef] [PubMed]
  2. Meah, V.L.; Cockcroft, J.R.; Backx, K.; Shave, R.; Stohr, E.J. Cardiac output and related haemodynamics during pregnancy: A series of meta-analyses. Heart 2016, 102, 518–526. [Google Scholar] [CrossRef] [PubMed]
  3. Mor, G.A. The immunology of pregnancy. In Creasy and Resnik’s Maternal-Fetal Medicine: Principles and Practice, 7th ed.; Creasy, R.K., Resnik, R., Iams, J.D., Lockwood, C.J., Moore, T.R., Greene, M., Eds.; Elsevier: Philadelphia, PA, USA, 2014; p. 80. [Google Scholar]
  4. Bauer, K.A. Maternal Adaptations to Pregnancy: Hematologic Changes 2022. Available online: (accessed on 1 November 2022).
  5. Allotey, J.; Stallings, E.; Bonet, M.; Yap, M.; Chatterjee, S.; Kew, T.; Zhou, D.; Coomar, D.; Sheikh, J.; Lawson, H.; et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: Living systematic review and meta-analysis. BMJ 2020, 370, m3320. [Google Scholar] [CrossRef] [PubMed]
  6. WAPM (World Association of Perinatal Medicine) Working Group on COVID-19. Maternal and perinatal outcomes of pregnant women with SARS-CoV-2 infection. Ultrasound Obstet. Gynecol. 2021, 57, 232–241. [Google Scholar] [CrossRef] [PubMed]
  7. Berghella, V.; Hughes, B.L. COVID-19: Overview of Pregnancy Issues. 2022. Available online: (accessed on 1 November 2022).
  8. McClymont, E.; Albert, A.Y.; Alton, G.D.; Boucoiran, I.; Castillo, E.; Fell, D.B.; Kuret, V.; Poliquin, V.; Reeve, T.; Scott, H.; et al. Association of SARS-CoV-2 Infection During Pregnancy with Maternal and Perinatal Outcomes. JAMA 2022, 327, 1983–1991. [Google Scholar] [CrossRef]
  9. Villar, J.; Ariff, S.; Gunier, R.B.; Thiruvengadam, R.; Rauch, S.; Kholin, A.; Roggero, P.; Prefumo, F.; do Vale, M.S.; Cardona-Perez, J.A.; et al. Maternal and Neonatal Morbidity and Mortality Among Pregnant Women with and Without COVID-19 Infection: The INTERCOVID Multinational Cohort Study. JAMA Pediatr. 2021, 175, 817–826. [Google Scholar] [CrossRef]
  10. Conde-Agudelo, A.; Romero, R. SARS-CoV-2 infection during pregnancy and risk of preeclampsia: A systematic review and meta-analysis. Am. J. Obstet. Gynecol. 2022, 226, 68–89.e3. [Google Scholar] [CrossRef]
  11. Papageorghiou, A.T.; Deruelle, P.; Gunier, R.B.; Rauch, S.; Garcia-May, P.K.; Mhatre, M.; Usman, M.A.; Abd-Elsalam, S.; Etuk, S.; Simmons, L.E.; et al. Preeclampsia and COVID-19: Results from the INTERCOVID prospective longitudinal study. Am. J. Obstet. Gynecol. 2021, 225, 289.e1–289.e17. [Google Scholar] [CrossRef]
  12. Englund, J.A. The influence of maternal immunization on infant immune responses. J. Comp. Pathol. 2007, 137 (Suppl. 1), S16–S19. [Google Scholar] [CrossRef]
  13. Sutton, D.; D’Alton, M.; Zhang, Y.; Kahe, K.; Cepin, A.; Goffman, D.; Staniczenko, A.; Yates, H.; Bugansky, A.; Coletta, J.; et al. COVID-19 vaccine acceptance among pregnant, breastfeeding, and nonpregnant reproductive-aged women. Am. J. Obstet. Gynecol. MFM 2021, 3, 100403. [Google Scholar] [CrossRef]
  14. Goncu Ayhan, S.; Oluklu, D.; Atalay, A.; Menekse Beser, D.; Tanacan, A.; Moraloglu Tekin, O.; Sahin, D. COVID-19 vaccine acceptance in pregnant women. Int. J. Gynaecol. Obstet. 2021, 154, 291–296. [Google Scholar] [CrossRef] [PubMed]
  15. Skjefte, M.; Ngirbabul, M.; Akeju, O.; Escudero, D.; Hernandez-Diaz, S.; Wyszynski, D.F.; Wu, J.W. COVID-19 vaccine acceptance among pregnant women and mothers of young children: Results of a survey in 16 countries. Eur. J. Epidemiol. 2021, 36, 197–211. [Google Scholar] [CrossRef]
  16. Tao, L.; Wang, R.; Han, N.; Liu, J.; Yuan, C.; Deng, L.; Han, C.; Sun, F.; Liu, M.; Liu, J. Acceptance of a COVID-19 vaccine and associated factors among pregnant women in China: A multi-center cross-sectional study based on health belief model. Hum. Vaccines Immunother. 2021, 17, 2378–2388. [Google Scholar] [CrossRef] [PubMed]
  17. Young, B.E.; Seppo, A.E.; Diaz, N.; Rosen-Carole, C.; Nowak-Wegrzyn, A.; Cruz Vasquez, J.M.; Ferri-Huerta, R.; Nguyen-Contant, P.; Fitzgerald, T.; Sangster, M.Y.; et al. Association of Human Milk Antibody Induction, Persistence, and Neutralizing Capacity With SARS-CoV-2 Infection vs mRNA Vaccination. JAMA Pediatr. 2022, 176, 159–168. [Google Scholar] [CrossRef] [PubMed]
  18. Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Akl, E.A.; Brennan, S.E.; et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ 2021, 372, n71. [Google Scholar] [CrossRef]
  19. Kadali, R.A.K.; Janagama, R.; Peruru, S.R.; Racherla, S.; Tirumala, R.; Madathala, R.R.; Gajula, V. Adverse effects of COVID-19 messenger RNA vaccines among pregnant women: A cross-sectional study on healthcare workers with detailed self-reported symptoms. Am. J. Obstet. Gynecol. 2021, 225, 458–460. [Google Scholar] [CrossRef]
  20. Lechosa-Muniz, C.; Paz-Zulueta, M.; Mendez-Legaza, J.M.; Irure-Ventura, J.; Cuesta Gonzalez, R.; Calvo Montes, J.; López-Hoyos, M.; Llorca, J.; Cabero-Pérez, M.J. Induction of SARS-CoV-2-Specific IgG and IgA in Serum and Milk with Different SARS-CoV-2 Vaccines in Breastfeeding Women: A Cross-Sectional Study in Northern Spain. Int. J. Environ. Res. Public Health 2021, 18, 8831. [Google Scholar] [CrossRef]
  21. McLaurin-Jiang, S.; Garner, C.D.; Krutsch, K.; Hale, T.W. Maternal and Child Symptoms Following COVID-19 Vaccination Among Breastfeeding Mothers. Breastfeed Med. 2021, 16, 702–709. [Google Scholar] [CrossRef]
  22. Shanes, E.D.; Otero, S.; Mithal, L.B.; Mupanomunda, C.A.; Miller, E.S.; Goldstein, J.A. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccination in Pregnancy: Measures of Immunity and Placental Histopathology. Obstet. Gynecol. 2021, 138, 281–283. [Google Scholar] [CrossRef]
  23. Theiler, R.N.; Wick, M.; Mehta, R.; Weaver, A.L.; Virk, A.; Swift, M. Pregnancy and birth outcomes after SARS-CoV-2 vaccination in pregnancy. Am. J. Obstet. Gynecol. MFM 2021, 3, 100467. [Google Scholar] [CrossRef]
  24. Abbott, D.S.; Radford, S.K.; Seed, P.T.; Tribe, R.M.; Shennan, A.H. Evaluation of a quantitative fetal fibronectin test for spontaneous preterm birth in symptomatic women. Am. J. Obstet. Gynecol. 2013, 208, 122.e1–122.e6. [Google Scholar] [CrossRef] [PubMed]
  25. Selma-Royo, M.; Bauerl, C.; Mena-Tudela, D.; Aguilar-Camprubi, L.; Perez-Cano, F.J.; Parra-Llorca, A.; Lerin, C.; Martínez-Costa, C.; Collado, M.C. 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. [Google Scholar] [CrossRef]
  26. Martínez-Varea, A.; Satorres, E.; Florez, S.; Domenech, J.; Desco-Blay, J.; Monfort-Pitarch, S.; Hueso, M.; Perales-Marín, A.; Diago-Almela, V. Comparison of Maternal–Fetal Outcomes among Unvaccinated and Vaccinated Pregnant Women with COVID-19. J. Pers. Med. 2022, 12, 2008. [Google Scholar] [CrossRef] [PubMed]
  27. Calil, V.; Palmeira, P.; Zheng, Y.; Krebs, V.L.J.; Carvalho, W.B.; Carneiro-Sampaio, M. CoronaVac can induce the production of anti-SARS-CoV-2 IgA antibodies in human milk. Clinics 2021, 76, e3185. [Google Scholar] [CrossRef] [PubMed]
  28. Atyeo, C.; DeRiso, E.A.; Davis, C.; Bordt, E.A.; De Guzman, R.M.; Shook, L.L.; Yonker, L.M.; Fasano, A.; Akinwunmi, B.; Lauffenburger, D.A.; et al. COVID-19 mRNA vaccines drive differential antibody Fc-functional profiles in pregnant, lactating, and nonpregnant women. Sci. Transl. Med. 2021, 13, eabi8631. [Google Scholar] [CrossRef] [PubMed]
  29. Bertrand, K.; Honerkamp-Smith, G.; Chambers, C.D. Maternal and Child Outcomes Reported by Breastfeeding Women Following Messenger RNA COVID-19 Vaccination. Breastfeed Med. 2021, 16, 697–701. [Google Scholar] [CrossRef]
  30. Charepe, N.; Gonçalves, J.; Juliano, A.M.; Lopes, D.G.; Canhão, H.; Soares, H.; Serrano, E.F. COVID-19 mRNA vaccine and antibody response in lactating women: A prospective cohort study. BMC Pregnancy Childbirth 2021, 21, 632. [Google Scholar] [CrossRef]
  31. Collier, A.Y.; McMahan, K.; Yu, J.; Tostanoski, L.H.; Aguayo, R.; Ansel, J.; Chandrashekar, A.; Patel, S.; Bondzie, E.A.; Sellers, D.; et al. Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women. JAMA 2021, 325, 2370–2380. [Google Scholar] [CrossRef]
  32. Esteve-Palau, E.; Gonzalez-Cuevas, A.; Guerrero, M.E.; Garcia-Terol, C.; Alvarez, M.C.; Casadevall, D.; Diaz-Brito, V. Quantification of Specific Antibodies Against SARS-CoV-2 in Breast Milk of Lactating Women Vaccinated With an mRNA Vaccine. JAMA Netw. Open 2021, 4, e2120575. [Google Scholar] [CrossRef]
  33. Rosenberg-Friedman, M.; Kigel, A.; Bahar, Y.; Werbner, M.; Alter, J.; Yogev, Y.; Dror, Y.; Lubetzky, R.; Dessau, M.; Gal-Tanamy, M.; et al. BNT162b2 mRNA vaccine elicited antibody response in blood and milk of breastfeeding women. Nat. Commun. 2021, 12, 6222. [Google Scholar] [CrossRef]
  34. Golan, Y.; Prahl, M.; Cassidy, A.G.; Gay, C.; Wu, A.H.B.; Jigmeddagva, U.; Lin, C.Y.; Gonzalez, V.J.; Basilio, E.; Chidboy, M.A.; 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. [Google Scholar] [CrossRef] [PubMed]
  35. Goncalves, J.; Juliano, A.M.; Charepe, N.; Alenquer, M.; Athayde, D.; Ferreira, F.; Archer, M.; Amorim, M.J.; Serrano, F.; Soares, H. 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. [Google Scholar] [CrossRef] [PubMed]
  36. Gray, K.J.; Bordt, E.A.; Atyeo, C.; Deriso, E.; Akinwunmi, B.; Young, N.; Baez, A.M.; Shook, L.L.; Cvrk, D.; James, K.; et al. Coronavirus disease 2019 vaccine response in pregnant and lactating women: A cohort study. Am. J. Obstet. Gynecol. 2021, 225, 303.e1–303.e17. [Google Scholar] [CrossRef] [PubMed]
  37. Guida, M.; Terracciano, D.; Cennamo, M.; Aiello, F.; La Civita, E.; Esposito, G.; Gargiulo, V.; Maruotti, G.; Portella, G.; Sarno, L. COVID-19 Vaccine mRNABNT162b2 Elicits Human Antibody Response in Milk of Breastfeeding Women. Vaccines 2021, 9, 785. [Google Scholar] [CrossRef] [PubMed]
  38. Jakuszko, K.; Kościelska-Kasprzak, K.; Żabińska, M.; Bartoszek, D.; Poznański, P.; Rukasz, D.; Kłak, R.; Królak-Olejnik, B.; Krajewska, M. Immune Response to Vaccination against COVID-19 in Breastfeeding Health Workers. Vaccines 2021, 9, 663. [Google Scholar] [CrossRef] [PubMed]
  39. Juncker, H.G.; Mulleners, S.J.; van Gils, M.J.; de Groot, C.J.M.; Pajkrt, D.; Korosi, A.; van Goudoever, J.B.; van Keulen, B.J. The Levels of SARS-CoV-2 Specific Antibodies in Human Milk Following Vaccination. J. Hum. Lact. 2021, 37, 477–484. [Google Scholar] [CrossRef] [PubMed]
  40. Kachikis, A.; Englund, J.A.; Singleton, M.; Covelli, I.; Drake, A.L.; Eckert, L.O. Short-term Reactions Among Pregnant and Lactating Individuals in the First Wave of the COVID-19 Vaccine Rollout. JAMA Netw. Open 2021, 4, e2121310. [Google Scholar] [CrossRef] [PubMed]
  41. Low, J.M.; Gu, Y.; Ng, M.S.F.; Amin, Z.; Lee, L.Y.; Ng, Y.P.M.; Shunmuganathan, B.D.; Niu, Y.; Gupta, R.; Tambyah, P.A.; et al. Codominant IgG and IgA expression with minimal vaccine mRNA in milk of BNT162b2 vaccinees. NPJ Vaccines 2021, 6, 105. [Google Scholar] [CrossRef]
  42. Mithal, L.B.; Otero, S.; Shanes, E.D.; Goldstein, J.A.; Miller, E.S. Cord blood antibodies following maternal coronavirus disease 2019 vaccination during pregnancy. Am. J. Obstet. Gynecol. 2021, 225, 192–194. [Google Scholar] [CrossRef]
  43. Montalti, M.; Guaraldi, F.; Di Valerio, Z.; Ragghianti, B.; Tedesco, D.; Mannucci, E.; Monami, M.; Gori, D. Adherence to and early adverse events of COVID-19 vaccine in a cohort of 600 Italian breastfeeding and pregnant physicians. Hum. Vaccines Immunother. 2022, 18, 2106747. [Google Scholar] [CrossRef]
  44. Olearo, F.; Radmanesh, L.S.; Felber, N.; von Possel, R.; Emmerich, P.; Pekarek, N.; Pfefferle, S.; Nörz, D.; Hansen, G.; Diemert, A.; et al. Anti-SARS-CoV-2 antibodies in breast milk during lactation after infection or vaccination: A cohort study. J. Reprod. Immunol. 2022, 153, 103685. [Google Scholar] [CrossRef] [PubMed]
  45. Perez, S.E.; Luna Centeno, L.D.; Cheng, W.A.; Marentes Ruiz, C.J.; Lee, Y.; Congrave-Wilson, Z.; Powell, R.L.; Stellwagen, L.; Pannaraj, P.S. Human Milk SARS-CoV-2 Antibodies up to 6 Months After Vaccination. Pediatrics 2022, 149, e2021054260. [Google Scholar] [CrossRef]
  46. Perl, S.H.; Uzan-Yulzari, A.; Klainer, H.; Asiskovich, L.; Youngster, M.; Rinott, E.; Youngster, I. SARS-CoV-2-Specific Antibodies in Breast Milk After COVID-19 Vaccination of Breastfeeding Women. JAMA 2021, 325, 2013–2014. [Google Scholar] [CrossRef] [PubMed]
  47. Pietrasanta, C.; Darwich, A.; Ronchi, A.; Crippa, B.; Spada, E.; Mosca, F.; Pugni, L.; Rescigno, M. Humoral response to anti-SARS-CoV-2 vaccine in breastfeeding mothers and mother-to-infant antibody transfer through breast milk. NPJ Vaccines 2022, 7, 63. [Google Scholar] [CrossRef] [PubMed]
  48. Prabhu, M.; Murphy, E.A.; Sukhu, A.C.; Yee, J.; Singh, S.; Eng, D.; Zhao, Z.; Riley, L.E.; Yang, Y.J. Antibody Response to Coronavirus Disease 2019 (COVID-19) Messenger RNA Vaccination in Pregnant Women and Transplacental Passage into Cord Blood. Obstet. Gynecol. 2021, 138, 278–280. [Google Scholar] [CrossRef] [PubMed]
  49. Rottenstreich, A.; Zarbiv, G.; Oiknine-Djian, E.; Zigron, R.; Wolf, D.G.; Porat, S. Efficient Maternofetal Transplacental Transfer of Anti- Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike Antibodies After Antenatal SARS-CoV-2 BNT162b2 Messenger RNA Vaccination. Clin. Infect. Dis. 2021, 73, 1909–1912. [Google Scholar] [CrossRef]
  50. Scrimin, F.; Campisciano, G.; Comar, M.; Ragazzon, C.; Davanzo, R.; Quadrifoglio, M.; Giangreco, M.; Stabile, G.; Ricci, G. IgG and IgA Antibodies Post SARS-CoV-2 Vaccine in the Breast Milk and Sera of Breastfeeding Women. Vaccines 2022, 10, 125. [Google Scholar] [CrossRef]
  51. Shimabukuro, T.T.; Kim, S.Y.; Myers, T.R.; Moro, P.L.; Oduyebo, T.; Panagiotakopoulos, L.; Marquez, P.L.; Olson, C.K.; Liu, R.; Chang, K.T.; et al. Preliminary Findings of mRNA COVID-19 Vaccine Safety in Pregnant Persons. N. Engl. J. Med. 2021, 384, 2273–2282. [Google Scholar] [CrossRef]
  52. Stuckelberger, S.; Favre, G.; Ceulemans, M.; Gerbier, E.; Lambelet, V.; Stojanov, M.; Winterfeld, U.; Baud, D.; Panchaud, A.; Pomar, L. Current Data on COVID-19 mRNA-Vaccine Safety during Pregnancy Might Be Subject to Selection Bias. Reply to Stroobandt, S.; Stroobandt, R. Data of the COVID-19 mRNA-Vaccine V-Safe Surveillance System and Pregnancy Registry Reveals Poor Embryonic and Second Trimester Fetal Survival Rate. Comment on “Stuckelberger et al. SARS-CoV-2 Vaccine Willingness among Pregnant and Breastfeeding Women during the First Pandemic Wave: A Cross-Sectional Study in Switzerland. Viruses 2021, 13, 1199”. Viruses 2021, 13, 1546. [Google Scholar]
  53. Fu, W.; Sivajohan, B.; McClymont, E.; Albert, A.; Elwood, C.; Ogilvie, G.; Money, D. Systematic review of the safety, immunogenicity, and effectiveness of COVID-19 vaccines in pregnant and lactating individuals and their infants. Int. J. Gynaecol. Obstet. 2022, 156, 406–417. [Google Scholar] [CrossRef]
  54. Zhu, F.; Zozaya, C.; Zhou, Q.; De Castro, C.; Shah, P.S. SARS-CoV-2 genome and antibodies in breastmilk: A systematic review and meta-analysis. Arch. Dis. Child. Fetal Neonatal Ed. 2021, 106, 514–521. [Google Scholar] [CrossRef] [PubMed]
Figure 1. PRISMA: preferred reporting items for systematic reviews and meta-analyses.
Figure 1. PRISMA: preferred reporting items for systematic reviews and meta-analyses.
Jpm 13 00040 g001
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Novillo, B.; Martínez-Varea, A. COVID-19 Vaccines during Pregnancy and Breastfeeding: A Systematic Review. J. Pers. Med. 2023, 13, 40.

AMA Style

Novillo B, Martínez-Varea A. COVID-19 Vaccines during Pregnancy and Breastfeeding: A Systematic Review. Journal of Personalized Medicine. 2023; 13(1):40.

Chicago/Turabian Style

Novillo, Blanca, and Alicia Martínez-Varea. 2023. "COVID-19 Vaccines during Pregnancy and Breastfeeding: A Systematic Review" Journal of Personalized Medicine 13, no. 1: 40.

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop