Neutralizing antibodies in milk and blood of lactating women vaccinated for SARS-CoV-2: a systematic review

Vieira, Ianne Stéfani Angelim; Rocha, Fernanda Mazzoli da; Vilarim, Marina; Rebelo, Fernanda; Marano, Daniele

doi:10.1590/1984-0462/2025/43/2023210

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Revista Paulista de Pediatria

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Review Article • Rev. paul. pediatr. 43 • 2025 • https://doi.org/10.1590/1984-0462/2025/43/2023210 copy

Neutralizing antibodies in milk and blood of lactating women vaccinated for SARS-CoV-2: a systematic review

Anticorpos neutralizantes no leite e no sangue de lactantes vacinadas para SARS-CoV-2: uma revisão sistemática

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Objective:

To compare the presence of neutralizing antibodies against SARS-CoV-2 found in the breast milk and blood of vaccinated lactating women with those not vaccinated.

Data source:

The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under CRD42021287554 and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Cohort, case-control, and cross-sectional studies that evaluated antibodies against SARS-CoV-2 in the milk and blood of vaccinated mothers and had as control group unvaccinated mothers were eligible. Health Sciences Descriptors (DeCs), Medical Subject Headings (MeSH) and Emtree descriptors were used for the Virtual Health Library (VHL), Medical Literature Analysis and Retrieval System Online (Medline/Pubmed), and Embase databases, respectively. In the Web of Science and Scopus, the strategy was adapted. No restrictions on the publication period and language were set.

Data synthesis:

The search identified 233 records, of which 128 duplicates and 101 papers that did not meet the inclusion criteria were excluded. Hence, four cohort studies were eligible. Nursing mothers vaccinated with the Pfizer-BioNTech and Moderna vaccines showed antibodies against SARS-CoV-2 in their blood and breast milk.

Conclusions:

Vaccinated lactating women had higher levels of immunoglobulin G (IgG) and A (IgA) in serum and breast milk than unvaccinated women.

Keywords:
COVID-19; Human milk; Vaccine; Antibodies; Systematic review

Reference/country of study	Study design	Vaccine technology (trade name)	Follow up time (days)	Sample size		Eligibility criteria	Exclusion criteria

				Vaccinated lactating women	Unvaccinated lactating women
Jakuszko et al.,¹³13. Jakuszko K, Kościelska-Kasprzak K, Żabińska M, Bartoszek D, Poznański P, Rukasz D, et al. Immune response to vaccination against COVID-19 in breastfeeding health workers. Vaccines (Basel). 2021;9:663. https://doi.org/10.3390/vaccines9060663 https://doi.org/10.3390/vaccines9060663... Poland	Cohort	mRNA (Pfizer)	43	32	28	Vaccinated and unvaccinated lactating women against COVID-19	Lactating women previously infected with SARS-CoV-2
Nir et al.,¹⁵15. Nir O, Schwartz A, Toussia-Cohen S, Leibovitch L, Strauss T, Asraf K, et al. Maternal-neonatal transfer of SARS-CoV-2 immunoglobulin G antibodies among parturient women treated with BNT162b2 messenger RNA vaccine during pregnancy. Am J Obstet Gynecol MFM. 2022;4:100492. https://doi.org/10.1016/j.ajogmf.2021.100492 https://doi.org/10.1016/j.ajogmf.2021.10... Israel	Cohort	mRNA (Pfizer)	59	64	11	Lactating women aged ≥18 years who received two doses of the BNT162 b2 mRNA vaccine against COVID-19 at least 14 days before childbirth	NI
Romero Ramírez et al.,⁵5. Romero Ramírez DS, Lara Pérez MM, Carretero Pérez MM, Suárez Hernández MI, Martín Pulido S, et al. SARS-CoV-2 antibodies in breast milk after vaccination. Pediatrics. 2021;148:e2021052286. https://doi.org/10.1542/peds.2021-052286 https://doi.org/10.1542/peds.2021-052286... Spain	Cohort	mRNA (Pfizer and Moderna)	62	100	24	Lactating healthcare workers who were breastfeeding their child at the time of SARS-CoV-2 vaccination	Participants with HIV infection, illnesses or treatment that cause immunosuppression, previous infections or ongoing symptoms compatible with COVID-19 at the time of recruitment
Valcarce et al.,¹⁴14. Valcarce V, Stafford LS, Neu J, Cacho N, Parker L, Mueller M, et al. Detection of SARS-CoV-2-specific IgA in the human milk of COVID-19 vaccinated lactating health care workers. Breastfeed Med. 2021;16:1004-9. https://doi.org/10.1089/bfm.2021.0122 https://doi.org/10.1089/bfm.2021.0122... United States	Cohort	mRNA (Pfizer and Moderna)	121	22^* *The group of vaccinated lactating women is the same group of unvaccinated (i.e., unexposed) women; however, before immunization.	22	Lactating women with no known history of COVID-19 infection; ≥18 years old, able to provide informed consent and receiving COVID-19 vaccine during lactation	Lactating women who did not complete sample collection

Reference	Vaccinated lactating women		Unvaccinated lactating women		Main results

	Antibodies in the blood	Antibodies in milk	Antibodies in the blood	Antibodies in milk
Jakuszko et al.¹³13. Jakuszko K, Kościelska-Kasprzak K, Żabińska M, Bartoszek D, Poznański P, Rukasz D, et al. Immune response to vaccination against COVID-19 in breastfeeding health workers. Vaccines (Basel). 2021;9:663. https://doi.org/10.3390/vaccines9060663 https://doi.org/10.3390/vaccines9060663...	IgM=ND	IgM=ND	IgM=ND	IgM=ND	The response to vaccination against SARS-CoV-2 is higher after the second dose. The levels of IgA and IgG antibodies in breast milk and serum of mothers after the COVID-19 vaccine were positively correlated. None of the serum and milk samples was positive for anti-SARS-CoV-2 IgM antibodies.
	IgG Day 8±1=4.62±3.57 Day 43±4=3,276.5±1,803.3	IgG Day 8±1=ND Day 43±4=6.43±4.33	IgG Day 8±1=3.41±0.80	IgG Day 8±1=ND
	IgA Day 8±1=0.33±0.37 Day 43±4=9.37±8.08	IgA Day 8±1=0.55±0.32 Day 43±4=2.73±2.13	IgA Day 8±1=0.17±0.07	IgA Day 8±1=0.69±0.39

Nir et al.¹⁵15. Nir O, Schwartz A, Toussia-Cohen S, Leibovitch L, Strauss T, Asraf K, et al. Maternal-neonatal transfer of SARS-CoV-2 immunoglobulin G antibodies among parturient women treated with BNT162b2 messenger RNA vaccine during pregnancy. Am J Obstet Gynecol MFM. 2022;4:100492. https://doi.org/10.1016/j.ajogmf.2021.100492 https://doi.org/10.1016/j.ajogmf.2021.10...	IgM=NI	IgM=NI	IgM=NI	IgM=NI	All blood and breast milk samples were positive for anti-SARS-CoV-2 IgG. Likewise, 98% of umbilical cord blood samples and 96% of neonatal blood were positive for anti-SARS-CoV-2 IgG.
	IgG=26.1 (22.0–39.7)	IgG=4.9 (3.8–6.0)	IgG=2.6 (0.9–3.5)	IgG=ND
	IgA=NI	IgA=NI	IgA=NI	IgA=NI

Romero Ramírez et al.⁵5. Romero Ramírez DS, Lara Pérez MM, Carretero Pérez MM, Suárez Hernández MI, Martín Pulido S, et al. SARS-CoV-2 antibodies in breast milk after vaccination. Pediatrics. 2021;148:e2021052286. https://doi.org/10.1542/peds.2021-052286 https://doi.org/10.1542/peds.2021-052286...	IgM=NI	IgM=0.04±0.08	IgM=NI	IgM=0.01±0.00	All vaccinated mothers developed anti-SARS-CoV-2 IgG antibodies in serum and milk samples. All breast milk samples contained IgG antibodies and 89% of them contained IgA antibodies. Highly significant correlation between antibody levels in serum and breast milk samples.
	IgG=3,379.64±1,639.46	IgG=12.19±11.74	IgG=0.41±0.37	IgG=0.02±0.05
	IgA=NI	IgA=1.73±1.59	IgA=NI	IgA=0.21±0.08

Valcarce et al.¹⁴14. Valcarce V, Stafford LS, Neu J, Cacho N, Parker L, Mueller M, et al. Detection of SARS-CoV-2-specific IgA in the human milk of COVID-19 vaccinated lactating health care workers. Breastfeed Med. 2021;16:1004-9. https://doi.org/10.1089/bfm.2021.0122 https://doi.org/10.1089/bfm.2021.0122...	IgM=NI	IgM=NI	IgM=NI	IgM=NI	Vaccines against COVID-19 induce the secretion of IgA and IgG in human milk. The peak of anti-SARS-CoV-2 IgA and IgG in human milk and plasma occurred seven to ten days after the second dose of the COVID-19 vaccine.
	IgG After the 2^nd dose=4.90±0.13	IgG After the 2^nd dose=1.77±0.20	IgG=3.27±0.04	IgG=0.08±0.02
	IgA After the 2^nd dose=3.66±0.05	IgA After the 2^nd dose=2.34±0.18	IgA=3.23±0.01	IgA=1.41±0.12

	Jakuszko et al.¹³13. Jakuszko K, Kościelska-Kasprzak K, Żabińska M, Bartoszek D, Poznański P, Rukasz D, et al. Immune response to vaccination against COVID-19 in breastfeeding health workers. Vaccines (Basel). 2021;9:663. https://doi.org/10.3390/vaccines9060663 https://doi.org/10.3390/vaccines9060663...	Nir et al.¹⁵15. Nir O, Schwartz A, Toussia-Cohen S, Leibovitch L, Strauss T, Asraf K, et al. Maternal-neonatal transfer of SARS-CoV-2 immunoglobulin G antibodies among parturient women treated with BNT162b2 messenger RNA vaccine during pregnancy. Am J Obstet Gynecol MFM. 2022;4:100492. https://doi.org/10.1016/j.ajogmf.2021.100492 https://doi.org/10.1016/j.ajogmf.2021.10...	Romero Ramírez et al.⁵5. Romero Ramírez DS, Lara Pérez MM, Carretero Pérez MM, Suárez Hernández MI, Martín Pulido S, et al. SARS-CoV-2 antibodies in breast milk after vaccination. Pediatrics. 2021;148:e2021052286. https://doi.org/10.1542/peds.2021-052286 https://doi.org/10.1542/peds.2021-052286...	Valcarce et al.¹⁴14. Valcarce V, Stafford LS, Neu J, Cacho N, Parker L, Mueller M, et al. Detection of SARS-CoV-2-specific IgA in the human milk of COVID-19 vaccinated lactating health care workers. Breastfeed Med. 2021;16:1004-9. https://doi.org/10.1089/bfm.2021.0122 https://doi.org/10.1089/bfm.2021.0122...
Selection
Representativeness of exposed cohort	0	0	0	0
Unexposed cohort selection	1	1	1	1
Determination of exposure	1	1	1	1
Demonstration that the outcome of interest was not present at the beginning of the study	1	1	1	1
Comparability
Adjustments for the most important risk factors	1	1	1	1
Adjustments for other risk factors	1	1	1	1
Outcome
Determination of outcome	1	1	1	1
Was the segment sufficient for the outcome to occur?	1	1	1	1
Adequacy of cohort monitoring	1	1	1	1
Total quality score	8	8	8	8

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[1] *Corresponding author. E-mail: iannevieira.enf@gmail.com (I.S.A. Vieira)