Vaccines in the Postpartum Period and Lactation | Article

This chapter should be cited as follows:
Jones CE, Ralph KM, Glob. libr. women's med.,
ISSN: 1756-2228; DOI 10.3843/GLOWM.419453

The Continuous Textbook of Women’s Medicine Series – Obstetrics Module

Volume 17

Maternal immunization

Volume Editors: Professor Asma Khalil, The Royal College of Obstetricians and Gynaecologists, London, UK; Fetal Medicine Unit, Department of Obstetrics and Gynaecology, St George’s University Hospitals NHS Foundation Trust, London, UK
Professor Flor M Munoz, Baylor College of Medicine, TX, USA
Professor Ajoke Sobanjo-ter Meulen, University of Washington, Seattle, WA, USA

Chapter

Vaccines in the Postpartum Period and Lactation

First published: May 2023

AUTHORS

Christine E Jones

Clinical and Experimental Sciences, University of Southampton and NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK

Kate MI Ralph

Faculty of Medicine, University of Southampton, Southampton, UK

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INTRODUCTION

Women may receive a vaccine in the postnatal period if they had not received these in childhood, pre-pregnancy, during pregnancy, or when she has risk factors for infection or severe disease. The purpose is to ensure adequate protection against infection or severe diseases in the mother as well as her newborn infant. Protection against infections, such as influenza or COVID-19, is greatest when the vaccine is administered in pregnancy, when the risk of severe disease is highest; however, where this has not been possible, it is important to take the opportunity to re-consider administration following delivery.

INACTIVATED VACCINES

Administration of inactivated vaccines to mothers in the postpartum period and mothers who are breastfeeding are generally safe for both the mother and infant. Inactivated vaccines discussed in this chapter are pertussis, influenza, tetanus, hepatitis B, and COVID-19.

Pertussis

Pertussis vaccination in pregnancy is recommended in over 40 countries worldwide as an important strategy to protect infants during the first weeks of life, the period of greatest vulnerability to severe disease due to pertussis infection.¹^,² However, for women who did not receive pertussis vaccine in pregnancy, administration of a pertussis-containing vaccine is recommended in the postpartum period.³ The aim of postpartum pertussis vaccination is to reduce the risk of pertussis infection in the mother, and consequently reduce the risk of transmission of pertussis to the infant.

One strategy to protect infants born to mothers who did not receive a pertussis-containing vaccine in pregnancy is to vaccinate all the close contacts of the infant, as this has been shown to be the primary source of infection for infants.³ This is known as cocooning. The US Advisory Committee on Immunization Practices (ACIP) previously recommended cocooning as the primary strategy of protection of infants against pertussis in the first weeks of life.⁴ However, in 2011, ACIP recommended antenatal vaccination as the preferred strategy, owing to greater efficacy of antenatal vaccination than cocooning and the logistical difficulties of cocooning.⁴^,⁵^,⁶^,⁷^,⁸^,⁹ For example, cocooning necessitates all household contacts to be vaccinated, increasing the cost of the strategy, but also requiring engagement of fathers and other family members.⁶ A case-control study in the US during the period when cocooning was the preferred strategy found that only 4.8% of close contacts of infants diagnosed with pertussis in the first 2 months of life and 10.0% of close contacts of matched controls achieved complete cocooning.⁵ In low and middle income countries (LMIC), the barriers to cocooning are particularly great, such as lack of knowledge, high cost, and lack of transportation.¹⁰ These factors have led to cocooning not being recommended in this setting, with antenatal vaccination becoming the sole strategy for the protection of infants against pertussis in LMIC. Even where cocooning has been implemented successfully in higher income countries, the efficacy of cocooning has been shown to be limited. A population-based cohort study in Australia found no difference in the incidence of pertussis amongst infants whose parents were both vaccinated in the postpartum period (1.9 infections per 1000 infants (95% confidence interval [CI]: 1.3–2.9)) compared to those whose parents were not vaccinated (2.2 infections per 1000 infants [95% CI: 1.6–2.9]).⁷ Nevertheless, postpartum pertussis vaccination is recommended for women who were not vaccinated during pregnancy as it has been shown to be effective in protecting infants in the first weeks of life.³^,¹¹^,¹²

Pertussis-containing vaccines are safe to be administered to breastfeeding women. Concentrations of secretory immunoglobulin A (sIgA) in breastmilk peak between day 10 and 14 following vaccination.¹¹ Breastmilk sIgA is likely to contribute to infant protection against pertussis infection, however breastmilk sIgA alone is not thought to be sufficient to protect the infant against severe disease.¹¹^,¹³^,¹⁴ Passive immunity gained through breastmilk does not affect immune responses to infant vaccines.¹¹^,¹³

The vaccine administration schedule for pertussis vaccine in the postpartum period is a single dose in the immediate postpartum period. The time taken for the mother to gain protection following the vaccine is approximately 2 weeks.

Influenza

Seasonal influenza vaccination is recommended in pregnant women due to the increased risk of severe disease and hospital admission (odds ratio 6.80, 95% CI 6.02–7.68) in pregnant women, compared to non-pregnant women.¹⁵ However, pregnancy is not associated with an increased risk of death from influenza.¹⁵ In contrast, women less than 4 weeks postpartum were found to be at significantly increased risk of death (odds ratio [OR] 4.43, 95% confidence interval [CI] 1.24–16.81) from pandemic influenza in a systematic review and meta-analysis.¹⁶ Another study has shown that there is an association with increased acute influenza-like illness episodes in healthy, unvaccinated postpartum women (OR 2.28, 95% CI 1.42–3.68).¹⁷ In the 2022 World Health Organization (WHO) Influenza position paper, it is also recognized that women less than 2 weeks post-partum are at particular risk of severe influenza.¹⁸ Therefore, if an influenza vaccine is given postpartum, priority should be given to administration soon after birth.

The Immunization Agenda 2030 recognizes that all people benefit from seasonal influenza vaccination.¹⁹ The United States Centers for Disease Control and Prevention (CDC) have recommended annual influenza vaccination for all people who do not have contraindications to vaccination, since 2010.²⁰ Vaccination can therefore be given in the postpartum period, if not given during pregnancy, when influenza is circulating in the community.²¹ However, there is variation in national guidelines as to whether postpartum women are identified as a high-risk group to be prioritized for vaccination. Post-partum women with additional health needs, and therefore classified as high-risk for severe influenza on the basis of health co-morbidities, must be prioritized for vaccination, if this has not occurred before or during pregnancy.

Any licensed and recommended influenza vaccine can be given post-partum, whether or not the woman is breastfeeding, including inactivated, recombinant, and live attenuated influenza vaccines, either before or during the influenza season.²¹ If a woman has received influenza in the previous influenza season pre-pregnancy, then she should still receive the currently recommended seasonal vaccine subsequently, either in pregnancy or the postpartum period.

Influenza vaccination in pregnancy has been shown to elicit anti-influenza milk sIgA, which is sustained for 6 months postpartum, suggesting active production throughout lactation.²² Moreover, exclusive breast feeding in the first 6 months of life was associated with significantly decreased respiratory illnesses with fever in infants of influenza-vaccinated mothers compared to control infants.²² Therefore, postnatal vaccination of lactating women may confer additional benefit to the infant, as well as the mother, through decreased transmission of influenza, as well as potentially through transfer of breastmilk influenza-specific sIgA.²³

Tetanus

The standard tetanus toxoid (TT) vaccination schedule consists of three doses in infancy, and three booster doses in childhood and adolescence.²⁴ However, pregnant women who have not previously been immunized against tetanus are recommended to commence a five-dose schedule of tetanus toxoid.²⁵^,²⁶ It is likely that one of these doses may fall in the postpartum period. The WHO recommends that all women who are due a dose of tetanus toxoid in the postpartum period receive this.²⁵ Women who have completed a tetanus toxoid schedule, whether in childhood or in a previous pregnancy, do not require further additional TT doses in subsequent pregnancies.²⁵

Tetanus toxoid administration is safe in the postpartum period and in women who are breastfeeding.²⁶

Hepatitis B

There are no contraindications to hepatitis B vaccines in postpartum or breast-feeding women. Therefore, women who are at risk of hepatitis B infection, or who request vaccination against hepatitis B vaccination, may receive hepatitis B vaccination following delivery, with no restrictions in lactating women.²⁷ In 2022, the Advisory Committee on Immunization Practice, in the United States, updated its recommendations to include universal vaccination of all adults 19–59 years of age, to increase the low vaccination coverage in the adult population particularly amongst those with risk factors, given the rise in rates of hepatitis B infection in adults over 40 years of age since 2016.²⁸

Crucially, infants born to women with hepatitis B infection must receive prophylaxis with hepatitis B vaccination within 24 hours of birth, along with hepatitis B immunoglobulin in those for whom it is indicated. Indications for hepatitis B immunoglobulin vary between countries, from universal administration to all infants born to women infected with hepatitis B, to just those infants at highest risk of infection.²⁷^,²⁹ In those infants appropriately vaccinated against hepatitis B, there is no restriction on breastfeeding; although hepatitis B virus can be found in breastmilk, breastfeeding is not associated with an increased risk of mother-to-infant transmission of hepatitis B, even in women with high infectivity.³⁰

COVID-19

Vaccines to protect against COVID-19 are universally recommended in the adult population and may be safely given in the postpartum period, including during lactation. Post-partum and lactating women should receive primary series and booster doses according to country-specific guidelines at the time.

Lactating women were excluded from the randomized controlled trials of COVID-19 vaccines, however now there is extensive real-world safety data especially for mRNA vaccines including Comirnaty (Pfizer-BioNTech COVID-19 Vaccine), Spikevax (Moderna COVID-19 vaccine), which have more commonly been recommended for use in the age group of women of childbearing potential.³¹^,³²^,³³ There is less data for other vaccines, such as Vaxzevria/Covishield (OxfordAstraZeneca viral vectored COVID-19 vaccine), the Valneva COVID-19 inactivated vaccine, Janssen viral vectored COVID-19 vaccine, Nuvaxovid (Novavax protein subunit COVID-19 vaccine).³⁴^,³⁵^,³⁶^,³⁷ However, there is no pre-clinical data to suggest that it would be harmful and none of the COVID-19 vaccines in use contain live virus. Side-effects of COVID-19 vaccination in lactating women are similar to those seen in the general population.³³

A systematic review, which included 18 published studies and six pre-print manuscripts, of women receiving a mRNA COVID-19 vaccine during lactation reported an increase in SARS-CoV2 specific secretory IgA and IgG in breastmilk, which was correlated with the concentration in maternal serum.³³ Secretory IgA and IgG concentrations increase a week after the first dose of vaccine and peak after the second dose. Moreover, these antibodies had neutralizing capacity against SARS-CoV-2. Together this suggests that vaccination of lactating women may add to the protection afforded to the infant through interruption of transmission of infection and by transfer of antibody via breastmilk. Reassuringly, there was very limited impact of vaccination on breastmilk supply.

LIVE VACCINES

Live vaccines are contraindicated in pregnancy, so women who are found to be non-immune to rubella, measles, mumps, varicella, or yellow fever immediately prior to or during pregnancy are recommended to receive these vaccines in the postpartum period. The exception to this recommendation is women who have any other contraindications to live vaccines, such as immunosuppression.

When a vaccine containing live viruses is administered to a woman who is breastfeeding, the live viruses replicate in the woman. However, most live viruses in vaccines are not excreted in breastmilk, and those that are excreted in breastmilk do not cause disease in the infant, with the exception of yellow fever vaccine.²⁶^,³⁸

Measles, mumps, and rubella

In many countries, measles, mumps, and rubella vaccination is carried out in childhood. However, in women who have not been vaccinated in childhood, these infections can cause serious disease in pregnancy. Rubella infection in the first 20 weeks of pregnancy can lead to congenital rubella syndrome in the infant, resulting in sequelae, such as deafness, cataracts, congenital heart disease, and learning disability.³⁸ Measles infection in pregnancy increases the risk of preterm labor, low birth weight, and miscarriage.³⁹ Mumps in pregnancy can also increase the risk of miscarriage.³⁹ Therefore measles, mumps, and rubella vaccines are recommended in the postpartum period to protect the infant in subsequent pregnancies.⁴⁰

Rubella vaccine virus and measles vaccine virus have been detected in the breastmilk of mothers who have received the rubella and measles vaccines.⁴¹ However, rubella virus is attenuated in rubella vaccine so if transmission through breastmilk does occur, infection is well tolerated in the infant.¹⁷^,²²^,²³^,²⁴^,²⁵ There is no evidence that measles transmission through breastmilk causes clinical disease in infants.⁴¹ As a result, the MMR vaccine can be safely given to breastfeeding women.⁴⁰

The vaccine schedule for MMR vaccine in the postpartum period is two doses with an interval of between 4 and 8 weeks.

Varicella

The Royal College of Obstetricians and Gynaecologists in the UK guidelines state that varicella vaccination should be considered in postpartum women who are found to be seronegative to varicella zoster virus immunoglobulin G (IgG).⁴² Varicella infection in pregnancy can lead to pneumonitis, hepatitis, or encephalitis in the mother, and congenital varicella syndrome or severe neonatal varicella infection in the infant.³⁸ Therefore, it is considered in postpartum women with a view to protecting the mother and infant in subsequent pregnancies.

The live virus in the varicella vaccine is not excreted in breastmilk, so there is no risk to the infant if the mother receives this vaccine whilst breastfeeding.²⁶^,⁴²^,⁴³ A small study in the US found no evidence of excretion of varicella vaccine virus in 217 breastmilk samples of 12 women who were vaccinated in the postpartum period.⁴³ In addition, no infants in this study had IgG to varicella detected in blood samples collected 4 weeks after the second dose of maternal varicella vaccination.⁴³ Varicella vaccine can therefore be safely given to breastfeeding women.

The vaccine schedule for varicella is two doses with a 4 to 8 week interval between the doses.

Yellow fever

Yellow fever vaccine administration should be avoided in breastfeeding women because of the risk of yellow fever vaccine associated acute neurotropic disease (YEL-AND) in the infant. YEL-AND has several clinical manifestations including meningoencephalitis, Guillain-Barré syndrome, acute disseminated encephalomyelitis, and bulbar palsy.⁴⁴ There have been three reported cases of YEL-AND in infants breastfed by mothers who were vaccinated with yellow fever vaccine in the postpartum period, one of which was confirmed by detection of the virus and yellow fever specific immunoglobulin M (IgM) in the infant’s cerebrospinal fluid (CSF) by reverse transcriptase polymerase chain reaction.⁴⁵^,⁴⁶^,⁴⁷^,⁴⁸^,⁴⁹ Nucleotide sequencing matched the viral RNA found in the infant’s CSF to the yellow fever vaccine strain.⁴⁷ In this confirmed case in Brazil, the infant’s symptoms began 8 days after the mother received the yellow fever vaccine, and the mother also experienced symptoms of headache, malaise, and fever.⁴⁵ The other two cases, one in Brazil and one in Canada, were infants who developed symptoms between 3 and 4 weeks after the mother received yellow fever vaccine.⁴⁷^,⁴⁸^,⁴⁹ Yellow fever specific IgM was detected in the serum of both infants and the CSF of one infant.⁴⁷^,⁴⁸^,⁴⁹ Despite this, no viral testing of breastmilk was carried out in any of these cases, therefore the mode of transmission of yellow fever virus to the infant cannot be confirmed. Indeed, the two unconfirmed cases had possible exposure to yellow fever through residence in or travel to endemic areas, so vector-borne transmission cannot be ruled out.⁴⁸^,⁴⁹ Other mechanisms of mother-to-child transmission have been suggested, such as exposure to maternal blood through a break in the skin of the mother and a break in the oral mucosa of the infant.⁴⁹

If a breastfeeding woman cannot avoid or postpone travel to an area endemic to yellow fever, then she may be given yellow fever vaccine, but these women should be counseled on the potential risk of transmission to their infant through breastfeeding.²⁶^,⁴⁴ There is limited data regarding whether ceasing breastfeeding for a period after yellow fever vaccination to reduce the risk of transmission to the infant. A small study (n = 11) detected no yellow fever viral RNA in the breastmilk of women who received the yellow fever vaccine at 8, 10, or 15 days post-vaccination.⁵⁰ The Brazilian Ministry of Health recommends interrupting breastfeeding for 10 days following receipt of yellow fever vaccine.⁵⁰ However, further data is needed to determine the duration of yellow fever virus excretion in breastmilk in order to guide these recommendations.

The vaccine schedule for yellow fever is one dose. The Brazilian Ministry of Health recommends that postpartum yellow fever vaccination is delayed until the infant is at least 6 months of age.⁴⁹^,⁵⁰

Monkeypox

In the spring of 2022, an outbreak of monkeypox virus has occurred in several continents, outside of central and western parts of Africa’s tropical rainforest, where it occurs sporadically. At the time of writing, most cases in this outbreak have occurred in men, with only small numbers in women.⁵¹

The Modified vaccinia virus Ankara-Bavarian Nordic (MVA-BN) vaccine (marketed as Imvanex in the European Union or Jynneos in the United States) is active against several of the orthopoxviruses and is approved for immunization against smallpox and monkeypox by the Food and Drug Administration (FDA) in the United States and has been previously used in multiple countries in response to previous incidents.⁵²^,⁵³ MVA-BN is a highly attenuated live non-replicating third-generation vaccine and has an 85% vaccine efficacy against monkeypox.⁵³ This vaccine is distinct from the first- and second-generation smallpox vaccines, which were replication competent, reactogenic, and associated with significant scarring.

MVA-BN may be administered in postpartum women, including those who are lactating, where there is substantial exposure to monkeypox virus for the prevention of severe disease, following discussion of the risks and benefits to the mother and breast-fed infant.⁵²^,⁵³ The vaccine should be administered subcutaneously, within 14 days of exposure, and ideally as soon as possible to increase the chance of preventing disease; two doses should be administered, at least 28 days apart.⁵²^,⁵³^,⁵⁴ The vaccine virus does not effectively replicate in humans and therefore it is very unlikely that MVA-BN would pass into breastmilk.⁵² However, the safety and efficacy of MVA-BN has not been specifically evaluated in breastfeeding women.

CONCLUSION

There are few restrictions on vaccination in women in the postnatal period, whether or not they are lactating. Ideally measles, mumps, rubella vaccine, tetanus toxoid, and varicella vaccine would be given in childhood or pre-pregnancy, however where this has not occurred, or a course is not complete, they may be given without restriction to women following delivery. Influenza and pertussis vaccination should be prioritized during pregnancy to protect the women in late pregnancy when the risk of severe influenza is increased or to protect the infant from birth from pertussis or influenza. However, where this had not been possible, both vaccines can safety be given postpartum and are likely to confer benefit for both mother and infant. Pregnant and lactating women were not given sufficient priority in the pivotal studies of COVID-19 vaccines, however subsequent observational data has shown that they can be safely given in breastfeeding women. Hepatitis B vaccination may be given wherever indicated to women following delivery. Vaccination against monkeypox should be given, following an assessment of the benefits and risks, to women with significant exposure. Although this vaccine is a live vaccine, it is high attenuated and therefore very unlikely to be present in breast milk. The only vaccine that is not recommended in postpartum lactating women is yellow fever vaccination due to the potential risk of YEL-AND in the infant. Postpartum and lactating women should be included in the clinical trials pipeline of new vaccines to ensure high-quality data is available to guide recommendations for this population.

Summary of recommendations for immunization in the postpartum period and during lactation.

Vaccine	Use in postpartum period	Use in lactating women	Comments
Inactivated vaccines
Pertussis			Vaccination in pregnancy preferrable. One dose.
Influenza			Vaccination in pregnancy preferrable. One dose, given in each influenza season.
Tetanus			Vaccination in childhood, pre-pregnancy or pregnancy preferrable. Total of five doses, complete doses postpartum if not all administered previously.
Hepatitis B			Use in women at risk of infection or who request vaccination. Ensure infant vaccination at birth if relevant.
COVID-19			Vaccination in pregnancy preferrable. Primary or booster may be given according to country-specific guidelines.
Live vaccines
Measles, mumps and rubella			Vaccination in childhood optimal, may be given where two doses not previously received.
Varicella			Two doses may be given in seronegative women.
Yellow fever			Do not give to lactating women, except where risk of exposure outweighs risk to infant.
Monkeypox			May be given where substantial exposure has occurred.

PRACTICE RECOMMENDATIONS

Women may receive a vaccine in the postnatal period if she had not received these in childhood, pre-pregnancy, during pregnancy, or when she has risk factors for infection or severe disease
Measles, mumps, rubella vaccine, tetanus toxoid, and varicella vaccine should ideally be given in childhood or pre-pregnancy, however where this has not occurred, or a course is not complete, they may be given without restriction to postpartum and lactating women
Influenza and pertussis vaccination should be prioritized for administration during pregnancy, however where this had not been possible, both vaccines can safety be given postpartum
Hepatitis B vaccination may be given wherever indicated to women following delivery
Yellow fever vaccine administration should be avoided in breastfeeding women because of the risk of yellow fever vaccine associated acute neurotropic disease in the infant
Vaccines to protect against COVID-19 are universally recommended in the adult population and may be safely given in the postpartum period, including during lactation
If there has been substantial exposure to monkeypox, vaccination may be administered in postpartum women, including those who are lactating, for the prevention of severe disease, following discussion of the risks and benefits to the mother and breast-fed infant
Postpartum and lactating women should be included in the clinical trials pipeline of new vaccines to ensure high-quality data is available to guide recommendations for this population

CONFLICTS OF INTEREST

Author(s) statement awaited.

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