Maternal Immunization to Prevent Serious Respiratory Illness

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Changed
Thu, 10/10/2024 - 09:50

Editor’s Note: Sadly, this is the last column in the Master Class Obstetrics series. This award-winning column has been part of Ob.Gyn. News for 20 years. The deep discussion of cutting-edge topics in obstetrics by specialists and researchers will be missed as will the leadership and curation of topics by Dr. E. Albert Reece.
 

Introduction: The Need for Increased Vigilance About Maternal Immunization

Viruses are becoming increasingly prevalent in our world and the consequences of viral infections are implicated in a growing number of disease states. It is well established that certain cancers are caused by viruses and it is increasingly evident that viral infections can trigger the development of chronic illness. In pregnant women, viruses such as cytomegalovirus can cause infection in utero and lead to long-term impairments for the baby.

Likewise, it appears that the virulence of viruses is increasing, whether it be the respiratory syncytial virus (RSV) in children or the severe acute respiratory syndrome (SARS) coronaviruses in adults. Clearly, our environment is changing, with increases in population growth and urbanization, for instance, and an intensification of climate change and its effects. Viruses are part of this changing background.

Dr. E. Albert Reece, University of Maryland School of Medicine
Dr. E. Albert Reece


Vaccines are our most powerful tool to protect people of all ages against viral threats, and fortunately, we benefit from increasing expertise in vaccinology. Since 1974, the University of Maryland School of Medicine has a Center for Vaccine Development and Global Health that has conducted research on vaccines to defend against the Zika virus, H1N1, Ebola, and SARS-CoV-2.

We’re not alone. Other vaccinology centers across the country — as well as the National Institutes of Health at the national level, through its National Institute of Allergy and Infectious Diseases — are doing research and developing vaccines to combat viral diseases.

In this column, we are focused on viral diseases in pregnancy and the role that vaccines can play in preventing serious respiratory illness in mothers and their newborns. I have invited Laura E. Riley, MD, the Given Foundation Professor and Chair of Obstetrics and Gynecology at Weill Cornell Medicine, to address the importance of maternal immunization and how we can best counsel our patients and improve immunization rates.

As Dr. Riley explains, we are in a new era, and it behooves us all to be more vigilant about recommending vaccines, combating misperceptions, addressing patients’ knowledge gaps, and administering vaccines whenever possible.
 

Dr. Reece is the former Dean of Medicine & University Executive VP, and The Distinguished University and Endowed Professor & Director of the Center for Advanced Research Training and Innovation (CARTI) at the University of Maryland School of Medicine, as well as senior scientist at the Center for Birth Defects Research.

 

 

The alarming decline in maternal immunization rates that occurred in the wake of the COVID-19 pandemic means that, now more than ever, we must fully embrace our responsibility to recommend immunizations in pregnancy and to communicate what is known about their efficacy and safety. Data show that vaccination rates drop when we do not offer vaccines in our offices, so whenever possible, we should administer them as well.

The ob.gyn. is the patient’s most trusted person in pregnancy. When patients decline or express hesitancy about vaccines, it is incumbent upon us to ask why. Oftentimes, we can identify areas in which patients lack knowledge or have misperceptions and we can successfully educate the patient or change their perspective or misunderstanding concerning the importance of vaccination for themselves and their babies. (See Table 1.) We can also successfully address concerns about safety.

Table 1: Key messages on flue, COVID-19, and RSV vaccines in pregnancy
Dr. Riley


The safety of COVID-19 vaccinations in pregnancy is now backed by several years of data from multiple studies showing no increase in birth defects, preterm delivery, miscarriage, or stillbirth.

Data also show that pregnant patients are more likely than patients who are not pregnant to need hospitalization and intensive care when infected with SARS-CoV-2 and are at risk of having complications that can affect pregnancy and the newborn, including preterm birth and stillbirth. Vaccination has been shown to reduce the risk of severe illness and the risk of such adverse obstetrical outcomes, in addition to providing protection for the infant early on.

Similarly, influenza has long been more likely to be severe in pregnant patients, with an increased risk of poor obstetrical outcomes. Vaccines similarly provide “two for one protection,” protecting both mother and baby, and are, of course, backed by many years of safety and efficacy data.

Dr. Laura E. Riley is Given Foundation Professor in Clinical Obstetrics and Gynecology, Obstetrics and Gynecology, Weill Cornell Medical College, New York
New York Presbyterian
Dr. Laura E. Riley


With the new maternal respiratory syncytial virus (RSV) vaccine, now in its second year of availability, the goal is to protect the baby from RSV-caused serious lower respiratory tract illness. The illness has contributed to tens of thousands of annual hospitalizations and up to several hundred deaths every year in children younger than 5 years — particularly in those under age 6 months.

The RSV monoclonal antibody nirsevimab is available for the newborn as an alternative to maternal immunization but the maternal vaccine is optimal in that it will provide immediate rather than delayed protection for the newborn. The maternal vaccine is recommended during weeks 32-36 of pregnancy in mothers who were not vaccinated during last year’s RSV season. With real-world experience from year one, the available safety data are reassuring.
 

Counseling About Influenza and COVID-19 Vaccination

The COVID-19 pandemic took a toll on vaccination interest/receptivity broadly in pregnant and nonpregnant people. Among pregnant individuals, influenza vaccination coverage declined from 71% in the 2019-2020 influenza season to 56% in the 2021-2022 season, according to data from the Centers for Disease Control and Prevention’s Vaccine Safety Datalink.4 Coverage for the 2022-2023 and 2023-2024 influenza seasons was even worse: well under 50%.5

Fewer pregnant women have received updated COVID-19 vaccines. Only 13% of pregnant persons overall received the updated 2023-2024 COVID-19 booster vaccine (through March 30, 2024), according to the CDC.6

Maternal immunization for influenza has been recommended in the United States since 2004 (part of the recommendation that everyone over the age of 6 months receive an annual flu vaccine), and flu vaccines have been given to millions of pregnant women, but the H1N1 pandemic of 2009 reinforced its value as a priority for prenatal care. Most of the women who became severely ill from the H1N1 virus were young and healthy, without co-existing conditions known to increase risk.7

It became clearer during the H1N1 pandemic that pregnancy itself — which is associated with physiologic changes such as decreased lung capacity, increased nasal congestion and changes in the immune system – is its own significant risk factor for severe illness from the influenza virus. This increased risk applies to COVID-19 as well.

As COVID-19 has become endemic, with hospitalizations and deaths not reaching the levels of previous surges — and with mask-wearing and other preventive measures having declined — patients understandably have become more complacent. Some patients are vaccine deniers, but in my practice, these patients are a much smaller group than those who believe COVID-19 “is no big deal,” especially if they have had infections recently.

This is why it’s important to actively listen to concerns and to ask patients who decline a vaccination why they are hesitant. Blanket messages about vaccine efficacy and safety are the first step, but individualized, more pointed conversations based on the patient’s personal experiences and beliefs have become increasingly important.

I routinely tell pregnant patients about the risks of COVID-19 and I explain that it has been difficult to predict who will develop severe illness. Sometimes more conversation is needed. For those who are still hesitant or who tell me they feel protected by a recent infection, for instance, I provide more detail on the unique risks of pregnancy — the fact that “pregnancy is different” — and that natural immunity wanes while the protection afforded by immunization is believed to last longer. Many women are also concerned about the safety of the COVID-19 vaccine, so having safety data at your fingertips is helpful. (See Table 2.)

Table 2: COVID-19 vaccine safety data: Examples of published reviews
Dr. Riley


The fact that influenza and COVID-19 vaccination protect the newborn as well as the mother is something that I find is underappreciated by many patients. Explaining that infants likely benefit from the passage of antibodies across the placenta should be part of patient counseling.
 

Counseling About RSV Vaccination

Importantly, for the 2024-2025 RSV season, the maternal RSV vaccine (Abrysvo, Pfizer) is recommended only for pregnant women who did not receive the vaccine during the 2023-2024 season. When more research is done and more data are obtained showing how long the immune response persists post vaccination, it may be that the US Food and Drug Administration (FDA) will approve the maternal RSV vaccine for use in every pregnancy.

The later timing of the vaccination recommendation — 32-36 weeks’ gestation — reflects a conservative approach taken by the FDA in response to data from one of the pivotal trials showing a numerical trend toward more preterm deliveries among vaccinated compared with unvaccinated patients. This imbalance in the original trial, which administered the vaccine during 24-36 weeks of gestation, was seen only in low-income countries with no temporal association, however.

In our experience at two Weill Cornell Medical College–associated hospitals we did not see this trend. Our cohort study of almost 3000 pregnant patients who delivered at 32 weeks’ gestation or later found no increased risk of preterm birth among the 35% of patients who received the RSV vaccine during the 2023-2024 RSV season. We also did not see any difference in preeclampsia, in contrast with original trial data that showed a signal for increased risk.11

When fewer than 2 weeks have elapsed between maternal vaccination and delivery, the monoclonal antibody nirsevimab is recommended for the newborn — ideally before the newborn leaves the hospital. Nirsevimab is also recommended for newborns of mothers who decline vaccination or were not candidates (e.g. vaccinated in a previous pregnancy), or when there is concern about the adequacy of the maternal immune response to the vaccine (e.g. in cases of immunosuppression).

While there was a limited supply of the monoclonal antibody last year, limitations are not expected this year, especially after October.

The ultimate goal is that patients choose the vaccine or the immunoglobulin, given the severity of RSV disease. Patient preferences should be considered. However, given that it takes 2 weeks after vaccination for protection to build up, I stress to patients that if they’ve vaccinated themselves, their newborn will leave the hospital with protection. If nirsevimab is relied upon, I explain, their newborn may not be protected for some period of time.
 

Take-home Messages

  • When patients decline or are hesitant about vaccines, ask why. Listen actively, and work to correct misperceptions and knowledge gaps.
  • Whenever possible, offer vaccines in your practice. Vaccination rates drop when this does not occur.
  • COVID-vaccine safety is backed by many studies showing no increase in birth defects, preterm delivery, miscarriage, or stillbirth.
  • Pregnant women are more likely to have severe illness from the influenza and SARS-CoV-2 viruses. Vaccines can prevent severe illness and can protect the newborn as well as the mother.
  • Recommend/administer the maternal RSV vaccine at 32-36 weeks’ gestation in women who did not receive the vaccine in the 2023-2024 season. If mothers aren’t eligible their babies should be offered nirsevimab.

Dr. Riley is the Given Foundation Professor and Chair of Obstetrics and Gynecology at Weill Cornell Medicine and the obstetrician and gynecologist-in-chief at New York Presbyterian Hospital. She disclosed that she has provided one-time consultations to Pfizer (Abrysvo RSV vaccine) and GSK (cytomegalovirus vaccine), and is providing consultant education on CMV for Moderna. She is chair of ACOG’s task force on immunization and emerging infectious diseases, serves on the medical advisory board for MAVEN, and serves as an editor or editorial board member for several medical publications.



References

1. ACOG Committee Opinion No. 741: Maternal Immunization. Obstet Gynecol. 2018;131(6):e214-e217.

2. Centers for Disease Control and Prevention. COVID-19 Vaccination for People Who are Pregnant or Breastfeeding. https://www.cdc.gov/covid/vaccines/pregnant-or-breastfeeding.html.

3. ACOG Practice Advisory on Maternal Respiratory Syncytial Virus Vaccination, September 2023. (Updated August 2024).4. Irving S et al. Open Forum Infect Dis. 2023;10(Suppl 2):ofad500.1002.

5. Flu Vaccination Dashboard, CDC, National Center for Immunization and Respiratory Diseases.

6. Weekly COVID-19 Vaccination Dashboard, CDC. https://www.cdc.gov/covidvaxview/weekly-dashboard/index.html

7. Louie JK et al. N Engl J Med. 2010;362:27-35. 8. Ciapponi A et al. Vaccine. 2021;39(40):5891-908.

9. Prasad S et al. Nature Communications. 2022;13:2414. 10. Fleming-Dutra KE et al. Obstet Gynecol Clin North Am 2023;50(2):279-97. 11. Mouen S et al. JAMA Network Open 2024;7(7):e2419268.

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Editor’s Note: Sadly, this is the last column in the Master Class Obstetrics series. This award-winning column has been part of Ob.Gyn. News for 20 years. The deep discussion of cutting-edge topics in obstetrics by specialists and researchers will be missed as will the leadership and curation of topics by Dr. E. Albert Reece.
 

Introduction: The Need for Increased Vigilance About Maternal Immunization

Viruses are becoming increasingly prevalent in our world and the consequences of viral infections are implicated in a growing number of disease states. It is well established that certain cancers are caused by viruses and it is increasingly evident that viral infections can trigger the development of chronic illness. In pregnant women, viruses such as cytomegalovirus can cause infection in utero and lead to long-term impairments for the baby.

Likewise, it appears that the virulence of viruses is increasing, whether it be the respiratory syncytial virus (RSV) in children or the severe acute respiratory syndrome (SARS) coronaviruses in adults. Clearly, our environment is changing, with increases in population growth and urbanization, for instance, and an intensification of climate change and its effects. Viruses are part of this changing background.

Dr. E. Albert Reece, University of Maryland School of Medicine
Dr. E. Albert Reece


Vaccines are our most powerful tool to protect people of all ages against viral threats, and fortunately, we benefit from increasing expertise in vaccinology. Since 1974, the University of Maryland School of Medicine has a Center for Vaccine Development and Global Health that has conducted research on vaccines to defend against the Zika virus, H1N1, Ebola, and SARS-CoV-2.

We’re not alone. Other vaccinology centers across the country — as well as the National Institutes of Health at the national level, through its National Institute of Allergy and Infectious Diseases — are doing research and developing vaccines to combat viral diseases.

In this column, we are focused on viral diseases in pregnancy and the role that vaccines can play in preventing serious respiratory illness in mothers and their newborns. I have invited Laura E. Riley, MD, the Given Foundation Professor and Chair of Obstetrics and Gynecology at Weill Cornell Medicine, to address the importance of maternal immunization and how we can best counsel our patients and improve immunization rates.

As Dr. Riley explains, we are in a new era, and it behooves us all to be more vigilant about recommending vaccines, combating misperceptions, addressing patients’ knowledge gaps, and administering vaccines whenever possible.
 

Dr. Reece is the former Dean of Medicine & University Executive VP, and The Distinguished University and Endowed Professor & Director of the Center for Advanced Research Training and Innovation (CARTI) at the University of Maryland School of Medicine, as well as senior scientist at the Center for Birth Defects Research.

 

 

The alarming decline in maternal immunization rates that occurred in the wake of the COVID-19 pandemic means that, now more than ever, we must fully embrace our responsibility to recommend immunizations in pregnancy and to communicate what is known about their efficacy and safety. Data show that vaccination rates drop when we do not offer vaccines in our offices, so whenever possible, we should administer them as well.

The ob.gyn. is the patient’s most trusted person in pregnancy. When patients decline or express hesitancy about vaccines, it is incumbent upon us to ask why. Oftentimes, we can identify areas in which patients lack knowledge or have misperceptions and we can successfully educate the patient or change their perspective or misunderstanding concerning the importance of vaccination for themselves and their babies. (See Table 1.) We can also successfully address concerns about safety.

Table 1: Key messages on flue, COVID-19, and RSV vaccines in pregnancy
Dr. Riley


The safety of COVID-19 vaccinations in pregnancy is now backed by several years of data from multiple studies showing no increase in birth defects, preterm delivery, miscarriage, or stillbirth.

Data also show that pregnant patients are more likely than patients who are not pregnant to need hospitalization and intensive care when infected with SARS-CoV-2 and are at risk of having complications that can affect pregnancy and the newborn, including preterm birth and stillbirth. Vaccination has been shown to reduce the risk of severe illness and the risk of such adverse obstetrical outcomes, in addition to providing protection for the infant early on.

Similarly, influenza has long been more likely to be severe in pregnant patients, with an increased risk of poor obstetrical outcomes. Vaccines similarly provide “two for one protection,” protecting both mother and baby, and are, of course, backed by many years of safety and efficacy data.

Dr. Laura E. Riley is Given Foundation Professor in Clinical Obstetrics and Gynecology, Obstetrics and Gynecology, Weill Cornell Medical College, New York
New York Presbyterian
Dr. Laura E. Riley


With the new maternal respiratory syncytial virus (RSV) vaccine, now in its second year of availability, the goal is to protect the baby from RSV-caused serious lower respiratory tract illness. The illness has contributed to tens of thousands of annual hospitalizations and up to several hundred deaths every year in children younger than 5 years — particularly in those under age 6 months.

The RSV monoclonal antibody nirsevimab is available for the newborn as an alternative to maternal immunization but the maternal vaccine is optimal in that it will provide immediate rather than delayed protection for the newborn. The maternal vaccine is recommended during weeks 32-36 of pregnancy in mothers who were not vaccinated during last year’s RSV season. With real-world experience from year one, the available safety data are reassuring.
 

Counseling About Influenza and COVID-19 Vaccination

The COVID-19 pandemic took a toll on vaccination interest/receptivity broadly in pregnant and nonpregnant people. Among pregnant individuals, influenza vaccination coverage declined from 71% in the 2019-2020 influenza season to 56% in the 2021-2022 season, according to data from the Centers for Disease Control and Prevention’s Vaccine Safety Datalink.4 Coverage for the 2022-2023 and 2023-2024 influenza seasons was even worse: well under 50%.5

Fewer pregnant women have received updated COVID-19 vaccines. Only 13% of pregnant persons overall received the updated 2023-2024 COVID-19 booster vaccine (through March 30, 2024), according to the CDC.6

Maternal immunization for influenza has been recommended in the United States since 2004 (part of the recommendation that everyone over the age of 6 months receive an annual flu vaccine), and flu vaccines have been given to millions of pregnant women, but the H1N1 pandemic of 2009 reinforced its value as a priority for prenatal care. Most of the women who became severely ill from the H1N1 virus were young and healthy, without co-existing conditions known to increase risk.7

It became clearer during the H1N1 pandemic that pregnancy itself — which is associated with physiologic changes such as decreased lung capacity, increased nasal congestion and changes in the immune system – is its own significant risk factor for severe illness from the influenza virus. This increased risk applies to COVID-19 as well.

As COVID-19 has become endemic, with hospitalizations and deaths not reaching the levels of previous surges — and with mask-wearing and other preventive measures having declined — patients understandably have become more complacent. Some patients are vaccine deniers, but in my practice, these patients are a much smaller group than those who believe COVID-19 “is no big deal,” especially if they have had infections recently.

This is why it’s important to actively listen to concerns and to ask patients who decline a vaccination why they are hesitant. Blanket messages about vaccine efficacy and safety are the first step, but individualized, more pointed conversations based on the patient’s personal experiences and beliefs have become increasingly important.

I routinely tell pregnant patients about the risks of COVID-19 and I explain that it has been difficult to predict who will develop severe illness. Sometimes more conversation is needed. For those who are still hesitant or who tell me they feel protected by a recent infection, for instance, I provide more detail on the unique risks of pregnancy — the fact that “pregnancy is different” — and that natural immunity wanes while the protection afforded by immunization is believed to last longer. Many women are also concerned about the safety of the COVID-19 vaccine, so having safety data at your fingertips is helpful. (See Table 2.)

Table 2: COVID-19 vaccine safety data: Examples of published reviews
Dr. Riley


The fact that influenza and COVID-19 vaccination protect the newborn as well as the mother is something that I find is underappreciated by many patients. Explaining that infants likely benefit from the passage of antibodies across the placenta should be part of patient counseling.
 

Counseling About RSV Vaccination

Importantly, for the 2024-2025 RSV season, the maternal RSV vaccine (Abrysvo, Pfizer) is recommended only for pregnant women who did not receive the vaccine during the 2023-2024 season. When more research is done and more data are obtained showing how long the immune response persists post vaccination, it may be that the US Food and Drug Administration (FDA) will approve the maternal RSV vaccine for use in every pregnancy.

The later timing of the vaccination recommendation — 32-36 weeks’ gestation — reflects a conservative approach taken by the FDA in response to data from one of the pivotal trials showing a numerical trend toward more preterm deliveries among vaccinated compared with unvaccinated patients. This imbalance in the original trial, which administered the vaccine during 24-36 weeks of gestation, was seen only in low-income countries with no temporal association, however.

In our experience at two Weill Cornell Medical College–associated hospitals we did not see this trend. Our cohort study of almost 3000 pregnant patients who delivered at 32 weeks’ gestation or later found no increased risk of preterm birth among the 35% of patients who received the RSV vaccine during the 2023-2024 RSV season. We also did not see any difference in preeclampsia, in contrast with original trial data that showed a signal for increased risk.11

When fewer than 2 weeks have elapsed between maternal vaccination and delivery, the monoclonal antibody nirsevimab is recommended for the newborn — ideally before the newborn leaves the hospital. Nirsevimab is also recommended for newborns of mothers who decline vaccination or were not candidates (e.g. vaccinated in a previous pregnancy), or when there is concern about the adequacy of the maternal immune response to the vaccine (e.g. in cases of immunosuppression).

While there was a limited supply of the monoclonal antibody last year, limitations are not expected this year, especially after October.

The ultimate goal is that patients choose the vaccine or the immunoglobulin, given the severity of RSV disease. Patient preferences should be considered. However, given that it takes 2 weeks after vaccination for protection to build up, I stress to patients that if they’ve vaccinated themselves, their newborn will leave the hospital with protection. If nirsevimab is relied upon, I explain, their newborn may not be protected for some period of time.
 

Take-home Messages

  • When patients decline or are hesitant about vaccines, ask why. Listen actively, and work to correct misperceptions and knowledge gaps.
  • Whenever possible, offer vaccines in your practice. Vaccination rates drop when this does not occur.
  • COVID-vaccine safety is backed by many studies showing no increase in birth defects, preterm delivery, miscarriage, or stillbirth.
  • Pregnant women are more likely to have severe illness from the influenza and SARS-CoV-2 viruses. Vaccines can prevent severe illness and can protect the newborn as well as the mother.
  • Recommend/administer the maternal RSV vaccine at 32-36 weeks’ gestation in women who did not receive the vaccine in the 2023-2024 season. If mothers aren’t eligible their babies should be offered nirsevimab.

Dr. Riley is the Given Foundation Professor and Chair of Obstetrics and Gynecology at Weill Cornell Medicine and the obstetrician and gynecologist-in-chief at New York Presbyterian Hospital. She disclosed that she has provided one-time consultations to Pfizer (Abrysvo RSV vaccine) and GSK (cytomegalovirus vaccine), and is providing consultant education on CMV for Moderna. She is chair of ACOG’s task force on immunization and emerging infectious diseases, serves on the medical advisory board for MAVEN, and serves as an editor or editorial board member for several medical publications.



References

1. ACOG Committee Opinion No. 741: Maternal Immunization. Obstet Gynecol. 2018;131(6):e214-e217.

2. Centers for Disease Control and Prevention. COVID-19 Vaccination for People Who are Pregnant or Breastfeeding. https://www.cdc.gov/covid/vaccines/pregnant-or-breastfeeding.html.

3. ACOG Practice Advisory on Maternal Respiratory Syncytial Virus Vaccination, September 2023. (Updated August 2024).4. Irving S et al. Open Forum Infect Dis. 2023;10(Suppl 2):ofad500.1002.

5. Flu Vaccination Dashboard, CDC, National Center for Immunization and Respiratory Diseases.

6. Weekly COVID-19 Vaccination Dashboard, CDC. https://www.cdc.gov/covidvaxview/weekly-dashboard/index.html

7. Louie JK et al. N Engl J Med. 2010;362:27-35. 8. Ciapponi A et al. Vaccine. 2021;39(40):5891-908.

9. Prasad S et al. Nature Communications. 2022;13:2414. 10. Fleming-Dutra KE et al. Obstet Gynecol Clin North Am 2023;50(2):279-97. 11. Mouen S et al. JAMA Network Open 2024;7(7):e2419268.

Editor’s Note: Sadly, this is the last column in the Master Class Obstetrics series. This award-winning column has been part of Ob.Gyn. News for 20 years. The deep discussion of cutting-edge topics in obstetrics by specialists and researchers will be missed as will the leadership and curation of topics by Dr. E. Albert Reece.
 

Introduction: The Need for Increased Vigilance About Maternal Immunization

Viruses are becoming increasingly prevalent in our world and the consequences of viral infections are implicated in a growing number of disease states. It is well established that certain cancers are caused by viruses and it is increasingly evident that viral infections can trigger the development of chronic illness. In pregnant women, viruses such as cytomegalovirus can cause infection in utero and lead to long-term impairments for the baby.

Likewise, it appears that the virulence of viruses is increasing, whether it be the respiratory syncytial virus (RSV) in children or the severe acute respiratory syndrome (SARS) coronaviruses in adults. Clearly, our environment is changing, with increases in population growth and urbanization, for instance, and an intensification of climate change and its effects. Viruses are part of this changing background.

Dr. E. Albert Reece, University of Maryland School of Medicine
Dr. E. Albert Reece


Vaccines are our most powerful tool to protect people of all ages against viral threats, and fortunately, we benefit from increasing expertise in vaccinology. Since 1974, the University of Maryland School of Medicine has a Center for Vaccine Development and Global Health that has conducted research on vaccines to defend against the Zika virus, H1N1, Ebola, and SARS-CoV-2.

We’re not alone. Other vaccinology centers across the country — as well as the National Institutes of Health at the national level, through its National Institute of Allergy and Infectious Diseases — are doing research and developing vaccines to combat viral diseases.

In this column, we are focused on viral diseases in pregnancy and the role that vaccines can play in preventing serious respiratory illness in mothers and their newborns. I have invited Laura E. Riley, MD, the Given Foundation Professor and Chair of Obstetrics and Gynecology at Weill Cornell Medicine, to address the importance of maternal immunization and how we can best counsel our patients and improve immunization rates.

As Dr. Riley explains, we are in a new era, and it behooves us all to be more vigilant about recommending vaccines, combating misperceptions, addressing patients’ knowledge gaps, and administering vaccines whenever possible.
 

Dr. Reece is the former Dean of Medicine & University Executive VP, and The Distinguished University and Endowed Professor & Director of the Center for Advanced Research Training and Innovation (CARTI) at the University of Maryland School of Medicine, as well as senior scientist at the Center for Birth Defects Research.

 

 

The alarming decline in maternal immunization rates that occurred in the wake of the COVID-19 pandemic means that, now more than ever, we must fully embrace our responsibility to recommend immunizations in pregnancy and to communicate what is known about their efficacy and safety. Data show that vaccination rates drop when we do not offer vaccines in our offices, so whenever possible, we should administer them as well.

The ob.gyn. is the patient’s most trusted person in pregnancy. When patients decline or express hesitancy about vaccines, it is incumbent upon us to ask why. Oftentimes, we can identify areas in which patients lack knowledge or have misperceptions and we can successfully educate the patient or change their perspective or misunderstanding concerning the importance of vaccination for themselves and their babies. (See Table 1.) We can also successfully address concerns about safety.

Table 1: Key messages on flue, COVID-19, and RSV vaccines in pregnancy
Dr. Riley


The safety of COVID-19 vaccinations in pregnancy is now backed by several years of data from multiple studies showing no increase in birth defects, preterm delivery, miscarriage, or stillbirth.

Data also show that pregnant patients are more likely than patients who are not pregnant to need hospitalization and intensive care when infected with SARS-CoV-2 and are at risk of having complications that can affect pregnancy and the newborn, including preterm birth and stillbirth. Vaccination has been shown to reduce the risk of severe illness and the risk of such adverse obstetrical outcomes, in addition to providing protection for the infant early on.

Similarly, influenza has long been more likely to be severe in pregnant patients, with an increased risk of poor obstetrical outcomes. Vaccines similarly provide “two for one protection,” protecting both mother and baby, and are, of course, backed by many years of safety and efficacy data.

Dr. Laura E. Riley is Given Foundation Professor in Clinical Obstetrics and Gynecology, Obstetrics and Gynecology, Weill Cornell Medical College, New York
New York Presbyterian
Dr. Laura E. Riley


With the new maternal respiratory syncytial virus (RSV) vaccine, now in its second year of availability, the goal is to protect the baby from RSV-caused serious lower respiratory tract illness. The illness has contributed to tens of thousands of annual hospitalizations and up to several hundred deaths every year in children younger than 5 years — particularly in those under age 6 months.

The RSV monoclonal antibody nirsevimab is available for the newborn as an alternative to maternal immunization but the maternal vaccine is optimal in that it will provide immediate rather than delayed protection for the newborn. The maternal vaccine is recommended during weeks 32-36 of pregnancy in mothers who were not vaccinated during last year’s RSV season. With real-world experience from year one, the available safety data are reassuring.
 

Counseling About Influenza and COVID-19 Vaccination

The COVID-19 pandemic took a toll on vaccination interest/receptivity broadly in pregnant and nonpregnant people. Among pregnant individuals, influenza vaccination coverage declined from 71% in the 2019-2020 influenza season to 56% in the 2021-2022 season, according to data from the Centers for Disease Control and Prevention’s Vaccine Safety Datalink.4 Coverage for the 2022-2023 and 2023-2024 influenza seasons was even worse: well under 50%.5

Fewer pregnant women have received updated COVID-19 vaccines. Only 13% of pregnant persons overall received the updated 2023-2024 COVID-19 booster vaccine (through March 30, 2024), according to the CDC.6

Maternal immunization for influenza has been recommended in the United States since 2004 (part of the recommendation that everyone over the age of 6 months receive an annual flu vaccine), and flu vaccines have been given to millions of pregnant women, but the H1N1 pandemic of 2009 reinforced its value as a priority for prenatal care. Most of the women who became severely ill from the H1N1 virus were young and healthy, without co-existing conditions known to increase risk.7

It became clearer during the H1N1 pandemic that pregnancy itself — which is associated with physiologic changes such as decreased lung capacity, increased nasal congestion and changes in the immune system – is its own significant risk factor for severe illness from the influenza virus. This increased risk applies to COVID-19 as well.

As COVID-19 has become endemic, with hospitalizations and deaths not reaching the levels of previous surges — and with mask-wearing and other preventive measures having declined — patients understandably have become more complacent. Some patients are vaccine deniers, but in my practice, these patients are a much smaller group than those who believe COVID-19 “is no big deal,” especially if they have had infections recently.

This is why it’s important to actively listen to concerns and to ask patients who decline a vaccination why they are hesitant. Blanket messages about vaccine efficacy and safety are the first step, but individualized, more pointed conversations based on the patient’s personal experiences and beliefs have become increasingly important.

I routinely tell pregnant patients about the risks of COVID-19 and I explain that it has been difficult to predict who will develop severe illness. Sometimes more conversation is needed. For those who are still hesitant or who tell me they feel protected by a recent infection, for instance, I provide more detail on the unique risks of pregnancy — the fact that “pregnancy is different” — and that natural immunity wanes while the protection afforded by immunization is believed to last longer. Many women are also concerned about the safety of the COVID-19 vaccine, so having safety data at your fingertips is helpful. (See Table 2.)

Table 2: COVID-19 vaccine safety data: Examples of published reviews
Dr. Riley


The fact that influenza and COVID-19 vaccination protect the newborn as well as the mother is something that I find is underappreciated by many patients. Explaining that infants likely benefit from the passage of antibodies across the placenta should be part of patient counseling.
 

Counseling About RSV Vaccination

Importantly, for the 2024-2025 RSV season, the maternal RSV vaccine (Abrysvo, Pfizer) is recommended only for pregnant women who did not receive the vaccine during the 2023-2024 season. When more research is done and more data are obtained showing how long the immune response persists post vaccination, it may be that the US Food and Drug Administration (FDA) will approve the maternal RSV vaccine for use in every pregnancy.

The later timing of the vaccination recommendation — 32-36 weeks’ gestation — reflects a conservative approach taken by the FDA in response to data from one of the pivotal trials showing a numerical trend toward more preterm deliveries among vaccinated compared with unvaccinated patients. This imbalance in the original trial, which administered the vaccine during 24-36 weeks of gestation, was seen only in low-income countries with no temporal association, however.

In our experience at two Weill Cornell Medical College–associated hospitals we did not see this trend. Our cohort study of almost 3000 pregnant patients who delivered at 32 weeks’ gestation or later found no increased risk of preterm birth among the 35% of patients who received the RSV vaccine during the 2023-2024 RSV season. We also did not see any difference in preeclampsia, in contrast with original trial data that showed a signal for increased risk.11

When fewer than 2 weeks have elapsed between maternal vaccination and delivery, the monoclonal antibody nirsevimab is recommended for the newborn — ideally before the newborn leaves the hospital. Nirsevimab is also recommended for newborns of mothers who decline vaccination or were not candidates (e.g. vaccinated in a previous pregnancy), or when there is concern about the adequacy of the maternal immune response to the vaccine (e.g. in cases of immunosuppression).

While there was a limited supply of the monoclonal antibody last year, limitations are not expected this year, especially after October.

The ultimate goal is that patients choose the vaccine or the immunoglobulin, given the severity of RSV disease. Patient preferences should be considered. However, given that it takes 2 weeks after vaccination for protection to build up, I stress to patients that if they’ve vaccinated themselves, their newborn will leave the hospital with protection. If nirsevimab is relied upon, I explain, their newborn may not be protected for some period of time.
 

Take-home Messages

  • When patients decline or are hesitant about vaccines, ask why. Listen actively, and work to correct misperceptions and knowledge gaps.
  • Whenever possible, offer vaccines in your practice. Vaccination rates drop when this does not occur.
  • COVID-vaccine safety is backed by many studies showing no increase in birth defects, preterm delivery, miscarriage, or stillbirth.
  • Pregnant women are more likely to have severe illness from the influenza and SARS-CoV-2 viruses. Vaccines can prevent severe illness and can protect the newborn as well as the mother.
  • Recommend/administer the maternal RSV vaccine at 32-36 weeks’ gestation in women who did not receive the vaccine in the 2023-2024 season. If mothers aren’t eligible their babies should be offered nirsevimab.

Dr. Riley is the Given Foundation Professor and Chair of Obstetrics and Gynecology at Weill Cornell Medicine and the obstetrician and gynecologist-in-chief at New York Presbyterian Hospital. She disclosed that she has provided one-time consultations to Pfizer (Abrysvo RSV vaccine) and GSK (cytomegalovirus vaccine), and is providing consultant education on CMV for Moderna. She is chair of ACOG’s task force on immunization and emerging infectious diseases, serves on the medical advisory board for MAVEN, and serves as an editor or editorial board member for several medical publications.



References

1. ACOG Committee Opinion No. 741: Maternal Immunization. Obstet Gynecol. 2018;131(6):e214-e217.

2. Centers for Disease Control and Prevention. COVID-19 Vaccination for People Who are Pregnant or Breastfeeding. https://www.cdc.gov/covid/vaccines/pregnant-or-breastfeeding.html.

3. ACOG Practice Advisory on Maternal Respiratory Syncytial Virus Vaccination, September 2023. (Updated August 2024).4. Irving S et al. Open Forum Infect Dis. 2023;10(Suppl 2):ofad500.1002.

5. Flu Vaccination Dashboard, CDC, National Center for Immunization and Respiratory Diseases.

6. Weekly COVID-19 Vaccination Dashboard, CDC. https://www.cdc.gov/covidvaxview/weekly-dashboard/index.html

7. Louie JK et al. N Engl J Med. 2010;362:27-35. 8. Ciapponi A et al. Vaccine. 2021;39(40):5891-908.

9. Prasad S et al. Nature Communications. 2022;13:2414. 10. Fleming-Dutra KE et al. Obstet Gynecol Clin North Am 2023;50(2):279-97. 11. Mouen S et al. JAMA Network Open 2024;7(7):e2419268.

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Maternal immunization is a priority

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Maternal immunization remains a priority for ob.gyns. – an opportunity to provide protection against serious infectious diseases for both the mother and the baby. With influenza vaccination rates in pregnant women still hovering around 50% and the emerging public health problem of vaccine hesitancy, we must fully embrace our responsibility to recommend immunizations and to effectively communicate what is known about their efficacy and safety. Ideally, we should offer them as well.

Dr. Laura E. Riley, a maternal-fetal medicine specialist at Weill Cornell Medical College, New York
Dr. Laura E. Riley

One reason for the low rates of influenza vaccination – one of the two vaccinations routinely recommended for all pregnant women in the United States – is that pregnant women do not always know the importance of the vaccine. This is actionable: Data clearly show that the physician’s recommendation makes a difference and that a clinician’s offer to administer the vaccination has an even greater impact.

A 2017 Centers for Disease Control and Prevention analysis of data from Internet panel surveys1 shows that women who reported receiving both a clinician recommendation and offer of vaccination had higher coverage during the 2015-2016 and 2016-2017 influenza seasons (63.7% and 70.5%) than did women who reported receiving a clinician recommendation but no offer (37.5% and 43.7%) and women who reported receiving no recommendation for vaccination (12.8% and 14.8%).

The analysis suggests there are consistently missed opportunities: Fewer than 70% (67.3%) of pregnant women in the 2016-2017 flu season reported receiving a clinician recommendation for and offer of vaccination. This is similar to the prior three flu seasons, according to the CDC.

This year, with the COVID-19 pandemic ensuing, the prevention of severe influenza illness – and other vaccine-preventable illnesses – takes on even greater importance. It is not known what the impact of two potentially devastating respiratory infections could be for pregnant individuals. Therefore, maximal protection against at least influenza will be critical.
 

Influenza and Tdap

Poor outcomes and disproportionately high death rates for pregnant women were observed in both the influenza pandemic of 1918-1919 and the 1957 “Asian flu” pandemic. Maternal immunization for influenza has been recommended in the United States since 2004 (part of the recommendation that everyone over the age of 6 months receive an annual flu vaccine), but it was the H1N1 influenza pandemic of 2009 that reinforced its value and led our field to more fully embrace influenza vaccination as a priority for prenatal care.

Surprisingly, most of the pregnant women who became severely ill from the H1N1 virus were young and healthy and did not have a coexisting condition known to increase risk, such as asthma or diabetes. In an analysis of California epidemiologic data, 2 only one-third of 94 pregnant women who were hospitalized with 2009 H1N1 influenza had established risk factors for complications from influenza, compared with almost two-thirds of nonpregnant women of reproductive age.

Nationally, 75 deaths of pregnant women were confirmed as because of H1N1 and 34 were possibly related to H1N1, most of which (64.3%) occurred in the third trimester.3 Records of the 1957 pandemic similarly show that pregnant women in the second and third trimesters were particularly affected.

That healthy pregnant women became so ill during the H1N1 pandemic raised several flags. For one, it became clearer that pregnancy is its own significant risk factor for severe illness from the influenza virus. Physiological changes believed to make a pregnant woman more susceptible to becoming ill include decreased lung capacity, increased nasal congestion, reduced colloid oncotic pressure, and changes in the immune system. The morbidity and mortality from H1N1 influenza also increased our drive as a specialty to convince women that vaccination is an important strategy in each influenza season.

The flu vaccine can be administered at any point during pregnancy. There is no evidence that the safety profile is any different during one trimester than another.

Patients should be reassured that vaccines recommended in pregnancy have undergone rigorous testing and that the influenza vaccine has been given to millions of pregnant women over decades. They also should understand that contracting influenza has risks for the fetus; research has demonstrated that pregnant women who contract influenza are at greater risk of spontaneous abortion as well as preterm birth and low birth weight.4

In addition, the issue of flu vaccine efficacy needs to be properly teased apart. Women read every year that the vaccine is not effective, so we need to discuss with patients what efficacy means. Does the vaccine prevent illness altogether, or does it prevent severe illness? For the most part, whereas influenza vaccines often do not offer an exact match for the year’s circulating strains – and therefore may not prevent all illness – data show that the vaccine can prevent severe illness.5 That is a worthy outcome.

Also worthy is the impact of influenza vaccination on the newborn. That maternal immunization also protects the baby – it can reduce the risk for influenza in infants under 6 months of age – is underappreciated and should be part of patient counseling. There is clear evidence that maternal immunization boosts the concentration of maternal antibodies that can cross the placenta and that infants benefit from this passive antibody protection.6

The Tdap vaccine (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis), the second vaccine routinely recommended during each pregnancy, is administered as early as possible during the third trimester precisely for this reason – to boost maternal immune response and maximize the passive transfer of antibodies to the newborn. The target is the prevention of pertussis and associated hospitalizations and death during the first 2 months of life in an era when sporadic and unpredictable outbreaks of the infection are occurring.

Data from the CDC of morbidity and mortality from pertussis in children (2001-2011) prior to routine maternal vaccination show that the highest rates of pediatric hospitalizations and deaths occurred in newborns. Research has demonstrated that the Tdap vaccine is highly effective in preventing infections and hospitalizations in newborns: Case-control and cohort studies in the United Kingdom7,8 have shown vaccine effectiveness of 91%-93%, and similar research9 done in the U.S. has demonstrated effectiveness of 78%-85%.

The Tdap vaccine is recommended for pregnant women at 27-36 weeks of gestation – in each pregnancy. The reason for revaccination with each pregnancy is that antibody levels do not remain high for too long; at 8 months post immunization, research has shown, maternal antibody levels have begun to wane.

The vaccine also is recommended for all individuals who will be in close contact with infants younger than 12 months (for example, parents, grandparents, and child-care providers) and who have not previously received it. However, “cocooning” the newborn is effective only when the mother also is immunized – a point that ob.gyns. need to better explain to their patients so that they understand the purpose of this strategy.
 

 

 

Other vaccines in pregnancy and post partum

As described in the American College of Obstetricians and Gynecologists’ committee opinion on maternal immunization, 4 it is the responsibility of the ob.gyn. or obstetric care provider to routinely assess the immunization status of every pregnant patient and recommend additional vaccines for those patients who have conditions or social/behavioral practices that put them at higher risk of acquiring vaccine-preventable diseases.

Patients who have asthma or diabetes, who smoke, or who have never been vaccinated for the prevention of pneumococcal disease should receive the PPV23 pneumococcal vaccine, for instance. For pregnant women with immune deficiencies such as HIV, the PCV13 vaccine followed by PPV23 is recommended. There are approximately 500,000 cases of invasive pneumococcal disease in the United States each year, resulting in 40,000 deaths, and many multidrug-resistant strains of Streptococcus pneumoniae.

Hepatitis A and B vaccines – both recombinant vaccines with no safety concerns – also can be given during pregnancy and are officially recommended for women who have high-risk exposures. In the case of hepatitis A, high risk entails traveling to countries where the disease is endemic. High-risk behavior for hepatitis B includes sex work or being the household contact or sexual partner of a person positive for hepatitis B surface antigen.

Other travel-related vaccines, such as Japanese encephalitis, yellow fever, smallpox, and inactivated polio vaccine, can be considered in pregnancy, but decisions should be driven by more in-depth conversations about potential risks and benefits. Unlike for other vaccinations, there are limited data on the safety of travel-related immunizations in pregnancy. Sometimes, the question of whether travel is advisable in the middle of pregnancy – whether potential risks are worth taking – is a valid question to pose in conversations with patients.

Standard obstetric practice includes assessment of rubella susceptibility at the beginning of pregnancy. In some locations such as New York, measles susceptibility is also routinely evaluated. After delivery, seronegative women should be vaccinated with MMR (measles, mumps, and rubella) vaccine prior to discharge. In recent years, with the growing problem of vaccine refusal and an increasingly mobile and global society, we’re seeing sporadic outbreaks of measles and rubella – diseases that were once eradicated.

Measles in particular is highly contagious and requires a herd immunity threshold of 92%-94% to prevent sustained spread of the disease. Postpartum immunization has important maternal and pediatric implications for subsequent pregnancies, before which vaccination is often missed.

Both the MMR vaccine and the varicella vaccine (another vaccine that can be initiated post partum) are live vaccines and therefore contraindicated during pregnancy but should be administered post partum, including to people who are breastfeeding.

Other immunizations that hold some promise to protect either the mother or fetus/neonate or both are in various stages of development or testing. These include vaccines for cytomegalovirus, malaria, respiratory syncytial virus, and group B streptococcus.
 

A word about COVID-19

In mid-July there were more than 120 vaccine candidates for COVID-19 in various phases of study and a host of questions. Will a vaccine be efficacious? Will it prevent severe illness, or illness altogether? And will it be safe for pregnant women?

Vaccines work by manipulating the immune system, and it is important to appreciate the possibility that there may be unique pregnancy-related issues to consider with future COVID-19 vaccines – issues that could influence the effectiveness, safety, and timing of vaccination – and to understand that with any new immunization, there will likely be reluctance on the part of pregnant women who routinely prioritize fetal safety over their own health.

Pregnant women have been excluded from COVID-19 vaccine trials, but there may come a time when experts decide that a vaccine against COVID-19 is beneficial in pregnancy. Thus far, we know that the disease is clearly different from influenza. A growing knowledge of the impact of COVID-19 on the health of pregnant women, particularly the risk of developing severe illness, will be important for the future of COVID-19 immunization, as many women will not want to accept any potential risk of a vaccine unless they believe there is a significant benefit.
 

References

1. MMWR Morb Mortal Wkly Rep. 2017 Sep 29;66(38):1016-22.

2. N Engl J Med. 2010 Jan 7;362(1):27-35.

3. Obstet Gynecol. 2015 Sep;126(3):486-90.

4. Obstet Gynecol. 2018 Jun;131(6):e214-e217.

5. MMWR Morb Mortal Wkly Rep. 2019 Feb 15;68(6):135-9.

6. Obstet Gynecol. 2019 Apr;133(4):739-53.

7. Lancet. 2014 Oct 25;384(9953):1521-8.

8. Clin Infect Dis. 2015 Feb 1;60(3):333-7.

9. Clin Infect Dis. 2017 Jan 1;64(1):9-14.

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Maternal immunization remains a priority for ob.gyns. – an opportunity to provide protection against serious infectious diseases for both the mother and the baby. With influenza vaccination rates in pregnant women still hovering around 50% and the emerging public health problem of vaccine hesitancy, we must fully embrace our responsibility to recommend immunizations and to effectively communicate what is known about their efficacy and safety. Ideally, we should offer them as well.

Dr. Laura E. Riley, a maternal-fetal medicine specialist at Weill Cornell Medical College, New York
Dr. Laura E. Riley

One reason for the low rates of influenza vaccination – one of the two vaccinations routinely recommended for all pregnant women in the United States – is that pregnant women do not always know the importance of the vaccine. This is actionable: Data clearly show that the physician’s recommendation makes a difference and that a clinician’s offer to administer the vaccination has an even greater impact.

A 2017 Centers for Disease Control and Prevention analysis of data from Internet panel surveys1 shows that women who reported receiving both a clinician recommendation and offer of vaccination had higher coverage during the 2015-2016 and 2016-2017 influenza seasons (63.7% and 70.5%) than did women who reported receiving a clinician recommendation but no offer (37.5% and 43.7%) and women who reported receiving no recommendation for vaccination (12.8% and 14.8%).

The analysis suggests there are consistently missed opportunities: Fewer than 70% (67.3%) of pregnant women in the 2016-2017 flu season reported receiving a clinician recommendation for and offer of vaccination. This is similar to the prior three flu seasons, according to the CDC.

This year, with the COVID-19 pandemic ensuing, the prevention of severe influenza illness – and other vaccine-preventable illnesses – takes on even greater importance. It is not known what the impact of two potentially devastating respiratory infections could be for pregnant individuals. Therefore, maximal protection against at least influenza will be critical.
 

Influenza and Tdap

Poor outcomes and disproportionately high death rates for pregnant women were observed in both the influenza pandemic of 1918-1919 and the 1957 “Asian flu” pandemic. Maternal immunization for influenza has been recommended in the United States since 2004 (part of the recommendation that everyone over the age of 6 months receive an annual flu vaccine), but it was the H1N1 influenza pandemic of 2009 that reinforced its value and led our field to more fully embrace influenza vaccination as a priority for prenatal care.

Surprisingly, most of the pregnant women who became severely ill from the H1N1 virus were young and healthy and did not have a coexisting condition known to increase risk, such as asthma or diabetes. In an analysis of California epidemiologic data, 2 only one-third of 94 pregnant women who were hospitalized with 2009 H1N1 influenza had established risk factors for complications from influenza, compared with almost two-thirds of nonpregnant women of reproductive age.

Nationally, 75 deaths of pregnant women were confirmed as because of H1N1 and 34 were possibly related to H1N1, most of which (64.3%) occurred in the third trimester.3 Records of the 1957 pandemic similarly show that pregnant women in the second and third trimesters were particularly affected.

That healthy pregnant women became so ill during the H1N1 pandemic raised several flags. For one, it became clearer that pregnancy is its own significant risk factor for severe illness from the influenza virus. Physiological changes believed to make a pregnant woman more susceptible to becoming ill include decreased lung capacity, increased nasal congestion, reduced colloid oncotic pressure, and changes in the immune system. The morbidity and mortality from H1N1 influenza also increased our drive as a specialty to convince women that vaccination is an important strategy in each influenza season.

The flu vaccine can be administered at any point during pregnancy. There is no evidence that the safety profile is any different during one trimester than another.

Patients should be reassured that vaccines recommended in pregnancy have undergone rigorous testing and that the influenza vaccine has been given to millions of pregnant women over decades. They also should understand that contracting influenza has risks for the fetus; research has demonstrated that pregnant women who contract influenza are at greater risk of spontaneous abortion as well as preterm birth and low birth weight.4

In addition, the issue of flu vaccine efficacy needs to be properly teased apart. Women read every year that the vaccine is not effective, so we need to discuss with patients what efficacy means. Does the vaccine prevent illness altogether, or does it prevent severe illness? For the most part, whereas influenza vaccines often do not offer an exact match for the year’s circulating strains – and therefore may not prevent all illness – data show that the vaccine can prevent severe illness.5 That is a worthy outcome.

Also worthy is the impact of influenza vaccination on the newborn. That maternal immunization also protects the baby – it can reduce the risk for influenza in infants under 6 months of age – is underappreciated and should be part of patient counseling. There is clear evidence that maternal immunization boosts the concentration of maternal antibodies that can cross the placenta and that infants benefit from this passive antibody protection.6

The Tdap vaccine (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis), the second vaccine routinely recommended during each pregnancy, is administered as early as possible during the third trimester precisely for this reason – to boost maternal immune response and maximize the passive transfer of antibodies to the newborn. The target is the prevention of pertussis and associated hospitalizations and death during the first 2 months of life in an era when sporadic and unpredictable outbreaks of the infection are occurring.

Data from the CDC of morbidity and mortality from pertussis in children (2001-2011) prior to routine maternal vaccination show that the highest rates of pediatric hospitalizations and deaths occurred in newborns. Research has demonstrated that the Tdap vaccine is highly effective in preventing infections and hospitalizations in newborns: Case-control and cohort studies in the United Kingdom7,8 have shown vaccine effectiveness of 91%-93%, and similar research9 done in the U.S. has demonstrated effectiveness of 78%-85%.

The Tdap vaccine is recommended for pregnant women at 27-36 weeks of gestation – in each pregnancy. The reason for revaccination with each pregnancy is that antibody levels do not remain high for too long; at 8 months post immunization, research has shown, maternal antibody levels have begun to wane.

The vaccine also is recommended for all individuals who will be in close contact with infants younger than 12 months (for example, parents, grandparents, and child-care providers) and who have not previously received it. However, “cocooning” the newborn is effective only when the mother also is immunized – a point that ob.gyns. need to better explain to their patients so that they understand the purpose of this strategy.
 

 

 

Other vaccines in pregnancy and post partum

As described in the American College of Obstetricians and Gynecologists’ committee opinion on maternal immunization, 4 it is the responsibility of the ob.gyn. or obstetric care provider to routinely assess the immunization status of every pregnant patient and recommend additional vaccines for those patients who have conditions or social/behavioral practices that put them at higher risk of acquiring vaccine-preventable diseases.

Patients who have asthma or diabetes, who smoke, or who have never been vaccinated for the prevention of pneumococcal disease should receive the PPV23 pneumococcal vaccine, for instance. For pregnant women with immune deficiencies such as HIV, the PCV13 vaccine followed by PPV23 is recommended. There are approximately 500,000 cases of invasive pneumococcal disease in the United States each year, resulting in 40,000 deaths, and many multidrug-resistant strains of Streptococcus pneumoniae.

Hepatitis A and B vaccines – both recombinant vaccines with no safety concerns – also can be given during pregnancy and are officially recommended for women who have high-risk exposures. In the case of hepatitis A, high risk entails traveling to countries where the disease is endemic. High-risk behavior for hepatitis B includes sex work or being the household contact or sexual partner of a person positive for hepatitis B surface antigen.

Other travel-related vaccines, such as Japanese encephalitis, yellow fever, smallpox, and inactivated polio vaccine, can be considered in pregnancy, but decisions should be driven by more in-depth conversations about potential risks and benefits. Unlike for other vaccinations, there are limited data on the safety of travel-related immunizations in pregnancy. Sometimes, the question of whether travel is advisable in the middle of pregnancy – whether potential risks are worth taking – is a valid question to pose in conversations with patients.

Standard obstetric practice includes assessment of rubella susceptibility at the beginning of pregnancy. In some locations such as New York, measles susceptibility is also routinely evaluated. After delivery, seronegative women should be vaccinated with MMR (measles, mumps, and rubella) vaccine prior to discharge. In recent years, with the growing problem of vaccine refusal and an increasingly mobile and global society, we’re seeing sporadic outbreaks of measles and rubella – diseases that were once eradicated.

Measles in particular is highly contagious and requires a herd immunity threshold of 92%-94% to prevent sustained spread of the disease. Postpartum immunization has important maternal and pediatric implications for subsequent pregnancies, before which vaccination is often missed.

Both the MMR vaccine and the varicella vaccine (another vaccine that can be initiated post partum) are live vaccines and therefore contraindicated during pregnancy but should be administered post partum, including to people who are breastfeeding.

Other immunizations that hold some promise to protect either the mother or fetus/neonate or both are in various stages of development or testing. These include vaccines for cytomegalovirus, malaria, respiratory syncytial virus, and group B streptococcus.
 

A word about COVID-19

In mid-July there were more than 120 vaccine candidates for COVID-19 in various phases of study and a host of questions. Will a vaccine be efficacious? Will it prevent severe illness, or illness altogether? And will it be safe for pregnant women?

Vaccines work by manipulating the immune system, and it is important to appreciate the possibility that there may be unique pregnancy-related issues to consider with future COVID-19 vaccines – issues that could influence the effectiveness, safety, and timing of vaccination – and to understand that with any new immunization, there will likely be reluctance on the part of pregnant women who routinely prioritize fetal safety over their own health.

Pregnant women have been excluded from COVID-19 vaccine trials, but there may come a time when experts decide that a vaccine against COVID-19 is beneficial in pregnancy. Thus far, we know that the disease is clearly different from influenza. A growing knowledge of the impact of COVID-19 on the health of pregnant women, particularly the risk of developing severe illness, will be important for the future of COVID-19 immunization, as many women will not want to accept any potential risk of a vaccine unless they believe there is a significant benefit.
 

References

1. MMWR Morb Mortal Wkly Rep. 2017 Sep 29;66(38):1016-22.

2. N Engl J Med. 2010 Jan 7;362(1):27-35.

3. Obstet Gynecol. 2015 Sep;126(3):486-90.

4. Obstet Gynecol. 2018 Jun;131(6):e214-e217.

5. MMWR Morb Mortal Wkly Rep. 2019 Feb 15;68(6):135-9.

6. Obstet Gynecol. 2019 Apr;133(4):739-53.

7. Lancet. 2014 Oct 25;384(9953):1521-8.

8. Clin Infect Dis. 2015 Feb 1;60(3):333-7.

9. Clin Infect Dis. 2017 Jan 1;64(1):9-14.

Maternal immunization remains a priority for ob.gyns. – an opportunity to provide protection against serious infectious diseases for both the mother and the baby. With influenza vaccination rates in pregnant women still hovering around 50% and the emerging public health problem of vaccine hesitancy, we must fully embrace our responsibility to recommend immunizations and to effectively communicate what is known about their efficacy and safety. Ideally, we should offer them as well.

Dr. Laura E. Riley, a maternal-fetal medicine specialist at Weill Cornell Medical College, New York
Dr. Laura E. Riley

One reason for the low rates of influenza vaccination – one of the two vaccinations routinely recommended for all pregnant women in the United States – is that pregnant women do not always know the importance of the vaccine. This is actionable: Data clearly show that the physician’s recommendation makes a difference and that a clinician’s offer to administer the vaccination has an even greater impact.

A 2017 Centers for Disease Control and Prevention analysis of data from Internet panel surveys1 shows that women who reported receiving both a clinician recommendation and offer of vaccination had higher coverage during the 2015-2016 and 2016-2017 influenza seasons (63.7% and 70.5%) than did women who reported receiving a clinician recommendation but no offer (37.5% and 43.7%) and women who reported receiving no recommendation for vaccination (12.8% and 14.8%).

The analysis suggests there are consistently missed opportunities: Fewer than 70% (67.3%) of pregnant women in the 2016-2017 flu season reported receiving a clinician recommendation for and offer of vaccination. This is similar to the prior three flu seasons, according to the CDC.

This year, with the COVID-19 pandemic ensuing, the prevention of severe influenza illness – and other vaccine-preventable illnesses – takes on even greater importance. It is not known what the impact of two potentially devastating respiratory infections could be for pregnant individuals. Therefore, maximal protection against at least influenza will be critical.
 

Influenza and Tdap

Poor outcomes and disproportionately high death rates for pregnant women were observed in both the influenza pandemic of 1918-1919 and the 1957 “Asian flu” pandemic. Maternal immunization for influenza has been recommended in the United States since 2004 (part of the recommendation that everyone over the age of 6 months receive an annual flu vaccine), but it was the H1N1 influenza pandemic of 2009 that reinforced its value and led our field to more fully embrace influenza vaccination as a priority for prenatal care.

Surprisingly, most of the pregnant women who became severely ill from the H1N1 virus were young and healthy and did not have a coexisting condition known to increase risk, such as asthma or diabetes. In an analysis of California epidemiologic data, 2 only one-third of 94 pregnant women who were hospitalized with 2009 H1N1 influenza had established risk factors for complications from influenza, compared with almost two-thirds of nonpregnant women of reproductive age.

Nationally, 75 deaths of pregnant women were confirmed as because of H1N1 and 34 were possibly related to H1N1, most of which (64.3%) occurred in the third trimester.3 Records of the 1957 pandemic similarly show that pregnant women in the second and third trimesters were particularly affected.

That healthy pregnant women became so ill during the H1N1 pandemic raised several flags. For one, it became clearer that pregnancy is its own significant risk factor for severe illness from the influenza virus. Physiological changes believed to make a pregnant woman more susceptible to becoming ill include decreased lung capacity, increased nasal congestion, reduced colloid oncotic pressure, and changes in the immune system. The morbidity and mortality from H1N1 influenza also increased our drive as a specialty to convince women that vaccination is an important strategy in each influenza season.

The flu vaccine can be administered at any point during pregnancy. There is no evidence that the safety profile is any different during one trimester than another.

Patients should be reassured that vaccines recommended in pregnancy have undergone rigorous testing and that the influenza vaccine has been given to millions of pregnant women over decades. They also should understand that contracting influenza has risks for the fetus; research has demonstrated that pregnant women who contract influenza are at greater risk of spontaneous abortion as well as preterm birth and low birth weight.4

In addition, the issue of flu vaccine efficacy needs to be properly teased apart. Women read every year that the vaccine is not effective, so we need to discuss with patients what efficacy means. Does the vaccine prevent illness altogether, or does it prevent severe illness? For the most part, whereas influenza vaccines often do not offer an exact match for the year’s circulating strains – and therefore may not prevent all illness – data show that the vaccine can prevent severe illness.5 That is a worthy outcome.

Also worthy is the impact of influenza vaccination on the newborn. That maternal immunization also protects the baby – it can reduce the risk for influenza in infants under 6 months of age – is underappreciated and should be part of patient counseling. There is clear evidence that maternal immunization boosts the concentration of maternal antibodies that can cross the placenta and that infants benefit from this passive antibody protection.6

The Tdap vaccine (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis), the second vaccine routinely recommended during each pregnancy, is administered as early as possible during the third trimester precisely for this reason – to boost maternal immune response and maximize the passive transfer of antibodies to the newborn. The target is the prevention of pertussis and associated hospitalizations and death during the first 2 months of life in an era when sporadic and unpredictable outbreaks of the infection are occurring.

Data from the CDC of morbidity and mortality from pertussis in children (2001-2011) prior to routine maternal vaccination show that the highest rates of pediatric hospitalizations and deaths occurred in newborns. Research has demonstrated that the Tdap vaccine is highly effective in preventing infections and hospitalizations in newborns: Case-control and cohort studies in the United Kingdom7,8 have shown vaccine effectiveness of 91%-93%, and similar research9 done in the U.S. has demonstrated effectiveness of 78%-85%.

The Tdap vaccine is recommended for pregnant women at 27-36 weeks of gestation – in each pregnancy. The reason for revaccination with each pregnancy is that antibody levels do not remain high for too long; at 8 months post immunization, research has shown, maternal antibody levels have begun to wane.

The vaccine also is recommended for all individuals who will be in close contact with infants younger than 12 months (for example, parents, grandparents, and child-care providers) and who have not previously received it. However, “cocooning” the newborn is effective only when the mother also is immunized – a point that ob.gyns. need to better explain to their patients so that they understand the purpose of this strategy.
 

 

 

Other vaccines in pregnancy and post partum

As described in the American College of Obstetricians and Gynecologists’ committee opinion on maternal immunization, 4 it is the responsibility of the ob.gyn. or obstetric care provider to routinely assess the immunization status of every pregnant patient and recommend additional vaccines for those patients who have conditions or social/behavioral practices that put them at higher risk of acquiring vaccine-preventable diseases.

Patients who have asthma or diabetes, who smoke, or who have never been vaccinated for the prevention of pneumococcal disease should receive the PPV23 pneumococcal vaccine, for instance. For pregnant women with immune deficiencies such as HIV, the PCV13 vaccine followed by PPV23 is recommended. There are approximately 500,000 cases of invasive pneumococcal disease in the United States each year, resulting in 40,000 deaths, and many multidrug-resistant strains of Streptococcus pneumoniae.

Hepatitis A and B vaccines – both recombinant vaccines with no safety concerns – also can be given during pregnancy and are officially recommended for women who have high-risk exposures. In the case of hepatitis A, high risk entails traveling to countries where the disease is endemic. High-risk behavior for hepatitis B includes sex work or being the household contact or sexual partner of a person positive for hepatitis B surface antigen.

Other travel-related vaccines, such as Japanese encephalitis, yellow fever, smallpox, and inactivated polio vaccine, can be considered in pregnancy, but decisions should be driven by more in-depth conversations about potential risks and benefits. Unlike for other vaccinations, there are limited data on the safety of travel-related immunizations in pregnancy. Sometimes, the question of whether travel is advisable in the middle of pregnancy – whether potential risks are worth taking – is a valid question to pose in conversations with patients.

Standard obstetric practice includes assessment of rubella susceptibility at the beginning of pregnancy. In some locations such as New York, measles susceptibility is also routinely evaluated. After delivery, seronegative women should be vaccinated with MMR (measles, mumps, and rubella) vaccine prior to discharge. In recent years, with the growing problem of vaccine refusal and an increasingly mobile and global society, we’re seeing sporadic outbreaks of measles and rubella – diseases that were once eradicated.

Measles in particular is highly contagious and requires a herd immunity threshold of 92%-94% to prevent sustained spread of the disease. Postpartum immunization has important maternal and pediatric implications for subsequent pregnancies, before which vaccination is often missed.

Both the MMR vaccine and the varicella vaccine (another vaccine that can be initiated post partum) are live vaccines and therefore contraindicated during pregnancy but should be administered post partum, including to people who are breastfeeding.

Other immunizations that hold some promise to protect either the mother or fetus/neonate or both are in various stages of development or testing. These include vaccines for cytomegalovirus, malaria, respiratory syncytial virus, and group B streptococcus.
 

A word about COVID-19

In mid-July there were more than 120 vaccine candidates for COVID-19 in various phases of study and a host of questions. Will a vaccine be efficacious? Will it prevent severe illness, or illness altogether? And will it be safe for pregnant women?

Vaccines work by manipulating the immune system, and it is important to appreciate the possibility that there may be unique pregnancy-related issues to consider with future COVID-19 vaccines – issues that could influence the effectiveness, safety, and timing of vaccination – and to understand that with any new immunization, there will likely be reluctance on the part of pregnant women who routinely prioritize fetal safety over their own health.

Pregnant women have been excluded from COVID-19 vaccine trials, but there may come a time when experts decide that a vaccine against COVID-19 is beneficial in pregnancy. Thus far, we know that the disease is clearly different from influenza. A growing knowledge of the impact of COVID-19 on the health of pregnant women, particularly the risk of developing severe illness, will be important for the future of COVID-19 immunization, as many women will not want to accept any potential risk of a vaccine unless they believe there is a significant benefit.
 

References

1. MMWR Morb Mortal Wkly Rep. 2017 Sep 29;66(38):1016-22.

2. N Engl J Med. 2010 Jan 7;362(1):27-35.

3. Obstet Gynecol. 2015 Sep;126(3):486-90.

4. Obstet Gynecol. 2018 Jun;131(6):e214-e217.

5. MMWR Morb Mortal Wkly Rep. 2019 Feb 15;68(6):135-9.

6. Obstet Gynecol. 2019 Apr;133(4):739-53.

7. Lancet. 2014 Oct 25;384(9953):1521-8.

8. Clin Infect Dis. 2015 Feb 1;60(3):333-7.

9. Clin Infect Dis. 2017 Jan 1;64(1):9-14.

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