ACIP Evidence to Recommendations for Use of Pfizer RSVpreF in Pregnant People

About

The Evidence to Recommendations (EtR) frameworks describe information considered in moving from evidence to ACIP vaccine recommendations.

Summary

Question: Should Pfizer RSVpreF vaccine be recommended for pregnant people to be given during 32 through 36 weeks gestation to prevent RSV lower respiratory tract infection in infants?

Population: Pregnant people

Intervention: Pfizer RSVpreF Vaccine given at 32–36 weeks gestation

Comparison: No vaccine

Outcomes:

  • Medically attended RSV-associated lower respiratory tract infection in infants
  • Hospitalization for RSV-associated lower respiratory tract infection in infants
  • Intensive care unit (ICU) admission from RSV hospitalization in infants
  • Mechanical ventilation from RSV hospitalization in infants
  • RSV-associated death in infants
  • All-cause hospitalization for lower respiratory tract infection in infants
  • All-cause medically attended lower respiratory tract infection in infants
  • Serious adverse events in pregnant people
  • Reactogenicity (grade 3+) in pregnant people
  • Serious adverse events in infants
  • Preterm birth

Background

RSV is the most common cause of hospitalization in U.S. infants.1 The highest hospitalization rates are in the first months of life and risk declines with increasing age in infancy and during early childhood. During the 2017–2020 seasons prior to the COVID-19 pandemic, RSV transmission followed a consistent seasonal pattern, beginning earliest in Florida and the Southeast and peaking during December–February across most the United States. However, the COVID-19 pandemic interrupted seasonal circulation of RSV and many other respiratory viruses. Following over a year of limited RSV circulation, the United States experienced an interseasonal RSV wave that peaked in July 2021 and continued throughout the Fall into late December. Although some limited regional interseasonal transmission occurred in Summer 2022, largely in the South- and South-Central United States, the RSV season peaked in November and returned to off-season levels in January, suggesting that RSV circulation may be returning to typical winter seasonality.2 RSV transmission patterns in 2023 also suggest that patterns are shifting towards pre-pandemic seasonal RSV trends.3

It has been estimated that each year among U.S. children aged less than 5 years, RSV is associated with 100 – 300 deaths, 58,000 – 80,000 hospitalizations, nearly 520,000 emergency department visits and approximately 1,500,000 outpatient visits.4-8

On August 21, 2023, the U.S. Food and Drug Administration (FDA) approved the Biologics License Application of RSVpreF vaccine for use in pregnant people 32 through 36 weeks gestation for prevention of RSV in infants younger than 6 months of age.9 Following FDA’s regulatory action, the Advisory Committee on Immunization Practices (ACIP) met on September 22, 2023 and voted to recommend Pfizer RSV maternal vaccine, using seasonal administration.

Additional background information supporting the ACIP recommendation on the use of RSVpreF vaccine can be found in the relevant publication of the recommendation referenced on the ACIP website.

Public Health Problem

Criteria Work Group Judgements Evidence Additional Information
Is the problem of public health importance? Yes

Each year among U.S. children aged less than 5 years, RSV is associated with an estimated 100 – 300 deaths, 58,000 – 80,000 hospitalizations, nearly 520,000 emergency department visits, and approximately 1,500,000 outpatient visits.1-5

RSV is the most common cause of hospitalization in U.S. infants.6 The highest hospitalization rates are in the first months of life and risk declines with increasing age in infancy and during early childhood.7 Prematurity and other chronic diseases increase risk of RSV-associated hospitalization, but most hospitalizations are in healthy, term infants.7,8
 The Work Group felt that RSV in infants is of public health importance.

Benefits and Harms

Criteria Work Group Judgements Evidence Additional Information
How substantial are the desirable anticipated effects? Large

The Pfizer phase 31 and phase 2b2 clinical trial dosing interval was 24 through 36 weeks gestation. In these clinical trials, a numerical imbalance in preterm births among RSVpreF vaccine recipients was observed compared with placebo recipients that was not statistically significant; available data were insufficient to establish or exclude a causal relationship between preterm birth and RSVpreF vaccine.3,4 FDA approved RSVpreF vaccine for use in pregnant people at 32–36 weeks’ gestation to avoid the risk of preterm births at <32 weeks’ gestation which have increased risk of morbidity and mortality and to reduce the potential risk of preterm birth.3,4

For the GRADE assessment, the trial dosing interval of 24 through 36 weeks was used for all outcomes. Additional information limited to maternal participants who received vaccine or placebo during the approved dosing interval of 32 through 36 weeks gestation are presented later in this section.

GRADE

The estimated efficacy for medically attended RSV lower respiratory infection (LRTI) in infants, which was a critical outcome was 51.3% (95% confidence interval [CI]: 29.4%, 66.8%) from 0–180 days of life and there were no concerns in the certainty assessment. Vaccine efficacy for hospitalization for RSV-associated LRTI in infants, also a critical outcome, was 56.8% (99.17% CI: 10.1%, 80.7%) with serious concern for imprecision. For the important outcome of ICU admission from RSV hospitalization in infants, vaccine efficacy was 42.9% (95% CI: -124.8%, 87.7%) with very serious concern for imprecision. Vaccine efficacy for mechanical ventilation from RSV hospitalization in infants, an important outcome, was 100% (95% CI: -9.1%, 100%) with very serious concern for imprecision. In relation to RSV-associated death in infants, an important outcome, 1 RSV-associated death occurred in the placebo arm of the phase 3 trial that was recorded at day 120 after birth. No RSV-associated deaths were recorded in the phase 2b trial. As there was only 1 event observed in both trials, this outcome was not evaluated as part of GRADE. For the important outcomes of all-cause medically attended LRTI and all-cause hospitalization in infants, there were data from the phase 3 trial, showing a vaccine efficacy of 2.5% (99.17% CI: -17.9%, 19.4%) and 28.9% (95% CI: -2.0%, 50.8%), respectively; for both outcomes there was serious concerns for imprecision.1,2

Severe medically attended RSV-associated LRTI

The outcome of severe medically attended RSV-associated LRTI was not included by the Work Group as an a priori GRADE outcome critical or important to vaccine policy decision making.  As the co-primary end point of the phase 3 trial, the work group felt it was important to present as supplemental data in the Evidence to Recommendations. Severe medically attended RSV-associated LRTI was defined as a medically attended visit (inpatient and outpatient encounters), RT-PCR test or nucleic acid amplification test positive for RSV, and at least 1 of the following signs/symptoms: fast breathing (respiratory rate ≥70 (<2 month of age [60 days]) or ≥60 (≥2 to 12 months of age), peripheral capillary oxygen saturation (SpO2) measured in room air <93%, high-flow nasal cannula or mechanical ventilation, ICU admission for >4 hours, or unresponsive/unconscious. For the trial dosing interval of 24–36 weeks gestation, vaccine efficacy against severe medically attended RSV-associated LRTI at 180 days after birth was 69.4% (97.58% CI: 44.3%, 84.1%).

FDA approved dosing interval of 32 through 36 weeks gestation4

The table below contains the vaccine efficacy estimates for the benefit outcomes used for GRADE as well as the co-primary endpoint of the phase 3 trial of severe medically attended RSV-associated LRTI in infants, limited to those whose mothers received vaccine or placebo from 32 through 36 weeks gestation. The point estimates are relatively similar for each of the outcomes, but the confidence intervals are wider for the 32–36-week gestation interval. This is to be expected as the trial was designed and powered using the trial dosing interval of 24 through 36 weeks gestation.

Medically attended RSV-associated lower respiratory tract infection in infants (0–180 days) 57.3% (95% CI: 29.8%, 74.7%)
Hospitalization for RSV-associated lower respiratory tract infection in infants (0–180 days) 48.2% (95% CI: -22.9, 79.6)
ICU admission from RSV hospitalization in infants (0–180 days) 1 event in the vaccine group 2 events in the placebo group
Mechanical ventilation from RSV hospitalization in infants (0–180 days) 0 events in the vaccine group 2 events in the placebo group
All-cause medically attended lower respiratory tract infection in infants (0–180 days) 7.3% (95% CI: -15.7, 25.7)
All-cause hospitalization for lower respiratory tract infection in infants (0–180 days) 34.7% (95% CI: -18.8, 64.9)
Severe medically-attended RSV-associated LRTI in infants (0–180 days) 76.5% (95% CI: 41.3%, 92.1)
The Work Group felt that the desirable anticipated effects were moderate to large with a slight majority selecting large.
How substantial are the undesirable anticipated effects? Small

GRADE

For the critical outcome of serious adverse events in pregnant people, data from the phase 3 and phase 2b trial showed a relative risk of 1.06 (95% CI: 0.95, 1.17) with serious concern for imprecision and serious concern for indirectness. For the important outcome of reactogenicity of grade 3 or higher in pregnant people, data from the phase 3 and phase 2b trials showed a relative risk of 0.97 (95% CI: 0.72, 1.31), and there was serious concern for indirectness as this only includes systemic reactions. For the critical outcome of serious adverse events in infants, data from the phase 3 and phase 2b trials showed a relative risk of 1.01 (95% CI: 0.91, 1.11) with serious concerns for impression and serious concern for indirectness. For the critical outcome of preterm birth, defined as birth at <37 weeks gestation, data from the phase 3 and phase 2b trials showed a relative risk of 1.20 (95% CI: 0.99, 1.46) with very serious concern for imprecision and serious concern for indirectness.1,2

FDA approved dosing interval, 32 through 36 weeks gestation4

Similar to the benefits section, the table below contains the relative risks for the harm outcomes used for GRADE, limited to those who received vaccine or placebo from 32 through 36 weeks gestation. Again, the point estimates for the relative risks are generally very similar, but the confidence intervals are wider.

Serious adverse events in pregnant people 1.02 (95% CI: 0.87, 1.20)
Reactogenicity (grade 3+) in pregnant people 0.98 (95% CI: 0.62, 1.55)
Serious adverse events in infants 1.04 (95% CI: 0.90, 1.20)
Preterm birth (<37 weeks) 1.15 (95% CI: 0.82, 1.61)

Specifically for preterm birth, the relative risk in the vaccinated group compared with the placebo group, using the trial dosing interval of 24–36 weeks was 1.20 (95% CI 0.99, 1.46), whereas the relative risk with the dosing interval of 32 through 36 weeks was 1.15 (95% CI: 0.82, 1.61), with a wider confidence interval, consistent with the decreased power to detect this outcome. The confidence intervals are overlapping between the two estimates.

Additional safety outcomes presented as part of Evidence to Recommendations were low birth weight, defined as less than or equal to 2500 grams, and neonatal jaundice.5
  • 24–36 weeks gestation dosing interval
    • Preterm birth (<37 weeks gestation) was observed in 5.7% (95% CI: (4.9%, 6.5%) of the vaccine group and 4.7% (95% CI: 4.1%, 5.5%) of the placebo group.
  • Low birth weight was observed in 5.1% (95% CI: 4.4%, 5.8%) of the vaccine group and 4.4% (95% CI: 3.7%, 5.1%) of the placebo group.
  • Neonatal jaundice was observed in 7.2% (95% CI: 6.4%, 8.1%) of the vaccine group and 6.7% (95% CI: 5.9%, 7.6%) of the placebo group.
  • 32–36 weeks gestation dosing interval
    • Preterm birth (<37 weeks gestation) was observed in 4.2% (95% CI: 3.3%, 5.3%) of the vaccine group and 3.7% (95% CI: 2.8%, 4.7%) of the placebo group.
    • Low birth weight was observed in 4.1% (95% CI: 3.2%, 5.2%) of the vaccine group and 3.4% (95% CI: 2.5%, 4.4%) of the placebo group.
    • Neonatal jaundice was observed in 6.3% (95% CI: 5.1%, 7.6%) of the vaccine group and 6.7% (95% CI: 5.5%, 8.0%) of the placebo group.

Additional data on preterm birth were presented including births by week, preterm birth rates by calendar month, and preterm birth rates by country for both the 24–36 and 32–36 weeks dosing intervals.5

  • For the trial 24–36 weeks dosing interval, the imbalance in preterm births began at 33 weeks. The imbalance was overall less prominent in those who received vaccine or placebo in the approved 32–36 weeks dosing interval and only clearly present at 36 weeks.
  • In the United States, in the trial with 24 through 36 weeks dosing, the 5.7% of births in the vaccine arm were preterm compared with 5.3% in the placebo arm. However, in the later window of 32 through 36 weeks gestation, 4.0% of births in the vaccine arm compared with 4.4% in the placebo arm were preterm.

Also presented were pregnancy-related serious adverse events occurring at any time after vaccination up to 6 months after delivery for the phase 3 trial population.5 Note: FDA is requiring postmarketing studies to assess hypertensive disorders of pregnancy, including pre-eclampsia.

  • Overall, maternal SAEs occurred in 16.2% of the vaccine arm compared with 15.2% of the placebo arm, with overlapping confidence intervals.
  • Pre-eclampsia occurred in 1.8% of vaccine recipients versus 1.4% of placebo recipients.
  • Gestational hypertension occurred in 1.1% of vaccine recipients and 1.0% of placebo recipients.
  • Hypertension occurred in 0.4% of vaccine recipients and 0.2% of placebo recipients.

An additional consideration is that the Pfizer maternal RSV vaccine is the same formulation and dose approved for use in older adults, and within the trials for this product among adults ages 60 years and older, a potential safety signal of inflammatory neurologic events was identified. A total of 3 cases of interest were recorded among 20,255 investigational vaccine recipients aged 60 years and older, whereas no cases were observed in placebo recipients.6

  • 1 case of Guillain-Barré Syndrome (GBS)
  • 1 case of Miller Fisher syndrome (a GBS variant)
  • 1 case of undifferentiated motor-sensory axonal polyneuropathy (with worsening of preexisting symptoms)

No GBS or other demyelinating events were reported in the phase 2b or 3 trials among pregnant people. Background rate of GBS in pregnant people is much lower than among older adults.7 Incidence rate of GBS in pregnant people in the Vaccine Safety Datalink during 2004-2015 was 2.8 (95% CI 0.5–9.3) per million person-years (based on 2 cases).5,7

The Work Group chose preterm birth as a critical outcome because a trial for a similar maternal RSV vaccine manufactured by GSK, also a stabilized prefusion F protein vaccine, was halted due to an imbalance of preterm births in the vaccinated compared to placebo groups, with more preterm births among RSVpreF vaccine recipients than placebo recipients. Importantly, there was also an imbalance in neonatal deaths, which was determined to be a consequence of the preterm birth imbalance. The imbalance in preterm births was seen in low and middle-income countries but not high-income countries, and the imbalance was observed from April-December 2021, but not consistently after December 2021.  The reason for the imbalance in preterm births in the GSK trial remains unclear.8

Work Group members found the following data reassuring regarding preterm birth imbalance in the Pfizer trials:
  • When using the full trial dosing interval, most preterm births (60%) were >30 days after vaccination, and there is no known biologic mechanism for vaccines to cause preterm birth, particularly >30 days after vaccination.
  • When assessed among those who received vaccine or placebo during the approved interval (32–36 weeks gestation), the imbalance in preterm birth was still present but was less pronounced, and most infants born preterm in the vaccine group were born at 36 weeks gestation.
  • In the United States—which was the single largest contributing country in the trial, the imbalance in preterm births reversed from the trial dosing interval; in the approved dosing interval in the US, there was a higher percentage of preterm births in placebo recipients.

Work Group members found the following points concerning:

  • Although not statistically significant, an imbalance in preterm births was seen in the full trial population.
  • The trial was powered for efficacy outcomes and was not designed or powered to detect a 20% increase in preterm birth.
  • There may have been less precise dating of gestational age in some sites and countries in the trial, but there is no reason this should bias towards a preterm birth imbalance among vaccinated compared with placebo participants.
  • The preterm birth signal in the GSK maternal RSV vaccine trial (which was also a stabilized prefusion F protein vaccine) also adds to the Work Group’s concern.

When asked “how substantial are the undesirable anticipated effects of the Pfizer maternal RSVpreF vaccine for the critical and important outcomes?”, the work group responded that they were small.

Do the desirable effects outweigh the undesirable effects? Favors intervention When asked regarding the balance of desirable and undesirable effects, the work group determined that the balance favored the intervention
What is the overall certainty of this evidence for the critical outcomes?

For the critical outcomes, the certainty of evidence was high for medically attended RSV-associated LRTI in infants. There was moderate certainty that Pfizer RSVpreF maternal vaccine may be effective in preventing hospitalization for RSV-associated LRTI in infants. The certainty of evidence that SAEs in pregnant people and infants were balanced between vaccine and placebo groups was low. Additionally, the certainty of evidence was very low for preterm birth.

In relation to important outcomes, the certainty of evidence was moderate for all-cause medically attended LRTI, all-cause hospitalization for LRTI in infants, and reactogenicity (grade 3+) in pregnant people. The certainty of evidence was low for ICU admission from RSV hospitalization in infants and mechanical ventilation from RSV hospitalizations in infants. RSV-associated death in infants was not able to be evaluated. 1 RSV-associated death occurred in the placebo arm of the phase 3 trial that was recorded at day 120 after birth. No RSV-associated deaths were recorded in the phase 2b trial.
The overall certainty of this evidence was rated as very low.1,2

Values

Criteria Work Group Judgements Evidence Additional Information
Does the target population feel that the desirable effects are large relative to undesirable effects? Probably yes

The University of Iowa, RAND corporation, and CDC worked together to conduct a survey, which included 523 participants of whom 58.1% were currently pregnant and 44.9% had given birth in the last 12 months. The distribution of participants by race and ethnicity entails 66.0% Non-Hispanic White, 16.5% Non-Hispanic Black, 9.8% Hispanic and 7.7% Other Race/Ethnicity. 68% of respondents had knowledge of RSV prior to taking the survey.1

In this survey, 61% of respondents said they ‘definitely’ or ‘probably’ would get an RSV vaccine while pregnant. Additionally, when asked how many vaccines they would be willing to get in the same healthcare visit, 17% said they would only be willing to receive one vaccine, 32% would be willing to receive two vaccines, 9% would receive three vaccines and 20% would receive four vaccines.1
 The Work Group determined that pregnant people probably felt that the desirable effects are large relative to undesirable effects.
Is there important uncertainty about or variability in how much people value the main outcomes? Probably important uncertainty or variability / probably not important uncertainty or variability

Among those who did not respond that they ‘definitely would’ get an RSV vaccine while pregnant, safety concerns, lack of RSV knowledge, and concerns about vaccination causing or intensifying RSV infection were the top reasons for not wanting an RSV vaccine during pregnancy.1

It is also important to look at the uptake of other vaccines in pregnancy. In the United States, coverage for recommended vaccines among pregnant people has decreased during the pandemic and varies by race and ethnicity. Tetanus, Diphtheria, Pertussis (Tdap) vaccination coverage was 53.5% in the 2020–21 season and 45.8% in 2021–22 season.
Rates of Tdap coverage were higher in White, non-Hispanic women than among Black, non-Hispanic women during the 2020–21 and 2021–22 seasons.2
 The Work Group varied in whether they felt there was important uncertainty about, or variability in, how much people value the main outcomes. The Work Group was split between ‘there probably is important uncertainty or variability’ and ‘there probably is not important uncertainty or variability’.

Acceptability

Criteria Work Group Judgements Evidence Additional Information
Is the intervention acceptable to key stakehold-ers? Yes

No published studies on healthcare providers in the United States was identified to inform the acceptability domain.  A study conducted in England assessed support of an RSV vaccine among maternity healthcare professionals, specifically obstetricians and midwives, if it was routinely recommended. Reportedly, 47% would definitely and 34% likely would support a routinely recommended vaccine. However, 14% were not sure, 4% were unlikely and 0.5% were very unlikely to support routine recommendation of an RSV vaccine.1

The American College of Obstetricians and Gynecologists recently released a statement supporting the use of maternal RSV vaccine in pregnancy.2
 The majority of the Work Group felt that the Pfizer Maternal RSVpreF vaccine ‘is acceptable’ to key stakeholders with a substantial minority choosing that Pfizer Maternal RSVpreF vaccine ‘is probably acceptable’ to key stakeholders.

Feasibility

Criteria Work Group Judgements Evidence Additional Information
Is the intervention feasible to implement? Yes

The Pfizer maternal RSVpreF vaccine is supplied as a single 0.5mL dose or in packs of single-dose kits. Reconstitution is required, which entails a single dose vial of lyophilized powder, and reconstitution supplies are included in the kit. The product should be refrigerated and protected from light. After reconstitution, the product should be administered within 4 hours.1,2

Another important consideration is that RSV vaccine is one of two available preventive products for RSV in infants. Either RSV vaccination during pregnancy or nirsevimab (a monoclonal antibody) administration for the infant after birth can be used to prevent RSV disease in infants, but the Work Group felt strongly that both products are not needed for most infants. The pregnant person and their prenatal care provider will need to make the decision during pregnancy regarding which RSV prevention product to use. Many prenatal care providers may not have time to discuss options for RSV prevention with their patients. Prenatal care providers may not feel equipped to discuss nirsevimab, as this product will be given to the infant after birth.
Regarding the timing of RSV vaccine dosing during the calendar year, RSV vaccine dosing could be implemented for pregnant people as a seasonal campaign or year-round. The Work Group supported use of a seasonal dosing strategy for maternal RSV vaccine. A seasonal dosing strategy would maximize cost-effectiveness and would maximize benefits for infants because it targets RSV vaccine dosing to infants who will be in the first months of life during RSV season. Importantly, another product, nirsevimab, is available for infants who are born out of season, for whom maternal vaccine-induced protection would potentially have waned by the peak of the RSV season.
The Work Group supported seasonal dosing beginning in September and continuing through January in most of the continental United States based on typical (or pre-pandemic) RSV seasonality. This aligns with implementation of influenza vaccine and thus would simplify implementation for prenatal care providers. The Work Group felt that jurisdictions in which RSV seasonality differs from most of the continental United States, including Alaska and jurisdictions with tropical climates, should have flexibility regarding start and stop of administration of RSV vaccine in pregnant people.
 The majority of the Work Group felt that the Pfizer Maternal RSVpreF vaccine was feasible to implement among pregnant people at 32–36 weeks gestation, and a substantial minority felt that it ‘probably was feasible’ to implement.

Resource Use

Criteria Work Group Judgements Evidence Additional Information
Is the intervention a reasonable and efficient allocation of resources? Probably yes, with seasonal dosing RSVpreF vaccine may improve RSV outcomes but will also increase costs. The societal incremental cost effectiveness ratio (ICER) for use of RSVpreF vaccine, assuming year-round dosing, cost of $295 per dose, and typical RSV seasonality in most of the continental United States, was $400,304 per quality-adjusted life year (QALY) saved. Assuming a pre-COVID-19 typical RSV seasonality in most of the continental United States, the societal ICER for administering RSVpreF to pregnant people during September through January would be $167,280/QALY saved.

The Work Group felt that this vaccine would not be cost-effective under the base-case conditions, year-round dosing of this vaccine and typical RSV seasonality in most of the continental United States. However, cost-effectiveness would be improved by using a seasonal dosing strategy during September through January in most of the continental United States. The Work Group supported use of a seasonal dosing strategy.

The Work Group majority felt that Pfizer Maternal RSVpreF vaccine use among pregnant people at 32–36 weeks gestation is probably a reasonable and efficient allocation of resources with a substantial minority choosing that Pfizer Maternal RSVpreF vaccine use among pregnant people at 32–36 weeks gestation is a reasonable and efficient allocation of resources.
Work Group responses were based on seasonal dosing during September–January for RSVpreF vaccine in most of the United States.

Equity

Criteria Work Group Judgements Evidence Additional Information
What would be the impact of the intervention on health equity? No majority opinion; ranged from probably no impact to increase

Data showing seasonal population-based rates of RSV-associated hospitalization among U.S. infants less than 6 months by race and ethnicity during the 2018-2019 and 2021-2022 season from Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV-NET), indicates that there were differences in hospitalization rates among infants aged less than 6 months old by race and ethnicity across these seasons, but these differences varied by season. It is important to note that these rates have not been adjusted for RSV testing practices, and thus may under-represent RSV hospitalization rates. However, this should not affect distributions of rates by race and ethnicity.1

Rates of RSV-associated intensive care unit (ICU) admissions among U.S. infants less than 6 months old by race and ethnicity during those same seasons in RSV-NET, shows that population-based ICU admission rates for non-Hispanic Black infants in RSV-NET were 1.2 to 1.6 times higher than for non-Hispanic White infants across the four seasons.1
In addition, research suggests that some American Indian and Alaska Native children experience high rates of severe RSV disease. A recent study found the incidence of RSV-associated hospitalization among some American Indian and Alaska Native infants and children aged <24 months were elevated as compared with that of similar-aged children across seven sites in the United States.2 This disparity is thought to be due to social determinants of health, such as poor indoor air quality, lack of running water, and household crowding. These studies have been limited to specific populations and might not be broadly representative of risk in all American Indian and Alaska Native children.3
By federal law, all states provide Medicaid coverage to pregnant women with incomes up to 138% of the federal poverty level.4 In 2021, 41% of mothers had Medicaid at the time of birth, making Medicaid the largest payer for maternity care in the United States.5
Beginning on October 1, 2023, when the Inflation Reduction Act provisions become effective, state Medicaid agencies will be required to cover vaccines and their administration without cost-sharing for nearly all full-benefit adult beneficiaries covered under traditional Medicaid, if the CDC/ACIP recommendations apply.6
Following recommendation, ACIP also voted 11-1 in favor of a Vaccines for Children resolution for the Pfizer RSV vaccine for pregnant people <19 years of age, which will improve coverage for those eligible for this program, including uninsured and underinsured.
Under the Affordable Care Act and its implementing regulations, ACIP recommendations that have been adopted by CDC “with respect to the individual involved” and are “listed on the Immunization Schedules of the Centers for Disease Control and Prevention” generally are required to be covered by group health plans and health insurance issuers offering group or individual health insurance coverage without imposing any cost-sharing requirements (such as a copayment, coinsurance, or deductible).6
 The Work Group varied in their opinion on Pfizer Maternal RSVpreF vaccine’s impact on health equity, ranging from ‘probably no impact’ to ‘increase equity’.

Work Group Interpretation Summary

The majority of the Work Group was supportive of the intervention with Pfizer maternal RSV vaccine for pregnant people with the approved interval dosing during 32 through 36 weeks gestation. The majority of the Work Group found the data on preterm birth when assessed among those vaccinated during the approved interval of 32–36 weeks to be reassuring. The Work Group felt the approved dosing interval reduces the potential risk of preterm birth and the potential for complications from preterm birth, which was their major safety concern. All Work Group members endorsed the importance of post-introduction vaccine safety monitoring.

The Work Group supported use of a seasonal dosing strategy which would maximize benefits and cost-effectiveness. The Work Group supported that RSV vaccine dosing should occur during September–January in most of the continental United States and felt that jurisdictions in which RSV seasonality differs from most of the continental United States should have flexibility regarding start and stop of administration of RSVpreF vaccine in pregnant people.

The Work Group considered the implications of RSV vaccine being one of two available preventive products for RSV in infants. The Work Group expressed that pregnant people should have multiple options for RSV prevention, as nirsevimab may not be readily available in all settings, and pregnant people and their providers may have preferences regarding these two products. The Work Group also stated that pregnant people should be made aware that they can either receive RSV vaccine during pregnancy or nirsevimab can be given to the infant, but most infants will not need both. The Work Group expressed that pregnant people should be informed regarding the risks and benefits of both products before making a decision.

The Work Group had extensive discussions regarding a full recommendation versus a shared clinical decision-making recommendation. Most work group members support a full recommendation. They felt that the approved dosing interval reduces the potential risk of complications from preterm birth. They also stressed the importance of clear vaccine recommendations. They noted that providers who will help pregnant people decide which product to receive generally have less familiarity with the data than ACIP. They expressed that shared clinical decision-making recommendations are confusing, hard to implement for providers, can lead to lower vaccine confidence and uptake of vaccination, and could potentially influence support for the vaccine in lower- and middle-income countries, where nirsevimab may not be available. A minority of the Work Group supported a recommendation with shared clinical decision-making. They noted that without shared clinical decision-making, a full recommendation could result in some providers recommending RSV vaccine during pregnancy without discussing with pregnant patients that nirsevimab is an option. They cited the potential risk for preterm birth and neuroinflammatory events, and that the same vaccine is recommended under shared clinical decision-making for adults ages 60 years and older. It is important to note that ACIP generally makes shared clinical decision-making recommendations when individuals may benefit from vaccination, but broad vaccination of people in that group is unlikely to have population-level impacts.

The Work Group noted that currently there are no data available on the efficacy of the first lifetime dose during subsequent pregnancies nor the safety of additional doses given in subsequent pregnancies. The Work Group felt that it was too early decide whether additional doses should be given in subsequent pregnancies given the lack of data. Additional data are needed to inform whether additional doses in subsequent pregnancies would be indicated, and recommendations can be updated in the future.

Balance of consequences

The majority of the Work Group felt that the desirable consequences probably outweigh undesirable consequences in most settings. A minority felt that the desirable consequences clearly outweigh undesirable consequences in most settings.

Is there sufficient information to move forward with a recommendation? Yes

Policy options for ACIP consideration

The majority of the Work Group recommended the intervention; however, a minority of the Work Group recommended the intervention using shared clinical decision-making.

Policy options for ACIP consideration

ACIP recommends the intervention.

ACIP recommends the intervention using shared clinical decision-making.

ACIP does not recommend the intervention

Draft recommendation

Maternal RSV vaccine is recommended for pregnant people during 32 through 36 weeks gestation, using seasonal administration, to prevent RSV lower respiratory tract infection in infants.

Final deliberation and decision by ACIP

On September 22, 2023, ACIP voted 11-1 in favor of recommendation.

Final recommendation

ACIP recommends the intervention.

References

Background

  1. Suh M, Movva N, Jiang X, et al. Respiratory Syncytial Virus Is the Leading Cause of United States Infant Hospitalizations, 2009-2019: A Study of the National (Nationwide) Inpatient Sample. J Infect Dis. 2022 Aug 15;226(Suppl 2):S154-S63.
  2. Hamid S, Winn A, Parikh R, et al. Seasonality of Respiratory Syncytial Virus — United States, 2017–2023. MMWR Morb Mortal Wkly Rep. 2023;72:355–361. doi: 10.15585/mmwr.mm7214a1.
  3. Thompson WW, Shay DK, Weintraub E, et al. Mortality Associated with Influenza and Respiratory Syncytial Virus in the United States. 2003;289(2):179–186. doi:10.1001/jama.289.2.179
  4. Hansen CL, Chaves SS, Demont C, Viboud C. Mortality Associated with Influenza and Respiratory Syncytial Virus in the US, 1999-2018. JAMA Netw Open. 2022;5(2):e220527. doi:10.1001/jamanetworkopen.2022.0527
  5. Hall CB, Weinberg GA, Iwane MK, et al. The Burden of Respiratory Syncytial Virus Infection in Young Children. New England Journal of Medicine. 2009;360(6):588–98. doi: 10.1056/NEJMoa080487
  6. Rha B, Curns AT, Lively JY, et al. Respiratory Syncytial Virus–Associated Hospitalizations Among Young Children: 2015–2016. 2020;146(1):e20193611. doi: 10.1542/peds.2019-3611
  7. McLaughlin JM, Khan FL, Schmitt H-J, et al. Respiratory Syncytial Virus-Associated Hospitalization Rates among US Infants: A Systematic Review and Meta-Analysis. Open Forum Infectious Diseases. 2020;7(Supplement_1): S843. doi: 10.1093/ofid/ofaa439.1897
  8. Centers for Disease Control and Prevention (CDC). Increased Respiratory Syncytial Virus (RSV) Activity in Parts of the Southeastern United States: New Prevention Tools Available to Protect Patients. Health Alert Network. https://emergency.cdc.gov/han/2023/han00498.asp
  9. Food and Drug Administration (FDA). FDA Approves First Vaccine for Pregnant Individuals to Prevent RSV in Infants. Press briefing. https://www.fda.gov/news-events/press-announcements/fda-approves-first-vaccine-pregnant-individuals-prevent-rsv-infants

Public Health Problem

  1. Thompson WW, Shay DK, Weintraub E, et al. Mortality Associated with Influenza and Respiratory Syncytial Virus in the United States. 2003;289(2):179–186. doi:10.1001/jama.289.2.179
  2. Hansen CL, Chaves SS, Demont C, Viboud C. Mortality Associated with Influenza and Respiratory Syncytial Virus in the US, 1999-2018. JAMA Netw Open. 2022;5(2):e220527. doi:10.1001/jamanetworkopen.2022.0527
  3. Hall CB, Weinberg GA, Iwane MK, et al. The Burden of Respiratory Syncytial Virus Infection in Young Children. New England Journal of Medicine. 2009;360(6):588-98. doi: 10.1056/NEJMoa080487
  4. Rha B, Curns AT, Lively JY, et al. Respiratory Syncytial Virus–Associated Hospitalizations Among Young Children: 2015–2016. Pediatrics. 2020;146(1):e20193611. doi: 10.1542/peds.2019–3611
  5. McLaughlin JM, Khan FL, Schmitt H-J, et al. Respiratory Syncytial Virus-Associated Hospitalization Rates among US Infants: A Systematic Review and Meta-Analysis. Open Forum Infectious Diseases. 2020;7(Supplement_1): S843. doi: 10.1093/ofid/ofaa439.1897
  6. Suh M, Movva N, Jiang X, et al. Respiratory Syncytial Virus Is the Leading Cause of United States Infant Hospitalizations, 2009-2019: A Study of the National (Nationwide) Inpatient Sample. J Infect Dis. 2022;226(Suppl 2):S154–S63.
  7. Hall CB, Weinberg GA, Blumkin AK, et al. Respiratory Syncytial Virus–Associated Hospitalizations Among Children Less Than 24 Months of Age. Pediatrics. 2013;132 (2): e341–e348. doi: 10.1542/peds.2013-0303
  8. Langley GF and Anderson LJ. Epidemiology and Prevention of Respiratory Syncytial Virus Infections Among Infants and Young Children. The Pediatric Infectious Disease Journal. 2011;30(6): 510–517. doi: 10.1097/INF.0b013e3182184ae7

Benefits and harms

  1. Kampmann B, Madhi SA, Munjal I, et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants. New England Journal of Medicine. 2023;388(16): 1451-1464. https://doi.org/10.1056/NEJMoa2216480
  2. Simões EAF, Center KJ, Tita ATN, Swanson KA, Radley D, Houghton J, et al. Prefusion F Protein–Based Respiratory Syncytial Virus Immunization in Pregnancy. New England Journal of Medicine. 2022;386(17): 1615-1626. https://doi.org/10.1056/NEJMoa2106062
  3. FDA. Abrysvo package insert. https://www.fda.gov/media/171482/download?attachment
  4. FDA. FDA Approves First Vaccine for Pregnant Individuals to Prevent RSV in Infants. Press Release. Silver Spring, MD: US Department of Health and Human Services, Food and Drug Administration; 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-vaccine-pregnant-individuals-prevent-rsv-infants
  5. Fleming-Dutra KE. Evidence to Recommendations Updates. Presentation to ACIP September 2023. https://www.cdc.gov/acip/downloads/slides-2023-09-22/06-Mat-Peds-Fleming-Dutra-508.pdf
  6. Melgar M, Britton A, Roper LE. Use of Respiratory Syncytial Virus Vaccines in Older Adults: Recommendations of the Advisory Committee on Immunization Practices — United States, 2023. MMWR Morb Mortal Wkly Rep 2023;72:793–801. http://dx.doi.org/10.15585/mmwr.mm7229a4.
  7. Myers TR, McCarthy NL, Panagiotakopoulos L, et al. Population Incidence of Guillain-Barré Syndrome: A Systematic Review and Meta-Analysis. Neuroepidemiology 2011;36:123–133
  8. GSK. Preterm birth signal in a maternal immunization study with a respiratory syncytial virus prefusion F protein vaccine candidate. Presentation to ReSViNET 2023. https://www.youtube.com/watch?v=P45AbqFeYBY

Values

  1. CDC and University of Iowa/RAND survey, unpublished
  2. Flu, Tdap, and COVID-19 Vaccination Coverage Among Pregnant Women – United States, April 2022 | FluVaxView | Seasonal Influenza (Flu) | CDC

Acceptability

  1. Wilcox CR, Calvert A, Metz J, et al. Attitudes of Pregnant Women and Healthcare Professionals Toward Clinical Trials and Routine Implementation of Antenatal Vaccination Against Respiratory Syncytial Virus: A Multicenter Questionnaire Study. The Pediatric Infectious Disease Journal. 2019. 38(9):944-951, September 2019. https://doi.org/10.1097/INF.0000000000002384
  2. The American College of Obstetricians and Gynecologists. ACOG Unequivocally Supports ACIP's Recommendation Approving Use of Maternal RSV Vaccine in Pregnancy. https://www.acog.org/news/news-releases/2023/09/acog-supports-acip-recommendation-approving-use-maternal-rsv-vaccine-in-pregnancy

Feasibility

  1. FDA. ABRYSVO- respiratory syncytial virus vaccine. Package insert. https://labeling.pfizer.com/ShowLabeling.aspx?id=19589
  2. Pfizer. Bivalent RSV Prefusion F Vaccine for Maternal Immunization to Protect Infants. Vaccines and Related Biological Products Advisory Committee Meeting Presentation. May 18, 2023. https://www.fda.gov/media/168255/download
  3. FDA. Review of Efficacy and Safety of Respiratory Syncytial Virus Vaccine (ABRYSVO). Vaccines and Related Biological Products Advisory Committee Meeting Presentation. May 18, 2023. https://www.fda.gov/media/168258/download
  4. CDC. Diphtheria, Tetanus, and Pertussis Vaccine Recommendations. https://www.cdc.gov/diphtheria/hcp/clinical-overview/index.html
  5. U.S. Department of Health and Human Services, OASH Office of Women's Health. Prenatal care and tests. https://www.womenshealth.gov/pregnancy/youre-pregnant-now-what/prenatal-care-and-tests
  6. CDC. Timing and Spacing of Immunobiologics—General Best Practice Guidelines for Immunization. https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/timing.html
  7. Peterson JT, Agnieszka AM, Fitz-Partick D, Essink BJ, Scott DA, Swanson KA, et al. Safety and Immunogenicity of a Respiratory Syncytial Virus Prefusion F Vaccine When Coadministered with a Tetanus, Diphtheria, and Acellular Pertussis Vaccine. The Journal of Infectious Diseases. 2022;225(1): 2077–2086. https://doi.org/10.1093/infdis/jiab505
  8. Pfizer. Presentation to ACIP, June 2023. https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/02-RSV-Adults-Gurtman-508.pdf
  9. Liang JL, Tiwari T, Moro P, Messonnier NE, Reingold A, Sawyer M, et al. Prevention of Pertussis, Tetanus, and Diphtheria with Vaccines in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2018. 67(RR-2):1–44. http://dx.doi.org/10.15585/mmwr.rr6702a1
  10. CDC. Flu, Tdap, and COVID-19 Vaccination Coverage Among Pregnant Women – United States, April 2022. https://www.cdc.gov/flu/fluvaxview/pregnant-women-apr2022.htm
  11. Unpublished data, Fall 2022 DocStyles

Resource Use

  1. Hutton, DW. Economic Analysis of RSVpreF Maternal Vaccination. Presentation to ACIP, September 2023. https://www.cdc.gov/acip/downloads/slides-2023-09-22/04-Mat-Peds-Hutton-508.pdf

Equity

  1. RSV-NET: unpublished data from 2018-2022
  2. Atwell JE, Hartman RM, Parker D, Taylor K, Brown LB, Sandoval M, et al. RSV among American Indian and Alaska Native children: 2019 to 2020. Pediatrics 2023;e2022060435. https://doi.org/10.1542/peds.2022-060435
  3. Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, editors. American Academy of Pediatrics, Committee on Infectious Diseases. Respiratory Syncytial Virus [Section 3]. In: Red Book: 2021–2024 report of the Committee on Infectious Diseases. Itasca, IL: American Academy of Pediatrics; 2021:628–36.
  4. Gomez I, Ranji U, Salganicoff A, and Frederiksen B. Medicaid Coverage for Women. KFF. https://www.kff.org/womens-health-policy/issue-brief/medicaid-coverage-for-women/
  5. Centers for Medicare and Medicaid Services. 2023 Medicaid and CHIP Beneficiary Profile: Enrollment, Expenditures, Characteristics, Health Status, and Experience. https://www.medicaid.gov/sites/default/files/2023-04/beneficiary-profile-2023.pdf
  6. ACIP Shared Clinical Decision-Making Recommendations. ACIP Shared Clinical Decision-Making Recommendations | Advisory Committee on Immunization Practices (ACIP) | CDC

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List of Evidence to Recommendations Framework Tables
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Content Source:
National Center for Immunization and Respiratory Diseases (NCIRD)