Mind the Gap: The Impact of Maternal Immunization on Pertussis in Young Infants.

Abstract

The evidence that pertussis poses the greatest threat to the youngest infants is robust and persuasive. We know that about half of infants diagnosed with pertussis are hospitalized. Apnea occurs in 3 out of 5 of these infants hospitalized for pertussis and pneumonia in 1 out of 4. For every 100 infants hospitalized for pertussis, 1 to 2 die of related complications.1 Most deaths from pertussis occur in infants younger than 3 months,2 an age when no infant is old enough to have been adequately immunized against this deadly vaccine-preventable disease.This well-understood and consequential gap in protection against pertussis for the youngest infants has inspired efforts to evaluate the impact of alternative pertussis immunization strategies for decades. The most pragmatic strategy to close the infant pertussis gap came into sharper focus for the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices (ACIP) in 2011. Infant pertussis cases were rising and vaccine trials had demonstrated that initiating the primary pertussis series in infants early with a birth dose was ineffective.3 Cocooning programs had achieved only modest vaccine coverage among postpartum mothers, with very limited success in immunizing fathers or other family members to protect vulnerable infants.4 Pregnant women had been receiving diphtheria and tetanus toxoid vaccines worldwide since the 1960s to protect their newborns against tetanus, another life-threatening and vaccine-preventable disease, with no evidence of adverse fetal effects. Antibody studies had demonstrated active placental transfer of pertussis antibodies from mothers to their infants.5–7 ACIP carefully considered this evidence and recommended in 2012 that every pregnant woman should receive tetanus, diphtheria, and pertussis vaccine (Tdap) regardless of prior receipt of the vaccine.8In this month’s Hospital Pediatrics, Kim et al9 estimate the impact the 2012 ACIP guideline for universal pertussis immunization during pregnancy on admissions for pertussis in infants younger than 1 month of age. The authors used data from the Kids’ Inpatient Database, the largest all-payer pediatric inpatient database in the US, from 2000 to 2016 to estimate the impact of the guideline. They found more than a 4-fold reduction in the pertussis hospitalization rates in the post guideline period after adjusting for time and covariates. This analysis was limited to infant data from the first 4 years after the guideline, because the Kid’s Inpatient Database is updated every 3 years and does not include maternal immunization data. Premature infants and infants older than 1 month were excluded from the analysis to ensure that their mothers had the opportunity to receive the vaccine and infants had not yet had their first dose of pertussis vaccine. The precipitous decline in pertussis hospitalizations following the guideline, demonstrated by this study by Kim et al, is consistent with previous studies.10,11 Interestingly, their analysis was unable to demonstrate a similar decline in infant mortality rates in the post guideline period. Furthermore, the authors reported demographic trends including race/ethnicity and payer status but were unable to draw comparisons before and after the 2012 ACIP guideline due to wide variability in the reported proportions by year in each category.On the surface, the growing evidence that maternal pertussis immunization during pregnancy has reduced infant hospitalizations for pertussis could reassure us that we are successfully closing the deadly pertussis gap for young infants. The problem with this favorable conclusion is the ample evidence of disparities in maternal pertussis immunization status. Immunization coverage among pregnant women is suboptimal and is plagued by substantial and persistent racial and ethnic disparities. The Centers for Disease Control and Prevention Tdap coverage survey rates among pregnant women in 2020 were 56.6%, with Hispanic and Black women at 35.8% and 38.8%, respectively, compared with White women at 65.5%. Moreover, Tdap coverage rates declined among Hispanic women from 2019 to 2020 compared with the previous season.12 A recent study found that only 13.4% of women with Medicaid received Tdap during pregnancy compared with 68.6% of privately insured women.13 Given the high proportion of publicly insured and Hispanic infants included in the current study, it is worth considering whether suboptimal maternal immunization rates may significantly diminish the potential impact of the 2012 ACIP guideline on adverse infant outcomes. Viewed from a health equity perspective and based on the health inequities faced by their mothers, the deadly pertussis gap is likely wider and deeper for the most vulnerable young infants.The natural next question is what more can we do to close this gap? Unfortunately, the evidence for how to improve pertussis immunization rates in pregnant women is not as compelling as the evidence that affords protection against severe disease in young infants. A recent systematic review of interventions to improve pertussis vaccine uptake in pregnancy evaluated the impact of 6 studies, including 3 randomized trials. None of the trials demonstrated improved vaccine uptake during pregnancy leading the authors to conclude that “interventions solely focused on educating pregnant women on the benefits of vaccines might not be an effective strategy.”14 Despite this disheartening observation, the authors make several points that are worth noting. Namely, these trials may have been limited by the accessibility of existing patient education for women from culturally and linguistically diverse backgrounds and low resource settings. The authors also highlight the need to improve messaging on the evidence-based role maternal pertussis immunization plays in preventing severe disease in the youngest infants.There is no question that effectively addressing this gap is challenging, particularly in this time of pervasive vaccine hesitancy and immunization inequity. The American Academy of Family Physicians recently issued a call to action to immunize pregnant women.15 National professional societies endorsed this statement, including nurse-midwives, obstetricians, and obstetric and neonatal nurses. But what about pediatricians?It would be tempting to conclude that we are too late to the game to directly influence maternal decisions about immunizations during pregnancy. However, the evidence to support both the strength of our influence and our ingenuity in addressing immunization health disparities is also robust and persuasive. We are highly qualified and experienced champions for immunization. We have many clinical opportunities to influence our colleagues who care for pregnant women, and we have established relationships with many of the mothers of our future patients. Unless we fully embrace this maternal immunization challenge as our own, instead of closing the pertussis gap, we may witness it widening and deepening, particularly for our most vulnerable patients.