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Tetanus, Diphtheria, Acellular Pertussis Vaccination During Pregnancy and Risk of Pertussis in the Newborn in Publicly and Privately Insured Mother-infant Pairs in the United States

Mott, Katrina MHS, ScD*; Huybrechts, Krista F. MS, PhD; Glynn, Robert J. PhD; Mogun, Helen MS; Hernández-Díaz, Sonia MD, DrPH*

Author Information
The Pediatric Infectious Disease Journal: July 2021 - Volume 40 - Issue 7 - p 681-687
doi: 10.1097/INF.0000000000003099

Abstract

Outbreaks of pertussis in the United States increased from fewer than 10,000 cases per year before 2003, up to a peak of 48,277 reported cases in 2012.1 This resurgence might be due to a variety of factors including waning immunity and vaccine hesitancy.2–4 The disease burden falls primarily on young infants, with one-third of pertussis cases occurring in infants under 12 months; and young infants are at the highest risk for complications (22% develop pneumonia) and death (1%).5–7 In particular, preterm infants are at increased risk for pertussis infection and morbidities.8,9

For several years, the CDC Advisory Committee on Immunization Practices (ACIP) recommended “cocooning”: protecting infants from pertussis infection before their initial DTaP dose at 2 months by giving Tdap booster vaccines to parents and close contacts of newborns. However, this strategy was shown to be ineffective.10 In late 2011, as cases in the US climbed, the ACIP updated their recommendation to include vaccination of pregnant women who were previously unvaccinated.11,12 This was expanded in 2012 to include all pregnant women, and to recommend vaccination between 27 and 36 weeks of gestation, when the highest antibody concentrations in cord blood at delivery are attained.11,13,14

Six years after the updated guideline, a 2018 report by the CDC estimated that 54% of pregnant women received Tdap vaccine during their pregnancy, indicating much room for improved compliance with the ACIP recommendation.15 This survey also found that black and Hispanic women did not receive the vaccine as often as their white counterparts (43% vs. 60%). Racial disparities in vaccination rates have been reported across age groups, locations, and vaccines, and this appears to also apply to the pregnant population.16–20

There is little evidence on the effectiveness of vaccination in the real world.21 A study of privately insured women in the US found a 46% lower risk of infant pertussis before 6 months for women with Tdap vaccination during pregnancy compared with those without a perinatal or postpartum vaccination.22 Maternal vaccination during the delivery period was associated with a 20% lower risk of infant pertussis.22 The study did not evaluate the timing of vaccination during pregnancy or pertussis risk by preterm status.

Further evidence of the effectiveness of Tdap vaccination during pregnancy may increase provider and patient confidence in the recommendation and increase compliance. Therefore, we conducted a study in 2 large healthcare claims database pregnancy cohorts of publicly and privately insured women in the US to determine the effectiveness of both prenatal and early postpartum maternal vaccination against pertussis infection in infants. Additionally, we evaluated prenatal vaccination rates by race and the impact of preterm delivery on both the opportunity to be vaccinated and the risk of pertussis infection in those with and without prenatal vaccination.

METHODS

Population

Two cohorts of mother-infant pairs were included in this analysis; the first based in the IBM MarketScan Commercial Database (MarketScan) from privately insured individuals across the United States and the second in the Medicaid Analytic eXtract (MAX) from Medicaid enrolled individuals from 49 states. The MAX cohort included pregnancies ending in livebirth from 2010 to 2014. The MarketScan cohort included pregnancies ending in livebirth from 2011 to 2015. Infants were linked to their mothers as described elsewhere, primarily using insurance family ID numbers and birth dates.23,24 Gestational age at birth was estimated based on a validated algorithm.23,24

To be included in the analysis, mothers must have been 12–55 years of age at the time of delivery and had continuous drug and medical insurance coverage from 90 days before estimated last menstrual period (LMP) through 30 days postpartum. In MAX, women were excluded if they had restricted benefits or other private insurance. Infants were required to be enrolled for a minimum of 1 month after date of birth. Women were excluded if they had Tdap vaccination during the baseline period (90 days before LMP). Figure 1 illustrates the study design.25 Women were excluded if their geographic location could not be determined. The unit of analysis for this study is the pregnancy. Women may have contributed more than 1 pregnancy to the study if they met the inclusion and exclusion criteria.

FIGURE 1.
FIGURE 1.:
Study design diagram.

Follow-up of newborns began on day 7 postpartum, due to the incubation period of pertussis, and continued until pertussis diagnosis, infant death, end of enrollment, or at 6 months.

Exposure

Exposure to Tdap vaccination was captured by the presence of a CPT (90715), ICD-9 procedure (99.37 or 99.39), ICD-9 diagnosis code (V06.1, V06.3 or V03.6), or NDC code for Tdap in the mother’s outpatient, inpatient, or prescription claims. The primary pregnancy exposure was defined as any Tdap code between LMP and up to 1 day before delivery. As a secondary exposure, we defined delivery exposure as any Tdap code between 1 day before delivery through 7 days postpartum. The 2 exposed groups were compared with women with no evidence of a Tdap exposure between 90 days before LMP through 7 days after delivery. To determine comparability, the 3 exposure groups were compared on baseline and pregnancy health care utilization and demographics. We also differentiated vaccinations before and after 37 weeks gestation (when full-term deliveries begin).

Outcome

Pertussis infection was defined as the infant meeting one of the following criteria between 7 and 183 days after delivery: (1) an inpatient diagnosis of pertussis infection (ICD-9 codes 033.0, 033.1, 033.8, 033.9, 484.3) or (2) at least 2 of these 3 criteria: (i) an outpatient diagnosis of pertussis infection recorded on 2 separate dates, (ii) an outpatient pertussis diagnostic lab code followed by an outpatient diagnosis code within 14 days or (iii) an outpatient diagnosis code followed by a prescription dispensing of either erythromycin, clarithromycin, azithromycin, or trimethoprim/sulfamethoxazole within 7 days.

Statistical Analysis

Crude and weighted absolute risks of pertussis were calculated as the 183-day cumulative hazard of pertussis per 10,000 infants, with the baseline hazard calculated with the Breslow estimator, and assuming proportional hazards to estimate hazards in the 2 treated groups.26,27 Weighted survival curves were generated using the same method. Hazard ratios (HR) were estimated with weighted Cox proportional hazards models to account for censoring. To adjust for confounding, we estimated the average vaccine effect with stabilized inverse probability of treatment weighting, calculated using multinomial logistic regression separately in the Medicaid and MarketScan databases.28 The 3 levels in the multinomial regression were pregnancy vaccination, delivery vaccination, and unvaccinated. Weights were truncated at the 99.9 and 0.1 percentile. The selection of variables for adjustment was based on their potential as Department of Epidemiology, Harvard T.H. Chan School of Public Health, sociation with both maternal Tdap vaccination and pertussis infection. All analyses included adjustment, via inverse probability of treatment weighting, for mother’s age at delivery, year and month of delivery, region, living in a metropolitan statistical area, multiparity, healthcare utilization, and influenza vaccination during pregnancy. The model also adjusted for indicators of preterm delivery since length of gestation affects both the probability of maternal vaccination (ie, fewer weeks to get the vaccine for preterm deliveries) and the risk of neonatal infection (ie, preterm infants have a higher risk of infection). We assumed no meaningful effect of maternal vaccination on the risk of prematurity.

In addition, local pertussis circulation was considered a potential confounder via increased vaccination effort from physicians and public health action and via increased pertussis infection risk. Measures of pertussis incidence were generated using weekly reports to the CDC by state health departments, and each pregnancy was assigned a value based on geography (state) and time.29,30 Two state-specific measures were created: (1) pertussis incidence in the 12 weeks before week 27 of pregnancy and (2) an indicator of an uptick in pertussis: higher incidence in the 2 weeks before delivery compared with the previous month. These were chosen to represent circulation of pertussis during a time preceding the vaccination decision for a pregnancy, and to represent an infant’s increased risk of pertussis if they are born at the beginning of a local pertussis outbreak. Estimates from the 2 databases for the primary and subgroup analyses were pooled using random-effects meta-analysis, DerSimonian and Laird method.31 Vaccine effectiveness was estimated as (1-HR) × 100.

Secondary and Sensitivity Analyses

We compared the frequency of maternal vaccination during pregnancy and risk of pertussis between preterm and term infants, using the absolute risk measures described above. We also estimated the effect of vaccination during pregnancy on the risk of pertussis infection for preterm and term infants separately. To do so, the model from the primary analysis was stratified by preterm status of the infant. Within full-term infants, we assessed the effect of maternal vaccination before and after 37 weeks; all pregnancy vaccinations in preterm infants occur before 37 weeks by definition. Subgroup analysis was also conducted for deliveries occurring during a pertussis uptick, since vaccine effectiveness may be modified by local population pertussis risk.

As a sensitivity analysis for the primary model, we used a pertussis definition of inpatient pertussis cases (Part A of the primary outcome definition) for a more specific, but less sensitive outcome definition. We also limited the outcome to the first 60 days (before recommended initial DTaP dose for infants) to estimate the effectiveness in infants with the highest risk of morbidity and to assess potential time-varying HRs. Another sensitivity analysis reclassified exposure in the last 2 weeks of pregnancy as a delivery exposure since vaccinations just before delivery will not provide enough time for a robust antibody response to develop and be provided to the infant at delivery.32 We also conducted an analysis from 2011 to 2014 in both databases, to compare the results during the same time period. Finally, we estimated the effect of the maternal vaccine on a negative control outcome, gastrointestinal infection.

RESULTS

The MarketScan cohort included 445,638 commercially insured pregnancies, of which 114,067 (25.6%) were vaccinated with Tdap during pregnancy and 20,415 (4.6%) during the delivery period. The pregnancy Tdap coverage increased from 6.4% in 2012 to 48.9% in 2015 (Table 1 and Figure, Supplemental Digital Content 1, http://links.lww.com/INF/E318). Of women vaccinated in pregnancy, 81.4% were vaccinated between 27 and 36 weeks (up to 87% in 2015). The MAX cohort included 695,262 publicly insured pregnancies, of which 33,286 (4.8%) were vaccinated with Tdap during pregnancy and 22,821 (3.3%) during the delivery period (Table 1). The pregnancy Tdap coverage increased from 0.6% in 2010 to 3.5% in 2012 and up to 18.8% in 2014 (Table 1 and Figure, Supplemental Digital Content 1, http://links.lww.com/INF/E318). Of women vaccinated in pregnancy, 65.5% were vaccinated between weeks 27 and 36 (up to 78.5% in 2014).

TABLE 1. - Distribution of Demographic, Health Utilization, and Risk Factors for Pertussis by Exposure Group
IBM MarketScan MAX
Pregnancy (n = 114,067) Delivery (n = 20,415) Unexposed (n = 311,156) Pregnancy (n = 33,286) Delivery (n = 22,821) Unexposed (n = 639,155)
Sociodemographic variables
 Maternal age, mean (SD) 31.8 (4.3) 31.3 (4.5) 31.6 (4.5) 25.9 (5.9) 24.8 (5.6) 25.2 (5.9)
 Year of delivery, row % (n)
  2010 0.6 (1086) 2.2 (3657) 97.2 (163,128)
  2011 3.6 (78) 4.7 (102) 91.7 (1985) 1.5 (2794) 3.8 (6877) 94.7 (171,868)
  2012 6.4 (9884) 5.5 (8597) 88.1 (137,035) 3.5 (6083) 4.1 (7215) 92.5 (162,887)
  2013 23.5 (26,785) 4.2 (4850) 72.3 (82,537) 11.0 (12,167) 3.3 (3644) 85.7 (94,501)
  2014 42.0 (46,812) 4.1 (4586) 53.8 (59,960) 18.8 (11,156) 2.4 (1428) 78.8 (46,771)
  2015 48.9 (30,508) 3.7 (2280) 47.5 (29,639)
 Race, row % (n)
  American Indian 7.2 (771) 4.9 (526) 87.9 (9427)
  Asian/Pacific islander 6.8 (2462) 2.1 (764) 91.1 (32,984)
  Black or African American 3.5 (6989) 3.0 (5993) 93.4 (185,065)
  Hispanic/Latino 5.4 (6635) 2.1 (2612) 92.5 (113,829)
  White 5.0 (13,037) 4.2 (11,057) 90.8 (237,755)
  Other/unknown 5.2 (3392) 2.9 (1869) 92.0 (60,095)
Region, row % (n)
  Northeast 23.8 (21,558) 3.9 (3502) 72.4 (65,604) 3.6 (4888) 3.9 (5331) 92.5 (125,351)
  North Central 29.0 (31,713) 4.0 (4346) 67.0 (73,128) 6.6 (11,560) 4.4 (7808) 89.0 (156,301)
  South 22.1 (36,711) 5.4 (8921) 72.5 (120,484) 2.3 (4107) 3.4 (6017) 94.3 (166,049)
  West 30.2 (24,085) 4.6 (3646) 65.2 (51,940) 6.1 (12,731) 1.8 (3665) 92.1 (191,454)
 Metropolitan statistical area, % (n) 91.8 (104,705) 87.9 (17,950) 88.7 (276,133) 82.7 (27,532) 75.4 (17,205) 82.7 (52,8641)
Healthcare utilization variables
 Healthcare visits, baseline, mean (SD) 2.5 (3.7) 2.2 (3.4) 2.4 (3.6) 2.6 (5.2) 2.4 (4.2) 2.2 (3.9)
 Healthcare visits, pregnancy, mean (SD)* 7.4 (5.1) 6.9 (5.0) 7.2 (5.1) 8.5 (7.9) 7.4 (6.4) 6.9 (6.0)
 Generic medications, baseline, mean (SD) 1.6 (2.4) 1.5 (2.3) 1.6 (2.4) 1.9 (2.6) 2.0 (2.6) 1.8 (2.5)
 Generic medications, pregnancy, mean (SD)* 2.0 (2.3) 2.1 (2.2) 2.1 (2.4) 3.5 (3.2) 3.4 (3.0) 3.3 (3.0)
 Flu vaccine, pregnancy % (n) 51.5 (58,708) 30.7 (6269) 25.8 (80,130) 48.4 (16,113) 19.0 (4337) 14.1 (89,827)
 Ultrasound, % (n) 98.0 (111,793) 96.4 (19,690) 96.4 (300,040) 79.0 (26,283) 72.9 (16,632) 68.4 (437,029)
Pertussis risk factors
 Preterm, % (n) 8.5 (9639) 9.7 (1979) 10.9 (33,904) 8.1 (2693) 8.7 (1990) 10.4 (66,364)
 Post-term, % (n) 16.2 (18,521) 11.8 (2412) 11.6 (36,146) 5.6 (1856) 9.1 (2082) 9.6 (61,063)
 Multiparous, % (n) 52.1 (59,455) 55.4 (11,307) 60.0 (186,767) 81.5 (27,124) 76.0 (17,338) 76.9 (491,221)
 Uptick in pertussis, % (n) 32.9 (37,562) 36.5 (7449) 34.1 (106,178) 26.5 (8830) 33.1 (7549) 33.0 (210,768)
 High pertussis before week 27, % (n) 11.0 (12,554) 9.1 (1857) 9.8 (30,385) 7.1 (2365) 13.2 (3017) 10.2 (64,939)
Percentages are calculated across rows, within database.
*Generic medications and healthcare (outpatient) visits measured in first 140 days of pregnancy.

Women in the MAX cohort were on average 6 years younger than women in the MarketScan cohort, and within the same calendar year were less likely to be vaccinated. Table 1 and Table (Supplement Digital Content 2, http://links.lww.com/INF/E319) provides the distribution of demographic, healthcare utilization and pregnancy characteristics of the cohorts. Race and ethnicity data were not available in MarketScan. In MAX, black women were less likely to receive Tdap in either pregnancy or delivery (6.5% exposed), compared with Hispanic (7.5%), Asian (8.9%), white (9.2%) and American Indian (12.1%) women (Table 1). Nearly half of women given the Tdap were also given an influenza vaccine during pregnancy. Vaccinated women compared with unvaccinated women had more healthcare visits during pregnancy. The proportion of infants censored before follow-up ended was 24.5% in MarketScan and 16.3% in MAX; their characteristics were similar to the full cohorts.

In MarketScan, 23 infants of mothers vaccinated during pregnancy developed pertussis [2.3 per 10,000; 95% confidence interval (CI): 1.3–3.2], compared with 117 (4.1 per 10,000; 95% CI: 3.3–4.8) in infants of unvaccinated women. In MAX, 21 infants of mothers vaccinated during pregnancy (7.5 per 10,000; 95% CI: 4.3–10.7) developed pertussis compared with 745 (12.5 per 10,000 95% CI: 22.6–13.4) in infants of unvaccinated women (Table 2). Weighted survival curves are presented in Figure 2. No infants from multiple births had a pertussis event in either database.

TABLE 2. - Distribution of Infant Pertussis Outcomes and Crude 6-Month Infant Pertussis Cumulative Hazard Per 10,000 Pregnancies by Maternal Exposure Group
N Cases CH Per 10,000 Inpatient Cases CH Per 10,000
IBM MarketScan
Unexposed 311,156 117 4.1 87 3.0
Pregnancy 114,067 23 2.3 15 1.4
Delivery 20,415 <11 NA <11 NA
Before 37 weeks 108,029 21 2.2 13 1.3
After 37 weeks or unexposed 33,7609 122 3.9 90 2.9
MAX
Unexposed 639,155 745 13.4 516 8.6
Pregnancy 33,286 21 7.5 15 5.2
Delivery 22,821 27 13.0 20 9.6
Before 37 weeks 31,462 18 6.8 13 4.8
After 37 weeks or unexposed 663,800 775 12.5 538 8.7
CH, cumulative hazard.

FIGURE 2.
FIGURE 2.:
Inverse probability of treatment weighted pertussis-free survival of infants after delivery by maternal exposure to Tdap in MarketScan and MAX.

The primary analysis comparing vaccination at any time during pregnancy with no vaccination estimated an adjusted HR of 0.74 (95% CI: 0.42–1.29) and 0.50 (95% CI: 0.24–1.04) in MarketScan and MAX, respectively (Fig. 2). This corresponds to an adjusted risk difference of 1 fewer case per 10,000 pregnancies in MarketScan and 6.1 fewer per 10,000 in MAX. The pooled HR estimate is 0.64 (95% CI: 0.41–1.00), equal to a vaccine effectiveness of 36% (Fig. 3). For pregnancies in women vaccinated at delivery, the adjusted HR estimates are 0.40 (95% CI: 0.13–1.27) and 1.07 (95% CI: 0.66–1.72) in MarketScan and MAX, respectively (Fig. 2).

FIGURE 3.
FIGURE 3.:
Inverse probability of treatment weighted pertussis-free survival of infants after delivery by maternal exposure to Tdap group in MarketScan and MAX.

Mothers of preterm infants had a lower likelihood of vaccination (21% in MarketScan and 3.8% in MAX) than mothers of terms likely due to the shorter gestation reducing the opportunity for maternal vaccination. Preterm infants of unvaccinated mothers had a higher risk of pertussis during their first 6 months of life 8.4 (95% CI: 5.2–11.7) cases per 10,000 infants in MarketScan and 19.8 (95% CI: 16.2–23.3) in MAX) than terms. These preterm infants have a more protective HR when their mothers were vaccinated during pregnancy (pooled HR: 0.11, 95% CI: 0.03–0.36) than full-term infants (0.78, 95% CI: 0.48–1.29) of mothers vaccinated before 37 weeks (Fig. 3). Mothers with preterm births were vaccinated before 37 weeks by definition. However, gestational timing of vaccination does not seem to explain the stronger association since in full-term infants of mothers vaccinated before 37 weeks, HRs were similar to terms of mothers vaccinated anytime in pregnancy for both databases (Figs. 3 and 4).

FIGURE 4.
FIGURE 4.:
Pooled hazard ratios (95% CI) of primary analysis and subgroup analyses by preterm delivery and pertussis uptick at delivery. CI indicates confidence interval.

Pregnancies that delivered during an uptick in pertussis incidence in their state had a lower HR (pooled HR: 0.32, 95% CI: 0.15–0.65) than pregnancies delivering outside an uptick (0.80, 95% CI: 0.48–1.34). Sensitivity analyses yielded similar HRs to the primary analyses in all pregnancies when restricting to inpatient pertussis cases, restricting follow-up to the first 60 days after delivery, and reclassifying exposure in the last 2 weeks of pregnancy as delivery exposure (Table, Supplemental Digital Content 3, http://links.lww.com/INF/E320). When limiting the primary analysis of vaccination in pregnancy compared with unvaccinated to the years 2011–2014, shared by both datasets, the estimates in the 2 datasets are closer together, due to an increase in the HR in MAX (0.75 in MarketScan and 0.66 in MAX; Table, Supplemental Digital Content 3, http://links.lww.com/INF/E320). The negative control outcome, gastrointestinal illness, was not associated with maternal Tdap vaccination in the pregnancy or delivery period for either database (HR: 0.99, 95% CI: 0.94–1.04) in MarketScan and HR: 0.94 (95% CI: 0.78–1.13) in MAX comparing Tdap during pregnancy to unexposed).

DISCUSSION

This study’s findings suggest that effectiveness (reduction in hazard) of vaccination during pregnancy against infant pertussis infection is around 36% (95% CI: 0–59). Vaccination before 37 weeks of pregnancy resulted in similar hazard reductions for term infants but would cover a higher proportion of preterm infants, who have a higher risk of infection when their mothers are not vaccinated and a more substantial vaccine effectiveness (89%) when their mothers are vaccinated. The protection conveyed by maternal vaccination at delivery was more uncertain.

These findings are consistent with prior literature and with the biologic basis of the vaccination recommendation.22,33–39 There is ongoing debate regarding the timing of maternal Tdap vaccination.40 Some studies of antibody titer in infants suggest a maximum titer with prenatal vaccination in the early third trimester, which informed the current recommendation.35,41–43 Other titer studies indicated that second-trimester vaccination leads to higher antibody titer in cord blood, including for premature infants.44,45 One US-based case-control study did not find a clinical benefit to vaccination in the first or second trimester compared with the third although sample size was limited.46 This is an area for future observational research, but guidelines inherently reduce incidence of second-trimester vaccinations which has impacted the availability of evidence.

Previous observational studies have found a protective effect of the prenatal vaccination strategy.21,22,38,46–48 Prior studies, particularly those based in the United Kingdom, found stronger vaccine effectiveness (at or above 90%) than our estimates. There are several differences that could account for some of this disparity in findings. First, the studies led by Amirthalingam used a screening (case-coverage) approach adjusting only for age and calendar time, described by European Network of Centres for Pharmacoepidemiology and Pharmacovigilance as a supplementary method for estimating crude VE.47,49 While still very informative, this is a different approach than the direct cohort comparison with covariate adjustment conducted here. Additional study details that differ from ours include the use of lab-confirmed cases, exclusion of vaccinations close to delivery, primary analysis of infants under 3 months, and underlying differences in pertussis prevalence and healthcare utilization between the 2 countries. Other studies have estimated a range of vaccine effectiveness (39%–90%) with methods such as adjusted case-control estimates, as summarized in a 2020 review by Vygen-Bonnet.21,22,46,48,50

For maternal vaccination at delivery, Tdap should still offer protection to infants via a lower risk of infection from primary contacts and via antibody transfer in breastmilk. However, in this study, we did not observe such protection in the MAX database, and a protective point estimate but large confidence interval including the null in MarketScan.

The difference in vaccination prevalence between Medicaid and MarketScan population indicates a disparity in the uptake of the Tdap recommendation. Although this could be a reflection of racial disparities in maternal healthcare,51 the much larger differences in vaccination coverage found between Medicaid (18.8% in 2014) and commercially insured women (42% in 2014) strongly suggest that socioeconomic factors explain most of the disparity. This is similar to findings comparing privately and publicly insured pregnant women in CDC’s vaccination survey.15 Routine prevention measures, such as vaccination, reflect differences in standard of care, regardless of underlying disease prevalence. Additionally, the risk of pertussis infection in the newborn was higher in the Medicaid population and the absolute benefit from vaccination in pregnancy was stronger. Differences in results between these 2 databases should be interpreted with caution; however, when limiting analyses to the same calendar years, the primary analysis results were more homogenous.

One limitation of our study is an unknown outcome validity. We chose to require multiple criteria to consider a pertussis case diagnosed only in the outpatient setting to increase the specificity of our outcome for more accurate ratio estimation, at the cost sensitivity and an underestimated risk difference.52 Although our outcome is not validated, the rates of pertussis observed are similar to CDC’s surveillance reports (range 4.4–16.0 cases per 10,000 infants under 6 months during this time period).5,53–55 We did observe expected associations with variables in our study, such as race, multiparity and calendar year. Moreover, unlike pertussis outcomes, gastrointestinal infections had no association with maternal Tdap vaccination.

Missing vaccinations is possible from 2 main sources: free vaccinations and unclaimed inpatient vaccinations, but we do not expect these to be very common. Physicians may still bill for vaccine administration, even when the vaccine product is provided for free through the Vaccines For Children program or other state mechanisms.56

Studies of vaccine effectiveness should be interpreted in the context of evidence for vaccine safety. Prospective registries and retrospective cohort studies thus far have shown Tdap administration during pregnancy to have no strong association with adverse pregnancy events and fetal outcomes.21,57–63 Several studies have estimated an approximate 20% increase in risk of chorioamnionitis, but this is not consistent across the literature and sequalae of chorioamnionitis (eg, preterm birth) were not positively associated with vaccination in these studies as would be expected from a causal mechanism.21,33,60,64

Our results support the effectiveness of the current recommendation of Tdap vaccination during pregnancy to prevent infant pertussis. Compared with privately insured women, publicly insured lagged behind in the increasing trend of Tdap vaccination, even when the relative vaccine effectiveness was stronger in publicly insured pregnant women. Based on our findings, vaccinating early in the recommended 27–36-week window will provide the largest population benefit by increasing coverage of preterm infants, who benefit the most from this maternal vaccination.

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Keywords:

pertussis; pregnancy; Tdap; vaccine effectiveness

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