Effectiveness of Vaccination During Pregnancy to Prevent Infant Pertussis
TL;DR: This study strongly supports the United States’ current recommendation to administer Tdap during each pregnancy and was highly protective against infant pertussis, especially in the first 2 months of life.
Abstract: BACKGROUND: Vaccination against pertussis during pregnancy is recommended to protect newborns, yet there is limited information about the effectiveness of maternal tetanus toxoid, reduced diphtheria toxoid, acellular pertussis (Tdap) vaccine before the first infant dose of diphtheria, tetanus and acellular pertussis (DTaP) vaccine and during the first year of life in infants who have received DTaP. METHODS: In a retrospective cohort study of infants born at Kaiser Permanente Northern California from 2010 to 2015, we estimated the effectiveness of maternal pertussis vaccination for protecting newborns against pertussis in the first 2 months of life and in the first year of life accounting for each infant DTaP dose. RESULTS: Among 148 981 newborns, the vaccine effectiveness of maternal Tdap was 91.4% (95% confidence interval [CI], 19.5 to 99.1) during the first 2 months of life and 69.0% (95% CI, 43.6 to 82.9) during the entire first year of life. The vaccine effectiveness was 87.9% (95% CI, 41.4 to 97.5) before infants had any DTaP vaccine doses, 81.4% (95% CI, 42.5 to 94.0) between doses 1 and 2, 6.4% (95% CI, −165.1 to 66.9) between doses 2 and 3, and 65.9% (95% CI, 4.5 to 87.8) after infants had 3 DTaP doses. CONCLUSIONS: Maternal Tdap vaccination was highly protective against infant pertussis, especially in the first 2 months of life. Even after infant DTaP dosing, there was evidence of additional protection from maternal Tdap vaccination for the first year of life. This study strongly supports the United States’ current recommendation to administer Tdap during each pregnancy.
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01 Jan 2018
TL;DR: It is critical to fully understand the mechanisms by which IgG is transferred across the placenta to develop optimal maternal and infant immunization strategies.
Abstract: Pediatric vaccines have significantly reduced infectious disease-related infant mortality, but as protective immunity often require several infant vaccine doses; maternally-acquired antibodies are critical to protect infants during the first months of life. Consequently, immunization of pregnant women is an important strategy not only to protect mothers from infection, but also to provide immunity to young infants. Nevertheless, maternal immunization can also negatively impact early life immunity. In fact, maternal antibodies can interfere with the development of infant immune responses, though it is unclear if such interference is clinically significant. Moreover, the transplacental transfer of maternal immunoglobulin therapeutics can be harmful to the fetus. Thus, the risk/benefit of maternal immunization for both the mother and the fetus should be carefully weighed. In addition, it is critical to fully understand the mechanisms by which IgG is transferred across the placenta in order to develop optimal maternal and infant immunization strategies.
142 citations
TL;DR: Vaccination during pregnancy is an effective way to protect infants during the early months of life, and efforts should focus on maximizing Tdap uptake among pregnant women.
Abstract: Background Infants aged Methods We conducted a case-control evaluation among pertussis cases Results A total of 240 cases and 535 controls were included; 17 (7.1%) case mothers and 90 (16.8%) control mothers received Tdap during the third trimester of pregnancy. The multivariable VE estimate for Tdap administered during the third trimester of pregnancy was 77.7% (95% confidence interval [CI], 48.3%-90.4%); VE increased to 90.5% (95% CI, 65.2%-97.4%) against hospitalized cases. Conclusions Vaccination during pregnancy is an effective way to protect infants during the early months of life. With a continuing resurgence in pertussis, efforts should focus on maximizing Tdap uptake among pregnant women.
120 citations
TL;DR: Although an increased risk for a diagnosis of fever and chorioamnionitis was detected in pregnant women after pertussis vaccination, there was no association with a higher frequency of clinically relevant sequelae and overall positive benefit-risk ratio.
Abstract: Infants < 3 months of age are at highest risk for developing severe complications after pertussis. The majority of pregnant women has low concentrations of pertussis-specific antibodies and thus newborns are insufficiently protected by maternally transferred antibodies. Acellular pertussis vaccination during pregnancy was recently implemented in various countries. Here, we assessed the evidence for safety and effectiveness of pertussis vaccination during pregnancy. We searched Medline, Embase, and ClinicalTrials.gov from January 1st 2010 to January 10th 2019. We assessed risk of bias (ROB) using the Cochrane ROB tool and ROBINS-I. We evaluated the quality of evidence using the GRADE approach. We identified 1273 articles and included 22 studies (14 for safety; 8 for effectiveness), comprising 1.4 million pregnant women in safety studies and 855,546 mother-infant-pairs in effectiveness studies. No significant differences between vaccinated and unvaccinated women and their infants were observed for safety outcomes with the exception of fever and chorioamnionitis. Compared to no vaccination, three studies showed a significantly increased relative risk for the presence of the ICD-9 code for chorioamnionitis in electronic patient data after pertussis vaccination. However, no study reported an increased risk for clinical sequelae of chorioamnionitis after vaccination during pregnancy, such as preterm birth or neonatal intensive care unit admission. Vaccine effectiveness against pertussis in infants of immunized mothers ranged from 69 to 91% for pertussis prevention, from 91 to 94% for prevention of hospitalization and was 95% for prevention of death due to pertussis. Risk of bias was serious to critical for safety outcomes and moderate to serious for effectiveness outcomes. GRADE evidence quality was moderate to very low, depending on outcome. Although an increased risk for a diagnosis of fever and chorioamnionitis was detected in pregnant women after pertussis vaccination, there was no association with a higher frequency of clinically relevant sequelae. Vaccine effectiveness for prevention of infant pertussis, hospitalization and death is high. Pertussis vaccination during pregnancy has an overall positive benefit-risk ratio. In view of the overall quality of available evidence ongoing surveillance of chorioamnionitis and its potential sequelae is recommended when pertussis vaccination in pregnancy is implemented. PROSPERO CRD42018087814, CRD42018090357.
86 citations
Cites background from "Effectiveness of Vaccination During..."
...We judged the most recent cohort study from the USA by Becker-Dreps et al. [45] as having a serious RoB because no clear case definition based on laboratory criteria was reported and the proportion of lab-confirmed cases in the subgroups was unknown....
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...Five [16, 43, 45, 47, 49] of the eight studies were judged as having a serious RoB, while three studies had a moderate RoB [44, 46, 48]....
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...Abbreviations 95% CI: 95% confidence interval; GRADE: Grading of Recommendations Assessment, Development and Evaluation; ICD: International classification of diseases; LBW: Low birth weight; NICU: Neonatal intensive care unit; PICO: Population, intervention, comparator, outcome; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-analyses; RCT: Randomized controlled trial; RoB: Risk of bias; RR: Relative risk; Tdap: Tetanus-diphtheriaacellular pertussis; VE: Vaccine effectiveness; VLBW: Very low birth weight Acknowledgments The authors would like to thank Dr. Eva Hummers, Göttingen/Germany, who is a member of the pertussis working group of the German Standing Committee on Vaccination (STIKO), for contributing to the discussions of our results....
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...Of the 11 non-randomized studies, we judged eight as having a serious RoB and three studies to show a critical RoB (Additional file 1: Table S2)....
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...Pertussis in infants 0–3 months of age Three cohort [16, 43, 44] and two case-control studies [47, 49] reported on the effectiveness of Tdap vaccination in pregnancy to prevent pertussis in infants 0–2 months of age (Table 3)....
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TL;DR: Pregnant women would be willing to get all recommended vaccinations if they had at least one child and if they needed additional information, whereas the willingness was significantly lower among women who had reported high school as the highest level of education and who felt that the recommended vaccines administered during pregnancy were less dangerous for them and for the unborn child.
Abstract: The aims of this survey were to ascertain pregnant women's level of knowledge and acceptability on the vaccinations and to identify their associations with several characteristics. A cross-sectional study was performed from December 2017 through March 2018 in the geographic area of Naples, Italy. The study used two stages cluster sampling method for selection and recruitment of participants. Data were collected through face-to-face interviews with pregnant women present at the Obstetrics outpatient clinic of the selected hospitals. A total of 358 respondents agreed to be interviewed out of the 405 pregnant women selected. One-fourth knew at least one of the vaccinations recommended during pregnancy and only 2.8% correctly identified all of these. Women who had received information about the vaccinations during pregnancy from general practitioners or gynecologists or other sources and those with at least one child were more likely to know at least one of the recommended vaccinations, whereas women with middle school education were less knowledgeable. None of the women had received tetanus, diphtheria, and acellular pertussis vaccine and only 1.4% the seasonal influenza vaccination. Only 27.9% reported a positive willingness to receive all the recommended vaccinations during pregnancy. Pregnant women would be willing to get all recommended vaccinations if they had at least one child and if they needed additional information, whereas the willingness was significantly lower among women who had reported high school as the highest level of education, who were in the second trimester of pregnancy, and who felt that the recommended vaccines administered during pregnancy were less dangerous for them and for the unborn child. This study suggests important focus points to be taking into account for informing and for implementing education activities on the benefits regarding vaccinations in order to increase the level of knowledge and the uptake in pregnant women.
82 citations
TL;DR: COVID-19 vaccination during pregnancy, compared with vaccination after pregnancy and with no vaccination, was not significantly associated with increased risk of adverse peripartum outcomes.
Abstract: Importance
There is limited comparative epidemiological evidence on outcomes associated with COVID-19 vaccination during pregnancy; monitoring pregnancy outcomes in large populations is required.
Objective
To evaluate peripartum outcomes following COVID-19 vaccination during pregnancy.
Design, Setting, and Participants
Population-based retrospective cohort study in Ontario, Canada, using a birth registry linked with the provincial COVID-19 immunization database. All births between December 14, 2020, and September 30, 2021, were included.
Exposures
COVID-19 vaccination during pregnancy, COVID-19 vaccination after pregnancy, and no vaccination.
Main Outcomes and Measures
Postpartum hemorrhage, chorioamnionitis, cesarean delivery (overall and emergency cesarean delivery), admission to neonatal intensive care unit (NICU), and low newborn 5-minute Apgar score (<7). Linear and robust Poisson regression was used to generate adjusted risk differences (aRDs) and risk ratios (aRRs), respectively, comparing cumulative incidence of outcomes in those who received COVID-19 vaccination during pregnancy with those vaccinated after pregnancy and those with no record of COVID-19 vaccination at any point. Inverse probability of treatment weights were used to adjust for confounding.
Results
Among 97 590 individuals (mean [SD] age, 31.9 [4.9] years), 22 660 (23%) received at least 1 dose of COVID-19 vaccine during pregnancy (63.6% received dose 1 in the third trimester; 99.8% received an mRNA vaccine). Comparing those vaccinated during vs after pregnancy (n = 44 815), there were no significantly increased risks of postpartum hemorrhage (incidence: 3.0% vs 3.0%; aRD, -0.28 per 100 individuals [95% CI, -0.59 to 0.03]; aRR, 0.91 [95% CI, 0.82-1.02]), chorioamnionitis (0.5% vs 0.5%; aRD, -0.04 per 100 individuals [95% CI, -0.17 to 0.09]; aRR, 0.92 [95% CI, 0.70-1.21]), cesarean delivery (30.8% vs 32.2%; aRD, -2.73 per 100 individuals [95% CI, -3.59 to -1.88]; aRR, 0.92 [95% CI, 0.89-0.95]), NICU admission (11.0% vs 13.3%; aRD, -1.89 per 100 newborns [95% CI, -2.49 to -1.30]; aRR, 0.85 [95% CI, 0.80-0.90]), or low Apgar score (1.8% vs 2.0%; aRD, -0.31 per 100 newborns [95% CI, -0.56 to -0.06]; aRR, 0.84 [95% CI, 0.73-0.97]). Findings were qualitatively similar when compared with individuals who did not receive COVID-19 vaccination at any point (n = 30 115).
Conclusions and Relevance
In this population-based cohort study in Ontario, Canada, COVID-19 vaccination during pregnancy, compared with vaccination after pregnancy and with no vaccination, was not significantly associated with increased risk of adverse peripartum outcomes. Study interpretation should consider that the vaccinations received during pregnancy were primarily mRNA vaccines administered in the second and third trimester.
81 citations
References
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TL;DR: The assessment of the programme of pertussis vaccination in pregnancy in England is consistent with high vaccine effectiveness, which probably results from protection of infants by both passive antibodies and reduced maternal exposure, and will provide valuable information to international policy makers.
604 citations
Journal Article•
TL;DR: The updated recommendations on use of Tdap in pregnant women aim to optimize strategies for preventing pertussis morbidity and mortality in infants.
Abstract: In October 2011, in an effort to reduce the burden of pertussis in infants, the Advisory Committee on Immunization Practices (ACIP) recommended that unvaccinated pregnant women receive a dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap). Vaccination of women with Tdap during pregnancy is expected to provide some protection to infants from pertussis until they are old enough to be vaccinated themselves. Tdap given to pregnant women will stimulate the development of maternal antipertussis antibodies, which will pass through the placenta, likely providing the newborn with protection against pertussis in early life, and will protect the mother from pertussis around the time of delivery, making her less likely to become infected and transmit pertussis to her infant. The 2011 Tdap recommendation did not call for vaccinating pregnant women previously vaccinated with Tdap. On October 24, 2012, ACIP voted to recommend use of Tdap during every pregnancy. This report summarizes data considered and conclusions made by ACIP and provides guidance for implementing its recommendations. These updated recommendations on use of Tdap in pregnant women aim to optimize strategies for preventing pertussis morbidity and mortality in infants.
516 citations
TL;DR: Pertussis waned during the 5 years after the fifth dose of DTaP, and the odds of acquiring pertussis increased by an average of 42% per year after 2006 to 2011.
Abstract: Background In the United States, children receive five doses of diphtheria, tetanus, and acellular pertussis (DTaP) vaccine before 7 years of age. The duration of protection after five doses of DTaP is unknown. Methods We assessed the risk of pertussis in children in California relative to the time since the fifth dose of DTaP from 2006 to 2011. This period included a large outbreak in 2010. We conducted a case–control study involving members of Kaiser Permanente Northern California who were vaccinated with DTaP at 47 to 84 months of age. We compared children with pertussis confirmed by a positive polymerase-chain-reaction (PCR) assay with two sets of controls: those who were PCR-negative for pertussis and closely matched controls from the general population of health-plan members. We used logistic regression to examine the risk of pertussis in relation to the duration of time since the fifth DTaP dose. Children who received whole-cell pertussis vaccine during infancy or who received any pertussis-contain...
489 citations
"Effectiveness of Vaccination During..." refers methods in this paper
...We ran separate Cox models to estimate the VE of maternal Tdap during pregnancy in preventing infant pertussis during 2 follow-up periods: (1) model for the first 2 months of life (as described above) and (2) models for the first 12 months of life....
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...We identified 3 groups of infants based on the Tdap vaccination status during pregnancy of their birth mother: (1) vaccinated (Tdap vaccination during pregnancy at least 8 days before birth); or (2) vaccinated too close to birth to boost maternal antibody transfer (Tdap vaccination 1–7 days before birth); or (3) unvaccinated (no Tdap vaccination during pregnancy)....
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TL;DR: This review will discuss the use of animal models for vaccine research, clinical solutions for inhibition of vaccination by maternal antibodies, and the testing and development of potentially effective vaccines based on new mechanistic insight about the inhibitory mechanism of maternal antibodies.
Abstract: Neonates have an immature immune system which cannot adequately protect against infectious diseases. Early in life, immune protection is accomplished by maternal antibodies transferred from mother to offspring. However, decaying maternal antibodies inhibit vaccination as is examplified by the inhibition of seroconversion after measles vaccination. This phenomenon has been described in both human and veterinary medicine and is independent of the type of vaccine being used. This review will discuss the use of animal models for vaccine research. I will review clinical solutions for inhibition of vaccination by maternal antibodies, and the testing and development of potentially effective vaccines. These are based on new mechanistic insight about the inhibitory mechanism of maternal antibodies. Maternal antibodies inhibit the generation of antibodies whereas the T cell response is usually unaffected. B cell inhibition is mediated through a cross-link between B-cell receptor (BCR) with the Fcg receptor IIB (FcgRIIB) by a vaccine-antibody complex. In animal experiments, this inhibition can be partially overcome by injection of a vaccine-specific monoclonal IgM antibody. IgM stimulates the B-cell directly through cross-linking the BCR via complement protein C3d and antigen to the complement receptor 2 (CR2) signaling complex. In addition, it was shown that interferon alpha binds to the CD21 chain of CR2 as well as the interferon receptor and that this dual receptor usage drives B cell responses in the presence of maternal antibodies. In lieu of immunizing the infant the concept of maternal immunization as a strategy to protect neonates has been proposed. This approach would still not solve the question of how to immunize in the presence of maternal antibodies but would defer the time of infection to an age where infection might not have such a detrimental outcome as in neonates. I will review successful examples and potential challenges of implementing this concept.
374 citations
TL;DR: Determinant-specific masking of B cell epitopes and APC uptake of MatAb explain the pattern of pre-clinical and clinical responses to infant vaccines and allow the definition of the main determinants of the influence of Mat Ab on infant immunity.
328 citations