In a recent study published in the journal Pediatrics, researchers carried out a large-scale population-based cohort study across Australia to investigate maternal vaccination effectiveness (VE) against pertussis. They further evaluated whether the vaccination of a mother ≥14 days before the birth of her child would significantly alter the effectiveness of routine primary pertussis vaccine administration to the infant. Their results highlight that maternal vaccination reduced overall infection risk in infants and conferred pertussis resistance until eight months of age. While slightly lowering the VE of routine pertussis administered to infants, maternal pertussis was not associated with increased disease risk in infants.
Study: Maternal Pertussis Vaccination, Infant Immunization, and Risk of Pertussis. Image Credit: Kateryna Kon / Shutterstock
Pertussis and maternal vaccination
Pertussis is the medical term for the colloquially used 'whooping cough,' a highly contagious respiratory tract infection that affects individuals of all ages. However, it has the most severe morbidity and mortality repercussions in infants and young children. The name 'whooping cough' is derived from the high-pitched intake of breath that sounds like "whoop" that follows the disease's characteristic severe hacking cough. Other symptoms of infection include runny or blocked nasal tracts and frequent sneezing.
Prior to 1914, pertussis was one of the deadliest childhood diseases worldwide. In 1914, the while-cell pertussis vaccine was developed in the United States (US), significantly reducing the disease burden. In 1948, whole-cell pertussis vaccines were combined with two other notable childhood vaccines for tetanus and diphtheria toxoids, a formulation called 'DPT'. Widespread use of the DPT vaccine as routine pediatric care has severely hampered the demerits of whooping cough, but like most vaccines, it has been unable to eradicate its constituent pathogens. Most notably, 2012 and 2013 saw an increase in infection prevalence to epidemic proportions.
When pertussis occurs in infants and young children, its effects are far more severe than for adults, with children accounting for between 70% and 90% of all hospitalizations and deaths linked to the disease. Following the aforementioned epidemics and in response to the high morbidity and mortality associated with childhood pertussis, the US and United Kingdom (UK) in 2013 recommended maternal vaccination. Maternal vaccination is a process in which pregnant women are administered a vaccine on the hypothesis that resistance will be conferred not only to the mothers but, more importantly, to their unborn offspring.
Australia followed suit in 2014 with numerous states and territories implementing jurisdictional-funded vaccination drives for diphtheria-tetanus-acellular pertussis (dTpa) booster dosages at around 28 weeks of gestation. July 2018 saw these drives become federally funded under Australia's National Immunization Program.
While numerous studies have explored the effectiveness of maternal vaccination against pertussis with largely positive results, these studies have yet to agree upon the duration of resistance conferred on infants, the optimal gestational age for vaccination administration, and the infant's immune response to vaccination before birth. Notable, results for studies differ in their VE estimates, which range widely from 43% to 93% for babies under 2 months of age.
About the study
In the present study, researchers had two main objectives – 1. To estimate the infant VE of maternal vaccine administration on three scales (overall, by gestational age, and by infant age), and 2. Using real-world data to evaluate the potential 'blunting' effects that maternal vaccination would have on routine pediatric dTpa care. The study comprised data from the Links2HealthierBubs cohort, a population-based cohort of mother-infant pairs from the Northern Territory (NT), Western Australia (WA), and Queensland (QLD). All dyads wherein the gestational age was 20 weeks or greater or the infant was born weighing more than 400 g were included in this study.
Demographic and clinical data comprising perinatal birth, hospitalization, immunization, birth and death register, and disease data were collected from all participants. Mothers were recommended to receive maternal vaccination with dTpa between 28 and 32 weeks of gestation. Vaccination and maternal medication data were obtained from perinatal data collections, statutorily mandated databases archived at each jurisdiction. Hospital records were used to evaluate pertussis severity, and death records were used as proxies for infant mortality.
Statistical analyses comprised descriptive statistics using Chi-squared (χ2) tests (categorical variables) and Wilcoxon rank sum (continuous variables). A mixed effects Cox model was used to compare infection rates between infants whose mothers had received maternal vaccination versus those that had not.
"We used inverse probability of treatment (vaccination) weights to account for confounding. Treatment weights were derived from the predicted probability of pertussis vaccination during pregnancy, based on a fitted multivariable logistic regression model with maternal age, ethnicity, preexisting health conditions, pregnancy complications, parity, smoking status, initiation of prenatal care, year and season of conception, Socioeconomic Index for Areas quintile, and receipt of influenza vaccine during pregnancy as predictor variables."
Vaccine effectiveness (VE) was estimated by subtracting the hazard ratio (HR) of the weighted inverse probability of treatment (obtained from the Cox model) from one. For NT and QLD cohorts, models were fit to estimate the effects of maternal vaccination on subsequent routine dTpa infant vaccination (termed "blunting").
Study findings
The inclusion criteria listed above resulted in a sample cohort of 297,418 infants born to 252,444 mothers. Of these, 144,429 infants' mothers (51.7%) received maternal vaccination. Vaccination registration revealed that 14,028 (5%) received maternal vaccination before 28 weeks of gestation, 80,327 (28.7%) at 28-31 weeks, and 48,629 (17.4%) after 31 weeks but before birth.
"A total of 331 notified pertussis cases were Identified in the cohort up to 18 months of age, equating to 118 cases per 100 000 infants; 119 cases were identified among infants of vaccinated mothers (82 per 100 000 infants), and 212 cases were identified among infants of unvaccinated mothers (157 per 100 000 infants)."
VE model evaluations highlight that maternal vaccination conferred significantly higher pertussis resistance in infants compared to only routine vaccination. Maternal vaccination was found to persist till at least 8 months of age, more than 2 months longer than reported in previous studies. Immunological gestation time analysis found that contrasting previous work, which reported higher antibody titers (and hence, potentially better resistance) in cord blood of infants whose mothers were vaccinated closer to delivery, this study did not find differences in conferred resistance when adjusting for VE by the timing of delivery.
In infants under the influence of maternal vaccination, slight reductions in routine dTpa VE were observed. However, these reductions did not translate to reductions in pertussis resistance.
"Our interpretation of these findings, in combination with the published literature, is that maternal antibodies may "blunt" the response of infants to primary immunization, but maternal and/or infant antibodies are sufficient to protect maternally vaccinated infants from infection. However, further research is needed to confirm our findings."
Conclusions
The present study aimed to evaluate the benefits of maternal vaccination during gestation as a means to combat pertussis during the early months of an infant's life. Findings from a large cohort Australian sample group revealed that maternal vaccination confers significantly improved infant resistance against the disease, with effects persisting for at least eight months. This study also reveals that, while slightly lowering the effectiveness of subsequent routine dTpa vaccinations in infants, maternal vaccination does not result in increased infection risk in infants.
Overall, these findings highlight the pros of maternal vaccination as a low-risk, high-reward weapon in humanity's arsenal against pertussis, one of the more severe and deadly diseases in infants and young children. These findings could help policymakers, inform prospective parents, and form the basis for future studies aimed at determining the optimal time and dosage of maternal vaccination for the best possible clinical outcomes in infants.
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