Birth outcomes in Aboriginal mother–infant pairs from the Northern Territory, Australia, who received 23‐valent polysaccharide pneumococcal vaccination during pregnancy, 2006–2011: The PneuMum randomised controlled trial

Abstract

Background Pregnant women and infants <6 months old have a high baseline risk for pneumococcal disease compared to the general population, particularly among Indigenous populations living in poverty and low‐resource settings. Efficacy trials of pneumococcal vaccination in pregnancy examining adverse birth outcomes are lacking. Aims We report adverse birth events as secondary outcomes from the ‘PneuMum’ randomised controlled trial of 23‐valent pneumococcal polysaccharide vaccination (23vPPV) in pregnancy (August 2006–January 2011). Materials and methods Australian Aboriginal women aged 17–39 years with singleton uncomplicated pregnancies were randomised (1:2 ratio) to receive 23vPPV or no 23vPPV in pregnancy at 30–36 weeks gestation. We compared risks of stillbirth, preterm birth, low birthweight (LBW), and small for gestational age (SGA) between vaccinated and unvaccinated pregnant women. Cox proportional hazard ratios (HRs) were calculated on an intention‐to‐treat basis. Results Among 227 enrolled participants, 75 (33%) received 23vPPV in pregnancy. Risk differences in adverse birth outcomes between 23vPPV vaccinated and unvaccinated pregnant women were; preterm birth 9% vs 4% (HR 2.79; 95% CI 0.94–8.32) P = 0.07; LBW 9% vs 5% (HR 2.09; 95% CI 0.76–5.78) P = 0.15; and SGA 15% vs 17% (HR 1.02; 95% CI 0.50–2.06) P = 0.96. There were no stillbirths. Conclusions We found a numerically higher rate of preterm births among women who received 23vPPV in pregnancy compared to unvaccinated pregnant women. Although further investigation with larger participant numbers is needed to better evaluate this safety signal, the contribution of safety results from smaller studies using appropriate data analysis methodologies is critical, particularly as more clinical trials in pneumococcal vaccination in pregnancy are progressing.

Are maternal vaccines effective and safe for mothers and infants? A systematic review and meta-analysis of randomised controlled trials

“…The majority of vaccines did not contain any adjuvants, although some incorporated adjuvants including aluminium hydroxide or phosphate. The characteristics of the nine included studies are described in table 1 25–33…”

“…When assessing the RoB, four articles were identified as low RoB,25–27 33 one article with some concerns29 and four articles as high RoB 28 30–32. A detailed assessment of the RoB is available in online supplemental table S3.…”

“…Maternal pneumococcal vaccination was assessed in three articles based on one trial 30–32. The trial, conducted in Northern Territory, Australia, compared maternal 23-valent pneumococcal polysaccharide vaccine given between 30 and 36 weeks’ gestation with no vaccination during pregnancy.…”

At the cultural interface: A systematic review of study characteristics and cultural integrity from twenty years of randomised controlled trials with Indigenous participants

“…The AMSTAR 2 Risk of Bias for Systematic Review tool [ 14 ] was applied by the authors to the review process. In this context, two questions in the tool were deemed to be not applicable due to their focus on evidence synthesis or meta-analysis, as the systematic review focus was on quality of design and implementation.…”

Trends in Preterm birth in the Top End of the Northern Territory, Australia: a retrospective, longitudinal cohort study characterising trends and risk factors for premature birth

“…Several other NT studies have also investigated speci c factors and their impact on birth outcomes, including gestational age at birth. Such studies have examined the impact of sexually transmitted infections [7], vaccinations during pregnancy, [8,9]and young maternal age [10], none of which were signi cantly associated with PTB risk. One study showed a higher rate of PTB in those with (versus without) rheumatic heart disease, [11] whereas two studies found lower rates of PTB in those receiving enhanced models of pregnancy care [12,13].…”