Low-income settings are underrepresented in comparative maternal vaccine safety research, according to a recent study published in Vaccine: X.
Takeaways
- Maternal vaccination plays a critical role in reducing neonatal mortality, particularly in low- and middle-income countries where it remains a significant health concern.
- Despite the efficacy of vaccines, increasing global vaccine hesitancy emphasizes the importance of evidence-based research to maintain public trust.
- A recent study highlights a lack of representation from low-income countries in maternal vaccine safety research, indicating a need for more inclusive studies.
- Variability in adverse event reporting standards across studies underscores the necessity for standardized reporting practices to ensure consistency and transparency.
- The findings stress the need for prioritizing research infrastructure in low-income settings to address disparities in maternal vaccine safety research and improve maternal and neonatal health outcomes globally.
Nearly half of all under-5 deaths worldwide have been linked to neonatal mortality, indicating a severe health concern. Neonatal mortality is especially challenging in low- and middle-income countries.
Maternal vaccination has arisen as a method to manage neonatal mortality, with a maternal-neonatal tetanus program leading to elimination status of tetanus in all but 12 targeted countries. Vaccination during pregnancy has also been associated with reduced risks of diseases such as influenza and COVID-19.
While the safety and efficacy of vaccines has been proven, vaccine hesitancy has increased worldwide. This indicates a need for evidence-based vaccine research to improve public trust in vaccines.
Investigators conducted a review to evaluate the status of maternal vaccine adverse events following immunization (AEFI) reporting in comparative clinical vaccine trials. Interventional and observational studies involving vaccine administration to pregnant women were included in the analysis.
Exclusion criteria included not evaluating pregnant women, not including a comparator, and not being published in English. Studies were included if they compared vaccines against a placebo and had intervention efficacy, effectiveness, or safety as an outcome measure.
Studies were found through systematic searches of the Pubmed, Web of Science, EMBASE, and Cochrane databases. The searches utilized medical subject headings terms and keyword searches. Publications from 2014 to December 31, 2022, were included in the analysis.
Title and abstract screening were performed by 2 independent reviewers. The same reviewers then screened full texts, with a third reviewer consulted to resolve uncertainty. The variation of AEFI definitions across studies were assessed as the primary outcome of the review.
There were 116 original research papers and 60 review papers included in the final analysis. Of studies, 50.9% were retrospective cohort studies, 20.7% were randomized controlled trials, and 19.8% were prospective cohort studies.
AEFI was identified through electronic medical records in 41.4% of studies. Only 10.3% of studies were exclusively conducted in lower- or lower-middle-income countries, and studies conducted in high-income countries were more often larger.
Hypertensive disorders of pregnancy and chorioamnionitis were the most frequently reported AEFIs, with 19,430 and 18,273 events reported, respectively. For neonatal outcomes, small for gestational age, preterm birth, and congenital anomalies were the most common, with 30,929, 28,828, and 13,466 reported, respectively.
Brighton Collaboration Global Alignment on Immunization Safety Assessment in Pregnancy (GAIA) definitions were cited or used by 8 studies. GAIA definitions were used to improve respective study quality, assess vaccine safety during pregnancy, or present a modified stillbirth definition or outcome criteria.
Temporal and physiological thresholds often dictated the criteria for defined events, such as the gestational age when a fetal loss is classified as stillbirth vs spontaneous abortion. There were 12 thresholds identified for stillbirth across 39 studies, while 12 studies did not provide a definition. Similarly, 10 studies did not provide a definition for preterm birth.
Serious adverse events (SAE) were reported by 19 publications. Of these, 8 defined an SAE or provided a reference used for categorizing SAEs. The definition of SAE varied across studies, from serious, life-threatening conditions, to all outcomes of special interest in pregnancy.
These results indicated a lack of transparency and variability in reporting SAEs and a lack of research from low- and middle-income countries. Investigators recommended the establishment of capacity and infrastructure for studies be prioritized in these settings.
Reference
Davies HG, Thorely EV, Al-Bahadili R, et al. Defining and reporting adverse events of special interest in comparative maternal vaccine studies: a systematic review. Vaccine: X. 2024;18. doi:10.1016/j.jvacx.2024.100464
