Preclinical models of maternal asthma and progeny outcomes: a scoping review

Abstract

There is an increased risk of adverse perinatal outcomes in the ∼17% of women with asthma during pregnancy. The mechanisms linking maternal asthma and adverse outcomes are largely unknown, but reflect joint effects of genetics and prenatal exposure to maternal asthma. Animal models are essential to understand the underlying mechanisms independent of genetics and comorbidities, and enable safe testing of interventions. This scoping review aimed to explore the methodology, phenotype, characteristics, outcomes and quality of published studies using preclinical maternal asthma models. MEDLINE (PubMed), Embase (Elsevier) and Web of Science were systematically searched using previously validated search strings for maternal asthma and for animal models. Two reviewers independently screened titles and abstracts, full texts, and then extracted and assessed the quality of each study using the Animal Research: Reporting of In Vivo Experiments (ARRIVE) 2.0 guidelines. Out of 3618 studies identified, 39 were eligible for extraction. Most studies were in rodents (86%) and all were models of allergic asthma. Maternal and progeny outcomes included airway hyperresponsiveness, airway resistance, inflammation, lung immune cells, lung structure and serum immunoglobulins and cytokines. Experimental design (100%), procedural details (97%) and rationale (100%) were most often reported. Conversely, data exclusion (21%), blinding (18%) and adverse events (8%) were reported in a minority of studies. Species differences in physiology and timing of development, the use of allergens not relevant to humans and a lack of comparable outcome measures may impede clinical translation. Future studies exploring models of maternal asthma should adhere to the minimum core outcomes set presented in this review.

FIGURE 1

Preferred Reporting Items for Systematic Reviews – Scoping Review (PRISMA-ScR) flow diagram for database search of studies utilising a nonhuman model of maternal asthma.

FIGURE 2

Assessment of quality for all included studies (n=41) based on the Animal Research: Reporting of In Vivo Experiments (ARRIVE) 2.0 guidelines for a) the essential 10 and b) the recommended set. Data are percentages of studies that met each specific ARRIVE 2.0 recommendation.

FIGURE 3

Assessment of quality for included studies based on the Animal Research: Reporting of In Vivo Experiments (ARRIVE) 2.0 guidelines for a–c) the essential 10 and d–f) the recommended set separated into studies published before ARRIVE 1.0 (n=14, before 2010; a, d), after ARRIVE 1.0 (n=21, 2010–2019; b, e) and after ARRIVE 2.0 (n=6, 2020–2022; c, f). Data are percentages of studies that met each specific ARRIVE 2.0 recommendation.