Supplementary Material for: Low-dose aspirin and prevention of spontaneous preterm birth: is it worthwhile? A systematic review and meta-analysis

ABSTRACT
Introduction: Due to its anti-inflammatory properties, low-dose aspirin (LDA) has been theorized to mitigate spontaneous preterm birth (PTB). This systematic review and meta-analysis aims to report the available evidence to determine whether LDA administration prevents any spontaneous PTB.
Methods: Embase, PubMed, Scopus, Cochrane Central Register, and Web of Science databases were searched, and the protocol was registered within the PROSPERO database (CRD42021288021). Data were examined using Review Manager 5.4 Software.
Results: The search yielded 261 relevant articles, from which 11 pertinent studies were included in this meta-analysis. While LDA showed a reduction of spontaneous PTB rates (Odds Ratio OR 0.93; 95% CI 0.84-1.04), the results lacked statistical significance. Nevertheless, LDA significantly reduced the rate of spontaneous PTB < 34 weeks (6 studies; OR 0.85; 95% CI 0.78-0.93). Also, sub-group analysis of high-risk women (OR 0.96; 95% CI 0.78-1.17) and healthy women (OR 0.91; 95% CI 0.79-1.04) showed that LDA had a non-significant trend to reduce spontaneous PTB rates. Moreover, there was a statistically significant reduction in spontaneous PTB when LDA administration was initiated before 16 weeks (5 studies; OR 0.91; 95% CI 0.83-0.98), although not for LDA dosages below 100 mg (9 studies; OR 0.97; 95% CI 0.91-1.03).
Conclusion: This meta-analysis indicates a statistically significant reduction in spontaneous PTB rates associated with LDA administration only in spontaneous PTB pregnancies before 34 weeks (not any spontaneous PTB) and for LDA administration starting before 16 weeks. Although LDA can potentially prevent any spontaneous PTB, further well-conducted trials focusing specifically on this subgroup are warranted to provide robust evidence of its efficacy.