Impact of low-dose aspirin on maternal haemoglobin levels during pregnancy: a protocol for a systematic review and meta-analysis

Background Aspirin, a cyclooxygenase (COX) inhibitor with anti-inflammatory and antiplatelet properties, is widely used during pregnancy to prevent preeclampsia (PE) and intrauterine growth restriction (IUGR). Despite its benefits, low-dose aspirin (LDA) has been linked to obstetric haemorrhage, including postpartum haemorrhage (PPH), and may influence haemoglobin (Hb) levels via its iron-chelating effects. The potential combined impact of LDA on Hb levels and pregnancy outcomes, however, remains unclear. This systematic review protocol aims to evaluate the effect of LDA on maternal Hb levels during pregnancy. Methods Following PRISMA-P guidelines, comprehensive searches will be conducted in PubMed, Cochrane Library, Embase, Scopus, Web of Science, and ClinicalTrials.gov, as well as grey literature sources. Eligible studies will include randomised controlled trials (RCTs), cohort studies, and case-control studies reporting Hb levels in pregnant women using LDA. Two independent reviewers will perform screening, data extraction, and quality appraisal. Data will be synthesised using meta-analysis where feasible, with subgroup analyses to explore heterogeneity, and narrative synthesis for studies not suitable for pooling. Results The systematic review will generate pooled evidence on how LDA affects maternal Hb levels and associated pregnancy outcomes such as PE and fetal growth. Conclusions The findings may assist in refining clinical recommendations for LDA use in pregnancy by balancing its preventive benefits with potential risks related to anaemia, and haemorrhage. Systematic review registration PROSPERO CRD42024556220.