Objective: This systematic review estimated the pooled $R_0$ for early COVID-19 outbreaks and identified the impact of study-related factors such as methods, study location and study period on the estimated $R_0$. Methods: We searched electronic databases for human studies published in English between 1 December 2019 and 30 September 2020 with no restriction on country/region. Two investigators independently performed the data extraction of the studies selected for inclusion during full-text screening. The primary outcome, $R_0$, was analysed by random-effects meta-analysis using the restricted maximum likelihood method. Results: We identified 26,425 studies through our search and included 151 articles in the systematic review, among which 81 were included in the meta-analysis. The estimates of $R_0$ from studies included in the meta-analysis ranged from 0.4 to 12.58. The pooled $R_0$ for COVID-19 was estimated to be 2.66 (95% CI, 2.41–2.94). The results showed heterogeneity among studies and strong evidence of a small-study effect. Conclusions: The high heterogeneity in studies makes the use of the $R_0$ for basic epidemic planning difficult and presents a huge problem for risk assessment and data synthesis. Consensus on the use of $R_0$ for outbreak assessment is needed, and its use for assessing epidemic risk is not recommended.

Introduction: Orofacial clefts (OFCs), including cleft lip, cleft palate and combined cleft lip and palate, are among the most common craniofacial malformations in newborns and present significant healthcare challenges. Emerging evidence has raised concerns regarding the potential impact of prenatal exposure to antibiotics on fetal development. Antibiotics prescribed during pregnancy—particularly those that cross the placental barrier—may pose teratogenic risks. Previous studies investigating the association between prenatal antibiotic exposure and the risk of OFCs have yielded inconsistent results. However, no studies have yet attempted to summarise this evidence, highlighting the need for a comprehensive evaluation. This report describes a systematic review and meta-analysis protocol to retrospectively analyse the relationship between prenatal antibiotic exposure and the risk of developing OFCs, focusing on the role of antibiotic type and timing of exposure. The results of such a review will hopefully provide a comprehensive synthesis of the available evidence, helping to inform clinical practice and guide patient counselling regarding the use of antibiotics during pregnancy. Methods and analysis: The planned systematic review and meta-analysis will adhere to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines to ensure a comprehensive and systematic approach to summarising the available evidence on the topic. This study will include longitudinal cohort studies, case–control studies, and interventional trials that investigate the association between prenatal antibiotic exposure and OFCs. The search strategy will cover major databases, including CINAHL, Cochrane Library, ClinicalTrials.gov, EMBASE, PubMed, Scopus and Web of Science, using tailored search terms. A team of independent assessors will screen article titles, abstracts and full texts. Any discrepancies will be resolved through discussions. Quality assessment will use the Newcastle-Ottawa Scale and Grading of Recommendations Assessment, Development and Evaluation criteria. Data extraction will focus on the study characteristics, participant details, exposure specifics and outcome measures. A random-effects meta-analysis will aggregate summary effect sizes, and heterogeneity will be assessed using I ² and Q statistics. Ethics and dissemination: Ethical approval is not required for this systematic review, as it relies on already published data. The findings will be disseminated through peer-reviewed journals and conference presentations, providing critical insights into clinical practice and public health policies regarding antibiotic use during pregnancy. PROSPERO registration number: CRD42024565064