Prenatal alcohol exposure (PAE) can result in a range of adverse neonatal outcomes, including Fetal Alcohol Spectrum Disorder (FASD). This systematic review and meta-analysis sought to investigate the effectiveness of brief interventions (BIs) in eliminating or reducing 1) alcohol consumption during pregnancy; and 2) PAE-related adverse neonatal outcomes; and 3) cost-effectiveness of BIs. We conducted a systematic literature search for original controlled studies (randomized control trials (RCTs); quasi-experimental) in any setting, published from 1987 to 2021. The comparison group was no/minimal intervention, where a measure of alcohol consumption was reported. Studies were critically appraised using the Centre for Evidence-based Medicine Oxford critical appraisal tool for RCTs (1). The certainty in the evidence for each outcome was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) (2). Meta-analysis of continuous and binary estimates of effect-size for similar outcome measures for BIs versus control groups were pooled and reported as mean difference (MD) Hedges' g and odds ratios (ORs), respectively. In total, 26 studies, all from high income countries, met inclusion criteria. Alcohol abstinence outcome available in 12 studies (n = 2620) found modest effects in favor of BIs conditions by increasing the odds of abstinence by 56% (OR = 1.56, 95% confidence interval (CI) = 1.15-2.13, I = 46.75%; p = 0.04). BIs effects for reduction in mean drinks/week (Cohen's d = - 0.21, 95%CI = - 0.78 to 0.36; p = 0.08) and AUDIT scores (g = 0.10, 95%CI = - 0.06 to 0.26; p = 0.17) were not statistically significant. Among seven studies (n = 740) reporting neonatal outcomes, BI receipt was associated with a modest and significant reduction in preterm birth (OR = 0.67, 95% CI = 0.46-0.98, I = 0.00%; p = 0.58). No statistically significant differences were observed for mean birthweight or lower likelihood of low birth weight (LBW). Certainty in the evidence was rated as 'low'. No eligible studies were found on cost-effectiveness of BIs. BIs are moderately effective in increasing abstinence during pregnancy and preventing preterm birth. More studies on the effectiveness of BIs are needed from low- and middle-income countries, as well as with younger mothers and with a broader range of ethnic groups.