Association of Maternal Smoking Status during Pregnancy to the Incidence of Placenta Previa: A Systematic Review of Randomized Controlled Trials and Primary Studies

Abstract

Background: Placenta previa, defined as the implantation of the placenta over or proximate to the internal cervical os, constitutes a significant obstetric complication associated with substantial maternal and perinatal morbidity and mortality. Maternal cigarette smoking during pregnancy has been postulated as a modifiable risk factor for placenta previa through mechanisms involving placental hypoxia, vasoconstriction, and aberrant trophoblast invasion; however, the precise magnitude of this association and its dose-dependency remain subjects of ongoing scientific inquiry.

Methods: The study strictly adhered to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines. Studies published from 1980 through 2025 were eligible for inclusion. Randomized controlled trials, cohort studies, case-control studies, population-based registry analyses, meta-analyses, and high-quality systematic reviews were included. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) for observational studies. Data were synthesized narratively with quantitative reporting of odds ratios (OR) and relative risks (RR) with 95% confidence intervals (CI).

Results: A total of 20 studies were included in this systematic review, comprising approximately 40 million pregnancies across multiple countries and time periods. Primary epidemiological studies consistently demonstrated a statistically significant positive association between maternal smoking during pregnancy and the risk of placenta previa. The pooled odds ratio ranged from OR 1.29 (95% CI: 1.05–1.58) in registry-based cohort studies to OR 3.0 (95% CI: 1.1–8.6) in matched case-control studies. A significant dose-response relationship was identified, with women smoking ≥20 cigarettes per day exhibiting a greater than twofold increased risk compared to non-smokers (OR: 2.3, 95% CI: 1.5–3.5). One meta-analysis of five eligible studies yielded a pooled OR of 1.58, confirming the independent effect of smoking beyond other established risk factors. Smoking cessation was associated with a 33% reduction in placenta previa frequency, particularly when cessation occurred prior to or in early gestation.

Discussion: The biological plausibility of the smoking-placenta previa association is substantiated by evidence demonstrating that nicotine and carbon monoxide impair placental vascular development through endothelial dysfunction, enhanced angiogenesis at aberrant sites, and reduction in nitric oxide-dependent vasodilation. These hemodynamic perturbations promote compensatory placental hypertrophy and abnormal implantation, potentially favoring low uterine segment placentation. The observed dose-response gradient and the benefit of cessation provide strong causal inference from observational evidence.

Conclusion: Maternal smoking during pregnancy is an independent and dose-dependent risk factor for placenta previa, conferring an approximately 1.3- to 3.0-fold increase in risk after adjustment for confounders. Smoking cessation before or early in pregnancy is associated with measurable risk reduction. Comprehensive tobacco cessation programs should be integrated into standard antenatal care protocols worldwide to mitigate the obstetric burden attributable to this preventable exposure.