(A-284) Nicotine Replacement Therapy in Pregnancy: A Systematic Review, Meta-Analysis, and Network Meta-Analysis of Maternal-Neonatal Outcomes and Smoking Cessation

Background: Maternal smoking during pregnancy poses significant risks to neonatal and obstetric health. While nicotine replacement therapy (NRT) is widely used for smoking cessation, its safety and efficacy in pregnancy remain debated.

Objectives: To assess the impact of NRT on maternal and neonatal outcomes, and smoking cessation in pregnant women.

Methods: A systematic search of PubMed, Cochrane CENTRAL, Scopus, Google Scholar, and ClinicalTrials.gov was conducted (inception to October 31st, 2024) using keywords related to NRT and pregnancy. Randomized controlled trials (RCTs) comparing NRT with placebo/active controls were included. Heterogeneity was assessed using I² and Cochran’s Q test, with fixed- or random-effects models applied accordingly. Network meta-analysis (NMA) using a Bayesian random-effects consistency model was performed for low birth weight and gestational age outcomes (Using the 'Netmeta' package in R).

Results: Out of 151 non-duplicate research articles identified through database searching, a total of 20 high-quality studies with 11,052 patients, were included in this study. NRT was significantly associated with an increased risk of neonatal deaths (OR=2.89; 95% CI:1.18, 7.07; P=0.02), low birth weight (OR=1.32; 95% CI: 1.08, 1.62; P=0.007), and caesarean delivery (OR=1.35; 95% CI: 1.02, 4.21; P=0.0005).
NMA for low birth weight revealed nuanced risks: nicotine gum (OR = 0.08; 95% CrI: 0.003–1.64) and inhaler (OR = 0.35; 95% CrI: 0.02–6.87) showed non-significant reductions, while the patch trended toward harm (OR = 1.36; 95% CrI: 0.09–21.1). Cumulative ranking (SUCRA) identified nicotine gum as the safest (SUCRA: 89.8%), followed by inhaler (60.8%), placebo (29.5%), and patch (19.9%). SUCRA rankings for gestational age, however, paradoxically favored placebo (SUCRA: 85.1%), followed by inhaler (45.1%), and nicotine gum (19.8%).
On the other hand, NRT reduced the risk of congenital abnormalities (OR=0.62; 95% CI: 0.41, 0.95; P=0.03), assisted vaginal delivery (OR=0.72; 95% CI: 0.55, 0.95; P=0.02), and premature rupture of membrane (OR=0.29; 95% CI: 0.13, 0.68; P=0.004). Additionally, smoking cessation was found to be significantly higher in the NRT group compared to the control.

Conclusions: NRT in pregnancy presents a dual profile: while it increases smoking cessation, risks such as neonatal mortality and low birth weight persist. NMA highlights variability among NRT types—nicotine gum may offer a safer profile for birth weight outcomes compared to inhaler or patch. Clinicians must weigh these trade-offs, prioritizing formulations with favourable risk-benefit ratios. Further research is needed to optimize NRT selection in pregnancy.