© 2014 American Academy of Periodontology. Background: Data are limited on the potential effect of intensive oral hygiene regimens and periodontal therapy during pregnancy on periodontal health, gingival crevicular fluid (GCF) and serum cytokines, and pregnancy outcomes.Methods: A clinical trial was conducted on 120 communitydwelling, 16- to 35-year-old pregnant women at 16 to 24 weeks of gestation. Each participant presented with clinical evidence of generalized, moderate-to-severe gingivitis. Oral hygiene products were provided, together with instructions for an intensive daily regimen of hygiene practices. Non-surgical therapy was provided at baseline. Oral examinations were completed at baseline and again at 4 and 8 weeks. In addition, samples of blood and GCF were collected at baseline and week 8. Mean changes in clinical variables and GCF and serum cytokine levels (interleukin [IL]-1β, IL-6, tumor necrosis factor [TNF]-α) between baseline and week 8 were calculated using paired t test. Pregnancy outcomes were recorded at parturition.Results: Results indicated a statistically significant reduction in all clinical variables (P <0.0001) and decreased levels of TNF-α (P = 0.0076) and IL-1β (P = 0.0098) in GCF during the study period. The rate of preterm births (<37 weeks of gestation) was 6.7% (P = 0.113) and low birth weight (<2,500 g) was 10.2% (P = 1.00).Conclusions: Among the population studied, intensive instructions and non-surgical periodontal therapy provided during 8 weeks at early pregnancy resulted in decreased gingival inflammation and a generalized improvement in periodontal health. Large-scale, randomized, controlled studies are needed to substantiate these findings.