The contribution of periodontal disease to the development of adverse systemic consequences remains controversial. It is hypothesized that inconsistencies between studies is due in part to limitations in study design. This review assessed systemic conditions including adverse pregnancy outcomes and glycemic control for patients with diabetes in a combined manner based on a shared inflammatory mechanism of consequence. It is thought that the systemic consequences of periodontal inflammation can directly influence these systemic conditions. Therefore, this systematic review aimed to evaluate the consideration of the patients' medical management during the study and also the number of study participants as two important factors influencing the study outcomes. An article search was performed using OVID Medline, Cochrane library and EMBASE and a manual search was performed through November 2017. Randomized controlled trials published between 2000 and 2017 looking into the effectiveness of periodontal therapy on the rate of pre-term birth in a pregnant population and on glycated hemoglobin A1c in a type 2 diabetics were included. Primary outcomes were changes in HbA1c and differences in frequency of occurrence of pre-term birth. Medical management of the systemic condition under study was categorized from 0-3, based on stringency of study design and consideration for medical management during study participation. Risk of bias regarding randomization, allocation of sequence concealment, blinding, incomplete outcome data, selective outcome reporting and other biases were averaged using a cumulative assessment of factors considered in prior systematic reviews with shared studies. After article selection, randomized controlled trials including 17 on diabetes and 13 on pregnancy were combined for evaluation. Both increased sample size (R2=0.09, R value = 0.3) and improved stringency of medical management (Figures 13 & 14) were associated with diminished effects of periodontal therapy on systemic outcomes. Interestingly, risk of bias as assessed in previous systematic reviews showed a modest correlation (R2=0.104, R value= 0.32) with primary outcomes. This systematic review demonstrates that the disparate results in studies of periodontal therapy affecting systemic outcomes may be explained in part by study design, specifically stringency in consideration of medical management and sample size. The potential for confounding factors influencing outcomes remains a concern.