Preconception periodontitis and adverse pregnancy outcomes in a prospective cohort of pregnancy planners

高血压疾病的患病率（如妊娠期高血压、先兆子痫和子痫）和

The prevalence of hypertensive disorders (e.g. gestational hypertension, pre-eclampsia, and eclampsia) and metabolic disorders (e.g. Gestational Diabetes Mellitus) is high and significantly contribute to maternal morbidity and mortality. Further, these conditions are primary risk factors for preterm birth and low-birthweight outcomes, and thus also contribute dramatically to neonatal morbidity and mortality. Given the increasing rates of these disorders in recent years, and the associated detrimental health outcomes, prevention and early detection are critical for improving maternal and neonatal outcomes. Systemic inflammation prior to pregnancy is regarded as a contributing factor in the development of these conditions and outcomes, yet the underlying causes are mostly unknown. Understanding and addressing sources of systemic inflammation in the preconception period may hinder the development of hypertensive and metabolic disorders during pregnancy, as well as reduce the incidence of preterm birth and low birthweight outcomes. Periodontitis is the most common chronic inflammatory condition among U.S adults, affecting 38% of women aged 30 years and older. The associations between periodontitis and pregnancy-related conditions and outcomes have been studied in recent decades. However, results of this work have been mixed, owing to the restricted measurement of periodontitis during pregnancy, the lack of data on important confounders, and difficulty in obtaining enough data to provide meaningful, precise results. Through the use of prospective data obtained from PREgnancy STudy Online (PRESTO), an ongoing internet-based preconception cohort study of nearly 17,000 North American women planning a pregnancy, this proposal aims to: 1. Estimate the associations between preconception periodontitis and hypertensive and metabolic disorders in pregnancy, preterm birth, and low birthweight outcomes. 2. Evaluate the validity of the associations through the conduct of probabilistic quantitative bias analyses and the incorporation of inverse probability weighting to explore the plausibility of alternative explanations for the observed results (e.g., unmeasured confounding, exposure misclassification bias, and selection bias). Completion of the proposed aims will enhance our understanding of the role that periodontitis may play in maternal and neonatal morbidity and mortality and may provide a foundation for mechanistic studies that elucidate inflammatory pathways underlying these associations. Eventually, this work could lead to therapeutic interventions to reduce the population-level burden of these serious reproductive health conditions and outcomes.