Effectiveness of nitric oxide agents in preventing the early onset of pre-eclampsia and possible modification of metabolic factors in high-risk pregnancies: a systematic review protocol.

OBJECTIVES: To determine the effectiveness of nitric oxide agents in modifying the metabolic factors of pre-eclampsia and its effectiveness in preventing the onset of pre-eclampsia in high-risk pregnancies.
INTRODUCTION: Pre-eclampsia is a major cause of maternal death during the prenatal and neonatal periods. Nitric oxide is a vasodilator and platelet aggregation inhibitor responsible for the vascular adaptation of the placenta. Although various studies have established that nitric oxide is effective in preventing complications from pre-eclampsia, there is limited evidence to show that administering nitric oxide agents to high-risk women before 20 weeks' gestation will prevent the onset of pre-eclampsia. INCLUSION CRITERIA: This review will consider randomized controlled trials that compare nitric oxide donors and precursors with a placebo or no intervention on pregnant women (18 to 44 years) with ≤ 20-week gestational age that are at high risk of pre-eclampsia. The primary outcome of interest will be the onset of pre-eclampsia. Secondary outcomes include increased systolic and diastolic blood pressure, elevated asymmetric dimethylarginine levels, decreased endothelial nitric oxide synthase activity, reduced maternal placental vasculature, and abnormal Doppler ultrasound waveforms.
METHODS: Data sources will be drawn up from MEDLINE, CINAHL, ProQuest (Health and Medicine), and Web of Science from inception till current date. No language restrictions will be applied in the search strategy. Selected studies will be assessed against the JBI critical appraisal checklist, and the certainty of evidence and strength of recommendations from findings will also be ascertained. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42018099298.