Cushing’s Syndrome and Pregnancy: A Systematic Review Protocol on Maternal and Neonatal Outcomes

Abstract

Introduction: Cushing’s syndrome (CS) is a potentially life-threatening disorder caused by excessive cortisol production due to either adrenocorticotropic hormone (ACTH) or autonomous adrenal cortisol secretion. CS is associated with an increased risk of cardiovascular complications and comorbidities such as hypertension (HTN), dysglycemia, and coagulopathies. Although rare, pregnancy in patients with CS poses significant maternal-fetal risks. Hypercortisolism exacerbates physiological changes in pregnancy, leading to increased maternal morbidity in 60-70% of cases, primarily due to HTN, diabetes mellitus, glucose intolerance, and heart failure. Given the high risk of adverse outcomes, evaluating the association between CS and pregnancy is crucial. Objective: This study aims to assess the impact of CS on pregnancy in terms of disease control and maternal and neonatal outcomes. Methods: A systematic review will be conducted following the Joanna Briggs Institute methodology for systematic reviews of etiology and risk. Observational studies (prospective and retrospective cohorts, case series with at least three participants), regardless of the year of publication, involving pregnant women diagnosed with CS before, during, or within 12 months after pregnancy will be included. Maternal outcomes include disease control, preterm birth, gestational diabetes, HTN, and miscarriage. Newborn outcomes include perinatal mortality, congenital malformations, low birth weight, and small-for-gestational-age status. Comprehensive search strategies have been developed for the Embase, MEDLINE, LILACS, and CENTRAL databases. Two independent reviewers will assess study eligibility, extract data, and evaluate the risk of bias. Proportional meta-analyses will be conducted using Stata version 18 with the metaprop_one command. Conclusion: This systematic review will provide insights into the maternal and fetal risks associated with CS during pregnancy. The findings will help guide clinical management and counseling for women with CS who wish to conceive. PROSPERO Registration Number: CRD42024597682.