title: Cushing's syndrome and pregnancy outcomes: a systematic review of published cases.
abstract: Pregnancy in Cushing's syndrome (CS) is extremely rare due to the influence of hypercortisolism on the reproductive axis. Purpose of this study is to investigate whether the etiology of CS in pregnancy determines a different impact on the fetal/newborn and maternal outcomes. We performed a systematic review of cases published in the literature from January 1952 to April 2015 including the words "Cushing AND pregnancy". We included 168 manuscripts containing 220 patients and 263 pregnancies with active CS during pregnancy and with a history of CS but treated and cured hypercortisolism at the time of gestation. Adrenal adenoma was the main cause of active CS during pregnancy (44.1 %). Women with active CS had more gestational diabetes mellitus (36.9 vs. 2.3 %, p = 0.003), gestational hypertension (40.5 vs. 2.3 %, p < 0.001) and preeclampsia (26.3 vs. 2.3 %, p = 0.001) than those with cured disease. The proportion of fetal loss in active CS was higher than in cured CS (23.6 vs. 8.5 %, p = 0.021), as well as global fetal morbidity (33.3 vs. 4.9 %, p < 0.001). The predictors of fetal loss in active CS were etiology of hypercortisolism [Odds Ratio -OR-for pregnancy-induced CS 4.7 (95 % Confidence Interval-CI 1.16-18.96), p = 0.03], publication period [OR for "1975-1994" 0.10 (95 % CI 0.03-0.40), p = 0.001] and treatment during gestation (p = 0.037, [OR medical treatment 0.25 (95 % CI 0.06-1.02), p = 0.052], [OR surgical treatment 0.34 (95 % CI 0.11-1.06), p = 0.063]). The period of diagnosis of CS (before, during or after pregnancy) was the only predictor of overall fetal morbimortality [OR for diagnosis during pregnancy 4.66 (95 % CI 1.37-15.83), p = 0.014]. Patients with active CS, especially in pregnancy-induced CS, experienced more problems in pregnancy and had the worst fetal prognosis in comparison to other causes. Diagnosis of CS during pregnancy was also associated with worse overall fetal morbimortality. Both medical treatment and surgery during pregnancy appeared to be protective in avoiding fetal loss.
authors.affiliation: Endocrinology/Medicine Departments, Hospital Sant Pau, Barcelona, Spain.
authors.forename: Francisca
authors.initials: F
authors.lastname: Caimari
authors.affiliation: Endocrinology/Medicine Departments, Hospital Sant Pau, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Unidad 747), IIB-Sant Pau, Instituto de Salud Carlos III, Madrid, Spain.|Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Valassi
authors.affiliation: Teaching Unit Hospital Sant Pau, UAB, Barcelona, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Garbayo
authors.affiliation: Department of Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Steffensen
authors.affiliation: Endocrinology/Medicine Departments, Hospital Sant Pau, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Unidad 747), IIB-Sant Pau, Instituto de Salud Carlos III, Madrid, Spain.|Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Santos
authors.affiliation: Endocrinology/Medicine Departments, Hospital Sant Pau, Barcelona, Spain.|Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.|CIBER Bioengineering, Biomaterials and Nanotechnology, Instituto de Salud Carlos III, Zaragoza, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Corcoy
authors.affiliation: Endocrinology/Medicine Departments, Hospital Sant Pau, Barcelona, Spain. swebb@santpau.cat.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Unidad 747), IIB-Sant Pau, Instituto de Salud Carlos III, Madrid, Spain. swebb@santpau.cat.|Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. swebb@santpau.cat.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Webb
mesh_terms: D000236:Adenoma / Q000150:complications*; D000306:Adrenal Cortex Neoplasms / Q000150:complications*; D003480:Cushing Syndrome / Q000209:etiology*; D005260:Female; D006801:Humans; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology*; D011256:Pregnancy Outcome
keywords: Cushing’s syndrome; Fetal outcomes; Maternal mortality; Pregnancy