title: The impact of unrecognized autoimmune rheumatic diseases on the incidence of preeclampsia and fetal growth restriction: a longitudinal cohort study.
abstract: The burden of pregnancy complications associated with well defined, already established systemic rheumatic diseases preexisting pregnancy such as rheumatoid arthritis, systemic lupus erythematosus or scleroderma is well known. Systemic rheumatic diseases are characterized by a long natural history with few symptoms, an undifferentiated picture or a remitting course making difficult a timely diagnosis. It has been suggested that screening measures for these diseases could be useful but the impact of unrecognized systemic rheumatic disorders on pregnancy outcome is unknown. The objective of the study was to evaluate the impact of previously unrecognized systemic autoimmune rheumatic on the incidence of preeclampsia and fetal growth restriction (FGR).
  
  
  
  A longitudinal cohort-study with enrolment during the first trimester of pregnancy of women attending routine antenatal care using a two-step approach with a self-reported questionnaire, autoantibody detection and clinical evaluation of antibody-positive subjects. The incidence of FGR and preeclampsia in subjects with newly diagnosed rheumatic diseases was compared to that of selected negative controls adjusting for potential confounders by logistic regression analysis.
  
  
  
  The prevalence of previously unrecognized systemic rheumatic diseases was 0.4 % for rheumatoid arthritis (19/5232), 0.25 % (13/5232) for systemic lupus erythematosus, 0.31 % (16/5232) for Sjögren's syndrome, 0.3 % for primary antiphospholipid syndrome (14/5232) and 0.11 % (6/5232) for other miscellaneous diseases. Undifferentiated connective tissue disease was diagnosed in an additional 131 subjects (2.5 %). The incidence of either FGR or preeclampsia was 6.1 % (36/594) among controls and 25.3 % (50/198) in subjects with unrecognized rheumatic diseases (excess incidence = 3.9 % (95 % CI = 2.6-9.6) or 34 % (95 % CI = 22-44) of all cases of FGR/preeclampsia). The incidence of small for gestational age infant (SGA) was higher among subjects with unrecognized rheumatic diseases (41/198 as compared to 46/594; adjOdds Ratio = 3.1, 95 % CI =1.96-4.95) than in controls. The excess incidence associated with unrecognized rheumatic diseases was 2.7 % (95 % CI = 1.5-4) or 25 % (95 % CI = 12.8-34.8) of all SGA cases.
  
  
  
  Unrecognized autoimmune systemic rheumatic disorders are associated with a significant proportion of preeclampsia and fetal growth failure, suggesting that their role in the etiology of adverse pregnancy outcome is probably undervalued.
authors.affiliation: Department of Obstetrics and Gynecology, University of Pavia, IRCCS Policlinico San Matteo Foundation, P.le Golgi 19, 27100, Pavia, Italy. @smatteo.pv.it.
authors.forename: Arsenio
authors.identifier: 0000-0002-7755-1084
authors.initials: A
authors.lastname: Spinillo
authors.affiliation: Department of Obstetrics and Gynecology, University of Pavia, IRCCS Policlinico San Matteo Foundation, P.le Golgi 19, 27100, Pavia, Italy.
authors.forename: Fausta
authors.initials: F
authors.lastname: Beneventi
authors.affiliation: Department of Obstetrics and Gynecology, University of Pavia, IRCCS Policlinico San Matteo Foundation, P.le Golgi 19, 27100, Pavia, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Locatelli
authors.affiliation: Department of Rheumatology, University of Pavia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors.forename: Vèronique
authors.initials: V
authors.lastname: Ramoni
authors.affiliation: Department of Rheumatology, University of Pavia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Caporali
authors.affiliation: Laboratory Medicine, University of Pavia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Alpini
authors.affiliation: Laboratory Medicine, University of Pavia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Albonico
authors.affiliation: Department of Obstetrics and Gynecology, University of Pavia, IRCCS Policlinico San Matteo Foundation, P.le Golgi 19, 27100, Pavia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cavagnoli
authors.affiliation: Department of Rheumatology, University of Pavia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors.forename: Carlomaurizio
authors.initials: C
authors.lastname: Montecucco
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000150:complications* / Q000175:diagnosis; D057210:Delayed Diagnosis / Q000009:adverse effects*; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D011225:Pre-Eclampsia / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D011247:Pregnancy; D011256:Pregnancy Outcome; D012216:Rheumatic Diseases / Q000150:complications* / Q000175:diagnosis
chemical_list: D001323:Autoantibodies
keywords: Autoimmune rheumatic diseases; Connective tissue diseases; Preeclampsia: Fetal growth restriction; Pregnancy