Maternal and neonatal outcomes in pregnant women with autoimmune diseases in Pavia, Italy

The increased number of childbearing women with autoimmune diseases leads to a growing interest in studying relationship among maternal disease, therapy, pregnancy and off-spring.

Mazzucchelli et al BMC Pediatrics (2015) 15:217 DOI 10.1186/s12887-015-0532-3 RESEARCH ARTICLE Open Access Maternal and neonatal outcomes in pregnant women with autoimmune diseases in Pavia, Italy Iolanda Mazzucchelli1,2*† , Lidia Decembrino1†, Francesca Garofoli1, Giulia Ruffinazzi1, Véronique Ramoni3, Mariaeva Romano3, Elena Prisco4, Elena Locatelli4, Chiara Cavagnoli4, Margherita Simonetta4, Annalisa De Silvestri5, Piermichele Paolillo6, Arsenio Spinillo4 and Mauro Stronati1 Abstract Background: The increased number of childbearing women with autoimmune diseases leads to a growing interest in studying relationship among maternal disease, therapy, pregnancy and off-spring The aim of this study was to determine the impact of autoimmune disease on pregnancy and on neonatal outcome, taking into account the maternal treatment and the transplacental autoantibodies passage Methods: We studied 70 infants born to 70 pregnant women with autoimmune disease attended in Fondazione IRCCS Policlinico San Matteo, Pavia, Italy from June 2005 to June 2012 Maternal and neonatal characteristics were collected and relevant clinical, laboratory, therapeutics, sonographic and electrocardiographic investigations were recorded and analyzed Results: We observed a high rate of spontaneous abortions in medical history, 29 %, and 18.6 % of preterm births and 22.9 % of low birth weight (< 2500 g) Transplacental autoantibodies passage wasn’t related to maternal or obstetrical complication, but anti-Ro/SSA positive pregnancies correlated with abnormal fetal heart rate (P = 0.01) Pregnant women on therapy showed an higher incidence of maternal (p = 0.002), obstetric (p = 0.007) complications and an increased rate of intrauterine growth restriction (p = 0.01) than the untreated ones Conclusions: Autoimmune diseases in pregnancy require to be carefully monitored to ensure the best possible management of mothers, fetuses and newborns due to the high rate of morbidity specially in case of maternal polytherapy and/or anti-Ro/SSA positivity Keywords: Autoimmune disease, Pregnancy, Maternal and neonatal outcome Background Autoimmune diseases are a group of heterogeneous disorders characterized by the attack of the immune system against its own cells, tissue or organs In this context the resultant autoinflammatory reaction could be antibodies mediated or cytokines/protein mediated, with consequently multiple clinical and laboratory aspects [1] Diseases are more frequent in female gender than in male * Correspondence: iolanda.mazzucchelli@unipv.it † Equal contributors Neonatal Unit and Neonatal Intensive Care Unit, IRCCS San Matteo Hospital Foundation, Pavia, Italy Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy Full list of author information is available at the end of the article (78 %) and they could become critical during pregnancy when the immune system is actively involved to tolerate a successful gestation process [2, 3] A pregnant woman with an autoimmune disease, should be considered high risk because of the modulation of inflammatory process, the possible effects of therapy on the fetus and the transplacental passage of autoantibodies [4, 5] High frequency of gestational and perinatal complications such as preeclampsia, stillbirth, spontaneous abortions (11– 24 %), preterm birth (13.9 %) and intrauterine growth restrictions (IUGR) (2.3 %) have been reported [6, 7] Immunoglobulin G isotype antibodies can freely cross the placenta with a linear relationship between gestational age and placental transfer [5] Literature data © 2015 Mazzucchelli et al Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated Mazzucchelli et al BMC Pediatrics (2015) 15:217 report that anti-Ro/SSA and anti-La/SSB antibodies are associated with neonatal lupus erythematosus and other associated abnormalities such as congenital heart block (CHB), cardiomyopathy, cutaneous lupus lesions, hepatobiliary disease, and hematologic cytopenias [8, 9] Furthermore, an important issue concerns the use of drugs to control maternal symptoms and exacerbations: these substances and their metabolites can cross the placental barrier and enter into the fetal circulation; this could influence the pregnancy progression, the fetus state and the perinatal outcomes [4] The aim of this study was to expose our experience about the impact of autoimmune diseases on pregnancy, fetus and neonate outcome, taking into account the transplacental autoantibodies passage and the maternal therapy Methods This retrospective study was performed at Fondazione IRCCS Policlinico San Matteo, Pavia, Italy from June 2005 to June 2012 and data of 70 women with a diagnosed autoimmune disease and of their 70 babies were collected and analyzed The hospital, located in the north of Italy, is characterized by clinical, teaching and research mission All the women gave written informed consent and the data was collected in a database and analyzed as anonymous data for research purpose The study was approved by the Ethics Committee, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy All the enrolled women had a diagnosed autoimmune diseases in our Division of Rheumatology according to widely used criteria [10] and had a positive test for at least one autoantibody Exclusion criteria were: multiple pregnancy, congenital infections, perinatal asphyxia, chromosomal syndromes Any abnormalities occurring during pregnancy were registered as well as obstetrical and maternal information Blood tests to evaluate maternal autoantibodies were performed during pregnancy according to the clinical protocol used in our Department Neonatal gestational age, weight, length, head circumference, Apgar score and cord pH were collected at birth and adjusted for gestational and chronological age Maternal and neonatal antinuclear autoantibodies (ANA) were tested by a standard indirect immunofluorescence technique, while anti-extractable nuclear antigen antibodies (ENA) were evaluated by commercially available ELISA kits Cardiac and cerebral ultrasound scans were performed in the neonate at birth, while electrocardiogram (ECG) testing was done within the first week of life Electrocardiographic parameters were evaluated with particular attention to PR interval (nv