title: Obstetric and perinatal outcome in anti-Ro/SSA-positive pregnant women: a prospective cohort study.
abstract: Anti-Ro/SS-A is one specific type of antinuclear antibodies. They are in the majority of cases associated with primary Sjögren syndrome (SS) but also in Systemic Lupus Erythematosus (SLE), rheumatoid arthritis (RA), and in healthy people. During pregnancy, they are mainly associated to congenital heart block (CHB) and neonatal lupus (NL). The aim of this study was to compare the rate of maternal and fetal complications between a series of anti-Ro/SS-A positive pregnant women prospectively followed. Forty-two anti-Ro/SSA antibodies positive pregnant women that were referred to our hospital between 2011 and 2015. Data about pregnancy follow-up and outcomes were prospectively recorded from electronic databases. Data included demographic characteristics of the patients and their diseases (type, treatments, profile of anti-Ro/SSA, and antiphospholipid antibodies), pregnancy complications (CHB, preeclampsia, preterm delivery), ultrasound examinations and conditions, and mode of delivery. Maternal age was 35.22 ± 3.42 years and most of them were either SLE (n = 16, 40%) or Sjögren syndrome (n = 15, 37.5%). The rest of them were asymptomatic carriers (n = 8; 20%), and there was only one case of rheumatoid arthritis (n = 1; 2.5%). The incidence of anti-Ro52 and anti-Ro60 positive was n = 13, 82.4% and n = 16, 100%, respectively. Anti-La/SSB antibodies were present in n = 17, 48,6% of the patients. Half of the patients were taking hydroxycloroquine (n = 18, 45%). Seven pregnancies were complicated by fetal anti-Ro-related cardiac disease (17.9%) including four cases (57.1%) of second-degree heart block, two cases of third degree heart block (28.6%) and one case (14.3%) of intense and diffuse hyperechogenicity in atrioventricular valves without heart block. Gestational age at diagnosis of these conditions was 23.2 ± 3.5 weeks. One of the 18 patients having hydroxychloroquine (5.6%) compared with the six of them in women not having this medication (6/22, 27.3%) (p = 0.10). Concerning about Doppler evaluation, the Z score of umbilical pulsatility index (PI) was significantly higher in the SLE patients (p = 0.02). There were no cases of preeclampsia. Labor was induced in 21 cases (52.5%) and cesarean section rate was 45%. Gestational age at birth was 39 (37-40) weeks, and the general prematurity rate was 20% (n = 8). Birthweight was 2985 g (2425-3185 g) and 2850 (12.25-52.50) centiles for gestational age. The rate of small for gestational age (SGA) infants was 31.3% for SLE patients (5/16), 13.3% for Sjögren syndrome (2/15), and 12.5% for asymptomatic women (1/8). The rate of neonatal acidosis (pH < 7.20) was 20% (8/34) and it was higher in the SLE cases (6/15, 40%) when delivered after 38 weeks. The main pregnancy complication associated to anti-Ro/SS-A antibodies is CHB. The prevalence of CHB in patients taking hydroxychloriquine is lower without distinguishing between high or low risk patients. Preterm delivery occurs in anti-Ro/SS-A patients at the same rate as in the general population if no complications such as CHB or intrauterine growth restriction (IUGR) occur. The SGA rate also is higher probably because of SLE not because anti-Ro/SS-A antibodies. Finally, the finding of high umbilical artery PI will allow to predict fetus at risk of adverse pregnancy outcomes.
  
  
  
  •Anti-Ro/SS-A and anti-La/SS-B are clinically very relevant during pregnancy mainly because of their association to congenital heart block and neonatal lupus. •In our cohort, the prevalence of congenital heart block detected in patients taking hydroxycloroquine is much lower than in patients not taking it without distinguishing between high and low risk patients. •High umbilical artery pulsatility index in Doppler scans studies has been detected in our anti-Ro/SSA population (basely in SLE patients) demonstrated this measurement as a predictor of SGA and adverse pregnancy outcomes in general population such as cesarean section for fetal distress. The small for gestational age rate is higher probably because of SLE not because anti-Ro/SS-A •Preterm delivery happens in anti-Ro/SS-A patients at the same rate as in the general population if no complications such as congenital heart block or intrauterine growth restriction occur.
authors.affiliation: Obstetric and Gynecology Department, High Risk Pregnancy Unit, Autoimmune diseases and pregnancy clinic, University Hospital La Paz, Paseo de la Castella 261, 28046, Madrid, Spain. doctora.martinezsanchez@gmail.com.|Calle Villanueva nº2, escalera 3, 7ºB, 28001, Madrid, Spain. doctora.martinezsanchez@gmail.com.
authors.forename: Nuria
authors.initials: N
authors.lastname: Martínez-Sánchez
authors.affiliation: Internal Medicine External Rotating in Internal Medicine Department, University Hospital La Paz, Paseo de la Castellana 261, 28046, Madrid, Spain.|Internal Medicine Department, Nuestra Señora de Sonsoles Hospital, Avenida Juan Carlos I s/n, 05004, Ávila, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Pérez-Pinto
authors.affiliation: Internal Medicine Department, University Hospital La Paz, Paseo de la Castellana 261, 28046, Madrid, Spain.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Robles-Marhuenda
authors.affiliation: Internal Medicine Department, University Hospital La Paz, Paseo de la Castellana 261, 28046, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Arnalich-Fernández
authors.affiliation: Obstetric and Gynecology Department, High Risk Pregnancy Unit, Autoimmune diseases and pregnancy clinic, University Hospital La Paz, Paseo de la Castella 261, 28046, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Martín Cameán
authors.affiliation: Obstetric and Gynecology Department, High Risk Pregnancy Unit, Autoimmune diseases and pregnancy clinic, University Hospital La Paz, Paseo de la Castella 261, 28046, Madrid, Spain.
authors.forename: Edurne
authors.initials: E
authors.lastname: Hueso Zalvide
authors.affiliation: Obstetric and Gynecology Department, High Risk Pregnancy Unit, Autoimmune diseases and pregnancy clinic, University Hospital La Paz, Paseo de la Castella 261, 28046, Madrid, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Bartha
mesh_terms: D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006327:Heart Block / Q000151:congenital* / Q000175:diagnosis / Q000453:epidemiology; D006801:Humans; D007231:Infant, Newborn; D008180:Lupus Erythematosus, Systemic / Q000151:congenital* / Q000175:diagnosis / Q000453:epidemiology; D008297:Male; D007752:Obstetric Labor, Premature / Q000175:diagnosis* / Q000453:epidemiology; D011247:Pregnancy; D011256:Pregnancy Outcome; D015995:Prevalence; D011446:Prospective Studies; D012859:Sjogren's Syndrome / Q000175:diagnosis* / Q000453:epidemiology; D018608:Ultrasonography, Doppler; D014469:Umbilical Arteries / Q000000981:diagnostic imaging*
chemical_list: D000974:Antibodies, Antinuclear; C035356:SS-A antibodies
keywords: Anti-Ro/SSA antibodies; Congenital heart block; Neonatal lupus; Pregnancy; Sjögren syndrome