Background Rheumatic diseases pose risks to pregnant women, leading to complications like preterm birth, congenital heart block, and pregnancy loss. These diseases are expected to deteriorate during pregnancy and further in the postpartum period. The impact of these diseases on the pregnancy will add further burden on the patient, fetus, physician, and healthcare system. Advances in diagnosis and treatment have improved outcomes making them similar to that of healthy women, but close follow-up in a multidisciplinary clinic is essential. The objective of this study is to study the outcome of pregnancy in women with rheumatological disease and the behavior of the disease during pregnancy. Methods A retrospective cohort study was conducted in King Abdulaziz Medical City (KAMC) in Riyadh, Saudi Arabia, to compare the outcomes of pregnancy across three rheumatological diseases: Sjogren syndrome (SS), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA) from 2016 to 2021. A total of 128 pregnancies in 107 women with rheumatological diseases were included in this study. Pregnancy measures and outcomes were investigated by assessing maternal health, fetal health, and pregnancy complications, specifically maternal disease activity, medications to control the disease, infection, preterm birth, birth weight, abortions/stillbirths, mode of delivery, bleeding, preeclampsia, congenital heart block, and neonatal lupus. Results There were 55 patients with RA (63 RA pregnancies), 44 with SLE (54 SLE pregnancies), and eight with primary SS (11 SS pregnancies). In most of the pregnancies (n= 108; 95.58%), the patients were in clinical remission before pregnancy. Lupus nephritis, which was in remission before pregnancy, has been reported in nine (16.67%) out of 54 SLE pregnancies. Vaginal delivery was the most common mode of delivery (n=87; 67.97%). On the other hand, there were 38 cesarean sections (29.69%). Rheumatological disease flares occurred in 10 pregnancies (7.87%). One hundred and twenty-two live births were delivered. Preterm infants were born in 25 pregnancies (20.16%), and 16 (13.22%) of the newborns needed neonatal intensive care unit (NICU) care. Interestingly, congenital heart block (CHB) was found in five (12.2%) neonates out of 41 anti-SS-related antigen A (anti-SSA) positive mothers; one of those five died from heart block. Eleven neonates were delivered with positive serology, and five were diagnosed with neonatal lupus. Conclusion The outcome of pregnancy in patients with rheumatological disease is favorable. A multidisciplinary team approach and close clinical follow-up are the cornerstone for such success. A small dose of prednisolone (5 mg or less) is safe and will not have a negative impact on maternal or fetal health. CHB is a concern for pregnant women with positive anti-SSA.

Congenital complete heart block (CCHB) is a very rare condition, with high risk of mortality. Prematurity is associated with immaturity of the cardiovascular system. Morbidity related to CCHB and prematurity has never been described. We describe a tertiary perinatal center experience over a 15-year period on CCHB management and complications in preterm infants. This is a single-center observational cohort study. All neonates admitted to neonatal intensive care unit with a diagnosis of isolated CCHB between January 2006 and January 2021 were identified. All preterm neonates (< 37 weeks) were compared with a control cohort of term neonates (≥ 37 weeks). Antenatal data, complications of prematurity, medical, and surgical management of CCHB were recorded. Twenty-four neonates with isolated CCHB (16 preterm and 8 term) were born during the study period, including 5 very preterm (< 32 weeks) and 11 preterm (32 to 37 weeks). All very preterm were born via emergency caesarian section without antenatal steroid administration. They had multiple severe morbidities including chronic lung disease, necrotizing enterocolitis, grades 3-4 intraventricular hemorrhage, cystic periventricular leukomalacia, and longer periods of mechanical and non-invasive ventilatory support than preterm. Thirteen out of sixteen preterm infants had permanent pacemakers inserted, compared to 1/8 for term newborns. All babies born before 35-week gestation were either paced or died.Conclusion: Premature neonates with CCHB have high risk of mortality and morbidity especially if undiagnosed and born by unnecessary emergency caesarian section without antenatal steroids. Prematurity below 35 weeks may be associated with death or pacemaker insertion. This supports better antenatal screening to avoid induced prematurity. What is Known: • Congenital complete heart block is a very rare condition associated with high morbidity and mortality. • Antenatal risk factors for poor outcome include fetal hydrops, low ventricular rate (HR <55 beats per minute), and congenital heart defect. What is New: • Infants born <32 weeks with CCHB had no antenatal steroid administration, and sustained high burden of morbidity (chronic lung disease, intraventricular hemorrhage, and cystic periventricular leukomalacia). • Birth <35 weeks is strongly associated with requiring pacing prior to discharge or death.

To investigate fetal/perinatal and maternal outcomes from a large multicentre cohort of women diagnosed with UCTD.
This multicentre retrospective cohort study describes the outcomes of 224 pregnancies in 133 consecutive women with a diagnosis of UCTD, positive for ANA and aged <45 years old at study inclusion.
Of the 224 pregnancies analysed, 177 (79%) resulted in live births, 45 (20.1%) in miscarriages (defined as pregnancy loss before 12 weeks\' gestation), 2 (0.9%) in stillbirths (pregnancy loss after 20 weeks\' gestation) and 6 (2.7%) cases showed intrauterine growth restriction. Miscarriages and stillbirths were strongly associated with the presence of aPL and ENA antibodies (P < 0.05). Maternal pregnancy complications were as follows: 5 (2.2%) cases developed pre-eclampsia, 11 (4.9%) cases gestational hypertension and 12 (5.4%) cases gestational diabetes. Joint involvement represented the most frequent clinical manifestation of the cohort (57.9%), followed by RP (40.6%), photosensitivity (32.3%) and haematological manifestations (27.1%). The rate of disease evolution of our cohort from a diagnosis of UCTD to a diagnosis of definite CTD was 12% within a mean time of 5.3 ± 2.8 years. With a total follow-up after first pregnancy of 1417 patient-years, we observed the evolution to a defined CTD in one out of every 88 patient- years.
In our multicentre cohort, women with UCTD had a live birth rate of 79%. Women with UCTD should be referred to specialist follow-up when planning a pregnancy. ENA profiling and aPL testing should be mandatory in this setting, and further therapeutic approaches and management should be planned accordingly.

OBJECTIVE: To describe aetiologies and temporal trends in young patients with atrioventricular block (AVB).
RESULTS: We identified all patients in Denmark, receiving their first pacemaker because of AVB before the age of 50 years between 1996 and 2015. Medical records were reviewed and clinical information and diagnostic work-up results were obtained to evaluate the aetiology. We used Poisson regression testing for temporal trends. One thousand and twenty-seven patients were identified, median age at time of implantation was 38 (interquartile range 25-45) years, 584 (56.9%) were male. The aetiologies were complications to cardiac surgery [n = 157 (15.3%)], congenital AVB [n = 93 (9.0%)], cardioinhibitory reflex [n = 52 (5.0%)], congenital heart disease [n = 43 (4.2%)], complication to radiofrequency ablation [n = 35 (3.4%)], cardiomyopathy [n = 31 (3.0%)], endocarditis [n = 18 (1.7%)], muscular dystrophy [n = 14 (1.4%)], ischaemic heart disease [n = 14 (1.4%)], sarcoidosis [n = 11 (1.1%)], borreliosis [n = 9 (0.9%)], hereditary [n = 6 (0.6%)], side-effect to antiarrhythmics [n = 6 (0.6%)], planned His-ablation [n = 5 (0.5%)], complication to alcohol septal ablation [n = 5 (0.5%)], and other known aetiologies [n = 11 (1.1%)]. The aetiology remained unknown in 517 (50.3%) cases. While the number of patients with unknown aetiology increased during the study period (P < 0.001), we observed no significant change in the number of patients with identified aetiology (P = 0.35).
CONCLUSIONS: In a nationwide cohort, the aetiology of AVB was identified in only half the patients younger than 50 years referred for first-time pacemaker implantation. The number of patients with unknown aetiology increased during the study period. These findings indicate need for better insight into aetiologies of AVB and improved diagnostic work-up guidelines.

In this study we aimed to investigate foetal and maternal pregnancy outcomes from a large multicentre cohort of women diagnosed with MCTD and anti-U1RNP antibodies.
This multicentre retrospective cohort study describes the outcomes of 203 pregnancies in 94 consecutive women ever pregnant who fulfilled the established criteria for MCTD with confirmed U1RNP positivity.
The foetal outcomes in 203 pregnancies were as follows: 146 (71.9%) live births, 38 (18.7%) miscarriages (first trimester pregnancy loss of <12 weeks gestation), 18 (8.9%) stillbirths (pregnancy loss after 20 weeks gestation) and 11 (5.4%) cases with intrauterine growth restriction. Maternal pregnancy outcomes were as follows: 8 (3.9%) developed pre-eclampsia, 2 (0.9%) developed eclampsia, 31 (15.3%) developed gestational hypertension and 3 (1.5%) developed gestational diabetes. Women with MCTD and aPL and pulmonary or muscular involvement had worse foetal outcomes compared with those without. Moreover, we report a case of complete congenital heart block (0.45%) and a case of cutaneous neonatal lupus, both born to a mother with positive isolated anti-U1RNP and negative anti-Ro/SSA antibodies.
In our multicentre cohort, women with MCTD had a live birth rate of 72%. While the true frequency of heart block associated with anti-U1RNP remains to be determined, this study might raise the consideration of echocardiographic surveillance in this setting. Pregnancy counselling should be considered in women with MCTD.

OBJECTIVE: Assuming that autoimmune congenital heart block (CHB) is a progressive disease amenable to therapeutic modulation, we introduced a surveillance program for at-risk pregnancies with the dual aim of investigating if fetal atrioventricular block (AVB) could be detected and treated before becoming complete and irreversible, and to establish the incidence of AVB I, II and III in a large prospective cohort.
METHODS: This was a prospective study of 212 anti-Ro52 antibody-exposed pregnancies at risk of fetal AVB that were followed weekly between 18 and 24 weeks\' gestation at our tertiary fetal cardiology center from 2000 to 2015. A 12-lead electrocardiogram (ECG) was recorded within 1 week after birth. Fetal Doppler atrioventricular (AV) intervals were converted to Z-scores using reference standard values derived from normal pregnancies. Each fetus was represented by the average value of the two recordings, obtained at two consecutive visits, which resulted in the longest AV interval. AV interval values were classified into normal AV conduction (Z-score ≤ 2.0) and three levels of delayed AV conduction: Z-score > 2.0 and ≤ 3.0, Z-score > 3.0 and ≤ 4.0, and Z-score > 4.0.
RESULTS: AVB II or III developed in 6/204 (2.9%) pregnancies without a CHB history and 1/8 (12.5%) of those with a CHB history. AV intervals > 2 and ≤ 3, > 3 and ≤ 4, and > 4 were detected in 16.0%, 7.5% and 2.8% of cases, respectively, and were related to the PR interval on 185 available ECGs. Three of the five cases with AVB III and one of two cases with 2:1 AVB II developed within 1 week of AV interval Z-score of 1.0, 1.9, 2.8 and 1.9, respectively. Transplacental treatment with betamethasone was associated with restoration of 1:1 AV conduction in the two fetuses with AVB II, with a better long-term result (normal ECG vs AVB I or II) observed in the case in which treatment was started within 1 week after AVB developed. Betamethasone treatment did not reverse AVB III, although a temporary effect on AV conduction was observed in 1/5 cases. Notably, the three cases in which treatment was started within 1 week after AVB III development responded with a higher ventricular rate than the other two cases and did not require pacemaker implantation until a later age (2-5 years vs 1.5-2 months).
CONCLUSIONS: Fetal AV interval is a poor predictor of CHB progression, but CHB surveillance still allows detection of fetuses with AVB II or III shortly after its development, allowing for timely treatment initiation and potentially better outcome. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Recent studies have suggested that prenatal exposure to HCQ reduces the risk of cardiac neonatal lupus. The aim of this study is to assess if maternal intake of antimalarials (AMs) throughout pregnancy lowered the risk of cardiac and non-cardiac neonatal lupus.
Consecutive children seen between 1 January 1984 to 1 October 2013 born to women with a CTD and positive anti-Ro and/or anti-La antibodies were eligible for this single-centre retrospective cohort study. A total of 315 individuals were screened and 268 participants were included. Exposure to AMs was defined as HCQ or chloroquine throughout pregnancy. Outcomes were cardiac and non-cardiac neonatal lupus. Frequentist and Bayesian analyses were performed. We hypothesized that prenatal AM exposure would decrease the risk of cardiac but not non-cardiac neonatal lupus.
A total of 268 pregnancies were included; 73 were exposed to AMs throughout pregnancy. Ninety-nine children developed neonatal lupus, 117 remained unaffected and 52 children did not develop cardiac neonatal lupus but could not be categorized as unaffected since their full non-cardiac neonatal lupus status was unknown. Logistic regression suggested a protective effect of AM on cardiac neonatal lupus, but results were not statistically significant [odds ratio (OR) 0.21; P = 0.07]. Bayesian analysis showed that the probability of obtaining a protective effect (OR < 1.0) for cardiac neonatal lupus was significant (98.7%). The effect of AMs on non-cardiac neonatal lupus was not significant (OR 0.78; P = 0.21).
In this large single-centre cohort study, exposure to AMs throughout pregnancy was associated with a decreased probability of developing cardiac but not non-cardiac neonatal lupus.

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.

BACKGROUND: Children from mothers with systemic lupus erythematosus are frequently born with congenital heart block. This study aimed at evaluating long-term outcome because long-term data are scarce.
METHODS: In the database of pediatric and congenital heart disease (University Hospitals Leuven), 19 children from systemic lupus erythematosus mothers and who were born with or developed atrioventricular block were identified. All records were reviewed for disease course and outcome.
RESULTS: Median follow-up time was 7 years (interquartile ranges [IQR] 4.5-13 years). One child had no heart block at birth and developed only a first-degree block during follow-up. One had a second-degree heart block and developed a complete heart block. Seventeen patients (89%) were born with a complete heart block. Seventeen patients (89%) needed a definitive pacemaker. In all, epicardial leads were used at first implantation. Eighty-two percent received their pacemaker in the first year of life. The first battery had a median lifetime of 5 years (IQR 3.5-5 years), the second 6 years (IQR 4.5-6.3 years), and the third 5 years (IQR 5-6 years). Note that 47% of patients needed a lead replacement due to lead problems. Only one pericardial tamponade after pacemaker implantation. No device or lead infections occurred. The left ventricular systolic function at latest follow-up was normal for all. No patients died.
CONCLUSIONS: In children with heart block born from systemic lupus erythematosus mothers, an early need for pacemaker implantation was documented. The overall battery life was acceptable, but there was a high need for lead replacement. Complication rate was low. Late outcome was good.

OBJECTIVE: To examine the association between anti-Ro antibodies, namely anti-Ro60/SS-A and anti-Ro52/TRIM21, together and separately, and a prolonged QT interval corrected for heart rate (QTc) in systemic sclerosis (SSc) patients.
METHODS: A total of 689 SSc patients enrolled in a multicenter cohort study underwent a 12-lead resting EKG at baseline. The QTc interval was measured, and a QTc ≥ 440ms was considered prolonged. Detailed clinical data and sera of these patients were collected and positivity for anti-Ro60/SS-A and anti-Ro52/TRIM21 antibodies was determined using an addressable laser bead immunoassay (ALBIA).
RESULTS: QTc prolongation was common in this SSc cohort (25%). In a univariate analysis, Ro antibodies, together or separately, were not associated with prolongation of the QTc interval [mean difference in QTc in anti-Ro antibody positive versus negative subjects was -2.2ms (p = 0.5748), in anti-Ro60/SS-A antibody positive versus negative subjects was 1.3ms (p = 0.8616), and in anti-Ro52/TRIM21 antibody positive versus negative subjects was -3.3ms (p = 0.4106)]. In a multivariate logistic regression analysis adjusting for possible confounders, there was no association between prolonged QTc and anti-Ro antibodies [odds ratio (OR) = 0.74, 95% confidence interval (CI): 0.45, 1.22], anti-Ro60/SS-A antibodies (OR = 1.57, 95% CI: 0.72, 3.41), and anti-Ro52/TRIM21 antibodies (OR = 0.76, 95% CI: 0.46, 1.26). However, in both univariate and multivariate analyses, QTc prolongation was associated with longer disease duration, greater disease severity, and the presence of anti-RNA polymerase III antibodies.
CONCLUSIONS: QTc prolongation is common in SSc, although anti-Ro antibodies do not seem to be associated with it as is the case in systemic lupus erythematosus. The reasons for this difference as well as the cause of abnormalities in cardiac repolarization in SSc will require additional studies.