Understanding the Clinical and Immunological changes of Autoimmune Rheumatic Disease in Pregnancy.

Abstract

Background: Autoimmune rheumatic diseases (ARDs) include conditions such as Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), Juvenile Idiopathic Arthritis (JIA), Sjogren’s syndrome and Myositis. These conditions can affect anyone, but all of them have a predilection for females of reproductive age, who may plan, or achieve or discover an unplanned pregnancy. Females of childbearing age with ARDs require specialised and careful management in pregnancy. Active or poorly controlled ARDs are associated with an increased risk of adverse pregnancy outcomes (APOs). Improvement in disease activity has been reported for many females with RA during pregnancy, followed by a relapse of disease activity in the postpartum period. However, current evidence available for SLE pregnancies remains unclear and variable, as the majority of studies have been conducted retrospectively, and have not used validated scoring tools to assess disease activity. Furthermore, it is recognised that people with ARD who experience APOs have an increased risk of long-term health problems. The levels of risk and APOs reported across different ARD pregnancies are varied. To date, there have been no studies published that have directly compared; SLE with RA and JIA pregnancies, and these ARD pregnancies with healthy pregnancies.

Aims: The overarching aims of this prospective comparative analysis study were to (i) to compare the pregnancy outcomes of people with SLE with those who have RA and JIA (ii) to compare the pregnancy outcomes of ARD pregnancies with a healthy pregnant population, to determine whether: (a) ARD pregnancies have a higher risk of APOs in comparison to a healthy pregnant population who lacked an ARD (b) SLE pregnancies have a higher risk of experiencing APOs when compared with RA and JIA pregnancies. This research aimed to obtain contemporary real-life data to investigate how pregnancy is associated with disease activity, and how the course of disease activity changes between SLE, RA and JIA cohorts in pregnancy. A secondary aim of this study was to describe and compare the patterns of medications used in ARD pregnancies, and to understand how medications may be associated with the course of disease activity and pregnancy. This research also assessed the risk factors that may be associated with flares of disease activity in the postpartum period for the pregnant ARD participants.

Methods: This research was a pragmatic, prospective, observational, case-controlled study that involved the recruitment of 183 females of childbearing age at University College London Hospital NHS Foundation Trust. Within the sample, 123 were patients with ARDs (SLE, RA and JIA) who were pregnant (n=60 participants) and non-pregnant (n=63 participants), and 60 were healthy pregnant females who lacked an ARD. Disease activity was measured for all ARD groups using validated disease activity scoring tools and the physician’s global assessment score, for the purpose of direct comparative analysis for all three ARDs. Comparisons of the disease activity changes for each individual ARD pregnant group, and non-pregnant groups were conducted. Disease activity and medication data were collected from the pre-pregnancy period to the post-partum period, with data collected over an equivalent time period for non-pregnant controls. Pregnancy outcomes data were collected from all pregnant study participants. SLE pregnancy outcomes were directly compared with RA and JIA pregnancy outcomes, and all ARD pregnancy outcomes were compared against the healthy pregnancy outcomes. Pregnancy outcomes were also associated with disease activity findings among the ARD cohorts. The medication profiles of each ARD pregnant group were examined to understand the patterns of prescribing in pregnancy.

Results: This research has identified comparable pregnancy outcomes between SLE versus RA and JIA pregnancies with well controlled disease. The SLE pregnancies evaluated in this study seemed to have similar rate of APOs compared with RA pregnancies, and an increased rate of APOs compared with JIA pregnancies. There was a four-fold percentage increase of maternal complications arising in ARD pregnancies, compared with a healthy pregnant population. Infants born to mothers with ARD were identified to have a five-fold percentage increase in experiencing a complication, in comparison to healthy infants. This study has identified that there were lower levels of vaginal deliveries in the ARD pregnancies, when compared with a healthy pregnant population. There was a two-fold higher rate of emergency caesarean sections in the ARD pregnancies, when compared with the healthy pregnant population. Furthermore, there were no differences identified in the mode of delivery for SLE pregnancies, when compared with RA and JIA pregnancies. In relation to the comparisons of disease activity between individual ARD groups, my analyses identified that the course of disease activity for the majority of SLE pregnancies remained stable and well controlled in pregnancy, and exhibited the fewest fluctuations during pregnancy and through to the postpartum period, in comparison with RA and JIA mothers. Disease activity improved in RA pregnancy and relapsed in the postpartum period. In JIA pregnancy disease activity was stable at low disease levels throughout pregnancy and in the postpartum period. In terms of anti-rheumatic medications used in ARD pregnancies, comparative analyses conducted indicated that, notably, the pregnant SLE group required the least number of changes to medications from the pre-conception period to the postpartum period, when compared with the RA and JIA group.

Conclusion: This study is the first prospective, longitudinal, comparative analysis of pregnancy outcomes, disease activity and medication use in SLE, RA and JIA, and healthy pregnant and non-pregnant ARD populations. This study provides largely reassuring outcomes from well controlled ARD pregnancies and provides an insight into the benefits of close monitoring by specialised rheumatology-obstetric services of ARD pregnancies. It also provides reassuring evidence that people with ARDs can achieve successful pregnancy outcomes when high-risk pregnancies are carefully managed by a modern approach that has involved a multi-disciplinary team of rheumatologist and obstetric physicians, to ensure good disease control is achieved prior to conception, and maintained throughout pregnancy. This study’s findings also indicate that ARD pregnancies have largely comparable pregnancy outcomes, with a slight increased risk of maternal and fetal complications, when compared with a healthy pregnant population. Furthermore, this study highlights that in a modern era of biologic medications, disease control can be promptly achieved with the use of safe and compatible biologics, prior to conception and/or during pregnancy to enhance the chances of successful pregnancy outcomes. Future research is required with a larger sample size and multi-centre input to aid the validation of this study’s findings.

Date of Award	22 Apr 2026
Original language	English
Awarding Institution	University of Bath
Supervisor	Emma Solomon-Moore (Supervisor), Peter Rouse (Supervisor), Ian Giles (Supervisor) & David Isenberg (Supervisor)