The interaction of pregnancy and systemic lupus erythematosus: Results from a prospective multicenter study

Abstract

The interaction of pregnancy and systemic lupus erythematosus - results from a prospective multicenter study: Systemic Lupus Erythematosus (SLE) is a chronic rheumatic disease affecting young women. Pregnancy in these women entails increased risk of preeclampsia, preterm birth (< 37 weeks) and growth retardation of the child. High disease activity before conception and during pregnancy is a well-known risk factor, while inactive disease or low disease activity is a good basis for the least complicated course if there are no other risk factors present. SLE is a fluctuating disease, with inactive disease alternating with flares. Earlier studies have found that one of two pregnant women with SLE has measurable disease activity, with a similar proportion experiencing flares during pregnancy. RevNatus is a nationwide Norwegian pregnancy register established in 2006. Women with rheumatic diseases are ideally included before conception (visit 0), and have follow-up each trimester (visit 1-3) and at 6 weeks, 6 and 12 months after birth (visit 4-6). The Medical Birth Registry of Norway (MBRN) is a registry with mandatory notification of all pregnancy outcomes after week 12 (miscarriages, fetal deaths and live births), existing since 1967. This thesis includes three papers focusing on the influence of pregnancy on SLE and how SLE affects pregnancy and pregnancy outcomes. Data was extracted from RevNatus during 2006 to 2016 (paper 1, 2 and 3) and from MBRN during 2006 to 2015 (paper 2). The aim of the first paper was to describe disease activity during pregnancy and the first year after birth in women with SLE included in RevNatus, applying a disease activity score validated for use in pregnancy. Disease activity was registered longitudinally at visit 1 through 6. The disease activity scores indicated inactive disease in 51.6%, low disease activity in 42.1% and only 6.3% indicated moderate disease activity. The model showed a statistically significant and clinically meaningful change over time, illustrating the relapsing and remitting course of the disease. The women had higher disease activity 6 and 12 months after birth compared to 3rd trimester and 6 weeks after birth. In the second paper we wanted to estimate and compare the occurrence of preeclampsia and preterm birth in women with inactive SLE, women with active SLE and population controls, and to estimate and compare birthweight (expressed as z-score) in offspring of these three groups. Data from RevNatus were linked with data from MBRN. We found that the occurrence of preeclampsia and preterm birth was higher in women with SLE than population controls, and highest in women with active SLE. We found no increased odds for preeclampsia in women with inactive disease compared to population controls, while women with active SLE had increased odds compared to both population controls and women with inactive SLE. Preterm birth had higher odds in women with inactive SLE than population controls, and higher odds in women with active SLE compared to both population controls and inactive SLE. Birthweight adjusted for gestational age and gender (z-score) was lower in offspring of women with inactive and active SLE compared to offspring of population controls, with an associated higher occurrence of small for gestational age (SGA) in offspring of women with SLE. In the third paper we sought to investigate possible differences in women with SLE and women with rheumatoid arthritis (RA) concerning the ability to get pregnant and time to pregnancy, and to register and compare health-related quality of life (HRQoL) in women achieving and not achieving pregnancy. We compared women with SLE and women with RA included in RevNatus before pregnancy (visit 0). There was a higher percentage of women with SLE achieving pregnancy during follow-up as compared to women with RA, and they had a substantially shorter time to pregnancy. Women with SLE not achieving pregnancy had lower HRQoL than women achieving pregnancy. Women with RA not achieving pregnancy were older and used NSAIDs more frequently compared to women achieving pregnancy. Women with RA had generally low HRQoL-scores whether or not achieving pregnancy. The results from the first paper demonstrate that most pregnant women with SLE in Norway have inactive disease or low disease activity during pregnancy and the first year after birth. This indicates satisfactory treatment and follow-up. Higher disease activity 6 and 12 months after birth substantiates the need for follow-up to include the first year after birth, to detect and treat flares and increased disease activity. Even though the women in our population had low disease activity, the results from the second paper demonstrates that active disease represents a considerable risk for complications compared to inactive disease. The clinical implication is to strive for inactive disease before and during pregnancy, to diminish the risk in more women with SLE. It also allows for a differentiated follow-up according to disease activity status. The results in the third paper points to the importance to discuss and reveal issues of family planning in women with rheumatic inflammatory disease early in the course of the disease.