Systemic autoimmune rheumatic diseases are associated with increased rates of adverse pregnancy outcomes, including spontaneous abortion, preeclampsia, fetal growth restriction (FGR) and prematurity. Although retrospective epidemiologic data suggest that adverse pregnancy outcomes often antedate the subsequent development of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc) or antiphospholipid syndrome (APS), the effect of preclinical autoimmune systemic diseases on pregnancy outcome has not been well studied. In a previous cohort study, using a two-step approach with a self-reported questionnaire and autoantibody detection, these authors evaluated the effects of well-defined rheumatic diseases diagnosed during the first trimester on pregnancy outcome. The purpose of the present study, carried out using a similar approach, was to evaluate the effects of preclinical or incomplete autoimmune systemic rheumatic disorders detected during the first trimester of pregnancy on pregnancy outcome.
Methods. In this longitudinal cohort study, patients were enrolled during the first trimester of pregnancy if they reported having had connective tissue disorder symptoms, were found to be positive for circulating autoantibodies and, on clinical evaluation, were judged to have a preclinical or incomplete rheumatic disorder. The incidence of fetal growth restriction (FGR), preeclampsia and adverse pregnancy outcomes in patients with preclinical rheumatic disorders was compared with that in selected controls, after adjustment for confounders by penalized logistic regression.
Results. Of 5,232 women screened, 150 (2.9%) were initially diagnosed as having a suspected rheumatic disorder. After a mean ± SD postpartum follow-up of 16.7 ± 5.5 months, 64 of these women (42.7%) had no clinically apparent rheumatic disease and 86 (57.3%) had persistent symptoms and positive autoantibody results, including 10 (6.7%) who developed a definitive rheumatic disease. The incidences of preeclampsia/FGR and of small-for-gestational-age infants were 5.1% (23 of 450) and 9.3% (42 of 450), respectively, among controls, 12.5% (8 of 640) (OR 2.7 [95% CI 1.1–6.4]) and 18.7% (12 of 64) (OR 2.2 [95% CI 1.1–4.5]), respectively, among women with no clinically apparent disease, and 16.3% (14 of 86) (OR 3.8 [95%CI 1.9–7.7]) and 18.6% (16 of 86) (OR 2.3 [95% CI 1.2– 4.3]), respectively, among those with persisting symptoms at follow-up. Mean ± SD umbilical artery Doppler pulsatility indices were higher among women with no clinically apparent disease (0.95 ± 0.2) and those with persisting symptoms (0.96 ± 0.21) than in controls (0.89 ± 0.12) (P = 0.01 and P < 0.001, respectively).
Conclusion. The evidence from this study suggest that in pregnant women with mild preclinical or incomplete rheumatic disease detected during the first trimester of pregnancy is associated with an increased risk of preeclampsia and FGR, SGA or other adverse pregnancy outcomes. Even positive autoantibody status during the first trimester with no clinically apparent rheumatic disease at postpartum follow-up is associated with an increased risk of fetal growth failure.
The impact of these findings and their utility in screening for FGR and preeclampsia need to be confirmed in population studies.
Excerpted and adapted from:
Spinillo A, Beneventi F, Locatelli E, et al. Early, Incomplete, or preclinical autoimmune systemic rheumatic diseases and pregnancy outcome. Arthritis Rheumatol. 2016 Oct;68(10):2555–2562.