ORIGINAL ARTICLE Uterine artery Doppler velocimetry and obstetric outcomes in connective tissue diseases diagnosed during the first trimester of pregnancy Fausta Beneventi 1 , Elena Locatelli 1 * , Véronique Ramoni 2 , Roberto Caporali 2 , Carlo Maurizio Montecucco 2 , Margherita Simonetta 1 , Chiara Cavagnoli 1 , Maria Ferrari 1 and Arsenio Spinillo 1 1 Department of Obstetrics and Gynecology, San Matteo Hospital, Pavia, Italy 2 Department of Rheumathology, San Matteo Hospital, Pavia, Italy *Correspondence to: Elena Locatelli. E-mail: elena.loc@libero.it ABSTRACT Objective To evaluate the effect of connective tissue disease (CTD) diagnosed during the first trimester on uterine arteries (UtA) Doppler velocities and on pregnancy outcomes. Method Pregnant women were screened for CTDs during the first trimester, using a questionnaire, testing for autoantibodies, rheumatologic examination and UtA Doppler evaluations. Results Out of 3932 women screened, 491 (12.5%) were screened positive at the questionnaire; of them, 165(33.6%) tested positive for autoantibodies, including 66 eventually diagnosed with undifferentiated connective tissue disease (UCTD), 28 with a definite CTD and 71 with insufficient criteria for a diagnosis. Controls were 326 women screened negative for autoantibodies. In logistic analysis, women diagnosed with either UCTD (OR = 7.9, 95% CI = 2.3–27.3) or overt CTD (OR = 24.9, 95% CI = 6.7–92.4), had increased rates of first trimester bilateral UtA notches compared with controls. The rates of bilateral UtA notches persisting in the second (15/94 vs 0/326, p < 0.001) and third trimesters (7/94 vs 0/326, p < .001) were higher among women with CTDs than in controls. The risk of complications (preeclampsia, fetal growth restriction, prematurity, diabetes, fetal loss) was higher (OR = 7.8, 95% CI = 3.6-17.0) among women with CTDs than in controls. Conclusion Women with undiagnosed CTDs have higher rates of bilateral UtA Doppler notches throughout pregnancy and increased rates of adverse pregnancy outcomes than controls. © 2012 John Wiley & Sons, Ltd. Funding sources: None Conflicts of interest: None declared INTRODUCTION Connective tissue diseases (CTDs) are a group of heterogeneous disorders characterized by an immunological reaction against self antigens, autoantibody production and immuno-complex deposition onto sensitive tissues. 1 Women with systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), rheumatoid arthritis (RA) and systemic sclerosis (SSc) pre- existing pregnancy are at an increased risk of preeclampsia, pre-term delivery and fetal growth restriction (FGR). 2–4 Undiffer- entiated connective tissue disease (UCTD) may be associated with an increased risk of small for gestational age (SGA), pre- term delivery, preeclampsia and fetal loss. 5 Uterine artery (UtA) Doppler examination can be used to indirectly assess trophoblast development and uteroplacental perfusion. 6,7 Uteroplacental circulation develops through trophoblast invasion starting at 8 to 10 weeks with endovascular plugging and destruction of the muscoloelastic media of intradecidual segments of the spiral arteries, subsequently involving also the inner third of their myometrial segments. 6,7 Abnormal uteroplacental circulation, as assessed with UtA Doppler velocimetry, has been linked to pregnancy com- plications such as hypertension, FGR and early pregnancy failure, both in women at high risk 8 and in the general population. 9,8,10,11 Complications of pregnancy such as FGR or preeclampsia are considered the results of an inadequate trophoblast invasion of spiral arteries and impaired perfusion through the fetal-placental unit. 12 In pregnancies complicated by preeclampsia or FGR, there is a superficial invasion of uterine spiral arteries with an increased resistance in Doppler flow velocity as early as 10 to 11 weeks of pregnancy. 13 In longitudinal studies, increased Doppler pulsatility of uterine arteries persisting through the second trimester of pregnancy was associated with an increased risk of preeclampsia, FGR and stillbirth. 7 In most cases, increased UtA resistance undergoes normalization as gestation advances. However, about 30% of women with persistently abnormal UtA Doppler findings in the early third Prenatal Diagnosis 2012, 32,1–8 © 2012 John Wiley & Sons, Ltd. DOI: 10.1002/pd.3964