Can uterine artery Doppler velocimetry predict adverse pregnancy outcome in women with antiphospholipid syndrome?

Abstract

Primary antiphospholipid syndrome is characterized by a group of autoantibodies including lupus anticoagulant (LA) and anticardiolipin antibodies (ACA), associated with vascular thrombosis, adverse pregnancy outcome and thrombocytopenia (1). The presence of these autoantibodies has also been shown to be associated with early onset pre-eclampsia (2), intrauterine growth retardation (IUGR) (3) and placental abruption (4). Uterine artery Doppler waveform analysis provides a non-invasive assessment of the utero-placental circulation and has been used as a screening test for pre-eclampsia and IUGR. The increase in flow resistance within the uterine arteries results in an abnormal waveform pattern which is represented by either an increase in resistance index (5), or by the presence of an early diastolic notch (6) which reflects failure of the second wave of trophoblastic invasion of the utero-placental vasculature. The aim of this study was to determine if uterine artery Doppler waveform analysis could predict adverse pregnancy outcome in women with antiphospholipid syndrome. During the period January 1995 to December 1999 we identified 43 pregnancies in 41 women attending the medical antenatal clinic at National Women's Hospital, Auckland with the diagnosis of antiphospholipid syndrome (1) and in whom uterine artery Doppler assessment was performed in the index pregnancy. Thirty-six (84%) cases were classified as having primary APS and seven (16%) had secondary APS (1). Color Doppler assessment of the utero-placental circulation was performed in the second or early third trimester (median 23 weeks; range 19–34 weeks) using color Doppler ultrasonic systems with a 3.5MHz curvilinear probe and 100Hz high pass filter. Both the placental and non-placental uterine arteries were considered abnormal if the RI was greater than the 95th centile for gestational age(5) or demonstrated an early diastolic notch (6). Only bilateral uterine artery Dopplers were considered abnormal. Seventy-four percent (32/43) of the pregnancies had normal and 26% (11/43) had abnormal uterine artery waveforms. No significant difference was observed in the gestational age at which the Doppler assessment was made (median 24 and 22 weeks respectively; p>0.05) or in the demographic features of the two groups. In those pregnancies with abnormal uterine artery Doppler waveforms, adjusted birthweight <10th centile and preterm delivery <34 weeks were both statistically increased (p=0.045 and p=0.003 respectively) (Table I). Three cases of severe pre-eclampsia and a placental abruption resulting in a 27 week neonatal death accounted for the four cases of preterm delivery in the abnormal Doppler group. This small retrospective study has demonstrated significant association between abnormal uterine artery Doppler waveforms and adverse pregnancy outcome in women classified as having antiphospholipid syndrome. Similar findings were reported by Caruso et al. (7) who demonstrated an association between abnormal uterine Dopplers and IUGR and preterm delivery in 28 women with antiphospholipid syndrome. Of more clinical importance was that in women with normal uterine artery Dopplers there were no cases of premature delivery and its associated mortality or morbidity. This does pose the question as to whether a normal uterine artery Doppler can result in a change in the subsequent antenatal management of these women in terms of number of antenatal visits or anticoagulation prophylaxis. The women included in this study all had diverse clinical determinants of APS ranging from first trimester losses to third trimester abruption and varying regimes for anticoagulant prophylaxis. As a result of the diversity in clinical aspects of the cases and small numbers included we are unable to comment on whether the results of the uterine artery Dopplers in women with recurrent first trimester or late abruption carry the same prognostic value. What is required is a large prospective analysis of uterine Doppler and pregnancy outcome in women with the same clinical criteria of antiphospholipid syndrome on the same anticoagulant prophylaxis. This must be the first step before any attempt at developing management guidelines in terms of antenatal care strategies and prophylaxis.