Doppler in Obstetrics by Nicolaides, Rizzo, Hecker & Ximenes
The 11-14 weeks scan by Nicolaides, Sebire, Snijiders & Ximenes
The 18-23 weeks scan by Pilu, Nicolaides, Ximenes & Jeanty
 
SYSTEMIC LUPUS ERYTHEMATOSUS


Systemic lupus erythematosus, which affects about one in 1000 adults, is an idiopathic multisystem chronic inflammatory disease, characterized by the presence of circulating autoantibodies directed against nuclear antigens.

In pregnant women with systemic lupus erythematosus, the rate of fetal loss in the first trimester is similar to that in normal women (about 15%), but, in the second and third trimesters, the fetal loss rate is about 10% 1,2. The mechanism for this increase in fetal loss is unclear but may be related to placental dysfunction. The most sensitive predictor of fetal death is the presence of antiphospholipid antibodies 3–5.

About 25% of pregnancies in women with systemic lupus erythematosus are complicated by pre-eclampsia 3. The reason for this increased frequency of pre-eclampsia may be related to the underlying renal disease 6. Fetal growth restriction is found in about 20% of pregnancies 1. Distinguishing between an exacerbation of systemic lupus erythematosus involving active nephritis and pre-eclampsia is difficult, since they may both present with proteinuria, hypertension and evidence of multi-organ dysfunction. In the typical problem case, the patient develops hypertension and increasing proteinuria in the latter half of pregnancy. Elevated levels of anti-dsDNA and an active urinary sediment strongly suggest lupus. In severe and confusing cases, renal biopsy may be necessary to make the correct diagnosis.

Neonatal lupus erythematosus, with a birth prevalence of about one in 20 000, is characterized by dermatological, cardiac or hematological abnormalities. The condition is due to maternal autoantibodies, particularly anti-Ro/SS-A and anti-SS-B/La, that cross the placenta 7. About half of the mothers who deliver an infant with neonatal lupus erythematosus have systemic lupus erythematosus or another autoimmune disease. The risk of a mother with anti-SS-A/Ro and/or anti-SS-B/La having a fetus or neonate with neonatal lupus erythematosus is fairly low and among all mothers with systemic lupus erythematosus, the risk of neonatal lupus erythematosus is less than 5% 8. The cardiac lesions associated with the condition are congenital complete heart block and endocardial fibroelastosis. The usual presentation is a fixed fetal bradycardia of 60–80 beats per min presenting at 15–25 weeks of gestation; in some cases there is associated hydrops fetalis. The histological lesion is one of fibrosis and interruption of the conduction system, especially in the area of the atrioventricular node. Because the lesion is permanent, a pacemaker may be necessary for neonatal survival. After prenatal  diagnosis of fetal heart block, administration of a glucocorticoid to the mother is associated with improvement in fetal cardiac function and limitation of further immunological damage to the fetal heart 9,10.

ANTIPHOSPHOLIPID SYNDROME


Antiphospholipid syndrome is an autoimmune condition characterized by the production of moderate to high levels of antiphospholipid antibodies (lupus anticoagulant or anticardiolipin antibody) and at least one clinical feature (venous or arterial thrombosis, autoimmune thrombocytopenia and/or pregnancy loss). The risk of thrombosis in pregnancy in women with antiphospholipid syndrome is sufficiently substantial to warrant prophylactic treatment with heparin.

Antiphospholipid syndrome is associated with early pregnancy loss; antiphospholipid antibodies are found in about 10% of women with recurrent first-trimester pregnancy loss (compared to about 2.5% in controls) 11–15. About 50% of women with antiphospholipid syndrome develop pre-eclampsia, which may start from as early as 15 weeks, or worsening hypertension 16,17 and about 10% of women with severe earlyonset (before 34 weeks) pre-eclampsia have antiphospholipid antibodies. The rate of pre-eclampsia does not appear to be markedly diminished by treatment with either glucocorticoids with low-dose aspirin or heparin with low-dose aspirin. The syndrome is also associated with fetal growth impairment, which is found in about 30% of treated pregnancies 16,17. In women with antiphospholipid syndrome, treatment with thromboprophylactic doses of heparin and low-dose aspirin improves the chances of a successful pregnancy outcome 18–21.

DOPPLER STUDIES


In pregnancies complicated by maternal systemic lupus erythematosus, increased impedance to flow in the umbilical arteries is associated with increased risk of pre-eclampsia and intrauterine growth restriction. Thus, Kerslake et al. carried out serial Doppler studies in 56 pregnancies complicated by maternal systemic lupus erythematosus 22. They reported that the absence of end-diastolic frequencies in the umbilical artery was a good predictor of the need for subsequent delivery by Cesarean section, whereas the presence of end-diastolic frequencies was associated with normotensive pregnancy 22. Similarly, Farine et al. examined 56 pregnancies complicated by maternal systemic lupus erythematosus and reported that absent or reversed enddiastolic frequencies, which were detected in 11% of the patients, were associated with increased risk of pre-eclampsia and intrauterine growth restriction 23.

In systemic lupus erythematosus, it is uncertain if impedance to flow in the uterine arteries is increased. Thus,Weiner et al. carried out serial Doppler studies of the uterine and umbilical arteries in five patients with systemic lupus erythematosus from week 10 to term 24. Impedance to flow in the uterine artery was within the normal range in all cases, whereas most values from the umbilical artery were above the 95th centile of the normal range. All five pregnancies resulted in healthy live births but one infant was growth-restricted; the highest impedance in the umbilical artery was observed in the case of growth restriction. Guzman et al. examined 27 pregnancies in women with systemic lupus erythematosus 25. In 18 pregnancies, there was normal impedance in both the uterine and umbilical arteries and they all had normal outcomes. In five pregnancies, there was normal impedance in the uterine arteries but increased impedance in the umbilical artery and, in this group, there were two cases of intrauterine growth restriction. In four pregnancies, there was increased impedance in both vessels; in all four, there was intrauterine growth restriction and three resulted in intrauterine or neonatal death.

In antiphospholipid syndrome there is thrombosis of the uteroplacental vasculature and placental infarction. There is some evidence that, in pregnancies with antiphospholipid syndrome, increased impedance in the uterine arteries identifies those cases that subsequently develop pre-eclampsia and intrauterine growth restriction. Thus, Caruso et al. examined 28 pregnancies in women with antiphospholipid syndrome and reported that increased impedance in the uterine arteries at 18–24 weeks of gestation provided useful prediction of both pre-eclampsia and intrauterine growth restriction 26. In this respect, the findings of Doppler studies in predicting the outcome of pregnancies with the antiphospholipid syndrome may be similar to those with placental insufficiency due to impaired trophoblastic invasion of the maternal spiral arteries. However, Trudinger et al. suggested that, in the antiphospholipid syndrome, infarction of the placental vessels may be an acute phenomenon causing rapid deterioration in the fetal condition without impairment in growth, which would necessitate chronic placental insufficiency 27. They examined six pregnancies in women with antiphospholipid syndrome and reported increased impedance to flow in the umbilical artery in four of the cases, despite the absence of pre-eclampsia or intrauterine growth restriction. Further evidence emphasizing the difference in the implications of antiphospholipid syndrome from impaired trophoblastic invasion was provided by the studies of Carroll 28. He examined 28 pregnancies complicated by antiphospholipid syndrome and reported that, in five of the six cases associated with intrauterine growth restriction, impedance to flow in the umbilical arteries was increased, whereas only two of these patients demonstrated abnormally elevated impedance in the uterine arteries.

CONCLUSIONS
  • Systemic lupus erythematosus is associated with increased risk of pre-eclampsia, intrauterine growth restriction and perinatal death.
  • In systemic lupus erythematosus, increased impedance to flow in the umbilical arteries is associated with increased risk of pre-eclampsia and intrauterine growth restriction.
  • In systemic lupus erythematosus, it is uncertain if impedance to flow in the uterine arteries is increased.
  • Antiphospholipid syndrome is characterized by thrombosis of the uteroplacental vasculature and placental infarction, and is associated with early pregnancy loss, pre-eclampsia and intrauterine growth restriction.
  • In antiphospholipid syndrome, the development of pre-eclampsia and intrauterine growth restriction is preceded by increased impedance to flow in the umbilical arteries and possibly the uterine arteries.
 
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Doppler in Obstetrics
Copyright © 2002 by Kypros Nicolaides, Giuseppe Rizzo, Kurt Hecker and Renato Ximenes
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