AT1 receptor autoantibodies

The presence of agonistic auto-antibodies against the angiotensin II AT1 receptor have been reported in the serum of individuals with PE (Xia et al., 2003). The antibody also downregulates the AT1 receptor in a similar manner to angiotensin II but stimulates superoxide production from placental or vascular tissue (Dechend et al., 2003). They also inhibit trophoblast invasion in an in vitro assay and increase trophoblast PAI-1 production (Xia et al., 2002, 2003) and thus may account for two features of pre-eclampsia (reduced invasion and increased PAI-1). In cross-sectional studies these auto-antibodies are claimed to be found in the majority of patients with severe pre-eclampsia. This, however, needs to be confirmed in prospective longitudinal studies. Whether these antibodies exist prior to development of pre-eclampsia or are found in individuals with mild disease remains to be determined.

Conclusion

The majority of pre-eclampsia occurs in nullipa-rous individuals and yet within this group 75% occurs at term in association with relatively low maternal and fetal morbidity. Less than 1% of the nulliparous population develop pre-eclampsia at <34 weeks. Such a low incidence of clinically significant disease may preclude the use of expensive screening tests in such a low-risk population.

The greatest expenditure associated with pre-eclampsia in the developed world is in the care of premature infants delivered of women with early onset or severe pre-eclampsia. Identification of individuals who may develop the early onset/severe pre-eclampsia phenotype is then the most desirable in terms of reducing neonatal and maternal morbidity and mortality and subsequent societal expense. Screening should perhaps focus primarily on multiparous individuals with a history of pre-eclampsia and women of any parity with underlying medical disease or multifetal pregnancy, as these women account for the majority of early onset severe pre-eclampsia resulting in preterm delivery. The inclusion of risk factors such as blood pressure at initial prenatal care visit, body mass index, family history and, possibly, smoking as well as short pre-conception exposure to paternal antigens, could expand the screen to include a greater number of otherwise low-risk nulliparas destined to develop early onset preeclampsia (Figure 15.2). A second round of screening or surveillance could then include the use of biochemical and biophysical markers, maternal and perhaps fetal genotype to identify such phenotypes and select the group of patients felt to be at highest risk for the development of preeclampsia. These biochemical/biophysical tests may also provide alternative and earlier definitions

Figure 15.2 Defining patients at risk of developing pre-eclampsia.

of disease than simply hypertension/proteinuria and suggest who may benefit from different therapeutic interventions (placental/vascular), as well as ongoing pregnancy surveillance. Current treatment is limited to the administration of steroids for fetal lung maturation and seizure prophylaxis for the mother, and resolution of disease is limited to delivery of the infant and its placenta. This does not dismiss the potential of future prophylactic treatments such as antiox-idants. Using such a two-step screening approach, a small percentage of nulliparas and multiparas destined to develop pre-eclampsia may be screen-negative (low risk by clinical and biochemical screen). The advantage of a two-step approach is to limit the number of individuals undergoing potentially costly screening and surveillance.

By far the majority of studies of pre-eclamptic women to date have been cross-sectional of women with mild disease at term. Although there are now more longitudinal studies emerging, they mostly still employ small patient numbers and a priori still focus on mild disease at term. What is needed are large-scale prospective studies powered to correlate predictive markers with clinically and economically significant outcomes for mother and fetus, i.e. they need to study early onset/ severe pre-eclampsia

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