RESUMO
OBJECTIVE: Recent studies have demonstrated that stimulating autoantibodies against the angiotensin II type 1 receptor (AT1R-AA) are frequently detected in the sera from women with preeclampsia, suggesting that they may play an important role in the pathogenesis of this disease. Nevertheless, the real clinical significance of AT1R-AA in preeclampsia is still controversial due to the paucity of appropriate large comparative studies that require cumbersome, time-consuming, and expensive bioassays to detect AT1R-AA. At present, the prevalence of AT1R-AA in large populations of preeclamptic women is unknown. In an attempt to clarify this issue, we assessed the presence and potential clinical significance of AT1R-AA in a large population of Mexican-Mestizo women with preeclampsia. METHODS: Using a cross-sectional design, we determined the presence of AT1R-AA in 525 pregnant women (99 healthy pregnant, 96 with mild preeclampsia, and 330 with severe preeclampsia) by a new bioassay that employs human embryonic kidney-293 cells stably expressing the recombinant rat AT1R and a 4x nuclear factor of activated T cells responsive luciferase construct as well as by the reference assay in Chinese hamster ovary (CHO) cells. RESULTS: We found that IgG obtained from sera of healthy pregnant women and patients with preeclampsia were unable to induce luciferase activity in both HEK-293 and Chinese hamster ovary cells expressing functional angiotensin II receptor type 1. Therefore, the frequency of patients with AT1R-AA was zero. CONCLUSION: We concluded that in Mexican-Mestizo women agonistic AT1R-AA cannot be invoked as a factor involved in the pathogenesis of preeclampsia. Whether these findings can be attributed to genetic or environmental factors remains unknown.
Assuntos
Autoanticorpos/sangue , Indígenas Norte-Americanos/genética , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/imunologia , Receptor Tipo 1 de Angiotensina/imunologia , Adulto , Animais , Autoanticorpos/imunologia , Autoanticorpos/farmacologia , Células CHO , Linhagem Celular , Cricetinae , Cricetulus , Estudos Transversais , Feminino , Humanos , Indígenas Norte-Americanos/etnologia , México , Pré-Eclâmpsia/etiologia , Gravidez , Ratos , Receptor Tipo 1 de Angiotensina/genética , TransfecçãoRESUMO
BACKGROUND: Abnormal placentation is a main preeclampsia characteristic. Its cause is a maternal spiral veins trophoblastic invasion failure, which conditions vascular resistances raise and uterus-placental perfusion decrease. OBJECTIVE: To determine the relationship between umbilical artery Doppler waveform and adverse perinatal outcome in patients with severe preeclampsia. PATIENTS AND METHOD: A prospective, observational and transversal study was done to analyze patients between 27 to 33 weeks of gestation with expectant management of severe preeclampsia from January 2004 to January 2006. Umbilical artery velocimetry studies were performed at least once a week by means of pulsed Doppler equipment with a 3.5 MHz transducer. Only the results of the last Doppler examination performed within 7 days of delivery were considered in the correlation with perinatal outcomes. The indications for delivery were maternal or fetal (non reassuring nonstress test or biophysical profile < or = 4). An abnormal Doppler velocimetry was defined as pulsatility index being higher than percentile 95 for gestational age, or absent or reversed end diastolic velocity waveforms in umbilical artery. The statistical analysis was done with chi2 test and Student t test. RESULTS: There were included 43 patients in this study. Twenty-two (52%) had an abnormal Doppler umbilical artery pulsatility index and 21 (49%) obtained a normal umbilical artery waveform. In the first group 13 (59%) had a positive end diastolic velocities with elevated pulsatility index values, end diastolic velocities were absent in seven cases (32%) and reversed in two cases (9%). Neonates with abnormal pulsatility index had a lower birth weight (1,174 vs 1,728 g), lower Apgar score at 5 minutes, higher admission to the neonatal intensive care unit (86.4 vs 43%), and significant neonatal morbidity compared with those with normal velocimetry (p < 0.05). There were no perinatal deaths with normal umbilical Doppler waveform. There were six perinatal deaths in the abnormal Doppler velocimetry. Two cases occurred with positive end diastolic velocity (15%), two cases with absent end diastolic velocity (28%) and two deaths with reversed flow of the umbilical artery (100%). CONCLUSION: An abnormal Doppler umbilical artery waveform is associated with poor perinatal outcome and is a strong predictor of perinatal mortality.