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Preeclampsia is characterized by blood pressure greater than 140/90 mmHg in the second half of pregnancy. This disease is a major contributor to preterm and low birth weight babies. The early delivery of the baby, which becomes necessary for maintaining maternal well-being, makes pre-eclampsia the leading cause for preterm labor and infant mortality and morbidity. Currently, there is no cure for this pregnancy disorder. The current clinical management of PE is hydralazine with labetalol and magnesium sulfate to slow disease progression and prevent maternal seizure, and hopefully prolong the pregnancy. This review will highlight factors implicated in the pathophysiology of preeclampsia and current treatments for the management of this disease.

BACKGROUND The addition of azithromycin to standard regimens for antibiotic prophylaxis before cesarean delivery may further reduce the rate of postoperative infection. We evaluated the benefits and safety of azithromycin-based extended-spectrum prophylaxis in women undergoing nonelective cesarean section. METHODS In this trial conducted at 14 centers in the United States, we studied 2013 women who had a singleton pregnancy with a gestation of 24 weeks or more and who were undergoing cesarean delivery during labor or after membrane rupture. We randomly assigned 1019 to receive 500 mg of intravenous azithromycin and 994 to receive placebo. All the women were also scheduled to receive standard antibiotic prophylaxis. The primary outcome was a composite of endometritis, wound infection, or other infection occurring within 6 weeks. RESULTS The primary outcome occurred in 62 women (6.1%) who received azithromycin and in 119 (12.0%) who received placebo (relative risk, 0.51; 95% confidence interval [CI], 0.38 to 0.68; P<0.001). There were significant differences between the azithromycin group and the placebo group in rates of endometritis (3.8% vs. 6.1%, P = 0.02), wound infection (2.4% vs. 6.6%, P<0.001), and serious maternal adverse events (1.5% vs. 2.9%, P = 0.03). There was no significant between-group difference in a secondary neonatal composite outcome that included neonatal death and serious neonatal complications (14.3% vs. 13.6%, P = 0.63). CONCLUSIONS Among women undergoing nonelective cesarean delivery who were all receiving standard antibiotic prophylaxis, extended-spectrum prophylaxis with adjunctive azithromycin was more effective than placebo in reducing the risk of postoperative infection. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; C/SOAP ClinicalTrials.gov number, NCT01235546.)

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ϩ T cells from placental ischemia (reduction in uteroplacental perfusion, RUPP) rats causes hypertension and elevated inflammatory cytokines during pregnancy. In this study we tested the hypothesis that adoptive transfer of RUPP CD4 ϩ T cells was associated with endothelin-1 activation as a mechanism to increase blood pressure during pregnancy. CD4 ϩ T cells from RUPP or normal pregnant (NP) rats were adoptively transferred into NP rats on gestational day 13. Mean arterial pressure (MAP) was analyzed on gestational day 19, and tissues were collected for endothelin-1 analysis. MAP increased in placental ischemic RUPP rats versus NP rats (124.1 Ϯ 3 vs. 96.2 Ϯ 3 mmHg; P ϭ 0.0001) and increased in NP recipients of RUPP CD4 ϩ T cells (117.8 Ϯ 2 mmHg; P ϭ 0.001 compared with NP). Adoptive transfer of RUPP CD4 ϩ T cells increased placental preproendothelin-1 mRNA 2.1-fold compared with NP CD4 ϩ T cell rats and 1.7-fold compared with NP. Endothelin-1 secretion from endothelial cells exposed to NP rat serum was 52.2 Ϯ 1.9 pg·mg Ϫ1 ·ml Ϫ1 , 77.5 Ϯ 4.3 pg·mg Ϫ1 ·ml Ϫ1 with RUPP rat serum (P ϭ 0.0003); 47.2 Ϯ .16 pg·mg Ϫ1 ·ml Ϫ1 with NPϩNP CD4 ϩ T cell serum, and 62.2 Ϯ 2.1 pg·mg Ϫ1 ·ml Ϫ1 with NPϩRUPP CD4 ϩ T cell serum (P ϭ 0.002). To test the role of endothelin-1 in RUPP CD4ϩ T cell-induced hypertension, pregnant rats were treated with an endothelin A (ETA) receptor antagonist (ABT-627, 5 mg/kg) via drinking water. MAP was 92 Ϯ 2 mmHg in NPϩETA blockade and 108 Ϯ 3 mmHg in RUPPϩETA blockade; 95 Ϯ 5 mmHg in NPϩNP CD4ϩ T cellsϩETA blockade and 102 Ϯ 2 mmHg in NPϩRUPP CD4ϩ T cellsϩETA blockade. These data indicate the importance of endothelin-1 activation to cause hypertension via chronic exposure to activated CD4 ϩ T cells in response to placental ischemia. pregnancy; T helper cells; placental ischemia PREECLAMPSIA, a hypertensive disorder of pregnancy, clinically characterized by new onset maternal hypertension and proteinuria after 20 wk gestation, typically affects 2-7% of pregnancies in the United States and contributes to almost 20% of maternal deaths in the United States (18,22). Hypertension in pregnancy, which occurs in response to placental ischemia, is associated with endothelial dysfunction, elevated circulating and placental inflammatory cytokines, and, in some cases, intrauterine growth restriction (2, 4, 7, 12). One hallmark of endothelial dysfunction is activation of the endothelin-1 (ET-1) pathway. Elevation of the vasoconstrictor peptide ET-1 and activation of the endothelin A (ET A ) receptor mediates vasoconstriction and elevated blood pressure. This serves as one mechanism of hypertension in response to placental ischemia that is hypothesized to play a role in the pathophysiology of preeclampsia (5,(22)(23)(24). A reduction in uteroplacental perfusion (RUPP), thought to be an initiating event in preeclampsia, contributes to wide-spread dysfunction of the maternal vascular endothelium during pregnancy (5,23,24). Serum from women with preeclampsia and serum from animal models of placental ischemia induced...