Vasoconstriction and defective placental angiogenesis are key factors in the etiology of preeclampsia. Prolactin levels are elevated in maternal blood throughout pregnancy and the human decidua produces prolactin that is transported to the amniotic fluid. Prolactin is cleaved to yield vasoinhibins, a family of peptides that inhibit angiogenesis and nitric oxidedependent vasodilation. Here, we conducted a case-control study to measure vasoinhibins in serum, urine, and amniotic fluid obtained from women with severe preeclampsia. We show that all three biological fluids contained significantly higher levels of vasoinhibins in preeclamptic women than in normal pregnant women. Amniotic fluid from preeclamptic women, but not from normal women, inhibited vascular endothelial growth factor-induced endothelial cell proliferation and nitric oxide synthase activity in cultured endothelial cells, and these actions were reversed by antibodies able to neutralize the effects of vasoinhibins. Furthermore, amniotic fluid does not appear to contain neutral prolactin-cleaving proteases, suggesting that vasoinhibins in amniotic fluid are derived from prolactin cleaved within the placenta. Also, cathepsin-D in placental trophoblasts cleaved prolactin to vasoinhibins, and its activity was higher in placental trophoblasts from preeclamptic women than from normal women. Importantly, birth weight of infants in preeclampsia inversely correlated with the extent to which the corresponding AF inhibited endothelial cell proliferation and with its concentration of prolactin þ vasoinhibins. These data demonstrate that vasoinhibins are increased in the circulation, urine, and amniotic fluid of preeclamptic women and suggest that these peptides contribute to the endothelial cell dysfunction and compromised birth weight that characterize this disease.

Objetivo: describir la frecuencia de complicaciones perinatales en gestaciones pretérmino de madres con preeclampsia severa con y sin restricción del crecimiento intrauterino (RCIU). Materiales y métodos: estudio descriptivo en embarazo único, preeclampsia severa y parto entre 24 y 34 semanas, con y sin RCIU, entre enero 2007 y diciembre 2009. Se realizó monitoría fetal cada 48 horas, perfil biofísico fetal (PBF) dos veces por semana y Doppler fetoplacentario semanal. Resultados: se estudiaron 55 pacientes con edad promedio de 29.6 (DE 6.4) años, media de edad gestacional de 29.9 (DE 2.9) semanas, menor en el grupo con RCIU 28.8 (DE.3.1) vs 31.2 (DE 2.0). Hubo RCIU en 30 (54,5%) gestaciones, la mortalidad perinatal fue de 17 casos (31%), 15 en embarazos con RCIU. La mayoría ocurrió en gestaciones por debajo de 28.6 semanas. Conclusiones: la mortalidad perinatal en preeclampsia en edad gestacional temprana es alta en nuestro hospital, en especial en presencia de RCIU. Es probable que esta asociación actúe en forma sinérgica sobre las complicaciones por prematurez. Al mejorar la atención pre y neonatal esperamos superiores resultados perinatales.