Abstract-Adrenomedullin is a novel peptide that elicits a long-lasting vasorelaxant activity. Recently, we found high concentrations of adrenomedullin in maternal and umbilical cord plasma and in amniotic fluid in full-term human pregnancy, indicating a role of this peptide during gestation. To investigate the possibility that adrenomedullin is involved in the pathophysiology of preeclampsia, we measured its concentration in maternal and fetoplacental compartments. We studied 12 normotensive nonpregnant women, 13 hypertensive nonpregnant subjects, 29 patients with preeclampsia, and 30 normotensive pregnant women. In all patients, plasma was collected from the cubital vein, and amniotic fluid samples were obtained by transabdominal amniocentesis or at elective cesarean section. Plasma samples from umbilical vein and placental tissues were collected at delivery. Adrenomedullin was assayed on plasma and amniotic fluid samples using a specific radioimmunoassay, and its localization and distribution on placental sections was determined by immunohistochemistry. Adrenomedullin concentrations were higher in hypertensive than in normotensive nonpregnant patients. Pregnant women had higher adrenomedullin levels than nonpregnant subjects, although maternal plasma adrenomedullin concentrations did not differ between normal pregnant and preeclamptic women. Preeclamptic patients showed higher concentrations (PϽ0.01) than normotensive pregnant women of adrenomedullin in amniotic fluid (252Ϯ29 versus 112Ϯ10 fmol/mol creatinine) and umbilical vein plasma (18.1Ϯ2.1 versus 8.5Ϯ1.1 fmol/mL). Increased local production of adrenomedullin is associated with preeclampsia. The fetus seems to be responsible for the higher levels of this hormone. Increased adrenomedullin concentrations may be necessary to maintain placental vascular resistance and/or fetal circulation at a physiological level. (Hypertension. 1998;32:758-763.)

To determine whether S100␤, an acidic calcium-binding protein previously demonstrated as a reliable indicator of a brain lesion, could be helpful in the detection of brain distress in intrauterine growth-retarded (IUGR) fetuses, we studied, by a case-control study, the correlation between S100B protein and the degree of fetoplacental blood flow impairment. Maternal and umbilical blood samples and placental tissue specimens were collected at delivery from IUGR pregnancies with normal (n ϭ 10) or abnormal (n ϭ 10) umbilical artery Doppler findings and from 40 uncomplicated pregnancies. S100␤ protein levels were measured by means of a specific RIA, and flow velocimetry waveforms were recorded from uterine, umbilical, and fetal middle cerebral arteries. Overall mean S100␤ proteins in umbilical plasma levels were higher (p Ͻ 0.05) in IUGR patients (121.8 Ϯ 70.4 fmol/mL) than in control patients (54.7 Ϯ 21.9 fmol/mL). IUGR fetuses with redistribution of blood flow showed the higher concentration of the protein (163.7 Ϯ 55.2 fmol/mL).Fetal S100␤ concentrations correlated with middle cerebral artery pulsatility index (r ϭ Ϫ0.536, p Ͻ 0.03) and with umbilical artery pulsatility index to middle cerebral artery pulsatility index ratio (r ϭ 0.469, p Ͻ 0.03). No difference in the localization or intensity of S100␤ staining in the placental tissues or cord between uncomplicated and IUGR pregnancies was found. This study provides evidence that circulating S100␤ protein is increased in IUGR fetuses and correlates with cerebral hemodynamics, suggesting that it may represent an index of cerebral cell damage in the perinatal period. The S100 family of calcium-binding proteins, first isolated in 1965 by Moore (1) in a subcellular fraction from bovine brain, contains approximately 16 members, each of which exhibits a unique pattern of tissue-or cell type-specific expression. Although the distribution of these proteins is not restricted to the nervous system, the involvement of several members of this family in nervous system development, function, and disease has sparked new interest in these proteins. S100␤, one of the original two members of this family, is an acidic calcium-binding protein with a molecular weight of 21 kD. It is present extracellularly, intracellularly, and in the cytosol; its half-life is approximately 2 h, and it is mainly eliminated by the kidney (2). S100␤ is present in CNS and is concentrated in the glial cells, astrocytes, Schwann cells, and neurons. It regulates several cellular functions (cell-cell communication, cell growth, cell structure, energy metabolism, contraction, and intracellular signal transduction). Elevated plasma levels are found in patients with brain damage (3). Abnormal S100␤ levels have been associated with neurobehavioral abnormalities and microcephaly caused by in utero cocaine exposure (4), and abnormal S100␤ immunoreactivity cells in anencephalic fetuses have been shown (5).The S100␤ concentration in blood and in cerebrospinal fluid is increased as result of brain damage in adults a...

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This study suggests that elevated S100B protein represents a useful tool for the early detection of intraventricular hemorrhage in the postasphyxia period when clinical examination and cerebral ultrasound might still be silent.