Vasopressin Concentration in Amniotic Fluid as an Index of Fetal Hypoxia: Mechanism of Release in Sheep

Abstract

SummaryHypoxia is a potent stimulus to the release of vasopressin in fetal sheep and, in turn, plasma concentrations of the hormone correlate inversely with fetal oxygenation. Because the fetal kidney contributes to vasopressin clearance, we propose that measurement of increased amounts of vasopressin in amniotic fluid would be indicative of fetal hypoxia. We therefore measured concentrations of vasopressin in amniotic fluid under resting conditions, during and after fetal hypoxia, and with intravenous and intra-amniotic administration of vasopressin in 15 chronically instrumented fetal lambs 111-141 d gestation. In the resting state mean (+SE) vasopressin concentrations in amniotic fluid (1.6 + 0.3 pgml-') did not differ from those in maternal (1.4 f 0.4 p g ml-') or fetal (1.8 f 0.2 pg.ml-') plasma. After exposure of the ewe to 10% Oz or partial occlusion of the umbilical cord, vasopressin concentrations in fetal plasma increased significantly ( P < 0.001) to 200 f 59 pg.ml-' with a delayed increase in amniotic fluid concentrations ( P < 0.03) to 15.8 + 4.5 pg.ml-'.This rise in concentration of vasopressin in amniotic fluid was sustained for at least 24 h and levels at that time were highly correlated with peak plasma concentrations (r = 0.83, P < 0.001).Intravenous infusion of vasopressin into the fetus was accompanied by an equally significant ( P < 0.02) and sustained increase of vasopressin in amniotic fluid. After intraamniotic injection of vasopressin, levels remained increased for at least 24 h.In the third trimester of ovine gestation amniotic fluid vasopressin concentration was a reliable indicator of prior fetal hypoxia. Parallel amounts of antidiuretic activity measured by bioassay and vasopressin by radioimmunoassay confirmed the presence of active hormone in amniotic fluid. Hypoxia alone was not a stimulus to passage of meconium and increased concentrations of vasopressin in fetal plasma were not associated with expulsion of meconium in utero. Despite elevated concentrations of vasopressin in amniotic fluid, no associated changes in intra-uterine pressure were discerned.Evidence from a detailed review of long-term follow-up of infants by Paneth and Stark (19), supports the conclusion that asphyxia as indicated by clinical markers during the process of birth accounts for a smaller proportion of cerebral palsy and severe mental retardation than had been suspected. A major part of this discrepancy could be the result of asphyxia1 episodes occurring before the onset of labor. These episodes may not be reflected in the condition of the infant at birth, but could still lead to severe handicapped conditions. We have therefore endeavored to develop techniques for antipartum fetal surveillance.Data from both clinical and human studies have shown that hypoxic stress is a potent stimulus for the release of vasopressin as well as several other peptide hormones from the fetal pituitary.In the present study we investigated the potential utility of the measurement of vasopressin concentration in the amniotic flu...

Effect of Arginine Vasopressin and Parathyroid Hormone‐related Protein on Renal Function in the Ovine Foetus

“…Many stimuli cause the release of AVP in the foetus: hypoxia (Rurak 1978;Stark et al 1979;Robillard et al 1981;Stark et al 1984), haemorrhage (Rose et al 1978;Rurak 1979), umbilical cord constriction (Daniel et al 1978) and increased plasma osmolality (Weitzman et al 1978;Siege1 et al 1980;Bennett & Rose 1989). Fetal hypotonicity, induced by the infusion of hypotonic saline to the ewe, is claimed to cause a small, but significant, decrease in fetal plasma AVP (Leake et al 1987).…”

The unique endocrine milieu of the fetus.

“…Perhaps the major potential stress for the fetus is hypoxia, and recent evidence indicates that the VP response to hypoxia is greatly augmented relative to the maternal response and relative to the fetal VP responses to osmolar stimuli (44)(45)(46). Elevated plasma VP concentrations also have been observed in human cord blood in association with intrauterine bradycardia and meconium passage (47), and correlations with other parameters suggestive ofhypoxia, including low pH and acidosis, have been reported (45). There is evidence that the vasopressor action of VP may be important in the maintenance of fetal circulatory homeostasis during hemorrhage and a similar role is possible for hypoxia (48).…”