Amniotic fluid (AF) is an essential accompaniment of normal pregnancy, necessary for fetal movement, growth and development. Oligohydramnios, or reduced AF volume, occurs in 8 to 38 percent of all pregnancies. The majority of oligohydramnios patients have no identifiable medical or antepartum complication and only 7 percent of cases have associated fetal malformations. However, oligohydramnios is often associated with conditions of chronic fetal stress, such as intrauterine growth retardation, preeclampsia and postterm pregnancy. These conditions, together with the direct effect of reduced AF volume, results in significant perinatal morbidity and mortality. Increasing AF volume in laboring patients with oligohydramnios improves fetal outcome, though this generally requires rupture of fetal membranes. However, our studies demonstrate that modulation of AF production (fetal urine flow) and AF resorption (fetal swallowing and intramembranous flow) may be utilized to increase AF volume in patients with intact membranes. We have developed a novel model to increase AF volume utilizing maternal administration of the arginine vasopressin (AVP) antidiuretic agonist [desamino, D-Arg8]-AVP (DDAVP). Our studies in the ovine model indicate that maternal hydration and DDAVP induces maternal and fetal plasma hyponatremia, marked increases in fetal urine flow, reduced fetal swallowing and expansion of AF volume. Our human studies have supported the clinical utility of these interventions. Despite these promising results, critical issues of efficacy and safety of DDAVP therapy for both the mother and fetus must be resolved prior to clinical use. Firstly, in studies of efficacy, we will determine the minimum level of maternal hyponatremia which induces and maintains fetal fluid responses, and examine the effects of alterations in placental osmolality gradients. Long term studies will examine the effects of hyponatremia on ovine AF volume, maternal plasma volume and umbilical and uterine blood flows in both normal and oligohydramnios ovine pregnancies. Secondly, in studies of fetal safety, we will determine if fetal brain edema and/or loss of brain electrolytes are induced by hyponatremia. As AVP has important fetal fluid and cardiovascular regulatory roles, we will determine the effect of hyponatremia on fetal osmotic and non- osmotic stimulated AVP secretion. Finally, as permanent imprinting of AVP synthesis and secretion regulatory systems may occur in response chronic tonicity alterations in newborn rats, we will examine the effects of chronic tonicity alterations on fetal AVP transcription and translation. Physiologic assessments will focus on measurements of fetal fluid exchange and fetal plasma and AF volume and composition. Endocrine and molecular assessments will include determination of fluid regulatory hormones and hypothalamic AVP mRNA and pituitary AVP contents, utilizing our newly developed ovine 130 bp cDNA probe and solution and in situ hybridization techniques. The goal of this project is to determine critical efficacy and fetal safety issues central to maternal DDAVP treatment, prior to widespread clinical use in human pregnancies with oligohydramnios.
| van den Wijngaard, Jeroen P H M; Ross, Michael G; van Gemert, Martin J C (2008) Thrombosis of anastomoses may affect the staging sequence of twin-twin transfusion syndrome. Phys Med Biol 53:N69-80 |
| Shengbiao Wang; Amidi, Fataneh; Shengli Yin et al. (2007) Cyclic adenosine monophosphate regulation of aquaporin gene expression in human amnion epithelia. Reprod Sci 14:234-40 |
| VAN DEN Wijngaard, Jeroen P H M; Ross, Michael G; VAN Gemert, Martin J C (2007) Twin-twin transfusion syndrome modeling. Ann N Y Acad Sci 1101:215-34 |
| van den Wijngaard, Jeroen P H M; Westerhof, Berend E; Ross, Michael G et al. (2007) A mathematical model of twin-twin transfusion syndrome with pulsatile arterial circulations. Am J Physiol Regul Integr Comp Physiol 292:R1519-31 |
| Ross, Michael G; Desai, Mina; Khorram, Omid et al. (2007) Gestational programming of offspring obesity: a potential contributor to Alzheimer's disease. Curr Alzheimer Res 4:213-7 |
| Wang, Shengbiao; Amidi, Fataneh; Beall, Marie et al. (2006) Aquaporin 3 expression in human fetal membranes and its up-regulation by cyclic adenosine monophosphate in amnion epithelial cell culture. J Soc Gynecol Investig 13:181-5 |
| Ross, Michael G; Desai, Mina; Guerra, Catalina et al. (2005) Prenatal programming of hypernatremia and hypertension in neonatal lambs. Am J Physiol Regul Integr Comp Physiol 288:R97-103 |
| van den Wijngaard, Jeroen P H M; Ross, Michael G; van der Sloot, Jos A P et al. (2005) Simulation of therapy in a model of a nonhydropic and hydropic recipient in twin-twin transfusion syndrome. Am J Obstet Gynecol 193:1972-80 |
| Ross, Michael G; Desai, Mina (2005) Gestational programming: population survival effects of drought and famine during pregnancy. Am J Physiol Regul Integr Comp Physiol 288:R25-33 |
| Beall, Marie H; Amidi, Fataneh; Gayle, Dave A et al. (2005) Placental and fetal membrane Nephrin and Neph1 gene expression: response to inflammation. J Soc Gynecol Investig 12:298-302 |
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