There is significant perinatal morbidity and mortality associated with polyhydramnios and oligohydramnios because currently available therapies have limited efficacy. Yet, effective reduction of amniotic fluid (AF) volume and prevention of preterm delivery in pregnancies with polyhydramnios reduces neonatal morbidity and mortality. Similarly, increasing AF volume in laboring patients with reduced AF improves fetal outcome. The proposed studies will ask a number of questions about strategies to alter AF volume which potentially may be applied clinically for treatment of poly- or oligohydramnios. Our previous studies provided valuable insight into physiologic mechanisms of maternal-fetal-AF water and electrolyte exchange. Whereas AF is maintained by a balance of sites of fluid production and resorption, fetal urine flow is the single most important site influencing AF volume. Thus, alterations in urine flow and perhaps other fluid exchange sites may be utilized to modulate AF volume. We have developed two novel, ovine experimental models to alter AF volume, each utilizing the selective arginine vasopressin (AVP) antidiuretic agonist [desamino, D-Arg8]-AVP (dDAVP). Preliminary ovine and human studies have supported the potential clinical utility of these interventions. Firstly, we hypothesize that intraamniotic dDAVP administration will result in increased fetal plasma dDAVP levels, reduced fetal urine and lung fluid production and decreased AF volume. Intraamniotic dDAVP represents a promising treatment for patients with polyhydramnios. Secondly, as the antithesis of dehydration we hypothesize that maternal intravenous dDAVP will induce maternal and fetal plasma hypo-osmolality, marked increases in fetal urine flow rates, and expansion of AF volume. Thus maternal dDAVP represents a potential therapy for patients with oligohydramnios. We will explore acute and chronic effects of intraamniotic (fetal) dDAVP and maternal dDAVP-induced hypo-osmolality. Physiologic assessments will focus on measurements of fetal fluid exchange (urine flow, lung liquid, swallowing, placenta diffusion permeabilities) and fetal plasma and AF volume and composition in normal pregnancies and models of poly- and oligohydramnios. We also will measure the effects of elevated dDAVP on fetal and maternal renal AVP receptor populations and on other fluid regulatory hormones (atrial natriuretic factor, renin- angiotensin). The goal of this project is to identify safe and effective treatments which can reliably alter AF volume in cases of poly- or oligohydramnios.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
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Human Embryology and Development Subcommittee 1 (HED)
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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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