MATERNAL DEHYDRATION--FETAL/AMNIOTIC FLUID HOMEOSTASIS
Principal Investigator: MICHAEL GLENN ROSS
Affiliation: University of California
Abstract: 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.
Funding Period: 1989-04-01 - 2003-03-31
more information: NIH RePORT
- Prenatal programming of hypernatremia and hypertension in neonatal lambsMichael G Ross
Department of Obstetrics and Gynecology, University of California, Los Angeles, Harbor UCLA Medical Center, 1000 W Carson St, Box 3, Torrance, CA 90509, USA
Am J Physiol Regul Integr Comp Physiol 288:R97-103. 2005..In utero hypertonicity and perhaps maternal nutrient stress may program offspring osmoregulation and systemic arterial hypertension...
- Cyclic adenosine monophosphate regulation of aquaporin gene expression in human amnion epithelia- Shengbiao Wang
Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, Torrance, California90502, USA
Reprod Sci 14:234-40. 2007..Lack of effect of SP-cAMP, the protein kinase A activator, on AQP1, 8, and 9 mRNA expression suggests that cAMP upregulates human amnion AQP1, 8, and 9 mRNA expression via the protein kinase A independent pathway...
- Gestational programming of offspring obesity: a potential contributor to Alzheimer's diseaseMichael G Ross
Department of Obstetrics and Gynecology, Harbor UCLA Medical Center, Torrance, California 90502, USA
Curr Alzheimer Res 4:213-7. 2007..These findings suggest that potential risk factors for the development of Alzheimer's disease may be present as early as newborn life...
- Twin-twin transfusion syndrome modelingJeroen P H M van den Wijngaard
Laser Center and Department of Obstetrics and Gynecology, Academic Medical Center University of Amsterdam, The Netherlands
Ann N Y Acad Sci 1101:215-34. 2007..In the donor, vascular stiffness remains increased after laser, suggesting increased pulse wave velocities can be measured clinically...
- A mathematical model of twin-twin transfusion syndrome with pulsatile arterial circulationsJeroen P H M van den Wijngaard
Laser Center, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
Am J Physiol Regul Integr Comp Physiol 292:R1519-31. 2007....
- Aquaporin 3 expression in human fetal membranes and its up-regulation by cyclic adenosine monophosphate in amnion epithelial cell cultureShengbiao Wang
Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute, Harbor UCLA Medical Center, Torrance, California 90502, USA
J Soc Gynecol Investig 13:181-5. 2006....
- Simulation of therapy in a model of a nonhydropic and hydropic recipient in twin-twin transfusion syndromeJeroen P H M van den Wijngaard
Laser Center, Department of Obstetrics and Gynecology, Academic Medical Center University of Amsterdam, Amsterdam, The Netherlands
Am J Obstet Gynecol 193:1972-80. 2005..This study was undertaken to model the sequence of events that occurs after amnioreduction, laser therapy, and digoxin administration in twin-twin transfusion syndrome (TTTS) with and without a hydropic recipient twin...
- Cloning and cellular expression of aquaporin 9 in ovine fetal membranesShengbiao Wang
Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, Torrance, CA, USA
Am J Obstet Gynecol 193:841-8. 2005..As AF dynamics continued to be explored primarily in the ovine model, we sought to clone and characterize the expression of ovine AQP9 in fetal membranes...
- Placental and fetal membrane Nephrin and Neph1 gene expression: response to inflammationMarie H Beall
Department of Obstetrics and Gynecology, Harbor UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, California 90509, USA
J Soc Gynecol Investig 12:298-302. 2005..We sought to investigate whether nephrin and Neph1 were expressed in placenta and fetal membranes, and whether inflammation modified the expression...
- Protective effect of prenatal water restriction on offspring cardiovascular homeostasis in response to hemorrhageMina Desai
Dept of Obstetrics and Gynecology, LABioMed at Harbor UCLA Medical Center, 1124 West Carson St Box 446, RB 1 Bldg, Torrance, CA 90502, USA
Am J Physiol Heart Circ Physiol 288:H2659-65. 2005..Despite potential long-term adverse effects of systemic hypertension, these results suggest a protective effect of prenatal water restriction on offspring cardiovascular homeostasis during blood volume reduction...
- Gestational programming: population survival effects of drought and famine during pregnancyMichael G Ross
Department of Obstetrics and Gynecology, Harbor UCLA Medical Center, 1000 W Carson St, Box 3, Torrance, CA 90509, USA
Am J Physiol Regul Integr Comp Physiol 288:R25-33. 2005..Importantly, these results suggest that programming effects may be either potentiated or prevented by interventions during the neonatal period...
- Thrombosis of anastomoses may affect the staging sequence of twin-twin transfusion syndromeJeroen P H M van den Wijngaard
Laser Center, Academic Medical Center University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
Phys Med Biol 53:N69-80. 2008..These results may aid an improved knowledge of TTTS pathophysiology under conditions of a rapidly changing cardiovascular function, and contribute to the planning of optimal intervention under such circumstances...