Effects of prolonged hypoxemia on fetal renal function and amniotic fluid volume in sheep

doi:10.1016/S0002-9378(97)70492-7

American Journal of Obstetrics and Gynecology

Volume 176, Issue 2, February 1997, Pages 320-326

https://doi.org/10.1016/S0002-9378(97)70492-7 Get rights and content

Abstract

OBJECTIVE: Our purpose was to determine the effects of prolonged hypoxemia on fetal renal function and amniotic fluid volume and composition.

STUDY DESIGN: Twelve pregnant ewes underwent surgery at 115 ± 2 days after mating (term ~147 days) for the implantation of fetal vascular, bladder, and amniotic sac catheters. At 125 ± 1 days seven fetuses were studied during 6 days of hypoxemia and five control fetuses were studied over six days of normoxemia. Index values of fetal renal function and amniotic fluid volume were measured.

RESULTS: During hypoxemia fetal Sao₂ and Pao₂ were reduced from 60.9% ± 1.6% and 21.9 ± 0.6 mm Hg to 29.6% ± 3.8% and 14.9 ± 0.8 mm Hg, respectively. Fetal hypoxemia was associated with a transient acidemia (arterial pH 7.29 ± 0.02) at 4 hours. There were no sustained alterations in fetal urine production (9.5 ± 0.8 ml/hr/kg) or glomerular filtration rate (1.3 ± 0.1 ml/min/kg) during hypoxemia. In control fetuses the amniotic fluid volume increased over 7 days, from 717 ± 169 ml to 1031 ± 147 ml, whereas in the hypoxemic fetuses it did not change (741 ± 68 ml) over the same period.

CONCLUSION: During prolonged fetal hypoxemia in the absence of acidemia, fetal urine production is maintained, whereas the normal gestational increase in amniotic fluid volume is prevented, raising the possibility that intramembranous reabsorption of amniotic fluid is increased by hypoxemia.(Am J Obstet Gynecol 1997;176:320-60.)

Section snippets

Surgery

At 115 ± 2 days after mating (term 145 to 147 days) anesthesia was induced in 12 (10 singleton- and 2 twin-bearing) pregnant ewes with sodium thiopentobarbital (1 gm intravenously) and was maintained by 1.5% to 2.0% halothane in oxygen and nitrous oxide. Under aseptic conditions the fetus was exposed by incisions in the maternal abdominal wall and uterus.⁷ A blunt-ended catheter with side ports was inserted and tied into the fetal bladder through a small incision to measure urine production and

Results

The body weights of treated fetuses (3.15 ± 0.12 kg) at the postmortem examination were not different from those of control fetuses (3.25 ± 0.19 kg).

Comment

Ours is the first study to monitor amniotic fluid volume and fetal renal function during a prolonged period (6 days) of fetal hypoxemia. We observed that there were no sustained alterations in fetal urine production, glomerular filtration rate, or urinary osmolality throughout the 6-day period of hypoxemia, whereas renal Na⁺ reabsorption was inhibited and the normal gestational age–related increase in amniotic fluid volume was abolished. The reason for the decrease in amniotic fluid volume

Acknowledgements

We thank Alex Satragno for his excellent surgical assistance and Professor G.D. Thorburn (deceased) for his support.

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Blood flow in fetal renal arteries in severe preeclamptic and healthy normotensive pregnant women
2011, Progresos de Obstetricia y Ginecologia
Comparar el flujo sanguíneo de las arterias renales fetales en preeclámpticas graves y embarazadas normotensas sanas.
La muestra fue de 30 preeclámpticas graves (grupo A) y 30 embarazadas normotensas sanas (grupo B) con embarazos simples de más de 30 semanas. Se midieron los índices de pulsatilidad y resistencia de las arterias uterinas, umbilical, cerebral media fetal y renal fetal.
No se encontraron diferencias estadísticamente significativas en la edad materna, la edad gestacional y el peso de los recién nacidos (p = NS). Las pacientes del grupo A presentaron valores significativamente más altos del índice de pulsatilidad y resistencia de las arterias uterinas y la umbilical, con valores más bajos para ambas mediciones de la arteria cerebral media fetal que las embarazadas del grupo B (p = 0,0001). Las preeclámpticas graves presentaron valores del índice de pulsatilidad y resistencia de la arteria renal fetal significativamente más altos comparados con las pacientes del grupo B (p = 0,0001). El índice de pulsatilidad de la arteria renal fetal presentó una correlación significativa con el índice de pulsatilidad de la arteria uterina (p = 0,011) y de la arteria cerebral media fetal (p < 0,007). El índice de resistencia de la arteria renal fetal presentó una correlación con el índice de resistencia de los tres vasos (p < 0,05).
Las preeclámpticas graves tienen alteraciones del flujo sanguíneo de las arterias renales fetales al compararlo con las embarazadas normotensas sanas.
To compare the blood flow in fetal renal arteries in severe preeclamptic and healthy normotensive pregnant women.
The sample consisted of 30 women with severe preeclampsia (group A) and 30 healthy normotensive pregnant women (group B) with single pregnancies of more than 30 weeks. The pulsatility and resistance indexes of the uterine, umbilical, fetal middle cerebral and fetal renal arteries were measured.
There were no significant differences in maternal age, gestational age or newborn weight (p = ns). Pulsatility and resistance index values in the uterine and umbilical arteries were significantly higher and both measurements for the fetal middle cerebral artery were significantly lower in group A than in group B (p = 0.0001). Pulsatility and resistance index values in the fetal renal artery were significantly higher in group A than in group B (p = 0.0001). The fetal renal artery pulsatility index was significantly correlated with the pulsatility index of the uterine artery (p = 0.011) and the fetal middle cerebral artery (p < 0.007). The fetal renal artery resistance index was correlated with the resistance index of the three vessels (p < 0.05).
Women with severe preeclampsia show blood flow alterations in the fetal renal arteries compared with healthy normotensive pregnant women.
Nontraditional Sonographic Pearls in Estimating Gestational Age
2008, Seminars in Perinatology
Citation Excerpt :
Oligohydramnios in the setting of IUGR has historically been attributed to fetal shunting of blood away from the kidneys, thereby leading to decreased fetal urine production.42 However, this is not supported by an animal model (ewe) of induced hypoxemia,43,44 suggesting a possible alternative of decreased intramembranous flow as the cause of oligohydramnios.42 Although intrauterine growth restriction is typically suspected when the estimated fetal weight (by traditional biometry) falls below the 10th percentile, in the setting of oligohydramnios, IUGR and fetal compromise may also be present at higher estimated weight measurements.
Accurate gestational dating is one of the most important assessments obstetrical providers make in pregnancy, given that all of the various management strategies are dependent on knowing where the patient is in gestation. In addition to traditional biometry, ancillary biometric and nonbiometric measurements can help narrow the biologic variability between fetuses. Moreover, one can employ these nontraditional measurements both in late gestation to assist in determining appropriate gestational age and fetal lung maturity, and in other specific clinical situations—such as oligohydramnios, in which compression of the fetal head and abdomen can lead to difficulty in obtaining an accurate biparietal diameter and abdominal circumference. This chapter focuses on nontraditional fetal ultrasound measurements, including the transverse cerebellar diameter, fetal foot length, ratios of biometric and nonbiometric measurements, epiphyseal ossification centers, amniotic fluid volume, placental grading, and other miscellaneous markers in the context of evaluating a fetus with possible intrauterine growth restriction.
Amniotic fluid and fetal urinary responses to severe placental insufficiency in sheep
2002, American journal of obstetrics and gynecology
Citation Excerpt :
Under normal conditions, fetal urine production is a major determinant of amniotic fluid volume. Acute (3 hours), maternally induced fetal hypoxemia,1324 to 48 hours of fetal hypoxemia induced by restriction of uteroplacental blood flow,14and fetal hypoxemia for up to 6 days15are not associated with a reduction in fetal urine production. Further, fetal urine production is increased in response to prolonged maternally induced hypoxemia in the ovine fetus without altering amniotic fluid volume.16
Objective: Our purpose was to test the hypothesis that severe placental insufficiency leads to reductions in fetal urine production and amniotic fluid volume in late-gestation fetal sheep. Study Design: At 0.85 of gestation, chronically catheterized fetal sheep with ligated urachus were either embolized for 5 days by repeated injection of boluses of 15-μm microspheres into the common fetal umbilical artery until fetal arterial oxygen content was reduced by 50% (n = 6) or were infused with saline solution (n = 6). Amniotic fluid volume was measured daily before embolization by means of an indicator dilution technique and by drainage at autopsy. Fetal urine production, heart rate, and mean arterial blood pressure were measured continuously for 1 hour before embolization and 1 hour after embolization each day. Fetal arterial blood gases, oxygen content, electrolytes, and osmolality were also monitored. Results: Five days of placental insufficiency, which reduced fetal arterial oxygen content by 50% and arrested fetal growth, resulted in a reduced amniotic fluid volume without a reduction in fetal urine production. Compared with that of controls, amniotic fluid volume was reduced over the 5-day period by 547 ± 144 mL (−62%, P <.01). Amniotic fluid composition was also altered, with a significant increase in lactate and sodium concentrations and osmolality on days 4 to 5. On days 2 to 5, there was a progressive increase in amniotic fluid osmolality above that of controls, which paralleled the changes in amniotic fluid sodium concentration (P <.05). Fetuses became hypertensive on days 2 to 4 of embolization, although this response was attenuated by day 5. Conclusions: Chronic severe placental insufficiency caused a reduction in amniotic fluid volume not attributable to reduced fetal urine production. Changes in amniotic fluid composition induced by placental insufficiency suggest an excess intramembranous absorption of amniotic fluid water, in relation to solutes, into the fetal and maternal compartments, which may lead to the development of oligohydramnios. (Am J Obstet Gynecol 2002;186:1076-84)
Increased urinary flow without development of polyhydramnios in response to prolonged hypoxia in the ovine fetus
2001, American Journal of Obstetrics and Gynecology
Citation Excerpt :
Although we cannot rule out the possibility of a pressure-induced diuresis in this study because fetal arterial pressure was not measured, it is unlikely because fetal arterial pressure during 24 hours of nitrogen insufflation to the maternal ewe has been shown to be unchanged from baseline.13 The observed increase in fetal urinary output during 4 days of hypoxia is inconsistent with a recent report that fetal urinary production is unchanged during 6 days of hypoxia produced by reducing uterine blood flow with subsequent intratracheal nitrogen insufflation as needed to maintain the hypoxia.11 These observations suggest that the change in fetal urine production during fetal hypoxia depends on the method used to create the hypoxia.
Objective: In the ovine fetus subjected to 24 hours of hypoxia, urinary flow is normal within a few hours from the onset of hypoxia and there is a maintained inhibition of swallowing. We hypothesized that 4 days of fetal hypoxia would lead to polyhydramnios. Study Design: Five late-gestation fetal sheep were subjected to hypoxia for 4 days and 7 other late-gestation fetal sheep served as time control animals. Fetal hypoxia was produced on postsurgical days 5 through 9 by continuous intratracheal nitrogen insufflation to the ewe. On days 3, 5, 7, and 9 after surgery, amniotic fluid volume, fetal urinary flow rate, and the compositions of maternal and fetal blood, amniotic fluid, and fetal urine were measured. A 3-factor analysis of variance was used for statistical analysis. Results: During the period of experimental hypoxia the mean (±SE) fetal PaO₂ was 16.0 ± 0.6 mm Hg, versus 21.2 ± 0.7 mm Hg in control sheep (P <.001). Fetal hypoxia was associated with increased urinary flow on days 7 and 9, averaging 1410 ± 310 and 2101 ± 345 mL/d, respectively, versus 585 ± 92 and 699 ± 78 mL/d, respectively, in control animals (P <.001). Amniotic fluid volume was unchanged with time and averaged 960 ± 159 mL in hypoxic fetuses on postsurgical days 7 through 9 and 851 ± 130 mL in control animals (P =.60). Fetal blood lactate increased in the hypoxic animals, averaging 3.4 ± 2.1 mmol/L versus 1.6 ± 0.3 mmol/L in control animals (P =.02). Fetal urinary excretions of sodium, potassium, chloride, and lactate increased significantly during hypoxia, by 170% to 400%. Conclusion: Four days of nitrogen-induced hypoxia in the ovine fetus resulted in excess fetal urinary flow approximating 1000 mL/d greater than normal without the development of polyhydramnios. Because amniotic fluid volume did not change and hypoxia is a known inhibitor of fetal swallowing, we speculate that intramembranous absorption of amniotic water, electrolytes, and lactate increased. (Am J Obstet Gynecol 2001;184:1008-14.)
Relationship of amniotic fluid index and cord blood erythropoietin levels in small for and appropriate for gestational age fetuses
1999, Obstetrics and Gynecology
Objective: To determine whether low amniotic fluid index (AFI) reflects an increase in cord blood erythropoietin levels and is a marker of antenatal fetal hypoxia in small for gestational age (SGA) and appropriate for gestational age (AGA) fetuses in the third trimester.
Methods: Erythropoietin levels in cord blood were measured in 134 high-risk obstetric patients, including 40 with low AFI (7 cm or less) and 94 with normal AFI (greater than 7 cm), which were sampled at elective cesarean delivery of fetuses with a gestational age of 32 to 39 weeks. The infants were divided into the SGA and AGA groups based on birth weight. Partial correlations of AFI with cord blood erythropoietin levels were evaluated by Pearson correlation coefficient after logarithmic transformation of erythropoietin levels in each group.
Results: Cord blood erythropoietin levels in SGA fetuses with low AFI (n = 24) were significantly higher than those in SGA fetuses with normal fluid volume (n = 16) (171.6 ± 207.4 mIU/dL compared with 36.1 ± 24.1 mIU/dL, P < .001). Conversely, cord blood erythropoietin levels in AGA fetuses with low AFI (n = 16) were not significantly different than those in AGA fetuses with normal fluid volume (n = 78) (32.1 ± 18.7 mIU/dL compared with 29.5 ± 15.3 mIU/dL). A significant partial correlation between AFI and erythropoietin levels was demonstrated only within the SGA group (P < .001, r = −.67).
Conclusion: Low AFI could indicate the degree of antenatal fetal hypoxia in SGA fetuses. The impact of a reduced amniotic fluid volume on antenatal fetal condition might be less severe in AGA fetuses than in SGA fetuses.
Relationship between graded degrees of anemia and amniotic fluid volume in the ovine fetus
1999, American Journal of Obstetrics and Gynecology
Objective: Severe fetal anemia is associated with polyhydramnios in both human and ovine fetuses. This study examined the relationship between varying degrees of anemia and amniotic fluid volume in fetal sheep. Study Design: Eleven long-term catheterized ovine fetuses at 126 ± 1 days’ gestation (mean ± SE) were subjected to hemorrhage of 20 to 80 mL daily for 9 consecutive days to produce varying degrees of fetal anemia. Five additional animals served as time control animals. Statistical analysis was by least squares regression and 3-factor analysis of variance. Results: Amniotic fluid volume was 793 ± 147 mL and did not change with time in the control fetuses. In the fetuses that were subjected to hemorrhage the amniotic fluid volume changed little through the hematocrit range of 40% to 25%. As fetal hematocrit fell below approximately 25%, amniotic fluid volume began to increase. With greater degrees of anemia the amniotic fluid volume increased as an exponential function of hematocrit and approached 2000 mL excess fluid as hematocrit dropped to <15%. According to bivariate regression the increase in amniotic fluid volume was related to fetal hematocrit, PaO₂, and urinary flow rate as well as to plasma and amniotic fluid lactate concentrations. According to multivariate regression only fetal PO₂ and urinary flow rate were significantly related to the increase in amniotic fluid volume. Conclusions: Although mild anemia was not associated with increased amniotic fluid volume, moderate to severe fetal anemia was associated with an exponential rise in amniotic fluid volume. This rise may have been mediated by a hypoxemia-induced diuresis, by a diuresis related to a lactate-induced osmotic accumulation of fetal fluid, or by both mechanisms. (Am J Obstet Gynecol 1999;181:1552-9.)

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^☆: From the Fetal and Neonatal Research Unit, Department of Physiology, Monash University.

^☆☆: Supported in part by the National Health and Medical Research Council of Australia.

^★: Reprint requests: Megan L. Cock, BSc, Fetal and Neonatal Research Unit, Department of Physiology, Monash University, Melbourne, Victoria 3168, Australia.

^★★: 6/1/78405

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Effects of prolonged hypoxemia on fetal renal function and amniotic fluid volume in sheep☆,☆☆,★,★★

Abstract

Section snippets

Surgery

Results

Comment

Acknowledgements

Am J Obstet Gynecol

Lancet

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Normal amniotic fluid volume changes throughout pregnancy

Am J Obstet Gynecol

The association between oligohydramnios and intrauterine growth retardation

Obstet Gynecol

Second trimester oligohydramnios: a predictor of poor fetal outcome

Obstet Gynecol

Developmental aspects of the renal responses to hypoxemia in the lamb fetus

Circ Res

Oxygen, glucose and lactate uptake in the fetus and placenta during prolonged hypoxaemia

Am J Physiol

Endocrine responses of fetal sheep to prolonged hypoxemia with and without acidemia: relation to urine production

Am J Physiol

Collateral arterial blood supply to the pregnant uterus in the sheep

J Anat