Human maternal and fetal response to graded exercise

Six healthy active women in the third trimester of pregnancy participated in a graded exercise protocol to levels of exertion perceived to be equivalent to that of their usual exercise regimen. Fetal heart rate response (FHR) was documented by ultrasound transducer and confirmed (n = 1) by ultrasonic visualization. Resting maternal O2 consumption was 277 +/- 50 (SD) ml/min and rose to 1,132 +/- 202 ml/min at a mean final exercise intensity of 79 +/- 9 W after 12.8 +/- 1.7 min on a cycle ergometer. There was no significant change in maternal serum insulin, growth hormone, glucose, or pH values. Maternal leukocyte count, hemoglobin, and venous lactate levels rose significantly during the exercise (P less than 0.05). FHR prior to exercise was 142 +/- 4 beats/min and decreased to 84 +/- 34 beats/min during exercise. The decrease in FHR was documented within 1 min of initiating exercise in all cases. During exercise, fetal movements were not accompanied by FHR accelerations. Within 1 min following the cessation of exercise, FHR rose to 143 +/- 8 beats/min and fetal movements were accompanied by FHR accelerations. Since the recovery of FHR occurred immediately after cessation of maternal exercise, this level of maternal exercise does not appear to be harmful to the fetus.     

Fetal lung metabolism: Response to maternal fasting

• 1.1. Fetal lung metabolic response to maternal fasting late in gestation was investigated.
• 2.2. Maternal fasting 4 days before term was associated with low fetal plasma glucose and insulin levels but increased levels of fetal plasma glucagon, glycerol, lactate and fatty acids.
• 3.3. Fetuses from fasted mothers showed a significant decrease in body weight (30%), lung weight (30%) and lung glycogen (46%), but no change in lung protein, phospholipid or total lung DNA, suggesting that lung size is affected more than maturation.
• 4.4. Fetal lung slices incubated in vitro showed that lactate oxidation to CO₂ equalled that of glucose in control fetal lungs and was unaffected by maternal fasting, while glucose oxidation was depressed (23%).
• 5.5. Maternal fasting significantly decreased in vitro incorporation of [U-¹⁴C]-glucose, [U-¹⁴C]lactate and [1-¹⁴C]palmitate into lung phospholipids.
• 6.6. Fetal lungs from fasted mothers showed increased conversion of lactate to glucose, indicating gluconeogenic potential by fetal lung.
• 7.7. These studies show that plasma lactate serves as an important energy fuel and substrate for lipid synthesis for the fetal lung, and maternal fasting markedly alters fetal lung metabolism.

     

Fetal diuretic responses to maternal hyponatremia: contribution of placental sodium gradient.

Maternal hyponatremia induces fetal hyponatremia and increased fetal urine flow. We sought to examine the relative contributions of the placental Na(+) gradient vs. the absolute decrease in fetal plasma Na(+) in the fetal diuretic response to hyponatremia. Seven ewes with singleton fetuses (130 +/- 2 days) were prepared. Ewes received intravenous 1-desamino-8-D-arginine vasopressin (20 microg) and warm tap water (2 liters). Maternal plasma Na(+) was decreased to achieve two levels of maternal hyponatremia. Maternal and fetal blood volume were measured with radiolabeled red blood cells. In response to the first decrease in maternal plasma Na(+), fetal plasma Na(+) did not change initially. Subsequently, fetal plasma Na(+) decreased, normalizing the gradient. The second decrease in maternal plasma Na(+) similarly induced a reduced and normalized placental gradient at lower fetal plasma Na(+) values. Fetal urine flow increased in direct proportion to the degree of fetal hyponatremia (13, 38, 63, 100%, respectively). Maternal, although not fetal, blood volume significantly increased in response to hyponatremia. These results suggest that chronic fetal hyponatremia will result in a persistent diuresis, despite placental equilibration.     

Aldosterone response to angiotensin II during hypoxemia

Exercise in humans causes increases in plasma renin activity (PRA) and plasma aldosterone concentrations (PAC) except when performed at high altitude or while the subjects breathe hypoxic gas. Under those conditions, PRA increases with exercise but PAC does not. We speculated that the PAC suppression during hypoxemic exercise was due to hypoxemia-induced release of a circulating inhibitor of angiotensin II-mediated aldosterone secretion. To test this hypothesis, we measured the PAC response to graded infusions of angiotensin II during hypoxemia and normoxemia. Eight normal volunteers were given increasing doses of angiotensin II (first 2 ng X kg-1 X min-1 and then 4, 8, and finally 12 ng X kg-1 X min-1, each for 20-min periods) on 2 separate days, once while breathing room air and the other day while breathing hypoxic gas adjusted to maintain the subjects' hemoglobin saturation at 90%. The PAC response to different doses of angiotensin II did not significantly differ during hypoxemia from normoxemia. We conclude that our model of hypoxemia does not cause release of an inhibitor of angiotensin II-mediated aldosterone release.     

Metabolic response to starvation in late pregnant rats. II. Fetal response

Effect of prolonged maternal fasting on the fetal liver and heart glycogen and triglyceride content and on concentration of glucose, urea, uric acid and alpha amino-nitrogen in the amniotic fluid has been studied in rats. The animals were divided into four groups: fed (control), fasted for one day (from 20 to 21 day of pregnancy), fasted for two days (from 19 to 21 day) and fasted for three days (from 18 to 21 day). Maternal fasting for two and three days resulted in reduction in fetal growth. The fetal liver glycogen content was reduced already after one day of fasting, stabilized after two days and then further decreased after three days. The fetal heart glycogen content was reduced only after three days of fasting. The fetal liver triglyceride content increased gradually during the first two days of fasting and then stabilized. The content of triglycerides in the heart was elevated after two and three days of food deprivation. The amniotic fluid glucose concentration decreased after one day of fasting and then stabilized. Fasting did not effect the concentration of the nitrogenous compounds in the amniotic fluid. It is concluded that maternal fasting affects markedly metabolism of energy substrates stored in the fetal liver and the heart and the composition of the amniotic fluid.     

Fetal breathing and cardiovascular responses to graded methemoglobinemia in sheep

Graded methemoglobinemia (MetHb) was produced in unanesthetized fetal sheep to determine the effects on brain oxygenation. MetHb was induced by infusing methemoglobin-containing erythrocytes in exchange for fetal blood. During the hour after MetHb was established, fetal methemoglobin concentrations averaged 1.23 +/- 0.12 (mild MetHb), 1.71 +/- 0.13 (moderate MetHb), and 2.27 +/- 0.17 g/dl (severe MetHb). MetHb reduced mean arterial O2 content by approximately 19 (mild MetHb), 29 (moderate MetHb), and 39% (severe MetHb). The average preductal arterial PO2 fell by 1.6 (-7%), 2.8 (-11%), and 4.0 Torr (-16%) for mild, moderate, and severe MetHb, respectively. Fetal heart rate increased significantly during mild and moderate MetHb, and mean arterial pressure fell slightly during moderate and severe MetHb. The incidences of fetal breathing and eye movements were reduced in a dose-dependent manner when the calculated brain end-capillary PO2 was less than 14 Torr. We conclude that: 1) the effective capillary PO2 in the fetal brain can be significantly reduced by increasing the distance between non-methemoglobin-laden erythrocytes in capillaries and 2) hypoxic inhibition of fetal breathing probably arises from discrete areas of the brain having a PO2 less than 3 Torr.     

Fetal blood calcium response to maternal hypercalcemia induced in the cow by calcium infusion or by solanum glaucophyllum ingestion.

Bovine fetuses chronically catheterized in utero during the last month of gestation were used to study the relationships of maternal-fetal calcium and phosphate levels. Calcium infusion into the pregnant cows induced a rapid and marked increase in maternal plasma calcium but no change in fetal plasma calcium concentrations. Oral administration of Solanum glaucophyllum to the mother for 6 days raised the plasma concentrations of calcium and phosphate in both the mother and the fetus.     

Fetal sheep adrenal blood flow responses to hypoxemia after splanchnicotomy using fluorescent microspheres

Buchwalder, Lynn F., Michelle Lin, Thomas J. McDonald, andPeter W. Nathanielsz. Fetal sheep adrenal blood flow responses tohypoxemia after splanchnicotomy using fluorescent microspheres. J. Appl. Physiol. 84(1): 82-89, 1998.Adrenal gland blood flow (ABF) increases during hypoxemia infetal sheep, but regulation of ABF is poorly understood. The purpose ofthis study was to determine the effects of splanchnic nerve section onfetal ABF responses to hypoxemia using the fluorescent microsphere (FM) technique. At 125 days of gestation, 14 unanesthetized fetal sheep [bilateral splanchnicotomy (Splx,n = 6) and control (Cont,n = 8)] were injectedwith FM before and at 60 min ofN₂-induced hypoxemia (~40%decrease in fetal arterial PO₂).Adrenal tissue and reference blood samples were digested and filtered, and FM dye was extracted for spectrometer analysis. Baseline whole, medullary, and cortical ABF for the Cont group were similar to published values using radioactive microspheres and did not differ fromSplx values. Hypoxemia increased whole, medullary, and cortical ABF(mean ± SE) from baseline for the Cont group by 281 ± 35, 258 ± 31, and 496 ± 81% (P < 0.05). The increase for the Splx group was attenuated compared with theCont group (P < 0.05) for whole andmedullary ABF (139 ± 27 and 43 ± 27%) but not cortical ABF(326 ± 91%). We conclude that1) the FM technique is valid formeasuring fetal ABF and 2) in fetalsheep the splanchnic nerve is not necessary to maintain basal ABF butplays an important role in regulating the hypoxemia-induced increase inABF through the medullary, but not cortical, ABF response.

     

Fetal and maternal contributions to risk of pre-eclampsia: population based study

Objective: To use familial patterns of recurrence of pre-eclampsia to investigate whether paternal genes expressed in the fetus contribute to the mother’s risk of pre-eclampsia and whether mother’s susceptibility to pre-eclampsia is related to maternal inheritance by mitochondrial DNA. Design: Linked data on pregnancies of different women who had children with the same father, and subsequently linked data on pregnancies of half sisters who either had same mother and different fathers or had same father and different mothers. Setting: Population based data from the Medical Birth Registry of Norway covering all births since 1967 (about 1.7 million) and the Norwegian Central Population Register. Main outcome measures: Relative risk of pre-eclampsia after a previous pre-eclamptic pregnancy in the family. Relative risks approximated by odds ratios. Results: If a woman becomes pregnant by a man who has already fathered a pre-eclamptic pregnancy in a different woman her risk of developing pre-eclampsia is 1.8 (95% confidence interval 1.2 to 2.6). If the woman has a half sister who had pre-eclampsia and with whom she shares the same mother but different fathers the risk of pre-eclampsia is 1.6 (0.9 to2.6). If the two sisters have the same father but different mothers the risk is 1.8 (1.01 to 2.9). Conclusions: Both the mother and the fetus contribute to the risk of pre-eclampsia, the contribution of the fetus being affected by paternal genes. Mitochondrial genes, which are transmitted by mothers, do not seem to contribute to the risk.

Key messages

• Paternal genes in the fetus may contribute substantially to a pregnant woman’s risk of pre-eclampsia
• The role of the fetus may be as important as that of the mother
• Purely maternal inheritance (specifically by mitochondrial DNA) is probably not involved in pre-eclampsia
• Search for specific genes that predispose for pre-eclampsia should include the fetus as well as the mother

     

Fetal breathing and sleep state responses to graded carboxyhemoglobinemia in sheep

To investigate CO effects on brain oxygenation, graded carboxyhemoglobinemia (HbCO) was produced in nine unanesthetized fetal sheep by infusing CO-laden erythrocytes in exchange for fetal blood. For the 1st h after this procedure, the mean fetal carboxyhemoglobin levels were 16.5 +/- 0.4% [control (C) = 1.4 +/- 0.4%] for mild HbCO, 22.7 +/- 0.6% (C = 1.8 +/- 0.4%) for moderate HbCO, and 27.8 +/- 0.5% (C = 2.1 +/- 0.7%) for severe HbCO. This induction of HbCO significantly reduced mean preductal arterial PO2 values to 4.3 Torr below control for mild HbCO, 4.6 Torr below control for moderate HbCO, and 5.5 Torr below control for severe HbCO. The respective arterial O2 contents were decreased by 17, 21, and 29%. Mean arterial pH was lowered only during severe HbCO, and arterial PCO2 values were unchanged. HbCO produced a fetal tachycardia. Mean arterial blood pressure was only increased during severe HbCO. The incidences of rapid eye movements and breathing activity were decreased by HbCO in a dose-dependent manner. When related to calculated brain tissue PO2, these decreases were similar to those measured during hypoxic hypoxia and anemia, suggesting that carboxyhemoglobin effects result solely from diminished oxygenation. It is concluded that 1) the peripheral arterial chemoreceptors in the fetus apparently have little effect on hypoxic inhibition of breathing and 2) the carboxyhemoglobin concentrations required to inhibit fetal breathing are greater than those likely to be encountered clinically.     

Fetal and maternal thyroid hormones

It is well known that insufficient production of thyroid hormones during the fetal and neonatal period of development may result in permanent brain damage unless treatment with thyroid hormone is instituted very soon after birth. But congenital hypothyroidism is not the only situation in which brain damage may be related to insufficient thyroid function. Cretinism is the most severe manifestation of iodine deficiency disorders found in areas where iodine intake is greatly reduced. Some of the manifestations of cretinism suggest that the insult to the developing brain starts earlier than in the case of congenital hypothyroidism. Hypothyroxinemia of mothers with adequate iodine intake may also leave permanent, though less severe, mental retardation. For these reasons the possible role of maternal transfer of thyroid hormones during early fetal development have been reinvestigated, using the rat to obtain various experimental models. It has been shown that thyroid hormones are found in embryonic tissues before onset of fetal thyroid function and that thyroidectomy of the mother results in delayed development of the concepta. The concentrations of T4 and T3 in embryonic tissues from thyroidectomized dams were undetectable before the onset of fetal thyroid function, and still reduced in some tissues near term, despite the onset of fetal thyroid function. Treatment of control and thyroidectomized dams with methyl-mercaptoimidazole to block fetal thyroid function reduced thyroid hormone concentrations in fetal tissues near term, but this decrease could be partially avoided by infusion of physiological doses of thyroxine to the mothers. Iodine deficiency of the mothers resulted in thyroid hormone deficiency of the developing embryo, which was very marked until term in all tissues including the brain. The results strongly support a role of maternal thyroid hormones in fetal thyroid hormone economy both before and after the onset of the fetal thyroid function, at least in the rat. They also support a role of the hypothyroxinemia of iodine-deficient mothers in initiating the brain damage of the endemic cretin, a damage which would not be corrected once the fetal thyroid becomes active, as iodine-deficiency of the fetus would impair adequate production of hormones by its own thyroid, and maternal transfer would continue to be low.     

Fetal infection after maternal reinfection with rubella: criteria for defining reinfection.

Five cases of asymptomatic maternal reinfection with rubella are described that occurred in England and Wales during 1985-8 and resulted in intrauterine infection. The criteria for diagnosing reinfection are described. In four cases the rubella contact was with the woman''s own children. Two women had therapeutic abortions, rubella virus being recovered from the products of conception, and three were delivered of infants with congenitally acquired disease. Though the risks associated with maternal reinfection with rubella are very small and being measured in a prospective study, it is hoped that the recently introduced augmented programme of rubella vaccination will reduce rubella in the community and therefore this small risk still further.     

Prolonged hypobaric hypoxemia attenuates vasopressin secretion and renal response to osmostimulation in men.

Effects of hypobaric hypoxemia on endocrine and renal parameters of body fluid homeostasis were investigated in eight normal men during a sojourn of 8 days at an altitude of 4,559 m. Endocrine and renal responses to an osmotic stimulus (5% hypertonic saline, 3.6 ml/kg over 1 h) were investigated at sea level and on day 6 at altitude. Several days of hypobaric hypoxemia reduced body weight (-2.1 +/- 0.4 kg), increased plasma osmolality (+5.3 +/- 1.4 mosmol/kgH(2)O), elevated blood pressure (+12 +/- 1 mmHg), reduced creatinine clearance (122 +/- 6 to 96 +/- 10 ml/min), inhibited the renin system (19.5 +/- 2.0 to 10.9 +/- 0.9 mU/l) and plasma vasopressin (1.14 +/- 0.16 to 0.38 +/- 0.06 pg/ml), and doubled circulating levels of norepinephrine (103 +/- 16 to 191 +/- 35 pg/ml) and endothelin-1 (3.0 +/- 0.2 to 6.3 +/- 0.6 pg/ml), whereas urodilatin excretion rate decreased from day 2 (all changes P < 0.05 compared with sea level). Plasma arginine vasopressin response and the antidiuretic response to hypertonic saline loading were unchanged, but the natriuretic response was attenuated. In conclusion, chronic hypobaric hypoxemia 1) elevates the set point of plasma osmolality-to-plasma vasopressin relationship, possibly because of concurrent hypertension, thereby causing hypovolemia and hyperosmolality, and 2) blunts the natriuretic response to hypertonic volume expansion, possibly because of elevated circulating levels of norepinephrine and endothelin, reduced urodilatin synthesis, or attenuated inhibition of the renin system.     

Fetal monitoring during maternal cardiac surgery with cardiopulmonary bypass.

Fetal cardiac activity was monitored with an external ultrasound transducer in two patients with clinical class III heart disease due to severe mitral stenosis complicated by pulmonary hypertension, undergoing open heart surgery with cardiopulmonary bypass in the 2nd trimester of pregnancy. Fetal distress was detected in one patient, who had mitral valvuloplasty, and was corrected by increasing the rate of blood flow, and the other patient had a mitral valve replacement but no fetal distress was noted. The postoperative course of both mothers and fetuses was uneventful.     

Fetal functional capabilities in response to maternal hypertonicity associated with altered central and peripheral angiotensinogen mRNA in rats

Although a number of studies have shown neural, hormonal, and behavioral capabilities in the control of body fluid regulation under conditions of dehydration in adults, limited information is available on the development of fetal functional abilities in response to osmotic challenge in rats. This study was performed to investigate the influence of maternal hypertonicity on fetal osmoregulatory capabilities at late gestational time in rats. Maternal and fetal plasma osmolality and blood sodium levels were determined and compared at continuous time points from 0.5 to 9h following maternal injection of hypertonic NaCl. Subcutaneous administration of hypertonic saline evoked a rise in plasma osmolality and sodium concentrations in maternal rats and fetuses associated with an up-regulation in angiotensinogen gene mRNA in the fetal liver and down-regulation of the same gene in the fetal brain. The increased levels of fetal blood osmolality and sodium were less than that in their mothers, and the fetus took less time to balance the enhanced osmolality and sodium concentrations. The results suggest that there may exist additional mechanisms in utero at near-term in protecting fetuses from hypertonic challenge. In addition, molecular results in the present study provide new data on fetal angiotensinogen gene expressed differently in the liver and brain under the same condition of prenatal salt loading, indicating osmotic signals of intracellular dehydration related to an acute increase in angiotensinogen mRNA in the fetal liver, and subsequent decrease in angiotensinogen mRNA levels in the fetal brain.