Biomedical subjects
Publications and source records attributed to C H Rodeck.
Fetal plasma renin activity (PRA) was measured in 42 pregnancies. Compared to control fetuses, PRA was elevated in three of four hypoxemic fetuses, in two of five with hydrops and in two of five with uropathies. PRA did not change with transfusion in seven alloimmunized fetuses. This study demonstrates PRA in human fetuses and suggests that the renin-angiotensin system can respond to stimuli in fetal life.
A case of hydrops fetalis caused by massive fetomaternal hemorrhage was initially successfully treated by intrauterine intravascular transfusion. Unexplained intrauterine death occurred 2 weeks afterwards. The investigation of fetomaternal hemorrhage by fetal blood sampling and the management are discussed.
Transabdominal fetal blood sampling under ultrasonic guidance was performed at the intrahepatic vein on 214 occasions in 177 fetuses. In 72 cases, an intravascular transfusion was also attempted at the same site. In 91.1% of the samplings, more than 1 mL of pure fetal blood was obtained, and in 89.9% of transfusions, fetal hematocrit or platelet concentration was raised to a satisfactory level. Fetal bradycardia and intraperitoneal bleeding occurred in 2.3% of the cases. Among fetuses at low risk, there was only one intrauterine death, which occurred 3 weeks after the procedure, and one spontaneous abortion in a patient with twin pregnancy. In fetuses with Rh/Kell alloimmunization or perinatal alloimmune thrombocytopenia, the survival rate was 86%. Four liver enzymes were assayed in the blood of 13 fetuses that underwent transfusions at the intrahepatic vein and 13 controls in whom the site of sampling was the umbilical vein at the placental cord insertion. No differences were found between the groups at the subsequent transfusion 2-5 weeks later. The intrahepatic vein is an alternate site of sampling/transfusion when access is difficult or failure occurs at the placental cord insertion. This approach minimizes the risks of fetal blood loss, fetomaternal hemorrhage, arterial vasospasm, and cord tamponade.
Amniotic pressure was measured in 49 pregnancies with abnormal quantities of amniotic fluid. Among 17 with polyhydramnios, the pressure was always above the normal mean for gestation and exceeded the upper limit of normal in nine. In polyhydramnios, amniotic pressure correlated positively with the depth of the deepest pool (r = 0.65, P = .04) and negatively with fetal PO2 (r = -0.57, P = .03) and pH (r = -0.56, P = .04). Amniotic pressure was raised in all those with a deepest pool of greater than 15 cm, and was normal in all with a deepest pool less than 15 cm. Amniotic pressure fell significantly with drainage of amniotic fluid in those with raised pressure (mean 12.7 mmHg, 95% confidence interval 7.0-18.3; P = .002) but not in those with normal pressure (mean 0.3, 95% confidence interval -3.2 to +3.9; P = .82). Restoration of normal amniotic pressure in one pregnancy was accompanied by marked improvement in fetal acid-base status. Among 24 pregnancies with severe oligohydramnios, amniotic pressure was always below the normal mean, falling below the lower limit of normal in eight; whereas in another eight pregnancies with mild/moderate oligohydramnios, amniotic pressure was scattered evenly within the normal range. Amnioinfusion of 55-500 mL of normal saline in cases of severe oligohydramnios led to a significant rise in pressure (4.7 mmHg, 95% confidence interval 3.5-5.9; P less than .0001). We conclude that amniotic pressure is high in polyhydramnios and low in oligohydramnios. Pressure monitoring may be beneficial during amnioinfusion and therapeutic amniocentesis.
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A technique is described for measuring pressure within the amniotic cavity and within fetal vessels and/or body compartments. Two saline-filled catheters were connected at one end to needles inserted during indicated invasive procedures and at the other to silicon strain gauge transducers. In 36 pregnancies with normal liquor volume, stable intra-amniotic pressure (IAP, range 1-14 mmHg) increased with gestation (r = 0.48, p less than 0.01). In pregnancies complicated by severe oligohydramnios, IAP was less than or equal to 1 mm Hg and rose to normal levels with saline amnioinfusion. Raised IAP (range 17-26 mm Hg), found in pregnancies with gross polyhydramnios, fell with drainage of amniotic fluid. Subtraction manometry was used to determine supra-amniotic pressure within the intervillus space, umbilical vein, umbilical artery, abdominal and thoracic cavities, and the urinary tract in normal and/or pathological fetuses. Low intravesical and intrapelvicalyceal pressures (median 6.5, range 2-10 mm Hg) were noted in fetuses with obstructive uropathies. Intrauterine subtraction manometry appears to be a useful tool in the understanding of fetal pathophysiology and may be of clinical benefit in the therapeutic drainage and infusion of amniotic fluid and in the assessment of certain fetal disease states.
Primary hyperoxaluria type 1 (PH1) is caused by a deficiency of the hepatic peroxisomal enzyme alanine: glyoxylate aminotransferase (AGT, EC 2.6.1.44) (Danpure and Jennings, FEBS Lett., 201, 20-24, 1986). The activity of AGT has been measured in fetal livers of gestational age 14-21 weeks. Activity increases up to 17 weeks and then levels off between 17 and 21 weeks. At this time, the mean AGT activity is about 30 per cent of the mean normal postnatal level. As in adult liver, the AGT enzyme activity and the AGT immunoreactive protein are peroxisomal. Prenatal diagnosis has been performed by measuring AGT enzyme activity and immunoreactive AGT protein on liver biopsies from two fetuses at risk for primary hyperoxaluria type 1. One was unaffected and one was affected.
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Intraperitoneal and umbilical vein pressure readings were obtained during intrauterine transfusion in patients with Rh alloimmunization. In 15 nonacidotic fetuses, mean umbilical vein pressure before transfusion (4.5 mm Hg, SD = 2.3) increased by 4.6 mm Hg (delta umbilical vein pressure confidence intervals +2.8 to +6.4; p less than 0.0001) with transfusion. delta Umbilical vein pressure correlated positively with the increase in hematocrit level (r = 0.55; p less than 0.05) and negatively with gestational age (r = -0.58; p less than 0.05). Basal umbilical vein pressure was raised in the only acidotic fetus, whereas delta umbilical vein pressure was 0. Intraperitoneal pressure was recorded in 11 fetuses before and after transfusion, five of which were associated with fetal heart rate changes or preexisting ascites. Basal intraperitoneal pressure (2.5 mm Hg, confidence intervals 1.4 to 3.6) was significantly lower than basal umbilical vein pressure (confidence intervals, 3.2 to 5.8; p less than 0.02). In uncomplicated intraperitoneal transfusions, intraperitoneal pressure rose significantly (delta intraperitoneal pressure = +5.8; confidence intervals 2.9 to 8.8; p less than 0.005). In four transfusions associated with fetal bradycardia or tachycardia, delta intraperitoneal pressure (range, 16 to 26) was greater than in uncomplicated transfusions (range, 1 to 9). delta Intraperitoneal pressure was 0 in the fetus with ascites. These results implicate increases in umbilical vein pressure and intraperitoneal pressure in immediate complications of intrauterine transfusion, and support a role for intraperitoneal pressure monitoring during intraperitoneal transfusion.
Insulin was measured in the blood collected in utero from three midtrimester anencephalic fetuses. The hyperinsulinism found could be due to an underutilization of glucose in the absence of most of the brain and could be responsible for the relatively normal growth in anencephaly despite the absence of the hypothalamohypophysial axis.
The mechanism by which oligohydramnios produces lung hypoplasia is not understood. The current theory that extrinsic compression of the fetal thorax causes hypoplasia, either by inhibiting breathing movements or by squeezing out lung liquid, is not supported by observational or experimental data, or by our finding of decreased amniotic pressure around the fetus in oligohydramnios. We hypothesize that lung hypoplasia results from excess loss of lung liquid because of a reduction in amniotic pressure, and hence an increase in the alveolar-amniotic pressure gradient. The magnitude of this increased pressure gradient is calculated to exceed the small standing tracheal pressure; thus low amniotic pressure overcomes the normal laryngeal retentive mechanisms and allows a larger quantity of lung liquid to escape. In the prevention of pulmonary hypoplasia, a role is suggested for the instillation of artificial amniotic fluid to restore normal amniotic pressure.
Maternal and fetal glucose concentrations were measured simultaneously in 54 pregnancies in which fetal blood sampling was conducted between 18 and 34 weeks gestation. Twenty-five pregnancies were normal (group 1), 13 were complicated by fetomaternal alloimmunization (group 2), and 16 by intrauterine growth retardation (group 3). The maternal glucose concentration was similar in the three groups. The fetal glucose level was significantly lower in growth-retarded (mean = 2.7 mmol/L) than in normal pregnancies (mean = 3.5 mmol/L). There was a statistically significant gradient between maternal and fetal glucose concentrations in groups 1 and 3, but no gradient was found in group 2. Maternal and fetal glucose concentrations were significantly correlated in all groups, but the correlations were distinct. For a given maternal glucose concentration, fetal glucose was higher in patients with alloimmunization and lower in patients with intrauterine growth retardation than in normal pregnancies. In patients with intrauterine growth retardation, fetal PO2 correlated positively with fetal glucose and inversely with maternal fetal glucose gradient.
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Our previous work on the in vitro generation of cytotoxic T lymphocytes from the blood of 15-22-week-old fetuses, and on the induction of immunological tolerane in both radiation chimeras and neonatal mice, using T lymphocyte-depleted allogeneic bone marrow cells, has led us to believe that it should be possible to establish red cell chimerism in human fetuses by the infusion of allogeneic adult bone marrow cells. The essential prerequisite appears to be the removal of immunocompetent T lymphocytes from the bone marrow transplant, for new T cells generated from donor stem cells become tolerant to the histocompatibility antigens of the host's thymus and cannot, therefore, cause graft-versus-host disease (GVHD). Such an approach could be used in the treatment of fetuses diagnosed at an early stage as suffering from life-threatening inherited blood disorders. The experiments described here were designed to test this hypothesis in a sub-human primate species, Macaca fascicularis. Twenty-two cynomolgus monkeys received infusions of haploidentical (paternal) bone marrow between days 51 and 95 of gestation. There was no evidence of chimerism in animals inoculated after day 75 from mating. Eight out of 14 fetuses inoculated before day 70 were late intra-uterine deaths, four were hydropic and in one, histological confirmation of GVHD was obtained, indicating that tolerance can be induced at this time, as GVHD can occur only if donor cells survive. The T cell-depletion technique used here did not appear to prevent GVHD.
The functional maturation of an independent foetal thyroid activity was investigated in the present study. Serum concentrations of total T4, free T4, TSH and TBG were measured in 23 foetuses between 18 and 31 weeks' gestational age. Foetal samples were collected by transabdominal needling from the placental cord insertion. TT4, FT4, TBG and TSH levels significantly increased with gestational age. FT4 levels were comparable with the adult range by 28 weeks' gestation; TBG levels reached adult values at approximately 30 weeks, while TT4 was lower than adult levels throughout the whole period studied. TSH values were, in all cases, higher than the normal adult range. A significant positive correlation was present between TT4 and TBG, TT4 and TSH, and TBG and TSH levels; on the contrary, no correlation was demonstrated between FT4 and TSH levels. The TSH/TT4 ratio significantly decreased with gestational age. The results suggest an incomplete responsiveness of the foetal thyroid gland to TSH, while the feedback control system between pituitary and thyroid is operating at a different set point from that in post-natal life. The normal range of thyroid parameters established is of clinical relevance for the antenatal diagnosis, and eventual treatment of thyroid disorders that may seriously damage foetal development and maturation.
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