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Fetal microcirculation of abnormal human placenta. II. Scanning electron microscopy of placental vascular casts from fetus with severe erythroblastosis fetalis.

The latex injection-corrosion cast technique coupled with scanning electron microscopy was applied to the study of severe Rh sensitization of the placenta. The main observed ultrastructural changes in fetal vasculature in this type of placenta were very similar to those of the small for gestational age placenta; large-sized vessels exhibited less branching than those of the normal placenta, and the capillary network showed numerous vascular buds and "H"-shaped anastomoses. In addition, in Rh-sensitized placentas, the capillary network was remarkably sparse, and the cast also revealed smooth-surfaced veins with distinct U shapes undulating through the placental stroma. These U-shaped veins may be the result of umbilical flow impedance with subsequent umbilical venous hypertension, which stretches the veins into undulating form.

Adult↗

Fetal blood group determination in first-trimester pregnancy for the management of severe immunization.

The presence or absence of Rho (D) and Kell antigens on fetal red blood cells was determined in the first trimester of pregnancy on erythrocytes obtained by chorionic villi sampling with the use of mixed agglutination and solid phase microimmunofluorescence techniques. Pregnancies in one Kell-sensitized woman and seven severely RH-sensitized women with a poor obstetric history and a partner heterozygous for the offending antigen were examined. A conclusive diagnosis could be made in seven of the eight cases studied.

Blood Grouping and Crossmatching↗

Intravenous immunoglobulin treatment of pregnant patients with recurrent pregnancy loss caused by antiphospholipid antibodies and Rh immunization.

A patient with antiphospholipid antibodies and nine consecutive fetal deaths and a severely Rh-immunized woman with one previous live birth and seven fetal/neonatal deaths achieved live births after antepartum administration of intravenous immunoglobulin. This agent shows promise as a new treatment for patients with previous repetitive fetal deaths from immunologic causes.

Adult↗

Pathophysiology of pressure changes during intrauterine transfusion.

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.

Acid-Base Equilibrium↗

Does midtrimester delta OD450 of amniotic fluid reflect severity of Rh disease?

Thirty-two patients with Rh-immunized pregnancies had amniocenteses between 16 and 20 weeks' gestation. Serial amniotic fluid values of delta optical density at 450 nm were studied to predict the severity of Rh disease. A value greater than 0.15 indicated severe Rh immunization. Values less than 0.09 indicated mild or no Rh disease; delta optical density at 450 nm between 0.09 and 0.15 require further evaluation to determine the trend. Midtrimester amniocentesis is a simple technique that helps to determine which patients may or may not require fetal blood sampling.

Amniotic Fluid↗

Two hundred intrauterine exchange transfusions in severe blood incompatibilities.

Two hundred intrauterine exchange transfusions were performed under local anesthesia in 107 cases of blood incompatibilities (60 fetuses with severe anemia and 47 with hydrops). Under sonographic guidance, depending on fetal and placental position, an optimal puncturing site was selected along the umbilical vein: placental insertion, fetal insertion, or fetal intraabdominal segment. Tests were immediately performed to confirm fetal origin of blood obtained and estimate hemoglobin level. Blood used for exchange transfusion was compatible with maternal blood and had a hematocrit value of 75%. Exchange transfusion was continued until a hemoglobin level of 16 gm/dl was reached. This procedure was first associated with intraperitoneal transfusions and was subsequently used independently once a month to maintain an adequate hemoglobin level. In 4 fetuses with hydrops, antenatal regression of this sign was observed in 33 cases (70.2%). Overall outcome of 107 fetuses after exchanges was 84 living neonates (78.5%), 15 deaths in utero, and eight neonatal deaths. The survival rate was 91.6% for fetuses without hydrops and 61.7% for those with hydrops. The advantage of exchange transfusion appears to be rapid and efficient correction of anemia with elimination of incompatible fetal red blood cells.

Birth Weight↗

Amniotic fluid erythropoietin predicts fetal distress in Rh-immunized pregnancies.

Repeated amniotic fluid erythropoietin measurements in 23 Rh-immunized pregnancies were done to evaluate erythropoietin levels of amniotic fluid as an indicator of fetal distress (umbilical artery, pH 7.14 or less, or 1-minute Apgar score of 4 or less). Amniotic fluid erythropoietin levels did not vary significantly between 168 and 273 gestational days in the pregnancies without fetal distress. Increasing levels of amniotic fluid erythropoietin predicted highly reliably severe fetal distress at birth. Whether erythropoietin levels of amniotic fluid can also predict fetal distress in other pathologic pregnancies needs further study.

Amniotic Fluid↗

Maternal-fetal glucose gradient in normal pregnancies and in pregnancies complicated by alloimmunization and fetal growth retardation.

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.

Blood Glucose↗

Acute fetal hemodynamic alterations after intrauterine transfusion for treatment of severe red blood cell alloimmunization.

One of the compensatory hemodynamic mechanisms seen in the anemic human fetus is an increased cardiac output. With Doppler techniques, cardiac output was measured in 21 fetuses before and immediately after 38 intrauterine transfusions for severe red cell alloimmunization. Umbilical venous pressures were measured before and after transfusion; amniotic fluid pressure was also quantitated. After subtraction of amniotic pressure, umbilical venous pressure increased by 1.7 +/- 2.8 mm Hg (p less than 0.01). Left and right ventricular output declined by 19% and 22%, respectively (p less than 0.001). Four factors are known to affect cardiac output: heart rate, cardiac contractility, preload, and afterload. Fetal heart rate and mean acceleration, a measure of myocardial contractility, were unchanged after transfusion. A calculated mean increase in the fetoplacental volume of 18% in conjunction with an increase in umbilical venous pressure would indicate that cardiac preload was increased. We propose that intravascular intrauterine transfusion leads to an increased cardiac afterload, possibly by increasing blood viscosity. The fetal heart responds to the increased afterload by a decrease in stroke volume, leading to a fall in cardiac output.

Blood Transfusion, Intrauterine↗

Intrauterine transfusion--intraperitoneal versus intravascular approach: a case-control comparison.

Intravascular fetal transfusion has gained widespread acceptance and has supplanted the use of intraperitoneal fetal transfusion in management of severe alloimmune disease in many centers. This study compares the two methods with regard to multiple objective end points of performance, therapy, and outcome in a highly matched case-control fashion. The intravascular approach is better on almost every level. More surviving infants who are in better condition at a mature gestation and whose mothers have fewer complications and sequelae are the result. Whereas intraperitoneal transfusion should not be abandoned altogether, it is a second-line procedure used only in very limited circumstances. Intravascular fetal transfusion offers realistic prognosis for intact survival at virtually any extreme of alloimmune disease.

Blood Group Incompatibility↗

Congenital heart block: successful prophylactic treatment with intravenous gamma globulin and corticosteroid therapy.

In mothers with anti-Ro-positive antibodies whose previous pregnancies have ended in deliveries of infants with congenital heart block, prophylactic therapeutic strategies are used to try to diminish the production and passage into fetal circulation of autoantibodies. Intravenous gamma globulin was given at 14 and 18 weeks' gestation and prednisone was given from 14 weeks' gestation to a woman with Sjögren's syndrome. The pregnancy ended with delivery of an infant without congenital heart block.

Adult↗

Amniotic fluid bilirubin and fetal hemolytic disease.

Six different methods for assessing amniotic fluid bilirubin were compared in 111 samples from 37 patients. When the Liley methods were compared, the chloroform extraction and 5% correction methods resulted in 20% and 4% reductions, respectively, in the mean change in optical density at 450 nm when compared with the uncorrected mean (0.086 +/- 0.06 [p less than 0.05] and 0.104 +/- 0.07 [p, not significant] vs 0.108 +/- 0.08). This reduction was observed in spite of significant visual blood contamination being rarely noted. The predictions based on amniotic fluid analysis were compared with the first fetal or neonatal hematocrit. The chloroform-extracted change in optical density at 450 nm accurately predicted fetal status in all patients, whereas lesser degrees of accuracy were observed with other methods. Hydrops fetalis did not occur during the observation period, and fetuses needing transfusion (n = 5) or early delivery (n = 10) were indicated correctly. The chloroform extraction change in optical density at 450 nm accurately predicts fetal status, and its use should continue.

Amniotic Fluid↗

Human fetal bilirubin levels and fetal hemolytic disease.

The development of secondary fetal anemia in association with maternal red blood cell alloimmunization requires hemolysis. In specimens obtained at the time of a clinically indicated cordocentesis, total and direct umbilical venous bilirubin was measured and the indirect umbilical venous bilirubin calculated in 43 antigen-positive and 30 control fetuses. Twenty-two (51%) of the antigen-positive fetuses had or subsequently developed severe anemia (hematocrit less than 30%). Umbilical venous total bilirubin (r = 0.47, p = 0.0008) and direct bilirubin (r = 0.520, p = 0.04) levels each rose with gestation. Indirect bilirubin did not vary significantly with gestation. Bilirubin was unrelated to hemoglobin. In contrast to the control fetuses, umbilical venous total bilirubin for antigen-positive fetuses was inversely related to hemoglobin (r = -0.57, p less than 0.0001) independent of gestational age (r = 0.53, p less than 0.0001) (multiple R of hemoglobin and gestational age for umbilical venous total bilirubin = 0.76, p less than 0.0001). Eighteen of 22 (82%) fetuses in whom anemia developed had an umbilical venous total bilirubin greater than or equal to 97.5 percentile compared with only eight of 21 (38%) fetuses in whom anemia did not develop (p = 0.009). In longitudinal study the umbilical venous total bilirubin frequently rose above normal weeks before the development of anemia. An umbilical venous total bilirubin greater than 3 mg/dl represented the warning line. Fifteen of 16 (94%) fetuses in whom either severe antenatal anemia or significant postnatal hyperbilirubinemia developed had an umbilical venous total bilirubin greater than 3 mg/dl. We conclude that the normal placental capacity for the transport of fetal bilirubin is exceeded in the face of enhanced fetal hemolysis. An elevated fetal bilirubin often precedes the development of antenatal anemia. The antigen-positive fetus with an elevated bilirubin is at high risk to develop anemia antenatally.

Bilirubin↗

Erythropoietic suppression in fetal anemia because of Kell alloimmunization.

OBJECTIVE: Our purpose was to test the hypothesis that maternal anti-Kell alloimmunization produces fetal anemia by erythroid suppression. STUDY DESIGN: Erythropoiesis in 11 anemic fetuses from maternal anti-Kell alloimmunization was compared with that in 11 fetuses where the mother was alloimmunized to RhD; each was matched for hematocrit, gestational age, hydrops, and perinatal outcome. Comparisons of the difference were performed by either paired t or Wilcoxon tests. RESULTS: The anti-Kell group had reduced reticulocytosis (p = 0.007) and erythroblastosis (p = 0.045) and lower amniotic fluid bilirubin concentrations (p = 0.02) in comparison with the anti-D group. No correlation was found between hematocrit and reticulocytosis in the anti-Kell group, whereas the anti-D group had a significant linear relationship (r = 0.63, p < 0.05), indicating a progressive reticulocytosis in response to the degree of anemia. CONCLUSION: These findings suggest that erythroid suppression, rather than hemolysis, is the predominant mechanism in producing fetal anemia related to maternal Kell alloimmunization. Fetal blood sampling is the investigation of choice in the evaluation of anemia related to maternal Kell alloimmunization, because reduced hemolysis means amniotic fluid bilirubin concentrations correlate poorly with anemia.

Erythroblastosis, Fetal↗

The predictive value of maternal serum testing for detection of fetal anemia in red blood cell alloimmunization.

OBJECTIVE: Current management protocols for pregnancies complicated by red blood cell alloimmunization use the maternal antibody titer to predict the need for invasive testing for detection of fetal anemia. We investigated the use of three maternal serum tests to assess their usefulness in predicting fetal disease: indirect Coombs' titer, Marsh score, and monocyte monolayer assay. STUDY DESIGN: Forty-seven serum samples from pregnant women with red blood cell antibodies associated with fetal anemia were analyzed at cordocentesis. Fetal blood was analyzed for hematocrit (corrected for gestational age) and antigen status. Fetal anemia was defined as a hematocrit value of < 2 SD from the mean value for gestational age. Fetuses were classified into three groups: Antigen positive with anemia (n = 19), antigen positive without anemia (n = 17), antigen negative (n = 11). Statistical methods included Kruskal-Wallis test, Newman-Keuls test, Spearman's rank correlation, and receiver-operator characteristic curves; p < 0.05 was considered significant. RESULTS: The median monocyte monolayer assay (phagocytosis, adherence, and association) did not differ among the three groups. Both maternal titers and Marsh scores were significantly higher in fetuses with anemia compared with the other two groups of fetuses (256 vs 64 vs 64, p < 0.001, and 86 vs 69 vs 64, p = 0.02, respectively). Both titer and Marsh score exhibited significant correlations with corrected fetal hematocrit (r = -0.70, p < 0.001; r = -0.63, p < 0.001, respectively). Comparison of the overall receiver-operator characteristic curves for titer and Marsh score revealed no statistical difference; however, a Marsh score of 57 was noted to have a superior specificity than a titer of 16 (p = 0.02). CONCLUSION: The maternal Marsh score can be performed in conjunction with standard indirect Coombs' titers to enhance the predictability of fetal anemia.

Coombs Test↗

Measurement of fetal surfactant production by fluorescence polarization of amniotic fluid in complicated pregnancies.

The results are presented of fluorescence polarization as a method for measurement of surfactant production in 159 specimens of amniotic fluid collected from pregnant women with diabetes, hypertension, Rh immunization, premature rupture of membranes (for more than 48 h prior to delivery) and intrauterine growth retardation (IUGR). The predictability of the development of respiratory distress syndrome has been assessed by this assay. Its specificity, sensitivity and overall accuracy were similar to the lecithin/sphingomyelin (L/S) ratio. The influence of the conditions detailed on fetal lung maturation was determined, lung development being enhanced until near term by Rh immunization, rupture of membranes and hypertension with IUGR.

Amniotic Fluid↗