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PubMed1985

The relationship of fetal plasma protein concentration and hemoglobin level to the development of hydrops in rhesus isoimmunization.

Fetoscopic samples of pure fetal blood were obtained at 18 to 25 weeks' gestation from seven hydropic and 10 nonhydropic fetuses affected by rhesus isoimmunization, and the fetal plasma albumin, plasma total protein, and hemoglobin concentrations were determined. All fetuses with sonographic evidence of hydrops had a hemoglobin of 3.8 gm/dl or less, whereas all but one of those without hydrops had a hemoglobin greater than 4.0 gm/dl. The plasma total protein was less than 2 standard deviations below the mean of the normal range in all hydropic fetuses and in six of 10 of those without hydrops. Hypoalbuminemia was found in six of the seven hydropic fetuses and in two of the nonhydropic fetuses. Ascitic fluid total protein and albumin concentrations were also determined in four hydropic fetuses, and the values in three were found to be more than 50% of the corresponding plasma levels.

Albumins↗
PubMed1989

Prediction of hematocrit decline after intravascular fetal transfusion.

Fetal blood sampling and intravascular transfusion via cordocentesis allow more precise fetal evaluation and treatment in isoimmunized pregnancies. However, the timing of repeat transfusion has remained empiric. In this report we review our experience with fetal transfusions in isoimmunized pregnancies to evaluate the ability to predict fetal hematocrit decline and thereby determine the optimum timing for repeat transfusions. Between March 1986 and March 1988, 60 intravascular fetal transfusions were performed in 20 patients. Fetal transfusions were excluded from analysis if blood samples were unable to be obtained before and after transfusion, as well as at the beginning of the next transfusion or birth. Fifty-three procedures were analyzed. Two equations were used to predict the fetal hematocrit at the subsequent transfusion. The difference between observed and predicted hematocrits at the beginning of a subsequent transfusion or birth was -0.9% +/- 5.8% with equation 2, which was the more accurate formula in the majority of fetuses. Prediction of fetal hematocrit decline may be used to determine the optimum timing of repeat transfusion.

Blood Transfusion, Intrauterine↗
PubMedDate not supplied

Blood gas and pH in the human fetus with severe anemia.

Leiden University Hospital is the national referral center for the management of fetal isoimmunization in The Netherlands. In this observational study, blood gas and acid-base measurements from 286 pretransfusion samples and 214 paired posttransfusion samples of 113 fetuses were analyzed. In umbilical arterial blood, we found a significant positive correlation between the degree of anemia and pH, as well as a significant negative correlation between degree of anemia and pO2. However, umbilical venous blood gas and pH remained virtually unchanged even in severe anemia. During intrauterine transfusion with unbuffered adult red cells, there was a small but statistically significant decrease of pH and pO2 in fetal blood. We conclude that severe fetal anemia is associated with decreased umbilical arterial pH, but that umbilical venous pH remains normal until shortly before death.

Adult↗
PubMed1986

Rise in maternal serum alpha-fetoprotein concentration after chorionic villus sampling and the possibility of isoimmunization.

Maternal serum alpha-fetoprotein concentrations were determined by radioimmunoassay in 72 patients immediately before and after chorionic villus sampling for prenatal diagnosis. Fifty percent showed a rise of greater than or equal to 5 ng/ml. Assuming such rises represent fetal blood crossing the intervillous space, in 14% of the cases greater than or equal to 60 microliters of fetal blood was transferred at the time of chorionic villus sampling. A positive correlation was found between the magnitude of rise in maternal serum alpha-fetoprotein levels and the amount of villi removed (r = 0.39, p less than 0.001). When cases were examined by number of passes, a greater rise in maternal serum alpha-fetoprotein levels was noted with multiple passes than with single passes for a given sample size. The transfer of greater than or equal to 60 microliters of fetal blood suggests that maternal sensitization to fetal antigens may occur after chorionic villus sampling. During biopsy, as small a sample of villi as necessary for diagnosis should be taken with as few catheter passes as possible.

Biopsy↗
PubMed1986

Ultrasonographic fetal surveillance in the management of the isoimmunized pregnancy.

During the past 20 years the management of pregnancies involving rhesus sensitization has been based on determinations of the optical density of amniotic fluid as an index of the bilirubin concentration and the degree of hemolysis. High values have dictated intervention in the form of delivery or intrauterine transfusion, depending on the gestational age. Since 1982 intensive surveillance with ultrasound imaging and electronic monitoring of the fetal heart rate have become useful in decisions about the timing of intervention. Using these tools, we followed 11 fetuses who would previously have been treated by multiple intrauterine transfusions or early delivery, for 8 to 63 days without treatment. All were born alive, in good condition and without hydrops, at gestational ages of 30.5 to 36.0 weeks. The lengths of stay for the neonates ranged from 8 to 48 days, and all were discharged alive. We conclude that rhesus sensitization in a select group of fetuses, who according to former standards would have been candidates for earlier delivery or intrauterine transfusion, can be managed expectantly for longer periods by careful observation with modern techniques of surveillance.

Cesarean Section↗
PubMedDate not supplied

Fetal intravascular transfusion for hydropic disease due to rhesus isoimmunization.

OBJECTIVE: To evaluate the management of hydropic fetuses, due to rhesus isoimmunization, with fetal intrauterine intravascular transfusions. MATERIAL AND METHODS: This is a retrospective analysis of 18 rhesus-negative pregnant women presenting at our hospital with fetal hydrops during a 7-year period. All cases were managed with serial intrauterine intravascular transfusions with the goal of delivery by cesarean section beyond 33 weeks of gestation. All patients received prophylactic ampicillin and ritodrine for 4 days after the procedure. RESULTS: There were 11 mildly and 7 severely hydropic fetuses. All fetuses with mild hydrops and 5 of the 7 with severe hydrops were delivered alive after 32 weeks of gestation in a good condition. Two fetuses both with severe hydrops died in utero, at 28 weeks of gestation. Intrauterine reversal of hydrops occurred in 90.9% of fetuses with mild hydrops and in 57.1% of severely hydropic fetuses. CONCLUSIONS: The survival rate for the hydropic fetuses in our study was 88.9% and it was associated with the severity of fetal hydrops.

Blood Transfusion, Intrauterine↗
PubMed2003

Infants with bilirubin levels of 30 mg/dL or more in a large managed care organization.

OBJECTIVE: To describe the incidence, etiology, treatment, and outcome of newborns with total serum bilirubin (TSB) levels >or=30 mg/dL (513 micro mol/L). DESIGN: Population-based case series. SETTING: Eleven Northern California Kaiser Permanente Medical Care Program hospitals and 1 affiliated hospital. PATIENTS: Eleven infants with TSB levels of >or=30 mg/dL in the first 30 days after birth, identified using computer databases from a cohort of 111,009 infants born 1995-1998. OUTCOME MEASURES: Clinical data from the birth hospitalization, rehospitalization, and outpatient visits in all infants; psychometric testing at age 5 (N = 3), neurologic examinations by child neurologists at age 5 (N = 3), or primary care providers (N = 7; mean age: 2.2 years); Parent Evaluation of Developmental Status (N = 8; mean age: 4.2 years). RESULTS: Maximum TSB levels of the 11 infants ranged from 30.7 to 45.5 mg/dL (525 micro mol/L to 778 micro mol/L; mean: 34.9 mg/dL [597 micro mol/L]). Four were born at 35 to 36 weeks gestation, and 7 were exclusively breastfed. Two had apparent isoimmunization; the etiology for the other 9 remained obscure, although only 4 were tested for glucose-6-phosphate dehydrogenase deficiency and 1 was bacteremic. None had acute neurologic symptoms. All received phototherapy and 5 received exchange transfusions. One infant died of sudden infant death syndrome; there was no kernicterus at autopsy. Two were lost to follow-up but were neurologically normal when last seen for checkups at 18 and 43 months. One child was receiving speech therapy at age 3. There were no significant parental concerns or abnormalities in the other children. CONCLUSIONS: In this setting, TSB levels >or=30 mg/dL were rare and generally unaccompanied by acute symptoms. Although we did not observe serious neurodevelopmental sequelae in this small sample, additional studies are required to quantify the known, significant risk of kernicterus in infants with very high TSB levels.

Adult↗
PubMed1986

Fetal liver ultrasound measurements in isoimmunized pregnancies.

Sixteen isoimmunized pregnancies at risk for erythroblastosis fetalis were managed by serial amniocenteses for bilirubin delta optical density at 450 nm (delta OD450). Before amniocentesis each fetus was evaluated ultrasonically and the fetal liver size, the abdominal circumference, and the umbilical vein diameter, in both the fetal liver and the umbilical cord, were measured. The ultrasonically determined fetal liver size, as well as its growth rate, was found to be greater than normal during the last two weeks before intervention (intrauterine transfusion or delivery) in all eight fetuses with severe hemolytic disease. The umbilical vein diameter in the fetal liver was above normal in only one fetus, whereas the abdominal circumference was increased in only three of the eight severely affected fetuses. These data suggest that serial fetal liver ultrasound measurements may be useful as an adjunct to amniotic fluid analysis to predict the severely affected fetus in need of prompt intervention (intrauterine transfusion or delivery).

Amniotic Fluid↗
PubMed1995

Anti-D administration in early pregnancy - time for a new protocol.

The use of anti-D immunoglobulin has dramatically reduced the incidence of rhesus isoimmunization arising from pregnancy. A critical shortage of anti-D has developed and consumption must be reduced, preferably without increasing the risk of isoimmunization. The standard dosage of anti-D currently given at all gestational ages is 1 ampoule containing 125 micrograms of anti-D. Of the anti-D administered half is during the first trimester when a much lower dose could be used; 30 micrograms would remove from the maternal circulation the entire fetoplacental blood volume (3 ml) of a 12 week's pregnancy. A dose of 30 micrograms would also be adequate for most fetomaternal transfusions after 12 weeks but prior to the third trimester. A larger dose could be administered if maternal Kleihauer testing suggests the need for a supplementary dose. In the third trimester, the current regimen is appropriate - a dose of 125 micrograms of anti-D supplemented when needed on the basis of maternal Kleihauer testing. A lower dose ampoule of anti-D should be available. In addition, existing protocols for anti-D administration should be modified so that smaller more appropriate doses are given, better utilizing the limited supply of anti-D.

Australia↗
PubMed1991

Relations between the fetal circulation and pituitary-thyroid function.

OBJECTIVE: To study the relation between changes in the fetal thyroid hormone and thyroid stimulating hormone (TSH) concentrations and alterations in the fetal circulation as assessed by Doppler ultrasound. DESIGN: A cross-sectional study of small for gestational age (SGA) and red-cell isoimmunized fetuses undergoing cordocentesis and Doppler studies for the assessment and determination of fetal karyotype, acid-base balance and haemoglobin concentration. SETTING: Harris Birthright Research Centre for Fetal Medicine, King's College, London. SUBJECTS: 38 growth retarded and 38 red-cell isoimmunised fetuses. INTERVENTIONS: Cordocentesis. MAIN OUTCOME MEASURES: Serum TSH total and free thyroxine (T4, FT4) and total and free triiodothyronine (T3, FT3) concentrations; middle cerebral artery (MCAVm) and descending thoracic aorta (AoVm) mean blood velocities; fetal Po2 and haemoglobin concentration (Hb). RESULTS: Delta values (delta) calculated as the number of SDs from the respective normal mean for gestation were used to compare the results with those from a previous study of normal fetuses. Mean AoVm was increased in the isoimmunized fetuses (P less than 0.001) but decreased in the SGA fetuses (P less than 0.001). Mean MCAVm was increased in both groups (P less than 0.01; P less than 0.001). There were significant associations between the gestational age adjusted values for TSH and MCAVm (r = 0.23, P less than 0.05) and between T4, FT4 or FT3 and AoVm (r = 0.41, P less than 0.01; r = 0.50, P less than 0.01; r = 0.36, P less than 0.01 respectively). In addition, T4 and FT4 were associated with delta Po2 and delta Hb. CONCLUSION: In the hypoxaemic hypoxia of growth retardation and the anaemic hypoxia of rhesus disease there are significant associations between changes in fetal thyroid hormone concentrations and changes in fetal blood flow as assessed by Doppler. Irrespective of whether altered blood flow is the cause or effect of changes in thyroid hormone concentrations, the observed changes could have beneficial effects for fetal survival, in the presence of a hostile intrauterine environment.

Blood Circulation↗
PubMed1990

Is fetal insulin secretion affected by fetal hypoxia?

Fifty-five pregnant Rhesus isoimmunized women were subjected to fetal blood sampling or fetal blood transfusion on 135 occasions. Glucose and C-peptide concentrations were measured in fetal blood, in addition to the routine investigations for complete blood count, blood gases and lactate concentration, in order to investigate whether fetal insulin secretion was affected by hypoxia from fetal anemia. We found a strong relation between the concentration of C-peptide and gestational age at sampling (r = 0.53, P less than or equal to 0.000001). Multiple regression analysis also demonstrated that glucose (P less than or equal to 0.0051) and lactate (P less than or equal to 0.0003) also affected the concentration of C-peptide. We were unable to find any relation between C-peptide concentrations and blood gas variables. We conclude that fetal insulin secretion, measured as C-peptide concentration in fetal blood, is not affected by hypoxia from anemia as long as hemoglobin concentration remains within the range 2.1-14.8 g/dl).

Age Factors↗
PubMed1991

Atrial natriuretic peptide: a vasodilator of the fetoplacental circulation?

Paired maternal and fetal atrial natriuretic peptide concentrations were measured in 62 percutaneous umbilical blood samplings performed principally for the assessment and treatment of rhesus isoimmunization. Pretransfusion fetal atrial natriuretic peptide levels were significantly higher than maternal atrial natriuretic peptide levels (median 117 pg/ml vs median 32 pg/ml; p less than 0.001); paired pretransfusion fetal and maternal atrial natriuretic peptide samples showed a weak correlation with each other (R2 = 17%; p = 0.002). Fetal atrial natriuretic peptide levels correlated inversely with hematocrit (R2 = 14%; p = 0.003), but not with albumin or gestational age. Paired pretransfusion and posttransfusion (median = 134 pg/ml) fetal atrial natriuretic peptide levels (n = 38) showed a significant rise after transfusion (p less than 0.001); this rise was related to the percentage of fetoplacental blood volume transfused (R2 = 33%; p = 0.035). In a subgroup of 26 procedures, change in fetal atrial natriuretic peptide levels was weakly correlated with transient reductions in the Doppler systolic/diastolic ratio of the umbilical artery (R2 = 14%; p = 0.07). These data support work in animals that indicate a role for atrial natriuretic peptide in the human fetus, but these data do not confirm that atrial natriuretic peptide modulates fetoplacental vascular impedance in the human fetus.

Atrial Natriuretic Factor↗
PubMed1989

Plasma atrial natriuretic peptide in human fetus: response to intravascular blood transfusion.

To investigate whether atrial natriuretic peptide is present in the human fetal circulation and changes in response to fetal blood volume expansion, the concentration of plasma atrial natriuretic peptide was measured by radioimmunoassay in samples obtained by cordocentesis. Twenty-four patients referred for intravascular blood transfusion because of red cell isoimmunization at 21 to 35 weeks' gestation were studied. Plasma atrial natriuretic peptide concentrations in fetal blood (median, 8.0 pmol/L; range, 1 to 27.3) were significantly higher than those of 25 young 18- to 32-year-old adult control subjects (median, 4.5 pmol/L; range, 1 to 11.3, p less than 0.002 but similar to those found in the umbilical cord blood of 10 normal neonates immediately after delivery (median, 7.35 pmol/L; range, 2.7 to 15.5). In seven patients in whom fetal and maternal plasma atrial natriuretic peptide was measured simultaneously, all fetal concentrations were higher (p less than 0.01). The concentration of fetal atrial natriuretic peptide before and immediately after blood transfusion (n = 12) rose significantly (p less than 0.05), and the rise correlated positively with the transfusion rate (p less than 0.05). We conclude that atrial natriuretic peptide is present in plasma of the human fetus as early as 21 weeks' gestation and that its concentration increases promptly in response to vascular volume expansion. These findings suggest that atrial natriuretic peptide may play a role in fetal volume homeostasis.

Adolescent↗
PubMed2003

[Monitoring of pregnancy complicated by maternal-fetal isoimmunization. A comparison between two clinical protocols].

AIM: Invasive techniques such as amniocentesis and cordocentesis are used for the diagnosis and treatment of fetus at risk for anemia due to maternal red-cell alloimmunization. The purpose of this study was to determine the value of non invasive measurements of the peak velocity middle cerebral artery in the fetus (PVMCA) for the diagnosis of fetal anemia. METHODS: From 1996 to September 2002, we studied 23 pregnancies with anti D title >1:32. In the 1(st) group of 11 women (from 1996 to 1999) fetal anemia was detected by invasive techniques (amniocentesis and cordocentesis). In the 2(nd) group of 12 women (from 1999 to 2002) fetal anemia was suspected on the basis of PVMCA. When PVMCA was significantly increased, cordocentesis was performed in order to rule out fetal anemia and to provide in utero transfusions. RESULTS: In the 1(st) period we performed 23 invasive techniques (7 amniocentesis and 16 cordocentesis) in 11 women, but we identified fetal anemia only in 4 cases. In the 2(nd) period we performed only 2 cordocentesis in women in which PVMCA was increased; the blood sampling confirmed fetal anemia in both cases. CONCLUSION: PVMCA and fetal hematocrit are highly significantly correlated: high values of PVMCA are associated with fetal anemia. Doppler velocity of PVMCA is related to fetal anemia with positive predictive value 100% and negative predictive value 100%. The middle cerebral artery blood velocity is a non invasive technique for detecting anemia in pregnancies complicated by alloimmunization.

Adult↗
PubMed2003

Prediction of fetal anemia by middle cerebral artery peak systolic velocity in pregnancies complicated by rhesus isoimmunization.

OBJECTIVES: To study the correlation of peak systolic velocity in the middle cerebral artery with hemoglobin concentration in fetuses at risk of anemia due to Rhesus isoimmunization. DESIGN: Peak systolic velocity of middle cerebral artery (MCA-PSV) was measured before 66 cordocentesis procedures in 20 isoimmunized fetuses. Reference values were derived from a study of 300 control fetuses. MCA-PSV values and hemoglobin concentrations were expressed as multiples of the median (MoM) for gestational age. The following hemoglobin concentration MoM thresholds defined degrees of anemia: mild, between 0.83 and 0.65; moderate, between 0.64 and 0.55; and severe, less than 0.55. Regression analysis was performed and receiver-operator-characteristic curves were constructed to determine the diagnostic accuracy of different thresholds of MCA-PSV for the prediction of moderate to severe anemia, either at the initial or repeat cordocentesis procedures. RESULTS: The mean (+/-SD) gestational age at cordocentesis was 28.5+/-4.6 weeks. Moderate to severe anemia was observed on 29 (44%) and hydrops on 27 (41%) occasions. MCA-PSV correlated weakly with hemoglobin concentrations. At threshold values 1.50 MoM, the sensitivity, specificity, and negative predictive value for moderate to severe anemia were 9.0, 100, and 48.0% at the initial cordocentesis procedures, and 44.0, 96.0, and 73.0% at repeat cordocentesis procedures, respectively. CONCLUSIONS: Although MCA-PSV is highly specific, negative values do not rule out fetal anemia. Further research is required before it can be recommended in clinical practice.

Anemia↗
PubMed1990

Effects of intravascular, intrauterine transfusion on prenatal and postnatal hemolysis and erythropoiesis in severe fetal isoimmunization.

In an investigation of the effects of intrauterine, intravascular transfusions (IUT) on fetal and neonatal hemolysis and erythropoiesis, 12 fetuses who received IUT for treatment of severe isoimmunization had serial measurements of hemoglobin concentration, Kleihauer-Betke stains to detect fetal hemoglobin-containing erythrocytes, and determination of plasma erythropoietin (EPO) concentration before each IUT, at birth, and postnatally. Reticulocyte counts and sensitizing antibody titers were measured in five fetuses. Mean values before the first IUT, before the final IUT, and at birth were as follows: hemoglobin level, 6.1, 9.1, and 11.3 gm/dl; reticulocyte count, 22.7%, 0.5%, and 0.9%; fetal hemoglobin-containing erythrocytes, 100%, 1.6%, and 1.5%; and EPO level, 12, 56, and 756 mU/ml, respectively. Only one neonate required exchange transfusion. In the first month postnatally, all infants had a profound anemia. All but one infant required simple blood transfusions postnatally. Before the first postnatal transfusion, mean hemoglobin concentration was 6.2 gm/dl, mean reticulocyte count was 0.8%, mean erythropoietin concentration was 23 mU/ml, and the sensitizing antibody titer remained markedly elevated. Except for the surge of EPO at birth, EPO levels did not rise prenatally or postnatally unless marked anemia (hemoglobin level less than 5 gm/dl) occurred. These observations suggest that the intrauterine and postnatal anemia in fetuses who receive IUTs may be explained both by hemolysis of newly formed erythrocytes by circulating antibody, which typically persisted for more than a month after birth, and by suppressed erythropoiesis.

Anemia, Neonatal↗
PubMed1992

The severely anemic and hydropic isoimmune fetus: changes in fetal hematocrit associated with intrauterine death.

Hydrops caused by isoimmune hemolytic anemia is frequently associated with fetal death following intrauterine intravascular transfusion. To identify possible predictors of procedure-related fetal death, we examined changes in fetal blood volume and hematocrit resulting from the initial transfusion performed on 19 severely anemic, hydropic fetuses. Seven fetuses (36.8%) died at 24-72 hours after transfusion, but in no case was the procedure associated with fetal distress. There were no significant differences between fetuses who died and those who survived in terms of total volume of blood transfused, volume transfused as a percentage of total fetoplacental blood volume, hematocrit of transfused blood, post-transfusion hematocrit, umbilical vein pH, or gestational age at transfusion. Significant differences were noted between hydropic fetuses who died compared with those who survived in the mean pretransfusion hematocrit, 6.7% (+/- 2.0) versus 8.7% (+/- 1.6) (P = .03), and the relative increase in post- over pre-transfusion hematocrit, 5.5-fold (+/- 1.4) versus 3.5-fold (+/- 0.8) (P = .001). Stepwise logistic regression analysis confirmed that only the relative increase in hematocrit was predictive of fetal loss. Moreover, six of seven fetal deaths occurred when the relative increase in hematocrit was greater than fourfold, whereas ten of 12 surviving fetuses had relative increases of less than fourfold. We conclude that large, acute increases in fetal hematocrit following intrauterine transfusion are associated with substantial mortality in hydropic fetuses.

Anemia↗
PubMed1986

Ultrasound contributions to the management of the severely isoimmunized fetus.

Twenty-four out of 81 fetuses affected by anti-D isoimmunization underwent ultrasonic guided intrauterine transfusions (2.8 I. U. T.s per fetus). The absolute value and trend of delta OD 450 micron value was correlated with the severity of fetal condition as evaluated by ultrasonography following simple semiquantitative grading of ascites (mild, moderate, severe) and diagnosis of hydrops. The evaluation of disease was monitored in this way during transfusion therapy. Transfusion procedures have been ultrasonically guided. When ascites was present a few milliliters of isolytic solution allowed the bubbling effect to be observed. In the case of no ascites we confirmed the needle positioning by a cineradiographic sequence lasting a few seconds. Fetal transfusions were repeated every 10 to 15 days and the amount of packed red cells to be injected was determined according to the week of gestation. Post-transfusion monitoring included ultrasonic reevaluation of fetal parameters and non-stress testing. All fetuses were delivered via cesarean section before the 35th week of gestation. In no case was treatment started after the 31st week. Seventeen fetuses were transfused before the 26th week (71%). In 13 fetuses transfusions were started before ascites had appeared. Only 5 fetuses worsened and the 3 which became hydropic eventually died. The delta OD-450 value of these 5 cases before therapy had already indicated that they were more severely affected. Survival rate in this group was 69%. Eleven fetuses showed different degrees of ascites or hydrops at the time of the first transfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Transfusion, Intrauterine↗