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PubMed2005

Pregnancy affected by isoimmunisation caused by a unique haemolytic rhesus type antibody in a Somali woman.

Clinical suspicion and biochemical evidence of isoimmunisation in pregnancy have from contemporary times led to clinical curiousity and intervention at various stages of pregnancy for the sake of the fetus. Some of these interventions only found unnecessary after the causative antibodies have been properly identified and characterised. Hundreds of these antibodies were identified accidentally or by planned clinical and biochemical investigation. Here we present a unique case of isoimmunisation in pregnancy caused by a unique haemolytic antibody.

Adult↗
PubMed2000

Splenic artery Doppler peak systolic velocity predicts severe fetal anemia in rhesus disease.

OBJECTIVE: We sought to determine whether main splenic artery Doppler peak systolic velocity predicts severe anemia in the rhesus-alloimmunized fetus. STUDY DESIGN: Splenic artery Doppler peak systolic velocity was obtained before cordocentesis in rhesus-alloimmunized fetuses. Normative values for mean peak systolic velocity based on gestational age were obtained cross-sectionally from a separate group of 144 normal fetuses. The peak systolic velocity values in the study group were expressed as multiples of the median for gestation, and threshold values were used as a screening test for severe anemia. The hemoglobin deficit was defined as mean hemoglobin for gestation minus measured hemoglobin. A hemoglobin deficit value of > or =5 g/dL was used to define severe anemia. We used the peak systolic velocity to screen for severe anemia in the overall study group and the subgroups with or without prior transfusions. RESULTS: The study population consisted of 26 singleton nonhydropic fetuses in which cordocentesis and Doppler measurements were performed on a total of 55 occasions. The mean gestational age and standard deviation at cordocentesis was 29.6 +/- 4.0 weeks. Severe anemia was noted in 20% of fetal cord blood specimens obtained. On the basis of a receiver operating characteristic curve, a peak systolic velocity of > or =1.4 multiples of the median had a detection rate of 100%, with a false-positive rate of 20.8% in the subgroup with no prior transfusion (relative risk, 4.8; 95% confidence interval, 2.2-10.5). For peak systolic velocity threshold of > or =1.50 multiples of the median, corresponding values in the group with one prior transfusion were 80% and 12.5%, respectively (relative risk, 2.5; 95% confidence interval, 1.2-5.3). There was no risk of severe anemia with a peak systolic velocity below the median for gestation. CONCLUSION: Fetal hydrops is rare, with a hemoglobin deficit of <5 g/dL. In the first such report the main splenic artery peak systolic velocity was noted to be a strong predictor of severe anemia. For the overall population, all such instances could be diagnosed while cordocentesis was performed 22.7% of the time. There is no risk of severe anemia with Doppler peak systolic velocities below the median for gestational age. The measurement is easily obtained and should be investigated as a clinical tool for minimizing the necessity for cordocentesis.

Anemia↗
PubMed1993

Deviation in amniotic fluid optical density at a wavelength of 450 nm in Rh-immunized pregnancies from 14 to 40 weeks' gestation: a proposal for clinical management.

OBJECTIVES: Our purpose was to study deviations in values of amniotic fluid optical density at 450 nm in Rh-immunized pregnancies in the second and third trimesters and to propose a clinical management plan. STUDY DESIGN: A total of 789 amniotic fluid single and serial values of deviations in optical density at 450 nm were performed on Rh-immunized pregnancies from 14 to 40 weeks' gestation. The relationship of the deviations in amniotic fluid values of optical density at 450 nm to varying degrees of fetal disease were examined. RESULTS: In Rh-negative fetuses (unaffected) amniotic fluid values rise until 22 to 26 weeks before decreasing to term. In fetuses at risk of dying in utero, values are higher and trends rise. A clinical management plan was devised on the basis of the amniotic fluid findings of deviations in optical density at 450 nm. CONCLUSIONS: A clinical management scheme consisting of four zones is outlined. Rh-negative fetuses have minimal invasive procedures. Fetuses at risk of death undergo early cordocentesis for evaluation and therapy. Values that fall in between can be separated into two zones on the basis of the degree of risk.

Amniotic Fluid↗
PubMed1992

Do abnormal Starling forces cause fetal hydrops in red blood cell alloimmunization?

OBJECTIVE: The purpose of the current investigation was to ascertain whether derangements in umbilical venous pressure and plasma colloid osmotic pressure are involved in the pathophysiologic condition of immune hydrops fetalis. STUDY DESIGN: Umbilical venous pressure (corrected for ambient amniotic fluid pressure) and colloid osmotic pressure were measured during intravascular transfusion. Fetal hydrops was defined as the presence of ascites by ultrasonography. The Mann-Whitney test was used for comparison of groups; a value of p < 0.05 was considered statistically significant. RESULTS: Fifteen hydropic fetuses were matched for gestational age with 15 nonhydropic fetuses also undergoing intrauterine transfusion for anemia. On comparison with their nonhydropic counterparts, hydropic fetuses had a statistically lower colloid osmotic pressure. Umbilical venous pressure was higher and the colloid osmotic pressure--umbilical venous pressure gradient was lower in association with fetal hydrops although these differences did not achieve statistical significance. CONCLUSION: Mild abnormalities of intravascular Starling forces may play a role in the formation of hydrops in anemic fetuses.

Blood Transfusion, Intrauterine↗
PubMed1987

Technical aspects of intravascular intrauterine transfusions: lessons learned from thirty-three procedures.

Our technique for performing intravascular transfusions is described and four failed attempts are presented. The appropriate choice of needle, insertion site, and premedication are discussed. A rationale for intravenous fetal muscle blockade in selected cases is presented and a transfusion setup designed to minimize movement of the needle hub is described. Finally, the judicious use of intraperitoneal transfusions in some cases is suggested.

Blood Transfusion, Intrauterine↗
PubMed1988

The cost of irregular antibody screening.

The cost of irregular antibody screening in the third trimester exceeds +600,000.00 per perinatal death averted. This cost appears prohibitive compared with the clinical impact of the disease and costs of other screening tests.

Antibodies↗
PubMed1997

The effect of the source of transfused blood on the rate of consumption of transfused red blood cells in pregnancies affected by red blood cell alloimmunization.

OBJECTIVE: Our purpose was to compare the rate of consumption of maternally donated red blood cells with the rate of red blood cells from volunteers in fetuses affected by red blood cell alloimmunization. STUDY DESIGN: The rate of hemoglobin decline was calculated in 293 fetal transfusions in 52 pregnancies, in 43 patients affected by red blood cell alloimmunization from 1987 to 1996. Fifty-eight transfusions were excluded from analysis. Hemoglobin decline was stratified by gestational age. The rates of consumption were compared with use of unpaired t tests. RESULTS: The rates of hemoglobin decline (in grams per deciliter per day) were 18 to 24 weeks, 0.47 volunteer and 0.38 maternal (p = 0.174); 25 to 28 weeks 0.41 volunteer, 0.34 maternal (p = 0.46); 29 to 32 weeks, 0.35 volunteer, 0.33 maternal; > or = 33 weeks, 0.37 volunteer, 0.25 maternal, p = 0.048). Hemoglobin decline was less for the maternal donation group than for the volunteer donation group throughout gestation, becoming significant only in fetuses at > or = 33 weeks. CONCLUSION: In the red blood cell-alloimmunized fetus, there is less consumption of maternal than of volunteer red blood cells. This difference reaches a statistical significance only in late gestation.

Blood Donors↗
PubMed1998

Detection of fetal messenger ribonucleic acid in maternal blood to determine fetal RhD status as a strategy for noninvasive prenatal diagnosis.

OBJECTIVES: Our purpose was to test the hypothesis that reverse transcriptase-polymerase chain reaction for fetal messenger ribonucleic acid in maternal blood is more sensitive than polymerase chain reaction from genomic deoxyribonucleic acid in prenatal determination of fetal RhD blood type. STUDY DESIGN: Fetal nucleated erythrocytes in peripheral blood from 35 RhD-negative women were enriched by triple-density gradient centrifugation, anti-CD71 magnetic sorted, and deoxyribonucleic acid and ribonucleic acid extracted. Sensitivities of reverse transcriptase-polymerase chain reaction and polymerase chain reaction were compared to predict definitive fetal RhD blood type determined in fetal tissues. RESULTS: Reverse transcriptase-polymerase chain reaction was significantly more accurate (P = .03) than genomic-polymerase chain reaction in predicting fetal RhD blood type, both overall (28 of 35 vs 22 of 35) and when the fetus was RhD-positive (12 of 19 vs 6 of 19). CONCLUSIONS: Reverse transcriptase-polymerase chain reaction is more sensitive than genomic-polymerase chain reaction in detection of fetal RhD sequences in maternal blood.

Female↗
PubMed2001

Dual natriuretic peptide response to volume load in the fetal circulation.

OBJECTIVE: To measure atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in control fetuses and fetuses with Rhesus isoimmunisation before and after intravascular transfusion. The current study was designed to investigate the response of ANP and BNP to cardiac short-term and long-term volume load in the human fetus. METHODS: Fetal blood samples were collected from 18 human fetuses (nine controls, nine anemic fetuses with Rhesus isoimmunisation before and after intravascular transfusion). Fetal ANP and BNP concentrations were measured and compared to maternal plasma levels. RESULTS: Both ANP and BNP were significantly higher in fetal blood compared to the mothers. Fetuses with Rhesus isoimmunisation, characterized by long-term cardiac overload, showed significantly elevated ANP but not BNP concentration compared to the fetal controls (ANP: 80.8+/-16.6 vs. 31.6+/-7.7 pg/ml, P<0.05). However, short-term volume load due to intravascular transfusion leads to a significant increase in the fetal BNP- but not ANP-plasma level (BNP: 112.9+/-14.1 vs. 64.8+/-6.6 pg/ml, P<0.05). CONCLUSION: ANP and BNP respond differently to cardiac short- and long-term volume load in the fetal circulation. Therefore, the data suggest that in the fetus, similar to adults, ANP and BNP constitute a dual natriuretic peptide system responsive to changes in cardiac filling pressure.

Analysis of Variance↗
PubMed1989

Neutropenia and thrombocytopenia in infants with Rh hemolytic disease.

To assess the incidence and mechanisms of thrombocytopenia and neutropenia in neonates with Rh hemolytic disease, we studied 20 consecutive patients with this condition who were born at our hospital. All five patients with severe disease (hydrops) had neutropenia and thrombocytopenia before and after exchange transfusions. Two of six patients with moderately severe disease (not hydropic but requiring exchange transfusion) had neutropenia; all six had thrombocytopenia. Of nine patients with mild disease (not treated with exchange transfusions), two had neutropenia but none had thrombocytopenia. The mean platelet volume was low or normal (7.5 +/- 0.2 ft) in the patients with thrombocytopenia, and the neutropenia was not accompanied by a "left shift" (ratio of immature to total neutrophils 0.26 +/- 0.03, mean +/- SEM). In two severely affected patients, erythroid progenitor levels were elevated and their proliferative rates (tritiated thymidine suicide) were increased, whereas their granulocyte-macrophage progenitor levels and the proliferative rates of those progenitors were diminished. In a severely affected patient, the in vitro maturation of multipotent progenitors was altered, with production of a greater than normal proportion of normoblasts (p less than 0.01) but fewer neutrophils (p less than 0.02) and megakaryocytes (p less than 0.03). It appears that the marked increase in erythropoiesis in fetuses with Rh hemolytic disease can be accompanied by a down-modulation of neutrophil and platelet production.

Agranulocytosis↗
PubMed1997

Outcome for children treated with fetal intravascular transfusions because of severe blood group antagonism.

OBJECTIVE: To describe the outcome for 92 fetuses treated between May 1987 and January of 1993 with intrauterine (intravascular) transfusions for severe hemolytic disease in comparison with a high-risk and a healthy control group. STUDY DESIGN: Information on the perinatal period was obtained from the patient records. The children regularly attended the outpatient clinic, and a general pediatric examination was performed on each visit. The psychometer development of the child until age 4 1/2 years was assessed according to Gesell. At the age of 5 years, the adaptation part of the Denver Developmental Screening Test and a Dutch-language test were used. A neurologic examination was performed according to Touwen. RESULTS: In our study, 77 (83.7%) of 92 fetuses were born alive after intravascular transfusions. The overall survival rate was 79.3%. The follow-up group included 69 infants, with an age range of 6 months to 6 years. Correlation between antenatal and perinatal features showed a significant negative relationship between the number of intrauterine transfusions and the duration of phototherapy (p = 0.002). The probability that neurologic abnormalities would occur was significantly greater when perinatal asphyxia had been present (p < 0.05) and with a lower cord hemoglobin level at birth (p = 0.03). The total number of children with disabilities was 10.1% (7/69). CONCLUSIONS: The neurodevelopmental outcome for the group of survivors compared favorably with a group of high-risk, very low birth weight infants (10.1% to 18%), and less favorably with a healthy control group (10.1% to 6%).

Blood Transfusion, Intrauterine↗
PubMed2001

Fetal splenic rupture following transfusion.

BACKGROUND: Splenic rupture in the newborn is a rare complication in erythroblastosis fetalis. There are no reports of splenic rupture in the fetus affected by hemolytic disease of the newborn. CASE: A 41-year-old gravida 3, para 2-0-0-2 with severe rhesus alloimmunization was managed with serial intrauterine transfusions resulting in fetal death after the fourth procedure. Autopsy findings revealed intra-abdominal clotted blood and splenic capsular defects consistent with splenic rupture. CONCLUSION: Fetal splenic rupture might occur in hemolytic disease of the newborn associated with splenomegaly. Acute hemodynamic changes with increased intra-abdominal pressure from intrauterine transfusion might precipitate splenic rupture. (Obstet Gynecol 2001;97:824-5.

Adult↗
PubMed2001

Fetal DNA in maternal plasma: emerging clinical applications.

OBJECTIVE: To review the potential clinical diagnostic applications of fetal DNA analysis in maternal plasma or serum for noninvasive prenatal diagnosis and screening. DATA SOURCES: We conducted a MEDLINE search of articles published between January 1970 and March 2000 using the key terms "fetal DNA," "plasma," and "serum." METHODS OF STUDY SELECTION: All 369 articles describing the detection of fetal DNA in maternal plasma were reviewed. RESULTS: The diagnostic use of circulating fetal DNA in maternal plasma is currently limited to genes that are present in the fetus but not in the mother. From a clinical perspective, the most advanced application is for noninvasive detection of fetal rhesus D (Rh[D]) genotype. The results of studies performed by four different groups showed that prenatal diagnosis of fetal Rh(D) status by molecular analysis of maternal plasma or serum is routinely possible beginning in the second trimester. Noninvasive fetal genotyping should be useful for the treatment of sensitized Rh(D)-negative women whose partners are heterozygous for the Rh(D) gene because no further diagnostic or therapeutic procedures are necessary if the fetus is Rh(D) negative. Future clinical applications of fetal DNA may be in its use as a screening test for Down syndrome, preeclampsia, or preterm labor. However, these applications currently rely on the detection of Y chromosomal sequences and consequently are limited presently to male fetuses. CONCLUSION: The recent discovery of high concentrations of fetal DNA in maternal plasma represents a promising noninvasive approach to prenatal diagnosis. Compared with the analysis of the cellular fraction of maternal blood, the analysis of fetal DNA extracted from maternal plasma has the advantage of being rapid, robust, and easy to perform. The fetal DNA detected is limited to the current pregnancy. However, universal fetal gene sequences must be identified that allow analysis of genetic material from both male and female fetuses. Study of fetal DNA in maternal plasma can improve our understanding of fetomaternal biology and physiology. The long-term effects of maternal exposure to relatively high amounts of foreign DNA are unknown but represent an exciting area for future inquiry.

DNA↗
PubMed2001

Noninvasive techniques to detect fetal anemia due to red blood cell alloimmunization: a systematic review.

OBJECTIVE: To estimate, in maternal red blood cell alloimmunization, the diagnostic value of fetal ultrasonography and Doppler blood flow velocity in the evaluation and prediction of fetal anemia. METHODS: Literature from 1970 to 2000 was identified using general bibliographic databases (MEDLINE and EMBASE), the Cochrane Library and relevant specialist register of the Cochrane Collaboration, and by checking reference lists of known primary and review articles. Studies were selected if the accuracy of the fetal ultrasound parameters or Doppler studies of blood flow in the fetal vessels was estimated compared with a reference standard (fetal hemoglobin). The diagnostic tests evaluated were ultrasound measurement of the fetal spleen perimeter and Doppler studies of blood velocity estimates in the umbilical vein, ductus venosus, middle cerebral artery, thoracic aorta, and umbilical vessel combined with the thoracic aorta. Study selection, quality assessment, and data abstraction were performed independently and in duplicate. Data from the selected studies were abstracted as 2 x 2 tables comparing the diagnostic test result with the reference standard. Diagnostic accuracy was expressed as likelihood ratios. RESULTS: The review included eight primary studies with 362 pregnancies affected by red cell alloimmunization. Prospective patient recruitment and complete population details were reported in half of the selected studies (four of eight). Only one study reported masking the diagnostic test results to clinicians. The diagnostic test performance varied widely according to the type of the test evaluated and the cutoff level used to define fetal anemia, which varied from study to study. The diagnostic test study of highest methodological quality reported a positive likelihood ratio of 8.45 (95% confidence interval 4.69, 15.56) and negative likelihood ratio of 0.02 (95% confidence interval 0.001, 0.25) for maximum middle cerebral artery Doppler velocity. CONCLUSION: The literature reporting noninvasive techniques to predict fetal anemia is methodologically poor and a standard approach to the evaluation of these techniques is lacking. A recommendation for practice cannot be generated without further rigorous research.

Blood Flow Velocity↗