Need For Intrauterine Transfusion Research Articles

The Role of Plasmapheresis in the Management of Severe Rhesus Incompatibility During Pregnancy: A Literature Review

ABSTRACTIntroductionTo evaluate the effectiveness and safety of plasmapheresis in cases complicated by severe alloimmunization.MethodsWe reviewed multiple studies from databases like Medline, Embase, and Cochrane, looking specifically for research on ‘Rhesus incompatibility’, ‘plasmapheresis’, and ‘pregnancy’. After narrowing down, we included 46 studies that met our criteria to see how this treatment affected both prenatal and postnatal health.ResultsOut of 208 pregnancies analysed, about 22.1% sadly resulted in foetal loss, with one neonatal death. However, starting plasmapheresis as early as 3 weeks helped delay or avoid the need for Intrauterine blood transfusions in cases of severe foetal anaemia. Most of the babies born (77.4%) had positive outcomes, although many needed phototherapies after birth. Combining IVIG with plasmapheresis appears to be safe, with good postnatal outcomes.ConclusionsPlasmapheresis shows promise as a treatment for severe Rhesus sensitisation, potentially reducing the need for Intrauterine transfusions and improving newborn outcomes. More studies are needed to refine treatment protocols and confirm these early findings.

Incidence and Risk Factors of Cholestasis in Newborns with Hemolytic Disease-A Case-Control Study.

Background/Objectives: One of the rare causes of cholestasis may be hemolytic disease of the fetus and newborn (HDFN). Methods: We retrospectively analyzed 88 medical records of HDFN newborns with cholestasis and 186 records of children with HDFN without cholestasis and conducted an observational, case-control, retrospective study. Results: Factors influencing the risk of cholestasis were lower gestational age at birth (36.83 ± 1.9 vs. 37.57 ± 1.8, p = 0.002), Rh or Kidd HDFN (80.7% vs. 53.2%), and the need for intrauterine transfusion (27.3 vs. 11.8%). The subjects had lower hemoglobin concentrations at birth (14.01 ± 3.8 vs. 16.39 ± 2.8 g/dL) and during whole hospital stay, higher cord blood total bilirubin concentration (4.26 ± 1.8 vs. 2.39 ± 1.4 mg/dL), higher maximum bilirubin concentration (15.27 ± 5.8 vs. 10.24 ± 3.4 mg/dL), and more frequent liver ultrasound abnormalities (19.9 vs. 6.3%). They also required more extended hospitalization due to higher rates of postnatal blood transfusion (33 vs. 3.8%), more frequent need for exchange transfusion (8.8% vs. 2.2%), more extended time and higher risk of phototherapy (94.3 vs. 59.1%), and higher usage of immunoglobulins (55.7 vs. 8.1%), parenteral nutrition (45.5 vs. 12.9%), and antibiotics (14.8 vs. 4.8%). Conclusions: The risk factors for cholestasis in children with HDFN are lower gestational age at delivery, Rh and Kidd serological type of HDFN, and the need for intrauterine transfusions.

Maternal IVIG Administration in Rhesus Alloimmunized Pregnancies: A Systematic Review

Background: Rhesus (Rh) alloimmunization occurs when an Rh negative mother is exposed to red blood cells (RBC) from an Rh positive fetus. The mother develops antibodies in the current pregnancy that attack Rh positive fetus in subsequent pregnancy, causing hemolytic disease of the fetus and newborn (HDFN). RhD is the most common antigen to result in fetal anemia requiring intrauterine transfusions (IUT). Although the traditional method of management and highly effective, IUTs carry significant risk particularly when performed early in gestation, potentially resulting in procedure-related fetal deaths. Intravenous immunoglobulin (IVIG) therapy may postpone or even replace invasive intrauterine treatment in fetuses of mothers with severe alloimmunization in previous pregnancies. Objective: To evaluate whether maternal administration of IVIG in high-risk Rhesus alloimmunized pregnancies is effective in delaying the need for IUTs as well as delaying the onset of severe fetal anemia and thus in diminishing its clinical consequences. Study design: A systematic literature search was conducted for maternal intravenous immunoglobulin administration in pregnancies with Rh isoimmunization in the following databases: Medline, Embase and Cochrane Library from 1946 to 2 February 2023. Inclusion criteria was studies done during pregnancy in which IVIG was administered to the mother in Rh alloimmunized pregnancies/fetal anemia. All non-english papers, animal papers, systematic reviews, editorials and studies in which IVIG was administered to non-pregnant patients were excluded. Data was extracted from these full texts and analyzed for inclusion based on the quantity of usable data and patient information. Extracted data included maternal antibody type and titer, number of maternal IVIG administrations, number of IUTs, and fetal Hb levels prior to first IUT and at delivery. Time interval (weeks) between IVIG and first IUT was also included in the extracted data along with gestational age at delivery. Individual patient data extraction was done for studies that provided data. Results: 16 studies were included in data analysis. Analysis of extracted data is ongoing.

Effect of Anti-D titers in RhD-negative pregnant women on fetuses and newborns: A retrospective study

BackgroundTransplacental-derived anti-D IgG in RhD-negative pregnant women can trigger an immune response to Rh D-positive red cells in fetuses and newborns. We assessed the effect of anti-D titers in RhD-negative pregnant women on fetuses and newborns. MethodsThe clinical data of 142 singleton RhD-sensitized pregnancies were retrospectively collected. The pregnant women received routine prenatal care and the newborns had standard care. Based on the tertile categories of the pregnancies, the maximum titers of anti-D IgG in the pregnant women were divided into three groups ranging from low to high as follows: low-titer group (anti-D titer: 1:4–1:128, n = 57); medium-titer group (anti-D titer: 1:256–1:512, n = 50); and high-titer group (anti-D titer: 1:1024–1:4096, n = 35). ResultsThe frequencies of major neonatal complications did not significantly differ among the three groups. The high-titer group had the highest frequency of pregnancies requiring intrauterine transfusion (IUT) and number of IUTs among the three groups. The high-titer group had a significantly higher frequency of newborns treated with top-up transfusion, number of top-up transfusions, frequency of newborns treated with exchange transfusion (ET), and number of ETs when compared to the low-titer group. ConclusionHigher anti-D titers in RhD-negative pregnant women predict more severe fetal and neonatal hemolytic anemia. Increasing maternal anti-D titers results in an increased need for IUTs, and neonatal top-up transfusions and ETs. Methods for reducing titers of anti-D IgG in RhD-sensitized pregnant women warrants further investigation.

Immunomodulation for early-onset haemolytic disease of the fetus/newborn: Can we delay the need for intrauterine transfusions?

When cases of severe fetal anaemia due to maternal red-cell alloimmunization present in the early second trimester, standard treatment with intrauterine transfusion often results in fetal loss. The report by Vlachodimitropoulou et al. offers new insight into the use of maternal intravenous immune globulin to delay the need for intrauterine transfusion. Performing these procedures at a later gestational age increases the likelihood of technical success and subsequent perinatal survival. Commentary on: Vlachodimitropoulou et al. Intravenous immune globulin in the management of severe early onset of red cell alloimmunization. Br J Haematol 2023; 200:97-103.

Intravenous immunoglobulin in the management of severe early onset red blood cell alloimmunisation.

Our objective was to assess the effect of maternal intravenous immunoglobulin (IVIG) administration for severe red blood cell (RBC) alloimmunisation on fetal outcomes. This is a case-control study. Women with a history of severe early onset alloimmunisation resulting in fetal loss in a previous pregnancy and high anti-D or anti-K antibody titres received IVIG in a subsequent pregnancy. We assessed gestational age at first transfusion and fetal outcomes in the subsequent pregnancy and compared these with the outcomes in the previous pregnancy. The most responsible antibody was anti-D in 17 women and anti-K in two others, whilst seven had more than one antibody. In all, 19 women received IVIG in 22 pregnancies, two of which did not even need an intrauterine transfusion (IUT). For previous early losses despite transfusion, IVIG was associated with a relative increase in fetal haemoglobin between treated and untreated pregnancies of 36.5 g/L (95% confidence interval 19.8-53.2, p=0.0013) and improved perinatal survival (eight of eight vs. none of six, p=0.001). For previous losses at <20 weeks, it enabled first transfusion deferral in subsequent pregnancies to at least 19.9 weeks (mean 23.2 weeks). Overall, IVIG decreases the severity of haemolytic disease of the fetus and newborn and allows deferral of the first IUT to a safer gestation in severe early-onset RBC alloimmunisation and rarely may even avoid the need for IUT entirely.

Maternal intravenous immunoglobulin: A non-invasive treatment option for Rhesus D-sensitised women with previous adverse pregnancy outcomes

Background. Maternal intravenous immunoglobulin (IVIG) may delay the onset and severity of fetal anaemia in Rhesus D (RhD)- sensitised pregnancies, thereby minimising the need for intrauterine transfusion and its associated complications. Objective. To compare the pregnancy outcomes of RhD-sensitised women who received antenatal IVIG with those who did not receive antenatal IVIG. Methods. This was a retrospective cross-sectional analysis of RhD-sensitised women who attended the Wits Fetal Medicine Centre (Johannesburg) from 1 January 2008 to 31 May 2018. Criteria for maternal IVIG administration were: (i) previous adverse pregnancy outcome (early neonatal death, intrauterine fetal death or miscarriage related to RhD sensitisation), ( ii ) women with high antibody titre levels (≥1:64) in the absence of fetal anaemia; and ( iii ) rising antibody titre levels. Maternal antibody titre levels, pregnancy and neonatal outcomes were compared in women who received IVIG v. those who did not receive IVIG. Results. Of the 42 RhD-sensitised women, 14 received IVIG. A greater proportion of women experienced a decrease in antibody titres in the IVIG v. no-IVIG group (43% v. 11%, respectively; p =0.04). Nine of the 10 women in the IVIG group with a previous adverse pregnancy outcome had a successful pregnancy outcome following IVIG treatment. Conclusion. Maternal IVIG may provide a successful pregnancy outcome in RhD-sensitised women with previous adverse pregnancy outcomes related to Rh disease, or women with raised or increasing maternal antibody titre levels who present in the first or early second trimester.

Outcome of fetuses with congenital parvovirus B19 infection: systematic review and meta-analysis.

To explore the outcome of fetuses affected by congenital parvovirus B19 (PB19) infection, with or without signs of hydrops on ultrasound. PubMed, EMBASE and CINAHL databases were searched for studies reporting on prenatal diagnosis and outcome of fetal PB19 infection. The outcomes explored were miscarriage, perinatal death (PND), intrauterine death, neonatal death, spontaneous resolution of hydrops or fetal anemia, need for intrauterine transfusion (IUT), resolution of hydrops or anemia after transfusion, fetal loss following transfusion, abnormal brain scan after birth and abnormal neurodevelopmental outcome. Outcomes were reported according to the presence or absence of signs of hydrops on ultrasound. A subgroup analysis was performed including hydropic and non-hydropic fetuses diagnosed at < 20 weeks and ≥ 20 weeks of gestation. Meta-analyses of proportions and meta-analyses using individual-data random-effects logistic regression were performed to analyze the data. Thirty-five observational studies were included, involving 611 fetuses affected by PB19 infection. The risks of miscarriage (odds ratio (OR), 11.5; 95% CI, 2.7-49.7) and PND (OR, 4.2; 95% CI, 1.6-11.0) were higher in fetuses with PB19 infection presenting, compared with those not presenting, signs of hydrops on ultrasound. In fetuses affected by hydrops, spontaneous resolution of the infection, defined as disappearance of hydrops without need for IUT, occurred in 5.2% (95% CI, 2.5-8.8%) of cases whereas, in the group of fetuses not affected by hydrops, infection resolved in 49.6% (95% CI, 20.7-78.6%) of cases. IUT was performed in 78.7% (95% CI, 66.4-88.8%) of hydropic and in 29.6% (95% CI, 6.0-61.6%) of non-hydropic fetuses affected by congenital PB19 infection and resolution of the infection after IUT occurred in 55.1% (95% CI, 34.0-75.3%) and in 100% (95% CI, 57.3-100%) of cases, respectively. The risk of fetal loss after IUT was higher in fetuses affected compared with those not affected by hydrops (OR, 9.8; 95% CI, 2.8-34.6). The prevalence of abnormal brain imaging was 9.8% (95% CI, 2.5-21.0%) in fetuses affected and 0.0% (95% CI, 0.0-7.0%) in those not affected by hydrops, whilst the corresponding figures for abnormal neurodevelopmental outcome were 9.5% (95% CI, 2.6-20.2) and 0.0% (95% CI, 0.0-7.5), respectively; however, statistical power to assess these outcomes was inadequate due to the small number of included cases. Hydrops is the main determinant of mortality and adverse perinatal outcome in fetuses with PB19 infection. Perinatal outcome in non-hydropic fetuses is generally favorable. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

531: Anti-Rh(D) Alloimmunization: Outcomes at a single institution

To review outcomes in gravidas with anti-Rh(D) alloimmunization in their first alloimmunized pregnancy. Data collected from pregnancies complicated by anti-Rh(D) alloimmunization at The Ohio State University from 1969 through June 2017 was reviewed retrospectively. Only the first sensitized pregnancy for each patient was included in this descriptive study, and we excluded women with more than one red blood cell antibody. Antibody titers were reviewed, with a critical titer defined as >16. Significant hemolytic disease of the fetus and newborn (HDFN) was diagnosed in the setting of intrauterine fetal demise (IUFD), hydrops fetalis, need for intrauterine transfusions (IUTs), and need for neonatal red blood cell transfusions (exchange or simple). Of the 590 patients who met the inclusion criteria, 178 (31.2%) maintained an anti-D titer <16. A critical titer was identified in 392 patients (68.8%), 234 (57.7%) of whom did not develop HDFN. Outcomes for the 178 pregnancies (31.2% of the entire cohort) complicated by HDFN are depicted in Figure 1. Of the 173 women who reached a critical titer in the first or second trimester, 82 (47.4%) developed HDFN while this disease occurred in only 76 (34.7%) of the 219 patients who achieved a critical titer in the third trimester (RR 1.37, 95% CI 1.07 to 1.74). A critical titer was identified at an average gestational age of 26 weeks and 3 days in women with HDFN compared to 28 weeks and 5 days in patients without disease. Alloimmunization to the Rh(D) antigen is relatively uncommon in the age of Rh immune globulin (RhIg) prophylaxis, but cases persist due to unrecognized fetomaternal bleeding and failure to properly administer prophylaxis. Essentially, in a patient’s first pregnancy complicated by anti-Rh(D) alloimmunization, approximately 1/3 of women will maintain a low antibody titer, 1/3 will reach a critical titer without developing sequelae, and 1/3 will develop significant HDFN. Understanding the natural history of this disease allows physicians to provide appropriate counseling about the likelihood of related outcomes.

Severe Rh alloimmunization and hemolytic disease of the fetus managed with plasmapheresis, intravenous immunoglobulin and intrauterine transfusion: A case report

Rh alloimmunization remains a potentially devastating complication of pregnancy, with fetal anemia causing hydrops and intrauterine death. Intrauterine transfusion is the standard treatment, but is particularly dangerous before 20 weeks gestation. When the need for intrauterine transfusion is anticipated early in pregnancy, immune-modulating therapies such as plasmapheresis and IVIG have been used to delay transfusion to a later gestational age. We report a 35-year-old G5P1 Rh(D)-negative woman with severe Rh alloimmunization managed successfully with sequential plasmapheresis, intravenous immune globulin and intrauterine transfusion. The optimal plasmapheresis treatment protocol and incremental benefit of IVIG remains unknown.

Therapeutic plasma exchange and intravenous immunoglobulin as primary therapy for D alloimmunization in pregnancy precludes the need for intrauterine transfusion

Maternal D alloimmunization detected in early gestation requires aggressive intervention to prevent severe fetal anemia. An intrauterine transfusion (IUT) is indicated to prevent fetal death once severe fetal anemia has been detected, but is not without risk. Protocols combining therapeutic plasma exchange (TPE) and intravenous immunoglobulin (IVIG) have been described, but they usually bridge to IUT. We describe a 27-year-old G4, P0-1-2-0 Caucasian female with a history of ruptured ectopic pregnancy presented at 12 weeks' gestation with a very high anti-D titer (2048). TPE was performed on that week and twice more in the following week, with a fourth final exchange during Week 14. A loading dose of IVIG (2 g/kg) was administered over 2 days after the third TPE and then 1 g/kg per week until Week 28 (total, 14 doses). The antibody titer decreased to 256 by the beginning of 15 weeks' gestation and remained stable at that level for the remainder of the pregnancy. Doppler ultrasonographic measurements of the fetal middle cerebral artery peak flow velocity performed throughout gestation showed no evidence of fetal anemia. A healthy male infant was delivered at 37 weeks' gestation with mild immune-mediated hemolysis. The infant underwent successful treatment with an IVIG dose of 750 mg/kg and a red blood cell exchange. Our unique TPE-IVIG protocol was successful at preventing the onset of severe fetal anemia in a patient with high titer anti-D. Since IUT may be fatal, our approach offers a safer and less-invasive treatment regime that can adequately sustain a fetus until term.

Non-Invasive Protocol For The Screening, Diagnosis and Treatment Of Hemolytic Perinatal

A protocol-based and multidisciplinary follow-up of the pregnant woman including Primary Care, Hematology Deparment, and Fetal Medicine, is required for the appropriate prophylaxis and treatment of the hemolytic disease of the newborn (HDN). The combined application of new monitoring techniques, such as the study of the fetal D antigen (RhD) by PCR in maternal blood and the determination of the blood flow of the middle cerebral artery (MCA) in the fetus by Doppler ultrasonography allows the child's prenatal follow up without invasive procedures. ObjectivesTo evaluate the results obtained using this strategy of combined monitorization in our institution from 2009. Secondary aims were:To review all cases of immunized pregnant women and to analyze the outcomes of selective anti D prophylaxis at week 28, according to fetal RHD analyzed by PCR in maternal blood.Patients andMethods38,000 pregnant women are included in the analysis. Antibody (Ab) screening is made during the first 3 months of pregnancy, and titer is evaluated using agglutination tests in immunized women with clinically significant (CS) Ab. RhD negative women immunized against RhD undergo fetal RHD and SRY determination using a new multiplex RT-PCR assay for fetal cell-free DNA in maternal plasma as soon as possible.In addition, in patients with CS-Ab and previous obstetric complications or antibody titer >1/32 or rising, MCA Doppler is performed to assess the degree of fetal anemia and evaluate the need for intrauterine transfusion (IUT), or to advance childbirth to week 34.On the other hand, non-immunized RhD negative, women are controlled again in the 28th week to re-assess the presence of antibodies and well as fetal RHD and SRY determination and only those with RHD positive fetuses receive anti D gammaglobulin. ResultsAb were found in 290 pregnant women. 116 were not clinically significant and did not require further control. 174 women had CS-Ab against Rh, Kell, Jk, Fy, and Lu antigen systems.Out of them, 29 RhD negative women were immunized against anti D (all of them due to previous incomplete or no prophylaxis). The study of fetal RHD revealed that 9 of these 29 women had RHD- fetuses and were released from hospital. The remaining 20 RhD- patients together with those 145 women with other CS-Ab underwent obstetric history assessment as wellas antibody titers assay, and MCA Doppler, according to the criteria mentioned above. Remarkably, after these assessments only 11 IUTs were required in 6 pregnant women, all of them were performed without any complications. Involved antibodies in these 6 patients were: Rh, Kell and Jk.Fetal RHD testing in 4,064 RhD negative women at the 28thweek detected 1,423 who had RHD- fetuses which did not require prophylaxis. There were no false negatives among the newborns. Conclusions1. A combined monitorization strategy of the pregnant woman avoids unnecessary controls and invasive procedures.2. Anti D prophylaxis has 100% efficacy in all pregnant women requiring it.3. Those women immunized against RhD, who had RHD- fetuses, can have a quiet gestation since week 12 without further immunohematologic assessments. Disclosures:No relevant conflicts of interest to declare.

Postnatal outcome in neonates with severe Rhesus c compared to Rhesus D hemolytic disease

Neonates with Rhesus c (Rh c) hemolytic disease of the fetus and newborn (HDFN) are often managed in the same way as neonates with Rhesus D (Rh D) HDFN, although evidence to support this policy is limited. The objective of this study was to evaluate neonatal outcome in severe Rh c HDFN compared to Rh D HDFN. A retrospective study of (near-)term neonates with severe Rh c (n = 22) and Rh D HDFN (n = 103; without additional antibodies) admitted to the Leiden University Medical Center between January 2000 and October 2011 was conducted. The need for intrauterine transfusions (IUTs), phototherapy, exchange transfusions (ETs), and top-up transfusions up to 3 months of age were recorded and compared between both groups. Although there was a trend for a slightly more severe antenatal course for Rh D HDFN reflected by an earlier need for and higher number of IUTs (median [interquartile range], 2 [1.5-4] vs. 2 [1-2] in Rh c HDFN; p = 0.070), no significant differences were found for the postnatal course between Rh c and Rh D group in days of phototherapy (mean, Days 4.8 and 4.6, respectively; p = 0.569), need for ET (50% vs. 44%, respectively; p = 0.589), and top-up transfusions (62% vs. 78%, respectively; p = 0.128). Postnatal outcome in neonates with severe Rh c HDFN is similar compared to neonates with severe Rh D hemolytic disease in terms of days of phototherapy, need for ET, and need for top-up transfusions. These results justify a similar postnatal management of neonates with Rh D and Rh c HDFN.

Investigation and outcome of fetal anaemia in fetal parvovirus infection in pregnancy

BackgroundParvovirus infection may affect 1–5% of pregnant women. Clinical impact of maternal infection on the fetus is diverse (uncomplicated pregnancy, fetal anaemia, hydrops or intrauterine death). In mothers with proven...

Plasmapheresis and intravenous immune globulin for the treatment of D alloimmunization in pregnancy

The alloimmunized pregnancy can result in fetal and newborn mortality due to fetal anemia. Control of fetal anemia has not been possible until recently, and management consists of following the degree of fetal anemia during gestation until intrauterine transfusion is feasible to support the fetus until delivery. Cordocentesis and intrauterine transfusion have potential complications that have been well documented. Control of fetal anemia via immune modulation utilizing plasmapheresis and intravenous immune globulin administration has been attempted alone and in combination with varying results. We present a case report of an Rh(D) alloimmunized pregnancy, in which successful management consisted of initial therapeutic plasmapheresis (TPE) followed by intravenous immunoglobulin (IVIG) administration until delivery at 37 weeks gestation without the need for intrauterine transfusion.

Pregnancy outcome for Rh-alloimmunized women

Objective: To compare perinatal results of Rh-alloimmunized pregnancies managed with spectrophotometric amniotic fluid analysis or fetal middle cerebral artery Doppler ultrasonographic velocimetry. Method: A descriptive observational study involving 291 consecutive Rh-negative pregnancies. Group 1 consisted of 74 isoimmunized women managed with amniotic fluid spectrophotometry; group 2 of 25 isoimmunized women managed with Doppler ultrasonography; and group 3 of 192 nonimmunized Rh-negative women. The variables analyzed were need for intrauterine or neonatal transfusion, mode and time of delivery, birth weight, neonatal hematocrit, and perinatal mortality. Results: Need for intrauterine transfusion, birth weight, prematurity, rate of cesarean section, and perinatal mortality were similar in groups 1 and 2. Neonatal hematocrit was significantly lower and the need for neonatal transfusion was significantly higher when spectrophotometry rather than Doppler ultrasonographic velocimetry was used. Conclusion: Fetuses managed with Doppler ultrasonographic velocimetry had a higher hematocrit at birth and a lesser need for neonatal transfusion, suggesting that this noninvasive method of monitoring fetal anemia is a better choice.

Unusual antibody titer in a severe case of rhesus incompatibility

Unusual antibody titer in a severe case of rhesus incompatibility

Management of Rhesus Alloimmunization in Pregnancy

Rhesus immune globulin has decreased the prevalence of rhesus D alloimmunization in pregnancy so that only approximately six cases occur in every 1,000 live births. The rarity of this condition warrants consideration of consultation with or referral to a maternal-fetal medicine specialist with experience in the monitoring and treatment of patients with red cell alloimmunization in pregnancy. Evaluation for the presence of maternal anti-D antibody should be undertaken at the first prenatal visit. First-time sensitized pregnancies are followed with serial maternal titers and, when necessary, serial Doppler assessment of the peak systolic velocity in the middle cerebral artery. In cases of a heterozygous paternal genotype, new DNA techniques now make it possible to diagnose the fetal blood type through free fetal DNA in maternal plasma. When there is a history of an affected fetus or infant, maternal titers are no longer predictive of risk in subsequent pregnancies. Serial peak middle cerebral artery velocities using Doppler ultrasonography can be used in these pregnancies to detect fetal anemia. In some situations, intrauterine transfusion is necessary through ultrasound-directed puncture of the umbilical cord with the direct intravascular injection of red cells. Perinatal survival rates of more than 90% have been reported; hydrops fetalis reduces the chance for a viable outcome by up to 11%. Neonatal and infant outcomes are complicated by the need for repeated transfusions secondary to suppressed erythropoiesis. Long-term studies have revealed normal neurologic outcomes in more than 90% of cases. Future therapy will involve selective modulation of the maternal immune system, making the need for intrauterine transfusions a rarity.

Intravenous immunoglobulin as primary therapy or adjuvant therapy to intrauterine fetal blood transfusion: a new approach in the management of severe Rh-immunization.

Maternal high dose intravenous immunoglobulin (IVIG) has shown promise in the management of severe Rh-immunization. Intravenous immunoglobulin, blocks Fe mediated antibody transport across the placenta and blocks destruction of fetal red cells and reduces maternal antibody levels. We have tried this new therapy in 6 patients with severe Rh-immunization, with high maternal antibody titres and previous hydrops and intrauterine deaths. Intravenous immunoglobulin was given from 13-18 weeks of gestation 3-4 weekly, till intrauterine transfusion (IUT) or delivery. Intensive fetal monitoring was done. No fetal hydrops or deaths occurred in any of the 6 cases. Only 2 cases needed intrauterine transfusion. IVIG delayed the onset of fetal anemia by 8-17 weeks thus deferring the need for IUT. All pregnancies continued till 32-36 weeks and all 6 babies did well in the neonatal period.

Noninvasive assessment of fetal anaemia

In pregnancies complicated by severe red cell alloimmunization, fetal haemolytic anaemia can lead to intrauterine demise as early as 17 weeks' gestation. Intrauterine intraperitoneal blood transfusion, introduced by Liley in 1963, proved to be the first successful example of fetal therapy. The use of this complex procedure, involving X-ray guided puncture of the fetal peritoneal cavity, was limited to fetuses with a gestational age ranging from 24 to 33 weeks. When performed below 26 weeks, survival rates were as low as 16%. The need for intrauterine transfusion was mainly based on determination of bilirubin levels in amniotic fluid, and plotting the results in a three-zone chart devised by Liley. This chart was based on correlations of amniotic fluid bilirubin concentrations with the degree of neonatal anaemia, and ranged from 27 to 41 weeks' gestation. In the 1980s, with the introduction of ultrasound-guided intravascular transfusion, treatment became possible from 17–18 weeks' gestation onwards. Consequently, there was a need for diagnostic tests to assess the degree of anaemia in the second trimester fetus. The use of the Liley chart was shown to be unreliable in the prediction of disease severity before 27 weeks' gestation. Ultrasonographic detection of fetal hydrops in these pregnancies reliably indicates severe anaemia, but for reasons that are still unclear, a significant number of severely anaemic fetuses do not show ultrasonographic signs of hydrops. In 1988, Nicolaides et al studied the use of several ultrasonographic parameters to predict anaemia in nonhydropic fetuses. Their results were disappointing, and they concluded that the only reliable diagnostic test to assess the degree of fetal disease was fetal blood sampling.