Extended matched intrauterine transfusions reduce maternal Duffy, Kidd, and S antibody formation.

BACKGROUND: Severe alloimmune hemolytic disease of the fetus is treated with intrauterine transfusions (IUTs). Despite C, c, E, e, and K matching between mother and donor, IUT results in new antibodies in approximately 25% of women. Newly formed Fy(a), Fy(b), Jk(a), Jk(b), and S antibodies are in 83% presumably induced by the IUT donor. Therefore, we intentionally extended matching between mother and IUT donor for these additional antigens. The results, after almost 8 years of applying this protocol, are reported. STUDY DESIGN AND METHODS: Data from February 2007 to August 2014 on IUT patients were retrieved from the Leiden University Medical Center database and from donors from the Sanquin National Donor Database. Maternal data included red blood cell (RBC) antigen profiles, RBC antibodies, and date and consecutive number of each IUT. From the fathers, children, and IUT donors the RBC antigen profiles were retrieved. RESULTS: A total of 182 fetuses from 159 women were treated with 481 IUTs. Of these, 317 IUTs (66%) were matched for Duffy, Kidd, and S antigens. Only matched IUTs were received by 77 women (48%) and 82 (52%) received (partly) nonmatched IUTs. Evaluable for new antibodies were 142 women. Duffy, Kidd, or S antibodies were formed by three of 69 women (4.3%) after matched IUTs and by eight of 73 women (11.0%) after nonmatched IUTs. CONCLUSION: Extended matching for all IUTs was not possible for approximately 50% of women. Strict adherence to Duffy, Kidd, and S antigens-matched IUTs decreased immunization against these antigens by 60% compared to nonmatched IUTs.

Implementation of routine screening for Kell antibodies: does it improve perinatal survival?

BACKGROUND: In 1998 a national program for first-trimester screening for red cell (RBC) antibodies in all pregnant women was implemented. The aim of our study was to assess the impact on perinatal mortality caused by Kell alloimmunization STUDY DESIGN AND METHODS: Prospectively collected data on all pregnant women referred to our center from 1988 until 2005 for intrauterine transfusion (IUT) for fetal anemia due to Kell alloantibodies were analyzed. The cohort was divided into two groups, those treated before 1998 and those treated after 1998. The primary outcome was fetal and neonatal survival. Secondary outcome variables were gestational age, fetal hemoglobin (Hb) levels at first IUT, severity of hydrops, and total number of IUTs per pregnancy. Causes for mortality were analyzed in detail. RESULTS: A total of 43 pregnancies were included, 18 before introduction of screening and 25 thereafter. Perinatal survival increased from 61 percent in the first period to 100 percent after introduction of screening. After 1998, fetal hydrops was generally less severe at first IUT, while gestational age and fetal Hb levels at first IUT were similar. CONCLUSION: Implementation of routine screening for Kell antibodies in pregnancy was associated with an increased referral rate for suspected fetal anemia, more timely referrals, and a higher perinatal survival rate after intrauterine treatment.

Hypoalbuminemia: a cause of fetal hydrops?

OBJECTIVE: The pathophysiology of fetal hydrops is still unclear. One factor that is believed to contribute to hydrops is hypoalbuminemia. Our research question was whether hypoalbuminemia in immune hydrops is causative or a secondary effect. STUDY DESIGN: Between 1987 and 2005, fetal blood samples were taken at the first fetal blood transfusion in 224 Rh-D alloimmunized pregnancies. We measured hemoglobin concentration and albumin concentration and assessed the severity of hydrops. RESULTS: A decrease in albumin concentration occurred only below a hemoglobin deficit of >8 SDs in 27 fetuses. In 161 nonhydropic, 44 mildly hydropic, and 19 severely hydropic fetuses, albumin concentrations were >2 SDs below the mean for gestational age in 6%, 14%, and 63%, respectively. CONCLUSION: Our finding that most fetuses with immune hydrops have an albumin concentration within the normal range (71%) suggests that hypoalbuminemia is unlikely to cause the initial development of immune hydrops.

Obstetric intensive care admissions: a 12-year review in a tertiary care centre.

OBJECTIVE: To review all pregnant women who required admission to an Intensive Care Unit (ICU) during pregnancy, childbirth or puerperium. STUDY DESIGN: Retrospective follow-up study in a tertiary care centre in The Netherlands. The files of all obstetric ICU admissions over the period 1990-2001 were reviewed. RESULTS: Over these 12 years, 142 women required ICU admission (0.76% of all deliveries, 0.70% of all adult ICU admissions). The most common reasons for ICU admission were (pre)eclampsia (62.0%) and obstetric haemorrhage (18.3%). Twenty-seven out of 142 women (19.0%) were of non-caucasian origin. The most common therapeutic interventions were transfusion of erythrocytes (66.2%), caesarean section (50.7%) and artificial ventilation (44.4%). We observed seven maternal deaths (4.9%). CONCLUSION: We need better information about high-risk obstetric patients in order to prevent severe maternal morbidity and to improve maternal care. The high number of non-caucasian women requiring ICU admission indicates the need for a study into the role of ethnicity. We have initiated a nationwide confidential enquiry into the causes of severe maternal morbidity.

Complications of intrauterine intravascular transfusion for fetal anemia due to maternal red-cell alloimmunization.

OBJECTIVE: The purpose of this study was to establish the true procedure-related complication rate of intrauterine transfusion therapy. STUDY DESIGN: A cohort study of 254 fetuses treated with 740 intrauterine blood transfusions for red-cell alloimmunization in a single center in the years 1988 to 2001. Our database was searched for perinatal deaths, emergency deliveries, infections, and preterm rupture of membranes associated with intrauterine blood transfusion. Complications were categorized by two independent obstetricians as procedure-related (PR) or not procedure-related (NPR). Logistic regression analysis was used to identify risk factors for complications. RESULTS: Overall survival was 225/254 (89%). Fetal death occurred in 19 cases (7 PR) and neonatal death in 10 cases (5 PR). There were two cases of intrauterine infection with Escherichia coli (both PR) and two other cases of preterm premature rupture of membranes (1 PR) within a week of a procedure. Emergency delivery after a transfusion was performed in 18 pregnancies (15 PR). The total PR complication rate was 3.1%, resulting in an overall PR loss rate of 1.6% per procedure. Arterial puncture, transamniotic cord puncture, refraining from fetal paralysis, and advancing gestational age were associated with the occurrence of PR complications. CONCLUSION: Our study shows that intrauterine transfusion is a safe procedure, with a relatively low PR perinatal loss rate. Arterial puncture and transamniotic cord needling carry a high risk for serious complications, whereas fetal paralysis improves the safety of the procedure. This information on risks of intrauterine transfusion therapy may help to further improve the safety of intrauterine transfusions. Data on complication rates of intrauterine transfusions are essential in counseling patients.

Treatment of fetal anemia due to red-cell alloimmunization with intrauterine transfusions in the Netherlands, 1988-1999.

OBJECTIVE: To assess pregnancy outcome after intrauterine transfusion (IUT) for fetal anemia due to red-cell alloimmunization in the Netherlands over 11 years, in order to improve care and counseling. METHODS: A retrospective cohort study was conducted from January 1, 1988, to January 1, 1999. Data were collected prospectively on all red-cell alloimmunized pregnancies requiring intrauterine blood transfusions. Primary outcome variables were fetal and neonatal survival in relation to the type of antibody, gestational age and presence or absence of hydrops. In addition, we studied short-term neonatal morbidity and procedure-related complications. RESULTS: A total of 210 fetuses from 208 pregnancies received 593 transfusions. Overall survival rate was 86%. Survival of hydropic fetuses (78%) was significantly different from those without hydrops (92%). Low survival rates were especially found in hydropic fetuses with the first transfusion at gestational ages of 20 weeks or less (55%) or between 28 and 32 weeks (59%). In maternal rhesus D [Rh(D)] immunization 89% of fetuses survived, whereas survival in the case of Kell immunization was 58%. All fetuses with anemia due to Rh(c) immunization survived. The overall fatal procedure-related complication rate was 1.7% per procedure, resulting in a fetal loss rate of 4.8%. CONCLUSIONS: Intrauterine intravascular transfusions are effective in the management of fetal alloimmune anemia. Fetal hydrops, mostly associated with late referral, decreases the chance of survival. To improve the outcome of red-cell alloimmunized pregnancies early diagnosis of fetal anemia and referral to a specialized center are important, enabling the start of treatment before hydrops develops.

Effect of an increase of the hematocrit on middle cerebral artery peak and umbilical vein maximum velocities in anemic fetuses.

OBJECTIVE: To measure the effects of acute large increases of the hematocrit on fetal peak arterial and maximum venous blood flow velocities. METHODS: Middle cerebral artery peak flow velocities and umbilical vein maximum flow velocities were measured before, immediately after, and 12-24 h after intrauterine transfusions. All measurements were standardized for gestational age. RESULTS: Complete measurements were obtained at 60 intrauterine transfusions. The mean hematocrit before intrauterine transfusion was 0.19 l/l and after 0.40 l/l. The middle cerebral artery peak flow velocity decreased immediately after transfusion in 59 of the 60 cases. There was a rise in umbilical vein maximum flow velocity immediately after intrauterine transfusion in 37 of the 60 cases. The sensitivity of middle cerebral artery peak flow velocity for severe anemia before intrauterine transfusion was 54% and the specificity 57%. The sensitivity of umbilical vein maximum flow velocity for severe anemia before intrauterine transfusion was 67% and the specificity 57%. CONCLUSIONS: An acute large increase of the fetal hematocrit significantly decreases middle cerebral artery peak flow velocity. The effect on umbilical vein maximum velocity is, however, unpredictable.

Amniotic fluid delta OD 450 values accurately predict severe fetal anemia in D-alloimmunization.

OBJECTIVE: To assess the diagnostic accuracy of amniotic fluid Delta OD 450 values in the second and third trimesters of D-alloimmunized pregnancies. METHODS: We searched our database for singleton D-alloimmunized pregnancies with nonhydropic fetuses, where amniocentesis was performed within 4 days of first fetal blood sampling. Amniotic fluid Delta OD 450 values were plotted on an extrapolated Liley's chart. Sensitivity and specificity were calculated for two commonly used cutoff levels, Liley's zone 3 and the upper third of Liley's zone 2. Severe fetal anemia was defined as a hemoglobin concentration of more than 5 standard deviations below the normal mean for corresponding gestational age. RESULTS: Seventy-nine pregnancies met our inclusion criteria. Overall accuracy of the extrapolated Liley's curve in predicting severe fetal anemia was 75% (95% confidence interval [CI] 64, 84) for zone 3 and 86% (95% CI 77, 93) when the upper third of zone 2 was included. Sensitivity of Delta OD 450 values in Liley's zone 3 or the upper third of Liley's zone 2 was 95% (95% CI 74, 100) before and 98% (95% CI 89, 100) after 27 weeks. CONCLUSION: Liley's extrapolated curve predicts severe fetal anemia with reasonable accuracy and high sensitivity.