Haemolytic disease of the foetus and newborn (HDFN) is a condition in which the red blood cells of the foetus and the newborn child are destructed due to maternal alloantibodies. This can lead to... Show moreHaemolytic disease of the foetus and newborn (HDFN) is a condition in which the red blood cells of the foetus and the newborn child are destructed due to maternal alloantibodies. This can lead to anaemia already in early pregnancy. In case of severe anaemia, it can be necessary to perform one or more blood transfusions to the anaemic foetus, so called intrauterine transfusions (IUTs). This thesis evaluates the current therapy for HDFN and describes exogenous erythropoietin as potential new therapeutic agent to treat anaemia. It also gives starting points to individualise the treatment of these children in the future, as predictive values were identified for a more severe neonatal disease course. In addition to short-term outcomes measures after birth, the long-term effects of IUTs were also critically evaluated to optimise the treatment of HDFN. Show less
Ree, I.M.C.; Besuden, C.F.J.; Wintjens, V.E.H.J.; Verweij, J.J.T.; Oepkes, D.; Haas, M. de; Lopriore, E. 2021
Aim: To investigate the school performance and behavioral difficulties in children with hemolytic disease of the fetus and newborn (HDFN) treated with intrauterine transfusion (IUT) compared to... Show moreAim: To investigate the school performance and behavioral difficulties in children with hemolytic disease of the fetus and newborn (HDFN) treated with intrauterine transfusion (IUT) compared to Dutch norm data.Study design: Cros-sectional cohort study. Subjects: Children who received one or multiple IUTs for severe Rh-or K (Kell)-mediated HDFN between January 2008 and January 2015 at the LUMC.Outcome measures: School performance reports were assessed as well as behavioral difficulties as assessed with the Dutch child behavioral checklist (CBCL) by parents and caregivers and the Teacher Report Form (TRF) completed by teachers.Results: A response rate of 56% (70 children, aged 5-12 years) was obtained. Grade repetition occurred in 13 cases (19%), 16 children (23%) received some form of additional help, most often support by a speech therapist (n = 8), but also support for dyslexia (n = 4), physical therapy (n = 2) and social-emotional support (n = 2). None of the children in our study group attended special-needs education. School performance levels for reading comprehension, spelling and mathematics according to the Dutch National Pupil Monitoring System were similar for the study population and Dutch norm data. The incidence of behavioral problems as reported by parents was similar to the Dutch norm data, teachers reported less behavioral difficulties in the study group. Conclusion: This study shows favorable and reassuring school development in children treated with IUT in an experienced fetal-therapy center. A normal distribution in school and behavioral development is to be expected for children with HDFN treated with IUTs. Show less
Ree, I.M.C.; van't Oever, R.M.; Zwiers, C.; Verweij, E.J.T.; Oepkes, D.; Haas, M. de; Lopriore, E. 2021
BACKGROUND: Fetal bilirubin is routinely measured at our center when taking a pretransfusion blood sample at intrauterine transfusions in hemolytic disease of the fetus and newborn. However, the... Show moreBACKGROUND: Fetal bilirubin is routinely measured at our center when taking a pretransfusion blood sample at intrauterine transfusions in hemolytic disease of the fetus and newborn. However, the clinical value of fetal bilirubin assessment is not well known, and the information is rarely used. We speculated that there could be a role for this measurement in predicting the need for neonatal exchange transfusion.OBJECTIVE: This study aimed to evaluate the predictive value of fetal bilirubin for exchange transfusions in severe hemolytic disease of the fetus and newborn.STUDY DESIGN: A total of 186 infants with Rh alloantibody-mediated hemolytic disease of the fetus and newborn treated with one or more intrauterine transfusions at the Leiden University Medical Center between January 2006 and June 2020 were included in this observational study. Antenatal and postnatal factors were compared between infants with and without exchange transfusion treatments. The primary outcome was the fetal bilirubin levels before the last intrauterine transfusion in relation to the need for exchange transfusion.RESULTS: In a multivariate logistic regression analysis, the fetal bilirubin level before the last intrauterine transfusions (odds ratio, 1.32; 95% confidence interval, 1.09-1.61 per 1 mg/dL) and the total number of intrauterine transfusions (odds ratio, 0.63; 95% confidence interval, 0.44-0.91 per intrauterine transfusion) were independently associated with the need for exchange transfusion. The area under the curve was determined at 0.71. A Youden index was calculated at 0.43. The corresponding fetal bilirubin level was 5 mg/dL and had a sensitivity of 79% and a specificity of 64%.CONCLUSION: A high fetal bilirubin level before the last intrauterine transfusion was associated with a high likelihood of neonatal exchange transfusion. Show less
Ree, I.M.C.; Besuden, C.F.J.; Wintjens, V.E.H.J.; Verweij, J.J.T.; Oepkes, D.; Haas, M. de; Lopriore, E. 2021
Background and objectives Guidelines and indications for exchange transfusion in haemolytic disease of the foetus and newborn (HDFN) have changed drastically in the past decades, causing a decline... Show moreBackground and objectives Guidelines and indications for exchange transfusion in haemolytic disease of the foetus and newborn (HDFN) have changed drastically in the past decades, causing a decline in exchange transfusion rate. This study aims to evaluate the incidence of exchange transfusions (ETs) in neonates with Rh-mediated HDFN over the past 20 years at our centre, and report potentially ET-related complications as well as indicators for bilirubin encephalopathy.Material and methods In this observational study, 438 neonates were included with HDFN, born >= 35 weeks gestational age at the Leiden University Medical Centre between January 2000 and July 2020. The incidence of ET and procedure-related complications were assessed in three consecutive time periods determined by changes in guidelines and indications for ET.Results The incidence of ET in our centre declined from (104/156) 67% (time period 2000-2005), to (39/181) 22% (2006-2015) and to (10/101) 10% (2015-2020, p < 0 center dot 001). The maximum bilirubin levels in neonates after birth increased from 13 center dot 6 mg/dL (or 233 mu mol/L), to 15 center dot 0 mg/dL (257 mu mol/L) and to 15 center dot 3 mg/dL (263 mu mol/L). The incidence of complications associated with the use of ET (including sepsis, haematologic disorders and respiratory failure) remained stable throughout the years, and no neonates died during the study period.Conclusion Exchange transfusion incidence declined significantly over the past two decades. Decrease in ET incidence, and concomitant decrease in exposure and expertise, was not associated with an increase in procedure-related complications. Show less
Ree, I.M.C.; Lopriore, E.; Zwiers, C.; Bohringer, S.; Janssen, M.W.M.; Oepkes, D.; Haas, M. de 2020
BACKGROUND: Infants with severe hemolytic disease of the fetus and newborn often require 1 or multiple intrauterine transfusions to treat fetal anemia. Intrauterine transfusions may have an... Show moreBACKGROUND: Infants with severe hemolytic disease of the fetus and newborn often require 1 or multiple intrauterine transfusions to treat fetal anemia. Intrauterine transfusions may have an inhibiting effect on fetal and neonatal erythropoiesis.OBJECTIVE: To quantify the effect of 1 or multiple intrauterine transfusions on the fetal erythropoiesis by assessing the fetal reticulocyte counts in a population with severe hemolytic disease of the fetus and newborn.STUDY DESIGN: This was an observational cohort study in infants admitted to the Leiden University Medical Center who received 1 or multiple intrauterine transfusions for hemolytic disease of the fetus and newborn caused by (Rh)D or Kell antibodies and were born between January 2005 and December 2018.RESULTS: A total of 235 patients were included, of whom 189 were patients with D-mediated hemolytic disease of the fetus and newborn and 46 with Kell-mediated hemolytic disease of the fetus and newborn. Absolute fetal reticulocyte count in D-mediated hemolytic disease of the fetus and newborn declined exponentially over the course of consecutive intrauterine transfusions, with a 62% decline after 1 intrauterine transfusion (95% confidence interval, 56-67). A similar exponential decline was observed in Kell-mediated hemolytic disease of the fetus and newborn, with 32% (95% confidence interval, 19-45) decline after 1 intrauterine transfusion. This decline was not associated with the varying gestational age at the time of the first intrauterine transfusion or the total number of intrauterine transfusions. The number of red blood cell transfusions for postnatal anemia was greater for infants with D and Kell-mediated hemolytic disease of the fetus and newborn with >2 intrauterine transfusions (median of 3 [interquartile range, 2-3] vs 2 [interquartile range, 1-3], P=.035, in D-mediated disease and median of 2 [interquartile range, 1-2] vs 1 [interquartile range, 1-1], P<.001, in Kell-mediated disease). Infants born after >2 intrauterine transfusions less often required exchange transfusion in D-mediated hemolytic disease of the fetus and newborn (19/89 [21%] vs 31/100 [31%], P=.039), compared with infants with 1-2 intrauterine transfusions.CONCLUSION: Treatment with intrauterine transfusions causes an exponential decrease in fetal reticulocyte counts in both D- and Kell-mediated hemolytic disease of the fetus and newborn. Suppression of the compensatory erythropoiesis leads to prolonged postnatal anemia and an increased requirement of red blood cell transfusions after birth. Show less
Ree, I.M.C.; Haas, M. de; Middelburg, R.A.; Zwiers, C.; Oepkes, D.; Bom, J.G. van der; Lopriore, E. 2019
