Jeanine M.M. van Klink

Assessment of Parental Psychological Stress in Pediatric Cancer: A Review

OBJECTIVES We present an overview of the literature between 1997 and 2007 on parental stress reactions following the diagnosis of childhood cancer and we evaluate methodological strengths and weaknesses of the studies. METHODS PubMed, PsychInfo, and Cinahl databases were used. Sixty-seven were included in the review. RESULTS The conceptualization of parental stress and timing of assessment varies considerably between the studies, which makes comparison difficult. Most emotional stress reactions are seen around the time of diagnosis, with mothers reporting more symptoms than fathers. As a group, parents seem relatively resilient, although a subset of parents reports continuing stress even up to 5 years or more postdiagnosis. CONCLUSIONS The authors recommend clear definitions of parental stress, fixed points in time to assess parental stress, and an approach that highlights both parental strengths and weaknesses. Improved assessment can contribute to tailoring psychological care to those parents most in need.

Long-term neurodevelopmental outcome after intrauterine transfusion for hemolytic disease of the fetus/newborn: the LOTUS study

OBJECTIVE To determine the incidence and risk factors for neurodevelopmental impairment (NDI) in children with hemolytic disease of the fetus/newborn treated with intrauterine transfusion (IUT). STUDY DESIGN Neurodevelopmental outcome in children at least 2 years of age was assessed using standardized tests, including the Bayley Scales of Infant Development, the Wechsler Preschool and Primary Scale of Intelligence, and the Wechsler Intelligence Scale for Children, according to the childrens age. Primary outcome was the incidence of neurodevelopmental impairment defined as at least one of the following: cerebral palsy, severe developmental delay, bilateral deafness, and/or blindness. RESULTS A total of 291 children were evaluated at a median age of 8.2 years (range, 2-17 years). Cerebral palsy was detected in 6 (2.1%) children, severe developmental delay in 9 (3.1%) children, and bilateral deafness in 3 (1.0%) children. The overall incidence of neurodevelopmental impairment was 4.8% (14/291). In a multivariate regression analysis including only preoperative risk factors, severe hydrops was independently associated with neurodevelopmental impairment (odds ratio, 11.2; 95% confidence interval, 1.7-92.7). CONCLUSION Incidence of neurodevelopmental impairment in children treated with intrauterine transfusion for fetal alloimmune anemia is low (4.8%). Prevention of fetal hydrops, the strongest preoperative predictor for impaired neurodevelopment, by timely detection, referral and treatment may improve long-term outcome.

Intrauterine transfusion for parvovirus B19 infection: long-term neurodevelopmental outcome

OBJECTIVE To evaluate long-term neurodevelopmental outcome of children treated with intrauterine transfusions for fetal anemia because of parvovirus B19 infection. STUDY DESIGN Children treated with intrauterine transfusions for fetal anemia because of parvovirus B19 infection underwent standardized age-appropriate neurodevelopmental testing. Main outcome was the incidence of neurodevelopmental impairment. RESULTS Twenty-eight children were evaluated at a median age of 5 years (range, 1.5-13 years). Neurodevelopmental impairment was diagnosed in 3 of 28 (11%) children, including 1 child with combined cerebral palsy and severe developmental delay and 2 children with isolated severe developmental delay. CONCLUSION Neurodevelopmental impairment in children treated with intrauterine transfusion for parvovirus B19 infection is increased compared with the general population. Large long-term follow-up studies are required to determine potential risk factors.

Long-term neurodevelopmental outcome in monochorionic twins after fetal therapy.

Monochorionic (MC) twins are at risk for several disorders, including twin-twin transfusion syndrome (TTTS), Twin Reverse Arterial Perfusion (TRAP) and selective intrauterine growth restriction (sIUGR). Several fetal interventions, such as serial amnioreduction (AR), fetoscopic laser coagulation of placental anastomoses (FLC) and selective feticide have lead to improved perinatal morbidity and mortality rates. Nevertheless, the rate of cerebral lesions in MC twins after fetal therapy appears to be high. Follow-up studies show a high incidence of cerebral palsy (CP) and neurodevelopmental impairment (NDI). We performed a systematic review on the long-term neurodevelopmental outcome in MC twins with TTTS following AR and FLC and MC twins following selective feticide of the co-twin due to TTTS, TRAP, sIUGR and congenital anomalies.

Long-Term follow up after intra-Uterine transfusionS; the LOTUS study

BackgroundThe Leiden University Medical Center (LUMC) is the Dutch national referral centre for pregnancies complicated by haemolytic disease of the fetus and newborn (HDFN) caused by maternal alloimmunization. Yearly, 20-25 affected fetuses with severe anaemia are transfused with intra-uterine blood transfusions (IUT). Mothers of whom their fetus has undergone IUT for HDFN are considered high responders with regard to red blood cell (RBC) antibody formation. Most study groups report high perinatal survival, resulting in a shift in attention towards short- and long-term outcome in surviving children.Methods/DesignWe set up a large long-term observational follow-up study (LOTUS study), in cooperation with the Sanquin Blood Supply Foundation and the LUMC departments of Obstetrics, Neonatology and ImmunoHematology & Bloodtransfusion.The first part of this study addresses several putative mechanisms associated with blood group alloimmunization in these mothers. The second part of this study determines the incidence of long-term neurodevelopment impairment (NDI) and associated risk factors in children treated with IUT. All women and their life offspring who have been treated with IUT for HDFN in the LUMC from 1987-2008 are invited to participate and after consent, blood or saliva samples are taken. RBC and HLA antigen profile and antibodies are determined by serologic or molecular techniques. Microchimerism populations are tested by real time polymerase chain reaction (RT PCR).All children are tested for their neurological, cognitive and psychosocial development using standardised tests and questionnaires. The primary outcome is neurodevelopmental impairment (NDI), a composite outcome defined as any of the following: cerebral palsy, cognitive or psychomotor development < 2 standard deviation, bilateral blindness and/or bilateral deafness.DiscussionThe LOTUS study includes the largest cohort of IUT patients ever studied and is the first to investigate post-IUT long-term effects in both mother and child. The results may lead to a change in transfusion policy, in particular future avoidance of certain incompatibilities. Additionally the LOTUS study will provide clinicians and parents better insights in the long-term neurodevelopmental outcome in children with HDFN treated with IUTs, and may improve the quality of antenatal counselling and long-term guidance.

Long-term neurodevelopmental and cardiovascular outcome after intrauterine transfusions for fetal anaemia: a review.

Perinatal survival rates after intrauterine transfusions (IUT) for red cell alloimmunisation now exceed 90%, which demonstrates the safety and efficacy of one of the most successful procedures in fetal therapy. However, improved perinatal survival could lead to an increased number of children with long‐term disabilities. The importance of long‐term follow‐up studies in fetal therapy lies in both the necessity of evaluation of antenatal management as well as in evidence‐based preconceptional and prenatal counselling. This review describes the possible long‐term cardiovascular and neurodevelopmental sequelae after IUT treatment for different indications including red cell alloimmunisation, parvovirus B19 infection, fetomaternal haemorrhage and twin anaemia‐polycythaemia sequence.

Long-term neurodevelopmental outcome after intrauterine transfusion for fetal anemia

The long-term neurodevelopmental outcome of children born after intrauterine blood transfusion (IUT) for red cell alloimmunization is considered favorable. Severe hydrops has been identified as a strong predictor for neurodevelopmental impairment. However, the long-term outcome of survivors of IUT for congenital Parvovirus B19 infection and fetomaternal hemorrhage is not well known. Limitations of the follow-up studies to date are small sample size, lack of controls, unclear criteria for impairment and lack of standardized developmental tests. Future research should take into account more subtle impairments, since cognitive functioning <-1 SD, behavioral and learning problems already have a significant impact on care requirements and future socio-economic potential. A better understanding of the effect of IUT and fetal anemia on child development over time will allow more accurate parental counseling and targeted interventions to optimize child development when needed.

Neonatal management and outcome in alloimmune hemolytic disease

ABSTRACT Introduction: Hemolytic disease of the fetus and newborn (HDFN) occurs when fetal and neonatal erythroid cells are destroyed by maternal erythrocyte alloantibodies, it leads to anemia and hydrops in the fetus, and hyperbilirubinemia and kernicterus in the newborn. Postnatal care consists of intensive phototherapy and exchange transfusions to treat severe hyperbilirubinemia and top-up transfusions to treat early and late anemia. Other postnatal complications have been reported such as thrombocytopenia, iron overload and cholestasis requiring specific management. Areas covered: This review focusses on the current neonatal management and outcome of hemolytic disease and discusses postnatal treatment options as well as literature on long-term neurodevelopmental outcome. Expert commentary: Despite major advances in neonatal management, multiple issues have to be addressed to optimize postnatal management and completely eradicate kernicterus. Except for strict adherence to guidelines, improvement could be achieved by clarifying the epidemiology and pathophysiology of HDFN. Several pharmacotherapeutic agents should be further researched as alternative treatment options in hyperbilirubinemia, including immunoglobulins, albumin, phenobarbital, metalloporphyrins, zinc, clofibrate and prebiotics. Larger trials are warranted to evaluate EPO, folate and vitamin E in neonates. Long-term follow-up studies are needed in HDFN, especially on thrombocytopenia, iron overload and cholestasis.

Long-Term Neurodevelopmental Outcome in Survivors of Twin-to-Twin Transfusion Syndrome.

Twin-twin transfusion syndrome (TTTS) is a severe complication of monochorionic (MC) twin pregnancies associated with high perinatal mortality and morbidity rates. Management in TTTS is a major challenge for obstetricians and neonatologists. Twins with TTTS are often born prematurely after an extremely distressing and highly hazardous fetal period. Follow-up studies report varying rates of cerebral palsy (CP) and long-term neurodevelopmental impairment (NDI). This review discusses the latest findings on the long-term outcome of TTTS survivors, possible risk factors for long-term impairment, and provides recommendations for future research.

Immunoglobulins in Neonates with Rhesus Hemolytic Disease of the Fetus and Newborn: Long-Term Outcome in a Randomized Trial

Objective: Prophylactic intravenous immunoglobulin (IVIg) does neither reduce the need for exchange transfusion nor the rates of other adverse neonatal outcomes in neonates with rhesus hemolytic disease of the fetus and newborn (rhesus HDFN) according to our randomized controlled trial analysis. Our objective was to assess the long-term neurodevelopmental outcome in the children included in the trial and treated with either IVIg or placebo. Methods: All families of the children included in the trial were asked to participate in this follow-up study. The long-term neurodevelopmental outcome in children at least 2 years of age was assessed using standardized tests. The primary outcome was the incidence of neurodevelopmental impairment defined as at least one of the following: cerebral palsy, severe cognitive and/or motor developmental delay (with a test score of less than -2 SD), bilateral deafness or blindness. Results: Sixty-six of the 80 children (82.5%) who had been recruited to the initial randomized controlled trial participated in the follow-up study. The children were assessed at a median age of 4 years (range 2-7). The median cognitive score was 96 (range 68-118) in the IVIg group and 97 (range 66-118) in the placebo group (p = 0.79). There was no difference in the rate of neurodevelopmental impairment between the IVIg and the placebo group [3% (1/34) vs. 3% (1/32); p = 1.00]. Conclusions: The long-term neurodevelopmental outcome in children treated with IVIg was not different from that in children treated with placebo. Standardized long-term follow-up studies with large enough case series and sufficient power are needed to replicate these findings.