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.

Severe Cholestasis in Neonates with Hemolytic Disease of the Fetus and Newborn-A Case Report.

Hemolytic disease of the fetus and newborn (HDFN) may cause severe cholestasis with direct bilirubin concentrations reaching up to 50 times the upper limit of normal. This case report describes twins whose highest direct bilirubin concentrations were 32.2 mg/dL and 50.2 mg/dL, with no significant signs of hepatic impairment. The index pregnancy was complicated by Rhesus factor immunization with anti-D antibodies present in maternal serum, which caused fetal anemia requiring intrauterine blood transfusions. Complementary tests demonstrated Rhesus D alloimmunization as the sole cause of cholestasis. To the best of our knowledge, this is the first study to describe such elevated direct bilirubin concentrations caused by HDFN.

Liver Dysfunction with Severe Cholestasis and Coagulation Disorders in the Course of Hemolytic Disease of the Newborn Requiring Chelation Therapy-A Case Report and Review of the Literature.

Severe hemolytic disease of the fetus and newborn (HDFN) requiring intrauterine transfusions (IUTs) may cause iron accumulation, resulting in liver damage, which may lead to cholestasis and coagulation disorders. In this article, we reported a case of a female neonate who underwent chelation therapy with a positive outcome, and we reviewed the English and Polish literature on chelation therapy in HDFN available in PubMed. The patient with maximum ferritin concentration above 33,511.2 ng/mL developed liver dysfunction with coagulation disorders requiring multiple transfusions of fresh frozen plasma (FFP), Octaplex® and cryoprecipitate, and hypoalbuminemia treated with numerous albumin infusions. Furthermore, severe cholestasis was observed with direct bilirubin levels up to 33.14 mg/dL. Additionally, the child developed transient myelosuppression with neutropenia, thrombocytopenia, and low reticulocyte count due to several blood transfusions. The differential diagnosis tests were conducted to rule out any causes of hepatic failure other than hemolytic disease of the newborn. This case proves that adequate treatment of severe HDFN with anemia requiring IUT and hepatic failure can lead to positive outcomes with no long-term consequences.

Evaluation of selected parameters of immune response to rubella virus, hepatitis B virus and varicella-zoster virus infections in children born to mothers after kidney or liver transplantation.

BACKGROUND: The immune status of children exposed prenatally to immunosuppressants is not fully understood. MATERIAL AND METHODS: A single-center study evaluated possible differences in antibody levels between children prenatally exposed to immunosuppressants born to mothers after hepatic or kidney transplantation (study group) compared to children without prenatal exposure to immunosuppressants (control group). Children from the study and control group were age-matched at the time of the examination and gestational age-matched, so as to obtain similar stages of the vaccination schedule and to enable reliable comparison of the results. The selection of children was made in a 1:1 ratio. The study population, a total of 138 children, was divided according to the age of the children at the time of the study into three age groups: newborns, infants (from 29 days to 1 year) and children aged >1 year. Immunoenzymatic tests were used to analyze the titers of the chickenpox virus (VZV-IgG), rubella (RuV-IgG) and hepatitis B virus (HBV, HBsAb). The studied differences were compared depending on the age group and the immunosuppressive regimen used by the pregnant mother. RESULTS: In neonates born to mothers after liver transplantation, significant differences were found in HBsAb levels (>250 mIU/ml) compared to newborns without prenatal exposure to immunosuppressants taken by pregnant mothers (11/16, 69% vs. 4/14, 29%, respectively; p = .028). A similar difference in the level of HbsAb was no longer noted at later stages of children's lives. In infants, these values were 80% (4/5) vs. 33% (2/6), and in children over 1 year of age 15% (7/48) vs. 12% (6/49), respectively. No other significant differences were noted when compared the distribution of measured parameters of VZV and RuV in both analyzed groups (children of mothers after kidney or liver transplantation chronically treated with immunosuppression and children without prenatal exposure to immunosuppression). CONCLUSIONS: Prenatal exposure to immunosuppressive therapy does not appear to affect VZV, RuV and HBV antibody levels in children of mothers who have had a kidney or liver transplant. Initially elevated HBSAb levels in newborns of mothers after liver transplantation are not observed in later stages of life.

Neurological development of children born to mothers after kidney transplantation.

BACKGROUND: Pregnancies after kidney transplantation are at high risk of complications such as preterm birth and foetal growth restriction. Until now, the impact of these factors on neurological development of children born to transplant mothers has not been established. AIMS: A comparison of neurological examinations performed in 36 children of kidney transplant women (study group) and 36 children born to healthy mothers (control group). The children from both groups were born at a similar gestational age and in the similar time period from 12/1996 to 09/2012. Neurological examinations were performed from 07/2010 to 11/2013. Each examination was adjusted to the patient's age and performed after the neonatal period. Three years later children were re-consulted, if they presented neurological deviations or were less than 12 months old at the time of the first examination. RESULTS: Normal neurological development was found in 86% of children in both groups (p = .999). Mild neurological deviations were observed in four (11%) children born to kidney transplant mothers and in five (14%) children born to healthy mothers (p = .999). Moderate deviations were diagnosed in one premature child born to transplant mother, whose pregnancy was complicated with a severe preeclampsia and foetal growth restriction. In the study population, no severe neurological disorders were found. Almost all (8/10) children with neurological deviations were born prematurely in good general conditions. The neurological deviations observed in the first year of life were mild and transient. In children over 1 year of age, deviations were more pronounced and continued to maintain. CONCLUSIONS: The neurological development of children of kidney transplant women is similar to that of the general population and possible deviations seem to be the result of intrauterine hypotrophy and prematurity. Therefore, in clinical practice, it is necessary to plan post-transplant pregnancies especially in women at high risk of these complications.

Evaluation of the body mass index (BMI) in children born to organ transplant recipients.

BACKGROUND: Overweight and obesity are one of the most serious clinical health problems. Until now, the long-term development of children born to mothers after transplantation is unknown. In this study, we attempted to present the analysis of the prevalence of overweight in the population of mothers after kidney or liver transplants. METHODS: A comparison of body mass index (BMI) measurements performed in 61 children of kidney transplant women (study group) and 64 children born to healthy mothers (control group). The children from both groups were born at a similar gestational age and in the similar time period from 12/1996 to 11/2010. BMI was measured once on one of the follow-up visits in the time period from 07/2010 to 11/2013. BMI was assessed in infants older than one month as well as in toddlers or children in the preschool or school age. The results obtained in the study group of children born to transplanted mothers were compared with control group results and with the theoretical population data. RESULTS: There were no differences in the incidence of underweight and overweight, when BMI values of children born to transplanted mothers were compared to those of children of healthy mothers. There was a trend towards a greater incidence of obesity in children of studied group compared to controls (16 versus 6%, p = .072). Among analysed factors, it was noted that prenatal exposure to tacrolimus was associated with a 2.8-fold increased risk of developing a higher BMI in later follow-up. CONCLUSIONS: Obesity among children of mothers after kidney or liver transplants seems to be more frequently observed. This observation may be an important factor in the further paediatric care, especially in children born to transplanted mothers treated chronically with tacrolimus.

Immunological Status of Children Born to Female Liver Recipients.

BACKGROUND Immunosuppressive treatment in pregnant organ recipients can affect functions of the fetal and newborn immune system. The aim of this study was to evaluate the effect of this treatment on selected parameters of the immune system of children born to mothers after liver transplantation. MATERIAL AND METHODS The study included 52 children born to liver recipients and 52 children in the control group. The study was conducted in the 1st Department of Obstetrics and Gynecology, Medical University of Warsaw. Children from the 1st day of life to 10 years of age were examined. Serum antibody concentrations of IgG, IgM, and IgA were measured by the immune agglutination method on a Cobas 6000 analyzer. RESULTS Comparison of mean IgG, IgM, and IgA levels and with reference values did not show a significant difference between the study and control group (p>0.05). Immunoglobulin concentrations were also analyzed in the groups of children according to their age at the time of the test and the type of calcineurin inhibitor used in the mother's treatment. The analysis showed a significant difference in the distribution of IgA concentrations in comparison to the normal values (p<0.05), as well as mean IgA (p<0.05) and IgM concentrations (p<0.05) according to the type of immunosuppressive treatment of the mother (tacrolimus or cyclosporin treatment regimen). CONCLUSIONS Analysis of the type of immunosuppressive therapy used during pregnancy revealed a possible influence of the type of calcineurin inhibitor on selected parameters of the immune system of the children; however, further research is needed to confirm these findings.

[Severe hemolytic disease of the newborn as a result of late and undiagnosed alloimmunization--case report]. / Ciezka choroba hemolityczna noworodka w wyniku póznej i nierozpoznanej immunizacji--opis przypadku.

We report a case of a hemolytic disease in a newborn from the first pregnancy due to anti-D antibodies. The maternal blood group was A Rhesus negative. She had an antibody screening test twice during the pregnancy (in the second trimester) and it was negative. The pregnancy was uneventful, without any invasive procedures and bleeding. The infant was born at 39 weeks of gestation in good overall condition. After the delivery the blood group of the neonate was indicated - A Rhesus positive, BOC positive. Anti-D antibodies were detected in maternal blood. Neonatal blood tests revealed severe anemia (hemoglobin level: 6.0g/dl, hematocrit: 22.2%, erythrocytes: 2.01T/L). During the first day of neonatal life, the newborn received two transfusions of red blood cells. Bilirubin level and rate of rise were not recommendation enough for exchange transfusion. The newborn was treated with continuous phototherapy since the delivery The perinatal period was complicated with intrauterine infection and respiratory failure. Hematopoietic vitamins and iron supplementation was initiated in the second week of neonatal life due to persistent anemia. The child remained under medical care of a hematologic clinic and received human recombinant erythropoietin treatment.