Joanna Schreiber-Zamora

Intrauterine Hypotrophy and Premature Births in Neonates Delivered by Female Renal and Liver Transplant Recipients

BACKGROUND Neonates born to mothers, who underwent organ transplantation require close medical monitoring. It is unknown how chronically diseased mothers organs or immunosuppressive drugs affect fetal growth and development; some immunosuppressants are teratogenic and contraindicated during pregnancy. The aim of this study was to determine the prevalence of prematurity and intrauterine growth restriction in neonates born to women who have undergone renal or liver transplantation. METHODS Our retrospective analysis identified 53 (25 renal and 28 liver) cases of neonates delivered by female graft recipients between January 2005 and December 2009. Hypotrophy was defined as a birth weight<10th percentile for gestational age. We excluded newborns diagnosed with severe hypotrophy (<5th percentile). RESULTS Neonates born prematurely were predominate in the renal (16/25, 64%), but less than half of the liver cohort (13/28, 46%). Hypotrophy less than the 10th percentile was noted significantly more often among renal than liver recipients; 36% versus 14% (P<.05). Severe hypotrophy was also observed significantly more often among renal than liver transplant neonates: 28% versus 3.6% (P<.001). CONCLUSIONS Compared with liver insufficiency, chronic kidney diseases have stronger effects on the fetus, leading to adverse neonatal complications. A greater prevalence of preterm births, as well as hypotrophic newborns, especially less than the 5th percentile, was observed among neonates delivered by mothers after kidney transplantation.

Ultrasonography of the brain, abdomen, and heart in neonates born to liver or renal transplant recipient mothers.

BACKGROUND Pregnancies in graft recipients are associated with increased risk of a number of pathologies. The aim of the study was to analyze results of brain and abdominal ultrasonography and echocardiography (ECHO) in neonates born to liver (LTx) or renal recipients (RTx). MATERIAL/METHODS The study group consisted of 82 neonates born to transplanted women (46 neonates of liver recipients and 36 neonates of renal recipients), enrolled in a retrospective study. The control group consisted of 74 neonates from the general population. Sonographic examination of the brain was performed to check for the presence of intra-/periventricular hemorrhage (IVH/PVH) according to Papile, and periventricular leukomalacia (PVL).The results of abdominal ultrasonography and 2-dimensional echocardiography (ECHO) were compared between the groups. The immunosuppressive therapy used during pregnancy was also analyzed. RESULTS No significant differences were observed between the frequency of IVH in LTx and RTx groups and LTx, RTx, and control groups. Abdominal ultrasonography revealed 1 case of suprarenal hemorrhage, 1 case of cystic kidney, and 3 cases of pyelocalyceal system dilatation in the study group. There were no abnormalities in the echocardiography in 97.8% of children born to mothers after LTx and in 94.4% after RTx. There were significant differences in the immunosuppressive therapy between the pregnant women after LTx and RTx. CONCLUSIONS The risk was not increased in intra-/periventricular hemorrhage and congenital abnormalities of the gastrointestinal tract and heart in neonates of mothers after organ transplantation, regardless of the immunotherapy used, and risk was similar to that of the general population.

Neurological development of children born to liver transplant recipients.

INTRODUCTION Immunosuppressive treatment used in pregnant liver recipients may have a negative impact on fetal development and successively a child. AIM The aim of the study was to make a neurological assessment of infants and children born to liver transplant recipients (LTRs) born between December 4, 2001, and February 11, 2013, in the 1(st) Department of Obstetrics and Gynecology, Medical University of Warsaw. METHODS AND MATERIALS The study involved 88 children, of whom 44 children were born to LTR mothers, and 44 children born to women who were not organ recipients and delivered at a similar gestational age. The gestational age of neonates ranged from 33 to 41 weeks, and the birth weight ranged from 1420 g to 4100 g. The neurological examination was performed in children from 7 weeks to 10 years of age. The neurological development was assessed by a specialist in pediatric neurology. The results of the examination were divided according to the following criteria: 1) normal development, 2) slight disorders, 3) moderate disorders, and 4) severe disorders. The Fishers exact test was used for statistical analysis. RESULTS Normal development was found in 35 of 44 (79.54%) children in the LTR group and 39 of 44 (88.63%) children in the control group (P = .3827). Slight disorders were observed in 6 of 44 (13.63%) children in LTR group and 5 of 44 (11.36%) children in the control group. Moderate disorders were found only in 3 of 44 (6.81%) children in the LTR group. No severe disorders were observed in both groups. CONCLUSIONS Neurological development of children born to the liver recipients who were exposed to chronic immunosuppressive treatment in their fetal lives is the same as that of children whose mothers have not undergone organ transplantation.

Low Transfer of Tacrolimus and Its Metabolites into Colostrum of Graft Recipient Mothers

Currently, the majority of neonates born to organ recipient mothers on chronic immunosuppressive therapy are formula fed. However, over the past few years, evidence has grown, suggesting that breastfeeding might be possible and beneficial. We designed a study assessing the transfer of tacrolimus into the colostrum of posttransplant mothers. We assessed the amount of tacrolimus and its metabolites, M-1 and M-3, that would be ingested by the breastfed neonates. Concentrations of tacrolimus and its metabolites were measured in colostrum from 14 posttransplant mothers as well as in venous cord blood and venous blood of the neonates. Test material analysis was performed by liquid chromatography coupled with mass spectrometry (LC/MS). The amount of ingested formula was registered, which allowed for estimation of the amount of tacrolimus and its metabolites that would be ingested by breastfed infants. The mean amount of tacrolimus that would be ingested by the neonates in maternal milk was 151.4 ng/kg/24 h (standard deviation SD ± 74.39); metabolite M-1: 23.80 ng/kg/24 h (SD ± 14.53); and metabolite M-3: 13.25 ng/kg/24 h (SD ± 9.05). The peak level of tacrolimus and metabolite M-1 in colostrum was noted 8 h after an oral dose (3.219 ng/mL SD ± 2.22 and 0.56 ng/mL SD ± 0.60, respectively) and metabolite M-3 after 6 h (0.29 ng/mL SD ± 0.22). Low concentrations of tacrolimus and its metabolites, M-1 and M-3, in colostrum show that neonates will ingest trace amounts of the drug. Further studies are required to fully assess the safety of breastfeeding by posttransplant mothers.

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

Abstract 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/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.

Neurological development of children born to mothers after kidney transplantation

Abstract 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 Selected Markers of the Immune System in Children of Renal Transplant Recipients

OBJECTIVE The aim of this study was to evaluate whether chronic use of immunosuppressive drugs during pregnancy in women after renal transplantation affects the concentration of immunoglobulin G (IgG) and IgM in the serum of their children. MATERIAL Seventy-eight children aged 1 day to 15 years were enrolled. The study group consisted of 39 children born to renal transplant recipient mothers. The control group comprised 39 children whose mothers had not received immunosuppressive medications during pregnancy and were born at similar gestational age. METHODS Serum concentrations of IgG and IgM were evaluated with the use of agglutination immunoassays on Siemens or Cobas device. Age-adjusted reference values for immunoglobulins formulated by Wolska-Kusnierz et al were used. Statistical analysis was performed with the use of Statistica 10.0 software with P value <.05 considered significant. RESULTS Normal IgG concentrations were found in 82.05% (32) of children from the study group and 79.49% (31) of the control group. IgG concentrations below normal range were observed in 12.82% (5) of children from the study group and in 15.38% (6) of the control group. Normal concentrations of IgM were found in 53.85% (21) of children from the study group and in 61.54% (24) of the control group. Decreased levels of IgM were observed in 38.46% (15) of children from the study group and 35.9% (14) of the control group. There were no significant differences regarding the analyzed values between the groups. CONCLUSION The exposure to chronic intrauterine immunosuppression had no significant effect on the concentration of IgG or IgM in children born to kidney transplant recipients.

Analysis of the Selected Biochemical Parameters of Liver and Kidney Function in Children of Mothers After Liver Transplantation

INTRODUCTION Children of mothers after liver transplantation (LT) are exposed during fetal life to the immunosuppressive agents. These drugs may have hepatotoxic and nephrotoxic effects. OBJECTIVES The aim of the work was to assess liver and kidney parameters of children born from mothers who had LT. MATERIALS AND METHODS The research included 51 children of mothers after LT and 51 children from a control group who were born in the First Department of Obstetrics and Gynecology in Warsaw between 2001 and 2013. The control group consisted of children born in the similar gestational age. Analysis concerned neonates, infants, and children older than 12 months. Two liver parameters (alanine transaminase [ALT] and aspartate transaminase [AST]) as well as two kidney parameters (urea and creatinine) were assessed. For statistical analysis we used Fishers exact test and the Mann-Whitney test. RESULTS All children from the LT group had correct ALT levels. In the control group, 5 of 51 cases (9.8 %) had levels that were greater than the norm, and those cases concerned only children younger than 12 months. The average concentration of ALT in the LT group was 15.14 U/L and the average for the control group was 22.6 U/L (P = .012699, Mann-Whitney test). Three of 51 children in the LT group (5.9%) and 8 of 51 (15.7%) in the control group had AST levels that were increased (P = .2003; Fishers exact test). Incorrect AST levels were reported in all age groups. Incorrect values of kidney parameters concerned only neonates. Increased creatinine levels were reported in 3 of 51 cases (5.9%) in the LT group and in 1 of 51 cases (1.96%) in the control group (P = .6175; Fishers exact test). The average concentration of creatinine in children of mothers after LT was 0.51 mg/dL, and the average of the control group was 0.44 mg/dL (P = .223698; Mann-Whitney test). Only 1 of 51 children in the LT group (1.96%) had an increased urea level. All children from both the LT and the control groups had normal ultrasound images of urinary tract and liver. CONCLUSION Exposure to immunosuppressive drugs during fetal life does not result in the occurrence of serious disturbances of liver function and kidneys function in children of mothers after LT.