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.

Food Supplement Use Differs from the Recommendations in Pregnant Women: A Multinational Survey.

The aim was to investigate, among pregnant women, (1) the use of food supplements and (2) the awareness of food supplement recommendations and beliefs about food supplement use in four European countries: Finland, Italy, Poland, and the United Kingdom. The participants (n = 1804) completed an online questionnaire with predefined statements. Daily intakes of vitamins and minerals were calculated using uploaded pictures or weblinks of the supplement packages. Country differences were assessed. Most participants (91%) used at least one food supplement during pregnancy. A prenatal multivitamin was the most commonly used supplement type (84% of the users), and 75% of the participants thought consumption of multivitamin is recommended. Of the participants, 81% knew that folic acid is recommended during pregnancy while 58% knew the recommendation for vitamin D. In 19% of the supplement users, the daily safe upper intake limit of at least one nutrient was exceeded. Nevertheless, most participants agreed that they knew which supplements (91%) and doses of supplements (87%) needed to be used during pregnancy. To conclude, the majority of the participants used food supplements, but lower proportions knew and adhered to the recommended intakes. Between-country differences were observed in the use and knowledge of and beliefs regarding supplements. The results suggest a need for assessment and monitoring of supplement use in antenatal care to ensure appropriate use.

Low Content of Cyclosporine A and Its Metabolites in the Colostrum of Post-Transplant Mothers.

The rate of post-transplant mothers who breastfeed while on immunosuppression is progressively increasing. Data on breastfeeding while on cyclosporine-based regimens are limited. Therefore, we assessed the amount of cyclosporine and its metabolites that might be ingested by a breastfed infant by measuring the concentration of cyclosporine and its metabolites in the colostrum of seven post-transplant mothers. The mean concentration of cyclosporine in the colostrum was 22.40 ± 9.43 mcg/L, and the estimated mean daily dose of the drug was 1049.22 ± 397.41 ng/kg/24 h. Only three metabolites (AM1, DHCsA, and THCsA) had mean colostrum amounts comparable to or higher than cyclosporine itself, with the daily doses being 468.51 ± 80.37, 2757.79 ± 1926.11, and 1044.76 ± 948.56 ng/kg/24 h, respectively. Our results indicate a low transfer of cyclosporine and its metabolites into the colostrum in the first two days postpartum and confirm the emerging change to the policy on breastfeeding among post-transplant mothers. A full assessment of the safety of immunosuppressant exposure via breastmilk will require further studies with long-term follow-ups of breastfed children.

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.

Transfer of Everolimus into Colostrum of a Kidney Transplant Mother.

BACKGROUND Transplanted women are increasingly expressing their desire to breast-feed. Due to the unknown effects that might occur in newborns of everolimus-treated mothers, it is now recommended to inhibit lactation. This report discusses the assessment of everolimus levels in maternal, umbilical, and neonatal blood, and colostrum of a kidney transplant mother. CASE REPORT A 28-year-old white primipara after second kidney transplant, treated with everolimus, conceived unintentionally. Due to the high risk of recurrence of primary disease, the immunosuppressive treatment remained unchanged. At 37 weeks of gestation, due to mild preeclampsia, the woman was qualified for induction of labor and vaginally delivered a healthy infant. The highest concentration of everolimus in the colostrum was observed 4 h after drug administration and was 0.066 ng/ml. The estimated maximal dose of everolimus in colostrum was 0.38% of the mother's dose. CONCLUSIONS Breast-feeding in transplanted women treated with everolimus seems possible, particularly in mothers who are willing to breast-feed, especially in the first days after labor, when levels of immunoglobulins in colostrum are high and the concentrations of everolimus are low.