Fetal Thyrotoxicosis due to Maternal TSH Receptor Stimulating Antibodies Causes Infant Central Hypothyroidism.

INTRODUCTION: Women with a current diagnosis or past history of Graves' disease (GD) are at risk of developing fetal thyrotoxicosis (FT) during pregnancy when they are inadequately treated, or because of placental passage of TSH receptor antibodies (TRAb). It is known that FT induced by high maternal thyroid hormone concentrations may result in infant (central) hypothyroidism. CASE PRESENTATION: In a euthyroid woman with a history of GD treated with radioactive iodide (I131), persistently high levels of maternal TRAb resulted in recurrent FT during two separate pregnancies, followed by neonatal hyperthyroidism and infant central hypothyroidism. DISCUSSION: This case demonstrates the novel insight that FT due to high fetal thyroid hormone concentrations stimulated by high maternal TRAb levels might also result in (central) hypothyroidism, requiring long-term evaluation of the hypothalamus-pituitary-thyroid axis in these children.

Fibroblast growth factor 23 and calcium-phosphate metabolism in relation to cardiovascular risk factors in patients with type 1 diabetes.

BACKGROUND: Cardiovascular disease (CVD) is the major cause of mortality in type 1 diabetes (T1D). The objective of this study is to evaluate fibroblast growth factor 23 (FGF23) and calcium-phosphate metabolism in relation to cardiovascular risk factors in adults with and without T1D. METHODS: A case-control study was conducted using data from patients with T1D and age- and sex matched controls without T1D from the Lifelines Cohort Study. RESULTS: We included 302 adults in the T1D group and 302 adults in the control group. Median age was 42 years. Median glycosylated hemoglobin (HbA1c) in the T1D group was 7.8%. FGF23 of all patients with T1D was not significantly different from controls. Females with T1D had significantly higher FGF23 than males with T1D (83.3 vs 69.3 U/mL, p = 0.002), this was not observed in controls. Serum phosphate, calcium, and alkaline phosphatase were higher and parathyroid hormone was lower in patients with T1D, compared to controls (all p < .001), all within normal range. In the T1D group, FGF23 was positively correlated with serum phosphate (p < .001), alkaline phosphatase (p = .01), and calcium (p = .030), these correlations were not observed in controls. Median FGF23 was significantly higher in current smokers than in nonsmokers with T1D (84.9 vs 73.5 U/mL, p < .05). CONCLUSIONS: Serum calcium, phosphate, and alkaline phosphatase were higher in patients with T1D than in controls and were positively correlated to FGF23 in patients with T1D. Current smokers with T1D had higher FGF23 than nonsmokers with T1D. These findings may contribute to the increased risk of CVD in patients with T1D.

A novel mutation in PTHLH in a family with a variable phenotype with brachydactyly, short stature, oligodontia and developmental delay.

Mutations in PTHLH (PTH-like hormone), cause brachydactyly type E (BDE) characterized by shortening of metacarpals, metatarsals and/or phalanges with short stature. In this report we describe three siblings and their mother with a novel heterozygous mutation c.25 T > C, p.Trp9Arg in exon 2 of the PTHLH gene. Beside the known clinical features of PTHLH mutations all had a delay in speech and language development, unknown if this is related to the mutation. Patients with PTHLH mutation may have a variable phenotypic presentation.

Thrombocytopenia in neonates with polycythemia: incidence, risk factors and clinical outcome.

BACKGROUND: Polycythemia occurs in 1 to 5% of neonates and is associated with complications, including an increased risk of thrombocytopenia. OBJECTIVE: To evaluate incidence, risk factors, management and outcome of thrombocytopenia in neonates with polycythemia. STUDY DESIGN: All neonates with polycythemia admitted to our neonatal intensive care unit between 2006 and 2013 were included in this retrospective study. We evaluated the incidence of thrombocytopenia (platelet count <150 × 10(9)/l) and severe thrombocytopenia (platelet count <50 × 10(9)/l) and the correlation between platelet counts and hematocrit values. RESULTS: The incidence of thrombocytopenia and severe thrombocytopenia was 51 (71/140) and 9% (13/140), respectively. Platelet count was negatively correlated with hematocrit (spearman correlation coefficient -0.233, p = 0.007). After multiple regression analysis, we found an independent association between thrombocytopenia and being small for gestational age (OR: 10.0; 95%; CI: 1.2-81.7; p = 0.031). CONCLUSION: Thrombocytopenia occurs in 51% of neonates with polycythemia and is independently associated with growth restriction. Increased hematocrit is associated with decreased platelet count.

Neonatal morbidity after exchange transfusion for red cell alloimmune hemolytic disease.

BACKGROUND: Exchange transfusion (ET) is a high-risk procedure. The type and rate of complications in neonatal red cell alloimmune hemolytic disease exclusively are not clear. OBJECTIVES: Our aim was to study the type and rate of complications associated with ET in a large series of neonates with hemolytic disease of the fetus and newborn (HDFN) due to red cell alloimmunization. METHODS: All neonates with HDFN due to red cell alloimmunization admitted to our center between January 2001 and June 2011 were eligible for this study. We recorded the number and rate of complications during admission in the group of neonates treated with ET (ET group) and not treated with ET (no-ET group). Multivariate logistic regression analysis was performed to measure the independent risk of complications of ET treatment. RESULTS: A total of 347 infants with red cell alloimmune hemolytic disease were included; 39% (134/347) were treated with at least one ET (ET group), and 61% (213/347) did not require ET (no-ET group). Comparison between the ET group and no-ET group showed that ET treatment was independently associated with proven sepsis [8 vs. 1%, respectively; odds ratio (OR) 8.3, 95% confidence interval (CI) 1.7-40.3; p = 0.009], leukocytopenia (88 vs. 23%, respectively; OR 36.0, 95% CI 17.5-73.8; p < 0.001), severe thrombocytopenia (platelet count <50 × 10(9)/l; 63 vs. 8%, respectively; OR 31.4, 95% CI 14.0-70.4; p < 0.001), hypocalcemia (22 vs. 1%, respectively; OR 27.4, 95% CI 5.9-126.8; p < 0.001) and hypernatremia (8 vs. 0%, respectively; p < 0.001). There were no neonatal deaths in the ET group. CONCLUSION: ET in neonates with HDFN is associated with an increased risk of sepsis, leukocytopenia, thrombocytopenia, hypocalcemia and hypernatremia.

Postnatal outcome in neonates with severe Rhesus c compared to rhesus D hemolytic disease.

BACKGROUND: Neonates with Rhesus c (Rh c) hemolytic disease of the fetus and newborn (HDFN) are often managed in the same way as neonates with Rhesus D (Rh D) HDFN, although evidence to support this policy is limited. The objective of this study was to evaluate neonatal outcome in severe Rh c HDFN compared to Rh D HDFN. STUDY DESIGN AND METHODS: A retrospective study of (near-)term neonates with severe Rh c (n = 22) and Rh D HDFN (n = 103; without additional antibodies) admitted to the Leiden University Medical Center between January 2000 and October 2011 was conducted. The need for intrauterine transfusions (IUTs), phototherapy, exchange transfusions (ETs), and top-up transfusions up to 3 months of age were recorded and compared between both groups. RESULTS: Although there was a trend for a slightly more severe antenatal course for Rh D HDFN reflected by an earlier need for and higher number of IUTs (median [interquartile range], 2 [1.5-4] vs. 2 [1-2] in Rh c HDFN; p = 0.070), no significant differences were found for the postnatal course between Rh c and Rh D group in days of phototherapy (mean, Days 4.8 and 4.6, respectively; p = 0.569), need for ET (50% vs. 44%, respectively; p = 0.589), and top-up transfusions (62% vs. 78%, respectively; p = 0.128). CONCLUSION: Postnatal outcome in neonates with severe Rh c HDFN is similar compared to neonates with severe Rh D hemolytic disease in terms of days of phototherapy, need for ET, and need for top-up transfusions. These results justify a similar postnatal management of neonates with Rh D and Rh c HDFN.

Cholestasis in neonates with red cell alloimmune hemolytic disease: incidence, risk factors and outcome.

BACKGROUND: Etiology of cholestatic liver disease in neonates with hemolytic disease of the newborn (HDN) has been associated with iron overload due to intrauterine red cell transfusions (IUTs). Data on the incidence and severity of cholestasis in neonates with HDN are scarce, and little is known about pathogenesis, risk factors, neonatal management and outcome. OBJECTIVE: To evaluate incidence, risk factors, management and outcome of cholestasis in neonates with red cell alloimmune hemolytic disease. METHODS: All (near-) term neonates with HDN due to red cell alloimmunization admitted to our center between January 2000 and July 2010 were included in this observational study. Liver function tests (including conjugated bilirubin) were routinely performed in the neonatal period. We recorded the presence of cholestasis, investigated several potential risk factors and evaluated the management and outcome in affected neonates. RESULTS: A total of 313 infants with red cell alloimmune hemolytic disease treated with or without IUTs were included. The incidence of cholestasis was 13% (41/313). Two risk factors were independently associated with cholestasis: treatment with at least one IUT (OR 5.81, 95% CI 1.70-19.80, p = 0.005) and rhesus D type of alloimmunization (OR 4.66, 95% CI 1.05-20.57, p = 0.042). Additional diagnostic tests to investigate possible causes of cholestasis were all negative. In 5 infants (12%), supportive medical and nutritional therapy was started, and one neonate required iron chelation therapy. CONCLUSION: Cholestasis occurs in 13% of neonates with HDN due to red cell alloimmunization, and it is independently associated with IUT treatment and rhesus D type of alloimmunization.

Hematological morbidity and management in neonates with hemolytic disease due to red cell alloimmunization.

Treatment of severe anemia with intrauterine red cell transfusions in fetuses with red cell alloimmunization has led to a dramatic increase in perinatal survival. Due to this increased survival focus is nowadays shifting towards improving postnatal treatment options. Phototherapy, exchange transfusions and intravenous immunoglobulin are used to treat hyperbilirubinemia and prevent kernicterus. Postnatal treatment of anemia consists of top-up transfusions, supplements to support erythropoiesis such as folic acid and iron, and occasionally erythropoietin treatment. In addition to anemia, other hematological complications such as thrombocytopenia, coagulation disturbances, leucopenia and iron overload have been reported. This review focuses on the hematological morbidity in neonates with red cell alloimmunization and summarizes the current evidence on management options.

Intravenous immunoglobulin in neonates with rhesus hemolytic disease: a randomized controlled trial.

BACKGROUND: Despite limited data, international guidelines recommend the use of intravenous immunoglobulin (IVIg) in neonates with rhesus hemolytic disease. OBJECTIVE: We tested whether prophylactic use of IVIg reduces the need for exchange transfusions in neonates with rhesus hemolytic disease. DESIGN AND SETTING: We performed a randomized, double-blind, placebo-controlled trial in neonates with rhesus hemolytic disease. After stratification for treatment with intrauterine transfusion, neonates were randomly assigned for IVIg (0.75 g/kg) or placebo (5% glucose). The primary outcome was the rate of exchange transfusions. Secondary outcomes were duration of phototherapy, maximum bilirubin levels, and the need of top-up red-cell transfusions. RESULTS: Eighty infants were included in the study, 53 of whom (66%) were treated with intrauterine transfusion(s). There was no difference in the rate of exchange transfusions between the IVIg and placebo groups (7 of 41 [17%] vs 6 of 39 [15%]; P = .99) and in the number of exchange transfusions per patient (median [range]: 0 [0-2] vs 0 [0-2]; P = .90) or in duration of phototherapy (4.7 [1.8] vs 5.1 [2.1] days; P = .34), maximum bilirubin levels (14.8 [4.7] vs 14.1 [4.9] mg/dL; P = .52), and proportion of neonates who required top-up red-cell transfusions (34 of 41 [83%] vs 34 of 39 [87%]; P = .76). CONCLUSIONS: Prophylactic IVIg does not reduce the need for exchange transfusion or the rates of other adverse neonatal outcomes. Our findings do not support the use of IVIg in neonates with rhesus hemolytic disease.