Long-Term Functional Outcome Following Neurosurgical Intervention for Suspected Abusive Head Trauma.

BACKGROUND: The purpose of this study was to evaluate the long-term functional and neurodevelopmental outcomes in pediatric patients who underwent neurosurgical intervention following suspected abusive head trauma (AHT). METHODS: We performed a single-center retrospective review (January 1, 2007, to December 31, 2019) of patients aged less than three years who had intracranial injury suspicious for AHT and received a neurosurgical procedure. Long-term functional outcome was measured using the Pediatric Cerebral Performance Category (PCPC), Pediatric Overall Performance Category (POPC), and the Mullen Scales of Early Learning (MSEL). RESULTS: Seventy-seven patients were identified; 53 survived to discharge and had at least one-year follow-up. To examine long-term functional outcome, PCPC at the last available visit was examined and found to be 1 or 2 (normal to mild disability) for 64% of patients and 3 or 4 (moderate to severe disability) for 36%. The last available MSEL composite score for neurodevelopmental assessment also demonstrated that 13% of patients scored in the "average" range, 17% in the "below average" range, and 70% in the "very low" range. There was no statistical difference in the last available PCPC or POPC score or the last available MSEL score for patients who received a craniotomy when compared with those who received an intracranial shunt. CONCLUSIONS: For patients with AHT who survived to discharge, functional improvements over time were noted in both patients who received craniotomy or who simply required shunt placement. These results suggest that, for patients who survive to discharge, operative management of AHT can lead to reasonable long-term functional outcomes.

Incidence and Mortality of Pediatric Abdominal Compartment Syndrome.

INTRODUCTION: Abdominal compartment syndrome (ACS) is the presence of intra-abdominal hypertension with systemic, multiorgan effects and is associated with high mortality, yet the national incidence and mortality rates of pediatric ACS remain unknown. The aim of this study is to evaluate the incidence and mortality of pediatric ACS over a 13-year period across multiple children's hospitals and between individual children's hospitals in the United States. METHODS: We performed a retrospective cohort study on children (aged < 18 y) with ACS in the Pediatric Health Information Systems database from 2007 to 2019. We identified ACS patients by International Classification of Diseases codes in the ninth and 10th revision. The primary outcomes were incidence and mortality, which were analyzed by year, age, and hospital of admission. RESULTS: Across 49 children's hospitals, we identified 2887 children with ACS from 2007 to 2019 in the Pediatric Health Information Systems database. The overall incidence of ACS was 0.17% and the overall mortality was 48.87%. There was no significant difference in annual incidence (P = 0.12) or mortality (P = 0.39) over the study period. There was no difference in incidence across age group (P = 0.38); however, mortality in patients 0-30 d old (58.61%) was significantly higher than older age groups (P < 0.0001). The hospital-specific incidence (0.04%-0.46%) and mortality (28.57%-71.43%) varied widely. CONCLUSIONS: The annual incidence and mortality of pediatric ACS are unchanged from 2007 to 2019. ACS mortality remains high, especially in neonatal intensive care unit patients. No obvious correlation is seen between incidence rates and mortality. Differing hospital-specific incidence and mortality could suggest inconsistencies between institutions that affect pediatric ACS care, perhaps with respect to recognition and diagnosis.

Maternal anemia and the risk of childhood cancer: A population-based cohort study in Taiwan.

BACKGROUND: Childhood cancer may be related to maternal health in pregnancy. Maternal anemia is a common condition in pregnancy, especially in low-income countries, but the association between maternal anemia and childhood cancer has not been widely studied. OBJECTIVE: To examine the potential relation between maternal anemia during pregnancy and childhood cancers in a population-based cohort study in Taiwan. METHODS: We examined the relationship between maternal anemia and childhood cancer in Taiwan (N = 2160 cancer cases, 2,076,877 noncases). Cases were taken from the National Cancer Registry, and noncases were selected from birth records. Using national health registries, we obtained maternal anemia diagnoses. We estimated the risks for childhood cancers using Cox proportional hazard analysis. RESULTS: There was an increased risk of cancers in children born to mothers with nutritional anemia (hazard ratio (HR): 1.32, 95% CI 0.99, 1.76). Iron deficiency anemia (HR: 1.30, 95% CI 0.97-1.75) carried an increased risk, while non-nutritional anemias were not associated with childhood cancer risk. CONCLUSION: Our results provide additional support for screening for anemia during pregnancy. Adequate nutrition and vitamin supplementation may help to prevent some childhood cancer.

Maternal anemia and childhood cancer: a population-based case-control study in Denmark.

BACKGROUND: Childhood cancer risk is associated with maternal health during pregnancy. Anemia in pregnancy is a common condition, especially in low-income countries, but a possible association between maternal anemia and childhood cancer has not been widely studied. METHODS: We examined the relation in a population-based study in Denmark (N = 6420 cancer cases, 160,485 controls). Cases were taken from the Danish Cancer Registry, and controls were selected from national records. We obtained maternal anemia diagnoses from the National Patient and Medical Births registries. In a separate analysis within the years available (births 1995-2014), we examined cancer risks among mothers taking prescribed vitamin supplements, using data from the National Prescription Register. We estimated the risks of childhood cancer using conditional logistic regression. RESULTS: The risks of neuroblastoma [odds ratio (OR= 1.83, 95% confidence interval (CI): 1.04, 3.22] and acute lymphoblastic leukemia (OR= 1.46, 95% CI 1.09, 1.97) were increased in children born to mothers with anemia in pregnancy. There was a two-fold increased risk for bone tumors (OR= 2.59, 95% CI: 1.42, 4.72), particularly osteosarcoma (OR= 3.54, 95% CI 1.60, 7.82). With regards to prescribed supplement use, mothers prescribed supplements for B12 and folate deficiency anemia (OR= 4.03, 95% CI 1.91, 8.50) had an increased risk for cancer in offspring. CONCLUSION: Our results suggest that screening for anemia in pregnancy and vitamin supplementation may be an actionable strategy to prevent some cases of childhood cancer.

Prevalence and Safety of Intravenous Immunoglobulin Administration During Maintenance Chemotherapy in Children with Acute Lymphoblastic Leukemia in First Complete Remission: A Health Maintenance Organization Perspective.

CONTEXT: Children with acute lymphoblastic leukemia (ALL) in first complete remission (CR1) experience hypogammaglobulinemia and are at risk of sepsis during maintenance chemotherapy. Intravenous immunoglobulin (IVIG) has been used to try to circumvent this risk, but no data exist regarding its safety and prevalence in a health maintenance organization. OBJECTIVE: To evaluate the prevalence and safety of IVIG in children with ALL in CR1 during maintenance chemotherapy. DESIGN: A multicenter, retrospective cohort study of consecutive children with ALL in CR1 during maintenance chemotherapy from 2008 to 2014. Groups treated with or without IVIG were compared using nonparametric statistics. Multivariate logistic regression involved all variables available before maintenance therapy began. RESULTS: One hundred eighteen patients were included (53% males), aged 9 months to 19 years. Thirty of 31 patients (97%) who had immunoglobulins analyzed before IVIG were hypogammaglobulinemic. Thirty-six patients (30%) received IVIG during maintenance chemotherapy. Patients received an average of 10.5 IVIG doses (range = 1-31). Ninety-seven percent of doses were administered without a transfusion reaction. Other factors associated with IVIG use were prior double-delayed intensification (odds ratio = 5.36, 95% confidence interval = 1.3-27.49, p = 0.026) and episodes of bacteremia or fungemia before maintenance chemotherapy (odds ratio = 3.04, 95% confidence interval = 1.25-7.51, p = 0.015). CONCLUSION: Use of IVIG in children with ALL in CR1 with hypogammaglobulinemia occurred in approximately 30% of patients and was well tolerated. Administration of IVIG significantly correlated with a history of double-delayed intensification and prior bacteremia or fungemia.

Right ventricular abnormalities in sickle cell anemia: evidence of a progressive increase in pulmonary vascular resistance.

OBJECTIVE: To assess the effects of sickle cell anemia (SCA) on the right ventricle (RV). STUDY DESIGN: Echocardiograms of 32 children with SCA were compared with age-matched healthy controls. RV measurements included diastolic area index, fractional area change, free-wall mass index, ejection time corrected for heart rate (ET(c)), and tricuspid regurgitation (TR) gradient. RESULTS: SCA subjects had elevated RV ETc (mean +/- standard deviation, 0.369 +/- 0.030 sec vs 0.351 +/- 0.022 sec; P < .01), diastolic area index (19.9 +/- 2.4 cm(2)/m(2) vs 13.2 +/- 2.1 cm(2)/m(2); P < .01) and free-wall mass index (33.2 +/- 4.4 g/m(2) vs 23.9 +/- 4.3 g/m(2); P < .01), whereas RV fractional area change (37 +/- 8% vs 36 +/- 4%) was not different from controls. Although RV diastolic area index in SCA paralleled the normal range over time, RV free-wall mass index continued to gradually rise throughout childhood (r = .42; P < .05). TR gradients > 2.5 m/sec, consistent with pulmonary hypertension, were found in 5 (16%) of SCA subjects, all older than 9 years. CONCLUSIONS: RV preload and systolic function do not worsen during childhood in SCA; however, RV mass index and the prevalence of pulmonary hypertension increase consistent with rising pulmonary vascular resistance.

Utility of Holter electrocardiogram in iron-overloaded hemoglobinopathies.

Cardiac arrhythmias are among the leading causes of morbidity and mortality of transfusion-dependent, iron-overloaded beta-thalassemia patients. Routine screening with Holter electrocardiogram has been recommended; however, infrequent electrocardiographic changes limit its clinical usefulness. The purpose of this study was to determine the diagnostic yield of Holter electrocardiogram monitoring and its correlation with patient symptoms and disease status. A retrospective analysis was performed on 27 transfusion-dependent thalassemia patients who underwent cardiac questionnaire and Holter screening yearly, in addition to echocardiogram and quantitative iron-level determination. Four patients had clinically significant arrhythmias detected on Holter screening, while 2 patients developed severe cardiac complications secondary to arrhythmias within 1 year of follow-up of normal Holter screening. Early detection of cardiac events among transfusion-dependent thalassemia patients with Holter electrocardiography is not clinically effective. Other screening modalities, including the transtelephonic event recorder, should be evaluated in arrhythmia surveillance.

Outcomes of preimplantation genetic diagnosis therapy in treatment of beta-thalassemia: A retrospective analysis.

Thalassemia is one of the most common single-gene disorders that can be cured by hematopoietic stem cell transplantation (HCT) from a human leukocyte antigen (HLA)-identical sibling donor. In families that have an affected child, preimplantation genetic diagnosis (PGD) can be used to select an unaffected, HLA-identical embryo. In brief, this procedure requires in vitro fertilization, oocyte retrieval, fertilization, and blastomere biopsy for identification of unaffected HLA-identical embryos. After delivery, umbilical cord blood from the sibling donor is collected for HCT. The objective of this study was to determine the outcomes of families using PGD therapy for cure of beta-thalassemia and to review the limitations of PGD therapy. Families affected with beta-thalassemia who attempted PGD therapy were retrospectively identified and reviewed for indication, attempted cycles, successful pregnancy, and transplantation outcomes. Eight identified families affected by thalassemia underwent PGD. The diagnosis of their affected children included six cases of beta-thalassemia major and two cases of transfusion-dependent hemoglobin E-beta-thalassemia patients. A total of 14 cycles of PGD were attempted, ranging from one to four attempts per family. Following successful identification of HLA-identical cells, two pregnancies occurred, of which one resulted in engraftment of a beta-thalassemia child. PGD therapy offers the possibility of recruiting a suitable donor for HCT, yet is limited by financial cost due to labor-intensive techniques, low probability of obtaining an HLA-matched unaffected embryo, variable implantation capacity, and significant emotional impact. Improvements in PGD therapy's efficacy and cost will make this a more viable option for affected families.

Successful correction of the human beta-thalassemia major phenotype using a lentiviral vector.

beta-thalassemias are the most common single gene disorders and are potentially amenable to gene therapy. However, retroviral vectors carrying the human beta-globin cassette have been notoriously unstable. Recently, considerable progress has been made using lentiviral vectors, which stably transmit the beta-globin expression cassette. Thus far, mouse studies have shown correction of the beta-thalassemia intermedia phenotype and a partial, variable correction of beta-thalassemia major phenotype. We tested a lentiviral vector carrying the human beta-globin expression cassette flanked by a chromatin insulator in transfusion-dependent human thalassemia major, where it would be ultimately relevant. We demonstrated that the vector expressed normal amounts of human beta-globin in erythroid cells produced in in vitro cultures for unilineage erythroid differentiation. There was restoration of effective erythropoiesis and reversal of the abnormally elevated apoptosis that characterizes beta-thalassemia. The gene-corrected human beta-thalassemia progenitor cells were transplanted into immune-deficient mice, where they underwent normal erythroid differentiation, expressed normal levels of human beta-globin, and displayed normal effective erythropoiesis 3 to 4 months after xenotransplantation. Variability of beta-globin expression in erythroid colonies derived in vitro or from xenograft bone marrow was similar to that seen in normal controls. Our results show genetic modification of primitive progenitor cells with correction of the human thalassemia major phenotype.