The Prevalence and Clinical Significance of Congenital Anomalies of the Kidney and Urinary Tract in Preterm Infants.

Importance: The prevalence and importance of congenital anomalies of the kidney and urinary tract (CAKUT) in preterm infants is unknown. Objective: To determine the prevalence of CAKUT in preterm infants and association with in-hospital morbidity and mortality. Design, Setting, and Participants: This cohort study included infants cared for in neonatal intensive care units managed by a large US network of hospitals and doctors. Eligible participants were infants born at 23 to 33 weeks' gestation between 2000 and 2020. Infants transferred from or to other health care facilities prior to discharge or death were excluded in analysis of outcomes. Data were analyzed from December 2021 until May 2022. Exposures: The presence of anomalies of the kidneys, ureters, bladder, or urethra was assessed. Covariates were discharge year, exposure to antenatal steroids, sex, maternal race, gestational age, birthweight, mechanical ventilation in first 72 hours of life, genetic disorders, and extrarenal anomalies. Main Outcomes and Measures: Death or in-hospital severe illness (acute kidney injury, kidney failure, intracranial hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, bacterial sepsis, or administration of inotrope or vasopressor). Results: In this cohort of 409 704 infants, 191 105 (46.6%) were girls, mean (SD) gestational age was 30.1 (2.84) weeks, and mean (SD) birth weight was 1.49 (0.53) kg. A total of 8093 infants (2.0%) had CAKUT, with urinary tract dilation comprising the majority of cases (5669 [70.0%]). The presence of CAKUT correlated with earlier gestational age and was associated with genetic disorders and extrarenal anomalies. Analysis of 323 957 infants after exclusions demonstrated an adjusted odds ratio of 3.96 (95% CI, 3.70-4.24) of death or severe illness. This risk was found across all forms of CAKUT including isolated urinary tract dilation. Conclusions and Relevance: The findings of this cohort study suggest that clinicians caring for preterm infants should have higher suspicion for CAKUT and consider screening, particularly those with extrarenal anomalies or genetic disorders, as preterm infants with CAKUT appear to be at significantly higher risk of death or severe illness. Detection of CAKUT can inform risk stratification and clinical decision making, and should also prompt clinicians to consider a genetic evaluation.

Thrombopoietic agents for the treatment of persistent and chronic immune thrombocytopenia in children.

OBJECTIVES: To determine the safety, tolerability, or efficacy of 2 licensed thrombopoietic agents in children with persistent and chronic immune thrombocytopenia (ITP). STUDY DESIGN: Retrospective analysis approved by the institutional review board of children with ITP not on-study who received thrombopoietin (TPO) therapy; 21 received romiplostim (11 at Children's Hospital of Orange County, 10 at Weill Cornell Medical Center) and 12 received eltrombopag (all at Weill Cornell Medical Center). Primary response measures were platelet counts ≥ 50 × 10(9)/L or ≥ 20 × 10(9)/L above baseline for 2 consecutive weeks and 50% of platelet counts ≥ 50 × 10(9)/L. Duration of treatment and adverse events, including bone marrow myelofibrosis (MF) consensus grades, were tabulated. RESULTS: Twenty-seven of 33 (82%) patients responded to TPO agents, 18 of 21 to romiplostim, and 9 of 12 to eltrombopag, after an average of 3.6 previous ITP therapies. These 27 patients had platelet counts ≥ 50 × 10(9)/L and ≥ 20 × 10(9)/L above baseline for 2 consecutive weeks; 26 had 50% of platelet counts ≥ 50 × 10(9)/L. Duration of romiplostim use ranged from 6 to 44 months (11/18 ongoing) and of eltrombopag 23 to 53 months (7/12 ongoing). One patient on eltrombopag experienced a provoked deep-vein thrombosis at site of ankle fracture. No other serious drug-related adverse events occurred. Among 24 bone marrows, 10 after greater than 2 years of therapy, 23 were normal (MF grades 0-1); 1 was MF-2. CONCLUSION: Retrospective analysis of off-study use of TPO agents in children with mainly chronic ITP showed increases in platelet counts in more than 4 of 5 children. The long-term use of TPO agents, up to 53 months, without tachyphylaxis supports their efficacy. These agents appear safe, effective, and tolerable in children with chronic ITP.

Rituximab and three dexamethasone cycles provide responses similar to splenectomy in women and those with immune thrombocytopenia of less than two years duration.

Adults with newly diagnosed or persistent immunothrombocytopenia frequently relapse upon tapering steroids; adults and children with chronic disease have an even lower likelihood of lasting response. In adults with newly-diagnosed immunothrombocytopenia, two studies showed that dexamethasone 40 mg/day × four days and 4 rituximab infusions were superior to dexamethasone alone. Studies have also shown three cycles of dexamethasone are better than one and patients with persistent/chronic immunothrombocytopenia respond less well to either dexamethasone or rituximab. Therefore, 375 mg/m(2) × 4 rituximab was combined with three 4-day cycles of 28 mg/m(2) (max. 40 mg) dexamethasone at 2-week intervals and explored in 67 ITP patients. Best long-term response was assessed as complete (platelet count ≥ 100 × 10(9)/L) or partial (50-99 × 10(9)/L). Only 5 patients had not been previously treated. Fifty achieved complete (n=43, 64%) or partial (n=7, 10%) responses. Thirty-five of 50 responders maintained treatment-free platelet counts over 50 × 10(9)/L at a median 17 months (range 4-67) projecting 44% event-free survival. Duration of immunothrombocytopenia less than 24 months, achieving complete responses, and being female were associated with better long-term response (P<0.01). Adverse events were generally mild-moderate, but 3 patients developed serum sickness and 2 colitis; there were no sequelae. Dexamethasone could be difficult to tolerate. Fourteen patients became hypogammaglobulinemic and half had increased frequency of minor infections; 9 of 12 evaluable patients recovered their IgG levels. Rituximab combined with three cycles of dexamethasone provides apparently better results to reported findings with rituximab alone, dexamethasone alone, or the combination with one cycle of dexamethasone. The results suggest medical cure may be achievable in immunothrombocytopenia, especially in women and in patients within two years of diagnosis. (clinicaltrials.gov identifier:02050581).