Early urine output monitoring in very preterm infants to predict in-hospital neonatal outcomes: a bicentric retrospective cohort study.

OBJECTIVE: To evaluate whether urine output (UO), rarely assessed in the literature, is associated with relevant neonatal outcomes in very preterm infants, and which UO threshold may be the most clinically relevant. DESIGN: Retrospective cohort study. SETTING: Two Level IV neonatal intensive care units. PATIENTS: Very preterm infants born between 240/7 and 296/7 weeks of gestation documented with eight UO measurements per day between postnatal day 1 and day 7. MAIN OUTCOME MEASURES: Composite outcome defined as death before discharge, or moderate to severe bronchopulmonary dysplasia, or severe brain lesions. The association between this outcome and UO was studied using several UO thresholds. RESULTS: Among 532 infants studied, UO <1.0 mL/kg/hour for at least 24 consecutive hours was measured in 55/532 (10%) infants and the primary outcome was recorded in 25 patients. The association between a UO threshold <1.0 mL/kg/hour and the primary outcome was found marginally significant (crude OR 1.80, 95% CI 1.02 to 3.16, p=0.04). The primary outcome was recorded in 112/242 (46%) patients with a UO <2.0 mL/kg/hour and only 64/290 (22%) patients with a UO ≥2.0 mL/kg/hour (p<0.001). This UO threshold was found significantly associated with the primary outcome (crude OR 3.1, 95% CI 2.1 to 4.7, p<0.001), an association confirmed using a multivariate logistic regression model including baseline covariates (adjusted OR 3.7, 95% CI 2.2 to 6.4, p<0.001). CONCLUSION: A UO <2 mL/kg/hour over 24 hours between postnatal day 1 and day 7 strongly predicts neonatal mortality or severe morbidities in very preterm infants.

Urine Output Monitoring for the Diagnosis of Early-Onset Acute Kidney Injury in Very Preterm Infants.

BACKGROUND AND OBJECTIVES: The current threshold used for oliguria in the definition of neonatal AKI has been empirically defined as 1 ml/kg per hour. Urine output criteria are generally poorly documented, resulting in uncertainty in the most accurate threshold to identify AKI in very preterm infants with known tubular immaturity. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a bicentric study including 473 very preterm infants (240/7-296/7 weeks of gestation) born between January 2014 and December 2018 with urine output measurements every 3 hours during the first 7 days of life and two serum creatinine measurements during the first 10 days of life. AKI was defined using the neonatal Kidney Disease Improving Global Outcomes (KDIGO) definition. We tested whether higher urine output thresholds (1.5 or 2 ml/kg per hour) in modified AKI definitions may better discriminate neonatal mortality compared with the current definition. RESULTS: Early-onset AKI was developed by 101 of 473 (21%) very preterm infants. AKI was diagnosed on the basis of urine output criteria alone (no rise in creatinine) for 27 of 101 (27%) participants. Early-onset AKI was associated with higher risk of death before discharge (adjusted odds ratio, 3.9; 95% confidence interval, 1.9 to 7.8), and the AKI neonatal KDIGO score showed good discriminative performance for neonatal mortality, with an area under the receiver operating characteristic (ROC) curve of 0.68 (95% confidence interval, 0.61 to 0.75). Modified AKI definitions that included higher urine output thresholds showed significantly improved discriminative performance, with areas under the ROC curve of 0.73 (95% confidence interval, 0.66 to 0.80) for the 1.5-ml/kg per hour threshold and 0.75 (95% confidence interval, 0.68 to 0.81) for the 2-ml/kg per hour threshold. CONCLUSIONS: Early-onset AKI was diagnosed on the basis of urine output exclusively for a quarter of the cases. Furthermore, modified AKI definitions that included higher urine output improved the discriminative performance for predicting mortality.

Renal follow-up in pediatrician practice after discharge from neonatology units: about a survey.

There is growing evidences of long-term renal and cardiovascular consequences of prematurity, intra-uterine growth restriction, and neonatal acute kidney injury (AKI). We performed an online survey to describe current pediatric management in this population, sent to 148 ambulatory pediatricians in Geneva. Among the 40% of pediatricians who completed the survey, 43% modify their blood pressure measurement practice in case of neonatal acute kidney injury, 24% and 19% in a context of prematurity or intra-uterine growth restriction, respectively. Twenty-five percent provide information about cardiovascular risk factors or catch up growth. In case of prematurity or intra-uterine growth restriction, renal tests (ultrasound, serum creatinine, micro albuminuria) or referral to nephrologist were realized by less than 5% of the pediatricians. For neonatal acute kidney injury, renal tests, and referral to specialists are performed by 30 and 60% of pediatricians, respectively. When prematurity or intra-uterine growth restriction was associated with abnormal blood pressure or abnormal renal tests, the referral to the specialist reached 80%.Conclusion: Ambulatory renal and cardio-vascular follow-up in case of neonatal medical history can be enhanced, with necessity to raise awareness and to edict guidelines available to pediatricians. What is Known: • There is a compelling evidence of long-term renal and cardiovascular consequences of prematurity and low birth weight. • Specific cardiovascular and renal follow-up guidelines, coming from professional organizations, are currently not available for these patients. What is New: • Pediatricians in ambulatory setting do not adapt their renal and cardiovascular follow-up in case of neonatal medical history. • There is a necessity to raise awareness about these long-term consequences among pediatricians and to edict guidelines available to them.

Neuroinflammation in the Developing Brain: Risk Factors, Involvement of Microglial Cells, and Implication for Early Anesthesia.

Microglia cells, the resident macrophages of the central nervous system, are key actors for specific brain functions that are critical for development and health. Microglial reactivity and functions, even when immature, play a major role if the developing brain is subjected to abnormal perinatal events. Brain exposure to general anesthesia, surgery, or analgesic drugs during early infancy may adversely affect its maturation and plasticity after injury. A better understanding of the regulation of microglial activation in the developing brain and interactions with specific anesthetic drugs is expected to give novel insights into the mechanisms underlying their potential adverse effects. This review recapitulates the most frequent perinatal circumstances associated with exacerbated systemic inflammation and neuroinflammation together with the double-edged role of microglia associated with subsequent brain damage. A role for microglial reactivity in both potential anesthetic toxicity and neuroprotection is emerging. However, further preclinical experiments are needed to better understand regulatory mechanisms of the developing microglia, and interaction between anesthesia and neuroinflammation in the developing brain.

Clostridium butyricum Strains and Dysbiosis Linked to Necrotizing Enterocolitis in Preterm Neonates.

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common and serious gastrointestinal disorder among preterm neonates. We aimed to assess a specific gut microbiota profile associated with NEC. METHODS: Stool samples and clinical data were collected from 4 geographically independent neonatal intensive care units, over a 48-month period. Thirty stool samples from preterm neonates with NEC (n = 15) and controls (n = 15) were analyzed by 16S ribosomal RNA pyrosequencing and culture-based methods. The results led us to develop a specific quantitative polymerase chain reaction (qPCR) assay for Clostridium butyricum, and we tested stool samples from preterm neonates with NEC (n = 93) and controls (n = 270). We sequenced the whole genome of 16 C. butyricum strains, analyzed their phylogenetic relatedness, tested their culture supernatants for cytotoxic activity, and searched for secreted toxins. RESULTS: Clostridium butyricum was specifically associated with NEC using molecular and culture-based methods (15/15 vs 2/15; P < .0001) or qPCR (odds ratio, 45.4 [95% confidence interval, 26.2-78.6]; P < .0001). Culture supernatants of C. butyricum strains from preterm neonates with NEC (n = 14) exhibited significant cytotoxic activity (P = .008), and we identified in all a homologue of the ß-hemolysin toxin gene shared by Brachyspira hyodysenteriae, the etiologic agent of swine dysentery. The corresponding protein was secreted by a NEC-associated C. butyricum strain. CONCLUSIONS: NEC was associated with C. butyricum strains and dysbiosis with an oxidized, acid, and poorly diversified gut microbiota. Our findings highlight the plausible toxigenic mechanism involved in the pathogenesis of NEC.

Pediatric en bloc kidney transplantation into pediatric recipients: the French experience.

Chronic shortage of available donor organs has led to re-evaluation of the use of en bloc kidney transplants. Although excellent results have been reported in adult patients, experience in pediatric patients remains limited because of potential early complications and poor long-term graft outcome. We report 14 pediatric en bloc renal transplantations into 14 pediatric recipients, performed between 1990 and 2007 in France. We retrospectively analyzed demographic data, postoperative complications, and graft function with a median follow-up of five yr. Donor age ranged from four to 54 months. Complications were vascular graft thrombosis in four patients, leading to graft loss in two cases, and to excellent long-term graft function in the two others. Two hemorrhagic complications resulted in death in one case and in graft loss in the other. Six acute rejection episodes occurred in four patients. Median glomerular filtration rate at three months, one, five, and 10 yr was 90.8, 106, 87.8, and 66.1 mL/1.73 m(2) /min. We believe that en bloc transplantation may be an option for children with end-stage kidney disease.

Transient neonatal myasthenia gravis revealing a myasthenia gravis and a systemic lupus erythematosus in the mother: case report and review of the literature.

Transient neonatal myasthenia gravis (TNMG) and neonatal lupus are rare conditions due to the transplacental passage of antibodies. We describe a unique case of TNMG, revealing a myasthenia gravis (MG) associated with systemic lupus erythematosus (SLE) in the mother. J. M., 8 days of age, was admitted for jaundice. Examination revealed poor sucking, facial weakness, and hypotonicity. TNMG was confirmed with a high level of antiacetylcholine receptor antibodies in the infant and his mother. No sign of neonatal lupus was observed. Clinical recovery was obtained. The elder brother had autism. In case of previous maternal MG, a low percentage of infants develop TNMG (10 to 20%), but monitoring is required at birth. Improvement is usually obtained within 3 weeks. No correlation has been found between maternal symptoms, antibodies titer, and signs of TNMG. Most cases of neonatal lupus are associated with positive anti-SSA/SSB antibodies in the mother. Both conditions, MG and SLE, are reported, but pregnancies are very few. Autism in the brother focuses on its relationship with immune diseases.

Adjuvant corticosteroid therapy in 2 children with hepatosplenic candidiasis-related IRIS.

First described in HIV-infected patients who recently initiated highly active antiretroviral therapy, the immune reconstitution inflammatory syndrome (IRIS) is best characterized as a collection of inflammatory disorders triggered by rapid resolution of immunosuppression. Treatment of IRIS is a clinical challenge due to the variety of clinical presentations and the presence of multiple pathogens capable of causing the syndrome. Hepatosplenic candidiasis, an uncommon form of invasive Candida species infection, was recently suggested to belong to the spectrum of fungus-related IRIS. We report 2 cases of probable hepatosplenic candidiasis according to the guidelines of the European Organization for Research and Treatment of Cancer and the Mycosis Study Group, occurring in pediatric patients with acute leukemia during rapid neutrophil recovery after cytotoxic chemotherapy. In both cases, abdominal computed tomography scan revealed multiple hepatic micronodules, and liver biopsy showed nonspecific granulomatous lesions. Hepatosplenic candidiasis symptoms (fever, nausea and vomiting, abdominal pain) resolved within 2 days after adjunction of corticosteroid therapy to antifungal treatment. Inflammatory markers and related radiologic abnormalities decreased or disappeared within 1 month. Recovery of neutrophil count in a context of hepatosplenic candidiasis may result in a heightened inflammatory response. Corticosteroid therapy in this setting is associated with prompt resolution of the symptoms.