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.

Cardiovascular diseases are one of the leading causes of mortality. Hypertension (HT) is one of the principal risk factors associated with death. Chronic kidney disease (CKD), which is probably underestimated, increases the risk and the severity of adverse cardiovascular events. It is now recognized that low birth weight is a risk factor for these diseases, and this relationship is amplified by a rapid catch-up growth or overfeeding during infancy or childhood. The pathophysiological and molecular mechanisms involved in the “early programming” of CKD are multiple and partially understood. It has been proposed that the developmental programming of arterial hypertension and chronic kidney disease is related to a reduced nephron endowment. However, this mechanism is still discussed. This review discusses the complex relationship between birth weight and nephron endowment and how early growth and nutrition influence long term HT and CKD. We hypothesize that fetal environment reduces moderately the nephron number which appears insufficient by itself to induce long term diseases. Reduced nephron number constitutes a “factor of vulnerability” when additional factors, in particular a rapid postnatal growth or overfeeding, promote the early onset of diseases through a complex combination of various pathophysiological pathways.

Background and objectivesThe 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, & measurementsWe 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.ResultsEarly-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.ConclusionsEarly-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.

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.

The structural and functional development of the kidney is responsible for a significant impact on postnatal adaptation to extrauterine life. Prenatal or neonatal impairment of nephrogenesis may carry long term, lifelong consequences in terms of reduced nephron endowment, chronic kidney disease, and cardiovascular risks at adulthood. Intrauterine growth restriction, preterm birth, congenital renal, and urinary tract anomalies are for long widely incriminated. Neonatal administration of nephrotoxic drugs has been associated with short-term acute kidney injury and longer chronic kidney disease. This review attempts at offering a comprehensive understanding of the renal development, the neonatal renal transition to extrauterine life and subsequent maturation phase during early infancy. It also focuses on developmental and maturational changes that impact lifelong renal function and adult health.

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.

Pediatric Intensive Care Units (PICUs) provide multidisciplinary care to critically ill children and their families. Grief is present throughout the trajectory of illness and can peak around the time of death or non-death losses. The objective of this study was to assess how PICUs around the world implement grief and bereavement care (GBC) as part of an integrated model of care. This is a multicenter cross-sectional, prospective survey study. Questionnaires with multiple-choice and open-ended questions focusing on unit infrastructure, personnel, policies, limited patient data, and practices related to GBC for families and health care professionals (HCPs) were completed by on-site researchers, who were HCPs on the direct care of patients. PICU fulfillment of GBC goals was evaluated using a custom scoring based on indicators developed by the Initiative for Pediatric Palliative Care (IPPC). We compared average total and individual items fulfillment scores according to the respective country's World Bank income. Patient characteristics and details of unit infrastructure were also evaluated as potential predictors of total GBC fulfillment scores. Statistical analysis included multilevel generalized linear models (GLM) with a Gaussian distribution adjusted by child age/gender and clustering by center, using high income countries (HICs) as the comparative reference. Additionally, we applied principals of content analysis to analyze and summarize open-ended answers to contextualize qualitative data. The study included 34 PICUs from 18 countries: high-income countries (HICs): 32.4%, upper middle-income countries (UMICs): 44.1%, low middle-income and low-income countries (LMI/LICs): 23.5%. All groups reported some compliance with GBC goals; no group reported perfect fulfillment. We found statistically significant differences in GBC fulfillment scores between HICs and UMICs (specifically, HCP grief support), and between HICs and LMICs (specifically, family grief support and HCP grief support). PICUs world-wide provide some GBC, independent of income, but barriers include lack of financial support, time, and training, overall unit culture, presence of a palliative care consultation service, and varying cultural perceptions of child death. Disparities in GBC for families and HCPs exist and were related to the native countries' income level. Identifying barriers to support families and HCPs, can lead to opportunities of improving GBC in PICUs world-wide.

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.