Aldosterone-Signaling Defect Exacerbates Sodium Wasting in Very Preterm Neonates: The Premaldo Study.

CONTEXT: The neonatal period, notably in preterm infants, is characterized by high sodium wasting, implying that aldosterone, the main hormone regulating sodium reabsorption, is unable to maintain sodium homeostasis. OBJECTIVE: This study sought to assess aldosterone secretion and action in neonates according to gestational age (GA). DESIGN AND SETTING: This was a multicenter prospective study (NCT01176162) conducted between 2011 and 2014 at five neonatology departments in France. Infants were followed during their first 3 months. PARTICIPANTS: The 155 newborns included were classified into three groups: Group 1 (n = 46 patients), <33 gestational weeks (GW); Group 2 (n = 67 patients), 33-36 GW; and Group 3 (n = 42 patients), ≥37 GW. MAIN OUTCOME MEASURES: Plasma aldosterone was measured in umbilical cord blood. Urinary aldosterone (UAldo) was assessed at day 0, day 3, month 1, and month 3 postnatal. The correlation between UAldo and the urinary Na/K ratio was determined as an index of renal aldosterone sensitivity. RESULTS: UAldo significantly increased with GA: from 8.8 ± 7.5 µg/mmol of creatinine (Group 1) to 21.1 ± 21.0 (Group 3) in correlation with plasma aldosterone levels in all groups (P < .001), demonstrating its reliability. The aldosterone/renin ratio significantly increased with GA, suggesting an aldosterone secretion defect in preterm infants. UAldo and urinary Na/K were correlated in very preterm but not in term neonates, consistent with very preterm neonates being renal-aldosterone sensitive and term neonates being aldosterone resistant. CONCLUSIONS: Very preterm infants have a previously unrecognized defective aldosterone secretion but conserved renal aldosterone sensitivity in the neonatal period, which modifies the current view of sodium balance in these infants and suggests alternative management approaches.

Effectiveness of chemotherapy in rhabdomyosarcoma: example of orbital primary.

The survival of patients with rhabdomyosarcoma has been progressively improved with successive protocols due to the development of multidisciplinary management and the data accumulated by international groups. Orbital rhabdomyosarcoma represents 10% of all cases and affects young children (median age: 6.8 years). It is a chemosensitive and radiosensitive tumour. Chemotherapy is designed to decrease the indications for local therapy (mainly radiotherapy) responsible for a high rate of sequelae (cosmetic, functional or secondary cancer). According to the International Society of Paediatric Oncology guidelines, local therapy is not indicated as first-line treatment in case of complete remission after chemotherapy. The 10-year survival of children with non-parameningeal orbital rhabdomyosarcoma is currently 87% and identical survivals are reported by the various collaborative groups despite the use of different treatments. Despite clinical trials demonstrating the efficacy of many types of chemotherapy (cisplatin, etoposide, doxorubicin, dacarbazine), the value of adding these drugs to combination chemotherapy comprising of an alkylating agent (cyclophosphamide or ifosfamide), vincristine and dactinomycin has not been formally demonstrated in terms of survival benefit for children with rhabdomyosarcoma. The authors review these various results and compare the current guidelines for the management of orbital rhabdomyosarcoma recommended by North American and European groups.