Ototoxic and nephrotoxic drugs in neonatal intensive care units: results of a Spanish and Italian survey.

Neonates face heightened susceptibility to drug toxicity, often exposed to off-label medications with dosages extrapolated from adult or pediatric studies. Premature infants in Neonatal Intensive Care Units (NICUs) are particularly at risk due to underdeveloped pharmacokinetics and exposure to multiple drugs. The study aimed to survey commonly used medications with a higher risk of ototoxicity and nephrotoxicity in Spanish and Italian neonatal units. A prospective cross-sectional study was conducted in Italian and Spanish neonatal units using a web-based survey with 43 questions. A modified Delphi method involved experts refining the survey through online consensus. Ethical approval was obtained, and responses were collected from January to July 2023. The survey covered various aspects, including drug-related ototoxic and nephrotoxic management, hearing screening, and therapeutic drug monitoring. Responses from 131 participants (35.9% from Spain and 64.1% from Italy) revealed awareness of drug toxicity risks. Varied practices were observed in hearing screening protocols, and a high prevalence of ototoxic and nephrotoxic drug use, including aminoglycosides (100%), vancomycin (70.2%), loop diuretics (63.4%), and ibuprofen (62.6%). Discrepancies existed in guideline availability and adherence, with differences between Italy and Spain in therapeutic drug monitoring practices. CONCLUSIONS: The study underscores the need for clinical guidelines and uniform practices in managing ototoxic and nephrotoxic drugs in neonatal units. Awareness is high, but inconsistencies in practices indicate a necessity for standardization, including the implementation of therapeutic drug monitoring and the involvement of clinical pharmacologists. Addressing these issues is crucial for optimizing neonatal care in Southern Europe. WHAT IS KNOWN: • Neonates in intensive care face a high risk of nephrotoxicity and ototoxicity from drugs like aminoglycosides, vancomycin, loop diuretics, and ibuprofen. • Therapeutic drug monitoring is key for managing these risks, optimizing dosing for efficacy and minimizing side effects. WHAT IS NEW: • NICUs in Spain and Italy show high drug toxicity awareness but differ in ototoxic/nephrotoxic drug management. • Urgent need for standard guidelines and practices to address nephrotoxic risks from aminoglycosides, vancomycin, loop diuretics, and ibuprofen.

Positional plagiocephaly from structure to function: Clinical experience of the service of pediatric osteopathy in Italy.

OBJECTIVE: Aim of the study is to evaluate disorders related to positional plagiocephaly and introduce a new model of early intervention based on the osteopathic integrated approach. METHODS: We review clinical experience of the "Program for Neurodevelopmental Follow-up and Pediatric Osteopathy", a service dedicated to newborns at risk for developmental disorders. RESULTS: We present clinical data of 310 newborns followed during first years of life. Data analysis examines perinatal history, general features and disorders that could be related to plagiocephaly. CONCLUSIONS: The experience confirms that plagiocephaly is not only a problem regarding the shape of the head, it involves the functions. In our Service most babies (81%) with positional plagiocephaly showed isolated or associated disorders that had an impact on growth, behavior and development. The early intervention based on the osteopathic integrated approach is addressed not only to the cranial shape but consider the baby as a whole, and the environment where he lives.

Early appearance of hypokalemia in Gitelman syndrome.

Inactivating mutations in the SLC12A3 gene that encodes the thiazide-sensitive co-transporter causes Gitelman syndrome. The main features of this syndrome include normal or low blood pressure, hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria, and hyperreninemia. These patients are at low risk for preterm birth and do not present with symptoms before school age. As a consequence, the condition is usually diagnosed in late childhood or in adult life. We report on four patients, two pairs of prematurely born twins, in whom hypokalemia was demonstrated early in life. In these children, a tendency towards hypokalemia was first noted during the third week of life. Overt hypokalemia subsequently appeared associated with normal blood pressure, hypochloremia, hyperreninemia, and an inappropriately high fractional excretion of potassium and chloride. Molecular biology studies failed to detect mutations in the SLC12A1, KCNJ1, and CLCNKB genes responsible for the Bartter syndromes type I, II and III, respectively. Compound heterozygous mutations in the SLC12A3 gene were detected in both pairs of twins: a frameshift mutation in exon 10 (c.1196_1202dup7bp), leading to the truncated protein p.Ser402X, and a missense mutation in exon 11, p.Ser475Cys (c.1424C>G) in the first pair; two missense mutations, p.Thr392Ile (c.1175C>T) in exon 9 and p.Ser615Leu in exon 15 (c.1844C>T), in the second pair. In conclusion, the diagnosis of Gitelman syndrome deserves consideration in infants with unexplained hypokalemia.

Fetal hydrops in GM(1) gangliosidosis: a case report.

UNLABELLED: GM(1) gangliosidosis is a rare disorder characterized by deficiency of the ss-galactosidase enzyme, with the resulting accumulation of glycolipids, oligosaccharides and especially GM(1) ganglioside. It can be classified into three clinical types according to the time of onset: infantile, juvenile and adult form. We report a case of GM(1) gangliosidosis presenting with fetal hydrops at 24 wk of gestation. The parents were consanguineous; the baby, born at 35 wk of gestation, was dysmorphic and presented severe generalized oedema. The most common cause of fetal hydrops was excluded. A lysosomal storage disease was suspected, and GM(1) gangliosidosis was diagnosed. The child developed severe growth and mental retardation and died when she was 21 mo old. CONCLUSION: We suggest that the possible association between inborn errors of metabolism and antenatal ascites should be considered, in order to offer genetic counselling due to the high recurrence risk and the availability of early antenatal diagnosis.

High-frequency partial liquid ventilation in two infants.

Two infants on high-frequency oscillatory ventilation for chronic lung disease and severe respiratory failure, received a bolus of warmed and oxygenated perfluorodecalin up to residual functional capacity, followed by a continuous infusion of 6 ml/kg/hour. Our aim was to improve gas exchange without increasing ventilatory-induced lung injury. Heart rate, oxygen saturation, blood pressure, and TcPO(2)/TcPCO(2) were continuously monitored during treatment. Arterial blood gas was evaluated every 3 hours. Both patients showed improvement of gas exchange with a 13.6 and 12.5% reduction of oxygenation index, respectively. High-frequency partial liquid ventilation is an experimental ventilation technique that could be considered as rescue treatment, to improve oxygenation in subjects with critical respiratory failure. This method could probably produce less damage, than other ventilation modes, to severely injured lungs.