Clinical use of gastric antisecretory drugs in pediatric patients with gastroesophageal reflux disease: a narrative review.

Background and Objective: Gastroesophageal reflux (GER) is a common condition in infants. Usually, it resolves spontaneously in 95% of cases within 12-14 months of age, but gastroesophageal reflux disease (GERD) may develop in some children. Most authors do not recommend pharmacological treatment of GER, while the management of GERD is debated. The aim of this narrative review is to analyze and summarize the available literature on the clinical use of gastric antisecretory drugs in pediatric patients with GERD. Methods: References were identified through MEDLINE, PubMed, and EMBASE search engines. Only articles in English were considered. The following keywords were used: "gastric antisecretory drugs", "H2RA", "PPI", "ranitidine", "GERD", "infant", "child". Key Content and Findings: Increasing evidence of poor efficacy and potential risks of proton pump inhibitors (PPIs) is emerging in neonates and infants. Histamine-2 receptor antagonists (H2RAs), including ranitidine, have been used successfully in older children, although less effective than PPIs at relieving symptoms and healing GERD. However, in April 2020, both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) requested manufacturers of ranitidine to remove all ranitidine products from the market due to the risk of carcinogenicity. Pediatric studies comparing effectiveness and safety of different acid-suppressing treatments for GERD are generally inconclusive. Conclusions: A proper differential diagnosis between GER and GERD is crucial to avoid the overuse of acid-suppressing medications in children. Further research should be directed towards the development of novel antisecretory drugs, with proven efficacy and good safety profile, for treating pediatric GERD, particularly in newborns and infants.

Paracetamol overdose in the newborn and infant: a life-threatening event.

PURPOSE: Paracetamol is the only drug recommended to treat fever in neonates. At recommended doses, paracetamol has not been associated with liver injury in neonates, while hepatotoxicity may occur after intake of a single high dose or multiple excessive doses. The aim of this narrative review is to critically analyze and summarize the available literature on newborns and infants exposed to supratherapeutic doses of paracetamol, with special focus on their clinical features, outcome, and management. METHODS: The PubMed, SCOPUS, and Google Scholar search engines were used to collect data, without time limitation. The following keywords were used: paracetamol/acetaminophen, overdose, hepatotoxicity, N-acetylcysteine, newborn, infant. RESULTS: The literature search identified a total of 27 case reports, a number of review articles, and few other relevant publications. Neonatal poisoning from paracetamol resulted from transplacental drug transfer after maternal overdose in some published cases, while it was the consequence of medication errors in other cases. Newborns and infants who have received a single overdose and have paracetamol concentrations below the Rumack-Matthew nomogram limits are at low risk of serious hepatic damage, while those who have recently ingested more than one supratherapeutic dose of paracetamol should be managed with caution. The treatment of choice for paracetamol poisoning is N-acetylcysteine, a specific antidote which reduces paracetamol hepatotoxic effects. N-Acetylcysteine should be given according to specific regimens through weight-based dosing tables. CONCLUSIONS: Caution should be used when paracetamol is administered to the newborn. In the event of an overdose, careful patient monitoring and personalization of post-overdose procedures are recommended.

Early diagnosis of acute kidney injury with urinary biomarkers in the newborn.

Biomarkers are biological parameters that can be objectively measured and evaluated, which act as indicators of normal or pathological processes, or of the response to intervention. Acute Kidney Injury (AKI) biomarkers must be easy to detect and measure, must correlate with severity (offering accurate prognosis), quantitatively describing the level of injury even in the absence of clinical signs. Finally, they must be adequate to indicate treatment initiation. So, the sensitivity (early appearance), specificity (typical of organ injury) and time-course are critical factors in determining the utility of a particular biomarker in the disease process. It is unlikely that a single biomarker will satisfy all of these requirements. As AKI is multifactorial in origin, a panel of biomarkers will be required on one hand to differentiate subtypes of AKI, on the other hand to define the phase and severity of injury. The aim of this review is to present the principal urinary biomarkers used in neonatology.

Off-label and unlicensed prescribing for newborns and children in different settings: a review of the literature and a consideration about drug safety.

This review aims to give an updated overview of the worldwide situation of off-label and unlicensed drug use in the paediatric field, also taking into account the safety of this kind of treatment. A Medline and Embase search was performed between 1990 and 2006 and a total of 52 studies were identified and included in the systematic review. From the authors' analysis of the literature, the extent of paediatric unlicensed/off label use is higher in neonatal and paediatric intensive care units and oncology wards, compared with primary care. Moreover, among the nine studies reporting the contribution of an off-label/unlicensed drug use to the occurrence of adverse events, the percentage of unlicensed and/or off-label prescriptions involved in an adverse drug reaction ranged between 23 and 60%. To ensure that children are not exposed to unnecessary risks, controlled clinical trials are required. In addition, future research should be directed towards the identification of individual drugs that cause serious adverse drug reactions and lack product information.