Development and validation of a predictive tool for adverse drug reactions in neonates under intensive care.

AIMS: Neonates hospitalized in neonatal intensive care units (NICUs) commonly experience adverse drug reactions (ADRs). Thus, we aimed to develop and validate a tool for predicting ADRs in neonates hospitalized in NICUs. METHODS: A nested case-control study in an open cohort with neonates admitted to the NICU of a maternity hospital in Natal, Brazil was conducted from January 2019 to January 2022 [Correction added on 4 December 2023, after first online publication: 2023 has been changed to 2019 in the preceding sentence.]. Neonates with ADR were randomly paired with 2 controls. For the development of the tool, a multivariate logistic regression was applied on 2/3 of the sample (cases with respective controls). The model's fit was evaluated using the Hosmer-Lemeshow test for calibration and the Brier score for performance assessment. Validation of the tool was performed by determining the area under the receiver operating characteristic curve with bootstrap adjusted c-statistics. RESULTS: In all, 450 neonates (150 cases and 300 controls) were included in the study. We identified 5 independent risk factors for ADR, 4 related to the neonate (current mechanical ventilation, heart rate ≥178 beats/min, intravenous medications, ≥5 prescription medications) and 1 to the mother (gestational hypertension). The tool had a classification cut-off point of ≥15, and its total score ranged from 0 to 34. In validation, the tool had an area under the receiver operating characteristic curve of 0.74 (95% confidence interval [CI] 0.66-0.81) with sensitivity of 52.02% (95% CI 47.40-56.64) and specificity of 81.35% (95% CI 77.75-84.95). CONCLUSION: The tool demonstrated adequate discriminative ability and utilized 5 commonly monitored variables in the NICU.

Assessment of severity and avoidability of adverse drug reactions in neonates: a reproducibility study of the Hartwig tool and LAAT.

OBJECTIVE: Tools for classifying adverse drug reactions (ADRs) have not yet been validated in the context of the neonatal intensive care unit (NICU). The study aims to investigate the inter-rater reliability of the Hartwig tool and the Liverpool avoidability assessment tool (LAAT) in assessing the severity and avoidability of ADR cases in hospitalized neonates. METHODS: An observational and prospective study was conducted in the NICU of a maternity hospital in Natal, Brazil. The Hartwig tool and LAAT were employed to assess the severity and avoidability of ADRs, respectively. Three experienced clinical pharmacists independently assessed all ADR cases. Inter-rater reliability was measured using Cohen's kappa coefficient (k) with corresponding 95% confidence intervals (CI). RESULTS: Among 79 ADR cases, the mean gestational age was 29.7 ± 4.4 weeks, and the birth weight averaged 1446.0 ± 1179.3 g. The assessment of ADR severity using the Hartwig tool revealed a significant overall correlation (overall k = 0.573; 95% CI 0.395 to 0.753) with exact agreement (EA) and extreme disagreement (ED) rates between evaluators of 86.5% and 2.5%, respectively. However, no statistically significant correlation was observed for determining avoidability using the LAAT (overall k = 0.017; 95% CI - 0.048 to 0.082), with an EA rate of 83.6% and ED rate of 10.1%. CONCLUSION: The Hartwig tool demonstrates good reproducibility among different evaluators in determining the severity of ADRs, unlike the LAAT for assessing avoidability.

Temporal profile of adverse drug reactions and associated clinical factors: a prospective observational study in a neonatal intensive care unit.

OBJECTIVE: Although adverse drug reactions (ADRs) are quite common in hospitalised neonates, pharmacovigilance activities in this public are still incipient. This study aims to characterise ADRs in neonates in a neonatal intensive care unit (NICU), identifying causative drugs, temporal profile and associated factors. DESIGN: Prospective observational study. SETTING: NICU of a public maternity hospital in Natal/Brazil. PARTICIPANTS: All neonates admitted to the NICU for more than 24 hours and using at least one medication were followed up during the time of hospitalisation. PRIMARY OUTCOME MEASURES: Incidence rate and risk factors for ADRs. The ADRs were detected by an active search in electronic medical records and analysis of spontaneous reports in the hospital pharmacovigilance system. RESULTS: Six hundred neonates were included in the study, where 118 neonates had a total of 186 ADRs. The prevalence of ADRs at the NICU was 19.7% (95% CI 16.7% to 23.0%). The most common ADRs were tachycardia (30.6%), polyuria (9.1%) and hypokalaemia (8.6%). Tachycardia (peak incidence rate: 57.1 ADR/1000 neonates) and hyperthermia (19.1 ADR/1000 neonates) predominated during the first 5 days of hospitalisation. The incidence rate of polyuria and hypokalaemia increased markedly after the 20th day, with both reaching a peak of 120.0 ADR/1000 neonates. Longer hospitalisation time (OR 0.018, 95% CI 0.007 to 0.029; p<0.01) and number of prescribed drugs (OR 0.127, 95% CI 0.075 to 0.178; p<0.01) were factors associated with ADRs. CONCLUSION: ADRs are very common in NICU, with tachycardia and hyperthermia predominant in the first week of hospitalisation and polyuria and hypokalaemia from the third week onwards.