Adverse drug reactions in neonates: a brief analysis of the FDA adverse event reporting system

IntroductionDrug trials in neonates are scarce, and the neonates may consequently be at risk of adverse drug reactions (ADRs). Spontaneous ADR reporting is an important tool for expanding the knowledge on drug safety in neonates. This study explores the quality of current neonatal ADR reports and the ADR reports of the most common drugs used in neonatal departments.MethodsAn observational cross-sectional study focused on neonates was conducted using data on spontaneous reports extracted from the U.S. Food and Drug Administration Adverse Events Reporting System (FAERS) from the third quarter of 2014 up to December 2022. Only the primary suspect drugs given to neonates or subjects aged <30 days were included in the analysis.ResultsSpontaneous reports from 13 million patients of all ages, totaling 50 million ADRs, were evaluated. Information regarding the age was missing in 40% of the reports, and data on 43,737 neonates with 948 different suspected drugs were identified and included in the analysis. We report the frequency of spontaneous ADR reports in the FAERS database for the ten most frequently administered drugs in neonatal intensive care units in the USA.ConclusionOverall, neonatal ADRs are still underreported. The FAERS database in its current form discriminates insufficiently between prenatal and postnatal drug exposures. Hence, improved neonatal pharmacovigilance systems are urgently needed

Simvastatin and oxidative stress in humans:A randomized, double-blinded, placebo-controlled clinical trial

Simvastatin reduces the blood concentration of cholesterol by inhibiting hydroxymethylglutaryl-coenzyme A reductase, the rate-limiting enzyme in cholesterol synthesis, and thereby reduces the risk of cardiovascular disease. In addition, simvastatin treatment leads to a reduction in fluxes in mitochondrial respiratory complexes I and II and might thereby reduce the formation of reactive oxygen species, which have been implicated in the pathogenesis of arteriosclerosis. Therefore, we hypothesized that simvastatin may reduce oxidative stress in humans in vivo. We conducted a randomized, double-blinded, placebo-controlled study in which subjects were treated with either 40 mg of simvastatin or placebo for 14 days. The endpoints were six biomarkers for oxidative stress, which represent intracellular oxidative stress to nucleic acids, lipid peroxidation and plasma antioxidants, that were measured in urine and plasma samples. A total of 40 participants were included, of which 39 completed the trial. The observed differences between simvastatin and placebo groups in the primary outcomes, DNA and RNA oxidation, were small and nonsignificant (p=0.68), specifically, 3% in the simvastatin group compared to 7.1% in the placebo group for DNA oxidation and 7.3% in the simvastatin group compared to 3.4% in the placebo group. The differences in biomarkers related to plasma were not statistically significant between the treatments groups, with the exception of total vitamin E levels, which, as expected, were reduced in parallel with the reduction in plasma cholesterol. In healthy young male volunteers, short-term simvastatin treatment, which considerably reduces cholesterol, does not lead to a clinically relevant reduction in a panel of measures of oxidative stress. Whether simvastatin has effects on oxidative stress in diseased populations, such as diabetes or hemochromatosis, where oxidative stress is prominent, is unknown but seems unlikely

Evaluation of Topical Corticosteroid Use in Pregnancy and Risk of Newborns Being Small for Gestational Age and Having Low Birth Weight

IMPORTANCE: Topical corticosteroids are frequently used during pregnancy. Limited data have raised concerns about an increased risk of the newborn being small for gestational age (SGA) and having low birth weight, in particular with use of potent to very potent agents during pregnancy. OBJECTIVE: To evaluate whether topical corticosteroid use in pregnancy is associated with increased risks of SGA and low birth weight. DESIGN, SETTING, AND PARTICIPANTS: From a source cohort of 1.1 million pregnancies with individual-level informed data from various registries, this nationwide cohort study identified topical corticosteroid–exposed pregnancies in Denmark from January 1, 1997, to December 31, 2016, for a total of 60 497, that were matched with 241 986 unexposed pregnancies on the basis of propensity scores, including a wide set of baseline characteristics. Data analysis was performed from September 8, 2020, to February 23, 2021. EXPOSURES: Filled prescriptions for topical corticosteroids during pregnancy. MAIN OUTCOMES AND MEASURES: Primary outcomes were SGA and low birth weight. Association between outcomes and exposure was assessed by relative risk ratios (RRs) and absolute risk differences (ARDs). RESULTS: Among the 60 497 matched pregnancies exposed to topical corticosteroids, 5678 (9.4%) of the delivered infants were born SGA compared with 22 634 infants (9.4%) among the matched unexposed pregnancies (RR, 1.00; 95% CI, 0.98-1.03 and ARD, 0.3; 95% CI, −2.3 to 2.9 per 1000 pregnancies). Low birth weight occurred in 2006 (3.3%) of the exposed pregnancies compared with 8675 (3.6%) of the unexposed pregnancies (RR, 0.92; 95% CI, 0.88-0.97 and ARD, −2.7; 95% CI, −4.3 to −1.1 per 1000 pregnancies). Exposure to potent to very potent topical corticosteroids at any amount was not associated with an increased risk of SGA (RR, 1.03; 95% CI, 0.99-1.07) or low birth weight (RR, 0.94; 95% CI, 0.88-1.00). Post hoc analyses did not find a significant increased risk among those receiving large amounts of potent to very potent topical corticosteroids (ie, >200 g throughout pregnancy) compared with unexposed pregnancies (RR, 1.17; 95% CI, 0.95-1.46 for SGA and RR 1.14; 95% CI, 0.81-1.60 for low birth weight). CONCLUSIONS AND RELEVANCE: This large cohort study found no association between topical corticosteroid use in pregnancy and an increased risk of SGA or low birth weight. These results suggest that a moderate to large increase in the risk is unlikely, even when large amounts of potent to very potent topical corticosteroids are used in pregnancy