JAMA Pediatrics最新文献

Importance: The American Academy of Pediatrics (AAP) higher-risk criteria for brief resolved unexplained events (BRUE) have a low positive predictive value (4.8%) and misclassify most infants as higher risk (>90%). New BRUE prediction rules from a US cohort of 3283 infants showed improved discrimination; however, these rules have not been validated in an external cohort.

Objective: To externally validate new BRUE prediction rules and compare them with the AAP higher-risk criteria.

Design, setting, and participants: This was a retrospective multicenter cohort study conducted from 2017 to 2021 and monitored for 90 days after index presentation. The setting included infants younger than 1 year with a BRUE identified through retrospective chart review from 11 Canadian hospitals. Study data were analyzed from March 2022 to March 2024.

Exposures: The BRUE prediction rules.

Main outcome and measure: The primary outcome was a serious underlying diagnosis, defined as conditions where a delay in diagnosis could lead to increased morbidity or mortality.

Results: Of 1042 patients (median [IQR] age, 41 [13-84] days; 529 female [50.8%]), 977 (93.8%) were classified as higher risk by the AAP criteria. A total of 79 patients (7.6%) had a serious underlying diagnosis. For this outcome, the AAP criteria demonstrated a sensitivity of 100.0% (95% CI, 95.4%-100.0%), a specificity of 6.7% (95% CI, 5.2%-8.5%), a positive likelihood ratio (LR+) of 1.07 (95% CI, 1.05-1.09), and an AUC of 0.53 (95% CI, 0.53-0.54). The BRUE prediction rule for discerning serious diagnoses displayed an AUC of 0.60 (95% CI, 0.54-0.67; calibration intercept: 0.60), which improved to an AUC of 0.71 (95% CI, 0.65-0.76; P < .001; calibration intercept: 0.00) after model revision. Event recurrence was noted in 163 patients (15.6%). For this outcome, the AAP criteria yielded a sensitivity of 99.4% (95% CI, 96.6%-100.0%), a specificity of 7.3% (95% CI, 5.7%-9.2%), an LR+ of 1.07 (95% CI, 1.05-1.10), and an AUC of 0.58 (95% CI, 0.56-0.58). The AUC of the prediction rule stood at 0.67 (95% CI, 0.62-0.72; calibration intercept: 0.15).

Conclusions and relevance: Results of this multicenter cohort study show that the BRUE prediction rules outperformed the AAP higher-risk criteria on external geographical validation, and performance improved after recalibration. These rules provide clinicians and families with a more precise tool to support decision-making, grounded in individual risk tolerance.

Importance: Gestational exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of adverse fetal kidney outcomes. However, details regarding timing, specific NSAIDs, and long-term childhood kidney outcomes are limited.

Objective: To evaluate the association between gestational exposure to NSAIDs and the risk of chronic kidney disease (CKD) in childhood.

Design, setting, and participants: This national cohort study assessed 1 025 255 children born alive in Taiwan from January 1, 2007, to December 31, 2017, with follow-up until December 31, 2021. Children without valid maternal-child linkage and with incomplete birth information were excluded. Data analysis was performed from November 30, 2023, to April 30, 2024.

Exposure: Maternal prescriptions for NSAIDs from the last menstrual period to birth.

Main outcomes and measures: The main outcome was childhood CKD, including congenital anomalies of the kidney and urinary tract and other kidney diseases. Cox proportional hazards regression models with stabilized inverse probability of treatment weighting (weighted hazard ratio [wHR]) and a robust sandwich estimator were used to estimate the relative risk of NSAID exposure in pregnancy, adjusted for newborn characteristics.

Results: This study included 163 516 singleton-born children (24.0%) whose mothers (mean [SD] age at birth of child, 31.25 [4.92] years) used at least 1 dispensing of an NSAID during pregnancy. Gestational NSAID exposure was significantly associated with a higher risk of childhood CKD (wHR, 1.10; 95% CI, 1.05-1.15). No association was observed between NSAID use and fetal nephrotoxicity in sibling comparisons. Elevated risks were revealed for exposure during the second trimester (wHR, 1.19; 95% CI, 1.11-1.28) and the third trimester (wHR, 1.12; 95% CI, 1.03-1.22) in singleton-born children. Specific NSAID exposures associated with higher CKD risk included indomethacin (wHR, 1.69; 95% CI, 1.10-2.60) and ketorolac (wHR, 1.28; 95% CI, 1.01-1.62) in the first trimester, diclofenac (wHR, 1.27; 95% CI, 1.13-1.42) and mefenamic acid (wHR, 1.29; 95% CI, 1.15-1.46) in the second trimester, and ibuprofen (wHR, 1.34; 95% CI, 1.07-1.68) in the third trimester.

Conclusions and relevance: In this study, gestational exposure to NSAIDs was not associated with a substantial increase in the risk of childhood CKD when comparing between siblings. However, the findings underscore the need for caution when prescribing NSAIDs during pregnancy, particularly indomethacin and ketorolac in the first trimester, mefenamic acid and diclofenac in the second trimester, and ibuprofen in the third trimester, to ensure the safety of the offspring's kidneys.