Despite the worldwide acceptance of acetaminophen (APAP) as a necessary medicine in pediatrics, evidence that early exposure to APAP causes neurodevelopmental injury in susceptible babies and children has been mounting for over a decade. The evidence is diverse and includes extensive work with laboratory animals, otherwise unexplained associations, factors associated with APAP metabolism, and limited studies in humans. Although the evidence has reached an overwhelming level and was recently reviewed in detail, controversy persists. This narrative review evaluates some of that controversy. Evidence from the pre- and postpartum periods was considered to avoid controversy raised by consideration of only limited evidence of risks during the prepartum period. Among other issues, the association between APAP use and the prevalence of neurodevelopmental disorders was considered. A systematic review revealed that the use of APAP in the pediatric population was never tracked carefully; however, historical events that affected its use were documented and are sufficient to establish apparent correlations with changes in the prevalence of neurodevelopmental disorders. Moreover, problems with the exclusive reliance on results of meta-analyses of large datasets with limited time frames of drug exposure were reviewed. Furthermore, the evidence of why some children are susceptible to APAPinduced neurodevelopmental injuries was examined. We concluded that available evidence demonstrates that early exposure to APAP causes neurodevelopmental injury in susceptible babies and small children.

Despite the worldwide acceptance of acetaminophen (APAP) as a necessary medicine in pediatrics, evidence that early exposure to APAP causes neurodevelopmental injury in susceptible babies and children has been mounting for over a decade. The evidence is diverse and includes extensive work with laboratory animals, otherwise unexplained associations, factors associated with APAP metabolism, and limited studies in humans. Although the evidence has reached an overwhelming level and was recently reviewed in detail, controversy persists. This narrative review evaluates some of that controversy. Evidence from the pre- and postpartum periods was considered to avoid controversy raised by consideration of only limited evidence of risks during the prepartum period. Among other issues, the association between APAP use and the prevalence of neurodevelopmental disorders was considered. A systematic review revealed that the use of APAP in the pediatric population was never tracked carefully; however, historical events that affected its use were documented and are sufficient to establish apparent correlations with changes in the prevalence of neurodevelopmental disorders. Moreover, problems with the exclusive reliance on results of meta-analyses of large datasets with limited time frames of drug exposure were reviewed. Furthermore, the evidence of why some children are susceptible to APAPinduced neurodevelopmental injuries was examined. We concluded that available evidence demonstrates that early exposure to APAP causes neurodevelopmental injury in susceptible babies and small children.

Despite the worldwide acceptance of acetaminophen (APAP) as a necessary medicine in pediatrics, evidence that early exposure to APAP causes neurodevelopmental injury in susceptible babies and children has been mounting for over a decade. The evidence is diverse and includes extensive work with laboratory animals, otherwise unexplained associations, factors associated with APAP metabolism, and limited studies in humans. Although the evidence has reached an overwhelming level and was recently reviewed in detail, controversy persists. This narrative review evaluates some of that controversy. Evidence from the pre- and postpartum periods was considered to avoid controversy raised by consideration of only limited evidence of risks during the prepartum period. Among other issues, the association between APAP use and the prevalence of neurodevelopmental disorders was considered. A systematic review revealed that the use of APAP in the pediatric population was never tracked carefully; however, historical events that affected its use were documented and are sufficient to establish apparent correlations with changes in the prevalence of neurodevelopmental disorders. Moreover, problems with the exclusive reliance on results of meta-analyses of large datasets with limited time frames of drug exposure were reviewed. Furthermore, the evidence of why some children are susceptible to APAPinduced neurodevelopmental injuries was examined. We concluded that available evidence demonstrates that early exposure to APAP causes neurodevelopmental injury in susceptible babies and small children.

Despite the worldwide acceptance of acetaminophen (APAP) as a necessary medicine in pediatrics, evidence that early exposure to APAP causes neurodevelopmental injury in susceptible babies and children has been mounting for over a decade. The evidence is diverse and includes extensive work with laboratory animals, otherwise unexplained associations, factors associated with APAP metabolism, and limited studies in humans. Although the evidence has reached an overwhelming level and was recently reviewed in detail, controversy persists. This narrative review evaluates some of that controversy. Evidence from the pre- and postpartum periods was considered to avoid controversy raised by consideration of only limited evidence of risks during the prepartum period. Among other issues, the association between APAP use and the prevalence of neurodevelopmental disorders was considered. A systematic review revealed that the use of APAP in the pediatric population was never tracked carefully; however, historical events that affected its use were documented and are sufficient to establish apparent correlations with changes in the prevalence of neurodevelopmental disorders. Moreover, problems with the exclusive reliance on results of meta-analyses of large datasets with limited time frames of drug exposure were reviewed. Furthermore, the evidence of why some children are susceptible to APAPinduced neurodevelopmental injuries was examined. We concluded that available evidence demonstrates that early exposure to APAP causes neurodevelopmental injury in susceptible babies and small children.

Methods: Patients undergoing elective PCDF at our urban academic medical center from 2014 to 2020 were included. Patients were categorized by mFI scores (0–0.08, 0.09–0.17, 0.18–0.26, and ≥0.27). Univariate statistics compared demographics, comorbidities, and clinical/surgical outcomes. Multiple linear regression analysis evaluated the magnitude of improvement in PROMs at 1 year. Results: A total of 165 patients were included and grouped by mFI scores: 0 (n=36), 0.09 (n=62), 0.18 (n=42), and ≥0.27 (n=30). The severe frailty group (mFI ≥0.27) was significantly more likely to be diabetic (p <0.001) and have a greater Elixhauser comorbidity index (p =0.001). They also had worse baseline Physical Component Score-12 (PCS-12) (p =0.011) and modified Japanese Orthopaedic Association (mJOA) (p =0.012) scores and worse 1-year postoperative PCS-12 (p =0.008) and mJOA (p =0.001) scores. On regression analysis, an mFI score of 0.18 was an independent predictor of greater improvement in ΔVisual Analog Scale neck (β =−2.26, p =0.022) and ΔVAS arm (β =−1.76, p =0.042). Regardless of frailty status, patients had similar 90-day readmission rates (p =0.752), complication rates (p =0.223), and revision rates (p =0.814), but patients with severe frailty were more likely to have longer hospital length of stay (p =0.006) and require non-home discharge (p <0.001). Conclusions Similar improvements across most PROMs can be expected irrespective of the frailty status of patients undergoing PCDF. Complication rates, 90-day readmission rates, and revision rates are not significantly different when stratified by frailty status. However, patients with severe frailty are more likely to have longer hospital stays and require non-home discharge.