These data demonstrate that despite peripheral hyperleptinemia, positive energy balance is achieved during pregnancy by a relative decrease in central leptin concentrations and resistance to leptin's effects on target neuropeptides that regulate energy balance.

BACKGROUND: Placenta accreta spectrum (PAS) is a disorder of abnormal placentation associated with severe postpartum hemorrhage, maternal morbidity, and mortality. Predelivery prediction of this condition is important to determine appropriate delivery location and multidisciplinary planning for operative management. This study aimed to validate a prediction model for PAS developed by Weiniger et al in 2 cohorts who delivered at 2 different United States tertiary centers. METHODS: Cohort A (Brigham and Women’s Hospital; N = 253) included patients with risk factors (prior cesarean delivery and placenta previa) and/or ultrasound features of PAS presenting to a tertiary-care hospital. Cohort B (Columbia University Irving Medical Center; N = 99) consisted of patients referred to a tertiary-care hospital specifically because of ultrasound features of PAS. Using the outcome variable of surgical and/or pathological diagnosis of PAS, discrimination (via c-statistic), calibration (via intercept, slope, and flexible calibration curve), and clinical usefulness (via decision curve analysis) were determined. RESULTS: The model c-statistics in cohorts A and B were 0.728 (95% confidence interval [CI], 0.662–0.794) and 0.866 (95% CI, 0.754–0.977) signifying acceptable and excellent discrimination, respectively. The calibration intercept (0.537 [95% CI, 0.154–0.980] for cohort A and 3.001 [95% CI, 1.899– 4.335] for B), slopes (0.342 [95% CI, 0.170–0.532] for cohort A and 0.604 [95% CI, −0.166 to 1.221] for B), and flexible calibration curves in each cohort indicated that the model underestimated true PAS risks on average and that there was evidence of overfitting in both validation cohorts. The use of the model compared to a treat-all strategy by decision curve analysis showed a greater net benefit of the model at a threshold probability of >0.25 in cohort A. However, no net benefit of the model over the treat-all strategy was seen in cohort B at any threshold probability. CONCLUSIONS: The performance of the Weiniger model is variable based on the case-mix of the population with regard to PAS clinical risk factors and ultrasound features, highlighting the importance of spectrum bias when applying this PAS prediction model to distinct populations. The model showed benefit for predicting PAS in populations with substantial case-mix heterogeneity at threshold probability of >25%.

Objective: To validate the Weiniger model, a multivariable prediction model for placenta accreta spectrum (PAS). Design: Multicentre external validation study. Setting: Two tertiary care hospitals in the United States. Population: Cohort A included patients with risk factors (prior caesarean delivery, placenta praevia) and/or ultrasound features of PAS (variable risk) presenting to a tertiary care hospital. Cohort B patients were referred to a tertiary care hospital specifically for ultrasound features of PAS (higher risk). Methods: Weiniger model variables (prior caesarean deliveries, placenta praevia and ultrasound features of PAS) were retrospectively collected from both cohorts and predictive performance of the model was evaluated. Main Outcome Measures: Surgical and/or pathological diagnosis of PAS. Results: The model c-statistic in cohorts A and B was 0.728 (95% CI: 0.662, 0.794) and 0.866 (95% CI: 0.754, 0.977) signifying acceptable and excellent discrimination, respectively. Based on calibration curves, the model underestimated average PAS risk in both cohorts. In both cohorts, high risk was overestimated and low risk underestimated. Use of this model compared to a “treat all” strategy had greater net benefit at a threshold probability of > 0.25 in cohort A, but no net benefit in cohort B. Conclusions: This study provides multicentre external validation of the Weiniger model for PAS prediction, making it a useful triaging tool for management of this high-risk obstetric condition. Clinical usefulness of this model is influenced by the incidence of risk factors and PAS ultrasound features, with better performance in a variable-risk population at threshold probability >25%.

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