External Validation of a Multivariable Prediction Model for Placenta Accreta Spectrum.

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%.

Cerebrospinal fluid levels of leptin, proopiomelanocortin, and agouti-related protein in human pregnancy: evidence for leptin resistance.

CONTEXT: Leptin suppresses appetite by modulating the expression of hypothalamic neuropeptides including proopiomelanocortin (POMC) and agouti-related peptide (AgRP). Yet during pregnancy, caloric consumption increases despite elevated plasma leptin levels. DESIGN AND PARTICIPANTS: To investigate this paradox, we measured leptin and soluble leptin receptor in plasma and leptin, POMC, and AgRP in cerebrospinal fluid (CSF) from 21 fasting pregnant women before delivery by cesarean section at a university hospital and from 14 fasting nonpregnant women. RESULTS: Prepregnancy body mass index was 24.6 ± 1.1 (SE) vs. 31.3 ± 1.3 at term vs. 26.5 ± 1.6 kg/m(2) in controls. Plasma leptin (32.9 ± 4.6 vs. 16.7 ± 3.0 ng/ml) and soluble leptin receptor (30.9 ± 2.3 vs. 22.1 ± 1.4 ng/ml) levels were significantly higher in pregnant women. However, mean CSF leptin did not differ between the two groups (283 ± 34 vs. 311 ± 32 pg/ml), consistent with a relative decrease in leptin transport into CSF during pregnancy. Accordingly, the CSF/plasma leptin percentage was 1.0 ± 0.01% in pregnant subjects vs. 2.1 ± 0.2% in controls (P < 0.0001). Mean CSF AgRP was significantly higher in pregnant subjects (32.3 ± 2.7 vs. 23.5 ± 2.5 pg/ml; P = 0.03). Mean CSF POMC was not significantly different in pregnant subjects (200 ± 13.6 vs. 229 ± 17.3 fmol/ml; P = 0.190). However, the mean AgRP/POMC ratio was significantly higher among pregnant women (P = 0.003), consistent with an overall decrease in melanocortin tone favoring increased food intake during pregnancy. CONCLUSIONS: 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.