Identifying placental metabolic biomarkers of preterm birth using nuclear magnetic resonance of intact tissue samples.

INTRODUCTION: Our understanding of the etiology of preterm birth (PTB) is incomplete; however, recent evidence has found a strong association between placental dysfunction and PTB. Altered placental metabolism may precede placental dysfunction and therefore the study of placental metabolic profiles could identify early biomarkers of PTB. In this study, we evaluated the placental metabolome in PTB in intact tissue samples using nuclear magnetic resonance (NMR) and spectral editing. METHODS: Placental tissue samples were collected from nine term pregnancies and nine preterm pregnancies (<37 weeks' gestation). 1H NMR experiments on unprocessed tissue samples were performed using a high field magnet (500 MHz spectrometer) and a comprehensive multiphase NMR probe. The relative concentrations of 23 metabolites were corrected for gestational age and compared between groups. RESULTS: The relative concentration of valine, glutamate and creatine were significantly decreased while alanine, choline and glucose were elevated in placentas from PTB pregnancies compared to controls (p < 0.05). Multivariate analysis using principal component analysis showed the PTB and control groups were significantly separated (p < 0.0001) and pathway analysis identified perturbations in the glycine, serine and threonine metabolism, aminoacyl-tRNA biosynthesis and valine, leucine and isoleucine biosynthesis pathways. CONCLUSION: PTB is associated with significant alterations in placental metabolism. This study helps improve our understanding of the etiology of PTB. It also highlights the potential for small molecule metabolites to serve as placental metabolic biomarkers to aid in the prediction and diagnosis of PTB. The results can be translated to clinical use via in utero magnetic resonance spectroscopy.

A Multidisciplinary Team-Based Approach to Improve Communication With Surrogates of Patients With Chronic Critical Illness.

BACKGROUND: Clinicians need to deliver prognostic information to surrogates of nondecisional, critically ill patients so that surrogates can make informed medical decisions that reflect the patient's values. Our objective was to implement a new approach for communicating with surrogates of patients with chronic critical illness. METHODS: Surrogate decision makers of patients who were difficult to liberate from mechanical ventilation were prospectively enrolled. Surrogates met with different members of the intensive care unit treatment team for sequential 15-minute appointments to receive patient-specific assessments and education on chronic critical illness. The feasibility and acceptability of this approach were determined. A 24-question comprehension instrument was developed to assess a participant's understanding that a family member was displaying features of chronic critical illness. Each question was scored from 1 to 5, with larger scores indicating greater comprehension. RESULTS: Over a 15-week period, educational sessions for 9 mechanically ventilated patients were conducted. On average, 2 surrogates per patient (range: 1-4) and 6 members of the interdisciplinary team (range: 4-6) were at each meeting. Surrogates and clinicians had very positive impressions of the communication intervention. The average preintervention comprehension score was 85 of 120 (standard deviation [SD]: 8, range: 71-101). The postintervention comprehension score was greater by 5 points on average (SD: 9, range: -11 to +20 points, P = .04). CONCLUSIONS: Surrogates of critically ill patients approved of this novel communication approach and had a greater understanding of the patient's medical condition after the intervention.