RESUMEN
Preterm birth is the principal contributor to neonatal death and morbidity worldwide. We previously described a plasma cell-free RNA panel that between 16 and 20 weeks of pregnancy had potential to predict spontaneous preterm birth (sPTB) ≤ 32 weeks caused by preterm labor (PTL) or preterm premature rupture of membranes (PPROM). The present study had three objectives: (1) estimate the RNA panel prognostic accuracy for PTL/PPROM ≤ 32 weeks in a larger series; (2) improve accuracy by adding clinical characteristics to the predictive model; and (3) examine the association of the RNA panel with preeclampsia. We studied 289 women from Memphis TN prospectively sampled 16.0-20.7 weeks and found: (1) PSME2 and Hsa-Let 7g were differentially expressed in cases of PTL/PPROM ≤ 32 weeks and together provided fair predictive accuracy with AUC of 0.76; (2) combining the two RNAs with clinical characteristics improved good predictive accuracy for PTL/PPROM ≤ 32 weeks (AUC 0.83); (3) NAMPT and APOA1 were differentially expressed in women with 'early-onset preeclampsia' (EOP) and together provided good predictive accuracy with AUC of 0.89; and (4) combining the two RNAs with clinical characteristics provided excellent predictive accuracy (AUC 0.96). Our findings suggest an underlying common pathophysiological relationship between PTL/PPROM ≤ 32 weeks and EOP and open inroads for the prognostication of high-risk pregnancies.
RESUMEN
OBJECTIVE: Morbidity and mortality due to preeclampsia in settings with limited resources often results from delayed diagnosis. The Congo Red Dot (CRD) test, a simple modality to assess the presence of misfolded proteins in urine, shows promise as a diagnostic and prognostic tool for preeclampsia. We propose an innovative mobile health (mHealth) solution that enables the quantification of the CRD test as a batch laboratory test, with minimal cost and equipment. METHODS: A smartphone application that guides the user through seven easy steps, and that can be used successfully by non-specialized personnel, was developed. After image acquisition, a robust analysis runs on a smartphone, quantifying the CRD test response without the need for an internet connection or additional hardware. In the first stage, the basic image processing algorithms and supporting test standardizations were developed using urine samples from 218 patients. In the second stage, the standardized procedure was evaluated on 328 urine specimens from 273 women. In the third stage, the application was tested for robustness using four different operators and 94 altered samples. RESULTS: In the first stage, the image processing chain was set up with high correlation to manual analysis (z-test P < 0.001). In the second stage, a high agreement between manual and automated processing was calculated (Lin's concordance coefficient ρc = 0.968). In the last stage, sources of error were identified and remedies were developed accordingly. Altered samples resulted in an acceptable concordance with the manual gold-standard (Lin's ρc = 0.914). CONCLUSION: Combining smartphone-based image analysis with molecular-specific disease features represents a cost-effective application of mHealth that has the potential to fill gaps in access to health care solutions that are critical to reducing adverse events in resource-poor settings.