A new risk score model to predict preeclampsia using maternal factors and mean arterial pressure in early pregnancy

The purpose of this study was to establish a multivariable risk-scoring model for preeclampsia (PE) prediction based on maternal characteristics and mean arterial pressure (MAP). Multivariate logistic regression analysis from 4600 pregnancies during a 10-year period was used to create the best fitting model. Significant risk factors and weighted scores consisted of age ≥30 years (3), BMI ≥25 kg/m2 (2), multifetal pregnancy (9), history of PE (9), adverse perinatal outcomes (6), pregnancy interval >10 years (5), nulliparous (5), underlying renal disease (10), chronic hypertension (6), autoimmune disease (5), diabetes (2) and MAP ≥95 mmHg (5). The model achieved an ROC area 0.771 with detection rates of 34%, 44%, 53% and 58% at 5%, 10%, 15% and 20% fixed false-positive rates, respectively. The new risk score model could be a clinically useful screening tool for PE. Pregnant women who have total scores of 9–13 (high risk) and more than 14 (very high risk) should receive aspirin prophylaxis.Impact Statement What is already known on this subject? Preeclampsia (PE) is the major cause of maternal and perinatal mortality and morbidity; it can be prevented by antiplatelet agents. What the results of this study add? A new model for identifying maternal at risk for PE using clinical risk factors and MAP was created. Weighted scores were defined for each variable for easy use in clinical practice. According to their probability for PE, pregnant women were classified into three subgroups: low risk (score 0–8), high risk (score 9–13) and very high risk groups (score ≥ 14). Aspirin should be prescribed to high risk and very high risk groups. For safety concerns, very high risk pregnancies should have close antenatal surveillance in a tertiary care hospital to reduce adverse outcomes during pregnancy and childbirth. What the implications are of these findings for clinical practice and/or further research? This new model for identifying pregnant women at high risk for PE has the potential to reduce the morbidity and mortality associated with this disease

Rapid diagnosis of intra-amniotic infection using nanopore-based sequencing

ObjectivesEarly diagnosis and treatment of intra-amniotic infection is crucial. Rapid pathogen identification allows for a definite diagnosis and enables proper management. We determined whether the 16S amplicon sequencing performed by a nanopore sequencing technique make possible rapid bacterial identification at the species level in intra-amniotic infection.MethodsFive cases of confirmed intra-amniotic infection, determined by either cultivation or 16S rDNA polymerase chain reaction (PCR) Sanger sequencing, and 10 cases of women who underwent mid-trimester genetic amniocentesis were included. DNA was extracted from amniotic fluid and PCR was performed on the full-length 16S rDNA. Nanopore sequencing was performed. The results derived from nanopore sequencing were compared with those derived from cultivation and Sanger sequencing methods.ResultsBacteria were successfully detected from amniotic fluid using nanopore sequencing in all cases of intra-amniotic infection. Nanopore sequencing identified additional bacterial species and polymicrobial infections. All patients who underwent a mid-trimester amniocentesis had negative cultures, negative 16S PCR Sanger sequencing and nanopore sequencing. Identification of the microorganisms using nanopore sequencing technique at the bacterial species level was achieved within 5-9 h from DNA extraction.ConclusionsThis is the first study demonstrating that the nanopore sequencing technique is capable of rapid diagnosis of intra-amniotic infection using fresh amniotic fluid samples

The amniotic fluid proteome predicts imminent preterm delivery in asymptomatic women with a short cervix

Abstract Preterm birth, the leading cause of perinatal morbidity and mortality, is associated with increased risk of short- and long-term adverse outcomes. For women identified as at risk for preterm birth attributable to a sonographic short cervix, the determination of imminent delivery is crucial for patient management. The current study aimed to identify amniotic fluid (AF) proteins that could predict imminent delivery in asymptomatic patients with a short cervix. This retrospective cohort study included women enrolled between May 2002 and September 2015 who were diagnosed with a sonographic short cervix ( 1.5 for each). The sensitivity at a 10% false-positive rate for the prediction of imminent delivery by a quantitative cervical length alone was 38%, yet it increased to 79% when combined with the abundance of four AF proteins (CXCL8, SNAP25, PTPN11, and MMP8). Neutrophil-mediated immunity, neutrophil activation, granulocyte activation, myeloid leukocyte activation, and myeloid leukocyte-mediated immunity were biological processes impacted by protein dysregulation in women destined to deliver within two weeks of diagnosis. The combination of AF protein abundance and quantitative cervical length improves prediction of the timing of delivery compared to cervical length alone, among women with a sonographic short cervix

Evidence for the participation of CHCHD2/MNRR1, a mitochondrial protein, in spontaneous labor at term and in preterm labor with intra-amniotic infection

Intra-amniotic inflammation (IAI), associated with either microbe (infection) or danger signals (sterile), plays a major role in the pathophysiology of preterm labor and delivery. Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 2 (CHCHD2) [also known as Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1)], a mitochondrial protein involved in oxidative phosphorylation and cell survival, is capable of sensing tissue hypoxia and inflammatory signaling. The ability to maintain an appropriate energy balance at the cellular level while adapting to environmental stress is essential for the survival of an organism. Mitochondrial dysfunction has been observed in acute systemic inflammatory conditions, such as sepsis, and is proposed to be involved in sepsis-induced multi-organ failure. The purpose of this study was to determine the amniotic fluid concentrations of CHCHD2/MNRR1 in pregnant women, women at term in labor, and those in preterm labor (PTL) with and without IAI. This cross-sectional study comprised patients allocated to the following groups: (1) mid-trimester (n = 16); (2) term in labor (n = 37); (3) term not in labor (n = 22); (4) PTL without IAI who delivered at term (n = 25); (5) PTL without IAI who delivered preterm (n = 47); and (6) PTL with IAI who delivered preterm (n = 53). Diagnosis of IAI (amniotic fluid interleukin-6 concentration ≥2.6 ng/mL) included cases associated with microbial invasion of the amniotic cavity and those of sterile nature (absence of detectable bacteria, using culture and molecular microbiology techniques). Amniotic fluid and maternal plasma CHCHD2/MNRR1 concentrations were determined with a validated and sensitive immunoassay. (1) CHCHD2/MNRR1 was detectable in all amniotic fluid samples and women at term without labor had a higher amniotic fluid CHCHD2/MNRR1 concentration than those in the mid-trimester (p = 0.003); (2) the amniotic fluid concentration of CHCHD2/MNRR1 in women at term in labor was higher than that in women at term without labor (p = 0.01); (3) women with PTL and IAI had a higher amniotic fluid CHCHD2/MNRR1 concentration than those without IAI, either with preterm (p p = 0.01); (4) women with microbial-associated IAI had a higher amniotic fluid CHCHD2/MNRR1 concentration than those with sterile IAI (p p  CHCHD2/MNRR1 is a physiological constituent of human amniotic fluid in normal pregnancy, and the amniotic concentration of this mitochondrial protein increases during pregnancy, labor at term, and preterm labor with intra-amniotic infection. Hence, CHCHD2/MNRR1 may be released into the amniotic cavity by dysfunctional mitochondria during microbial-associated IAI.</p

Pregnancy-specific responses to COVID-19 revealed by high-throughput proteomics of human plasma

Gomez-Lopez et al. profile the plasma proteome of pregnant and non-pregnant COVID-19 patients and controls. Shared and pregnancy-specific proteomic changes are identified in COVID-19 patients compared to controls, with the proteome accurately identifying COVID-19 patients, even when asymptomatic