Transcriptomics-Based Subphenotyping of the Human Placenta Enabled by Weighted Correlation Network Analysis in Early-Onset Preeclampsia With and Without Fetal Growth Restriction.

Background: Placental disorders contribute to pregnancy complications, including preeclampsia and fetal growth restriction (FGR), but debate regarding their specific pathobiology persists. Our objective was to apply transcriptomics with weighted gene correlation network analysis to further clarify the placental dysfunction in these conditions.

Methods: We performed RNA sequencing with weighted gene correlation network analysis using human placental samples (n=30), separated into villous tissue and decidua basalis, and clinically grouped as follows: (1) early-onset preeclampsia (EOPE)+FGR (n=7); (2) normotensive, nonanomalous preterm FGR (n=5); (2) EOPE without FGR (n=8); (4) spontaneous idiopathic preterm birth (n=5) matched for gestational age; and (5) uncomplicated term births (n=5).

Characterization of methylation profiles in spontaneous preterm birth placental villous tissue.

Preterm birth is a global public health crisis which results in significant neonatal and maternal mortality. Yet little is known regarding the molecular mechanisms of idiopathic spontaneous preterm birth, and we have few diagnostic markers for adequate assessment of placental development and function. Previous studies of placental pathology and our transcriptomics studies suggest a role for placental maturity in idiopathic spontaneous preterm birth.

Evaluation of a Maternal Plasma RNA Panel Predicting Spontaneous Preterm Birth and Its Expansion to the Prediction of Preeclampsia.

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: estimate the RNA panel prognostic accuracy for PTL/PPROM ≤ 32 weeks in a larger series; improve accuracy by adding clinical characteristics to the predictive model; and examine the association of the RNA panel with preeclampsia.

Conformation-dependent anti-Aβ monoclonal antibody signatures of disease status and severity in urine of women with preeclampsia.

Prior research has shown that urine of women with preeclampsia (PE) contains amyloid-like aggregates that are congophilic (exhibit affinity for the amyloidophilic dye Congo red) and immunoreactive with A11, a polyclonal serum against prefibrillar β-amyloid oligomers, thereby supporting pathogenic similarity between PE and protein conformational disorders such as Alzheimer's and prion disease. The objective of this study was to interrogate PE urine using monoclonal antibodies with previously characterized A11-like epitopes. Over 100 conformation-dependent monoclonals were screened and three (mA11-09, mA11-89, and mA11-205) selected for further confirmation in 196 urine samples grouped as follows: severe features PE (sPE, n = 114), PE without severe features (mPE, n = 30), chronic hypertension (crHTN, n = 14) and normotensive pregnant control (P-CRL, n = 38).

Endocan, a Soluble Marker of Endothelial Cell Activation Is a Molecular Marker of Disease Severity in Women with Preeclampsia.

Endocan is a proteoglycan secreted by activated endothelium that regulates angiogenesis via interaction with hepatocyte growth factor (HGF). We hypothesized that women diagnosed with preeclampsia (PE) and/or fetal growth restriction (FGR) have elevated circulating endocan concentrations in direct relationship with severity of clinical manifestations. Serum concentration of endocan and HGF were analyzed in 224 women grouped as healthy pregnant controls (P-CRL, n = 77), PE with severe features (sPE, n = 83), chronic hypertension (crHTN: n = 36), idiopathic FGR (n = 18), and healthy non-pregnant controls (NP-CRL, n = 7).

Controversies in treatment practices of the mother-infant dyad at the limit of viability.

In the setting of threatened extreme preterm birth, balancing maternal and fetal risks and benefits in order to choose the best available treatment options is of utmost importance. Inconsistency in treatment practices for infants born between 22 and 24 weeks of gestatotional age may account for inter-hospital variation in survival rates with and without impairment. Most importantly, non-biased and accurate information must be presented to the family as soon as extremely preterm birth is suspected, including counseling on morbidities and mortality associated with delivery at the limits of viability.

Higher dose docosahexaenoic acid supplementation during pregnancy and early preterm birth: A randomised, double-blind, adaptive-design superiority trial.

Background: Several meta analyses have concluded n-3 fatty acids, including docosahexaenoic acid (DHA), reduce early preterm birth (EPB, < 34 weeks), however, the amount of DHA required is unclear. We hypothesized that 1000 mg DHA per day would be superior to 200 mg, the amount in most prenatal supplements.

Methods: This randomised, multicentre, double-blind, adaptive-design, superiority trial was conducted in three USA medical centres.

Molecular signatures of labor and nonlabor myometrium with parsimonious classification from 2 calcium transporter genes.

Clinical phenotyping of term and preterm labor is imprecise, and disagreement persists on categorization relative to underlying pathobiology, which remains poorly understood. We performed RNA sequencing (RNA-seq) of 31 specimens of human uterine myometrium from 10 term and 21 preterm cesarean deliveries with rich clinical context information. A molecular signature of 4814 transcripts stratified myometrial samples into quiescent (Q) and nonquiescent (NQ) phenotypes, independent of gestational age and incision site.

Amniotic Fluid Proteasome and Immunoproteasome in the Setting of Intra-Amniotic Infection, Inflammation, and Preterm Birth.

Preterm birth is an important determinant of neonatal morbidity and mortality and intra-amniotic infection (IAI) and inflammation play a causative role. The constitutive proteasome and immunoproteasome are key players in maintenance of proteostasis and their alteration outside pregnancy has been linked to pathogenesis of numerous inflammatory diseases. Our goal was to evaluate the levels, activities, and potential origin of amniotic fluid (AF) proteasome in women with preterm birth induced by infection and/or inflammation.

Congo red test for identification of preeclampsia: Results of a prospective diagnostic case-control study in Bangladesh and Mexico.

Background: Misfolded proteins in the urine of women with preeclampsia bind to Congo Red dye (urine congophilia). We evaluated a beta prototype of a point-of-care test for the identification of urine congophilia in preeclamptic women.

Methods: Prospective diagnostic case-control study conducted in 409 pregnant women ( = 204 preeclampsia;  = 205 uncomplicated pregnancies) presenting for delivery in two tertiary level hospitals located in Bangladesh and Mexico.

Prevalence and Neighborhood Geomapping of COVID-19 in an Underserved Chicago Pregnant Population.

 The Chicago area is known to harbor some of the deepest racial and ethnic socioeconomic inequalities in the United States. We studied the prevalence and neighborhood distribution of patients who tested positive for COVID-19 after implementation of universal screening at an academic hospital providing obstetrical services to an underserved Chicago population.  From April 16 to June 16, 2020, a total of 369 patients were screened for COVID-19 at University of Illinois at Chicago with either the Abbott Point-of-Care (POC,  = 266) or reverse transcription polymerase chain reaction test (RT-PCR,  = 101).

Connecting the dots on vertical transmission of SARS-CoV-2 using protein-protein interaction network analysis - Potential roles of placental ACE2 and ENDOU.

We conducted a protein-protein interaction (PPI) network study searching for proteins relevant to pregnancy-associated COVID-19 in pregnancy complicated with severe preeclampsia (sPE) and intra-amniotic infection and/or inflammation (Triple-I). PPI networks from sPE and Triple-I were intersected with the PPI network from coronavirus infection. Common proteins included the SARS-CoV-2 entry receptor ACE2 and ENDOU, a placental endoribonuclease homologous to Nsp15, a protein produced by the virus to escape host immunity.

Antenatal N-acetylcysteine to improve outcomes of premature infants with intra-amniotic infection and inflammation (Triple I): randomized clinical trial.

Background: Intrauterine infection and/or inflammation (Triple I) is an important cause of preterm birth (PTB) and adverse newborn outcomes. N-acetylcysteine (NAC) is a Food and Drug Administration (FDA)-approved drug safely administered to pregnant women with acetaminophen toxicity.

Methods: We conducted a single-center, quadruple-blind, placebo-controlled trial of pregnant women with impending PTB due to confirmed Triple I.

Use of birth weight- vs. ultrasound-derived fetal weight classification methods: implications for detection of abnormal umbilical artery Doppler.

Objectives To compare a birth weight-derived (Brenner) and multiple ultrasound-derived [Hadlock, National Institute of Child Health and Human Development (NICHD), International Fetal and Newborn Growth Consortium (INTERGROWTH)] classification systems' frequency of assigning an antenatal estimated fetal weight (EFW) <10% and subsequent detection rate for abnormal umbilical artery Doppler (UAD). Methods We analyzed 569 consecutive non-anomalous singleton gestations identified by ultrasound with either an abdominal circumference (AC) <3% or EFW <10% at a tertiary medical center between 1/2012 and 12/2016. The biometric measurements were exported for all serial ultrasounds and the sensitivity, specificity, positive and negative predictive values, and area under the curve (AUC) were calculated for the diagnosis of any abnormal UAD, absent or reversed end-diastolic flow (AREDF), and small for gestational age (SGA) for each classification method.

Acute Glucose Load, Inflammation, Oxidative Stress, Nonenzymatic Glycation, and Screening for Gestational Diabetes.

Aims: To investigate if oral glucose tolerance test (OGTT) associates with changes in maternal symptoms (ie, flushing, sweating), blood nonenzymatic advanced glycation end products (AGE), acute-phase reactive inflammatory markers, and oxidative stress.

Methods: Prospective case-control study of patients screened for gestational diabetes mellitus (GDM). One hundred nonfasting, second-trimester consecutive pregnant women allocated to either 50 g OGTT or water.

MiR-29b is associated with perinatal inflammation in extremely preterm infants.

Background: Inflammation is strongly associated with premature birth and neonatal morbidities. Increases in infant haptoglobin, haptoglobin-related protein (Hp&HpRP), and interleukin-6 (IL-6) levels are indicators of intra-amniotic inflammation (IAI) and have been linked to poor neonatal outcomes. Inflammation causes epigenetic changes, specifically suppression of miR-29 expression.

Fetal and amniotic fluid iron homeostasis in healthy and complicated murine, macaque, and human pregnancy.

Adequate iron supply during pregnancy is essential for fetal development. However, how fetal or amniotic fluid iron levels are regulated during healthy pregnancy, or pregnancies complicated by intraamniotic infection or inflammation (IAI), is unknown. We evaluated amniotic fluid and fetal iron homeostasis in normal and complicated murine, macaque, and human pregnancy.

Unique transcriptomic landscapes identified in idiopathic spontaneous and infection related preterm births compared to normal term births.

Preterm birth (PTB) is leading contributor to infant death in the United States and globally, yet the underlying mechanistic causes are not well understood. Histopathological studies of preterm birth suggest advanced villous maturity may have a role in idiopathic spontaneous preterm birth (isPTB). To better understand pathological and molecular basis of isPTB, we compared placental villous transcriptomes from carefully phenotyped cohorts of PTB due to infection or isPTB between 28-36 weeks gestation and healthy term placentas.

Congo Red Dot Paper Test for Antenatal Triage and Rapid Identification of Preeclampsia.

Background: Proteins in the urine of women with preeclampsia (PE) bind Congo Red dye (urine congophilia). We sought to determine the diagnostic performance of a paper-based point-of-care test detecting urine congophilia for rapid triage and diagnosis of PE.

Methods: Prospective cohort study conducted in 346 consecutive pregnant women evaluated for PE in the Labour and Delivery triage unit at our institution.

Cord Blood Haptoglobin, Cerebral Palsy and Death in Infants of Women at Risk for Preterm Birth: A Secondary Analysis of a Randomised Controlled Trial.

Background: Antenatal exposure to intra-uterine inflammation results in precocious Haptoglobin (Hp) expression (switch-on status). We investigated the relationships between foetal Hp expression at birth with newborn and childhood outcomes.

Methods: We evaluated cord blood samples from 921 newborns of women at imminent risk for preterm delivery randomised to either placebo (n = 471, birth gestational age (GA) median [min-max]: 31 [24-41] weeks) or magnesium sulphate (n = 450, GA 31 [24-42] weeks]).

Fetal Myocardial Function as Assessed by N-Terminal Fragment Brain Natriuretic Protein in Premature Fetuses Exposed to Intra-amniotic Inflammation.

Objective: This study aimed to determine the relationship between fetal exposure to intra-amniotic infection/inflammation (IAI) and fetal heart ventricular function as assessed by circulatory levels of N-terminal fragment brain natriuretic protein (NT-proBNP) and the Tei index.

Study Design: We analyzed 70 samples of paired amniotic fluid (AF) and cord blood retrieved from mothers who delivered preterm at <34 weeks as follows: Yes-IAI ( = 36) and No-IAI ( = 34). IAI was diagnosed by amniocentesis and AF mass spectrometry.