scholarly journals Untargeted analysis of first trimester serum to reveal biomarkers of pregnancy complications: a case–control discovery phase study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
E. W. Harville ◽  
Y.-Y. Li ◽  
K. Pan ◽  
S. McRitchie ◽  
W. Pathmasiri ◽  
...  
Keyword(s):  
Pregnancy Complications ◽  
Predictive Power ◽  
Gestational Hypertension ◽  
Predictive Biomarkers ◽  
First Trimester ◽  
Resonance Spectroscopy ◽  
Renal Secretion ◽  
Global Alliance ◽  
Phase Study ◽  
High Resolution Mass Spectroscopy

AbstractUnderstanding of causal biology and predictive biomarkers are lacking for hypertensive disorders of pregnancy (HDP) and preterm birth (PTB). First-trimester serum specimens from 51 cases of HDP, including 18 cases of pre-eclampsia (PE) and 33 cases of gestational hypertension (GH); 53 cases of PTB; and 109 controls were obtained from the Global Alliance to Prevent Prematurity and Stillbirth repository. Metabotyping was conducted using liquid chromatography high resolution mass spectroscopy and nuclear magnetic resonance spectroscopy. Multivariable logistic regression was used to identify signals that differed between groups after controlling for confounders. Signals important to predicting HDP and PTB were matched to an in-house physical standards library and public databases. Pathway analysis was conducted using GeneGo MetaCore. Over 400 signals for endogenous and exogenous metabolites that differentiated cases and controls were identified or annotated, and models that included these signals produced substantial improvements in predictive power beyond models that only included known risk factors. Perturbations of the aminoacyl-tRNA biosynthesis, l-threonine, and renal secretion of organic electrolytes pathways were associated with both HDP and PTB, while pathways related to cholesterol transport and metabolism were associated with HDP. This untargeted metabolomics analysis identified signals and common pathways associated with pregnancy complications.

The first trimester aneuploidy biochemical markers in IVF/ICSI patients have no additional benefit compared to spontaneous conceptions in the prediction of pregnancy complications

2018 ◽  
Vol 46 (9) ◽  
pp. 953-959
Author(s):  
Iwona Szymusik ◽  
Przemyslaw Kosinski ◽  
Katarzyna Kosinska-Kaczynska ◽  
Damian Warzecha ◽  
Anetta Karwacka ◽  
...  
Keyword(s):  
Pregnancy Complications ◽  
Biochemical Markers ◽  
Gestational Hypertension ◽  
Statistical Significance ◽  
Protein A ◽  
First Trimester ◽  
Serum Markers ◽  
Control Group ◽  
Assisted Reproduction Technique

AbstractObjectives:The aim of this study was to determine if the levels of biochemical aneuploidy markers inin vitrofertilisation (IVF)/intracytoplasmic sperm injection (ICSI) pregnancies differ from those in spontaneous pregnancies and to verify if biochemical markers could predict pregnancy outcome in IVF/ICSI gestations.Methods:This was a prospective observational study performed in a group of 551 patients who underwent a combined first trimester prenatal screening (ultrasound scan and serum markers). All patients were divided into two groups according to the mode of conception: IVF/ICSI pregnancies (study group) and spontaneous conceptions (control group). The concentrations of first trimester biochemical markers were presented as multiples of median (MoM) and were compared between the study and control groups. Analysed pregnancy complications included: preterm delivery (PTD), small for gestational age (SGA), gestational hypertension (GH), preeclampsia (PE) and gestational diabetes (GDM).Results:The analysis was performed on 183 IVF/ICSI and 368 spontaneously conceived gestations, with complete data regarding obstetric outcome. There were no significant differences in the concentrations of biochemical markers between the analysed groups. Pregnancy-associated plasma protein-A (PAPP-A) levels were lower in hypertensive than in normotensive patients, although the difference was not significant. Twenty-three patients had GDM (12.5%), 16 had GH or PE (8.7%), SGA was diagnosed in 18 (9.8%) and 25 delivered preterm (13.6%).Conclusions:The trend for lower PAPP-A MoM was visible in all affected patients, although the results did not reach statistical significance. The first trimester biochemical markers in assisted reproduction technique (ART) pregnancies do not seem to have additional effect on predicting the risk of pregnancy complications.

scholarly journals Exposure to chemical components of fine particulate matter and ozone, and placenta-mediated pregnancy complications in Tokyo: a register-based study

2021 ◽  
Author(s):  
Takehiro Michikawa ◽  
Seiichi Morokuma ◽  
Shin Yamazaki ◽  
Akinori Takami ◽  
Seiji Sugata ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Organic Carbon ◽  
Pregnancy Complications ◽  
Fine Particulate Matter ◽  
First Trimester ◽  
Chemical Components ◽  
Specific Chemical ◽  
Network Database ◽  
Fine Particulate ◽  
Pollutant Concentrations

Abstract Background Maternal exposure to fine particulate matter (PM2.5) was associated with pregnancy complications. However, we still lack comprehensive evidence regarding which specific chemical components of PM2.5 are more harmful for maternal and foetal health. Objective We focused on exposure over the first trimester (0–13 weeks of gestation), which includes the early placentation period, and investigated whether PM2.5 and its components were associated with placenta-mediated pregnancy complications (combined outcome of small for gestational age, preeclampsia, placental abruption, and stillbirth). Methods From 2013 to 2015, we obtained information, from the Japan Perinatal Registry Network database, on 83,454 women who delivered singleton infants within 23 Tokyo wards (≈627 km2). Using daily filter sampling of PM2.5 at one monitoring location, we analysed carbon and ion components, and assigned the first trimester average of the respective pollutant concentrations to each woman. Results The ORs of placenta-mediated pregnancy complications were 1.14 (95% CI = 1.08–1.22) per 0.51 μg/m3 (interquartile range) increase of organic carbon and 1.11 (1.03–1.18) per 0.06 μg/m3 increase of sodium. Organic carbon was also associated with four individual complications. There was no association between ozone and outcome. Significance There were specific components of PM2.5 that have adverse effects on maternal and foetal health.

scholarly journals Maternal Risk Factors Associated with Limb Reduction Defects: Data from the Polish Registry of Congenital Malformations (PRCM)

Children ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. 138
Author(s):  
Anna Materna-Kiryluk ◽  
Katarzyna Wisniewska ◽  
Barbara Wieckowska ◽  
Jolanta Wierzba ◽  
Anna Jazdzewska ◽  
...  
Keyword(s):  
Risk Factors ◽  
Congenital Malformations ◽  
Gestational Hypertension ◽  
First Trimester ◽  
Smoking History ◽  
Upper Respiratory Tract ◽  
Maternal Risk ◽  
Limb Reduction ◽  
Integral Role ◽  
Tract Infections

Data from the Polish Registry of Congenital Malformations (PRCM) suggest that the prevalence of limb reduction defects (LRDs) in some Polish regions is significantly higher in comparison to that reported in the European Surveillance of Congenital Anomalies (EUROCAT) registry, but specific risk factors are still unknown. The objectives of this study were two-fold: to detect risk factors linked to isolated LRDs among Polish natives and to search for geospatial clusters of isolated LRDs to identify high-risk areas across the country. Among the 2,939,001 births accounted for in the PRCM, we determined that there were 852 children with distinct LRDs. Our data demonstrate that lower birth weight, prematurity, and maternal smoking history are strongly associated with isolated LRDs. Furthermore, our investigation pointed to various additional risk factors for isolated LRDs, including paternal education, gestational hypertension, upper respiratory tract infections, and exposure to anti-inflammatory drugs in the first trimester of pregnancy. We did not recognize statistically significant spatial or spatiotemporal clusters over the area of Poland using Kulldorff’s scan. Our study strengthens the hypothesis that maternal factors have an integral role in the etiology of isolated LRDs.

scholarly journals The Association of Familial Hypertension and Risk of Gestational Hypertension and Preeclampsia

2021 ◽  
Vol 18 (13) ◽  
pp. 7045
Author(s):  
Małgorzata Lewandowska
Keyword(s):  
Risk Factor ◽  
Pregnant Women ◽  
Odds Ratio ◽  
Independent Risk Factor ◽  
Gestational Hypertension ◽  
First Trimester ◽  
Chronic Hypertension ◽  
Modifiable Factors ◽  
The Family ◽  
Maternal Hypertension

It has not been established how history of hypertension in the father or mother of pregnant women, combined with obesity or smoking, affects the risk of main forms of pregnancy-induced hypertension. A cohort of 912 pregnant women, recruited in the first trimester, was assessed; 113 (12.4%) women developed gestational hypertension (GH), 24 (2.6%) developed preeclampsia (PE) and 775 women remained normotensive (a control group). Multiple logistic regression was used to calculate adjusted odds ratios (AOR) (and 95% confidence intervals) of GH and PE for chronic hypertension in the father or mother of pregnant women. Some differences were discovered. (1) Paternal hypertension (vs. absence of hypertension in the family) was an independent risk factor for GH (AOR-a = 1.98 (1.2–3.28), p = 0.008). This odds ratio increased in pregnant women who smoked in the first trimester (AOR-a = 4.71 (1.01–21.96); p = 0.048) or smoked before pregnancy (AOR-a = 3.15 (1.16–8.54); p = 0.024), or had pre-pregnancy overweight (AOR-a = 2.67 (1.02–7.02); p = 0.046). (2) Maternal hypertension (vs. absence of hypertension in the family) was an independent risk factor for preeclampsia (PE) (AOR-a = 3.26 (1.3–8.16); p = 0.012). This odds ratio increased in the obese women (AOR-a = 6.51 (1.05–40.25); p = 0.044) and (paradoxically) in women who had never smoked (AOR-a = 5.31 (1.91–14.8); p = 0.001). Conclusions: Chronic hypertension in the father or mother affected the risk of preeclampsia and gestational hypertension in different ways. Modifiable factors (overweight/obesity and smoking) may exacerbate the relationships in question, however, paradoxically, beneficial effects of smoking for preeclampsia risk are also possible. Importantly, paternal and maternal hypertension were not independent risk factors for GH/PE in a subgroup of women with normal body mass index (BMI).

Placental massive perivillous fibrinoid deposition is associated with adverse pregnancy outcomes: a clinicopathological study of 12 cases

2016 ◽  
Vol 5 (1) ◽  
pp. 35-39
Author(s):  
Maili Qi ◽  
Kenneth Tou En Chang ◽  
Derrick Wen Quan Lian ◽  
Chong Kiat Khoo ◽  
Kok Hian Tan
Keyword(s):  
Pregnancy Outcomes ◽  
Gestational Hypertension ◽  
Local Population ◽  
Fetal Loss ◽  
Perinatal Outcomes ◽  
First Trimester ◽  
Adverse Outcomes ◽  
Special Focus ◽  
Adverse Perinatal Outcomes ◽  
Adverse Pregnancy

Abstract Introduction: Massive perivillous fibrinoid deposition (MPFD) is a very rare placental condition characterized by abnormally extensive fibrinoid deposition in the placental villous parenchyma. The aim of this study is to document clinical and pathological features with special focus on pregnancy outcomes of this condition in consecutive cases of MPFD in our local population. Methods: This is a retrospective clinico-pathological study of cases affected by MPFD over the period January 2010–July 2014 in our hospital. We document clinical features (including perinatal outcome and subsequent pregnancies) and placental pathological characteristics. Results: Twelve cases of MPFD were identified among 3640 placentas (0.33%). There was no identified recurrence. The affected infants had adverse outcomes, including intrauterine growth restriction (IUGR) (75%), preterm birth (58.3%), and fetal loss (25%). A high frequency of reduced PAPP-A in the first trimester (25%), and concurrent gestational hypertension or pre-eclampsia (25%) was noted. Conclusion: MPFD is associated with adverse perinatal outcomes. Further research to better understand its pathogenesis and to improve clinical diagnosis and management is warranted.

Digital histological markers based on routine H&E slides to predict benefit from maintenance immunotherapy in esophagogastric adenocarcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16074-e16074
Author(s):  
Quoc Dang Vu ◽  
Caroline Fong ◽  
Katharina von Loga ◽  
Shan E Ahmed Raza ◽  
Daniel Nava Rodrigues ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Predictive Power ◽  
Low Cost ◽  
Predictive Biomarkers ◽  
Operating Characteristics ◽  
Treatment Benefit ◽  
Platinum Based Chemotherapy ◽  
Slide Image ◽  
Tumor Mutational Burden ◽  
Hematoxylin And Eosin

e16074 Background: Immune checkpoint inhibition (ICI) is an effective treatment for a subset of patients with inoperable esophagogastric (EG) adenocarcinoma. Robust predictive biomarkers are required to identify these patients and a variety of strategies including immunohistochemical staining of PD-L1 and tumor mutational burden (TMB) assessment have been employed. Here, we explore digital histological (dHis) markers based on routine hematoxylin and eosin (H&E) slides alone or in combination with molecular markers (PD-L1 and TMB) as predictive biomarkers of benefit from maintenance immunotherapy in patients with inoperable EG adenocarcinoma. Methods: We developed a deep learning based algorithm to construct novel digital histological (dHis) markers by summarizing the statistics of all different types of nuclei present in the tumor tissue sections, their morphological features and their colocalization across each of the whole slide image. The dHis markers were then input into a decision-tree based approach to test for prognostic and predictive power alone or in combination with molecular markers. We assessed two cohorts of patients randomized to surveillance (n=38) or maintenance durvalumab (n=35) after 18 weeks of first-line platinum-based chemotherapy in the PLATFORM trial (NCT02678182) according to the 12-week progression-free rate. We measured the accuracy as the area under the receiver operating characteristics curve (AUROC) to determine the prognostic and predictive power of each marker set. We conducted a stratified 3-fold cross-validation, repeated 5 times and report the overall AUROC results. Results: Molecular markers alone yielded an AUROC of 0.5581±0.0939 on the surveillance arm, 0.6671±0.1479 on the treatment arm, and 0.6376±0.0958 for both the arms. Digital histological markers alone yielded an AUROC of 0.8952±0.0638, 0.8995±0.0719 and 0.8488±0.0700 on surveillance, immunotherapy and both arms, respectively. When using these two sets of markers together for both arms, molecular markers offered a limited improvement (around 0.02). Patients with TMB in the highest tertile were associated with lower likelihood of having progressive disease 12 weeks after randomization. Interestingly, dHis markers from morphology of connective and inflammatory nuclei were highly predictive for treatment benefit. Conclusions: Preliminary results suggest digital histological markers offer significant improvement over PD-L1 and TMB markers alone for predicting benefit from immunotherapy in EG adenocarcinoma with the added advantages of scalable, rapid, low-cost and objective quantification on routine histology sections. We are further validating their effectiveness on a larger cohort. Clinical trial information: NCT02678182.

Modified Multiple Marker Aneuploidy Screening as a Primary Screening Test for Preeclampsia

2021 ◽  
Author(s):  
Tianhua Huang ◽  
H. Melanie Bedford ◽  
Shamim Rashid ◽  
Evasha Rasasakaram ◽  
Megan Priston ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Early Onset ◽  
Biochemical Markers ◽  
Gestational Hypertension ◽  
First Trimester ◽  
Second Trimester ◽  
Aneuploidy Screening ◽  
Maternal Characteristics ◽  
Screening Performance ◽  
Β Hcg

Abstract Background: Maternal biochemical markers used in multiple marker aneuploidy screening have been associated with adverse pregnancy outcomes. This study aims to assess if a combination of maternal characteristics and biochemical markers in the first and second trimesters can be used to screen for preeclampsia (PE), gestational hypertension and preterm birth. Methods: This case-control study used information on maternal characteristics and residual blood samples from pregnant women who have undergone multiple marker aneuploidy screening. The median multiple of the median (MoM) of first and second trimester biochemical markers in cases (women with PE, gestational hypertension and preterm birth) and controls were compared. Biochemical markers included pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PlGF), human chorionic gonadotropin (hCG), alpha feto-protein (AFP), unconjugated estriol (uE3) and Inhibin A. Logistic regression analysis was used to estimate screening performance using different marker combinations. Screening performance was defined as detection rate (DR) and false positive rate (FPR). Preterm and early-onset preeclampsia PE were defined as women with PE delivered < 37 and < 34 weeks of gestation.Results: There were 147 pregnancies with PE (81 term, 49 preterm and 17 early-onset), 295 with gestational hypertension, and 166 preterm birth. Compared to controls, PE cases had significantly lower median MoM of PAPP-A (0.77 vs 1.10, p<0.0001), PlGF (0.76 vs 1.01, p<0.0001) and free-β hCG (0.81 vs. 0.98, p<0.001) in the first trimester along with PAPP-A (0.82 vs 0.99, p<0.01) and PlGF (0.75 vs 1.02, p<0.0001) in the second trimester. The lowest first trimester PAPP-A, PlGF and free β-hCG were seen in those with preterm and early-onset PE. At a 20% FPR, 67% of preterm and 76% of early-onset PE cases can be predicted using a combination of maternal characteristics with PAPP-A and PlGF in the first trimester.Conclusions: Maternal characteristics with first trimester PAPP-A and PlGF measured for aneuploidy screening provided reasonable accuracy in identifying women at risk of developing early onset PE, allowing triage of high-risk women for further investigation and risk-reducing therapy.

scholarly journals Differential Diagnosis of Preeclampsia Based on Urine Peptidome Features Revealed by High Resolution Mass Spectrometry

Diagnostics ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1039
Author(s):  
Alexey S. Kononikhin ◽  
Natalia V. Zakharova ◽  
Viktoria A. Sergeeva ◽  
Maria I. Indeykina ◽  
Natalia L. Starodubtseva ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Resolution ◽  
High Resolution Mass Spectrometry ◽  
Gestational Hypertension ◽  
Characteristic Curve ◽  
First Trimester ◽  
Chronic Hypertension ◽  
High Resolution Mass ◽  
Diagnostic Potential ◽  
Resolution Mass

Preeclampsia (PE) is a severe pregnancy complication, which may be considered as a systemic response in the second half of pregnancy to physiological failures in the first trimester, and can lead to very serious consequences for the health of the mother and fetus. Since PE is often associated with proteinuria, urine proteomic assays may represent a powerful tool for timely diagnostics and appropriate management. High resolution mass spectrometry was applied for peptidome analysis of 127 urine samples of pregnant women with various hypertensive complications: normotensive controls (n = 17), chronic hypertension (n = 16), gestational hypertension (n = 15), mild PE (n = 25), severe PE (n = 25), and 29 patients with complicated diagnoses. Analysis revealed 3869 peptides, which mostly belong to 116 groups with overlapping sequences. A panel of 22 marker peptide groups reliably differentiating PE was created by multivariate statistics, and included 15 collagen groups (from COL1A1, COL3A1, COL2A1, COL4A4, COL5A1, and COL8A1), and single loci from alpha-1-antitrypsin, fibrinogen, membrane-associated progesterone receptor component 1, insulin, EMI domain-containing protein 1, lysine-specific demethylase 6B, and alpha-2-HS-glycoprotein each. ROC analysis of the created model resulted in 88% sensitivity, 96.8% specificity, and receiver operating characteristic curve (AUC) = 0.947. Obtained results confirm the high diagnostic potential of urinary peptidome profiling for pregnancy hypertensive disorders diagnostics.

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