scholarly journals PAPP‐A2 and Inhibin A as Novel Predictors for Pregnancy Complications in Women With Suspected or Confirmed Preeclampsia

2020 ◽  
Vol 9 (19) ◽  
Author(s):  
Rugina I. Neuman ◽  
Maaike M. Alblas van der Meer ◽  
Daan Nieboer ◽  
Langeza Saleh ◽  
Koen Verdonk ◽  
...  

Background We aimed to evaluate the value of inhibin A and PAPP‐A2 (pregnancy‐associated plasma protein‐A2) as novel biomarkers in the prediction of preeclampsia‐related complications and how they compare with angiogenic biomarkers. Methods and Results Making use of a secondary analysis of a prospective, multicenter, observational study, intended to evaluate the usefulness of sFlt‐1 (soluble Fms‐like tyrosine kinase‐1)/PlGF (placental growth factor) ratio, we measured inhibin A and PAPP‐A2 levels in 524 women with suspected/confirmed preeclampsia. Women had a median gestational age of 35 weeks (range, 20–41 weeks) while preeclampsia occurred in 170 (32%) women. Levels of inhibin A and PAPP‐A2 were significantly increased in women with preeclampsia and in maternal perfusate of preeclamptic placentas. Inhibin A and PAPP‐A2 (C‐index = 0.73 and 0.75) significantly improved the prediction of maternal complications when added on top of the traditional criteria; gestational age, parity, proteinuria, and diastolic blood pressure (C‐index = 0.60). PAPP‐A2 was able to improve the C‐index from 0.75 to 0.77 when added on top of the sFlt‐1/PlGF ratio for the prediction of maternal complications. To discriminate fetal/neonatal complications on top of traditional criteria, inhibin A and PAPP‐A2 showed additive value (C‐index = 0.79 to 0.80 and 0.82, respectively) but their discriminative ability remained inferior to that of sFlt‐1/PlGF ratio or PlGF. Interestingly, the PAPP‐A2/PlGF ratio alone showed remarkable value to predict pregnancy complications, being superior to sFlt‐1/PlGF ratio in the case of maternal complications. Conclusions Inhibin A and PAPP‐A2 show significant potential to predict preeclampsia‐related pregnancy complications and might prove beneficial on top of the angiogenic markers.

2021 ◽  
Vol 2 (1) ◽  
pp. 35-49
Author(s):  
Adi Sharabi-Nov ◽  
Tanja Premru Sršen ◽  
Kristina Kumer ◽  
Vesna Fabjan Vodušek ◽  
Teja Fabjan ◽  
...  

Objective: We previously provided evidence to confirm that maternal serum levels of soluble Fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and their ratio are useful tools to direct the management of preeclampsia (PE), fetal growth restriction (FGR), and PE+FGR near delivery. In this secondary analysis, we further examine the potential additive value of maternal serum Inhibin-A, which is a hormone marker of the transforming growth factor family, to the accuracy provided by maternal serum PlGF and sFlt-1. Methods: We conducted a secondary analysis where we extracted the data of a cohort of 125 pregnant women enrolled near delivery at the clinics of the University Medical Center of Ljubljana, Slovenia. The dataset included 31 cases of PE, 16 of FGR, 42 of PE+FGR, 15 preterm delivery (PTD), and 21 unaffected controls with delivery of a healthy baby at term. Cases delivered before 34 weeks’ gestation included 10 of PE, 12 of FGR, 28 of PE+FGR, and 6 of PTD. In addition to the recorded demographic characteristics and medical history and the maternal serum levels of PlGF and sFlt-1/PlGF ratio, which were previously published, we evaluated the added value of maternal serum Inhibin-A. The predictive accuracy of each biomarker, their ratios, and combinations were estimated from areas under the curve (AUC) of receiver operating characteristics (ROC) curves, Box and Whisker plots, and by multiple regression. We estimated accuracy by the continuous marker model and a cutoff model. Results: In this study, we combined Inhibin-A with PlGF or with the sFlt-1/PlGF ratio and showed a 10–20% increase in AUCs and 15–45% increase in the detection rate, at 10% false positive rate, of PE, and a lower, but significant, increase for PE+FGR and FGR in all cases but not for FGR in early cases delivered < 34 weeks. The use of a cutoff model was adequate, although a bit higher accuracy was obtained from the continuous model. The highest correlation was found for PlGF with all three complications. Conclusion: In this secondary analysis, we have found that maternal serum Inhibin-A improves the accuracy of predicting PE and PE+FGR provided by maternal serum angiogenic markers alone, bringing the results to a diagnostic level; thus, it could be considered for directing clinical management. Inhibin-A had smaller or no added value for the accuracy of predicting FGR alone, mainly of early cases delivered <34 weeks.


Hypertension ◽  
2020 ◽  
Vol 75 (4) ◽  
pp. 918-926 ◽  
Author(s):  
Holger Stepan ◽  
Martin Hund ◽  
Theresa Andraczek

Placental dysfunction underlies a spectrum of perinatal pathologies, including preeclampsia and fetal growth restriction. Angiogenesis-related factors, including sFlt-1 (soluble fms-like tyrosine kinase 1) and PlGF (placental growth factor), play an important role in placental dysfunction; altered levels are detectable several weeks before onset of pregnancy complications. In vitro diagnostic tests for these biomarkers can improve early diagnosis and facilitate prediction of maternal and fetal outcomes. We assessed evidence for combining angiogenic biomarkers with other biomarkers or clinical parameters to predict maternal/fetal outcomes in pregnant women with placental dysfunction. Pooled information on placental perfusion (ultrasonography, mean arterial pressure), clinical characteristics, and biomarker levels (PlGF) can improve first-trimester prediction and preeclampsia diagnosis. Angiogenic factors (sFlt-1/PlGF ratio; PlGF alone) with or without clinical characteristics can facilitate second-/third-trimester prediction of early-onset and late-onset preeclampsia. A combination of increased sFlt-1/PlGF ratio and ultrasound can rule out early fetal growth restriction. The sFlt-1/PlGF ratio is also a reliable tool for discriminating between pregnancy-related hypertensive disorders, including superimposed preeclampsia and gestational hypertension. Analysis of angiogenic factors with or without uterine Doppler substantially improves sensitivity and specificity for predicting adverse outcomes and iatrogenic preterm delivery. We propose to extend the American College of Obstetricians and Gynecologists definition of preeclampsia in the future to include the combination of new-onset hypertension and new-onset of altered angiogenic factors (sFlt-1/PlGF ratio or PlGF alone). In summary, altered angiogenic biomarkers indicate placental dysfunction, and their implementation into clinical practice will help reduce the considerable burden of morbidity and mortality associated with adverse pregnancy outcomes as a consequence of angiogenic-placental syndrome.


Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 405 ◽  
Author(s):  
Xiang-Qun Hu ◽  
Lubo Zhang

Hypoxia is a common and severe stress to an organism’s homeostatic mechanisms, and hypoxia during gestation is associated with significantly increased incidence of maternal complications of preeclampsia, adversely impacting on the fetal development and subsequent risk for cardiovascular and metabolic disease. Human and animal studies have revealed a causative role of increased uterine vascular resistance and placental hypoxia in preeclampsia and fetal/intrauterine growth restriction (FGR/IUGR) associated with gestational hypoxia. Gestational hypoxia has a major effect on mitochondria of uteroplacental cells to overproduce reactive oxygen species (ROS), leading to oxidative stress. Excess mitochondrial ROS in turn cause uteroplacental dysfunction by damaging cellular macromolecules, which underlies the pathogenesis of preeclampsia and FGR. In this article, we review the current understanding of hypoxia-induced mitochondrial ROS and their role in placental dysfunction and the pathogenesis of pregnancy complications. In addition, therapeutic approaches selectively targeting mitochondrial ROS in the placental cells are discussed.


Rheumatology ◽  
2021 ◽  
Author(s):  
Rugina I Neuman ◽  
Hieronymus T W Smeele ◽  
A H Jan Danser ◽  
Radboud J E M Dolhain ◽  
Willy Visser

Abstract Objectives An elevated sFlt-1/PlGF-ratio has been validated as a significant predictor of preeclampsia, but has not been established in women with rheumatoid arthritis (RA). We explored whether the sFlt-1/PlGF-ratio could be altered due to disease activity in RA, and could be applied in this population to predict preeclampsia. Since sulfasalazine has been suggested to improve the angiogenic imbalance in preeclampsia, we also aimed to examine whether sulfasalazine could affect sFlt-1 or PlGF levels. Methods Making use of a nationwide, observational, prospective cohort study on pregnant women with RA, sFlt-1 and PlGF were measured in the third trimester. A total of 221 women, aged 21–42 years, were included, with a median gestational age of 30 + 3 weeks. Results No differences in sFlt-1 or PlGF were observed between women with high, intermediate or low disease activity (p= 0.07 and p= 0.41), whereas sFlt-1 and PlGF did not correlate with DAS28-CRP score (r=-0.01 and r=-0.05, respectively). Four (2%) women with a sFlt-1/PlGF-ratio ≤38 developed preeclampsia in comparison to three (43%) women with a ratio &gt; 38, corresponding to a negative predictive value of 98.1%. Sulfasalazine users (n = 57) did not show altered levels of sFlt-1 or PlGF in comparison to non-sulfasalazine users (n = 164, p= 0.91 and p= 0.11). Conclusion Our study shows that in pregnant women with RA, the sFlt-1/PlGF-ratio is not altered due to disease activity and a cut-off ≤38 can be used to exclude preeclampsia. Additionally, sulfasalazine use did not affect sFlt-1 or PlGF levels in this population.


Medicina ◽  
2021 ◽  
Vol 57 (7) ◽  
pp. 651
Author(s):  
Praetip Praikaew ◽  
Kuntharee Traisrisilp ◽  
Chanane Wanapirak ◽  
Ratanaporn Sekararithi ◽  
Theera Tongsong

Background and Objectives: To establish normative models for median levels of serum biomarkers of the second trimester quad test (alpha-fetoprotein: AFP; free beta-human gonadotropins: hCG; inhibin-A; and unconjugated estriol: uE3) specific to Thai women and to compare multiples of the median (MoMs) derived from ethnicity-specific models and those derived from Caucasian models with ethnic correction. Materials and Methods: A cross-sectional study was undertaken in a tertiary, medical teaching center among low-risk pregnant Thai women between 14 and 21 weeks of gestation to measure the levels of the four serum biomarkers. The measured values of each biomarker were analyzed using the multivariable factorial polynomial technique for quantile regression as a function of gestational age and maternal weight. Results: The Thai-specific normative models for the four biomarkers were generated and available for use. The MoMs of all individuals generated from our models were significantly different from conventional (Caucasian) models with ethnic correction (Wilcoxon signed-rank test; p < 0.0001 for all biomarkers). The MoMs of AFP and hCG from both methods were in agreement, but those from Thai-specific models were significantly higher. However, those of inhibin-A and uE3 were markedly different and ethnic correction was unlikely to be useful. Conclusions: The Thai-specific normative models of the quad test as a function of gestational age and maternal weight were constructed using multivariable factorial polynomial models, better than simple quantile regression or log-linear regression used in earlier decades. The analysis of MoMs supports the use of ethnicity-specific models instead of Caucasian models with ethnic correction.


2018 ◽  
Vol 11 (02) ◽  
pp. 1-4
Author(s):  
M Tripathi ◽  
R Shrestha

Objectives: To evaluate maternal and neonatal complications and pregnancy outcomes of twin pregnancies. Methods: The cross sectional study was conducted using retrospective data on the twin pregnancies with more than 28 weeks of gestational age. The study used data over a period of five years, from March 10, 2010 to March 9, 2015 in the Department of Obstetrics and Gynecology, GMC Teaching Hospital Pokhara. Results: Of the 50 twin pregnancies, the most common maternal complication was preterm delivery (40%). Other maternal complications were anemia (36%), pregnancy induced hypertension (14%), premature rupture of membranes (14%), postpartum hemorrhage (12%) and antepartum hemorrhage (6%). Median gestational age at delivery was 37 weeks. Most common route of delivery was cesarean section (66%). Most common neonatal complication was low birth weight (48%) births first twin and second twin 56%. Conclusion: Twin pregnancy has high maternal and neonatal complications, especially preterm delivery that increases the risk of significant neonatal morbidity and mortality.


1969 ◽  
Vol 40 (2) ◽  
pp. 177-184
Author(s):  
Julián A. Herrera ◽  
Santiago Vélez Medina ◽  
Rodolfo Molano ◽  
Virna Medina ◽  
Javier E. Botero ◽  
...  

Objective: To determine the efficacy of periodontal intervention on pregnancy outcome in mild preeclamptic women. Methods: A sample of 60 pregnant women with mild preeclampsia (blood pressure levels < 160/110 mm and proteinuria >300 mg/l in 24 hours urine) from the Hospital Universitario del Valle (Cali, Colombia) was included to the study. Preeclamptic women were randomized in two groups, one with periodontal intervention (PIG, N=28) and another in which the periodontal intervention was practiced after childbirth (NPIG, N=32). Maternal socio-demographic, medical and periodontal data were obtained. PIG included patients in which supragingival and subgingival cleaning within ultrasonic and manual devices were performed after study inclusion. The progression from mild to severe preeclampsia, eclampsia or HELLP syndrome, the number of days of clinical stability and the percentile of birth-weight adjusted for gestational age were evaluated in both groups. Results: Most of the patients (60%) were multigravids. Gestational age at inclusion was 31.8±1.6 weeks. Chronic periodontitis was a frequent finding (61.7%). Social, demographic, medical and periodontal conditions were similar between both groups. Disease progression to severe preeclampsia, eclampsia or HELLP syndrome was also similar (89.2% PIG versus 84.4%, p=0.65) (OR=1.06 IC 95% 0.87-1.29, p=0.65). Days of clinical stability were similar between the groups (median 10 days , range 1-46, PIG versus 12 days, range 1-59, p=0.57) and the percentile of birth weight adjusted with gestational age had no differences between the groups (median percentil 50 range 5-90 PIG versus percentil 55 range 5-95, p=0.73). Conclusion: Periodontal intervention does not seem to harm the health, the severity or alter the frequency on maternal complications in mild preeclampsia subjects.


2019 ◽  
Vol 3 (1) ◽  
pp. 01-04
Author(s):  
Hend S Saleh ◽  
Hala E Sherif ◽  
Eman M Mahfouz

Objective Implantation of the pregnancy in a cesarean scar is a rare condition named ; Cesarean scar pregnancy (CSP). Maternal complications can be prevented with the early diagnosis and an appropriate management .It is a Prospective clinical study to evaluate the efficacy and success rate of single dose use of methotrexate (MTX) followed by dilation and suction (D&S) regimen in management of women with cesarean scar pregnancy (CSP) . Methods 50mg of MTX in the form of a single dose Intramuscular injection then cervical dilatation and suction aspiration with a Karman cannula(D&S) under guidance of ultrasound after 48 preeceeded by vaginal misoprostol 2 tablet (200 mg) 4 hours ago. Results The mean gestational age at diagnosis was (8.5±1.6 ) and The mean level of serum b-human chorionic gonadotropin was (7424±2.560 ) and The mean gestational age of pregnancy was (8.5±1.6 ) .88.7% is the successive rate without complication need intervention, 2 (5.7%) patients needed intrauterine Foley's catheter for 24 hours as a mechanical hemostasis . 2 (5.7 %) had laparotomy with wedge resection of the gestational sac lesion and successful repair of the uterine defect and one (2.8 %)underwent subtotal hysterectomy. Conclusion: Systemic single dose MTX injection followed by D&S is an effective and harmless management for CSP. Nevertheless more studies are required to prove the efficiency, safety, and reproductive outcome of variant modalities in treatment of CSP.


Author(s):  
Denny Khusen

Objective: To analyze risk factor, both clinical and laboratory findings, associated with maternal mortality from severe preeclampsia and eclampsia in Atma Jaya Hospital. Methods: This was a retrospective case control study. All medical records of maternal death associated with severe preeclampsia and eclampsia between 1st January 2009 and 31st December 2011 were obtained and then information about risk factors were collected and tabulated. Risk factor analyzed were maternal age, gestational age, parity, coexisting medical illness (hypertension), antenatal examination status, maternal complications, systolic and diastolic blood pressure at admission, and admission laboratory data. Results: There were 19 maternal deaths associated with severe preeclampsia and eclampsia during period of study (Consisted of 6 cases of eclampsia and 13 cases of severe preeclampsia). Maternal mortality rate for severe preeclampsia and eclampsia were 16.7% and 33.3% respectively. Multivariate analysis identified the following risk factors associated with maternal death: gestation age <32 week, history of hypertension, thrombocyte count < 100.0000/μl, post partum bleeding, acute pulmonary edema, HELLP syndrome, and sepsis. Conclusion: In this study, we found that gestational age, history of hypertension, and platelet count are the cause of maternal mortality. Maternal complications associated with maternal mortality are post partum bleeding, acute pulmonary edema, HELLP syndrome, and sepsis. [Indones J Obstet Gynecol 2012; 36-2: 90-4] Keywords: eclampsia, maternal mortality, preeclampsia


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