HtrA3 Isoform–Specific ELISAs for Early Detection of Preeclampsia

2016 ◽  
Vol 23 (10) ◽  
pp. 1092-1099 ◽  
Author(s):  
Yao Wang ◽  
Ying Li ◽  
Jonathan Hyett ◽  
Fabricio da Silva Costa ◽  
Guiying Nie
Keyword(s):  
Early Detection ◽  
Early Onset ◽  
Late Onset ◽  
Pdz Domain ◽  
First Trimester ◽  
Potential Utility ◽  
Third Trimester ◽  
The Third ◽  
Early Onset Preeclampsia ◽  
Singleton Pregnancies

Preeclampsia is a serious disorder of human pregnancy occurring after 20 weeks of gestation. It can be divided into subtypes of early onset (<34 weeks of gestation) and late onset (>34 weeks). Presymptomatic detection to identify those at high risk is important for managing this disease. HtrA3, a serine protease with high expression in the developing placenta, exists in long (HtrA3-L) and short (HtrA3-S) isoforms. They are identical, except HtrA3-S lacks the C-terminal PDZ domain. We have previously shown by Western blot analysis that serum HtrA3 levels at the end of the first trimester are significantly higher in women who later develop preeclampsia than in controls. In this study, using highly specific HtrA3 monoclonal antibodies, we established and fully validated two enzyme-linked immunosorbent assays to detect both HtrA3 isoforms together (HtrA3-T) and HtrA3-L alone in the human serum. We then determined serum HtrA3 at 11 to 13 weeks of gestation in a cohort of singleton pregnancies that proceeded without complications or developed preeclampsia in the third trimester. Compared with controls, those who developed late-onset preeclampsia had significantly higher levels of HtrA3-L, whereas those who developed early-onset preeclampsia had significantly lower ratios of HtrA3-L/HtrA3-T. These data support a potential utility of these HtrA3 ELISAs for early detection of preeclampsia.

scholarly journals Homocysteine during the third trimester is a risk factor for preeclampsia: A prospective study

2020 ◽  
Author(s):  
Sha Chen ◽  
Hong Shen ◽  
Xueya Zhao ◽  
Jun Luo ◽  
Weiwei Cheng
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Folic Acid ◽  
Prospective Study ◽  
Vitamin B12 ◽  
Early Onset ◽  
Third Trimester ◽  
The Third ◽  
Early Onset Preeclampsia ◽  
A Prospective Study

Abstract Background: The purpose of this study was to investigate the risk factors for elevating homocysteine during pregnancy and the relative effects on preeclampsia, so as to further understand whether Hcy had predictive value for PE.Method: This is a prospective study that only covers pregnant women with singleton who received regular prenatal care from July to September 2018 exclusively at IPMCH (N=1142). Homocysteine, folic acid and vitamin B12 were tested in the 1st trimester (10-14 weeks), 2nd trimester (24-28 weeks), and 3rd trimester (30-34 weeks), respectively, and MTHFR genes (rs1801133, rs1801131, rs17367504) were detected. Therefore, the analysis of this case includes the variation in Hcy levels during pregnancy, risk factors for elevating homocysteine and the risk factors on preeclampsia.Results: (1) Homocysteine was lowest in the 1st trimester. (2) Homocysteine was negatively correlated with folic acid (r=-0.17, p<0.001) and vitamin B12 (r=-0.15, p<0.001) in the same trimester. (3) Both of heterozygous CT (p=0.025, 95% CI 0.018, 0.275) and homozygous TT (p<0.001, 95% CI 0.185, 0.501) in MTHFR rs1801133 might be risk factors that caused an increase in Hcy. G-spot mutations in MTHFR rs17367504 might be a risk factor that caused a decline in homocysteine. (4) Homocysteine in the 3rd trimester might be significantly correlated with increasing risk of preeclampsia (OR = 1.2, 95% CI 1.01,1.42), particularly early-onset preeclampsia (OR = 3.63, 95% CI 1.71,7.71) and severe preeclampsia (OR = 3.63, 95% CI 1.71,7.71).Conclusions: The variation in homocysteine level in the third trimester might be associated with preeclampsia, especially early-onset preeclampsia and severe preeclampsia, and MTHFR, folic acid and vitamin B12 might be the three critical factors responsible for the changing homocysteine levels during pregnancy.

scholarly journals Diagnostic Performance of First Trimester Screening of Preeclampsia Based on Uterine Artery Pulsatility Index and Maternal Risk Factors in Routine Clinical Use

Diagnostics ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 182
Author(s):  
Max Mönckeberg ◽  
Valentina Arias ◽  
Rosario Fuenzalida ◽  
Santiago Álvarez ◽  
Victoria Toro ◽  
...  
Keyword(s):  
High Risk ◽  
Early Onset ◽  
Diagnostic Performance ◽  
Uterine Artery ◽  
Late Onset ◽  
First Trimester ◽  
Maternal Risk ◽  
Predictive Algorithm ◽  
First Trimester Of Pregnancy ◽  
Early Onset Preeclampsia

Preeclampsia is a pregnancy-specific disorder defined by new onset of hypertension and proteinuria after 20 weeks of gestation. The early detection of patients at risk of developing preeclampsia is crucial, however, predictive models are still controversial. We aim to evaluate the diagnostic performance of a predictive algorithm in the first trimester of pregnancy, in order to identify patients that will subsequently develop preeclampsia, and to study the effect of aspirin on reducing the rate of this complication in patients classified as high risk by this algorithm. A retrospective cohort including 1132 patients attending prenatal care at Clínica Dávila in Santiago, Chile, was conceived. The risk of developing preeclampsia (early and late onset) was calculated using algorithms previously described by Plasencia et al. Patients classified as high risk, in the first trimester of pregnancy, by these algorithms, were candidates to receive 100 mg/daily aspirin as prophylaxis at the discretion of the attending physician. The overall incidence of preeclampsia in this cohort was 3.5% (40/1132), and the model for early onset preeclampsia prediction detected 33% of patients with early onset preeclampsia. Among the 105 patients considered at high risk of developing preeclampsia, 56 received aspirin and 49 patients did not. Among those who received aspirin, 12% (7/56) developed preeclampsia, which is equal to the rate of preeclampsia (12% (6/49)) of those who did not receive this medication. Therefore, the diagnostic performance of an algorithm combining uterine artery Doppler and maternal factors in the first trimester predicted only one third of patients that developed preeclampsia. Among those considered at high risk for developing the disease using this algorithm, aspirin did not change the incidence of preeclampsia, however, this could be due either to the small study sample size or the type of the study, a retrospective, non-interventional cohort study.

scholarly journals Early onset and late onset preeclampsia-maternal and perinatal outcomes in a rural teritiary health center

2018 ◽  
Vol 7 (6) ◽  
pp. 2266 ◽  
Author(s):  
Gomathy E. ◽  
Lahari Akurati ◽  
Kondareddy Radhika
Keyword(s):  
Early Onset ◽  
Perinatal Outcome ◽  
Late Onset ◽  
Perinatal Outcomes ◽  
Retrospective Data ◽  
Perinatal Complications ◽  
Medical College ◽  
Gestation Age ◽  
Early Onset Preeclampsia ◽  
Singleton Pregnancies

Background: Preeclampsia is main cause of morbidity and mortality both mother and fetus. Preeclampsia occurs in 10-17% of pregnancies. Preeclampsia was divided into early onset preeclampsia is occur at less <34 weeks of gestation age and late onset preeclampsia is occur at >34 weeks of gestation age. Early and late onset preeclampsia have different etiology and should be considered as different disease as there are difference in clinical manifestation, maternal and perinatal outcome, prognosis and complication.Methods: An analytic observational study involving retrospective data done at RL Jalappa Hospital, Sri Devaraj Urs Medical College, Kolar. 217 women with singleton pregnancies with Pre eclampsia who were admitted and delivered in our hospital between June 2016 and May 2017 were recruited for this retrospective study.Results: The results showed that the incidence of EOPE (27.6%) was lower than LOPE (72.4%). Diastolic blood pressure is significantly higher in EOPE compared to LOPE. Complications in perinatal outcomes such as low birth weight (<2500 gram) are more in EOPE (98.3%) compared to LOPE (45.2%) and asphyxia is more on EOPE (11.7%) compared to LOPE (1.3%). Stillbirth in EOPE (15%) is more than LOPE group (3.2%).Conclusions: It is observed that EOPE incidence rate is lower than LOPE. Maternal and perinatal complications are greater in the EOPE group.

Correlations Between the Values of Maternal Glycemia from the Last Trimester of Pregnancy and Fetal Birth Weight

2013 ◽  
Vol 20 (3) ◽  
pp. 259-265
Author(s):  
Monica Vereş ◽  
Aurel Babeş ◽  
Szidonia Lacziko
Keyword(s):  
First Trimester ◽  
Mean Value ◽  
Fetal Macrosomia ◽  
Entire Group ◽  
Third Trimester ◽  
The Third ◽  
Group I ◽  
Fetal Birth Weight ◽  
First Trimester Of Pregnancy ◽  
The Mean

Abstract Background and aims: Gestational diabetes represents a form of diabetes diagnosed during pregnancy that is not clearly overt diabetes. In the last trimester of gestation the growth of fetoplacental unit takes place, thus maternal hyperglycemia will determine an increased transplacental passage, hyperinsulinemia and fetal macrosomia. The aim of our study was that o analyzing the effect of maternal glycemia from the last trimester of pregnancy over fetal weight. Material and method: We run an observational study on a group of 46 pregnant women taken into evidence from the first trimester of pregnancy, separated in two groups according to blood glucose determined in the third trimester (before birth): group I normoglycemic and group II with hyperglycemia (>92mg/dl). Results: The mean value of third trimester glycemia for the entire group was of 87.13±22.03. The mean value of the glycemia determined in the third trimester of pregnancy was higher in the second group (109.17 mg/dl) in comparison to the first group (74.,21 mg/dl). The ROC curve for third trimester glycemia as fetal macrosomia appreciation test has an AUC of 0.517. Conclusions: Glycemia determined in the last trimester of pregnancy cannot be used alone as the predictive factor for fetal macrosomia.

Deoxyribonuclease activity negative correlates with extracellular DNA in uncomplicated singleton pregnancies in the third trimester

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Barbora Vlková ◽  
Ľubica Janovičová ◽  
Petra Pšenková ◽  
Lívia Melníková ◽  
Barbora Balažovjechová ◽  
...  
Keyword(s):  
Pregnancy Complications ◽  
Extracellular Dna ◽  
Dnase Activity ◽  
Diffusion Method ◽  
Third Trimester ◽  
The Third ◽  
Healthy Women ◽  
Mitochondrial Origin ◽  
Singleton Pregnancies

Abstract Objectives It is not clear, which factors affect extracellular DNA (ecDNA) concentrations in healthy women with singleton uncomplicated pregnancies, although deoxyribonucleases (DNases) are hypothesized to be responsible for the cleavage of plasma ecDNA. The aim of this study was to analyze potential determinants of total ecDNA including plasma DNase activity. Methods Plasma samples were collected from 48 healthy women with singleton uncomplicated pregnancies in the third trimester (gestation week 37). DNA was isolated and quantified using fluorometry and real time PCR. DNase activity was assessed using the single radial enzyme-diffusion method. Results Neither ecDNA, nor DNase activity were affected by maternal age or BMI. DNase activity negatively correlated with total plasma ecDNA (r=−0.40, p=0.007). Similar associations were found for ecDNA of nuclear and mitochondrial origin, but not with fetal DNA quantified using Y-targeted PCR in male fetus-bearing pregnancies. Conclusions The role of plasma ecDNA of fetal and maternal origin is studied in the pathogenesis of pregnancy-complications. The results indicate that plasma DNase activity could negatively regulate ecDNA concentrations and should, thus, be analyzed in preeclampsia, preterm birth and other ecDNA-related pregnancy complications.

The effect of maternal vitamin D supplementation in the third trimester on the incidence of early-onset sepsis in their newborns

2020 ◽  
Vol 9 (2) ◽  
pp. 74
Author(s):  
Prathapa Shetty ◽  
Manasee Deka ◽  
ManojKumar Yadav ◽  
Geeta Gathwala ◽  
Sunny Lohia ◽  
...  
Keyword(s):  
Vitamin D ◽  
Early Onset ◽  
Vitamin D Supplementation ◽  
Third Trimester ◽  
Maternal Vitamin ◽  
The Third ◽  
Early Onset Sepsis

scholarly journals Infliximab clearance decreases in the second and third trimesters of pregnancy in inflammatory bowel disease

2020 ◽  
pp. 205064062096461
Author(s):  
Ana-Marija Grišić ◽  
Maria Dorn-Rasmussen ◽  
Bella Ungar ◽  
Jørn Brynskov ◽  
Johan F K F Ilvemark ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
First Trimester ◽  
Interquartile Range ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Second Trimester ◽  
Third Trimester ◽  
The Third ◽  
Inflammatory Bowel

Background Infliximab therapy during pregnancy in inflammatory bowel disease is challenged by a dilemma between maintaining adequate maternal disease control while minimizing fetal infliximab exposure. We investigated the effects of pregnancy on infliximab pharmacokinetics. Methods The study population comprised 23 retrospectively identified pregnancies. Patients with inflammatory bowel disease were generally in clinical remission at pregnancy conception (74%) and received steady infliximab maintenance therapy (5 mg/kg q8w n = 17; q6w n = 4; q10w n = 1; 10 mg/kg q8w n = 1). Trough blood samples had been obtained in the same patients prior to pregnancy ( n = 119), the first trimester ( n = 16), second trimester ( n = 18), third trimester ( n = 7), and post-pregnancy ( n = 12). Data were analyzed using nonlinear mixed-effects population pharmacokinetic modelling. Results Dose-normalized infliximab concentrations were significantly higher during the second trimester (median 15 µg/mL/kg, interquartile range 10–21) compared to pre-pregnancy (7, 2–12; p = 0.003), the first trimester (9, 1–12; p = 0.04), or post-pregnancy (6, interquartile range 3–11; p > 0.05) in patients with inflammatory bowel disease. Similar trends were observed in the third trimester (13, 7–36; p > 0.05). A one-compartment model with linear elimination described the pharmacokinetics of infliximab (volume of distribution = 18.2 L; clearance 0.61 L/day). Maternal infliximab exposure was influenced by the second and third trimester of pregnancy and anti-infliximab antibodies, and not by pregnancy-imposed physiological changes in, for example, body weight or albumin. Infliximab clearance decreased significantly during the second and third trimesters by up to 15% as compared to pre- and post-pregnancy and the first trimester. The increased maternal infliximab exposure was weakly associated with lowered clinical disease activity. Pharmacokinetic model simulations of virtual patients indicated the increased maternal infliximab trough concentrations imposed by pregnancy will not completely counteract the decrease in infliximab concentration if therapy is paused in the third trimester. Conclusion Infliximab clearance decreases significantly in the second and third trimesters, leading to increasing maternal infliximab concentrations in any given regimen. Maternal infliximab levels may thus be maintained as constant in a de-intensified regimen by therapeutic drug monitoring guidance in inflammatory bowel disease.

scholarly journals The Effect of Preserving Pregnancy in Cervical Cancer Diagnosed During Pregnancy: A Retrospective Study

2021 ◽  
Author(s):  
Zuoxi He ◽  
Chuan Xie ◽  
Xiaorong Qi ◽  
Zhengjun Hu ◽  
Yuedong He
Keyword(s):  
Cervical Cancer ◽  
Rare Event ◽  
Oncologic Outcome ◽  
First Trimester ◽  
Second Trimester ◽  
Third Trimester ◽  
Delayed Treatment ◽  
The Third ◽  
Survival Difference ◽  
Estimated Blood Loss

Abstract ObjectiveCervical cancer diagnosed during pregnancy is a rare event, and data regarding efficacy of cancer treatment during pregnancy is limited. This study aimed to assess the safety of continuation of the pregnancy for mother and fetus when concomitantly diagnosed with cervical cancer.MethodsThis study retrospectively analyzed all cervical cancer patients diagnosed while pregnant or immediately postpartum, inclusive from Jan 2010 to June 2019 at our institute. Patient clinical details and follow-up were obtained from hospital records. ResultsThe study comprised 40 patients with clinical cancer stages of ⅠA1 (1/40, 2.5%); ⅠB1 (15/40, 37.5%); IB2 (10/40, 25%); ⅡA (12/40, 30%); and ⅡB (2/40, 5%). There were 38 patients diagnosed during pregnancy, and 2 diagnosed in the postpartum period. Of the 38 patients, 17 were diagnosed in the first trimester, 13 in the second trimester, and 8 in the third trimester. Ten of 38 patients (26.3%) continued their pregnancy after learning of their diagnosis; 7 (70%) in the third trimester and 3 (30%) in the second trimester. The mean time from diagnosis to surgery in the patients who continued their pregnancy was 52.7 days, which was statistically significantly greater than the termination of pregnancy group (52.7 vs 16.3 days, P < 0.01). Notably, there was no survival difference between the 2 groups (100% vs 90.91%, P =0.54), and none of the pregnant women who ultimately died had delayed treatment due to pregnancy. Similarly, the surgical estimated blood loss and operative duration comparing the 2 groups were not significantly different. ConclusionsIn the present study, the gestational age of pregnancy at the time of initial diagnosis of cervical cancer was an important determinant in the disease management. Continuation of the pregnancy when diagnosed with cervical cancer did not affect the oncologic outcome of the mother nor increase either surgical or obstetric complications. Additionally, the use of neoadjuvant chemotherapy did not threaten the health of the fetus. These results may be useful in counseling patients facing the diagnosis of cervical cancer during pregnancy.

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