Predictive value of urine misfolded protein in preeclampsia in twin pregnancies

doi:10.21203/rs.3.rs-4818726/v1

Download PDF

Research Article

Predictive value of urine misfolded protein in preeclampsia in twin pregnancies

https://doi.org/10.21203/rs.3.rs-4818726/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Objective

To assess the utility of urinary misfolded proteins (MP) in predicting pre-eclampsia (PE) in high-risk twin pregnancies.

Methods

A prospective study was conducted on 600 high-risk twin pregnancies at Shanghai First Maternity and Infant Hospital from March to August 2021. Clinical data were collected, and urinary MP levels were measured. Subsequently, fetal outcomes were monitored. The patients were categorized into three groups based on the presence of PE: unaffected PE group, early-onset PE (ePE) group (gestational age < 34 weeks), and late-onset PE (lPE) group (gestational age ≥ 34 weeks). The predictive value of MP in PE was evaluated using analysis of variance, chi-square test, and ROC curve analysis.

Results

A total of 464 twin pregnancies were included in the study, among which 66 cases (14.2%) developed PE, including 19 cases of ePE (4.1%) and 47 cases (10.1%) of lPE. Significant differences were found in maternal age, pre-pregnancy BMI, BMI ≥ 28km/m², mean systolic blood pressure, diastolic blood pressure, Mean arterial pressure (MAP), MAP ≥ 85 mmHg, history of PE, history of chronic hypertension, and positive urine protein. The maternal and fetal complications of twin pregnancies with PE were higher than those without PE (P < 0.05). When maternal factors (MF), MAP, and MP were used to predict ePE and lPE alone, the area under the ROC curve of MF was the largest, at 0.739 (95%CI: 0.619–0.860) and 0.692 (95%CI: 0.603–0.782), respectively. The area under the ROC curve of the combination of the three factors was 0.770 (95%CI: 0.703–0.837), higher than that of a single index.In addition, MP predicted the positive predictive value (PPV) and negative predictive value (NPV) of PE from 12 to 15^+ 6 gestational weeks as 57.9% and 89.2%, respectively; from 16 to 27^+ 6 gestational weeks as 36.2% and 89.9%, respectively; and during the 12–27^+ 6 gestational weeks as 42.4% and 92.2%, respectively.

Conclusion

The detection of MP in the urine of twin pregnancies is a non-invasive and convenient method for predicting PE. If the test result is positive, enhanced monitoring and timely transfer to a superior hospital are necessary; If the test result is negative, it indicates a low risk of developing PE, reducing the need for excessive clinical examination and intervention.

misfolded protein

twin pregnancies

high-risk factors

Pre-eclampsia(PE) is an idiopathic hypertensive disorder of pregnancy, characterized by hypertension and proteinuria after 20 weeks of gestation. In recent years, with the development of assisted reproductive technology (ART), the incidence of twin pregnancies has increased significantly^[1].The incidence of PE in twin pregnancies reaches 10%-20% ^[2–4], which is 2–5 times higher than that of singleton pregnancies. Compared with singleton pregnancies, twin pregnancies carry higher risk, progress more rapidly and result in more severe diseases, contributing significantly fo maternal and perinatal death ^[5–6].

Therefore, predicting and preventing PE in twin pregnancies is of paramount importance ^[7].Recent guidelines suggest that screening for maternal risk factors is a common clinical strategy for identifying high-risk groups for PE^[8–10].The guidelines of National Institute for Health and Care Excellence (NICE) and American College of Obstetricians and Gynecologists (ACOG) categorize and assign scores to PE risk factors, facilitating clinical use. However, the predictive performance of this screening program is not ideal, and specific risk factors for PE in twin pregnancies, such as typing of fertilized eggs, monochorionic and assisted reproductive technology(ART), remain to be determined.

Consequently, prediction models incorporating specific biomarkers^[11], such as placental growth factor (PlGF) and pregnancy associated plasma protein-A (PAPP-A), have been developed. Although these models show good predictive performance for PE in singleton pregnancies^[12–13], Benk et al. ^[14] found that the distribution of early pregnancy biomarkers (MAP, UtA-PI, PLGF and PAPP-A) in twin pregnancies differs significantly from that in singleton pregnancies. Additionally, obtaining these biomarkers requires specialized examinations, which are expensive and challenging to implement in low-resource countries or regions ^[15].

It has been found that misfolding and aggregation of protein is related to the pathogenesis of PE ^[16].In patients with singleton PE, abnormal levels of misfolded proteins (MP) in urine and blood were detected 10 weeks before the onset of clinical symptoms ^[17]. These MP polymers are associated with amylose, hence they are also reffered as amyloid protein ^[18]. Due to their affinity with amylopectin, the Congo red dot (CRD) test provides a novel method for detecting urine folded proteins to predict PE ^[19].

Considering the limitations and high economic cost of existing PE predictive screening models in twin pregnancies, this study aims to evaluate the utility of detecting MP in the urine of twin pregnancies, combined with maternal high risk factors (MF) and mean arterial pressure(MAP), in predicting PE.

1.1 Research objects: A cohort of 600 high-risk women with twin pregnancies between 12 and 27⁺⁶gestational weeks who received regular antenatal care and delivery at Shanghai First Maternity and Infant Hospital was selected from March to August 2021. The study was approved by the Hospital Medical Ethics Committee, and all participants signed informed consent prior to inclusion in the research.
1.1.1 Inclusion criteria: High-risk pregnant women were identified as those possessing either one high-risk factor for PE^[20]or two moderate risk factors ^[8]. High-risk factors encompassed chronic hypertension, chronic kidney disease, pre-pregnancy diabetes, autoimmune disease, and a previous history of PE. Moderate risk factors included first-time parturition, multiple pregnancies, maternal age≥ 35 years, pregnancy interval ≥ 10 years, body mass index (BMI)≥28kg/m², systolic blood pressure (sBP)≥130mmHg, diastolic blood pressure (dBP)≥80mmHg, or persistent urinary protein ≥ the plus sign.
1.1.2 Exclusion criteria: Pregnant women were excluded for the following reasons: severe maternal medical or surgical diseases; chromosomal or structural abnormalities in the fetus; termination of pregnancy due to stillbirth, or social factors; pregnancy reduction, and pregnancy loss.
1.2 Research methods: Clinical information of enrolled subjects was collected and recorded during prenatal examinations from 12 to 27⁺⁶ gestational weeks, including maternal age, weight, height, parity, method of conception, intake of calcium tablets and folic acid, family history of PE, hypertension, or diabetes, and medication taken in the first three months of pregnancy. Blood pressure (measured in both arms) and MP levels in urine were also recorded. Maternal and fetal outcomes were subsequently followed up.

1.2.1 MP Detection: Each subject collected 2 mL of clean midstream urine independently and then handed to the testers. The testers applied the urine to the sample wells on the CRD card. After 3 minutes, the result was determined and recorded based on the negative and positive criteria indicated on the test card (CRD card registration number: 20202400438).
1.2.2 Measurement of MAP: In 2019, the FIGO guidelines stated^[15]that MAP served as a crucial component in assessing the risk of PE and should be measured using validated automated or semi-automated equipment. In this study, subjects rested in a consultation room for at least 5 minutes in a comfortable sitting position. Blood pressure was measured using an automatic sphygmomanometer (BPBI0320, Biospace, Cheonan, South Korea), with the arm positioned at heart level. Simultaneous measurements were taken for both arms, with two readings obtained at one-minute interval. sBP and dBP were averaged separately from these readings. MAP was calculated using the formula: MAP=dBP+ (sBP-dBP) /3.
1.3 Statistical methods: Statistical analysis was conducted using SPSS22.0 software. Continuous variables were compared using analysis of variance (ANOVA) test or Kruskal-Wallis test as appropriate. Categorical variables were compared using the chi-square test or Fisher exact test. The receiver operating characteristic (ROC) curve was employed to asses screening effectiveness. A significance level of P < 0.05 was considered statistically significant.

2.1 Research flow chart and main results.
In this study, 600 twin pregnancies between 12 to 27⁺⁶ gestational weeks were initially collected, and the pregnancy outcomes were followed up. During the follow-up period, 136 cases were excluded due to natural abortion (n=58), pregnancy reduction (n=37), and pregnancy loss (n=41). Finally, 464 cases were included in the analysis, comprising 377 cases (81.0%) without PE, 66 cases (14.2%) with PE (19 cases (4.1%) with ePE, 47 cases (10.1%) with lPE), and 21 cases (4.5%) with gestational hypertension. Among the 181 cases evaluated at 12-15⁺⁶ weeks of gestation.,26 cases tested positive on the CRD test. Of these, 13 cases (50.0%) developed PE, including 2 cases (7.7%) of ePE and 11 cases (42.3%) of lPE. Among the 155 cases with negative CRD test results during this period, 15 cases (9.7%) developed PE, including 3 cases (1.9%) of ePE and 12 cases (7.7%) of lPE.

Addionally, 283 cases were evaluated at 16-27⁺⁶ weeks of gestation. Among the 33 cases with positive CRD test results, 15 cases (45.5%) developed PE, including 6 cases (18.2%) of ePE and 9 cases (27.3%) of lPE. Among the 250 cases with negative CRD test results during this period, 23 cases (9.2%) developed PE, including 8 cases (3.2%) of ePE and 15 cases (6.0%) of lPE. Table 1 shows the details.

Table 1 Research flow chart and preliminary experimental results

2.2 Clinical characteristics of pregnant women unaffected PE and PE

In this study, 464 patients were classified into three groups according to the presence of PE: no PE group, ePE group, and lPE group. Significant differences were observed among these groups in maternal age, pre-pregnancy BMI, BMI≥28km/m², mean sBP, dBP, MAP, MAP ≥ 85 mmHg, history of PE, history of chronic hypertension, and positive urine protein. However, there were no significant differences in parity, intake of folic acid, chorionicity, pregnancy interval≥10 years, and gestational week at testing (P> 0.05) (Table 2).

Table 2 Maternal and pregnancy characteristics in the screening population

Variable	Unaffected (n＝377)	Early PE (n＝19)	Late PE (n＝47)	P值
Matermal age,years^a	34.7±2.3	32.0±1.4	35.0±1.1	0.000
Maternal BMI^b,kg/m²	21.9±3.2	24.1±5.0	23.7±4.7	0.000
BMI≥28,kg/m²	16(4.4)	3(15.8)	6(12.2)	0.009^c
Parity
≤2	299(79.3)	14(73.7)	39(81.6)	0.683
≥3	78(20.7)	5(26.3)	8(16.3)
Nulliparous	310(82.2)	16(84.2)	40(81.6)	0.960^c
Parous	67(17.8)	3(15.8)	7(14.9)
Folic acid	282(74.8)	11(57.9)	32(65.3)	0.185
Conception
Spontaneous	183(48.5)	5(26.3)	12(24.5)	0.020
In-vitro fertilization	118(31.3)	9(47.4)	21(42.9)
ICSI	68(18.1)	5(26.3)	14(28.6)
PGT	8(2.1)	0	0
Chorionicity
Monochorionic	173(45.9)	13(68.4)	27(57.4)	0.061
Dichorionic	204(54.1)	6(31.6)	20(42.6)
Blood pressure,mmHg
sBP,mmHg	113.1±9.1	120.5±11.2	117.0±11.2	0.001
dBP,mmHg	69.4±6.7	73.8±9.2	71.2±8.2	0.023
MAP,mmHg	83.8±6.6	89.3±9.0	86.5±8.6	0.001
MAP≥85,mmHg	179(47.4)	13(68.4)	27(57.4)	0.045
previous PE	7(2.1)	2(10.5)	2(4.3)	0.047
Chronic hypertension	10(2.7)	3(15.8)	2(4.3)	0.026^c
Pregnancy interval ≥ 10 years	8(2.1)	0	1(2.1)	1.000
dipstick proteinuria
1-2+	55(14.6)	10(52.6)	22(46.8)	0.000
≥3	11(2.9)	5(26.3)	8(20.5)	0.000
Gestational age at screening, weeks
12-15⁺⁶	148(39.3)	5(26.3)	23(48.9)	0.637^c
16-19⁺⁶	72(19.1)	6(31.6)	9(19.1)
20-23⁺⁶	60(15.9)	3(15.8)	6(12.9)
24-28	97(25.7)	5(26.3)	9(19.1)

Abbreviations:

BMI, body mass index; PE, pre-eclampsia;

ICSI, Intracytoplasmic sperm injection PGT,Preimplantation genetic technology

sBP,systolic systolic blood pressure;

dBP,diastolic Blood pressure; MAP, mean arterial pressure;

Early PE,PE defined as detection at less than 34 weeks gestation;

Late PE, PE defined as detection at greater than or equal to 34 weeks;

a,Maternal age at expected date of delivery;

b,Pre-pregnancy BMI; c,Tested by Fisher’s exact test.

2.3 Comparison of the area under the ROC curve of single and combined

detection in predicting PE.

The area under the ROC curve (AUC) of MF, MAP, and MP for predicting ePE and lPE were compared. MF exhibited the largest AUC [0.739 (95%CI: 0.619-0.860) and 0.692 (95%CI: 0.603-0.782)] among the single indices. The AUC of the combined detection of the three factors was 0.770 (95% CI: 0.703-0.837), which was higher than that of any single index alone (See Table 3 and Figure1-5).

Table 3. Areas under the receiver operating characteristic curves of MF, MAP, and MP in predicting PE

Screening	Areas under the receiver operating characteristic curve
Screening	Early PE (n＝19)	Late PE (n＝47)	All PE(n＝66)
MP	0.676(0.530-0.822)	0.678(0.584-0.772)	0.691(0.611-0.770)
MAP	0.675(0.530-0.820)	0.588(0.504-0.672)	0.604(0.531-0.678)
MF	0.739(0.619-0.860)	0.692(0.603-0.782)	0.699(0.627-0.772)
MF+MAP	0.740(0.604-0.876)	0.702(0.616-0.788)	0.710(0.640-0.779)
MF+MP	0.755(0.627-0.882)	0.753(0.665-0.842)	0.759(0.687-0.830)
MAP+MP	0.720(0.571-0.869)	0.731(0.648-0.815)	0.736(0.663-0.809)
MF+MAP+MP	0.755(0.619-0.891)	0.763(0679-0.847)	0.770(0.703-0.837)

Abbreviations:

MF,maternal factors;MAP,mean arterial pressure; MP,misfolded protein.

2.4 Predictive value of MP in PE

Table 4 presents the positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity, and Youden index for predicting PE using urinary MP. For pregnancies between 12 to 15⁺⁶gestational weeks, MP predicted a PPV and NPV of PE at 57.9% and 89.2%, respectively. For pregnancies between 16 to 27⁺⁶ gestational weeks, MP predicted a PPV and NPV of PE at 36.2% and 89.9%, respectively. Across 12-27⁺⁶gestational weeks, MP predicted a PPV and NPV of PE at 42.4% and 92.2%, respectively.Whlie MP alone exhibited a sensitivity and PPV for predicting PE of apporximately 50% during 12-27⁺⁶ gestational weeks, both specificity and NPV were apporximately 90%. Detaled values can be found in Table 4.

Table 4: Predictive values of MP detection for PE

Gestational weeks	Maker	PPV (%)	NPV (%)	Sensitivity (%)	Specificity (%)	Youden index
12-15⁺⁶	MP	57.9	89.2	42.1	88.5	0.306
16-27⁺⁶	MP	36.2	89.9	41.7	90.6	0.323
12-27⁺⁶	MP	42.4	92.2	46.5	93.4	0.399

Abbreviations: NPV, negative predictive value; PPV, positive predictive value.

This study determined that maternal factors (MF) exhibited the largest AUC for predicting PE in twin pregnancies, with values of 0.739(95%CI:0.619-0.860) for ePE and 0.692 (95%CI: 0.603 - 0.782) for lPE, respectively. When combining MF, MAP and MP, the AUV increased to 0.770 (95%CI: 0.73-0.837), surpassing that of any single index alone. Moreover, this study demonstrated that MP had a NPV of more than 90% for predicting PE in twin pregnancies during 12-27⁺⁶gestational weeks, effectively identifying the low-risk groups for PE among twins. Despite the onset of PE occurring in the second trimester, early changes in placental pathophysiology are evident in the first trimester^[21]. Studies have indicated that urine MP detection can yield positive results as early as 10 weeks before the onset of PE symptoms, suggesting its potential utility in PE prediction in early pregnancy.

Previous studies have demonstrated that complex models combining maternal factors with biomarkers perform better in predicting PE compared to models using MF alone^[12-13]. The guideline of the International Federation of Obstetrics and Gynecology recommended the use of UtA-PI, PlGF and PAPP-A as biomarkers for PE screening in early pregnancy^[15].Chen et al.^[22] combined MF with a logistic complex model incorporating MAP, PlGF and PAPP-A to predict the risk of PE in twin pregnancies in Shanghai. They reported detection rates of 40.7% for ePE and 22.0% for lPE (FPR=10%). In contrast, in the current study, the detection rate of PE was 42.1% when the CRD was positive at 12-15⁺⁶gestational weeks, and 41.7% when positive at 16-27⁺⁶ gestational weeks. These rates were higher compared to those reported by Chen et al.

In this study, the incidence of pre-eclampsia was 14.2%, aligning with existing literature^[2-4], which attributes this to the inclusion of individuals with PE risk factors. Compared to twin pregnancies without PE, those with PE exhibited higher BMI,BP, and MAP, along with chronic hypertension or pre-eclampsia, monochorionic and other characteristics, consistent with the Queensland guideline report^[23]. There was no significant correlation between parity, delivery timing, folic acid intake and the pregnancy interval ≥10 years. In this study, the sensitivity and PPV of MP in urine for predicting PE in the first and second trimesters were about 50%, higher than those reported in a systematic review by Khalil^[24] and a prospective study reported by Wang^[25], likely due to the inclusion of high-risk twins groups. In addition, the predicted specificity and NPV of PE were both high, around 90%, consistent with the specificity reported by Wang. Therefore, if the urine MP test results are negative in the twins, the risk of developing PE is low.

Currently, existing models for PE screening, including uterine artery examination or the detection of PlGF, require specialized instruments and are expensive, making them challenging to implement in underdeveloped areas or secondary clinics. This study, based on maternal risk factors and utilizing only pregnant women's urine, offers a simple, non-invasive, rapid and effective method for the screening of PE in twin pregnancies.

Urine MP detection in the early and middle trimesters of twin pregnancies, if positive, can enhance monitoring and prompt transfer to a higher-level hospital if necessary to ensure maternal and fetal safety. If the urine MP test is negative, it indicates a low probability of PE, reducing the need for excessive examinations and interventions by clinicians.

Advantages of this study :

(1) Large sample size in twin pregnancies and a prospective study;

(2) The CRD paper method requires only pregnant women’s urine, making it simple, non-invasive, and easy to implement.

Disadvantages of this study

Single-center study; focus only on twin pregnancies.

Author Contribution

Liang Qiufeng: Follow up cases,Data Collection, Manuscript writing.

Sun Luming: Article design and revision.

Statements & DeclarationsConflict of interest

The authors have stated explicitly that there are no conflicts of interest in connection with this article.

Funding

The research was funded by the National Key Research and Development Program of China (2022YFC2704700), the National Natural Science Foundation of China (82071656), and Shanghai Municipal Science and Technology Commission (No. 21Y11907500，23DZ2303400).

Competing Interests

The authors have no relevant financial or non-financial interests to disclose.

Ethics approval

The study was approved by the ethics committee of Tongji University (registration number: 2018yxy13), and informed consent was obtained from the patients.

Xie JL, Wang XJ,Wang BS (2023) Prediction progress of pre-eclampsia in twin pregnancy [J]. Chin J Perinat Med 26(7):601–606. 10.3760/cma.j.cn113903-20221008-00877
Chen W, Wang ZL (2021) Analysis of The tendency, characteristic and risk factors of twin pregnancy complicated with pre-eclampsia[J].J Sun Yat-sen Univ. (Med Sci) 42(1):145–153
Rissanen AS, Jernman RM, Gissler M et al (2019)Maternal complications in twin pregnancies in Finland during 1987–2014:a retrospective study[J]. BMC Pregnancy Childbirth, 19(1):337. 10.1186/s12884-019-2498-x
Laine K, Murzakanova G, Sole KB et al (2019)Prevalence and risk of pre-eclampsia and gestational hypertension in twin pregnancies:a population-based register study[J]. BMJ Open, 9(7):e029908. 10.1136/bmjopen-2019-029908
Rana S, Lemoine E, Granger J et al (2019)Pre-eclampsia:Pathophysiology, Challenges, and Perspectives[J].CircRes,124:1094–1112
Dadelszen P, Magee LA(2016)Preventing deaths due to the hypertensive disorders of Pregnancy[J]. Best Pract Res Clin Obstet Gynaecol, 36(10):83–102
Monden C, Pison G, Smits J(2021)Twin peaks: more twinning in humans than ever before[J]. Hum Reprod, 36(6):1666–1673. 10.1093/humrep/deab029
Hypertensive Disorders in Pregnancy Subgroup Society of Obstetrics and Gynecology, Chinese Medical Association(2020)Diagnosis and treatment of hypertension and pre-eclampsia in pregnancy: a clinical practice guideline. in China([J] Chin J Obstet Gynecol, 55(4): 227–238. 10.3760/cma.j.cn112141-20200114-00039
Webster K, Fishburn S, Maresh M et al(2019)Diagnosis and management of hypertension in pregnancy: summary of updated NICE guidance[J]. BMJ, 366: l5119. 10.1136/bmj.l5119
ACOG Practice bulletin No (2019) gestational hypertension and pre-eclampsia[J]. Obstet Gynecol 202(1):1. 10.1097/AOG.0000000000003018
Al-Rubaie Z, Askie LM, Ray JG et al(2016)The performance of risk prediction models for pre-eclampsia using routinely collected maternal characteristics and comparison with models that include specialised tests and with clinical guideline decision rules: a systematic review[J]. BJOG, 123(9): 1441–1452. 10.1111/1471-0528.14029
Chaemsaithong P, Sahota DS, Poon (2020) LC(2022)First trimester pre-eclampsia screening and prediction[J]. Am J Obstet Gynecol, 226(2S): S1071-S1097. e2. 10.1016/j. ajog. 07.020
Poon LC, Kametas NA, Maiz N et al (2009)First-trimester prediction of hypertensive disorders in pregnancy[J]. Hypertension, 53(5): 812–818. 10.1161/HYPERTENSIONAHA. 108.127977
Benkő Z, Wright A, Rehal A et al (2021) Prediction of pre-eclampsia in twin pregnancy by maternal factors and biomarkers at 11-13weeks' gestation: data from EVENTS trial[J]. Ultrasound Obstet Gynecol 57(2):257–265. 10.1002/uog.23531
Poon LC, Shennan A, Hyett JA et al (2019)The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia: A pragmatic guide for first-trimester screening and prevention[J]. Int J Gynaecol Obstet 145Suppl 1:1–33.10.1002/ijgo.12802
Gilbert JS Babcock SA,Granger JP(2007)Hypertension Produced by Reduced Uterine Perfusion in Pregnant Rats Is Associated With Increased Soluble Fms-Like Tyrosine Kinase-1 Expression[J]. Hypertension, 50(6),1142–1147
Buhimschi IA, Zhao G FunaiEF,(2008)Proteomic profiling of urine identifies specific fragments of SERPINA1 and albumin as biomarkers of pre-eclampsia[J]. Am J Obstet Gynecol, 199(5):551e1–55116
PerutzM F (1999) Trends Biochem[J] Sci 24:58–63
Rood KM Buhimschi CS,DibleT (2019)Congo Red Dot Paper Test for Antenatal Triage and Rapid Identifification of Pre-eclampsia. E Clin Med 8:47–56
ACOG Practice Bulletin Summary,222 (2020) Gestational hypertension and pre-eclampsia[J]. Obstet Gynecol 135(6):1492–1495
Francisco C, Wright D, Benkő Z et al(2017)Hidden high rate of pre-eclampsia in twin compared to singleton pregnancies. Ultrasound Obstet Gynecol 50(1):88–92
Chen J, Zhao D, Liu Y et al(2020)Screening for pre-eclampsia in low-risk twin pregnancies at early gestation[J]. Acta Obstet Gynecol Scand, 99(10): 1346–1353. 10.1111/aogs.13890
Queensland Clinical Guidelines( (2021) Hypertension and pregnancy. Guideline No.MN21.13-V9-R26. Queensland Health. February 2021. http://www.health.qld.gov.au/qcg
Khaliq OP, Phoswa WN, Moodley J(2023)The effectiveness of the Congo Red Dot paper test in hypertensive disorders of pregnancy:A systematic review and meta-analysis.Front. Reprod Health 5:112093710.3389/frph.2023.1120937
Wong STK, Sahota DS, Wong NKL, Wah IYM, Wang X, Lau SL, Chiu CPH, Ip PNP, Poon (2023) LC(2023)A point-of care urine test to predict pre-eclampsia development in Asian women with suspected pre-eclampsia. Pregnancy Hypertens 32:28–34 Epub 2023 Mar 30. PMID: 37003112

Download PDF

Reviewers agreed at journal
30 Jul, 2024
Reviewers invited by journal
30 Jul, 2024
Editor invited by journal
30 Jul, 2024
Editor assigned by journal
29 Jul, 2024
First submitted to journal
28 Jul, 2024

You are reading this latest preprint version

Predictive value of urine misfolded protein in preeclampsia in twin pregnancies

Status:

Version 1

Abstract

Objective

Methods

Results

Conclusion

Figures

Introduction

Objects and methods

Research Results

Discussion

Conclusion

Declarations

Advantages of this study :

Disadvantages of this study

References

Status:

Version 1