ABSTRACT
OBJECTIVES: To evaluate the correlation between maternal serum and urinary soluble Fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) levels and to assess their potential value in preeclampsia and fetal growth restriction. STUDY DESIGN: This case-control longitudinal prospective study was performed in 49 singleton pregnant women, divided into two clinical groups, low risk pregnancy (n = 23) and pregnancy complicated by preeclampsia (n = 26). Maternal serum and urinary sFlt-1 and PlGF levels were quantified by electrochemiluminescence. Every patient underwent an ultrasound for fetal biometry. Doppler assessment was done when estimated fetal weight was under the 10th centile. ROC curves were used to evaluate the predictive capability of serum and urinary angiogenic biomarkers and their ratios on preeclampsia. Linear regression was used to compare the values of serum and urinary sFlt-1 and PlGF and their ratios. RESULTS: Urine biomarkers were positively associated with their serum values, being the best associated urinary PlGF (R2 = 0.73), which also showed the highest predictive capability of preeclampsia of urine biomarkers (AUC 0.866). The predictive capability of urinary sFlt-1 was much lower (AUC 0.640), but increased when adjusting by serum creatinine, a more precise parameter (AUC 0.863). CONCLUSIONS: Urinary PlGF could be a lesser invasive alternative to circulating biomarkers to monitor pregnancies complicated with preeclampsia that need repeated controls of their pregnancy complication. Urinary sFlt-1 values need adjustment by serum creatinine to be reliable.
Subject(s)
Biomarkers , Creatinine , Placenta Growth Factor , Pre-Eclampsia , Vascular Endothelial Growth Factor Receptor-1 , Humans , Female , Pregnancy , Pre-Eclampsia/urine , Pre-Eclampsia/diagnosis , Pre-Eclampsia/blood , Vascular Endothelial Growth Factor Receptor-1/blood , Vascular Endothelial Growth Factor Receptor-1/urine , Placenta Growth Factor/blood , Placenta Growth Factor/urine , Adult , Biomarkers/urine , Biomarkers/blood , Case-Control Studies , Prospective Studies , Creatinine/urine , Creatinine/blood , Predictive Value of Tests , Longitudinal StudiesABSTRACT
PURPOSE: To assess a possible association between marked proteinuria and the risk of preeclampsia with severe features, as defined by the American College of Obstetricians and Gynecologists. METHODS: This retrospective study included data recorded at a tertiary university-affiliated hospital between 2017 and 2022. Women at or beyond 24 weeks of gestation with proteinuria (protein levels > 300 mg in a 24 h urine collection) and normal blood pressure during the initial 48 h of admission were included. Obstetrical and neonatal outcomes were compared between women with mild proteinuria (300-1000 mg/24 h) and marked proteinuria (≥ 1000 mg/24 h). RESULTS: Among the women with marked proteinuria (n = 48) compared to those with mild proteinuria (n = 108), the incidences were higher of preeclampsia (50.0% vs. 22.2%, p = 0.001) and of preeclampsia with severe features (18.8% vs. 2.8%, p < 0.001). In multivariate analysis that adjusted for maternal age, primiparity, multiple pregnancy, uric acid level > 6 mg/dL and aspirin treatment, marked proteinuria was a risk factor for preeclampsia with severe features (adjusted odds ratio [aOR] = 10.2, confidence interval [CI] 95% 1.9-54.0, p = 0.007) and for small-for-gestational-age infants (aOR = 2.4, 95% CI 1.02-5.6, p = 0.001). Among women with marked compared to mild proteinuria, rates were also higher of labor induction (58.3% vs. 25.9%, p < 0.001), indicated preterm delivery (41.7% vs. 25.0%, p = 0.04) and admission to the neonatal intensive care unit (44.1% vs. 25.8%, p = 0.017). CONCLUSIONS: Women with marked compared to mild isolated proteinuria showed higher risk of developing preeclampsia with severe features and of delivering small-for-gestational-age neonates.
Subject(s)
Pre-Eclampsia , Proteinuria , Humans , Adult , Proteinuria/epidemiology , Proteinuria/urine , Pre-Eclampsia/diagnosis , Pre-Eclampsia/epidemiology , Pre-Eclampsia/urine , Infant, Newborn , Retrospective Studies , Risk Factors , Pregnancy , Incidence , Pregnancy Outcome , Pregnancy Trimester, SecondABSTRACT
BACKGROUND: Phthalate exposure may contribute to hypertensive disorders of pregnancy (HDP), including preeclampsia/eclampsia (PE/E), but epidemiologic studies are lacking. OBJECTIVES: To evaluate associations of pregnancy phthalate exposure with development of PE/E and HDP. METHODS: Using data from 3,430 participants in eight Environmental influences on Child Health Outcomes (ECHO) Program cohorts (enrolled from 1999 to 2019), we quantified concentrations of 13 phthalate metabolites (8 measured in all cohorts, 13 in a subset of four cohorts) in urine samples collected at least once during pregnancy. We operationalized outcomes as PE/E and composite HDP (PE/E and/or gestational hypertension). After correcting phthalate metabolite concentrations for urinary dilution, we evaluated covariate-adjusted associations of individual phthalates with odds of PE/E or composite HDP via generalized estimating equations, and the phthalate mixture via quantile-based g-computation. We also explored effect measure modification by fetal sex using stratified models. Effect estimates are reported as odds ratios (OR) with 95% confidence intervals (95% CIs). RESULTS: In adjusted analyses, a doubling of mono-benzyl phthalate (MBzP) and of mono (3-carboxypropyl) phthalate (MCPP) concentrations was associated with higher odds of PE/E as well as composite HDP, with somewhat larger associations for PE/E. For example, a doubling of MCPP was associated with 1.12 times the odds of PE/E (95%CI 1.00, 1.24) and 1.02 times the odds of composite HDP (95%CI 1.00, 1.05). A quartile increase in the phthalate mixture was associated with 1.27 times the odds of PE/E (95%CI 0.94, 1.70). A doubling of mono-carboxy isononyl phthalate (MCiNP) and of mono-carboxy isooctyl phthalate (MCiOP) concentrations were associated with 1.08 (95%CI 1.00, 1.17) and 1.11 (95%CI 1.03, 1.19) times the odds of PE/E. Effect estimates for PE/E were generally larger among pregnancies carrying female fetuses. DISCUSSION: In this study, multiple phthalates were associated with higher odds of PE/E and HDP. Estimates were precise and some were low in magnitude. Interventions to reduce phthalate exposures during pregnancy may help mitigate risk of these conditions.
Subject(s)
Environmental Pollutants , Phthalic Acids , Pre-Eclampsia , Humans , Phthalic Acids/urine , Pregnancy , Female , Adult , Pre-Eclampsia/urine , Pre-Eclampsia/epidemiology , Environmental Pollutants/urine , Hypertension, Pregnancy-Induced/epidemiology , Hypertension, Pregnancy-Induced/urine , Maternal Exposure/statistics & numerical data , Male , Child Health , Cohort Studies , Environmental Exposure/analysis , Young Adult , ChildABSTRACT
BACKGROUND: Preeclampsia (PE) is one of the most common hypertensive diseases, affecting 2%-8% of all pregnancies. The high maternal and fetal mortality rates of PE are due to a lack of early identification of affected pregnant women that would have led to closer monitoring and care. Recent data suggest that misfolded proteins might be a promising biomarker for PE prediction, which can be detected in urine samples of pregnant women according to their congophilia (aggregated) characteristic. OBJECTIVE: The main purpose of this trial is to evaluate the value of the urine congophilia-based detection of misfolded proteins for the imminent prediction of PE in women presenting with suspected PE. The secondary objectives are to demonstrate that the presence of urine misfolded proteins correlates with PE-related maternal or neonatal adverse outcomes, and to establish an accurate PE prediction model by combining misfolded proteins with multiple indicators. METHODS: At least 300 pregnant women with clinical suspicion of PE will be enrolled in this prospective cohort study. Participants should meet the following inclusion criteria in addition to a suspicion of PE: ≥18 years old, gestational week between 20+0 and 33+6, and single pregnancy. Consecutive urine samples will be collected, blinded, and tested for misfolded proteins and other PE-related biomarkers at enrollment and at 4 follow-up visits. Clinical assessments of PE status and related complications for all participants will be performed at regular intervals using strict diagnostic criteria. Investigators and participants will remain blinded to the results. Follow-up will be performed until 42 days postpartum. Data from medical records, including maternal and fetal outcomes, will be collected. The performance of urine misfolded proteins alone and combined with other biomarkers or clinical variables for the prediction of PE will be statistically analyzed. RESULTS: Enrollment started in July 2023 and was still open upon manuscript submission. As of March 2024, a total of 251 eligible women have been enrolled in the study and enrollment is expected to continue until August 2024. Results analysis is scheduled to start after all participants reach the follow-up endpoint and complete clinical data are collected. CONCLUSIONS: Upon completion of the study, we expect to derive an accurate PE prediction model, which will allow for proactive management of pregnant women with clinical suspicion of PE and possibly reduce the associated adverse pregnancy outcomes. The additional prognostic value of misfolded proteins is also expected to be confirmed. TRIAL REGISTRATION: Chinese Clinical Trials Registry ChiCTR2300074878; https://www.chictr.org.cn/showproj.html?proj=202096. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/54026.
Subject(s)
Biomarkers , Pre-Eclampsia , Adult , Female , Humans , Pregnancy , Biomarkers/urine , Pre-Eclampsia/urine , Pre-Eclampsia/diagnosis , Predictive Value of Tests , Prospective Studies , Protein Folding , Clinical Trials as TopicABSTRACT
BACKGROUND: The early and accurate diagnosis of preeclampsia is crucial to avoid serious complications for both the mother and baby. However, the current diagnostic methods are limited, and there is a need for new diagnostic biomarkers. Previous studies have shown that cathepsin D (CTD) participates in the pathophysiology of preeclampsia and is present in urine samples, making it a potential biomarker for the disease. This study aimed to compare urinary and serum levels of CTD in preeclamptic and normotensive women and analyze its potential role as a diagnostic biomarker in preeclampsia. METHODS: The study included thirty-nine patients with preeclampsia and twelve normotensive pregnant women as controls. Biomarkers were determined using Multiplex Assay kit, and serum prolactin (Prl) and urinary TNF-α levels were also evaluated. Statistical analysis was conducted using the Mann-Whitney U test. RESULTS: We found that urinary and serum CTD levels were significantly higher in the preeclampsia group than in the normotensive group, suggesting that CTD could be a diagnostic biomarker for preeclampsia. No significant differences were found in the levels of serum prolactin or urinary TNF-α between the two groups. CONCLUSIONS: The study provides evidence that non-invasive biological samples such as urine can be used to improve new therapeutic strategies for the early management of preeclampsia.
Subject(s)
Biomarkers , Cathepsin D , Pre-Eclampsia , Prolactin , Humans , Female , Pre-Eclampsia/urine , Pre-Eclampsia/blood , Pre-Eclampsia/diagnosis , Pregnancy , Cathepsin D/urine , Cathepsin D/blood , Biomarkers/urine , Biomarkers/blood , Adult , Case-Control Studies , Prolactin/blood , Prolactin/urine , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factor-alpha/urine , Young AdultABSTRACT
OBJECTIVE: To assess the predictive accuracy of the sFlt-1/PlGF ratio cut-off 38 in addition to the standard-of-care spot urine protein/creatinine ratio (PCr) for multiple pregnancies in women with suspected pre-eclampsia. STUDY DESIGN: Post-hoc analysis of a prospective cohort study. MAIN OUTCOME MEASURES: Primary outcome was the occurrence of pre-eclampsia in one and four weeks after presentation with suspected pre-eclampsia. Test characteristics with 95% confidence intervals (CI) were calculated on pre-eclampsia development in one and four weeks. RESULTS: Twenty-three multiple pregnancies with suspected pre-eclampsia between 20 and 37 weeks gestation were included for analysis. Women who eventually developed pre-eclampsia had a significantly higher PCr (34.0 vs. 16.5, p = 0.015), sFlt-1 (17033 vs. 5270 pg/ml, p = 0.047) and sFlt-1/PlGF ratio (99 vs. 25, p = 0.033) at baseline. Furthermore, PCr ≥ 30 and sFlt-1/PlGF ratio > 38 was respectively seen in 1/16 (6.3 %) and 3/16 (18.8 %) of the women who did not develop pre-eclampsia. For predicting pre-eclampsia within one week the sFlt-1/PlGF ratio sensitivity was 75.0 % [95 % CI 19.4-99.4] and the negative predictive value 93.8 % [73.0-98.8], while no pre-eclampsia developed when PCr was < 30. Consequently, the combination of these tests did not lead to an improvement in test characteristics, with non-significant differences in positive predictive value (50.0 % [29.5-70.5] versus 80.0 % [37.3-96.4]) compared to PCr alone for pre-eclampsia development in one week. CONCLUSIONS: In addition to standard-of-care spot urine PCr measurements, this study has not been able to demonstrate that the sFlt-1/PlGF ratio cut-off 38 is of added value in the prediction of pre-eclampsia in multiple pregnancy. TRIAL REGISTRATION: Netherlands Trial Register (NL8308).
Subject(s)
Biomarkers , Creatinine , Placenta Growth Factor , Pre-Eclampsia , Predictive Value of Tests , Vascular Endothelial Growth Factor Receptor-1 , Humans , Female , Pregnancy , Pre-Eclampsia/urine , Pre-Eclampsia/diagnosis , Pre-Eclampsia/blood , Vascular Endothelial Growth Factor Receptor-1/blood , Adult , Biomarkers/urine , Biomarkers/blood , Placenta Growth Factor/blood , Placenta Growth Factor/urine , Creatinine/urine , Creatinine/blood , Prospective Studies , Proteinuria/urineABSTRACT
PURPOSE: New-onset proteinuria, as a pivotal sign of representative renal lesions in preeclampsia, is still the most common diagnostic tool for this condition and has been proven to be related to a significantly abnormal sFlt-1/VEGF ratio in circulation. At the same time, blood pressure control plays a vital role in the occurrence and evolution of proteinuria. Therefore, it is particularly helpful to investigate their interval, not only for performing urinalysis for protein more accurately but also for evaluating blood pressure as well as the aggravation of illness, as the related research is limited. METHODS: This retrospective study included 515 preeclampsia patients and 358 normotensive pregnant women who labored in the Second Hospital of Tianjin Medical University from January 2016 to January 2020. First, we described the onset circumstance of high blood pressure and proteinuria as well as the interval among the case group and the subgroups. Then, we determined whether there were significant differences in the basic information, laboratory test results, and newborns between the case and normal groups. Finally, multifactor ANOVA was used to determine the factors influencing the interval. RESULTS: 1. The two most common complications in preeclampsia were proteinuria (88.35%) and placental dysfunction (5.05%). Moreover, 72.04% of preeclampsia cases were diagnosed by abnormal blood pressure together with new-onset proteinuria. 2. The average interval between high blood pressure and proteinuria was 22 gestational days (from 0 to 106 days), and this interval was not significantly different between mild and severe PE (26 days vs. 21 days, P > 0.05) but significantly differed between early-onset and late-onset PE (9 days vs. 28 days, P < 0.05). 3. The number of prenatal visits, serum creatinine in the early trimester, gestational time and diastolic blood pressure value when increased blood pressure was initially detected may influence the interval between the onset of increased blood pressure and proteinuria. CONCLUSION: New-onset proteinuria was still the main parameter for identifying preeclampsia. The interval between increased blood pressure and proteinuria was probably related to the imbalance in the sFlt-1/VEGF ratio; therefore, we should pay attention to monitor proteinuria during the prenatal visits, especially for patients with a lower frequency of prenatal visits, higher serum creatinine in the early trimester, earlier onset and higher diastolic blood pressure at the initial onset of increased blood pressure.
Subject(s)
Pre-Eclampsia , Proteinuria , Humans , Female , Pregnancy , Pre-Eclampsia/diagnosis , Pre-Eclampsia/urine , Pre-Eclampsia/physiopathology , Proteinuria/urine , Retrospective Studies , Adult , Blood Pressure/physiology , Time Factors , Case-Control StudiesABSTRACT
OBJECTIVE: There are mixed findings regarding time preference for measuring spot urine protein to creatinine ratios (UPCR) in renal patients but no such literature among pregnant patients. We compare AM versus PM measurements for UPCR among pregnant patients with preeclampsia. STUDY DESIGN: This retrospective study included 163 patients diagnosed with preeclampsia. Laboratory tests of UPCR, urine specificity gravity, and uric acid were collected for these patients during the morning (AM) 12:00 AM (00:00) through 11:59 AM (11:59) and afternoon/evening (PM) 12:00 PM (12:00) through 11:59 PM (23:59). MAIN OUTCOME MEASURES: Outcomes were UPCR percentages indicative of preeclampsia, UPCR median values, abnormal uric acid, and normal urine specific gravity indicative of a quality sample for measuring UPCR. RESULTS: UPCR ≥ 0.3 indicative of preeclampsia significantly differed (p < 0.001) where the AM group (76.7 %) had a greater percentage than the PM group (52.8 %). Median UPCR significantly differed (p < 0.001) where the AM group had a greater median (0.44) than the PM group (0.32). None of the uric acid or urine specific gravity comparisons significantly differed between the AM and PM groups. Similar patterns occurred for subgroups of those with hypertension, nulliparous, and preeclampsia with severe features. CONCLUSION: We found that UPCR had greater median values and more values indicative of preeclampsia for AM measurements than PM measurements. Clinicians who use spot urine measurements and not 24-hour urine measurements should preferably measure UPCR in the AM rather than the PM.
Subject(s)
Pre-Eclampsia , Pregnancy , Female , Humans , Pre-Eclampsia/diagnosis , Pre-Eclampsia/urine , Creatinine/urine , Proteinuria/urine , Retrospective Studies , Uric AcidABSTRACT
OBJECTIVES: To evaluate the diagnostic performance and clinical utility of the urine Congo red dot test (CRDT) in predicting preeclampsia (PE) within 7 days, 14 days and 28 days of assessment. STUDY DESIGN: A prospective single center double blind non-intervention study conducted from January 2020 to March 2022. Urine congophilia has been proposed as a point-of-care test for the prediction and rapid identification of PE. In our study, urine CRDT and pregnancy outcomes were assessed in women presenting with clinical features of suspected PE after 20 weeks of gestation. RESULTS: Among the 216 women analyzed, 78 (36.1 %) women developed PE, in which only 7 (9.0 %) of them had a positive urine CRDT test. The median (IQR) interval between the initial test and the diagnosis of PE was significantly shorter for women with a positive urine CRDT compared with women with a negative urine CRDT (1 day (0-5 days) vs 8 days (1-19 days), P = 0.027). The negative predictive value of a negative urine CRDT test for PE within 7 days, 14 days and 28 days of assessment were 83.73 % (95 %CI 81.75 %- 85.54 %), 78.92 % (95 % confidence interval [CI] 77.07 %- 80.71 %) and 71.77 % (95 %CI 70.06 %- 73.42 %) respectively. The sensitivity of the urine CRDT in ruling in PE within 7 days, 14 days and 28 days of assessment were 17.07 % (95 %CI 7.15 %- 32.06 %), 13.73 % (95 %CI 5.70 %- 26.26 %) and 10.61 % (95 %CI 4.37 %- 20.64 %), respectively. CONCLUSIONS: Urine CRDT alone has high specificity yet low sensitivity in the short-term prediction of PE in women with suspected PE. Further studies are required to evaluate its clinical utility.
Subject(s)
Pre-Eclampsia , Pregnancy , Female , Humans , Male , Pre-Eclampsia/diagnosis , Pre-Eclampsia/urine , Prospective Studies , Pregnancy Outcome , Sensitivity and Specificity , Predictive Value of Tests , Congo Red , BiomarkersABSTRACT
Trace elements such as selenium and zinc are vital components of many enzymes, including endogenous antioxidants, and can interact with each other. Women with pre-eclampsia, the hypertensive disease of pregnancy, have been reported as having changes in some individual antioxidant trace elements during pregnancy, which are related to maternal and fetal mortality and morbidity. We hypothesised that examination of the three compartments of (a) maternal plasma and urine, (b) placental tissue and (c) fetal plasma in normotensive and hypertensive pregnant women would allow identification of biologically significant changes and interactions in selenium, zinc, manganese and copper. Furthermore, these would be related to changes in the angiogenic markers, placental growth factor (PlGF) and Soluble Fms-Like Tyrosine Kinase-1 (sFlt-1) concentrations. Venous plasma and urine were collected from healthy non-pregnant women (n = 30), normotensive pregnant controls (n = 60) and women with pre-eclampsia (n = 50) in the third trimester. Where possible, matched placental tissue samples and umbilical venous (fetal) plasma were also collected. Antioxidant micronutrient concentrations were measured by inductively coupled plasma mass-spectrometry. Urinary levels were normalised to creatinine concentration. Plasma active PlGF and sFlt-1 concentrations were measured by ELISA. Maternal plasma selenium, zinc and manganese were all lower in women with pre-eclampsia (p < 0.05), as were fetal plasma selenium and manganese (p < 0.05 for all); maternal urinary concentrations were lower for selenium and zinc (p < 0.05). Conversely, maternal and fetal plasma and urinary copper concentrations were higher in women with pre-eclampsia (p < 0.05). Differences in placental concentrations varied, with lower overall levels of selenium and zinc (p < 0.05) in women with pre-eclampsia. Maternal and fetal PlGF were lower and sFlt-1 higher in women with pre-eclampsia; maternal plasma zinc was positively correlated with maternal plasma sFlt-1 (p < 0.05). Because of perceptions that early- and late-onset pre-eclampsia have differing aetiologies, we subdivided maternal and fetal data accordingly. No major differences were observed, but fetal sample sizes were small following early-onset. Disruption in these antioxidant micronutrients may be responsible for some of the manifestations of pre-eclampsia, including contributing to an antiangiogenic state. The potential benefits of mineral supplementation, in women with deficient intakes, during pregnancy to reduce pre-eclampsia remain an important area for experimental and clinical research.
Subject(s)
Hypertension , Micronutrients , Placenta , Pre-Eclampsia , Selenium , Trace Elements , Female , Humans , Pregnancy , Antioxidants/metabolism , Biomarkers/metabolism , Copper , Hypertension/complications , Manganese , Micronutrients/metabolism , Micronutrients/pharmacology , Placenta/metabolism , Placenta Growth Factor , Pre-Eclampsia/blood , Pre-Eclampsia/metabolism , Pre-Eclampsia/urine , Trace Elements/metabolism , Vascular Endothelial Growth Factor Receptor-1 , Zinc/metabolismABSTRACT
Recent studies have reported that nucleic acid oxidation is elevated in preeclampsia. Furthermore, it is known that products of nucleic acid oxidation are eventually removed through the urine. The aim of this study was to check whether urine can be used as a non-invasive specimen to analyse nucleic acid oxidation in preeclampsia. We carried out a case-control study by enrolling preeclamptic pregnant (n = 31) and normotensive pregnant (n = 31) women. Urine samples from the study participants were collected and the levels of oxidised guanine species (a common product of nucleic acid oxidation) were determined by ELISA method. The urinary levels of oxidised guanine species were significantly higher in the preeclamptic pregnant group compared to the normotensive pregnant group (p = 0.001). The results were also analysed after stratifying the preeclamptic group in terms of severity and gestational age of onset. A significant difference was observed in both mild (p = 0.005) and severe preeclampsia (p = 0.01). However, a significant difference was observed only in the late onset (p = 0.001) and not in the early onset preeclampsia (p = 0.56). The results of this study show that oxidised guanine level is elevated in the urine of preeclamptic pregnant women. IMPACT STATEMENTWhat is already known on this subject? Nucleic acid oxidation is elevated in preeclampsia. However, the utility of urine (a non-invasive specimen) to analyse nucleic acid oxidation is not known.What do the results of this study add? This study shows that the levels of oxidised guanine (a marker of nucleic acid oxidation) are elevated in the urine of preeclamptic women.What are the implications of these findings for clinical practice and/or further research? Urinary levels of oxidised guanine may be developed as a non-invasive biomarker for preeclampsia.
Subject(s)
Nucleic Acids , Pre-Eclampsia , Biomarkers/urine , Case-Control Studies , Female , Guanine , Humans , Oxidative Stress , Pre-Eclampsia/diagnosis , Pre-Eclampsia/urine , PregnancyABSTRACT
BACKGROUND: Preeclampsia is a leading cause of maternal mortality and morbidity in South Africa. Iodine deficiency in pregnancy, which is amenable to correction through iodine supplementation, has been reported to increase the risk of preeclampsia. However, the association of iodine nutrition status with preeclampsia in South Africa has not been studied. METHODS: We enrolled 51 randomly selected normotensive pregnant controls at term together with 51 consecutively selected cases of preeclampsia and 51 cases of severe preeclampsia/eclampsia, all in the third trimester, from Mthatha Regional and Nelson Mandela Academic Hospital in the Eastern Cape Province. Urinary iodine concentration (UIC), serum thyroid-stimulating hormone (TSH), triiodothyronine (FT3), thyroxine (FT4) and thyroglobulin (Tg) levels were compared between cases and controls. RESULTS: The respective chronological and gestational ages at enrolment for normotensive, preeclampsia and severe preeclampsia/eclampsia participants were: age 23, 24 and 19 years (p = 0.001), and gestational age 38, 34, and 35 weeks (p < 0.001). The median gravidity was 1 for all three groups. The median UIC, FT4, FT3 revealed a decreasing and Tg a rising trend with the severity of preeclampsia (p < 0.05). TSH had a non-significant rising trend (p > 0.05). The respective median values for normotensive, preeclampsia and severe preeclampsia/eclampsia participants were UIC 217.1, 127.7, and 98.8 µg/L; FT4 14.2, 13.7, and 12. pmol/L; FT3 4.8, 4.4, and 4.0 pmol//L; Tg 19.4, 21.4, and 32. Nine microgram per liter; TSH 2.3, 2.3, and 2.5 mIU/L. UIC < 100 µg/L, Tg > 16 µg/L and FT4 < 11.3 pmol/L were independent predictors of preeclampsia/eclampsia syndrome. CONCLUSION: Women with severe preeclampsia/eclampsia had significantly low UIC and high Tg, suggesting protracted inadequate iodine intake. Inadequate iodine intake during pregnancy severe enough to cause elevated Tg and FT4 deficiency was associated with an increased risk of severe preeclampsia/eclampsia.
Subject(s)
Iodine/deficiency , Iodine/urine , Maternal Nutritional Physiological Phenomena , Nutritional Status , Pre-Eclampsia/blood , Pre-Eclampsia/urine , Adolescent , Adult , Case-Control Studies , Female , Humans , Patient Acuity , Pregnancy , South Africa/epidemiology , Thyroglobulin/blood , Thyrotropin/blood , Thyroxine/blood , Triiodothyronine/blood , Young AdultABSTRACT
OBJECTIVES: Dipstick tests are frequently used as bedside proteinuria tests to evaluate women suspected of preeclampsia and may inform diagnosis in low resource settings lacking laboratory facilities. This systematic review and meta-analysis aimed to (1) estimate the diagnostic accuracy of urine dipsticks in diagnosing proteinuria, (2) compare performance of different dipstick types and (3) estimate their related costs. METHODS: MEDLINE and EMBASE were searched up to August 1, 2020 for primary studies with cross-sectional diagnostic accuracy data on dipstick test(s) compared to a laboratory reference standard (24-hour protein ≥ 300 mg or protein-creatinine ratio ≥ 30 mg/mmol) in pregnant women ≥ 20 weeks of gestation suspected of preeclampsia. Risk of bias and applicability was assessed with QUADAS-2. Data were analysed using a bivariate model with hierarchical addition of covariates for subgroups. RESULTS: Nineteen studies were included. Protein-only dipsticks at 1 + threshold had a pooled sensitivity of 0.68 [95%CI: 0.57-0.77] and specificity of 0.85 [95% CI: 0.73-0.93] (n = 3700 urine samples, 18 studies). Higher specificity was found with automatedly (0.93 [95% CI: 0.82-0.98]) compared to visually (0.81 [95% CI: 0.65-0.91]) read dipsticks, whereas sensitivity was similar and costs were higher. The use of albumin-creatinine ratio (ACR) dipsticks was only reported in two studies and did not improve accuracy. Heterogeneity in study design and prevalence of preeclampsia amongst studies complicated interpretation of pooled estimates. CONCLUSION: Urine dipsticks performed poorly at excluding preeclampsia in hypertensive pregnant women. Further development of accurate and low-cost bedside proteinuria tests is warranted.
Subject(s)
Pre-Eclampsia/urine , Proteinuria/urine , Female , Humans , Point-of-Care Testing/standards , Pre-Eclampsia/diagnosis , Pregnancy , ROC Curve , Reagent StripsABSTRACT
OBJECTIVE: This study evaluated urinary angiotensinogen in preeclampsia. METHODS: Normal pregnant (n = 57) and preeclamptic patients (n = 31); Normal pregnant (n = 10) and preeclamptic rats (n = 10) were studied. Urinary angiotensinogen and plasma angiotensin II were assayed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Urinary angiotensinogen in preeclampsia patients (2.0 ± 1.1 ng/mg creatinine) was suppressed (*p < 0.05) compared to normal pregnant (2.7 ± 1.5 ng/mg creatinine). Plasma angiotensin II in preeclampsia patients (preeclampsia: 36.2 ± 7; normal pregnant: 48.1 ± 5 fmol/mL) was lower. The similar result was observed in preeclampsia rat model. CONCLUSIONS: The reduced urinary excretion of angiotensinogen was both in human preeclampsia patients and rat model of preeclampsia.
Subject(s)
Angiotensinogen/urine , Pre-Eclampsia/urine , Adult , Angiotensinogen/blood , Animals , Biomarkers/urine , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Female , Humans , Pre-Eclampsia/blood , Pregnancy , ROC Curve , RatsABSTRACT
OBJECTIVES: To demonstrate the use of urine congophilia quantification in the prediction and diagnosis of pre-eclampsia using Congo red dot test. STUDY DESIGN: A prospective cohort study in 378 consecutive pregnant women was conducted. All eligible, consenting women of gestational age between 10 and 34â¯weeks were enrolled in the study. The presence of urinary misfolded proteins was screened by a simple dot test technique on unsupported nitrocellulose membrane using Congo red dye. RESULTS: The urinary congophilia was increased in urine from women with pre eclampsia compared to healthy pregnant controls. The mean CRR value of pre eclamptic pregnant women (35.2⯱â¯9.4%) was five times higher than that of mean CRR value of normotensive pregnant women (6.9⯱â¯4.7%). The mean gestational age at which Congo red test showed positive was 26.95⯱â¯2.90â¯weeks and the time taken from CRD positive to development of PE was 4.92⯱â¯2.54â¯weeks of gestation. CONCLUSIONS: In our study, the CRD test was not only effective in predicting pre-eclampsia but was also useful in differentiating between pre-eclampsia and other forms of hypertension, as well as early onset and late onset pre-eclampsia, with positive predictive value of 80.36% and negative predictive value of 92.86.
Subject(s)
Congo Red , Pre-Eclampsia/diagnosis , Prenatal Diagnosis , Adolescent , Adult , Cohort Studies , Female , Humans , India , Pre-Eclampsia/urine , Predictive Value of Tests , Pregnancy , Prospective Studies , Tertiary Care Centers , UrinalysisABSTRACT
This retrospective study aimed to evaluate the correlation between ophthalmologic factors and proteinuria in patients with pre-eclampsia using swept-source optical coherence tomography (OCT) and OCT angiography. In total, 61 pregnant patients diagnosed with pre-eclampsia were recruited during their hospital stay. The authors investigated the relationship between urine protein-creatinine ratio (PCR) and chorioretinal measurements including choroidal thickness (CT), choroidal vascularity index (CVI), foveal avascular zone (FAZ), vascular density (VD), ganglion cell layer+ (GCL+) and GCL++. The associations between mean arterial pressure (MAP) and ophthalmologic factors were also evaluated. Central subfield CT of the right eye (p = 0.031) and paracentral CT of both eyes were related to higher PCR (≥1.35 mg/mg). A significant association with PCR after logarithm transformation was noted (r = 0.284, p = 0.026). Retinal measurements (FAZ, VD, GCL+ and GCL++) and CVI were not related with PCR. There was a positive association between MAP and PCR after logarithm transformation (r = 0.296, p = 0.021); however, chorioretinal factors were not related with MAP. In pregnant women with pre-eclampsia, CT using OCT is a novel factor that is correlated with PCR. Ocular structural alteration in patients with pre-eclampsia may be one of systemic vascular changes caused by pre-eclampsia rather than hypertension.
Subject(s)
Choroid/pathology , Macula Lutea/pathology , Pre-Eclampsia/diagnosis , Retina/pathology , Adult , Choroid/diagnostic imaging , Female , Fluorescein Angiography , Fovea Centralis/diagnostic imaging , Fovea Centralis/pathology , Humans , Macula Lutea/diagnostic imaging , Middle Aged , Pre-Eclampsia/diagnostic imaging , Pre-Eclampsia/pathology , Pre-Eclampsia/urine , Pregnancy , Proteinuria/urine , Retina/diagnostic imaging , Retinal Vessels/diagnostic imaging , Retinal Vessels/pathology , Tomography, Optical CoherenceABSTRACT
BACKGROUND: Proteinuria is one of the common manifestations of patients with preeclampsia (PE), but whether the severity of proteinuria is related to the pregnancy outcome of patients with preeclampsia remains controversial. The present study aimed to determine the relationship between 24-h proteinuria and adverse outcomes in patients with preeclampsia. METHODS: The present retrospective study included 329 pregnant women in Chongqing, China. Patients were divided into PE group and non-PE group. PE group was stratified into three subgroups based on the level of 24-h proteinuria. Correlation analysis was used to analyze the correlation between biochemical indexes and adverse pregnancy outcome, and Logistic regression analysis was used to analyze the risk factors of adverse pregnancy outcome. The receiver operating characteristic curve (ROC) was used to evaluate the ability of 24-h urinary protein to distinguish the adverse pregnancy outcome in patients with preeclampsia. RESULTS: (1) Between PE and non-PE group, cesarean section rate in PE group was significantly higher than that in non-PE group (84.4% vs. 25.9%, p < 0.001). Laboratory findings such as uric acid and creatinine level in PE group were higher than those in non-PE group. (2) Among mild (proteinuria < 0.3 g/24 h), moderate (0.3 g/24 h ⦠proteinuria < 2 g/24 h) and massive (proteinuria ⧠2 g/24 h) groups, the frequencies of induced labor (p = 0.006) and stillbirth (p = 0.002) increased with the increase of 24-h proteinuria. (3) Adverse outcomes were positively correlated with 24-h proteinuria (adverse maternal outcomes: r = 0.239, p = 0.002; adverse fetal outcomes: r = 0.336, p < 0.001). (4) The best 24-h proteinuria cutoff values to determine stillbirth, premature and fetal distress were 3965.0 mg/24 h, 984.75 mg/24 h and 1503.85 mg/24 h and their odds ratio (95% confidence interval) were 12.46 (3.46-44.88), 2.48 (1.15-5.37) and 10.02 (2.14-46.80), respectively. CONCLUSIONS: The severity of 24-h proteinuia may forecast adverse outcomes in women with preeclampsia. We suggest proteinuria should be retained as one of the monitoring indexes in patients with preeclampsia. TRIAL REGISTRATION: Retrospectively registered. (LTMCMTS202001).
Subject(s)
Pre-Eclampsia/urine , Pregnancy Outcome , Proteinuria/etiology , Adult , Area Under Curve , Birth Weight , Cesarean Section/statistics & numerical data , Delivery, Obstetric/statistics & numerical data , Female , Humans , Infant, Newborn , Infant, Newborn, Diseases/epidemiology , Logistic Models , Pregnancy , Pregnancy Complications/epidemiology , Procedures and Techniques Utilization , Proteinuria/epidemiology , ROC Curve , Retrospective Studies , Risk FactorsABSTRACT
OBJECTIVE: To evaluate the clinical and laboratory characteristics in pregnancy that differentiate preeclampsia from acute renal allograft rejection and to investigate the maternal, neonatal, and graft sequelae of these diagnoses. METHODS: We conducted a retrospective case-controlled registry study of data abstracted from Transplant Pregnancy Registry International deliveries between 1968 and 2019. All adult kidney transplant recipients with singleton pregnancies of at least 20 weeks of gestation were included. Acute rejection was biopsy proven and preeclampsia was diagnosed based on contemporary criteria. Variables were compared using χ2, Fisher exact, and Wilcoxon rank sum tests as appropriate. Multivariable linear regression was used to analyze preterm birth. Kaplan-Meier curves with log-rank test and Cox proportional hazards model were used to compare graft loss over time. RESULTS: There were 26 pregnant women with biopsy-confirmed acute rejection who were matched by the year they conceived to 78 pregnant women with preeclampsia. Recipients with acute rejection had elevated peripartum serum creatinine levels (73% vs 14%, P<.001), with median intrapartum creatinine of 3.90 compared with 1.15 mg/dL (P<.001). Conversely, only patients with preeclampsia had a significant increase in proteinuria from baseline. Although there were no significant differences in maternal outcomes, graft loss within 2 years postpartum (42% vs 10%) and long-term graft loss (73% vs 35%) were significantly increased in recipients who experienced acute rejection (P<.001 for both). The frequency of delivery before 32 weeks of gestation was 53% with acute rejection and 20% with preeclampsia. After controlling for hypertension and immunosuppressant use, acute rejection was associated with higher frequency of delivery at less than 32 weeks of gestation (adjusted odds ratio 4.04, 95% CI 1.10-15.2). CONCLUSION: In pregnancy, acute rejection is associated with higher creatinine levels, and preeclampsia is associated with increased proteinuria. Acute rejection in pregnancy carries a risk of prematurity and graft loss beyond that of preeclampsia for kidney transplant recipients. FUNDING SOURCE: The Transplant Pregnancy Registry International is supported in part by an educational grant from Veloxis Pharmaceuticals.
Subject(s)
Creatinine/blood , Graft Rejection/diagnosis , Kidney Transplantation/adverse effects , Pre-Eclampsia/diagnosis , Proteinuria/urine , Acute Disease , Adult , Case-Control Studies , Diagnosis, Differential , Female , Gestational Age , Graft Rejection/blood , Graft Rejection/pathology , Graft Rejection/urine , Graft Survival , Humans , Kaplan-Meier Estimate , Pre-Eclampsia/blood , Pre-Eclampsia/urine , Pregnancy , Premature Birth/etiology , Proportional Hazards Models , Registries , Retrospective Studies , Young AdultABSTRACT
Pregnancy-induced hypertension (PIH), including gestational hypertension and preeclampsia, accounts for the majority of maternal and perinatal morbidity and mortality. Strontium (Sr) has been recently associated with preeclampsia in a small group of women; however, the role of Sr in PIH is not fully understood and warrants further investigation. In this study, we examined the association between urinary Sr levels and PIH, and assessed the effect of maternal age on the association. Urinary Sr concentrations were measured in 5423 pregnant women before delivery by inductively coupled plasma mass spectrometry (ICP-MS). Logistic regression analysis adjusting for potential confounders was applied to explore the association between Sr and PIH, and to evaluate the Sr-PIH relationship stratified by maternal age. Among the participants, 200 (3.83%) women were diagnosed with PIH. Compared with non-PIH women, women who developed PIH had lower urinary Sr concentrations (131.26 vs. 174.98 µg/L creatinine, P<0.01). With the natural log-transformed urinary creatinine-standardized Sr concentrations increasing, the risk of PIH decreased significantly [adjusted OR=0.60 (95%CI: 0.51, 0.72)]. Furthermore, the significant association of Sr with PIH was found among women under 35 years (P<0.01). Our finding suggested that Sr may play a potential protective role in the pathogenesis of PIH, especially among young pregnant women under 35 years old.
Subject(s)
Hypertension, Pregnancy-Induced/urine , Pre-Eclampsia/urine , Strontium/urine , Adult , Body Mass Index , Creatinine/blood , Female , Gestational Age , Humans , Hypertension, Pregnancy-Induced/blood , Hypertension, Pregnancy-Induced/epidemiology , Hypertension, Pregnancy-Induced/pathology , Logistic Models , Pre-Eclampsia/epidemiology , Pre-Eclampsia/pathology , Pregnancy , Risk FactorsABSTRACT
PURPOSE: To evaluate the correlation between urine protein/creatinine ratio (UPCR) and proteinuria in a 24-h urine collection and to calculate the predicative accuracy of different cutoffs of UPCR for the diagnosis of proteinuria. METHODS: A retrospective cohort study including women who admitted for the evaluation for suspected preeclampsia (PET) beyond 20 weeks of gestation in a single tertiary center. Both UPCR test and quantification of proteinuria using 24-h urine collection were obtained during their index hospitalization no more than 48 h apart. Women with pre-existing diabetes mellitus, known renal disease or proteinuria prior to pregnancy or chronic hypertension were excluded. Predictive accuracy of UPCR for several cutoffs of proteinuria was evaluated. Multivariate logistic regression analysis was used to assess diagnostic accuracy of UPCR in sub-populations according to obstetrical characteristics. RESULTS: Overall 463 patients were included. Of them 316 (68.3%) have 24-h urine protein collection of ≥ 300 mg/day. Mean gestational age at evaluation was 34.0 ± 3.4 weeks. Median (and interquartile range) time interval between UPCR and 24-h urine collection was 1.8 (1.6-1.9) days. Sensitivity and specificity of UPCR of 0.3 for predicting proteinuria ≥ 300 mg/day were 90.1% and 63.3%, respectively. The corresponding values for difference proteinuria cutoffs: ≥ 1000 mg/day and 5000 mg/day were 98.4, 100% and 29.1, 36.0%, respectively. The optimal UPCR thresholds for 24-h urine protein collection of ≥ 300 mg/day, ≥ 1000 mg/day and 5000 mg/day were 0.31, 0.70 and 2.49, respectively. The predictive accuracy of UPCR > 0.30 in predicting proteinuria was unaffected by demographic and obstetrical characteristics as maternal age, pre-pregnancy BMI, gestational age at examination, creatinine levels or by multiple gestation [adjusted OR 18.27 (95% CI 9.97-33.47)]. CONCLUSION: UPCR was strongly correlated with various cutoffs of proteinuria obtained by 24-h urine collection. UPCR cutoff varied depending on the specific measured outcome. This correlation was not affected by gestational age at examination.