Urinary concentrations of phthalate metabolites in relation to preeclampsia and other hypertensive disorders of pregnancy in the environmental influences on child health outcomes (ECHO) program.

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.

Detection of Urinary Misfolded Proteins for Imminent Prediction of Preeclampsia in Pregnant Women With Suspected Cases: Protocol for a Prospective Noninterventional Study.

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.

Withstanding the test of time: Morning versus afternoon/evening urine protein-to-creatinine ratios in preeclampsia.

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.

A point-of care urine test to predict preeclampsia development in Asian women with suspected preeclampsia.

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.

Alterations in Antioxidant Micronutrient Concentrations in Placental Tissue, Maternal Blood and Urine and the Fetal Circulation in Pre-eclampsia.

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.

Oxidative nucleic acid damage as a biomarker for preeclampsia.

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.

Iodine deficiency in pregnancy along a concentration gradient is associated with increased severity of preeclampsia in rural Eastern Cape, South Africa.

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.

Diagnostic accuracy of urine dipstick tests for proteinuria in pregnant women suspected of preeclampsia: A systematic review and meta-analysis.

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.

Reduced urinary angiotensinogen excretion in preeclampsia.

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.

Congo red dot test in the early prediction and diagnosis of pre-eclampsia in a tertiary health care centre in India.

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 34 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€¯2.90 weeks and the time taken from CRD positive to development of PE was 4.92 ±â€¯2.54 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.

Differentiating Acute Rejection From Preeclampsia After Kidney Transplantation.

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.

Association of Urinary Strontium Levels with Pregnancy-induced Hypertension.

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.

Proteinuria may be an indicator of adverse pregnancy outcomes in patients with preeclampsia: a retrospective study.

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).

Relationship between proteinuria and optical coherence tomographic features of the chorioretina in patients with pre-eclampsia.

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.

Diagnostic accuracy of random urinary protein-to-creatinine ratio for proteinuria in patients with suspected pre-eclampsia.

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.

Interlaboratory bias of albuminuria and proteinuria in hypertensive pregnancy.

BACKGROUND: Measurement of proteinuria in women with hypertensive disorders of pregnancy is of major importance in the diagnosis and management of preeclampsia. Urinary protein/creatinine ratio, which is commonly used to detect kidney damage in preeclampsia, suffers from important analytical limitations, including poor harmonization of results between laboratories. Adoption of albuminuria could help reduce interlaboratory bias, since methods used to quantify it are better harmonized. METHODS: A total of 27 urinary samples collected from hypertensive women evaluated for preeclampsia were sent to four different clinical laboratories in Canada. Urinary proteins and albumin as well as urinary creatinine were measured in duplicates in one batch to calculate protein/creatinine (PCR) and albumin/creatinine (ACR) ratio. Statistical analyses were done to evaluate interlaboratory variability of urinary proteins and urinary albumin. RESULTS: Interlaboratory bias for urinary proteins ranged from 64.7% at low concentration to 3.9% at higher concentrations. In contrast, urinary albumin interlaboratory bias ranged from 29.2% to 4% from low to high concentrations. Coefficient of variation for urinary proteins reached a maximum of 91.5% in lower concentration while urinary albumin highest value was 42.7%. When looking at PCR and ACR ratio, eight samples had PCR measurement range that contained the diagnostic threshold used to detect kidney damage in HDP (30 mg/mmol), while only four samples had ACR ratio measurement range that contained the diagnostic threshold used outside of pregnancy in Canada (2 mg/mmol). CONCLUSION: Interlaboratory bias was lower for urinary albumin measurement compared to urinary proteins in hypertensive women evaluated for preeclampsia. Better harmonization with the use of albumin instead of protein measurement would reduce instances where results of different laboratories lead to opposite diagnosis of kidney damage in pregnancy.

Plasma CD59 concentrations are increased in preeclampsia with severe features and correlate with laboratory measures of end-organ injury.

OBJECTIVES: Dysregulation of CD59 may lead to increased complement-mediated end-organ injury in preeclampsia. We sought to determine if soluble CD59 concentrations are altered in preeclampsia with severe features. STUDY DESIGN: Observational case-control study, which enrolled subjects prospectively from six centers in Colombia from 2015 to 2016. Cases had preeclampsia with severe features and controls were either healthy or had chronic hypertension, gestational hypertension, or preeclampsia without severe features. Trained coordinators collected clinical data, blood and urine. Analyses were by test of medians and Spearman's correlation. MAIN OUTCOME MEASURES: Soluble CD59 concentration in plasma and urine, using enzyme linked immunosorbent assays. RESULTS: In total, 352 subjects were enrolled (104 cases; 248 controls). Compared to healthy women or those with other hypertensive disorders of pregnancy, women with preeclampsia with severe features had increased concentration of CD59 in plasma (P < 0.001) and decreased CD59 in urine (P = 0.01). In sub-group analyses, plasma CD59 concentrations were increased in preeclampsia with severe features compared to healthy controls (P < 0.001) or controls with either chronic hypertension (P = 0.002) or gestational hypertension (P = 0.02). Increased plasma CD59 concentrations correlated with decreased platelet count and increased lactate dehydrogenase, creatinine, aspartate transaminase, urine protein/creatinine ratio, systolic blood pressure and diastolic blood pressure (P < 0.01, all correlations). CONCLUSION: In women with preeclampsia with severe features, soluble CD59 concentrations were increased in plasma and decreased in urine, and plasma levels correlated with increased blood pressure and end-organ injury. Soluble CD59 concentrations may help identify a subset of women with preeclampsia that have altered regulation of terminal complement proteins.

Cystatin C as an indicator of renal damage in pre-eclampsia.

OBJECTIVE: To assess the predictive abilities of serum and urinary cystatin C levels for glomerular lesions in pregnant women with pre-eclampsia. METHODS: In this study, kidney function markers were compared between38 pregnant women with pre-eclampsia and 22 healthy pregnant women. RESULTS: The serum and urine levels of cystatin C and urea were significantly higher in the pre-eclampsia group than in the control group. Receiver operating characteristic curve analysis demonstrated that the serum cystatin C level (91.7%) had a superior diagnostic accuracy for pre-eclampsia than the other markers. CONCLUSION: Serum cystatin C level maybe a significant marker of pre-eclampsia.

Late pregnancy screening for preeclampsia with a urinary point-of-care test for misfolded proteins.

The aim was to describe and assess a new late pregnancy point-of-care urinary preeclampsia screening test. Urine samples were collected from a consecutive series of 1,532 pregnant women hospitalized at 20-41 weeks gestation in a Chinese single obstetric unit. A simple disposable Congo red based device was newly developed and employed to prospectively test misfolded proteins in pregnant women's urine. A total of 140 preeclampsia cases were clinically diagnosed, 101 severe and 87 pre-term. Detection and false positive rates were similar in the training and validation subsets with combined 74% and 3.0%. The detection rate was 83% in severe, 86% in pre-term, 49% and 50% in mild and term cases (P<0.0001) respectively. In conclusion, a simple point-of-care urinary test for misfolded proteins can be used to screen for preeclampsia in late pregnancy with very high screening performance. To the best of our knowledge, this is the first study to screen for preeclampsia using Congo red based device in Chinese pregnant population.