C-reactive protein level predicts need for medical intervention in pregnant women with SARS-CoV2 infection: A retrospective study.

AIM: To make effective use of the limited available hospital space during the Coronavirus disease 2019 (COVID-19) pandemic, we conducted this study to investigate the laboratory indices that identify pregnant women with SARS-CoV2 infection who require medical intervention. METHODS: We carried out a retrospective analysis of pregnant women positive for COVID-19 who were admitted to Hokkaido University Hospital from September 2020 to June 2021. Medical interventions included oxygen supplementation, systemic corticosteroids, or supplemental liquids to treat infection-related symptoms. RESULTS: Forty-two infected pregnant patients were admitted to the hospital, half of whom required medical intervention (n = 21). Fever, C-reactive protein (CRP), and platelet count are all associated with need for medical intervention. Of the 32 patients with a fever of ≥37.5°C on days 0-3 after onset of syndromes, 22 (69%) continued to have a fever on days 4-6, of which 19 (86.4%) required medical intervention. CRP level on days 4-6 predicted the presence or absence of medical intervention (area under the receiver operating characteristic curve = 0.913), with a sensitivity of 81% and specificity of 100% at a CRP cutoff of 1.28 mg/dL. CONCLUSIONS: The need for medical intervention in pregnant patients can be predicted with high accuracy using a CRP cutoff of 1.28 mg/dL on days 4-6 after onset of syndromes. The presence of fever also may be an easy marker for selecting subjects who need or will need therapeutic intervention. These could be an effective triage method to determine appropriate indications for the hospitalization of pregnant women in future outbreaks.

Cervical polyps in early pregnancy are a risk factor for late abortion and spontaneous preterm birth: A retrospective cohort study.

OBJECTIVE: To determine the association between cervical polyps in early pregnancy and late abortion and spontaneous preterm birth (SPTB). We also aimed to explore the relationship between cervical polyps and cervical insufficiency in the second trimester. METHODS: We conducted a retrospective cohort study of 2941 singleton pregnant women between January 2010 and December 2015. The frequency of late abortion and SPTB (before 28, 34, or 37 weeks of pregnancy) was compared between the two groups of 142 (4.8%) patients who had cervical polyps early in the pregnancy (P group) and 2799 who did not (non-P group). Multivariate analysis was performed to identify risk factors for late abortion and SPTB. RESULTS: The incidence of late abortion and SPTB was significantly higher in the P group than in the non-P group. Cervical polyps in early pregnancy were selected as independent risk factors for late abortion and SPTB before 28, 34, or 37 weeks of pregnancy. The P group had a significantly higher rate of cases requiring therapeutic cervical cerclage than the non-P group. CONCLUSION: Cervical polyps in early pregnancy are risk factors for late abortion and SPTB. They are also associated with the occurrence of cervical insufficiency.

Association between pre-pregnancy body mass index and gestational weight gain and perinatal outcomes in pregnant women diagnosed with gestational diabetes mellitus: The Japan Environment and Children's Study.

AIMS/INTRODUCTION: We investigated the association between gestational diabetes mellitus (GDM) and perinatal outcomes stratified by pre-pregnancy body mass index (BMI) and/or gestational weight gain (GWG). MATERIALS AND METHODS: Data from the national birth cohort in the Japan Environment and Children's Study from 2011 to 2014 (n = 85,228) were used. Japan uses the GDM guidelines of the International Association of Diabetes and Pregnancy Study Groups. The odds ratios (ORs) of perinatal outcomes were compared between women with and those without GDM. RESULTS: The OR (95% confidence interval) of having a small for gestational age infant in the GDM group with a pre-pregnancy BMI of ≥25.0 kg/m2 and insufficient GWG (<2.75 kg) was 1.78 (1.02-3.12). The OR of having a large for gestational age infant of the same BMI group with excessive GWG (>7.25 kg) was 2.04 (1.56-2.67). The OR of hypertensive disorders of pregnancy was higher in women with a BMI ≥18.5 kg/m2 in the GDM group than in the non-GDM group. CONCLUSIONS: Large for gestational age and hypertensive disorders of pregnancy were associated with pre-pregnancy BMI and GWG in either normal weight or overweight/obese women, and the relationship was strengthened when GDM was present. Women with GDM and a BMI of ≥25.0 kg/m2 are at risk of having small for gestational age and large for gestational age infants depending on GWG.

Survey of attitudes of individuals who underwent remote prenatal check-ups and consultations in response to the COVID-19 pandemic.

AIM: Perinatal telemedicine efforts have commenced worldwide in response to the COVID-19 pandemic. As there have been no prior studies on the acceptance of telemedicine by pregnant women, we conducted this survey to investigate the same. METHODS: We conducted an anonymous questionnaire survey of pregnant women who underwent telemedicine check-ups from March 4 to June 30, 2020, using a mobile fetal heart rate monitor and video call system through the Hokkaido University Hospital. RESULTS: Out of the 77 individuals who received prenatal telemedicine check-ups, 54 individuals (70%) had complications, and 64 individuals (83%) consented for the questionnaire survey. In the video call system, 18 individuals (28%) were found to be unwell and 17 individuals (27%) experienced difficulty using the mobile fetal heart rate monitoring device. Assuming scores for face-to-face consultations were five out of 10, the mean score for satisfaction was 4.2, but 19 (30%) women felt equal or greater satisfaction with face-to-face consultations. If not for the threat of COVID-19, only four individuals (6%) proactively expressed a desire for telemedicine, with a significantly less demand observed among primiparous women than multiparous women. The permissible additional financial burden enabling telemedicine was $10 or less for 80% of subjects. CONCLUSION: In this small preliminary study, 30% of the pregnant women felt equal or greater satisfaction with telemedicine than face-to-face consultations. A stronger demand for telemedicine was exhibited by multiparous women than primiparous women. Thus, a system that would be advantages by limiting subjects and enabling low-cost examinations is required for making perinatal telemedicine more popular.

Mild thrombocytopenia indicating maternal organ damage in pre-eclampsia: a cross-sectional study.

BACKGROUND: Currently, there is a disagreement between guidelines regarding platelet count cut-off values as a sign of maternal organ damage in pre-eclampsia; the American College of Obstetricians and Gynecologists guidelines state a cut-off value of < 100 × 109/L; however, the International Society for the Study of Hypertension in Pregnancy guidelines specify a cut-off of < 150 × 109/L. We evaluated the effect of mild thrombocytopenia: platelet count < 150 × 109/L and ≥ 100 × 109/L on clinical features of pre-eclampsia to examine whether mild thrombocytopenia reflects maternal organ damage in pre-eclampsia. METHODS: A total of 264 women were enrolled in this study. Participants were divided into three groups based on platelet count levels at delivery: normal, ≥ 150 × 109/L; mild thrombocytopenia, < 150 × 109/L and ≥ 100 × 109/L; and severe thrombocytopenia, < 100 × 109/L. Risk of severe hypertension, utero-placental dysfunction, maternal organ damage, preterm delivery, and neonatal intensive care unit admission were analyzed based on platelet count levels. Estimated relative risk was calculated with a Poisson regression analysis with a robust error. RESULTS: Platelet counts indicated normal levels in 189 patients, mild thrombocytopenia in 51 patients, and severe thrombocytopenia in 24 patients. The estimated relative risks of severe thrombocytopenia were 4.46 [95 % confidence interval, 2.59-7.68] for maternal organ damage except for thrombocytopenia, 1.61 [1.06-2.45] for preterm delivery < 34 gestational weeks, and 1.35 [1.06-1.73] for neonatal intensive care unit admission. On the other hand, the estimated relative risks of mild thrombocytopenia were 0.97 [0.41-2.26] for maternal organ damage except for thrombocytopenia, 0.91 [0.62-1.35] for preterm delivery < 34 gestational weeks, and 0.97 [0.76-1.24] for neonatal intensive care unit admission. CONCLUSIONS: Mild thrombocytopenia was not associated with severe features of pre-eclampsia and would not be suitable as a sign of maternal organ damage.

Feasibility and safety of urgently initiated maternal telemedicine in response to the spread of COVID-19: A 1-month report.

AIM: In Hokkaido, Japan, the number of people suffering from coronavirus disease 2019 (COVID-19) is rapidly increased, and by the end of February 2020, there were already 70 confirmed cases of the disease. We investigated the safety of urgently initiated maternal telemedicine in preventing the spread of the coronavirus infection. METHODS: This retrospective, single-institution study examined maternal telemedicine at the department of obstetrics of the Hokkaido University Hospital from March 4 to April 2, 2020. The physicians remotely examined the pregnant women from their homes using a visual communication system which kept communication confidential, performed prenatal checkup and administered medical care according to their various blood pressures, weights and cardiotocograms. RESULTS: Forty-four pregnant women received a total of 67 telemedicine interventions. Thirty-two pregnant women (73%) had complications, and 22 were primiparas (50%). Telemedicine interventions were provided 19 times at less than 26 weeks of gestation, 43 times between 26 and 36 weeks of gestation and 5 times after 37 weeks of gestation. There was one case with an abnormality diagnosed during the remote prenatal checkups, and the patient was hospitalized on the same day. However, there were no abnormal findings observed in mothers and children during the other 66 remote prenatal checkups and medical care. CONCLUSION: Maternal telemedicine can be safely conducted in pregnant women who are at risk of having an underlying disorder or fetal abnormality 1 month following the start of the attempt. It should be considered as a form of maternal medical care to prevent the spread of COVID-19.

Hypoproteinemia as a parameter of poor perinatal/neonatal outcomes in women with preeclampsia diagnosed as hypertension plus proteinuria.

OBJECTIVES: To investigate the relationship between serum total protein (TP) levels and maternal/neonatal outcomes among pregnant women with preeclampsia. STUDY DESIGN: TP was measured at preeclampsia diagnosis and delivery in 94 women with singleton pregnancies and preeclampsia as hypertension with proteinuria who delivered at ≥ 22 gestational weeks (GWs). As a control group, measurements were also made in 188 women with singleton pregnancies without hypertension and/or proteinuria. MAIN OUTCOME MEASURES: The relationship between serum TP levels and maternal outcomes. RESULTS: Serum TP levels showed a significantly negative relationship with urine protein-to-creatinine (P/C) ratio at preeclampsia diagnosis and delivery. Serum TP levels at delivery in the preeclampsia group (53 ± 7 g/L) were lower than in the control group (61 ± 4 g/L, P < 0.0001). In each group, there was no relationship between the daily decrease in TP and the daily increase maternal body weight. However, there was a positive relationship between the daily increase in P/C ratio and the daily increase in maternal body weight in the preeclampsia group (P = 0.0021). Severe hypoproteinemia at preeclampsia diagnosis was a predictor of abruptio placentae (TP < 49 g/L; odds ratio, 21.3) and peripartum cardiomyopathy (TP < 45 g/L; odds ratio, 43.5). Furthermore, women with severe hypoproteinemia at delivery had higher morbidity due to pulmonary edema (TP < 55 g/L; odds ratio, 26.4) and central serous chorioretinopathy (TP < 42 g/L; odds ratio, 264). CONCLUSIONS: Serum TP levels and proteinuria severity at preeclampsia diagnosis and delivery showed a positive relationship and predicted poor maternal outcome.

Glycemic control and fetal growth of women with diabetes mellitus and subsequent hypertensive disorders of pregnancy.

Pregnant women with diabetes mellitus (DM) are at high risk for hypertensive disorder of pregnancy (HDP). Women with poor control DM sometimes have heavy-for-dates infants. However, women with HDP sometimes have light-for-dates infants. We aim to clarify the relationship between glycemic control and fetal growth in women with DM and/or subsequent HDP. Of 7893 women gave singleton birth at or after 22 gestational weeks, we enrolled 154 women with type 1 DM (T1DM) or type 2 DM (T2DM) whose infants did not have fetal abnormalities. Among women with T1DM or T2DM, characteristics of the three groups (with HDP, without HDP, and with chronic hypertension [CH]) were compared. No women with T1DM had CH, but 19 (17.4%) of 109 with T2DM did. HDP incidence was similar between women with T1DM (22.2%) and T2DM without CH (16.7%). Among women with T1DM, the incidences of fetal growth restriction (FGR) with and without HDP were similar. However, among women with T2DM without CH, this incidence was significantly higher among those with HDP (33.3%) than among those without HDP (5.3%), was significantly more common with HbA1c levels at first trimester ≥ 7.2% (33.3%) than with those < 7.2% (5.6%), and significantly more numerous without pre-pregnancy therapies for DM (23.3%) than with them (3.3%). Among women with T2DM and HDP, those with FGR had smaller placenta SDs and higher insulin dosages at delivery than those without light-for-dates. In multivariate analysis, the presence of diabetic nephropathy was a predictor of T1DM and HDP (P = 0.0105), whereas HbA1c levels ≥ 7.2% before pregnancy was a predictor of T2DM and HDP (P = 0.0009). Insulin dosage ≥ 50U/day at delivery (P = 0.0297) and the presence of HDP (P = 0.0116) independently predicted T2DM, HDP, and FGR development. Insufficient pre-pregnancy treatment of DM increased the risk of HDP.

Low antithrombin activity before delivery predicts subsequent hypertensive disorders in pregnancy.

OBJECTIVE: To examine whether laboratory parameters can predict the onset of recurrent hypertensive disorders of pregnancy (HDP). METHODS: A retrospective study of 257 women with consecutive deliveries at a hospital in Sapporo, Japan, between 2009 and 2017. Women were divided into four groups according to whether or not they had HDP in the first and second peripartum periods (HDP-HPD, HDP-Non, Non-HDP, Non-Non). HDP was defined as gestational hypertension and/or proteinuria. Laboratory parameters measured on the day of or 1 day before delivery were compared between peripartum-1 and peripartum-2. RESULTS: Frequency of HDP in peripartum-2 was higher among the 24 (9.3%) women with HPD in peripartum-1 (6/24, 25.0%) than among the 233 (90.7%) women without (3/233, 1.3%) (P<0.001). In peripartum-1, women with HDP had lower median antithrombin activity than those without (74% vs 89%, P=0.021). Antithrombin activity in peripartum-1 was also lower in the HDP-HDP (67%) than in the HDP-Non (79%) group (P=0.021). Antithrombin activities of 77% or less at the first delivery predicted HDP in peripartum-1 (P<0.001) and 70% or less predicted HDP in peripartum-2 (P=0.018). CONCLUSION: Women with HDP in peripartum-1 had a higher incidence of HDP recurrence. Low antithrombin before a first delivery might predict recurrent HDP in a second pregnancy.

Maternal Anemia and Coagulation/Fibrinolysis after Fetoscopic Laser Photocoagulation for Twin-to-Twin Transfusion Syndrome.

AIM: This study was performed to evaluate maternal changes in laboratory characteristics after fetoscopic laser photocoagulation (FLP) for twin-to-twin transfusion syndrome (TTTS). METHODS: A retrospective review was conducted among 30 women with monochorionic diamniotic twin pregnancy with TTTS who underwent FLP at 16-26 weeks of gestation. Maternal laboratory parameters were measured before and after FLP. RESULTS: The pre-FLP mean hemoglobin level (10.0 g/dL), hematocrit level (30.0%), platelet count (229 × 109/mL), fibrinogen level (461 mg/dL), and antithrombin activity (96.8%) decreased after FLP (8.5 g/dL, 25.5%, 204 × 109/mL, 403 mg/dL, and 83.6%, respectively) and returned to normal spontaneously within 2 weeks (9.6 g/dL, 29.4%, 293 × 109/mL, 460 mg/dL, and 102.4%, respectively). The D-dimer level before FLP (2.41 µg/mL) increased after FLP (4.28 µg/mL), and the elevated level was maintained for 2 weeks (3.24 µg/mL). The symptomatic venous thromboembolism (VTE) was not detected after FLP in any of the 30 patients. However, one woman had pulmonary embolism after subsequent cesarean section. CONCLUSION: Changes in maternal anemia and coagulation/fibrinolysis after FLP for TTTS returned to normal spontaneously within 2 weeks. Maternal elevation of D-dimer level after FLP might be a warning indicator of VTE.

Increase in the number of patients diagnosed using the new classification of hypertensive disorders of pregnancy in Japan.

AIM: This study aimed to examine how the number of patients diagnosed with pre-eclampsia increased according to the Japanese classification of hypertensive disorders of pregnancy (HDP) that was revised in 2018. The effect of new classification on perinatal outcomes was also analyzed. METHODS: We enrolled 181 women with HDP who delivered at Hokkaido University Hospital between February 2011 and December 2017. All women were reclassified on the basis of the new classification, in which proteinuria was not required to diagnose pre-eclampsia in patients with maternal organ damage. The number and reasons of reclassification and the admission rate to the neonatal intensive care unit (NICU) and gestational age (GA) at the onset of HDP and at delivery were analyzed. RESULTS: In this cohort, 17 (9.4%) of 181 women with HDP were reclassified. Low platelet count (41.2%) and uteroplacental dysfunction (41.2%) were the two main causes for reclassification. GA at the onset of HDP (33.6 [29.9-36.1] weeks vs 37.4 [35.7-38.4] weeks; P < 0.001) and at delivery (35.9 [32.4-37.3] weeks vs 38.1 [37.3-39.6] weeks; P < 0.001) were significantly earlier in women with reclassification than women without reclassification. The NICU admission rate was higher in women with reclassification than women without reclassification (70.6% vs 20.4%; P < 0.001). CONCLUSION: Almost 10% of pregnant women were newly diagnosed with pre-eclampsia as per the new Japanese classification of HDP. Women with reclassification as pre-eclampsia had a greater risk of preterm delivery and NICU admission than those who were not reclassified.

Fetal middle cerebral artery peak systolic velocity as a predictor of fetal anemia in unselected women giving birth at or near term.

OBJECTIVE: This study was performed to evaluate the application of fetal middle cerebral artery peak systolic velocity (MCA-PSV) for prediction of newborn anemia with umbilical cord blood hemoglobin concentration at birth (UCB-Hb) < 10.0 g/dL among infants born at gestational week (GW) ≥ 36 to unselected women. MATERIALS AND METHODS: We reviewed the medical charts of 699 women giving birth to singleton infants at GW ≥ 36 with available data on MCA-PSV measured at GW ≥ 25 at the discretion of the attending physician. Multiple of the median (MoM) MCA-PSV (MCA-PSV MoM) > 1.5 was defined as a positive MCA-PSV test result. RESULTS: The MCA-PSV test was applied 2309 times (313 and 1996 times during second and third trimesters, respectively) in 699 women. The results were positive in 4.4% (102/2309) of tests and at least once in 9.9% (69/699) of women. Anemic infants were born to one (1.4%) and six (1.0%) of 69 and 630 women with and without at least one positive test result, respectively. MoM determined 4, 3, and 2 weeks before birth showed significant weak negative correlations with UCB-Hb at birth (correlation coefficient: 0.298-0.325). CONCLUSIONS: Among unselected women giving birth at or near term, the MCA-PSV test was unsatisfactory for prediction of newborn anemia in this retrospective observational study.

Serum placental growth factor and soluble fms-like tyrosine kinase 1 at mid-gestation in healthy women: Association with small-for-gestational-age neonates.

AIM: This study was performed to determine the associations between serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) levels at mid-gestation with the risk of small-for-gestational-age (SGA) neonates born at gestational week (GW) ≥ 36 in healthy women. METHODS: PlGF and sFlt-1 concentrations were determined at GW 24-27 in 183 women with births at GW ≥ 36, but without gestational diabetes mellitus and hypertension. RESULTS: Thirteen (7.1%) SGA neonates were born. Median (range) GW at blood sampling was similar between women with and without SGA (25 [24-25] and 24 [24-27], respectively, P = 0.671). Pre-pregnancy body mass index (BMI) and PlGF levels were significantly lower in women with than without SGA, while sFlt-1 levels and sFlt-1 : PlGF ratio (sFlt-1/PlGF) did not differ significantly between the two groups. PlGF and sFlt-1/PlGF, but not BMI or sFlt-1, showed significant correlations with birthweight z-score; the correlation was positive for PlGF and negative for sFlt-1/PlGF. Women with PlGF level < 10th percentile and those with sFlt-1/PlGF level > 90th percentile showed significantly increased risk of SGA compared to those with respective counterpart characteristics; relative risk was 3.8 (95% confidence interval, 1.3-11.3; 21% [4/19] vs 5.5% [9/164]) for PlGF and 7.9 (95% confidence interval, 3.0-20.8, 33.3% [6/18] vs 4.2% [7/165]) for sFlt-1/PlGF. CONCLUSION: Maternal PlGF and sFlt-1/PlGF determined during GW 24-27 were associated with the risk of SGA neonates born at GW ≥ 36, even in women with uncomplicated pregnancies.

Effects of childbirth on podocyturia in women with normotensive, uncomplicated pregnancies.

Changes in hemodynamics and blood pressure occur shortly before and after childbirth regardless of the mode of delivery. This study aimed to test the hypothesis that parturition induces a temporal increase in podocyturia monitored by podocyte-specific protein podocin mRNA expression levels (Pod-mRNA). A total of 105 urine specimens, consisting of 43 and 62 from 18 and 20 otherwise healthy women with vaginal delivery (VD) and elective cesarean delivery (ECS), respectively, were studied. Determination of urine protein and creatinine (Cr) concentrations and quantitative analyses of Pod-mRNA, nephrin mRNA (Nep-mRNA), synaptopodin mRNA (Syn-mRNA), and aquaporin 2 mRNA expression were performed using RT-PCR in pelleted urine samples. Levels of mRNA expression were corrected by urine Cr concentration. Podocyturia increased significantly, concomitant with a significantly decreased Nep:Pod-mRNA ratio (NPR) in the urine, collected immediately before or after childbirth regardless of the delivery mode compared with urine collected before commencement of labor or on postpartum day 3 or later. Podocyturia was significantly negatively correlated with NPR [correlation coefficient (r) = -0.614/-0.750 for VD/ECS women, respectively], as well as the Syn:Pod-mRNA ratio. Systolic blood pressure exceeded 140 mmHg during labor in 50% of VD women, and mean arterial pressure was significantly positively correlated with podocyturia during labor in VD women (r = 0.733). Thus parturition induces a transient increase in urine podocytes with reduced Nep- and Syn-mRNA expressions. Glomerular podocytes with reduced Nep- and Syn-mRNA levels were suggested to be likely to detach from the glomerular basement membrane around childbirth.

Risk factors for central serous chorioretinopathy in pregnant Japanese women.

AIM: This study was performed to determine risk factors for central serous chorioretinopathy (CSC) in pregnant women. METHODS: This retrospective observational study was performed in a cohort of all 1881 women giving birth at a single center. The hospital database was searched to abstract all women diagnosed with pre-eclampsia (PE) as well as those visiting the eye clinic during the current pregnancy. Medical chart review was performed in all women diagnosed with CSC and PE. RESULTS: PE developed in 73 (3.9%) women, six (8.2%) of whom visited the eye clinic for problems occurring in the current pregnancy; 47 of 1808 (2.6%) women without PE visited the eye clinic (P  = 0.015). Four women were identified as having developed CSC after onset of PE, and none of those without PE developed CSC (5.5% [4/73] vs 0.0% [0/1808], respectively, P <  0.0001). Stepwise regression analysis selected four risk factors for CSC: hematocrit value > 38.0% (odds ratio [OR], 22.9; 95% confidence interval [CI], 2.12-247), serum creatinine > 0.7 mg/dL (OR, 21.7; 95%CI, 1.12-422), time interval from diagnosis of PE until delivery > 14 days (OR, 20.0; 95%CI, 1.87-214), and urine protein : creatinine ratio (mg/mg) > 4.5 (OR, 15.7; 95%CI, 0.81-304). Hematocrit value > 38.0% was finally identified as the only independent risk factor (OR, 22.9; 95%CI, 2.12-1716) for CSC in PE women. CONCLUSION: CSC was likely to occur in PE women, especially in those with hemoconcentration as a result of plasma leakage from the circulating blood due to increased vascular permeability.

Increased podocyturia in pregnant women compared to non-pregnant women.

AIM: Hyperfiltration is a cause of podocyturia and occurs physiologically in the kidney of pregnant women. Podocyturia is increased in preeclamptic pregnancies, but it is unclear whether there is also any increase in uncomplicated pregnancies. This study was performed to examine whether podocyturia and urine aquaporin 2 mRNA expression are increased in healthy pregnant women (PW) compared to healthy non-pregnant women (NPW). METHODS: Eleven urines obtained from 11 NPW and longitudinal 76 urines from 40 PW with uncomplicated pregnancies (median number [range] of urine samples/person, 2 [1 - 3]) were studied. Determination of protein and creatinine concentrations and number of cells in urine other than blood cells, and quantitative analyses of the mRNA expression of aquaporin 2 (AQP2-mRNA), podocin (Pod-mRNA), and nephrin (Nep-mRNA) were performed using RT-PCR in pelleted urine samples. Podocyturia was monitored with urine Pod- and Nep-mRNA expression levels normalized relative to creatinine. RESULTS: Urine cell density and urine AQP2-, Pod-, and Nep-mRNA expression normalized relative to creatinine were significantly higher in PW than NPW. The number of cells per milligram of creatinine was significantly positively correlated with expression of all three mRNAs with correlation coefficients (R-value) of 0.442, 0.481, and 0.561 for Pod-, Nep-, and AQP2-mRNA, respectively. AQP2-mRNA expression was strongly (R  >  0.8) positively correlated with both Pod- and Nep-mRNA expression. CONCLUSION: Podocyturia monitored by Pod- and Nep-mRNA expression and urine cells expressing AQP2-mRNA were increased in uncomplicated pregnancies compared to healthy non-pregnant women. Urine cells expressing AQP2-mRNA increased with increasing podocyturia in healthy women.

Association between nephrinuria, podocyturia, and proteinuria in women with pre-eclampsia.

AIM: Podocyte depletion in the kidney is associated with end-stage kidney disease (ESKD). Pre-eclampsia (PE) increases the risk of ESKD in later life. This study was performed to determine whether nephrinuria (soluble nephrin in the urine) is correlated with proteinuria and/or podocyturia (podocytes in the urine) in PE women. METHODS: Eighty-three urine samples, consisting of 45 and 38 samples from 27 normotensive and nine PE women, respectively, underwent simultaneous determination of nephrin, protein, and creatinine concentrations in the urine supernatant and quantitative analysis of podocyte-specific protein mRNA expression. This included podocin (Pod-mRNA) and nephrin (Nep-mRNA), using real-time polymerase chain reaction in the pelleted urine. Nephrinuria and proteinuria were corrected by creatinine concentration. Pod- and Nep-mRNA expression levels were corrected by GAPDH. RESULTS: Nephrinuria, proteinuria, Pod-mRNA expression, and Nep-mRNA expression all increased with advancing gestation in PE women, while not in normotensive women. The nephrinuria was strongly correlated with proteinuria (R = 0.901, P <  0.001), Pod-mRNA expression level (R = 0.824, P < 0.001), and Nep-mRNA expression level (R  =  0.724, P <  0.001) in urine samples from PE women, while the nephrinuria was significantly correlated with proteinuria alone (R  =  0.419, P <  0.005) in urine samples from normotensive women. CONCLUSION: Nephrinuria reflected well the degrees of proteinuria and podocyturia in PE women. This suggested that increased nephrinuria/proteinuria was associated with podocyte loss in the kidneys of PE women.

Second-trimester urine nephrin:creatinine ratio versus soluble fms-like tyrosine kinase-1:placental growth factor ratio for prediction of preeclampsia among asymptomatic women.

This prospective observational study compare urine nephrin:creatinine ratio (NCR, ng/mg) with serum soluble fms-like tyrosine kinase-1:placental growth factor ratio (FPR, pg/pg) for preeclampsia (PE) prediction among unselected asymptomatic pregnant women in 2nd trimester. NCR and FPR were determined in 254 paired urine/blood samples collected simultaneously from 254 women at median gestational week (GW) 24 (range, 22-27) without hypertension or significant proteinuria in pregnancy (SPIP). Fifteen (5.9%) developed SPIP and hypertension at GW 34.0 (26.0-38.6) and 35.3 (27.6-38.6), respectively, and were diagnosed with PE at GW 35.7 (27.6-38.6). The 90th percentile level determined in 239 women normotensive throughout pregnancy gave NCR (139) sensitivity and positive predictive values (PPV) of 60% (9/15) and 27% (9/33), while those for serum FPR (4.85) were 40% (6/15) and 20% (6/30), respectively. Relative risks (95%CI) of later PE were 10.0 (3.82-26.4; 27% [9/33] vs. 2.7% [6/221]) and 4.98 (1.91-13.0; 20% [6/30] vs. 4.0% [9/224]) for NCR-positive and FPR-positive women, respectively. Cut-offs suggested by ROC gave NCR (86.6) sensitivity and PPV of 87% (13/15) and 17% (13/79), and FPR (8.8) values of 40% (6/15) and 40% (6/15), respectively. Thus, 2nd trimester NCR was superior to FPR for PE prediction.