Screening methods for gestational diabetes mellitus in Japan in 2018: a retrospective cohort study using a national surveillance questionnaire.

This study aimed to investigate the relationship between gestational diabetes mellitus (GDM) screening methods and GDM incidences. In 2018, a national questionnaire was administered at 231 institutions (56.6%) of all 408 perinatal medical centers in Japan. Of 100,485 women, 2,982 (3.0%) were diagnosed with GDM during their first pregnancy period (FPP) and 7,289 (7.3%) were diagnosed with GDM during their middle pregnancy period (MPP). The proportion of women diagnosed with GDM during FPP and MPP using 95 mg/dL as the cutoff value (CV) for random plasma glucose (PG) at FPP (4.3% and 9.2%) was significantly higher than that of women diagnosed with GDM using 100 mg/dL as the CV for random PG (2.7% and 6.9%, p < 0.0001, respectively). Compared with women screened for GDM using "random PG and random PG," women who were screened for GDM using "random PG and 50-g glucose challenge test (GCT)" had a significantly higher incidence of GDM (6.6% versus 8.9%, p < 0.0001). Using random PG and 50-g GCT, the incidence of GDM among women diagnosed at MPP using a CV of 95 mg/dL at FPP was significantly higher than that of women diagnosed using a CV of 100 mg/dL (16.5% versus 7.8%: p < 0.0001). While, using "random PG and random PG," the incidences of GDM among women were similar between institutions using a CV of 100 mg/dL and those using a CV of 95 mg/dL at FPP (6.7% versus 6.9%: p = 0.3581). This study showed random PG as a first-step screening method in MPP may overlook women with GDM.

Differences in the prevention and incidence of maternal venous thromboembolism according to the type of institution in Japan in 2018: A sub-analysis of national questionnaire surveillance.

AIM: To clarify the relation between institutions capacity to manage venous thromboembolism (VTE) and its incidence in pregnant women throughout Japan. METHODS: Among the 2299 institutions that received the surveillance questionnaire, 666 (29.0%) responded, after which data from 295 961 women who gave birth at those institutions in 2018 were analyzed. Incidences and characteristics of antepartum and postpartum VTE in perinatal medical centers (PMCs), general hospital with obstetric facilities (GHs), and maternal clinic with beds (MCs) were then determined. RESULTS: The frequencies at which routine antepartum and postpartum thromboprophylaxis for high-risk women and routine transport to the more advanced medical institutions upon antepartum and postpartum pulmonary thromboembolism (PE) onset were performed differed significantly according to types of institution (PMCs: 92.4%, 96.2%, 23.8%, and 21.2%; GHs: 76.5%, 80.6%, 58.8%, and 54.1%; MCs: 29.2%, 41.7%, 96.5%, and 96.2%, respectively). Among the 295 961 women analyzed, 243 (0.082%) developed VTE. Incidences of antepartum VTE differed significantly according to institution types (PMCs: 106.4, GHs: 51.6, and MCs: 11.6 per 100 000 women). PMCs and GHs had significantly higher incidences of postpartum VTE compared to MCs (43.3 and 26.6 vs. 10.7 per 100 000 women, respectively), although PMCs and GHs had similar incidences. Among the four women (1.4%) who died due to VTE, three and one developed a PE in a PMC and MC, respectively. CONCLUSIONS: PMCs had higher incidences of VTE despite their more frequent performance of thromboprophylaxis. Several pregnant women with higher risk of VTE transported to PMCs.

A retrospective cohort study using a national surveillance questionnaire to investigate the characteristics of maternal venous thromboembolism in Japan in 2018.

BACKGROUND: In Japan, the numbers of deliveries by women of older maternal age and women with overweight or obesity have recently increased. Since 2008, the guidelines and practices to prevent the maternal venous thromboembolism (VTE) have been recommended antepartum and postpartum thromboprophylaxis for each risk level of VTE. This study aimed to clarify the incidence and characteristics (type of VTE and thromboprophylaxis) of VTE in pregnant women in Japan to reduce the rate of mortality from VTE METHODS: Of 2299 institutions sent the surveillance questionnaire, 666 (29.0%) responded, and data from 295,961 women who gave birth in those institutions in 2018 were analyzed. We calculated the incidence and characteristics of VTE before and after the deliveries. RESULTS: At the responding institutions, 243 women (0.082%) had VTE in 2018. In 2018, deep vein thrombosis was significantly more common (0.0053%) than pulmonary thromboembolism (0.0019%; p < 0.0001). The incidence of antepartum VTE (0.0055%) was significantly higher than that of postpartum VTE (0.0026%; p < 0.0001). The incidence of VTE after cesarean Sect. (0.0074%) was significantly higher than that after vaginal delivery (0.0012%; p < 0.0001). Of the women with VTE, 4 (1.6%) died. CONCLUSIONS: Among the women thought to have a low risk of VTE during the antepartum period, and especially women who had a vaginal delivery, the actual incidence of VTE might have increased in Japan.

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.

Capacity of Japanese institutions to manage obstetrical disseminated intravascular coagulation in 2018: A national surveillance questionnaire and retrospective cohort study.

AIM: To investigate the management of obstetrical disseminated intravascular coagulation (DIC) in Japan. METHODS: We sent a surveillance questionnaire to 2299 institutions to collect details about the deliveries they performed in 2018. We investigated differences in the management of obstetrical DIC among three types of institutions: perinatal medical centers (PMCs), general hospitals with obstetrical facilities (GHs), and maternal clinics with beds (MCs). RESULTS: We received responses from 703 institutions (30.6% of the total mailed) with results of 306 799 women who gave birth in 2018. In Japan, the potential to treat postpartum hemorrhage and obstetrical DIC was high in the PMC group, moderate in the GH group, and low in the MC group. The incidence of obstetrical DIC in the PMC group (0.44%) was significantly higher than that in the GH (0.21%) and MC (0.06%) groups. The mortality of women with obstetrical DIC in PMCs (1.3%) was similar to that in GHs (0.6%) and MCs (0.0%). The percentages of PMCs that always or sometimes transfused fresh frozen plasma or fibrinogen concentrates (100% and 42.2%, respectively) were significantly higher than those in the GH (88.2% and 29.5%, respectively) and MC groups (29.4% and 5.3%, respectively). Furthermore, institutions whose internal protocols mandated that replacement therapy be always administered in women with obstetrical DIC scores of ≥8 had similar protocols to those for women with fibrinogen levels of ≤1.5 g/L. CONCLUSIONS: The capacity to provide therapy for postpartum hemorrhage and obstetrical DIC varied widely among the three groups of institutions.

Changes of cerebral oxygenation indices measured by near infrared time-resolved spectroscopy during spinal anesthesia for cesarean section: Simultaneous measurement with cerebral blood flow.

AIM: To measure the changes in cerebral oxygenation indices by near infrared time-resolved spectroscopy and the cerebral blood flow simultaneously after spinal anesthesia for cesarean section. METHODS: This prospective observational study was conducted for 25 pregnant women scheduled for elective cesarean section under spinal anesthesia. During a period of 15 min after spinal anesthesia, cerebral oxygenation (ScO2 ), and the total cerebral hemoglobin concentration (tHb) were measured using near infrared time-resolved spectroscopy and mean cerebral blood flow velocity (Vm) was measured using transcranial Doppler ultrasonography. Next, in the women who had nausea during the observed period, we compared these values when nausea was detected with those when it was not. RESULTS: Mean arterial pressure (MAP) decreased to around 60 mmHg (by 25% compared to the control) 6 min after spinal anesthesia. Compared to the control, ScO2 decreased by about 3% after 6 min and then gradually increased. The tHb, which reflects cerebral blood volume started to decrease just after spinal anesthesia and this continued until 12 min (the decrease was about 12%). Vm decreased by about 7%. In the 14 women who had nausea, MAP, Vm, and ScO2 values when nausea was detected were significantly lower than when it was not. CONCLUSION: The changes in cerebral hemodynamics may be small after spinal anesthesia in ordinary cesarean section compared to the reduction of systemic arterial blood pressure. There might be greater decreases in cerebral blood flow and oxygenation when nausea occurred in the pregnant women who experienced it after spinal anesthesia.

Predictors of recurrent gestational diabetes mellitus: A Japanese multicenter cohort study and literature review.

AIM: To clarify whether maternal characteristics or laboratory parameters could help predict the onset of recurrent gestational diabetes mellitus (GDM). METHODS: We enrolled 615 women with consecutive singleton deliveries at or after 28 GW from two perinatal medical centers between 2011 and 2019 and divided them into four groups according to whether they had GDM in the first and second pregnancies. The outcome of this study was to clarify the incidence and the predictors of recurrent GDM. RESULTS: We found that among 72 women (11.7%) who had GDM during their first pregnancy, the rate of recurrent GDM was 47.2%. The 34 women (5.5%) with recurrent GDM gained significantly less weight in the first and second pregnancies and lost less weight between the first delivery and the second conception compared with those women without GDM in both pregnancies. Of women with GDM during the first pregnancy, 21 scored 2 or 3 (multiple) positive points on a 75-g oral glucose tolerance test (OGTT) during their first pregnancies; the GDM recurrence rate among these women (66.7%) was significantly higher than that among the 51 women who scored 1 positive point (39.2%; p = 0.0411). During the first pregnancy, insulin administration therapy was significantly more frequent in women with recurrent GDM than in women without recurrent GDM (23.5% vs. 5.3%, p = 0.0396, respectively). CONCLUSION: A predictor of recurrent GDM onset was a score of 2 or 3 positive points on the OGTT during the first pregnancy.

Excessive gestational weight gain during the week prior to delivery as a predictor of maternal life-threatening complications in preeclamptic women.

AIM: To investigate the relationship between excessive gestational weight gain during the week prior to delivery (GWG) and severe morbidity and pregnancy termination among pregnant women with preeclampsia (hypertension with proteinuria). METHODS: We compared GWG, laboratory data, and complication(s) between 94 preeclamptic women (preeclampsia group) with singleton pregnancies who delivered at ≥22 gestational weeks and 188 healthy women (control group) with singleton pregnancies undergoing elective cesarean deliveries. The gestational weeks at delivery were matched in the preeclampsia and control groups. RESULTS: Among 282 total participants, median of GWG was significantly higher in the preeclampsia group than in the control group (1.6 kg vs. 0.5 kg, p < 0.0001). Furthermore, the GWG cutoff value for the preeclampsia group was 1.6 kg. The odds ratio for morbidity of preeclampsia among the women with GWG ≥1.6 kg at delivery was 12.5 (95% confidence interval, 6.31-24.5). In the preeclampsia group, 47 women with GWG ≥1.6 kg had significantly higher risks of hypoproteinemia, proteinuria, and renal dysfunction than those of 47 women with GWG < 1.6 kg. While, multivariate analysis showed 1.5 kg was a GWG cutoff value for predicting maternal morbidity (p < 0.0001); preeclamptic women with GWG ≥1.5 kg had a significantly higher risk of pulmonary edema than preeclamptic women with GWG < 1.5 kg (odds ratio, 7.77; 95% confidence interval, 1.64-36.7). CONCLUSION: Excessive GWG in women with preeclampsia might be a predictor for severe maternal life-threatening complications requiring pregnancy termination.

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.

Morphofunctional cardiac changes in singleton and twin pregnancies: a longitudinal cohort study.

BACKGROUND: This study aimed to compare the echocardiographic changes and cardiac biomarkers between women with singleton and twin pregnancies. METHODS: From April 2014 to March 2016, this longitudinal cohort study invited pregnant women who were scheduled to give birth at Hokkaido University Hospital. We analyzed prospectively collected data on simultaneously determined echocardiographic parameters and blood cardiac markers of 44 women with singleton and 22 women with twin pregnancies. Furthermore, we tested the mixed-effect models for echocardiographic parameters and cardiac biomarkers. RESULTS: During the third trimester and immediately postpartum (within 1 week after childbirth), the mean left atrial volume index and brain natriuretic peptide (BNP) level were significantly higher in women with twin pregnancies than in those with singleton pregnancies. Women with twin pregnancies also had significantly smaller second-trimester inferior vena cava diameters and significantly higher third-trimester creatinine levels than those with singleton pregnancies. BNP positively correlated with the left atrial volume index (ß = 0.49, p < 0.01) and the ratio of early diastolic transmitral to mitral annular velocity (E/e') (ß = 0.41, p < 0.01). At 1 month after childbirth in women with singleton pregnancies, BNP and N-terminal precursor protein BNP (NT-proBNP) fragments immediately postpartum negatively correlated with the later E/e' (r = - 0.33, p = 0.02 and r = - 0.36, p < 0.01, respectively). CONCLUSIONS: The intravascular cardiac load reached maximum within 1 week after childbirth and was greater in women with twin pregnancies than in those with singleton pregnancies. BNP/NT-proBNP significantly positively correlated with LA volume index and E/e'. In women with singleton pregnancies, BNP secreted immediately after childbirth might improve the diastolic functions 1 month after childbirth.

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.

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.

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.

Association of antenatal antithrombin activity with perinatal liver dysfunction: A prospective multicenter study.

BACKGROUND AND AIM: Liver dysfunction with decreased antithrombin (AT) activity and/or thrombocytopenia is life threatening in pregnant women. Whether AT is clinically useful for prediction of liver dysfunction remains unclear. METHODS: A total of 541 women were registered prospectively at gestational week 34.7 (20.0-41.4) with available data on antenatal AT and platelet count (PLC). RESULTS: Liver dysfunction defined as serum aspartate aminotransferase > 45 IU/L concomitant with lactate dehydrogenase > 400 IU/L occurred in five women antenatally (≤ 2 weeks before delivery) and in 17 women post-partum (within 1 week post-partum). Median (5th-95th) antenatal value was 85 (62-110)% for AT and 202 (118-315) × 109 /L for PLC in the 541 women and was significantly lower in women with than without perinatal liver dysfunction; 75 (51-108) versus 86 (62-110)% and 179 (56-244) versus 203 (121-316) × 109 /L, respectively. Nineteen (86%) women with liver dysfunction showed AT ≤ 62% or thrombocytopenia (PLC ≤ 118 × 109 /L) perinatally, but five lacked thrombocytopenia throughout the perinatal period. The best cut-off (AT, 77%; PLC, 139 × 109 /L) suggested by receiver operating characteristic curve gave antenatal AT and PLC sensitivity of 59% and 41% with positive predictive value of 8.6% and 14%, respectively, and combined use of AT and PLC improved sensitivity to 73% (16/22) with positive predictive value of 9.2% for prediction of perinatal liver dysfunction. CONCLUSIONS: Reduced AT not accompanied by thrombocytopenia can precede liver dysfunction. Clinical introduction of AT may enhance the safety of pregnant women.

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.

Perinatal mortality in Japanese women diagnosed with gestational diabetes mellitus and diabetes mellitus.

AIMS: The objective of this study was to determine how many pregnant Japanese women with diabetes mellitus (DM)/gestational diabetes mellitus (GDM) experience perinatal mortality in the presence of fetal anomalies. METHODS: Our investigation included data from 205 secondary/tertiary obstetric facilities located widely in Japan. The Japan Ministry of Health, Labour and Welfare Vital Statistics of Japan was used for comparison. RESULTS: Of 237 941 women giving birth at 205 hospitals, 1796 (0.8%) and 13 037 (5.5%) had DM and GDM, respectively. The perinatal mortality rates (per 1000 births) were 10.6 (19/1796) for women with DM, 5.2 (68/13037) for women with GDM, and 3.7 (7612/2039504) for the general Japanese population. Detailed information was available for 63 (72%) of the 87 perinatal deaths occurring in women with diabetes including DM and GDM; fetal anomalies were associated with 40% (25/63) of perinatal deaths, exceeding 16% (1211/7612) in the general Japanese population (P < 0.0001). The leading four fetal anomalies associated with perinatal mortality in women with diabetes were fetal trisomy (6 cases: 1 of trisomy-13 and 5 of trisomy-18), non-immune hydrops fetalis (5 cases), cardiac deformities (3 cases) and holoprosencephaly (2 cases). CONCLUSIONS: Perinatal mortality was more likely to occur in women with glucose intolerance. In the Japanese infants that succumbed to perinatal mortality, fetal anomaly was more prevalent in those born to women with a glucose intolerance than in those born to the general population.

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.

Post-partum podocyturia following pre-eclamptic pregnancy.

AIM: Urine podocin mRNA expression and urine podocin : nephrin mRNA expression ratio (PNR) increase with increasing proteinuria during pregnancy complicated with pre-eclampsia (PE). This suggests that urine podocytes with reduced nephrin mRNA expression are abundant in pathological podocyturia. The aim of this study was therefore to determine post-partum changes in podocyturia and PNR in relation to proteinuria after pre-eclampsia (PE). METHODS: A total of 137 peripartum urine specimens, consisting of 72 and 65 from 24 and 30 women with PE and normotensive control pregnancies (NCP), respectively, were studied. Determination of urine protein and creatinine concentration and quantitative analysis of podocyte-specific podocin and nephrin mRNA expression were carried out using reverse transcription-polymerase chain reaction in pelleted urine samples. Podocyturia was monitored via urine podocin mRNA expression. Podocyturia and proteinuria were normalized by urine creatinine concentration. RESULTS: Podocyturia and urine PNR decreased with decreasing proteinuria as well as with increasing time after delivery in the urine from PE women. In physiological proteinuria (i.e. protein : creatinine ratio [P/Cr] 0.005-0.1 mg/mg), however, both podocyturia and PNR were significantly greater in the urine from PE women compared with NPC women, although P/Cr was similar between the groups (median, 0.037 mg/mg for PE vs 0.029 mg/mg for NCP). CONCLUSIONS: Podocyturia decreases with decreasing proteinuria in PE women after childbirth. In PE women, however, pathological podocyturia consisting of podocytes with decreased nephrin mRNA expression persisted even after proteinuria decreased to a level similar to that in NCP women.