Prevalence of hyperglycaemia in singleton versus twin pregnancy.

BACKGROUND: There is conflicting information regarding the risk of gestational diabetes mellitus in twin pregnancies. This study was conducted to determine whether the risk of gestational diabetes mellitus is higher in pregnant Japanese women with twin versus singleton pregnancy. METHODS: The prevalence of gestational diabetes mellitus was studied in two different populations: 144 589 women registered with the Japan Society of Obstetrics and Gynecology (JSOG cohort) over 3 years between 2007 and 2009 in which patient selection bias was unavoidable; and 430 Japanese women who gave birth at a single centre over 5 years between 2008 and 2012 (single-centre cohort), consisting of 86 women with twins and 344 women with singletons matched for maternal age and prepregnancy body mass index. The gestational diabetes mellitus was diagnosed on the basis of the previous criteria in the JSOG cohort. The gestational diabetes mellitus was screened in a stepwise method and diagnosed on the basis of the new criteria in the single-centre cohort. RESULTS: In the single-centre cohort, neither frequency of random glucose level ≥105 mg/dL in the first trimester [9.0% (31/344) vs 5.8% (5/86)], positive result (≥140 mg/dL) on 50 g glucose challenge test in the second trimester [26.5% (90/339) vs 26.7% (23/86)], nor women diagnosed with GDM [8.4% (29/344) vs 9.3% (8/86)] differed between the two groups. The prevalence of hyperglycaemia was higher in singleton than in twin pregnancies in the JSOG cohort (2.6% vs 1.8%, p < 0.001). CONCLUSIONS: The risk of gestational diabetes mellitus may be similar between Japanese women with singleton and twin pregnancies. Difference in the risk of hyperglycaemia in the JSOG cohort may have been due to selection bias.

Gestational weight gain according to number of fetuses in Japanese women.

AIM: It is unknown whether weekly maternal weight gain differs between Japanese women with singleton, twin, and triplet pregnancies. METHODS: Gestational weight gain defined as net weight gain during pregnancy was analyzed in 135,036 pregnant Japanese women, including 128,838 with singletons, 5573 with twins, and 132 with triplets, who gave birth at ≥22 weeks of gestation between 2007 and 2009. Weekly weight gain was defined as follows: gestational weight gain÷[gestational week (GW) at Delivery-2]. RESULTS: Length of gestation (weeks, mean±SD) decreased significantly (38.2±2.6, 35.3±3.0, and 32.7±2.8) with increasing number of fetuses, while overall gestational weight gain (kg) was significantly smaller in women with singletons than in those with either twins or triplets (9.6±4.4 vs. 10.9±4.8 or 10.9±5.2, respectively). Thus, weekly maternal weight gain (kg/week) increased significantly with increasing number of fetuses (0.26±0.12, 0.33±0.13, and 0.35±0.16). Among women with delivery at or after GW 34, difference in gestational weight gain (kg) was prominent between the three groups (9.8±4.4, 11.4±4.7, and 13.0±5.1 for singleton, twin, and triplet pregnancies, respectively, P<0.001 between any two groups). CONCLUSIONS: Weekly maternal weight gain increases with increasing number of fetuses. Our figures may be useful for advising Japanese women with multifetal pregnancies regarding gestational weight gain.

Differentiation of acute fatty liver of pregnancy from syndrome of hemolysis, elevated liver enzymes and low platelet counts.

As proposed criteria (Swansea criteria) for the diagnosis of acute fatty liver of pregnancy (AFLP) do not include antithrombin (AT) activity, diagnosis of AFLP may be delayed. The aim of this review is to underscore problems in the differential diagnosis of AFLP and the syndrome of hemolysis, elevated liver enzymes and low platelet counts (HELLP syndrome) and to facilitate prompt diagnosis of AFLP. Published works dealing with liver dysfunction in pregnancy, HELLP syndrome and AFLP were reviewed. AFLP and HELLP syndrome shared common clinical, laboratory, histological and genetic features, and differential diagnosis between them was often difficult. However, HELLP syndrome was likely to occur in patients with hypertension, but AFLP occurred often in the absence of hypertension. In addition, AFLP was exclusively associated with pregnancy-induced antithrombin deficiency (PIATD). Approximately 50% of patients with AFLP did not have thrombocytopenia at presentation. As the Swansea criteria for AFLP did not include PIATD, diagnosis of AFLP was delayed until manifestation of life-threatening complications; 60% of women were admitted to intensive care and 15% to a specialist liver unit. In conclusion, incorporation of AT activity of less than 65% into the diagnostic criteria for AFLP may facilitate suspicion and prompt diagnosis of AFLP, decrease uncertainty regarding the diagnosis of AFLP, and contribute to better investigation and understanding of the process leading to the development of liver dysfunction.

Liver dysfunction in triplet pregnancies: relation to antenatal changes in antithrombin activity and platelet count.

AIM: The aim of this study was to determine whether antenatal decline in antithrombin (AT) activity occurs frequently and precedes the development of perinatal liver dysfunction in women with triplet pregnancies. MATERIAL AND METHODS: A retrospective observational study was conducted on all women who gave birth to triplets at gestational week ≥ 22 at a single centre during a study period from January 2001 to March 2013. The following eight blood parameters were monitored weekly during the last 5 weeks of pregnancy and postpartum: AT activity, platelet count, fibrinogen, D-dimer, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), uric acid and creatinine. Pregnancy-induced AT deficiency (PIATD) and gestational thrombocytopenia were defined as antenatal AT activity < 70% of normal level and antenatal platelet count < 150 × 10(9) /L, respectively. Liver dysfunction was defined as AST > 40 IU/L. LDH elevation was defined as LDH > 450 IU/L. RESULTS: Sixteen women were eligible for this study. All variables except LDH exhibited significant changes antenatally: AT activity, platelet count and fibrinogen decreased, while D-dimer, AST, urate and creatinine increased. LDH increased significantly postpartum. PIATD, gestational thrombocytopenia, perinatal liver dysfunction, and LDH elevation occurred in eight, seven, six, and eight women, respectively. Liver dysfunction was preceded by PIATD alone in three, by both PIATD and gestational thrombocytopenia in one and by gestational thrombocytopenia alone in none of the subjects. After delivery, laboratory abnormalities similar to HELLP syndrome were seen in three women exclusively in the presence of PIATD. CONCLUSIONS: Reduced AT activity was likely to precede perinatal liver dysfunction in women with triplets.

Successful pregnancy in a woman with uterine scarring by transverse fundal cesarean section.

There has been only one case to date of pregnancy outcome after fundal transverse cesarean section (FTC). We report a pregnancy established after FTC. The FTC was performed at gestational week (GW) 24 in this patient's first pregnancy, but the uterus was preserved. Magnetic resonance imaging studies performed four times in her second pregnancy consistently showed part of the uterine fundus in which the muscle layer was interrupted. Concern regarding spontaneous uterine rupture in the absence of labor pains prompted us to interrupt her pregnancy at GW 31(+5) , delivering a premature, but otherwise healthy female infant, weighing 1832 g. The infant required transient intratracheal intubation for respiratory distress syndrome (for less than 1 h), but had an otherwise uneventful clinical course. Two cases, including ours, suggest that successful pregnancy outcome is feasible at least in some women with uterine scarring due to FTC.

Problems in methods for the detection of significant proteinuria in pregnancy.

AIM: The aim of this study was to underscore problems associated with the dipstick test and determination of protein concentration alone in spot-urine (P-test) compared with spot-urine protein-to-creatinine ratio (P/Cr test) and to determine whether urine collection for 24-h test was complete. MATERIAL AND METHODS: Dipstick and P/Cr tests were performed simultaneously in 357 random spot-urine specimens from 145 pregnant women, including 35 with pre-eclampsia. Positive results were defined as ≥ 1+ on dipstick test, protein concentration ≥ 30 mg/dL on P-test, and P/Cr ratio ≥ 0.27 (mg/mg) on P/Cr test. Sixty-four 24-h urine tests (quantification of protein in urine collected during 24 h) were performed in 27 of the 145 women. We assumed that P/Cr ratio ≥ 0.27 predicted significant proteinuria (urinary protein ≥ 0.3 g/day). The 24-h urine collection was considered incomplete when urinary creatinine excretion was <11.0 mg/kg/day or >25.0 mg/kg/day. RESULTS: Forty-four percent (69/156) of specimens with a positive test result on dipstick test contained protein < 30 mg/dL. Dipstick test was positive for 25.7% (69/269) of specimens with protein < 30 mg/dL and for 28.8% (79/274) of specimens with P/Cr ratio < 0.27. P-test results were positive for 7.3% (20/274) and negative for 18.1% (15/83) of specimens with P/Cr ratio < 0.27 and ≥ 0.27, respectively. Incomplete 24-h urine collection occurred in 15.6% (10/64) of 24-h urine tests. Daily urinary creatinine excretion was 702-1397 mg, while creatinine concentration varied from 16 mg/dL to 475 mg/dL in spot-urine specimens. CONCLUSION: Dipstick test and P-test were likely to over- and underestimate risks of significant proteinuria, respectively. The 24-h urine collection was often incomplete.

Effects of caesarean section on serum levels of NT-proBNP.

OBJECTIVE: To determine the effects of delivery by caesarean on serum levels of N-terminal fragment of precursor protein brain-type natriuretic peptide (NT-proBNP). METHODS: Serum NT-proBNP levels were determined longitudinally at 24 and 36 weeks of gestation (GW) and on post-partum day 3 and month 1 (PPD3 and PPM1, respectively) in 78 women with normotensive singleton pregnancies. Thirty-nine women underwent caesarean delivery. Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were determined on PPD3. Effects of maternal demographic characteristics on NT-proBNP levels were also analysed. RESULTS: NT-proBNP levels (pg/ml) either in pregnancy or on PPM1 did not differ between women with vaginal and caesarean deliveries (44 ± 24 vs 41 ± 30, 24 GW; 37 ± 22 vs 29 ± 22, 36 GW; 43 ± 28 vs 39 ± 24, PPM1, respectively). Levels on PPD3 were significantly higher (94 ± 105 vs 247 ± 186, P < 0.0001) in women with caesarean delivery. Among women with caesarean delivery, a larger rise of NT-proBNP on PPD3 occurred in nulliparous than in multiparous women (319 ± 232 vs 185 ± 107, P = 0.023), while no rise occurred among multiparous women with vaginal delivery (108 ± 115 vs 47 ± 27). NT-proBNP levels on PPD3 were significantly and negatively correlated with PRA, PAC and maternal weight loss after childbirth on PPD3. These 3 variables on PPD3 were significantly lower in women undergoing caesarean than vaginal delivery (0.8 ± 0.4 vs 1.9 ± 1.4 ng/ml/h for PRA; 70 ± 38 vs 136 ± 88 pg/ml for PAC; 2.7 ± 1.2 vs 4.3 ± 1.1 kg for weight loss, each P < 0.0001). CONCLUSIONS: The transient post-partum rise in serum NT-proBNP may reflect transient volume overload after parturition and is remarkable in nulliparous women, especially after caesarean section.

Usefulness of transverse fundal incision method of cesarean section for women with placentas widely covering the entire anterior uterine wall.

AIM: To assess the usefulness of a new method for cesarean section (CS) that is comprised of a transverse incision into the uterine fundus, developed for women with placentas covering the entire anterior uterine wall, and introduced in September 2006. MATERIAL AND METHODS: Review of medical records of 12 and 29 women who underwent CS by the new and conventional methods, respectively, for placenta previa, placenta accreta (accreta, increta and percreta) or placenta widely covering the entire anterior uterine wall in which placenta accreta cannot be excluded, between June 2003 and March 2011. RESULTS: Placenta accreta (67% [8/12] vs 10% [3/29], P=0.0006) and cesarean hysterectomy (67% vs 10%) were significantly more frequent in the group with the new compared with the conventional method. There were no significant differences between groups with the new and conventional methods in amount of blood loss (1732±1067 vs 1847±1279g, respectively), prevalence of blood loss >3000g (8.3% vs 17%, respectively) or blood transfusion (92% vs 72%, respectively), time required for cesarean hysterectomy (210±58 vs 195±41min), or neonatal conditions at birth. The amount of blood loss for cesarean hysterectomy was significantly less for the new than conventional method (1959±1025g vs 4450±1145g, P=0.041). CONCLUSION: The new method was superior to the conventional method with respect to reduction of blood loss during cesarean hysterectomy. However, careful observations are mandatory in women with preserved uterus with respect to a possible increased risk of uterine rupture in future pregnancies.

Characteristics of insulin secretion patterns in Japanese women with overt diabetes and gestational diabetes defined according to the International Association of Diabetes and Pregnancy Study Groups criteria.

AIM: To characterize patterns of insulin secretion in women with overt diabetes and gestational diabetes (GDM) defined by the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. MATERIAL AND METHODS: A total of 228 Japanese women were examined retrospectively. All 228 women had a positive 50-g glucose challenge test (GCT) result at 25.2±1.2weeks of gestation and underwent a 75-g glucose tolerance test (GTT) at 27.4±1.8weeks of gestation. The immunoreactive insulin levels were determined during the GTT in four groups of pregnant women: five with overt diabetes, 20 with GDM according to both the previous Japan Society of Gynecology and Obstetrics (JSOG) and current IADPSG criteria (traditional GDM group), 43 with GDM according to only the IADPSG criteria (new GDM group), and 160 with non- GDM, but with a positive GCT result. RESULTS: Attenuated and slow rise in plasma insulin in concert with prolonged hyperglycemia were characteristic in women with overt diabetes, compared with women with GDM in whom excessive insulin secretion in the presence of hyperglycemia was characteristic. The new GDM group did not differ significantly from the traditional GDM group with respect to scores of such indices as the insulinogenic index, the homeostasis model assessment for insulin resistance, and the quantitative insulin sensitivity check index. CONCLUSION: Women with overt diabetes have both an impaired capacity for insulin secretion and elevated insulin resistance, while women with GDM exhibit a maintained insulin secretory capacity with an elevated insulin resistance.

Antithrombin activity, platelet count, hemoglobin concentration and hematocrit value determined immediately before vaginal delivery among healthy women.

AIMS: To determine the normal reference values for antithrombin (AT) activity, platelet count (Plt), hemoglobin concentration (Hb), and hematocrit value (Ht) immediately before vaginal delivery among healthy pregnant women with singleton pregnancies and to determine association of these blood parameters with fetal growth. METHODS: A complete blood count was performed and the AT activity was examined in 300 consecutive women admitted to hospital at > or = gestational week 36 for labor pains and/or the rupture of fetal membranes. All the women were normotensive and had singleton pregnancies, and none of the women had proteinuria, a weekly weight gain > or = 0.5 kg, or other specific complications upon admission. All the women attempted a vaginal delivery. RESULTS: The medians (5th-95th percentile) were 90% (71-110%) for AT activity, 234x10(9)/L (150-337x10(9)/L) for Plt, 11.0 g/dL (9.5-12.8 g/dL) for Hb, and 34.0% (30.4-38.6%) for Ht. Women with an Hb value of > or = the median (11.0 g/dL) gave birth to significantly smaller infants than their counterparts. CONCLUSIONS: A considerable number of healthy women exhibit a reduced AT activity and/or platelet count immediately before delivery. Hemoconcentration evidenced by a raised Hb value adversely effects on infant growth. Our data may be helpful when considering the normal ranges of these blood parameters for healthy parturient women.

Risk factors for postpartum hypertension in women with twin pregnancies.

OBJECTIVE: Which physical findings and blood parameters predict postpartum hypertension remain to be studied in women with twin pregnancies. METHODS: The antenatal systolic and diastolic blood pressures (SBP and DBP, respectively), and 16 laboratory variables were investigated in 150 normotensive women who gave birth to twins. RESULTS: When the median values of the 18 continuous variables were used as cut-off values, an SBP>120 mm Hg (relative risk [95% confidence interval], 2.81 [1.94-4.08]), a DBP>70 mm Hg (2.42 [1.68-3.49]), an aspartate aminotransferase level>18 U/L (2.22 [1.55-3.19]), and a uric acid level>5.3 mg/dL (1.68 [1.20-2.36]) were independent risk factors for postpartum hypertension. CONCLUSIONS: Antenatal blood pressure measurements and a laboratory work-up may be useful clinically for predicting postpartum hypertension in women with twin pregnancies.

Do uterotrophic drugs increase the risk of fatal hemorrhagic brain stroke?

OBJECTIVE: To evaluate whether uterotrophic agents increase the risk of fatal hemorrhagic brain stroke. METHODS: Between 1991 and 1992, there were 230 maternal deaths among 2,420,000 pregnant women in Japan and the causes of these deaths was investigated in 1994. Using information provided in this report, we identified 35 women who died from or were assumed to die from hemorrhagic brain stroke. We assumed that 93% of women would have tried vaginal delivery. The risk of fatal hemorrhagic brain stroke after uterotrophic agent use was calculated according to the assumption that 5.0-40% of women received uterotrophic agents. RESULTS: Use of uterotrophic agents for induction/augmentation of labor was confirmed in five (14.3%) of the 35 women who died from hemorrhagic brain stroke. The incidence of fatal brain stroke after the use of uterotrophic agents was only significantly higher than that for spontaneous hemorrhagic brain stroke if these agents were administered in ≤ 6.0% of women. CONCLUSIONS: Because more than 6.0% of women received uterotrophic agents, these agents are unlikely to increase the risk of fatal hemorrhagic brain stroke.

Relationships between fetal growth and maternal body mass indices, plasma glucose level, and plasma insulin level in Japanese women with mildly impaired glucose tolerance.

AIM: To identify variables which are strongly associated with fetal growth. MATERIAL AND METHODS: The study subjects were 203 Japanese women who had a plasma glucose level ≥140 mg/dL (7.8 mmol/L) on a 50-g glucose challenge test but were normoglycemic when challenged with a 75-g oral glucose tolerance test (GTT) according to the criteria previously used in Japan. All the subjects subsequently gave birth to singleton infants. The correlations between the standard deviation for birthweight (birthweight SD) and 15 other variables, including the maternal body mass index (BMI), plasma levels of glucose and insulin on the GTT, and various indices calculated using data from the GTT, were then examined. Univariate and multivariate regression analyses were performed. RESULTS: Univariate analyses revealed significant correlations between the birthweight SD and the fasting plasma glucose level (P = 0.0063), the pre-pregnancy BMI (P = 0.0001), and the BMI at delivery (P < 0.0001). Only the BMI at delivery remained as a significant factor that was independently correlated with the birthweight SD after a multivariate regression analysis. CONCLUSION: The suppression of maternal weight gain, rather than the suppression of the plasma glucose level, may be effective for avoiding infants with overgrowth among Japanese women with mildly impaired glucose tolerance.

Topological factors in placental surface arteries correlate with neonatal birth weight.

OBJECTIVES: There has been no study concerning association between topological factors of placental vascularization and neonatal growth in humans. The aim of study was to assess whether any network index of placental surface arteries was associated with neonatal birth weight. MATERIALS AND METHODS: Twenty-six placentas were randomly selected between 34 and 41 weeks of gestational ages. Placental weights ranged 385 to 770 g; and neonatal weights ranged 1960 to 3680 g. After visualization of placental surface arteries by a milk injection method, network indices including the number of nodes, network density, network diameter, average distance of nodes, and the degree centralization were determined. These network indices and placental weights were compared with neonatal birth weights. RESULTS: The number of nodes, network density, network diameter, average distance of nodes, and the degree centralization were found to be as follows (Mean +/- SD); 84.7 +/- 29.3, 0.0262 +/- 0.0088, 15.8 +/- 2.77, 7.83 +/- 1.13, 0.0263 +/- 0.0091, respectively. We found that neonatal birth weights correlated with the number of nodes of placental surface arteries (correlation coefficient R = 0.40) and placental weights (R = 0.52) both. However, the number of nodes of placental surface arteries was not associated with the placental weights or the gestational age. CONCLUSIONS: We for the first time found that a topological factor, i.e., the number of nodes of placental surface arteries correlated with neonatal growth. There was no correlation between numbers of nodes and placental weights. This suggests that the number of nodes affects fetal growth independent of placental weights. A topological factor of placental vascularization might significantly affect fetal growth in utero and determine risks of vascular diseases in their future lives.

Clinical significance of second-trimester 50-g glucose challenge test among Japanese women diagnosed as normoglycemic after first-trimester 75-g glucose tolerance test.

OBJECTIVE: This study was performed to determine how often Japanese women diagnosed as normoglycemic on first-trimester 75-g glucose tolerance test (75gGTT) later develop gestational diabetes mellitus (GDM). MATERIAL AND METHODS: Sixty-two women with random plasma glucose (PG) level ≥ 105 mg/dL during the first trimester and subsequent first-trimester diagnosis of normoglycemia with 75gGTT underwent 50-g glucose challenge test (50gGCT) during the second trimester. Twenty-one with a positive 50gGCT result (60-m PG ≥ 140 mg/dL) underwent second-trimester 75gGTT. First-trimester random PG levels and 75gGTT results were compared between 21 and 41 women with positive and negative 50gGCT results, respectively. Changes in immunoreactive insulin (IRI) associated with 75gGTT were determined simultaneously. RESULTS: All 21 women with a positive 50gGCT result showed normoglycemia on second-trimester 75gGTT. Thus, none of the 62 women developed GDM. Insulin resistance increased significantly in the 21 women with 75gGTT during the first and second trimesters, as indicated by increases in homeostasis model assessment for insulin resistance (HOMA-IR) and homeostasis model assessment for ß-cell function (HOMA-ß) with no significant changes in preload or afterload PG levels. Neither random PG levels (116 ± 12 vs. 116 ± 12 mg/dL, respectively) nor 75gGTT results (86 ± 6 vs. 84 ± 5 mg/dL for 0-minute [0-m] PG level, 130 ± 28 vs. 131 ± 25 mg/dL for 60-m PG, and 111 ± 19 vs. 118 ± 18 mg/dL for 120-m PG, respectively) during the first trimester differed significantly between the 41 and 21 women with negative and positive second-trimester 50gGCT results, respectively. CONCLUSION: Although insulin resistance increased in the second trimester, risk of developing GDM was < 1/62 among Japanese women in whom hyperglycemia was excluded with first-trimester GTT.

Clinical features of isolated gestational proteinuria progressing to pre-eclampsia: retrospective observational study.

OBJECTIVES: Some women with isolated gestational proteinuria (IGP) later develop hypertension and are diagnosed with pre-eclampsia (PE). This study was performed to determine whether clinical features of such proteinuria preceding PE (P-PE) differ from those of other PE (O-PE). DESIGN: Retrospective observational study after approval of the institutional review board of ethics. SETTING: A single university hospital. Proteinuria was defined as a protein-to-creatinine ratio (mg/mg; P/Cr) of ≥0.27 in the spot urine specimen. IGP was defined as proteinuria in the absence of hypertension. P-PE was defined as PE in which proteinuria preceded hypertension by more than 2 days. PARTICIPANTS: All of 10 and 18 consecutive women with P-PE and O-PE, respectively, who gave birth between January 2008 and August 2013. RESULTS: Proteinuria appeared earlier (at 30.2±3.0 vs 35.3±4.3 weeks, p=0.001), the P/Cr level was greater at birth (7.28±2.14 vs 3.19±2.49, p<0.001), net maternal weight gain during the last antenatal 1 week was greater (3.1±1.8 vs 1.3±1.7 kg, p=0.023) and length of pregnancy was shorter (32.5±1.9 vs 36.1±3.6 weeks, p=0.001) in women with P-PE than in O-PE. The duration of IGP was 10.0±5.9 days (range 3-20), and the time interval until delivery after diagnosis of PE was 6.1±8.2 days (range 0-23) in 10 women with P-PE. The P/Cr levels at birth were significantly inversely correlated with the antenatal lowest antithrombin activity and fibrinogen levels among the 28 women with PE. CONCLUSIONS: Women with P-PE were likely to exhibit greater proteinuria in the urine, greater water retention in the interstitial space and more enhanced coagulation-fibrinolysis, thus suggesting that they may constitute a more severe form of PE than women with O-PE do.

Essential thrombocythemia as a risk factor for stillbirth.

INTRODUCTION: The risk of abortion is known to be high in women with essential thrombocythemia (ET). However, a few studies have focused on the risk of stillbirth among fetuses reaching gestational age compatible with life. METHODS: Review of medical charts of pregnant women with ET who received cares at a single center between January 2003 and June 2013 and the English literature in which more than 20 pregnancies with ET were dealt with regarding outcomes. Outcomes were classified into three categories: spontaneous abortion or preterm delivery before GW 24, stillbirth at and after GW 24, and live birth (LB). Japan national statistics was used to estimate the risk of stillbirth among women with GW 22 or more. RESULTS: In all nine pregnancies in four women with ET at our hospital, two miscarriages, one stillbirth (intrauterine death at GW 35), and six LBs occurred. There were six reports in the English literature in which a total of 374 pregnancy outcomes were described: 110 miscarriages (29%), 14 stillbirths (3.7% of all 374 pregnancies and 5.3% of 264 pregnancies with GW≥24), and 250 LBs (67%) occurred. Japan national statistics between 1995 and 2011 indicated that the risk of stillbirth was less than 0.50% among women with GW≥22. CONCLUSIONS: The risk of stillbirth was extremely high among women with ET. More intensified monitoring of fetal wellbeing may be required to improve outcome of pregnancy complicated with ET.

Association of NT-proBNP with plasma renin activity and plasma aldosterone concentration in women with singleton pregnancy.

OBJECTIVE: To determine the association of the N-terminal fragment of precursor protein brain-type natriuretic peptide (NT-proBNP) levels with plasma renin activity (PRA) and plasma aldosterone concentration (PAC) in singleton pregnancies. DESIGN: Serum NT-proBNP levels, PRA and PAC were determined in 215 blood specimens from 139 women with singleton pregnancies, including 34 and 105 women who did and did not develop hypertensive disorders in pregnancy, respectively. Twenty-five blood specimens were obtained from 25 women who later developed hypertension (systolic BP⩾140mmHg and/or diastolic BP⩾90mmHg), but were normotensive at the time of blood sampling. RESULTS: The serum NT-proBNP levels [pg/ml, median (range), 32 (5-142)] did not change in normotensive women, but increased significantly to 97 (23-436) after the development of hypertension (D/H). The PRA [ng/ml/h, median (range), 7.1 (1-20)] did not change in normotensive women, but decreased significantly to 1.9 (1-16) after D/H. PAC (pg/ml) increased significantly from 397 (94-1750) to 667 (123-2010) between the 2nd and 3rd trimesters in normotensive women. However, as PAC of hypertensive women did not change significantly before and after D/H, PAC [293 (116-1720)] after D/H was significantly lower than that [667 (123-2010)] of the 3rd trimester in the normotensive women. The serum levels of NT-proBNP were significantly and negatively correlated with both PRA and PAC. CONCLUSIONS: The renin-angiotensin-aldosterone system is suppressed in pregnant women with cardiac conditions associated with higher NT-proBNP levels.

Changes in d-dimer levels in pregnant women according to gestational week.

We performed a retrospective review of medical charts regarding blood d-dimer levels determined cross-sectionally by the latex agglutination assay in 1952 samples from 1185 women to determine changes in d-dimer levels according to the stage of pregnancy. Three of 17 women in whom further investigations were performed were found to have clinical venous thromboembolism (VTE). The median and 95th percentile values of d-dimer (µg/mL) in the 1182 women without clinical VTE, 0.54 and 2.41 at gestational week (GW) 4-13, increased gradually to 1.22 and 5.03 at GW 14-27, 1.81 and 6.18 at GW 28-35, and 2.13 and 5.85 at GW 36-42, respectively. A total of nine women (0.76%), including three women with clinical VTE, exhibited a d-dimer level >14.0µg/mL, which was well above the 99th percentile for any stage of pregnancy. Thus, 3 (33%) of the nine with a d-dimer level >14µg/mL developed clinical VTE, while none of the remaining 1176 women with a d-dimer level ⩽14µg/mL developed clinical VTE. Although further prospective studies are required, our results suggested that there is a certain cut-off d-dimer value that would allow us to differentiate between pregnant women with and without clinical VTE.