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The increasing prevalence of advanced paternal age (APA) has mirrored the rise in maternal age. APA is associated with an increased risk of de novo pathogenic single-nucleotide variants, but this topic has been much less frequently discussed than advanced maternal age (AMA). To explore the awareness of pregnant women regarding paternal age effect (PAE) disorders, a self-administered questionnaire survey was conducted for pregnant women at their first prenatal visit before 17 weeks of gestation. A total of 120 valid respondents (95.2%) were included in the analyses. Of these, 63.3% of pregnant women were aware of PAE disorders. This was markedly lower than the 90.8% recognition of maternal age effect (MAE) disorders. One-third of women with awareness of MAE disorders were not aware of PAE disorders. Pregnant women who were parous, older than their male partners, with knowledge of prenatal testing prior to this pregnancy, and with experience of prenatal testing in a prior pregnancy were significantly more aware of PAE disorders than others. Awareness of PAE disorders was not associated with undergoing prenatal testing during the present pregnancy. Our results show that the prevalence of pregnant women’s awareness of PAE disorders was lower than that of MAE disorders. The current study served as a preliminary baseline of information about pregnant women’s awareness of PAE disorders. With the introduction of non-invasive prenatal testing, which has the potential to identify PAE disorders, these findings will help the development of a framework for comprehensive prenatal genetic counseling for APA pregnancies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12687-021-00555-y.

In-person models of genetic counseling (GC) have been the common method in Japan for pregnant women to receive GC. However, recent increases in the number of pregnant women considering undergoing prenatal testing have made it challenging to retain individualized in-person care. To explore pregnant women’s opinions toward pretest GC models and the ideal time duration, a self-administered questionnaire survey was conducted for women at their first prenatal visit. A total of 114 valid respondents (93.4%) were included in the analyses. Of these, 80.7% of women preferred in-person GC, followed by classroom (9.6%), group (3.5%), and telegenetic-based GC (2.6%). Women with experience in undergoing prenatal testing significantly did not prefer in-person GC (p = 0.05). Sixty-two women (54.4%) preferred a duration of 15–29 min for pretest GC sessions, followed by 30–59 min (28.9%) and

Objective Maternal characteristics and neonatal outcomes associated with cell-free DNA (cfDNA) results were analysed retrospectively to assess the details of false-positive and false-negative results after initial blood sampling in non-invasive prenatal testing (NIPT). Study design A multicentre retrospective study was performed for women undergoing NIPT who received discordant cfDNA results between April 2013 and March 2018. The NIPT data obtained using massive parallel sequencing were studied in terms of maternal background, fetal fraction, z-scores, invasive procedure results and neonatal outcomes after birth. Results Of the 56,545 women who participated in this study, 54 false-positive (0.095 %) and three false-negative (0.006 %) cases were found. Seven of the 54 false-positive cases (13.0 %) had vanishing twin on ultrasonography. Among the 18 false-positive cases of trisomy 18, confined placental mosaicism (CPM) was confirmed in three cases (16.7 %), while CPM was present in one of the three false-negative cases of trisomy 21. Conclusion These data suggest that the incidence of women with false-positive or false-negative results is relatively low, that such false results can often be explained, and that vanishing twin and CPM are potential causes of NIPT failure. Genetic counselling with regard to false results is important for clients prior to undergoing NIPT.

AIM To evaluate how many pregnant women would prefer to undergo prenatal genetic testing (GT) if they received adequate information during early gestation. METHODS We examined the preferences for prenatal GT among pregnant women visiting our general outpatient clinic before 16 weeks' gestation between September 2014 and September 2017. We provided them with informational brochures about prenatal GT at their first visit. Women always received genetic counseling (GC) before undergoing GT of their own choice. RESULTS Among 5700 pregnant women, 2077 (36.4%) received GC, and 1983 (34.8%) underwent some form of prenatal GT. The percentage undergoing GT was 9.4% (50/531) for 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.

Background H19 and IGF2 genes are imprinted and involved in regulating fetal and placental growth. The H19 differentially methylated region (DMR) is paternally methylated and maternally unmethylated and regulates the imprinted expression of H19 and IGF2. Epimutation at the H19-DMR in humans results in congenital growth disorders, Beckwith-Wiedemann and Silver-Russell syndromes, when erroneously its maternal allele becomes methylated and its paternal allele becomes unmethylated, respectively. Although H19 and IGF2 have been assessed for their involvement in pregnancy complications including fetal growth restriction (FGR) and pregnancy-induced hypertension (PIH)/hypertensive disorder of pregnancy (HDP) intensively in the last decade, it is still not established whether epimutation at the H19-DMR in the placenta results in pathogenic conditions in pregnancy. We aimed to assess the frequency of H19-DMR epimutation and its effects on the allelic expression patterns of H19 and IGF2 genes among normal and abnormal pregnancy cases. Results We enrolled two independently collected sets of placenta samples from normal pregnancies as controls and common pregnancy complications, FGR and PIH (HDP). The first set consisted of 39 controls and 140 FGR and/or PIH cases, and the second set consisted of 29 controls and 62 cases. For these samples, we initially screened for DNA methylation changes at H19-DMR and IGF2-DMRs by combined bisulfite restriction analysis, and further analyzed cases with methylation changes for their allelic methylation and expression patterns. We identified one case each of FGR and PIH showing hypomethylation of H19-DMR and IGF2-DMRs only in the placenta, but not in cord blood, from the first case/control set. For the PIH case, we were able to determine the allelic expression pattern of H19 to be biallelically expressed and the H19/IGF2 expression ratio to be highly elevated compared to controls. We also identified a PIH case with hypomethylation at H19-DMR and IGF2-DMRs in the placenta from the second case/control set. Conclusions Placental epimutation at H19-DMR was observed among common pregnancy complication cases at the frequency of 1.5% (3 out of 202 cases examined), but not in 68 normal pregnancy cases examined. Alteration of H19/IGF2 expression patterns due to hypomethylation of H19-DMR may have been involved in the pathogenesis of pregnancy complications in these cases. Electronic supplementary material The online version of this article (10.1186/s13148-019-0712-3) contains supplementary material, which is available to authorized users.

BACKGROUND Fetal surgery for myelomeningocele (MMC) has yet not been performed in Japan, and the clinical background of fetal MMC in Japan remains poorly described. We examined the prenatal characteristics and perinatal outcomes of fetal MMC to prepare for the introduction of fetal surgery. METHODS A nationwide questionnaire survey was conducted with regard to fetuses with MMC between January 2012 and December 2014 at perinatal centers in Japan. RESULTS In 50 tertiary centers, 188 cases of MMC were identified, of which 126 (67%) were isolated cases. Only half of the cases involved referral to tertiary centers with a diagnosis of MMC. The median time point for a prenatal diagnosis was 26 weeks' gestation (range, 12-38 weeks); in 54% of cases the diagnosis occurred after 26 gestational weeks, which is over the limit for fetal surgery for MMC. Furthermore, in 22% of cases the diagnosis was made before 22 gestational weeks, and in three-quarters of these cases termination of pregnancy was selected. No fetal or neonatal deaths were observed in the isolated MMC group. MMC repair, ventriculoperitoneal shunt and clean intermittent catheterization were required after birth in 100%, 73% and 55% of isolated MMC cases, respectively. In total, 96% of the tertiary centers cared for

OBJECTIVE To evaluate the reasons for nonreportable cell-free DNA (cfDNA) results in noninvasive prenatal testing (NIPT), we retrospectively studied maternal characteristics and other details associated with the results. METHODS A multicenter retrospective cohort study in pregnant women undergoing NIPT by massively parallel sequencing (MPS) with failed cfDNA tests was performed between April 2013 and March 2017. The women's data and MPS results were analyzed in terms of maternal characteristics, test performance, fetal fraction (FF), z scores, anticoagulation therapy, and other details of the nonreportable cases. RESULTS Overall, 110 (0.32%) of 34 626 pregnant women had nonreportable cfDNA test results after an initial blood sampling; 22 (20.0%) cases had a low FF (

Autophagy is activated by environment unfavorable for survival and requires Atg9a protein. Mice heterozygous for p57(Kip2), devoid of the imprinted paternal allele (p57(Kip2+/-)), are known to develop hypertension during pregnancy. To determine whether fetal Atg9a is involved in the intrauterine survival and growth of fetal mice, this study was performed on Atg9a heterozygous (Atg9a(+/-)) pregnant mice with and without p57(Kip2+/-). The pregnant mice heterozygous for both knockout alleles of Atg9a and p57(Kip2) (Atg9a(+/-)/p57(Kip2+/-)), but not those heterozygous for Atg9a alone, developed hypertension during pregnancy. Placental expression of Atg9a mRNA was significantly decreased in the Atg9a(-/-) mice compared to Atg9a(+/-) or Atg9a(+/+) mice. The Atg9a(-/-) fetal mice exhibited significantly retarded growth and were more likely to die in utero compared to Atg9a(+/+) and Atg9a(+/-) fetal mice. Growth retardation was observed in the presence of maternal hypertension in Atg9a(-/-) fetal mice. These results suggest that Atg9a(-/-) fetal mice from pregnant dams heterozygous for both knockout alleles of Atg9a and p57(Kip2) are more susceptible to hypertensive stress than fetuses with intact autophagic machinery.

Aim The aim of this study was to provide better counsel to pregnant women with suspected placental mesenchymal dysplasia (PMD) regarding the risks of preterm birth and intrauterine fetal death. Material and Methods We reviewed the outcomes of 109 PMD pregnancies with gestational week (GW) ≥ 24 abstracted from 63 reports in the English-language published reports, including two cases that we encountered recently. The prospective risk of stillbirth at GW N was defined as the number of women with stillbirth at GW ≥ N divided by the number of women giving birth at GW ≥ N. Results A total of 32 (29.4%) women experienced stillbirth at a median GW of 31 (range, 24–38). Preterm birth (GW

This literature review was conducted to provide better counsel to pregnant women who erroneously took angiotensin receptor blockers (ARBs) during the second and/or third trimesters regarding infant outcomes. Information was available on 83 fetuses in 34 literature reports, including one that we encountered recently. Fourteen pregnancies were terminated, and six were unknown regarding status of amniotic fluid volume (AFV). Fifty-eight and five fetuses did and did not show oligohydramnios, respectively, after being exposed to ARBs. Of the 58 fetuses that presented with oligohydramnios, 57 were exposed to ARBs at gestational week (GW) ⩾ 20, and 19 exhibited resolution of oligohydramnios 1-6 weeks after cessation of ARBs. The 24 mothers without oligohydramnios at delivery ceased taking ARBs earlier (GW of 26.8 ± 5.1 vs. 31.8 ± 4.0, respectively, P = 0.000) and had longer duration of gestation after cessation of ARBs (8.4 ± 5.2 vs. 0.7 ± 2.3 weeks, respectively, P = 0.000). The mothers without oligohydramnios also had better outcomes in terms of favorable infant outcomes (63% (15/24) vs. 15% (6/39), respectively, P = 0.000) and infant mortality rates (13% (3/24) vs. 56% (22/39), respectively, P = 0.001) than the 39 with oligohydramnios. Thus, a favorable outcome may be feasible if the fetuses are not indicated for prompt delivery at presentation and exhibit normal AFV or resolution of oligohydramnios after cessation of ARBs. Although the prevalence rate of oligohydramnios was high in this study, it may have been due to publication bias. A prospective study suggested a lower prevalence rate than that reported in the present study.

Key Clinical Message: Hypofibrinogenemia is rare in pulmonary thromboembolism. A pregnant woman with dyspnea, abdominal pain, restlessness, agitation and protein S deficiency exhibited normal blood oxygenation and high D-dimer (370 mu g/mL) and undetectable fibrinogen levels in the blood. The pathogenesis responsible for present findings may have some features similar to amniotic fluid embolism.

Objective The purpose of this study is to compare the fetal fractions during non-invasive prenatal testing (NIPT) in singleton pregnancies according to gestational age and maternal characteristics to evaluate the utility of this parameter for the prediction of pregnancy complications including gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP). Study design This study was a multicenter prospective cohort study. The present data were collected from women whose NIPT results were negative. The relationships between the fetal fractions and the gestational age, maternal weight and height, and incidences of miscarriage, preterm delivery, and pregnancy complications including GDM, HDP and placental abruption were assessed. Results A total of 5582 pregnant women with verified NIPT negative results were registered in the study. The demographic characteristics of the study populations were statistically analyzed, and the women with HDP tended to have a low fetal fraction in samples taken during early gestation. The area under the curve (AUC) in a receiver operating characteristic curve (ROC) analysis was 0.608 for women with HDP. Conclusion A low fetal fraction on NIPT might be correlated with future HDP. However, predicting HDP during early pregnancy in women with a low fetal fraction might be difficult.

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

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 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.

Aim To determine whether macrosomic infants with a birthweight of 4.0 kg or more have increased risk of cerebral palsy associated with neonatal encephalopathy (Enc-CP). Methods A retrospective review of 132 singleton infants with Enc-CP fulfilling all of the following criteria: born at gestational week (GW) 37 or more (n = 126) or weighing 2.5 kg or more at birth (n = 116) in or after January 2009 in Japan; no identifiable causes of cerebral palsy other than antenatal or intrapartum hypoxia; and exhibition of neonatal encephalopathy. National statistics of Japan were used to determine the numbers of infants according to birthweight categories. Results Of the 116 infants with a birthweight of 2.5 kg or more, 46 (39.7%), 49 (42.2%), 17 (14.7%) and four (3.4%) infants had birthweights of 2.5–2.99, 3.0–3.49, 3.5–3.99 and 4.0 kg or more, respectively. Corresponding figures among Japanese infants born in 2009–2011 were 42.8%, 45.4%, 10.9% and 0.90%, respectively. Infants with a birthweight of 4.0 kg or more had a relative risk (95% confidence interval) of Enc-CP of 3.89 (1.52–9.95) compared to those with a birthweight of 2.5–2.99 kg. Conclusion Japanese infants with a birthweight of 4.0 kg or more have increased risk of Enc-CP.

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.

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 25.0 mg/kg/day. Results Forty-four percent (69/156) of specimens with a positive test result on dipstick test contained protein

Aim Women with imminent premature labor (IPL) are transported to a tertiary hospital equipped with neonatal intensive care unit (NICU) even during the night. However, there have been no extensive studies of the occurrence rate of night IPL. The aim of this study was to determine the occurrence rate of night IPL in an area with a population of 2 million. Materials and Methods A retrospective analysis was conducted using data collected by the Sapporo Obstetric System for Emergency Patients launched in October 2008, in which women, physicians, and ambulance staff who sought appropriate obstetric/gynecological facilities available in the night (19.00–06.00 hours) were informed of candidate hospitals by coordinators through telephone consultation. This system covered the Sapporo area, which has a population of 2 000 000 and 17 000 births annually. Approximately 14% and 86% of women received antenatal care at six and 35 obstetric facilities with and without NICU, respectively, in this area. Night IPL was defined as a threatened premature labor and transport to one of six tertiary hospitals with NICU between 19.00 and 06.00 hours the next morning. Results During a 4-year period from 1 October 2008 to 30 September 2012, the Sapporo Obstetric System for Emergency Patients received 158 ± 23 (mean ± standard deviation) monthly telephone consultations (range 114–218 per month). The monthly number of patients with night IPL was 3.0 ± 2.2 (range 0–9 per month). Conclusions The monthly number of cases of night IPL was around three among women who received antenatal care at obstetrics facilities without NICU in an area with a population of 2 000 000.

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).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.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.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.

Background: The main purpose of screening and treatment for gestational diabetes mellitus (GDM) is to reduce dystocia arising from fetal overgrowth. This study was conducted to determine the risks of low-birth weight infants (LBWI) and overgrowth infants (OGI) defined as infants with birth weight

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 ± 1279 g, respectively), prevalence of blood loss >3000 g (8.3% vs 17%, respectively) or blood transfusion (92% vs 72%, respectively), time required for cesarean hysterectomy (210 ± 58 vs 195 ± 41 min), or neonatal conditions at birth. The amount of blood loss for cesarean hysterectomy was significantly less for the new than conventional method (1959 ± 1025 g vs 4450 ± 1145 g, 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.

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 ± 1.2 weeks of gestation and underwent a 75-g glucose tolerance test (GTT) at 27.4 ± 1.8 weeks 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.

Objective To determine how the D-dimer level changes after cesarean section, a topic that has not been studied extensively. Methods The D-dimer level (μg/mL) was measured in 792 and 119 women with singleton and twin pregnancies, respectively, on the day or one day before cesarean section and on postpartum days 1, 3, and 7. None of the women developed venous thromboembolism with clinical symptoms. The data for other two women who underwent a cesarean section and developed pulmonary thromboembolism on postpartum days 0 to 1 were also presented. Results The preoperative D-dimer level (median, μg/mL) of 2.4 increased on postpartum day 1 to 6.0, then decreased to 2.8 on postpartum day 3, and again increased to 4.5 on postpartum day 7 in the singleton pregnancies. A similar pattern, but with slightly higher values, was seen in the twin pregnancies. The 95 percentile value of D-dimer for singleton and twin pregnancies was 6.9 and 10.5 on days – 1/0, 19.7 and 25.7 on day 1, 9.7 and 13.5 on day 3, and 15.7 and 17.7 on day 7, respectively. The D-dimer level after pulmonary thromboembolism was greater than the 99 percentile value and the 98 percentile value in the two women, respectively. Conclusion Our data regarding the D-dimer level may be helpful when considering the normal range of D-dimer for postpartum women with cesarean delivery.

Two pregnant women who initially developed proteinuria alone followed by serious preeclampsia are presented to emphasize that there is no adequate technical term to express the period of proteinuria alone based on the current criteria of pregnancy-induced hypertension. Case 1 exhibited a urinary protein concentration of 46 mg/dL in the absence of hypertension, and abdominal pain due to placental abruption with hypertension at gestational week (GW) 29–3/7 and 29–4/7, respectively. Case 2 exhibited a urinary protein/creatinine ratio of 2.67, developed hypertension, required cesarean section, and developed posterior reversible encephalopathy syndrome at GW 28–1/7, 29–6/7, and 32–0/7, and on postpartum day 2, respectively. As women with proteinuria alone are not diagnosed as having preeclampsia and as a diagnosis of gestational proteinuria can be made only at 12 weeks postpartum, a prospective technical term applicable to the condition of proteinuria alone is needed to increase physicians’ attention to this condition.

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.

Aims To assess how the number of Japanese pregnant women with hyperglycemia changes after the adoption of the criteria proposed by the IADPSG. Methods The study subjects comprised 228 Japanese women with a plasma glucose level ≥7.8 mmol/L on a glucose challenge test and who subsequently underwent a glucose tolerance test among 1038 women with singleton pregnancies. Gestational diabetes mellitus (GDM) is currently diagnosed using the JSOG criteria in Japan. Results Of the 228 women, all 25 women with GDM and an additional 43 women without GDM according to the JSOG criteria were classified as having hyperglycemia according to the IADPSG criteria, resulting in an increase of patients with hyperglycemia from 2.4% (25/1038) to 6.6% (68/1038). The number of infants with a birthweight ≥3600 g was significantly larger among the 43 women with newly diagnosed GDM than among the 160 women who remained normoglycemic (14% [6/43] vs. 3.8% [6/160], p = 0.02). The calculated number of patients requiring treatment for a reduction of one infant with a birthweight ≥3600 g was at least 9.8 for women with newly diagnosed GDM. Conclusion The IADPSG criteria increase the number of patients by at least 2.7-fold but may be cost-effective with respect to the resulting reduction in macrosomia.

Epigenetic modifications are thought to serve as a memory of exposure to in utero environments. However, few human studies have investigated the associations between maternal nutritional conditions during pregnancy and epigenetic alterations in offspring. In this study, we report genome-wide methylation profiles for 33 postpartum placentas from pregnancies of normal and foetal growth restriction with various extents of maternal gestational weight gain. Epigenetic alterations accumulate in the placenta under adverse in utero environments, as shown by application of Smirnov-Grubbs’ outlier test. Moreover, hypermethylation occurs frequently at the promoter regions of transcriptional regulator genes, including polycomb targets and zinc-finger genes, as shown by annotations of the genomic and functional features of loci with altered DNA methylation. Aberrant epigenetic modifications at such developmental regulator loci, if occurring in foetuses as well, will elevate the risk of developing various diseases, including metabolic and mental disorders, later in life.

The aim of this study was to provide better counsel to pregnant women with suspected placental mesenchymal dysplasia (PMD) regarding the risks of preterm birth and intrauterine fetal death.We reviewed the outcomes of 109 PMD pregnancies with gestational week (GW) ≥ 24 abstracted from 63 reports in the English-language published reports, including two cases that we encountered recently. The prospective risk of stillbirth at GW N was defined as the number of women with stillbirth at GW ≥ N divided by the number of women giving birth at GW ≥ N.A total of 32 (29.4%) women experienced stillbirth at a median GW of 31 (range, 24-38). Preterm birth (GW 37) occurred in 52 (67.5%) of the 77 live-born infants. Only 25 (22.9%) women had full-term (GW ≥ 37) live-born infants. The prospective risks of stillbirth were 29.4% (32/109), 27.5% (25/91), 20.9% (14/67) and 13.0% (6/46) for women who reached GW 24(+0) , 28(+0) , 32(+0) and 36(+0) respectively.As women with PMD are at markedly elevated risk of intrauterine fetal death, early admission to the hospital and intensive monitoring of fetal status should be considered, although whether this policy improves outcome has not been validated.

Background: The prevalence of asymptomatic renal scarring, such as a focal segmental glomerulosclerosis (FSGS), was suggested to be high in women who develop preeclampsia. FSGS is a risk factor for endstage renal disease. Objective: To document preeclamptic women with proteinuria that developed eight weeks prior to hypertension with confirmed FSGS postpartum. Case: A 20-year-old nulliparous Japanese woman with a negative dipstick test result at gestational week (GW) 18 exhibited proteinuria 1+ on dipstick test at GW 22. Proteinuria determined from the random urine protein to creatinine ratio (P/Cr, g/g) was increased from 3.7 at GW 26 to 4.6 and 8.9 at GW 28 and 30, respectively. She developed hypertension (142/66 mmHg) at GW 30. Due to increased edema, emergency cesarean section was performed at GW 33. She gave birth to an otherwise healthy female small-for-gestational-age infant, weighing 1290 g. Postpartum course was uneventful except for persisting proteinuria: P/Cr of 9.8 just before delivery decreased to 3.6 and 1.7 on postpartum weeks 9 and 17, respectively. Renal biopsy on postpartum week 13 revealed FSGS in this patient. Conclusion: Hidden FSGS may have manifested as preeclampsia in this patient. This case highlighted the need to determine the prevalence of asymptomatic FSGS among women who later develop preeclampsia.

Introduction Twin pregnancy is a risk factor of complications, such as pregnancy-induced hypertension, venous thromboembolism, and postpartum hemorrhage, the pathogenesis of which may involve aberrations of the coagulation–fibrinolysis system. Materials and Methods Fibrinogen data for 129 and 1202 blood specimens from 84 and 902 women with twin and singleton pregnancies, respectively, at gestational week (GW) ≥ 32 were analyzed retrospectively. None of the 986 women developed complications in which blood fibrinogen levels may be altered. Thirty-six and 288 women with twin and singleton pregnancies were examined longitudinally, respectively. Results The fibrinogen levels of 403 ± 63 and 403 ± 77 mg/dL at GW 32 – 33 and 34 – 35, respectively, decreased significantly to 366 ± 57 mg/dL at GW 36–37 in women with twins, while corresponding levels (422 ± 79, 420 ± 65, and 415 ± 64, respectively) and that at GW ≥ 38 (408 ± 60 mg/dL) did not change significantly in women with singleton pregnancies. The fibrinogen levels determined within 3 weeks before delivery were consistently and significantly lower in women with twin than singleton pregnancies. The fibrinogen levels were significantly inversely correlated with GW in women with twins (R = –0.36, P = 0.002), but not in those with singleton pregnancies. Conclusions The fibrinogen level of twin pregnancy decreases significantly and is significantly lower than that in singleton pregnancy in the last few weeks of pregnancy.

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.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.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).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.

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.

To determine whether macrosomic infants with a birthweight of 4.0 kg or more have increased risk of cerebral palsy associated with neonatal encephalopathy (Enc-CP).A retrospective review of 132 singleton infants with Enc-CP fulfilling all of the following criteria: born at gestational week (GW) 37 or more (n = 126) or weighing 2.5 kg or more at birth (n = 116) in or after January 2009 in Japan; no identifiable causes of cerebral palsy other than antenatal or intrapartum hypoxia; and exhibition of neonatal encephalopathy. National statistics of Japan were used to determine the numbers of infants according to birthweight categories.Of the 116 infants with a birthweight of 2.5 kg or more, 46 (39.7%), 49 (42.2%), 17 (14.7%) and four (3.4%) infants had birthweights of 2.5-2.99, 3.0-3.49, 3.5-3.99 and 4.0 kg or more, respectively. Corresponding figures among Japanese infants born in 2009-2011 were 42.8%, 45.4%, 10.9% and 0.90%, respectively. Infants with a birthweight of 4.0 kg or more had a relative risk (95% confidence interval) of Enc-CP of 3.89 (1.52-9.95) compared to those with a birthweight of 2.5-2.99 kg.Japanese infants with a birthweight of 4.0 kg or more have increased risk of Enc-CP.

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 still birth was extremely high among women with ET. More intensified monitoring of fetal wellbeing may be required to improve outcome of pregnancy complicated with ET. (C) 2013 Elsevier Ltd. All rights reserved.

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 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.

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.

Objectives: To investigate the possibility of nephrinuria as a screening tool for the risk of pre-eclampsia (PE). Design: Prospective observational study. Setting: A single university hospital. Changes in urinary nephrin: creatinine ratio (NCR, ng/mg) and protein: creatinine ratio (PCR, mg/mg) in pregnancy were determined. Significant proteinuria in pregnancy (SPIP) was defined as PCR> 0.27. PE was diagnosed in women with both SPIP and hypertension. Participants: 89 pregnant women in whom neither hypertension nor SPIP was present at enrolment, providing 31, 125 and 93 random urine samples during first, second and third trimesters, respectively. Results: PE developed in 14 of the 89 women. NCR increased with increasing PCR in 14 women with PE (correlation coefficient, 0.862; p 122 (95th centile value for 75 women with normotensive pregnancies) was 5.93 (95% CI 2.59 to 13.6; 60% (6/10) vs 10% (8/79)) and 13.5 (95% CI 3.31 to 55.0; 75% (6/8) vs 5.5% (2/36)), respectively, compared with women with NCR

Women with imminent premature labor (IPL) are transported to a tertiary hospital equipped with neonatal intensive care unit (NICU) even during the night. However, there have been no extensive studies of the occurrence rate of night IPL. The aim of this study was to determine the occurrence rate of night IPL in an area with a population of 2 million.A retrospective analysis was conducted using data collected by the Sapporo Obstetric System for Emergency Patients launched in October 2008, in which women, physicians, and ambulance staff who sought appropriate obstetric/gynecological facilities available in the night (19.00-06.00 hours) were informed of candidate hospitals by coordinators through telephone consultation. This system covered the Sapporo area, which has a population of 2,000,000 and 17,000 births annually. Approximately 14% and 86% of women received antenatal care at six and 35 obstetric facilities with and without NICU, respectively, in this area. Night IPL was defined as a threatened premature labor and transport to one of six tertiary hospitals with NICU between 19.00 and 06.00 hours the next morning.During a 4-year period from 1 October 2008 to 30 September 2012, the Sapporo Obstetric System for Emergency Patients received 158 ± 23 (mean ± standard deviation) monthly telephone consultations (range 114-218 per month). The monthly number of patients with night IPL was 3.0 ± 2.2 (range 0-9 per month).The monthly number of cases of night IPL was around three among women who received antenatal care at obstetrics facilities without NICU in an area with a population of 2,000,000.

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.A complete blood count was performed and the AT activity was examined in 300 consecutive women admitted to hospital ator = 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 gainor = 0.5 kg, or other specific complications upon admission. All the women attempted a vaginal delivery.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 ofor = the median (11.0 g/dL) gave birth to significantly smaller infants than their counterparts.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.

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.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 was11.0 mg/kg/day or25.0 mg/kg/day.Forty-four percent (69/156) of specimens with a positive test result on dipstick test contained protein30 mg/dL. Dipstick test was positive for 25.7% (69/269) of specimens with protein30 mg/dL and for 28.8% (79/274) of specimens with P/Cr ratio0.27. P-test results were positive for 7.3% (20/274) and negative for 18.1% (15/83) of specimens with P/Cr ratio0.27 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.Dipstick test and P-test were likely to over- and underestimate risks of significant proteinuria, respectively. The 24-h urine collection was often incomplete.

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.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.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 loss3000g (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). 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.

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.

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.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.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.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.

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.