Pregnant women's opinions toward prenatal pretest genetic counseling in Japan.

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 <15 min (14.9%). Women's preference of ≥30 min in length was significantly associated with anhedonia, singleton pregnancies, acquaintance with people with trisomy 21, and awareness of prenatal testing. Women who were unaware of the need for agreement with the partner for prenatal testing and who did not know the average life expectancy of a trisomy 21 patient significantly preferred <15 min in length over other durations. While the majority of women preferred in-person GC for <30 min, their preferences varied by their background characteristics, experiences, attitudes, and knowledge. These findings will help establish a prenatal GC system offering a choice of GC models in Japan; however, further large-scale studies are needed to confirm these findings.

Attitudes toward and current status of disclosure of secondary findings from next-generation sequencing: a nation-wide survey of clinical genetics professionals in Japan.

The management of secondary findings (SFs), which are beyond the intended purpose of the analysis, from clinical comprehensive genomic analysis using next generation sequencing (NGS) presents challenges. Policy statements regarding their clinical management have been announced in Japan and other countries. In Japan, however, the current status of and attitudes of clinical genetics professionals toward reporting them are unclear. We conducted a questionnaire survey of clinical genetics professionals at two time points (2013 and 2019) to determine the enforcement of the SF management policy in cases of comprehensive genetic analysis of intractable diseases and clinical cancer genome profiling testing. According to the survey findings, 40% and 70% of the respondents stated in the 2013 and 2019 surveys, respectively, that they had an SF policy in the field of intractable diseases, indicating that SF policy awareness in Japan has changed significantly in recent years. Furthermore, a total of 80% of respondents stated that their facility had established a policy for clinical cancer genome profiling testing in the 2019 survey. In both surveys, the policies included the selection criteria for genes to be disclosed and the procedure to return SFs, followed by recommendations and proposals regarding SFs in Japan and other countries. To create a better list of the genes to be disclosed, further examination is needed considering the characteristics of each analysis.

Nonreportable rates and cell-free DNA profiles in noninvasive prenatal testing among women with heparin treatment.

OBJECTIVE: To evaluate the "nonreportable" rate in patients treated with heparin and to determine the effect of heparin on the results of noninvasive prenatal testing (NIPT). METHOD: This was a single-center retrospective study of NIPT. The "nonreportable" rate of NIPT was evaluated according to presence or absence of heparin treatment. After excluding true-positive cases, a matched cohort study evaluating Z-scores, GC bias, and cell-free DNA (cfDNA) profiles was performed to investigate the effect of heparin on NIPT results. RESULTS: Overall, 2651 singleton pregnancies with available clinical information were evaluated; 23 mothers were treated with heparin. The nonreportable rate was much higher among patients treated with heparin than among those who were not (8.70% vs 0.15%). In the matched cohort study, the Z-scores for chromosomes 13, 18, and 21, and GC bias were significantly higher in the heparin group than in the matched control group. Based on cfDNA library electrophoresis data, the proportion of short-sized cfDNA was higher in the heparin group. CONCLUSION: Heparin use increased the nonreportable rate of NIPT results by borderline Z-scores, possibly caused by the increased proportions of shorter and GC-rich cfDNA fragments. This information will be helpful for prenatal genetic counseling for patients requiring heparin treatment.

Pregnant women's preferences for prenatal genetic testing: A single-center study in Japan.

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 <30 years old, 19.0% (309/1623) for those 30-34 years old, 43.1% (989/2294) for those 35-39 years old, and 50.7% (635/1252) for those ≥40 years old. Older pregnant women tended to receive GC and GT more often than younger women (P < 0.001). The most common reason for receiving GC was advanced maternal age (79.7%). The most common prenatal GT was noninvasive prenatal testing (NIPT) (50%), followed by the combined test (29.0%) and quadruple test (11.2%). Pregnant women ≥35 years old tended to choose NIPT (60.5%), while those <35 years old tended to choose the combined test (52.9%). CONCLUSION: About one-third of the pregnant women preferred to receive prenatal GT by their own choice. Women's preferences for prenatal GT increased with maternal age; however, half of pregnant women with an advanced maternal age preferred not to undergo GT, even if they were well informed.

Attitudes of clinical geneticists and certified genetic counselors to genome editing and its clinical applications: A nation-wide questionnaire survey in Japan.

Genome editing of the human embryo using CRISPR/Cas9 has the potential to prevent hereditary diseases from being transmitted to the next generation. However, attitudes to this technology have not been examined sufficiently among the genetic professionals who will use it in the near future. We conducted a questionnaire survey of Japanese clinical geneticists and certified genetic counselors. Differences were observed between them in their recognition of this technology and impressions on its difficulty and cost. Both groups worried about misuse of it, with insufficient information and rules. As key elements for such rules, they considered ethics, safety, and purpose. Most disapproved of modifying physical traits as an enhancement, though they hoped for the treatment of severe diseases. At current clinical sites, they tended to adopt a prudent attitude by mentioning only the possibility of genome editing in the future. Academic policies and legislation are required, especially for application in human embryos, through a consensus of professionals and general citizens. Furthermore, professionals should maintain awareness of new developments and regularly reexamine attitudes for the ongoing development of more suitable rules, education systems, and clinical protocols. As preparation for changes, opportunities to address ethical issues and initiate discussions are also required.

Classification of factors involved in nonreportable results of noninvasive prenatal testing (NIPT) and prediction of success rate of second NIPT.

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 (<4%), and 18 (16.4%) cases including those with a maternal malignancy, were found to have altered genomic profile. Approximately half of the cases with nonreportable results had borderline z score. Among the women with nonreportable results because of altered genomic profile, the success rate of retesting using a second blood sampling was relatively low (25.0%-33.3%). Thirteen (11.8%) of the women with nonreportable results had required hypodermic heparin injection. CONCLUSIONS: The classification of nonreportable results using cfDNA analysis is important to provide women with precise information and to reduce anxiety during pregnancy.

Nationwide survey of fetal myelomeningocele in Japan: Background for fetal surgery.

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 <5 cases of fetal MMC per year. CONCLUSIONS: Gestational age at MMC diagnosis was late mid-gestation, therefore earlier detection is essential when considering fetal treatment of MMC in Japan. Although the survival rate was excellent, in three-quarters of isolated MMC cases ventriculoperitoneal shunt was required. Early detection and centralization of MMC cases at specialized centers should be considered.

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.

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.

Prospective risk of stillbirth in women with placental mesenchymal dysplasia.

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 < 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. CONCLUSION: 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.

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.

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.

Risk of cerebral palsy associated with neonatal encephalopathy in macrosomic neonates.

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.

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.

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.

Cost-Effectiveness Analysis of Maternal Respiratory Syncytial Virus Vaccine in Protecting Infants from RSV Infection in Japan.

INTRODUCTION: Respiratory syncytial virus (RSV) is one of the major causes of respiratory tract infections among children. Until recently, the monoclonal antibody palivizumab was the only RSV prophylaxis available in Japan. In 2024, the bivalent RSV prefusion F protein-based (RSVpreF) vaccine was approved for the prevention of RSV infection in infants by active immunization of pregnant women. In this study, we assessed the cost-effectiveness of a combined strategy of RSVpreF vaccine and palivizumab in Japanese setting. METHODS: Using a Markov model, we evaluated prevented cases and deaths of medically attended RSV infections from birth to age 11 months for each of the three healthcare settings: inpatient (hospitalization), emergency department visits, and outpatient visits. Incremental cost-effectiveness ratios (ICERs) were calculated from economic outcomes (intervention costs, medication costs, and productivity losses) and quality-adjusted life years (QALYs). Further, we calculated the maximum price of RSVpreF vaccine within which the program would be cost-effective. RESULTS: In comparison with the current prophylaxis (palivizumab alone), a combined prophylaxis of year-round RSVpreF vaccination of pregnant women and palivizumab prescription for premature infants born in < 32 weeks gestational age (wGA) and all infants with high risk prevented 14,382 medically attended cases of RSV (hospitalization, 7490 cases; emergency department, 2239 cases; outpatient, 4653 cases) and 7 deaths, respectively. From a healthcare payer perspective, when the price of RSVpreF vaccine was equal to or less than ¥23,948 (US $182), a combination prophylaxis was cost-effective under the ICER threshold of ¥5 million per QALY. The other combination prophylaxis of year-round RSVpreF vaccination and palivizumab prescription of premature born in < 32 wGA regardless of risk in infants was a dominant strategy (more effective and less costly). CONCLUSION: A combined prophylaxis of year-round RSVpreF vaccine and palivizumab could be a cost-effective strategy to protect neonates throughout the infant stage (< 1 years old) in Japan.

Number of women requiring care at a tertiary hospital equipped with a neonatal intensive care unit at night in an area with a population of 2 million.

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.

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.