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Background: Non-invasive prenatal testing (NIPT) is offered as a reproductive choice in many countries. However, pregnant women, particularly those who are primipara or lack knowledge of prenatal testing, experience difficulties understanding adequate information and making decisions on NIPT. This study developed a preconception education program about NIPT, focusing on interest in genetics, and aimed to clarify the effectiveness of the program to help women make decisions on future NIPT. Methods: This was a one-group, quasi-experimental, pre-post-test study. The study population was female undergraduate students in Japan who participated in the education program. This program included two games and was based on the Attention, Relevance, Confidence, and Satisfaction (ARCS) model, which is an instructional design that stimulates learning interest and motivation. The data of 73 pre-pregnant women who completed all three questionnaires—before, immediately after, and three months after the intervention—were analyzed to clarify the time effects. Moreover, all variables were analyzed using logistic regression analysis to investigate factors related to decisional conflict. Results: Interest in genetics, knowledge of genetics and prenatal testing, and indecisive attitudes toward NIPT significantly improved immediately after the intervention, and consequently, these changes and reduction of decisional conflict were maintained at three months. Moreover, low decisional conflict at follow-up was significantly associated with a high interest in genetics (adjusted odds ratio, 3.42). Conclusions: These findings provide preliminary evidence that this preconception education program, which focused on facilitating interest in genetics, assists pre-pregnant women to reduce decisional conflict about future NIPT. Trial registration: The trial was registered at the UMIN-CTR registry (January 16, 2023), registration number UMIN000050047. [ABSTRACT FROM AUTHOR]

Background: Breech presentation is observed in 3–4% at term of pregnancy and is one of the leading causes of cesarean section. There is no established treatment for breech presentation before 36 weeks. A retrospective cohort study was conducted to demonstrate that the lateral position is effective for breech presentation. However, there are no randomized controlled trials evaluating lateral position management for breech presentation. Here, we described the methodology of a randomized controlled trial of a cephalic version for breech presentation in the third trimester by lateral postural management (BRLT study). Methods: The BRLT study is an open-label, randomized controlled trial with two parallel groups allocated in a 1:1 ratio to examine the lateral position management for breech presentation, as compared with expectant management care. An academic hospital in Japan will enroll 200 patients diagnosed with a breech presentation by ultrasonography between 28 + 0 weeks and 30 + 0 weeks. Participants in the intervention group will be instructed to lie on their right sides for 15 min three times per day if the fetal back was on the left side or lie on their left sides if the fetal back was on the right side. The instruction will be given every 2 weeks after confirmation of fetal position, and the lateral position will be instructed until the cephalic version, and after the cephalic version, the reverse lateral position will be instructed until delivery. The primary outcome is cephalic presentation at term. The secondary outcomes are cesarean delivery, cephalic presentation 2, 4, and 6 weeks after the instruction, and at delivery, recurrent breech presentation after cephalic version, and adverse effects. Discussion: This trial will answer whether the lateral positioning technique is effective in treating breech presentation and, depending on the results, may provide a very simple, less painful, and safe option for treating breech presentation before 36 weeks, and it may impact breech presentation treatment. Trial registration: UMIN Clinical Trials Registry UMIN000043613. Registered on 15 March 2021 https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000049800. [ABSTRACT FROM AUTHOR]

Background: Noninvasive prenatal testing (NIPT) is used to screen for fetal chromosomal abnormalities, such as fetal aneuploidy, and has been offered at our hospital since 2013. We analyzed data from our center to determine if NIPT screenees could be given more-accurate information on NIPT outcomes. Methods: This retrospective observational study included 819 pregnant women who requested NIPT at Nippon Medical School Hospital from November 2013 to October 2021. We examined medical records for data on NIPT results and clinical outcomes. Results: Of the 819 women, 764 (93.2%) underwent NIPT, and 55 (6.7%) did not. Of the 764 women who underwent NIPT, 17 received a positive result (2.2%), of whom 2 (11.8%), 4 (23.5%), and 11 (64.7%) received a positive result for trisomy 13, 18, and 21, respectively. The true-positive rates after definitive diagnoses of trisomy 13, 18, and 21 were 1 (50%), 3 (75%), and 11 (100%), respectively. Of the 17 positive results, there were two false-positive results (11.8%) (for trisomy 13 and trisomy 18). Eleven women with fetal aneuploidy terminated their pregnancies, and four cases resulted in intrauterine fetal death. Five neonates with negative NIPT results had congenital disease without chromosomal abnormality. Two patients had indeterminate results from the first blood sampling, possibly because of treatment with unfractionated heparin. The results of repeat testing after heparin cessation were negative. Conclusions: Our results were generally similar to nationwide data for Japan. NIPT providers can provide more detailed and individualized genetic counseling for each situation by understanding their own medical facility's data in detail. [ABSTRACT FROM AUTHOR]

Prenatal diagnoses of mitochondrial diseases caused by defects in nuclear DNA (nDNA) or mitochondrial DNA have been reported in several countries except for Japan. The present study aimed to clarify the status of prenatal genetic diagnosis of mitochondrial diseases caused by nDNA defects in Japan. A comprehensive genomic analysis was performed to diagnose more than 400 patients, of which, 13 families (16 cases) had requested prenatal diagnoses. Eight cases diagnosed with wild type homozygous or heterozygous variants same as either of the heterozygous parents continued the pregnancy and delivered healthy babies. Another eight cases were diagnosed with homozygous, compound heterozygous, or hemizygous variants same as the proband. Of these, seven families chose to terminate the pregnancy, while one decided to continue the pregnancy. Neonatal- or infantile-onset mitochondrial diseases show severe phenotypes and lead to lethality. Therefore, such diseases could be candidates for prenatal diagnosis with careful genetic counseling, and prenatal testing could be a viable option for families. [ABSTRACT FROM AUTHOR]

Background: Screening of pregnant women carrying human T-lymphotropic virus type 1 (HTLV-1) has a crucial role in reducing the number of HTLV-1 carriers. A national HTLV-1 screening program for pregnant women was started in 2011 in Japan. The purpose of this study is to report on the implementation of this nationwide screening program.Methods: This was a retrospective repeated cross-sectional study. We used datasets from surveys of HTLV-1-antibody-positive pregnant women performed by the Japan Association of Obstetricians and Gynecologists in 2011, 2013, and 2016. Outcomes for evaluation included the number of persons (pregnant women) who conducted the screening test, the number of positive persons (women) identified by these tests, and the proportion of positive persons to the number of persons (women) who conducted the tests.Results: Numbers of target facilities changed yearly: 1857 in 2011, 2544 in 2013, and 2376 in 2016. The mean number of screening-test participants increased per facility, but the median increased or decreased. The mean number of positive individuals identified decreased. Multivariate analysis results revealed the number of screenings was slightly reduced yearly, although areas (Kanto and Kinki) and high volume in facility types increased. Regarding the positive rates, some areas (Hokkaido/Tohoku, Kanto, and Chugoku/Shikoku) exhibited decreases or increases by facility type. The number of western blotting (WB) implementations decreased in 2016, positive rates identified by WB decreased in 2016 in all areas, and the number of facility types increased. The number of PCR participants increased in 2016 in Kanto and Kinki, but a decrease in facility type was observed. Positive rates were decreased in all areas (except the central region) but facility types were increased.Conclusions: The nationwide screening program for HTLV-1 in Japan was almost fully implemented. However, regional variations in screening tests were observed during this implementation. Thus, some incentives are needed to encourage proper implementation across all regions. [ABSTRACT FROM AUTHOR]

Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-021-81015-y, published online 11 February 2021 The original version of this Article contained errors. One family had X chromosome-linked gene mutation; the other 12 families had autosomal recessive gene mutations. [Extracted from the article]

Introduction: The Non-Invasive Prenatal Testing (NIPT) guideline was issued and applied in 2013 by the Japanese Medical Association. Since being issued, the NIPT practice in Japan still has some problems related to indication, access, cost coverage and uniformity. Therefore, our study aimed to identify the Japanese challenges of adopting NIPT into prenatal diagnosis by comparing the system and process with other countries., Method: The United Kingdom, Germany, Italy, Sweden, and Taiwan were purposefully selected for comparison. All the countries, including Japan, introduced NIPT. The literature and information searches were conducted using PubMed, SCOPUS, Google Scholar, CiNii and Google searching engine., Results: The process of NIPT in Japan was very different from the other countries. Japan is the only country that indicated NIPT for only pregnant women over 35 years old in certificated facilities and did not have a policy regarding providing information on prenatal screening and NIPT to all women. Japan also did not have a policy regarding abortion due to fetal abnormalities. The practice of NIPT guidelines is different between non-certified and certified facilities. NIPT fee was the highest in Japan and was not covered by insurance., Conclusion: Pregnant women in Japan suffered from disparities in information access, economic burden, geographic location, and practice of NIPT guidelines between the certified and the non-certified facilities. Pregnant women-centered prenatal diagnosis policy, including NIPT, should be established in Japan by learning cases from other countries.

Background: Recent advances in prenatal screening and diagnosis have resulted in an increasing number of women receiving a diagnosis of fetal anomalies. In this study, we aimed to clarify the hopes for childbirth and parenting of women diagnosed with fetal anomalies and to suggest a family-centered care tailored for this situation in perinatal settings., Methods: A descriptive qualitative study was performed. We recruited women diagnosed with fetal anomalies who were over 22 years old, beyond 22 weeks of gestation, and had scheduled pregnancy and delivery management at a tertiary perinatal medical center specializing in neonatal and pediatric care in a metropolitan area of Japan from April 2019 to December 2019. Women who were willing to participate received support from a midwife to create birth plans. Data were collected from the documented birth plans submitted by 24 women and analyzed using content analysis., Results: We identified three themes of women's hopes based on the descriptions of the submitted birth plans: (1) Hopes as women who are expecting childbirth, (2) Hopes as mothers of a baby, (3) Hopes of being involved in the family needs. Several distinctive hopes were clarified in the context of the women's challenging situations. In describing their hopes, the women were neither overoptimistic or overstated their actual situations, nor caused embarrassment to the healthcare providers. The importance of supporting their involvement in baby matters in the way each family wants also emerged. However, several barriers to fulfilling the women's hopes were identified including the babies' conditions and hospital regulations against family visits or presence., Conclusion: All three themes identified in the study provide important insights for analyzing more deeply ways of implementing a family-centered care for women diagnosed with fetal anomalies in perinatal settings. To improve women's engagement in decision-making as a team member, women's hopes should be treated with dignity and respect, and included in the perinatal care of women with abnormal fetuses. Further research is needed to improve the inclusion of women's hopes in their care in clinical settings., Trial Registration: UMIN Clinical Trials Registry: UMIN000033622 (First registration date: 03/08/2018)., (© 2022. The Author(s).)

Objective: To evaluate clinical features of assisted reproductive technology (ART) patients with pregnancy-induced hypertension (PIH) compared to spontaneously conceived PIH patients. Methods: We retrospectively compared PIH incidence, maternal outcomes, and neonatal outcomes among these patients. Results: Preeclampsia, cesarean rate, and massive maternal bleeding were significantly more common in the ART group. Neonatal outcomes showed no significant difference between the groups. Multiple regression analysis revealed ART as an independent risk factor for preeclampsia. However, higher cesarean rate and massive bleeding were mainly associated with multiple pregnancy. Conclusion: ART patients with PIH had an increased incidence of preeclampsia, cesarean delivery, and massive maternal hemorrhage. [ABSTRACT FROM AUTHOR]

Background: Pervasive developmental disorder (PDD) has an uncertain etiology, no method of treatment, and results in communication deficiencies and other behavioral problems. As the reported recurrence risk is 5%-10% and there are no methods of either prevention or prenatal testing, mothers of PDD children may face unique challenges when contemplating second pregnancies. The purpose of this study was to explore the mothers' lived experiences of second child-related decision-making after the birth of a child with PDD. Methods: The participants for this study were restricted to mothers living within the greater Tokyo metropolitan area who had given birth to a first child with PDD within the past 18 years. The ten participants were encouraged to describe their experiences of second-child related decision-making after the birth of a child with PDD on the basis of semi-structured interviews. Data analysis was performed by using Interpretive Phenomenological Analysis (IPA), which is concerned with understanding what the participant thinks or believes about the topic under discussion. Results: We identified two superordinate themes. The first was balancing hopes and fears, in which hope was the potential joy to be gained by the birth of a new child without PDD and fears were characterized as uncertainty of PDD and perception of recurrence risk, burden on later-born children, and negative effects on a child with PDD. The second superordinate theme was assessing the manageability of the situation, which was affected by factors as diverse as severity of PDD, relationship between mother and father, and social support and acceptance for PDD. Our 10 participants suffered from extreme psychological conflict, and lack of social support and acceptance for PDD created numerous practical difficulties in having second children. Conclusions: Our participants faced various difficulties when considering second pregnancies after the birth of children with PDD in the Japanese society. As lack of social support and acceptance for PDD also played a large role in second child-related decision-making, creating a social environment that more fully accepts those disabled and providing flexible support systems for families of children with PDD are crucial. [ABSTRACT FROM AUTHOR]

In this article, I explore the reluctance of Japanese ob-gyns to discuss prenatal diagnosis (PND) tests with pregnant women. The analysis focuses on the culturally specific ways in which ob-gyns formulate their cautiousness and criticism toward PND while invoking a local moral economy. Analyzing ob-gyns' accounts, I show how the ambiguities of PND are constituted in a specific moment in Japanese culture, history, disability politics, and national reproductive policies and are formulated through local paradigms of thinking about pregnant women, their fetuses, and the process of becoming a person in Japanese society. Finally, I show how PND in Japan is pushed to a "back-stage" realm in which the diagnosis for fetal anomalies is practiced in secrecy. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the association between the urinary 8-hydroxy-2'-deoxyguanosine (U8-OHdG) levels and the incidence of small-for-gestational age (SGA) infants and to assess the utility of U8-OHdG as a biomarker to predict the incidence of SGA infants., Design: Prospective cohort study., Setting: The Japan Environment and Children's Study., Participants: Data of participants enrolled in the Japan Environment and Children's Study, a nationwide birth cohort study, between 2011 and 2014 were analysed; 104 062 fetal records were analysed. Data of women with singleton pregnancies ≥22 weeks of gestation were analysed., Primary and Secondary Outcome Measures: U8-OHdG levels were assessed using liquid chromatography-tandem mass spectrometry. Participants were categorised into the following three groups according to the quartile of the distribution of U8-OHdG: low U8-OHdG (<1.95 ng/mgCre), moderate U8-OHdG (the combined second and third quartiles; 1.95-2.95 ng/mgCre) and high U8-OHdG (>2.95 ng/mgCre) groups. Additionally, participants in the 90th percentile for U8-OHdG levels were analysed. Odds ratios (ORs) for SGA infants (<-1.5 and <-2.0 SD) were calculated using a logistic regression model while adjusting for confounding factors; the moderate U8-OHdG group was used as a reference. The cut-off value of U8-OHdG to predict the incidence of SGA infants was calculated using a receiver operating characteristic (ROC) curve analysis., Results: Data of 80 212 participants were analysed. The adjusted ORs for SGA infants (<-1.5 and<-2.0 SD) in the high U8-OHdG group were 1.16 (95% CI 1.07 to 1.25) and 1.22 (95% CI 1.07 to 1.38). The cut-off value of U8-OHdG (3.26 ng/mgCre) showed a poor ability to predict SGA infants (sensitivity, 21.9%; specificity, 83.6%; area under the ROC curve, 0.530)., Conclusions: Elevated U8-OHdG levels were associated with an increased incidence of SGA infants. However, this parameter would not be a useful screening tool for predicting SGA infants owing to its low sensitivity and specificity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Investigation into the detection rate (DR) of congenital heart diseases (CHDs) in fetuses is important for the assessment of fetal cardiac screening systems., Objectives: We highlight issues of fetal cardiac screening in Japan., Methods: We performed an initial national survey of fetal diagnosis of CHDs from the data of the national registry for congenital heart surgery from 2013 to 2017. Subjects were neonates and infants with moderate or severe CHDs. We investigated DR in each prefecture in Japan and emergency transfer (ET) for neonates by analyzing distance and admission day of ET with or without fetal diagnoses., Results: The overall average DR in Japan was 0.41 (0.02 increase every year). No regional significant relationship was found between DR and population in each prefecture. ET was performed in 12% of neonates with prenatal diagnosis and in 63% of neonates without resulting in significant risk for ET in fetuses without a fetal diagnosis [OR 13.3 (11.6-15.3), p<0.001]. The distance of ET was shorter and admission was earlier in the neonates with a prenatal diagnosis than in those without [median 6.6 km (IQR: 4.1-25.7) vs 17.0 km (IQR: 7.4-35.3), median 0.0 day (IQR: 0.0-0.0) vs 0.0 day (IQR: 0.0-1.0), p<0.001, p<0.001, respectively] CONCLUSIONS: Prenatal cardiac diagnosis reduces geographic and chronological risks of ET for moderate to severe CHDs. DR is still developing and periodic official surveillance is required for improving prenatal cardiac diagnosis in Japan., Competing Interests: Declaration of Competing Interest All authors have no conflicts of interest to declare except JSPS KAKENHI (a non-profit organization). All authors have no conflict of interest to disclose., (Copyright © 2021. Published by Elsevier Ltd.)

Japan, known as a pro-choice country in terms of abortion, is currently facing the increase of "selective abortions" thanks to new prenatal screening. Efforts to restrict proliferation of new technology has not been successful and it is likely that Japan will turn pro-life by strictly enforcing the Maternity Protection Act (MPA), which prohibits abortions due to "fetal cause". [ABSTRACT FROM AUTHOR]

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.

Background: Congenital heart disease (CHD) is often diagnosed prenatally using fetal echocardiography, but few studies have evaluated the accuracy of these fetal cardiac diagnoses in detail. We investigated the discrepancy between pre- and postnatal diagnoses of CHD and the impact of discrepant diagnoses.Methods and Results:This retrospective study at a tertiary institution included data from the medical records of 207 neonates with prenatally diagnosed CHD admitted to the cardiac neonatal intensive care unit between January 2011 and December 2016. Pre- and postnatal diagnoses of CHD differed in 12% of neonates. Coarctation of the aorta and ventricular septal defects were the most frequent causes of discrepant diagnosis. Unexpected treatments were added to 38% of discrepant diagnostic cases. However, discrepant diagnoses did not adversely affect the clinical course. The 9% of the 207 neonates who required invasive intervention within 24 h of delivery were accurately diagnosed prenatally., Conclusions: Pre- and postnatal diagnoses differed in only a few neonates, with differences not adversely affecting the clinical course. Neonates who required invasive intervention immediately after delivery were accurately diagnosed prenatally. Prenatal diagnosis thus seems to contribute to improved prognosis in neonates with CHD.

Background: Malignancy during pregnancy has become a significant cause of maternal death in developed countries, likely due to both an older pregnant population, and increases of cervical cancer in younger women. Our aim is to investigate the clinical aspects of malignancy during pregnancy in Japan and to use this information to identify opportunities for earlier detection and treatment.Methods: We provided a questionnaire to 1508 secondary or tertiary care hospitals in Japan. We reviewed the clinical characteristics of cases with malignancy during pregnancy for the period of January to December, 2008. From the 760 institutions which responded, we obtained clinical information for 227 unique cases. The questionnaire provided clinical information, including disease site, pregnancy outcome and how the disease was detected.Results: The most common type of malignancy was cervical cancer (n = 162, 71.4%) followed by ovarian (n = 16, 7.0%) and breast cancer (n = 15, 6.6%). Leukemia (n = 7, 3.1%), colon cancer (n = 5, 2.2%), gastric cancer (n = 5, 2.2%), malignant lymphoma (n = 4, 1.8%), thyroid cancer (n = 3, 1.3%), brain cancer (n = 3, 1.3%), endometrial cancer (n = 2, 0.9%), and head and neck cancer (n = 2, 0.9%) accounted for the remaining cases. Overall, gynecological malignancies accounted for 79.3% (95% confidence interval 74.0-84.6) of pregnancy associated malignancies diagnosed in the present study. The majority of cervical cancers, 149 (92.0%) of 162, were diagnosed by a Pap (Papanicolaou) smear during early gestation. Ten (62.5%) of the ovarian cancer cases were diagnosed by ultrasonography during a prenatal checkup or at the time of initial pregnancy diagnosis. Out of 14 breast cancers, only one (7.1%) was diagnosed by screening breast exam.Conclusions: From this study, we reaffirm the clear and significant benefits of prenatal checkups starting at an early gestational age for the detection of gynecological cancers during pregnancy. Conversely, breast cancer detection during pregnancy was poor, suggesting new strategies for early identification of this disease are required. [ABSTRACT FROM AUTHOR]

There is a paucity of information on perinatal data regarding gestational diabetes mellitus (GDM) by the new criteria from a real experience because the number of health care associations implementing the new criteria is still limited. The aim of this study is to investigate perinatal features of the new criteria-defined GDM. We reviewed a total of 995 women with singleton pregnancy that underwent GDM screening followed by a diagnostic oral glucose tolerance test (OGTT). All women found to have GDM underwent self-monitoring of blood glucose measurements as well as dietary management. Insulin treatment was initiated when dietary treatment did not achieve the glycemic goal. Of the 995 women, 141 had GDM (14.2%): 104 with one, 27 with two, and 10 with three abnormal OGTT values. Women with two or three abnormal OGTT values (2/3-AV) needed insulin treatment more frequently than those with one abnormal OGTT value (1-AV) (70.3% vs 23.1%, P < 0.0001). After adjustment for age, pregravid overweight, gestational weeks at diagnosis, a first-degree family history of diabetes was correlated with the implementation of insulin treatment in women with 1-AV (adjusted odds ratio 3.9; 95% Confidence Interval 1.7-9.2; P = 0.001). When compared perinatal outcomes between women with normal glucose tolerance and GDM, fetal growth and the occurrence of pregnancy-induced hypertension were comparable between the two groups. Our data suggest that the IADPSG-defined GDM with 1-AV show less severe glucose intolerance, but might be at risk of insulin requirement when a first-degree family history of diabetes exists.

This study examines the attitudes of young Japanese, Chinese, and South Koreans toward birth and child-rearing. The survey targeted four-year university students (n＝1,668) who responded to an anonymous survey using self-report questionnaires between December 2012 and April 2013. The collection rates were 72.5%, 94.7%, and 96.5% for the Japanese, Chinese, and South Korean students, respectively. Correlations among the respondents' attributes, medical and scientific literacy levels, and views of preferred qualities of children were analyzed using chi-square test, supplemented by residual analysis (significance level set at p＜0.05). Participants were asked whether they were willing to use the following methods for obtaining preferred qualities in their children:(1) choosing a spouse (43.2%, 72.6%, and 85.1% of the Japanese, Chinese, and South Koreans, respectively, agreed);(2) using a sperm bank (cryobank) (5.8%, 60.1%, and 81.7% of the Japanese, Chines, and South Koreans, respectively, agreed);and (3) using an egg cell bank (ova bank or cryobank) (5.3%, 47.2%, and 70.3% of the Japanese, Chinese, and South Koreans, respectively, agreed). The proportion of affirmative responses (indicating "eugenic inclination") to these statements was significantly higher among the Chinese and South Korean participants than their Japanese counterparts (p＜0.001). Significant differences were also found in the attitudes of the 3 groups toward methods for obtaining the preferred qualities for their children:prenatal diagnosis, pre-implantation diagnosis, the environment during pregnancy, and child-rearing.

The aim of this study is to investigate glucose metabolism longitudinally during pregnancy to explore mechanisms underlying gestational diabetes mellitus (GDM). We reviewed a total of 62 pregnant Japanese women who underwent a 75g oral glucose tolerance test (OGTT) twice during pregnancy (median: early, 13; late, 28 weeks' gestation) because of positive GDM screening. All showed normal OGTT results in early pregnancy. Based on late OGTT, 15 had GDM (late-onset GDM) and 47 normal glucose tolerance (NGT). In early pregnancy, there were no significant differences in insulin sensitivity (insulin sensitivity index derived from OGTT [IS(OGTT)] and homeostasis model assessment for insulin resistance [HOMA-IR]) and insulin secretion (a ratio of the total area-under-the-insulin-curve to the total area-under-the-glucose-curve [AUC(ins/glu)] and insulinogenic index [IGI]) between the NGT and late-onset GDM groups. In each group, insulin sensitivity significantly decreased from early to late pregnancy, most in the late-onset GDM group (each p < 0.05). The insulin secretion showed no significant changes with advancing pregnancy in both of the groups, although late-onset GDM showed significantly lower IGI compared with NGT in late OGTT (p < 0.05). When assessed beta cell function by OGTT-derived disposition index (i.e. Insulin Secretion-Sensitivity Index-2 and IGI/fasting insulin), the indices significantly decreased from early to late pregnancy in the both groups (each p < 0.05). Women with late-onset GDM showed significantly lower indices compared with NGT (each p < 0.05). The failure of beta cell to compensate for decreased insulin sensitivity could contribute to the development of the late-onset GDM.

Background: There are few large studies of fetal congenital bradyarrhythmia. The aim of the present study was to investigate the effects and risks of transplacental treatment for this condition., Methods and Results: Using questionnaires, 128 cases of fetal bradyarrhythmia were identified at 52 Japanese institutions from 2002 to 2008. Of the 128 fetuses, 90 had structurally normal hearts. Among these 90 fetuses, 61 had complete atrioventricular block (CAVB), 16 had second-degree AVB, 8 had sinus bradycardia, and 5 had other conditions. The 61 CAVB fetuses were divided into those who did (n = 38) and those who did not (n = 23) receive transplacental medication. Monotherapy with β-sympathomimetics, steroid monotherapy, and combination therapy with these agents was given in 11, 5 and 22 cases, respectively. Beta-sympathomimetics improved bradycardia (P<0.001), but no medication could significantly improve the survival rate. Fetal hydrops was associated with a 14-fold increased risk of perinatal death (P = 0.001), and myocardial dysfunction was a significant risk factor for poor prognosis (P = 0.034). Many adverse effects were observed with steroid treatment, with fetal growth restriction increasing significantly after >10 weeks on steroids (P = 0.043)., Conclusions: Treatment with β-sympathomimetics improved bradycardia, but survival rate did not differ significantly in fetuses with and without transplacental medication. It is recommended that steroid use should be limited to <10 weeks to avoid maternal and fetal adverse effects, especially fetal growth restriction and oligohydramnios.

Background: Data on the clinical presentation and genotype-phenotype correlation of patients with congenital long-QT syndrome (LQTS) diagnosed at perinatal through infantile period are limited. A nationwide survey was conducted to characterize how LQTS detected during those periods is different from that in childhood or adolescence., Methods and Results: Using questionnaires, 58 cases were registered from 33 institutions. Diagnosis (or suspicion) of LQTS was made during fetal life (n=18), the neonatal period (n=31, 18 of them at 0 to 2 days of life), and beyond the neonatal period (n=9). Clinical presentation of LQTS included sinus bradycardia (n=37), ventricular tachycardia/torsades de pointes (n=27), atrioventricular block (n=23), family history of LQTS (n=21), sudden cardiac death/aborted cardiac arrest (n=14), convulsion (n=5), syncope (n=5), and others. Genetic testing was available in 41 (71%) cases, and the genotype was confirmed in 29 (71%) cases, consisting of LQT1 (n=11), LQT2 (n=11), LQT3 (n=6), and LQT8 (n=1). Ventricular tachycardia/torsades de pointes and atrioventricular block were almost exclusively observed in patients with LQT2, LQT3, and LQT8, as well as in those with no known mutation. In LQT1 patients, clues to diagnosis were mostly sinus bradycardia or family history of LQTS. Sudden cardiac death/aborted cardiac arrest (n=14) was noted in 4 cases with no known mutations as well as in 4 genotyped cases, although the remaining 6 did not undergo genotyping. Their subsequent clinical course after aborted cardiac arrest was favorable with administration of beta-blockers and mexiletine and with pacemaker implantation/implantable cardioverter-defibrillator., Conclusions: Patients with LQTS who showed life-threatening arrhythmias at perinatal periods were mostly those with LQT2, LQT3, or no known mutations. Independent of the genotype, aggressive intervention resulted in effective suppression of arrhythmias, with only 7 deaths recorded.

A nationwide survey in 2000 investigated the causative and associated central nervous system (CNS) lesions of congenital hydrocephalus in Japan. The etiology and associated diseases in 393 patients with congenital hydrocephalus were analyzed and compared between 193 patients with prenatally diagnosed (fetal) hydrocephalus and 181 with postnatally diagnosed (infantile) hydrocephalus. Of 393 patients of congenital hydrocephalus, 355 (90.3%) had primary hydrocephalus and 28 (7.1%) had secondary hydrocephalus. Of 355 patients with primary hydrocephalus, 85 (23.9%) had simple hydrocephalus associated with no other CNS anomaly and 270 (76.1%) had complicated hydrocephalus associated with other CNS anomalies. Destructive cystic lesions, holoprosencephaly, and agenesis of the corpus callosum were significantly predominant in fetal hydrocephalus. Arachnoid cyst was somewhat predominant in infantile hydrocephalus. The majority of cases of congenital hydrocephalus were primary hydrocephalus and two thirds were complicated hydrocephalus. Several complications showed marked predominance in fetal hydrocephalus.

Objectives: To elucidate the prenatal and postnatal course of fetal congenital atrioventricular block (CAVB) during the past decade in the Japanese population., Design: Retrospective multicentre study. All fetuses with CAVB in 10 Japanese institutions in the period from January 1990 to August 2001 were included., Patients: Of the 48 fetuses with CAVB, 17 had a congenital heart defect (CHD) (14 with left atrial isomerism) and 31 had a structurally normal heart (22 with positive maternal autoantibodies). Gestational age at diagnosis was 15 to 38 (median 26) weeks., Results: Of the 17 fetuses with a CHD, three were aborted, one died before birth, and eight died after birth (three in the neonatal period and five after the neonatal period). Of the 31 fetuses without a CHD, two died before birth and two died after birth. CHD (p = 0.005) and the presence of fetal hydrops (p = 0.05) were significant risk factors for death. However, fetal ventricular and atrial heart rates, gestational age at delivery, and birth weight were not related to death. Transplacental medication of sympathomimetics increased the fetal heart rate in five of eight fetuses treated. Dexamethasone did not improve the degree of heart block in any of the six fetuses treated. Postnatally, pacemakers were implanted in 30 of 40 babies. Four fetuses with maternal autoantibodies had decreased cardiac function., Conclusions: CHD and fetal hydrops are risk factors for prenatal and postnatal death. The fetal ventricular rate of 55 beats/min did not appear to be a threshold value by which to predict fetal hydrops. Patients with CAVB should be subjected to close long term follow up to check for the need for pacemaker implantation or for late onset cardiac dysfunction.

A critical review from standpoints of ethical, legal and social implications (ELSI) is required to properly develop and distribute genetic services, including genetic testing. In addition to assure analytical validity, clinical validity and clinical utility of the testing, public opinion and perceptions of the community regarding implementation of the testing are important for obtaining informed consent prior to testing. Otherwise, the testing could be done on only limited numbers of community members. Development of effective inversion in clinical practices and regulation to provide confidentiality of all genetic information should bolster the attitude of the community. Education of the public and mass media is the most important factor if progress is to be made in the clinical application of human genome research, and to avoid "genohype".

Since vaccination legislation was revised in 1994, rubella vaccination has been changed from application to all junior high school girls with no history of clinical rubella to application to individual infants and junior high school students. This may decrease the vaccination acceptance rate and increase the chance of pregnant women's infection with rubella causing congenital rubella syndrome (CRS). We studied 5 children with CRS developed after a 1987-1988 epidemic in Japan to determine how their mothers were infected, and reviewed auditory findings. They were CRS-confirmed or CRS-compatible cases who met CRS diagnostic criteria formulated by the U.S. Center for Disease Control (CDC) in 1983. Two mothers had not been vaccinated because this was not legislated when they were in junior high school. Three were eligible for vaccination at 14, but 2 were not vaccinated. The children were born in 1991-1997. Complications were low birth weight in 3, delay in neck stabilization in 2, and cataract in 1. No case was serious. Ages at first ENT examination ranged from 3 months to 1 year and 8 months. ABR showed hearing loss of > or = 90 dBnHL. They started using hearing aids at 6 months to 1 year and 10 months. Tsumori mental development tests showed delays in developmental age in 2 who started auditory training after ages of 1 year and 6 months. Findings indicated that infants, students, and potentially pregnant women should be vaccinated. Complete serologic testing are important in pregnant women and fetal rubella infection should be diagnosed early by PCR.

Using the polymerase chain reaction method (PCR), we examined the allele frequencies and heterozygosities of 7 polymorphic sites (pERT87, and CA polymorphisms in the 5' and 3' regions) of the dystrophin gene in 20 Japanese Duchenne muscular dystrophy and Becker muscular dystrophy (DMD or BMD) families consisting of 36 males, including 23 cases of DMD and BMD, and 28 females. The allele frequencies of three primer and enzyme sets in the pERT87 locus were well comparable to those in the previously reported Japanese female cases but different from in other countries. The frequencies of 5' markers of the dystrophin gene in Japanes were different from the reported Caucasian frequencies. As for 5'DYS-I and 5'DYS-II, the numbers of alleles in our cases were less than in Caucasians, and the heterozygosities of all three markers (5'DYS-I, II and III) were lower than in Caucasians. However, the 3'CA polymorphisms showed almost the same frequencies and heterozygosities as in Caucasians. All of our females showed a heterozygous pattern for at least one locus, with the combination of the seven markers. The usefulness of linkage analysis involving PCR methods with these intragenic, and 5' and 3' markers of the dystrophin gene in the carrier and prenatal diagnosis of DMD and BMD was confirmed by the successful prenatal diagnoses in 15 fetuses, the exception being one case considered to have a new mutation.

Complete deficiency of hypoxanthine guanine phosphoribosyltransferase (HPRT) causes Lesch-Nyhan syndrome. We examined the HPRT gene mutation for prenatal diagnosis in a Japanese family. A single nucleotide substitution of C to T in exon 3 was identified by direct sequencing analysis of the HPRT gene of a Lesch-Nyhan patient. This substitution resulted in a nonsense mutation, CGA (Arg) to TGA (stop), at codon 51. Utilizing an Xho I restriction site which was lost in the mutation as an indicator, a family study showed that the mother was heterozygous, but the grandmother normal. By the same method, prenatal genetic diagnosis was performed using chorionic villus samples (CVS), and showed that the fetus had the mutant allele.

Comprehensive genetic studies in which the genetic structure of a population is considered against the background of ecological factors, including environmental and social variables, often supply valuable information for the solution of a number of problems in human biology, including reproductive compensation and inbreeding depression. In the first section of this paper we consider the incidence of genetic diseases in Japan in reference to other populations. Some of the genetic disorders found elsewhere do not occur or are of lower frequencies in Japan. On the other hand, a number of genetic diseases occur at higher than usual frequencies, leading to an incidence of genetic disease of the order of about 1 per 100 in newborn Japanese. We next review the studies of consanguinity in Japan and report evidence of very high levels, ranging from 8.6% to 58.0%, for villages during the early part of the twentieth century. The rates are declining rapidly for the country but, because of traditional social values, inbreeding rates remain significant in many small villages. In the final section we consider the probable trends in the frequency of inbreeding on a worldwide basis and point out that frequencies of certain genetic diseases are likely to remain high and even increase in some societies because of various socially prescribed mating patterns.

We analyzed published data from 1980-85 on maternal age specific rates of Down syndrome in nineteen malformation monitoring systems. In the comparisons, we used maternal age specific Down syndrome baseline rates collected in Sweden using multiple sources and from a period before intense prenatal diagnosis. We supposed that no real maternal age specific risk difference exists between different populations, and that ascertainment of cases is independent of maternal age. With these suppositions, most programs had an ascertainment level of 70-90%, and some had about the same but none had a higher ascertainment level than that in the Swedish baseline. Marked differences in maternal age distribution in the populations studied resulted in a 12.3% standard deviation of the average population Down syndrome rate. The highest theoretical rate (estimated from actual maternal age distribution and Swedish baselines) was found in Spain (20% above average), the lowest in Czechoslovakia (24% below average). The estimated average effect of prenatal diagnosis was a decrease of only 6%, but in Denmark it was 25% and in Sweden and France:Paris 13%.