Search

Aim Methods Results Conclusions In Japan, noninvasive prenatal testing (NIPT) has been performed by facilities accredited by the Japanese Society of Obstetrics and Gynecology since 2013. However, since 2016, with the implementation of NIPT, which can only be performed by blood sampling, non‐obstetricians have been involved in prenatal testing. Therefore, in July 2022, a new government‐involved NIPT certification system based on Health Sciences Council guidelines was introduced to ensure access to prenatal testing information for pregnant women.This survey was conducted in February 2023 and was the first survey after the certification system implementation. We conducted a web‐based survey of 1227 pregnant women and nursing mothers who underwent NIPT after July 2022 to evaluate their experiences.Respondents were categorized by certification status as certified (C: 56%), non‐certified (non‐C: 23%), or uncertain (Q: 20%). The C group with a higher mean age at examination (35.0 ± 4.5 years) paid lower examination fees, received longer pre‐ and post‐examination explanations, and underwent more weekday examinations (80%) than the other groups. Most respondents, 67%, 48%, and 53% in the C, non‐C, and Q groups, respectively (p < 0.0001), stated that “NIPT needs to be regulated by the government or academic societies.” The non‐C group was more likely to say, “Insufficient post‐test explanations at the laboratory made me more anxious,” than the other groups when the testing results were non‐negative (p = 0.015).Despite government regulation, some pregnant women choose convenience over certified facilities, risking inadequate care. The government should ensure that NIPT is a safe option for all pregnant women. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of fetal echocardiography in reducing the mortality from congenital heart disease (CHD) is largely unknown. Objectives: This study aimed to evaluate whether the widespread use of fetal echocardiography owing to the initiation of insurance coverage in Japan was associated with a decreasing trend in the annual number of CHD‐related deaths. Methods: Data regarding the number of deaths from CHD in infants aged <12 months were extracted from Japanese demographic statistics (2000–2018). Segmented regression analysis was performed on the interrupted time series data by stratifying the sample into CHD subgroups based on ICD‐10 classification and sex. Results: After the initiation of insurance coverage for fetal echocardiography in 2010, a decrease was observed in the trends of annual deaths in patients with congenital malformations of aortic and mitral valves (ratio of trends before and after the initiation of insurance coverage for fetal echocardiography 0.96, 95% confidence interval 0.93, 0.99). In this group, the decrease persisted after adjusting for annual total infant deaths and cardiac surgery mortality and in the analysis of trends in the proportion of deaths in this group per total CHD deaths. However, a decrease in trends was not observed in other patient groups with CHD. In the sex‐stratified analysis, a decrease was noted only in male patients with congenital malformations of aortic and mitral valves. Conclusions: The nationwide trend in annual CHD deaths decreased after the initiation of insurance coverage for fetal echocardiography only among patients with congenital malformation of aortic and mitral valves. These findings suggest that prenatal diagnosis with fetal echocardiography has led to improved mortality outcomes among these patients in Japan. [ABSTRACT FROM AUTHOR]

Objective: This study examined how clients' selection and preference for noninvasive prenatal testing (NIPT) for aneuploidy changed with genetic counseling (GC) performed by certified geneticists at a primary hospital specializing in obstetrics, where other multiple prenatal genetic tests options were available. Methods: A total of 334 couples who underwent GC between 2017 and 2019 were included in the study. The average age of the pregnant women who underwent GC was 35.1 years. Results: Among the 95 couples (28.4%) who wanted NIPT at the start of GC, 10 (10.5%) switched to other tests, and 4 (4.2%) chose not to undergo any test. Among the 106 (31.7%) couples who wanted the combination of ultrasonography and the serum marker test, 12 (11.3%) chose not to undergo the test. Among the 92 (27.5%) couples who were undecided before GC, 21 (22.8%) wanted NIPT, 31 (33.7%) selected combined tests, and 18 (19.6%) did not undergo any test. Conclusion: We have demonstrated the significance of GC before prenatal genetic testing under widespread use of NIPT. Ideally, obstetric facilities should provide GC, or at least, pre‐counseling at their own facilities, and offer multiple prenatal genetic testing options or refer to other facilities for the same. [ABSTRACT FROM AUTHOR]

The 2017 clinical guidelines for obstetrical practice by the Japan Society of Obstetrics and Gynecology and the Japan Association of Obstetricians and Gynecologists were revised and published as the 2020 edition (in Japanese). The aim of these guidelines is to present appropriate standard obstetric diagnosis and management procedures that have reached consensus among Japanese obstetricians. The 2020 guidelines include 113 clinical questions and an appendix, followed by answers (CQ&A; originally 112 in the 2017 edition), a discussion, list of references, and some tables and figures presenting common problems and questions encountered in obstetrical practice. Each answer comes with a recommendation level of A, B, or C and has been prepared based principally on evidence or a consensus among Japanese obstetricians in situations where "evidence" is weak or lacking. Answers with a recommendation level of A or B represent current standard care practices in Japan. All 113 CQ&As and the appendix are presented here to promote a better understanding of the current standard care practices for pregnant and lactating women in Japan. [ABSTRACT FROM AUTHOR]

Objective: The objectives of this study were to identify the topics that Japanese public health nurses (PHNs) find difficult during genetic consultations and to identify the relationships between these difficulties and PHNs’ genetic education. Methods: We conducted a mail survey delivered to PHNs employed by local Japanese governmental agencies in the Tokyo metropolitan area, between July and October 2015. The self-administered questionnaire queried the (1) experience with genetic consultation, (2) perceived difficulties in genetic consultation, (3) genetics education background, and (4) demographics. The association between the perceived difficulties in genetic consultations and the genetics education opportunities was examined using logistic regression. Results: Of the 907 mailed surveys, 536 PHNs responded (59.1% response rate). Most of the respondents (89.7%) had previously conducted genetic consultations. The majority of respondents (72.7%) had partaken in consultations regarding a possible hereditary disorder in the client or their families, and of those, 76.6% perceived difficulties during the genetic consultation. Respondents who had previously studied decision-making support for genetic testing were significantly less likely to perceive difficulties in genetic consultations on prenatal diagnosis (OR = 0.04, 95% CI [0.00–0.73]). Conclusions: Our results suggest that PHNs receive training in genetic consultation, which can be integrated into everyday practice. [ABSTRACT FROM AUTHOR]

Aim: To review new challenges of fetal therapy in Japan after the establishment of four existing fetal therapies as standard prenatal care with National Health Insurance coverage over the past 20 years. Methods: Reported studies and our current research activities related to four fetal therapies newly performed in Japan were reviewed. Results: Fetoscopic endoluminal tracheal occlusion (FETO) for congenital diaphragmatic hernia (CDH) aims to occlude the trachea using a detachable balloon to promote lung growth. Following the recent successful completion of an international randomized controlled trial for CDH, in which we participated, FETO is offered for severe left CDH to perform balloon insertion at 27–29 weeks and removal at 34 weeks of gestation. Fetal cystoscopy (FC) for low urinary tract obstruction was introduced to overcome the demerits of vesicoamniotic shunting. FC may provide a proper diagnosis by visual observation of the urethra and physiological treatment of the posterior urethral valve. The effectiveness of open fetal surgery for myelomeningocele (MMC), direct surgery with laparotomy and hysterotomy, for ameliorating hindbrain herniation and the motor function was demonstrated, but it was also associated with substantial maternal and fetal risks. Fetal aortic valvuloplasty (FAV), ultrasound‐guided fetal aortic balloon dilation for critical aortic stenosis with evolving hypoplastic left heart syndrome may improve left heart development and maintain biventricular circulation. Feasibility and safety studies for FC, MMC open fetal surgery, and FAV are currently ongoing. Conclusions: Clinical research on FETO, FC, MMC open fetal surgery, and FAV has proceeded with careful preparations in Japan. [ABSTRACT FROM AUTHOR]

We report a case of a neonatal diagnosis of Prader–Willi syndrome caused by uniparental disomy. A 34‐year‐old pregnant woman underwent noninvasive prenatal testing (NIPT) in a hospital that was not certified by the Japanese Association of Medical Sciences. The results of trisomy 13, 18, and 21 were negative; however, a possible abnormality in chromosome 15 was indicated by the Z‐score. Genetic counseling was not performed; thus, the woman did not understand the implication of this result. Therefore, she continued with the pregnancy and delivered a boy weighing 1892 g with hypogonadism at 38 weeks and 5 days. The infant was diagnosed with Prader–Willi syndrome caused by uniparental disomy derived from trisomy rescue. The NIPT results may have reflected placental mosaicism, emphasizing the importance of understanding the limitations of NIPT due to the presence of congenital chromosomal abnormalities that cannot be detected by NIPT platforms. [ABSTRACT FROM AUTHOR]

Aims: Noninvasive prenatal testing (NIPT) of pregnant women has been performed worldwide since 2011, and it is currently performed in more than 90 countries. However, the rate of adoption in Japan remains at less than 2%. This review seeks to identify the ethical and practical issues surrounding noninvasive prenatal screening—including the purpose of the test, its pros and cons, issues surrounding fair treatment, and social factors—to better understand why the adoption rate remains low. Methods: This study examines the complex ethical issues surrounding noninvasive prenatal testing, including the purpose of the test, its pros and cons, issues related to fair treatment, and social factors. Results: Although cell‐free DNA analysis for common fetal trisomies using maternal blood is highly accurate, lack of access to such testing and discriminatory attitudes in society remain important barriers. Personal choices such as whether to undergo noninvasive prenatal screening and whether to continue a pregnancy are sometimes criticized by those who believe that it leads to the "selection of life" or discrimination against people with disabilities. Conclusions: Obstetrics has changed dramatically in recent years, and prenatal diagnosis technology has also advanced. To keep up with these advances, better information should be provided to ensure the public has a more nuanced understanding of the screening beyond the overused argument that it leads to "selection of life." [ABSTRACT FROM AUTHOR]

We have been conducting a survey on the birth prevalence of orofacial clefts, including cleft lip with or without cleft palate and cleft palate, in the Tokai area in central Japan every year for 37 years. Along with the yearly trends in the birth prevalence of orofacial clefts in that area for the past 37 years, we discuss whether the artificial abortion rate of fetuses with orofacial clefts has increased through the improved performance of ultrasonic imaging equipment. We also compare the yearly trends in the birth prevalence of congenital anomalies, including orofacial clefts, in Japan with those in other countries or areas where artificial abortion due to birth defects is legally permitted, and discuss the impact of improved accuracy of ultrasound imaging on the rate of artificial termination of pregnancy. The fact that the birth prevalence of orofacial clefts has basically remained unchanged for more than 30 years, even with recent more detailed prenatal diagnosis based on the improvement of ultrasonic diagnostic equipment, has allowed us tentatively to conclude that prenatal diagnosis is not currently threatening the right to life of the fetuses with orofacial clefts. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to evaluate changes in prenatal testing among women with twin pregnancies before and after the introduction of noninvasive prenatal testing (NIPT). To date, no consensus on prenatal testing for twin pregnancies has been reached in Japan. Methods: Women pregnant with twins who requested prenatal testing at Kyushu Medical Center from 2005 to 2018 were included in this study. Genetic counseling was provided to all participants. Their chosen methods of testing were collected and classified as invasive diagnosis (ID), noninvasive screening (NIS), and no test requested (NR). Parity, chorionicity, and methods of conception were assessed as attributes. The study period was divided into three terms according to testing availability in our center. Results: After NIPT was introduced in our center, the use of ID methods decreased and eventually disappeared while NIS came to the forefront. NR was also the preferred choice of women with twin pregnancies before the introduction of NIPT and decreased but did not disappear after introducing NIPT. Women with twin pregnancies who underwent assisted reproduction initially showed hesitation to undergo testing but showed a strong preference for NIS after the introduction of NIPT. Differences in choice according to parity, chorionicity, and methods of conception were found before the introduction of NIPT but disappeared after introducing NIPT. Conclusion: Increasing information about NIPT has apparently influenced the attitudes of women with twin pregnancies to prenatal testing in Japan. In particular, those who conceive through assisted reproductive technologies exhibited a strong preference for NIPT. [ABSTRACT FROM AUTHOR]

Aim: This study is to investigate the role of amniocentesis for prenatal diagnosis before and after the beginning of noninvasive prenatal testing (NIPT) in Japan. Methods: We performed a retrospective analysis of genetic amniocentesis at mid‐trimester (15–20 gestational weeks) for fetal karyotype analysis at Nagoya City University between April 2006 and March 2020. The indications, test results, and the detection rate of fetal abnormal karyotype were compared before (phase 1, P1) and after (phase 2, P2) beginning of NIPT at April 2013. Results: A total of 2458 (P1: 1132, P2: 1326) amniocentesis were enrolled in this study. The most frequent indication was advanced maternal age in both phases (P1: 78.2% %, P2: 81.1%). In P2, 110 patients (8.3%) received amniocentesis after positive or nonreportable NIPT results. Other indications were fetal abnormal findings by ultrasounds (P1: 15.4%, P2: 17.7%), abnormal maternal serum screening results (P1: 8.0%, P2: 10%), previous child with fetal chromosome aberration (P1: 6.5%, P2: 3.5%), and translocation of either partner (P1:1.5%, P2: 2.1%). The detection rate for fetal chromosomal aberrations including all indications was significantly increased in P2 (15.9%, 95% CI 14.0–18.0) as compared to P1 (9.0%, 7.4–10.8). However, if the indication was only advanced maternal age, the positive detection rate kept low in both phases (P1: 5.2%, 3.7–7.1, P2: 4.2%, 2.9–5.9). Conclusion: Since the initiation of NIPT, the detection rate of fetal chromosomal abnormalities was higher in this study, suggesting that amniocentesis cannot be strongly recommended for advanced maternal age alone. [ABSTRACT FROM AUTHOR]

Aim: We aimed to evaluate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of noninvasive prenatal testing (NIPT) in high‐risk pregnant women. Methods: Pregnant women who underwent GeneTech NIPT, the most commonly used NIPT in Japan, between January 2015 and March 2019, at Japan NIPT Consortium medical sites were recruited for this study. The exclusion criteria were as follows: pregnant women with missing survey items, multiple pregnancy/vanishing twins, chromosomal abnormalities in the fetus other than the NIPT target disease, and nonreportable NIPT results. Sensitivity and specificity were calculated from the obtained data, and maternal age‐specific PPV and NPV were estimated. Results: Of the 45 504 cases, 44 263 cases fulfilling the study criteria were included. The mean maternal age and gestational weeks at the time of procedure were 38.5 years and 13.1 weeks, respectively. Sensitivities were 99.78% (95% confidence interval [95% CI]: 98.78–99.96), 99.12% (95% CI: 96.83–99.76), and 100% (95% CI: 88.30–100) for trisomies 21, 18, and 13, respectively. Specificities were more than 99.9% for trisomies 21, 18, and 13, respectively. Maternal age‐specific PPVs were more than 93%, 77%, and 43% at the age of 35 years for trisomies 21, 18, and 13, respectively. Conclusion: The GeneTech NIPT data showed high sensitivity and specificity in the detection of fetal trisomies 21, 18, and 13 in high‐risk pregnant women, and maternal age‐specific PPVs were obtained. These results could provide more accurate and improved information regarding NIPT for genetic counseling in Japan. [ABSTRACT FROM AUTHOR]

Aim: In Hokkaido, Japan, the number of people suffering from coronavirus disease 2019 (COVID‐19) is rapidly increased, and by the end of February 2020, there were already 70 confirmed cases of the disease. We investigated the safety of urgently initiated maternal telemedicine in preventing the spread of the coronavirus infection. Methods: This retrospective, single‐institution study examined maternal telemedicine at the department of obstetrics of the Hokkaido University Hospital from March 4 to April 2, 2020. The physicians remotely examined the pregnant women from their homes using a visual communication system which kept communication confidential, performed prenatal checkup and administered medical care according to their various blood pressures, weights and cardiotocograms. Results: Forty‐four pregnant women received a total of 67 telemedicine interventions. Thirty‐two pregnant women (73%) had complications, and 22 were primiparas (50%). Telemedicine interventions were provided 19 times at less than 26 weeks of gestation, 43 times between 26 and 36 weeks of gestation and 5 times after 37 weeks of gestation. There was one case with an abnormality diagnosed during the remote prenatal checkups, and the patient was hospitalized on the same day. However, there were no abnormal findings observed in mothers and children during the other 66 remote prenatal checkups and medical care. Conclusion: Maternal telemedicine can be safely conducted in pregnant women who are at risk of having an underlying disorder or fetal abnormality 1 month following the start of the attempt. It should be considered as a form of maternal medical care to prevent the spread of COVID‐19. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to clarify ultrasound screening and management for vasa previa (VP) in perinatal centers and primary facilities in Japan. Methods: A questionnaire survey about antepartum ultrasound screening and management for VP was delivered in 2018. Questions were sent by email or post to perinatal centers and randomly selected primary hospitals or clinics throughout Japan. Results: Seventy‐seven perinatal centers and 300 primary facilities answered. VP was screened in 85.7% of perinatal centers and 81.3% of primary facilities. The reported incidence of VP was 0.05% (86/158 323) and 0.05% (28/54 791) in perinatal centers and primary facilities, respectively. When patients were diagnosed with VP, 88.7% of primary facilities referred the patient to a tertiary hospital. Routine hospitalization (100%) and steroid administration (46%) were frequently performed in perinatal centers. The median gestational age at planned cesarean section was significantly earlier in perinatal centers (34 weeks) than in primary facilities (37 weeks). Of the 31 reported cases of VP, 30 were reported as intact survival, but 1 case required an emergency cesarean section at 38 weeks of gestation without an antenatal diagnosis, resulting in neonatal death. Conclusion: More than 80% of obstetric facilities both perinatal centers and clinics in Japan perform ultrasound screening with for VP with similar detection rate. However, to further improve perinatal outcomes related to VP, pathophysiology and diagnosis of VP should be more widely recognized by obstetric caregivers throughout Japan. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The purpose of this study was to describe the characteristics of women with twin pregnancies who undergo noninvasive prenatal testing (NIPT) as well as the post‐partum and neonatal outcomes of such cases in Japan. Methods: The study population consisted of women who were pregnant with twins and who underwent NIPT using massively parallel sequencing (MPS) at Nagoya City University Hospital between April 2013 and June 2016. Questionnaires were completed pre‐NIPT and post‐partum. Results: Among 4009 women who underwent NIPT during the study period, 75 women (1.9%) were pregnant with twins. Fifteen women (20%) experienced vanishing twin/intrauterine fetal deaths at <22 weeks, and 60 women (80%) had normal twin pregnancies at the time of genetic counseling for NIPT. The use of NIPT was correlated with increased proportions of women using assisted reproductive technology (ART). The test had a high performance, with a false‐positive rate of 1.7% and no false negatives. Conclusion: In this study, NIPT had a high performance, with a false positive rate of 1.7% and no false negatives. When treating women with twin pregnancies, the efficacy of NIPT should be explained during genetic counseling. Further larger studies are required to assess the reliability and validity of NIPT in twin pregnancies. [ABSTRACT FROM AUTHOR]

Aim The purpose of this study was to report the 3-year experience of a nationwide demonstration project to introduce non-invasive prenatal testing (NIPT) of maternal plasma for aneuploidy, and review the current status of NIPT in Japan. Methods Tests were conducted to detect aneuploidy in high-risk pregnant women, and adequate genetic counseling was provided. The clinical data, test results, and pregnancy outcomes were recorded. We discuss the problems of NIPT on the basis of published reports and meta-analyses. Results From April 2013 to March 2016, 30 613 tests were conducted at 55 medical sites participating in a multicenter clinical study. Among the 30 613 women tested, 554 were positive (1.81%) and 30 021 were negative (98.1%) for aneuploidy. Of the 289, 128, and 44 women who tested positive for trisomies 21, 18, and 13, respectively, and underwent definitive testing, 279 (96.5%), 106 (82.8%), and 28 (63.6%) were determined to have a true-positive result. For the 13 481 women with negative result and whose progress could be traced, two had a false-negative result (0.02%). The tests were performed on the condition that a standard level of genetic counseling be provided at hospitals. Conclusion Here, we report on the 3-year nationwide experience with NIPT in Japan. It is important to establish a genetic counseling system to enable women to make informed decisions regarding prenatal testing. Moreover, a welfare system is warranted to support women who decide to give birth to and raise children with chromosomal diseases. [ABSTRACT FROM AUTHOR]

Aim This retrospective study was performed to determine the frequency of malformed infants born at a tertiary center in Hokkaido, Japan. The accuracy of prenatal diagnosis rates was also investigated. Methods An observational study was performed using data of 1509 and 1743 newborn infants at a single center during two study periods, 2005-2009 (first) and 2010-2014 (second), respectively. Cases including minor anomalies (accessory auricle, nevus and fistula auris congenita) were not included. Results In total, 274 and 569 malformations were identified in 191 and 337 newborn infants in the first and second study periods, respectively. The number of malformed infants increased significantly over time (13% [191/1509] vs 19% [337/1743], respectively; P < 0.001), mainly as a result of an increase in cases of congenital heart disease (CHD), from 59 to 141 (31% [59/191] vs 42% [141/337] of all malformed infants in the first and second periods, respectively). The overall accurate prenatal diagnosis rate improved over time from 47% (128/274) to 58% (329/569) because of significant improvements in accurate prenatal diagnosis of CHD subtypes (23% [16/70] vs 65% [151/232] in the first and second periods, respectively, P < 0.0001). Conclusions The frequency of malformed newborns was higher in the tertiary center than in the general population. The increased number of cases with prenatal suspicion and diagnosis of CHD contributed to the increased frequency of malformed infants during the study period. [ABSTRACT FROM AUTHOR]

Objective: To investigate the rates of termination of pregnancy (TOP) for fetal chromosomal abnormalities and factors related to such parental decision in Japan.Methods: A multicenter retrospective cohort study of chromosomal abnormalities diagnosed before 22 weeks of gestation between April 2008 and March 2015. The pregnancy outcomes and parental decisions were investigated.Results: Among 931 fetuses with chromosome abnormalities, the total TOP rate was 75.1% (699/931). TOP rates were 89.3% (585/655) in autosomal aneuploidies and 40.8% (51/125) in sex chromosome aneuploidies. Trisomy 21 showed the highest TOP rate (93.8% [390/416]) followed by trisomy 18 (84.5% [163/193]) and trisomy 13 (71.9% [23/32]). Indications for karyotyping were related to a parental decision for TOP (p < 0.01): in cases of autosomal aneuploidy, with fetal abnormal ultrasound findings as the reference value, diagnoses made following positive results at non-invasive prenatal testing (adjusted odds ratio [OR]: 13.7, 95% confidence interval [CI] 4.07-45.9) and those because of advanced maternal age (adj. OR 2.91, 95% CI 1.15-7.35) were significantly more frequent.Conclusions: In Japan, pregnancies with fetal trisomy 21 are more likely to result in TOP when diagnosed in utero than any other chromosome anomaly. The indications for prenatal karyotyping strongly affect the decision to TOP. © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aim Our purpose was to assess the background of couples who were undergoing non-invasive prenatal testing (NIPT) in Japan. Methods The characteristics of 2486 women who had visited Nagoya City University Hospital for NIPT were compared with Japanese Demographic Trends as controls. The questionnaire included items regarding the maternal and paternal age, maternal age at marriage, age at first live birth, and conception mode. Results Compared with the controls, the percentage of women who were 4 or more years older than their partners was larger in the NIPT group (11.8% vs 6.5%). The maternal age at marriage, age at first live birth, and the duration between marriage and first birth tended to be greater in the NIPT group (32.6 years vs 29.3 years, 36.9 years vs 30.4 years, and 3.6 years vs 2.4 years, respectively), and the percentage of women who underwent assisted reproductive technology tended to be higher in the NIPT group (35-39 years: 21.2% vs 7.5%, 40-45 years: 36.2% vs 12.6%), compared with the controls. Conclusion Knowing the specific backgrounds of couples who have undergone NIPT may be important for improving the quality of genetic counseling for NIPT. [ABSTRACT FROM AUTHOR]

Aim In order to investigate the current status of prenatal testing for genetic disorders, we conducted a multicenter retrospective questionnaire survey. Methods The questionnaire was sent to 105 facilities with genetic counseling systems. The questionnaire consisted of two parts: (i) the number of prenatal tests conducted for genetic disorders from January 2010 to December 2012, whether the laboratory was combined with the counseling facility or separate, the sampling procedure method, the testing results, and the outcomes of the affected fetus in addition to treatment; and (ii) a survey of personal comments regarding prenatal testing for genetic disorders. Results We received responses from 69 of the 105 facilities (65.7%), and genetic testing was performed at 26 of these facilities. Nucleic acid sequential testing was performed on 45 disorders and 252 cases during a three-year period. There were 67 cases of affected fetuses. Six cases continued pregnancy and were treated. The comment survey highlighted difficulties in locating a laboratory to assess prenatal samples, as well as inadequate counseling and preparation for genetic disorders. Conclusions Our study revealed that a number of prenatal testing for genetic disorders are conducted in Japan; however, it is difficult for counselors to locate a laboratory capable of testing for specific genetic disorders. Inadequate counseling and healthcare providers' lack of knowledge is a current problem. A well-established system of prenatal testing for genetic disorders and the further education of general physicians is required. [ABSTRACT FROM AUTHOR]

The number of pregnant women of advanced maternal age has increased worldwide. Women in this group have an increased chance of fetal abnormality. To explore Japanese women's experiences regarding maternal age-specific risks and prenatal testing, we conducted a descriptive qualitative study. Semi-structured interviews were conducted with 16 women aged 35 years or over who had given birth within the previous three months to a healthy, term infant. Thematic analysis of transcribed interview data was performed and three major themes were identified: inadequate understanding of genetic risks; insufficiently informed choice regarding prenatal testing; and need for more information from health professionals. Some participants were not aware of maternal age-specific risks to the fetus. Many took their cues from health professionals and did not raise the topic themselves, but would have considered prenatal testing if made aware of the risks. Nurses, midwives and other health professionals need to adequately inform pregnant women about the genetic risks to the fetus and offer testing at an appropriate stage early in the pregnancy. [ABSTRACT FROM AUTHOR]

Background Congenital cystic lung disease ( CCLD), which includes congenital cystic adenomatoid malformation, bronchopulmonary sequestration, and congenital lobar emphysema, has been reported to increase the risk of recurrent respiratory infection. In particular, respiratory syncytial virus ( RSV) causes severe lower respiratory tract disease in high-risk infants. The objective of this study was to investigate the risk of severe RSV infection in infants with CCLD. Methods Infants antenatally diagnosed as having CCLD and admitted to a neonatal intensive care unit at the National Center for Child Health and Development in Tokyo between September 2002 and October 2011 were included in this study. We investigated retrospectively whether the infants were hospitalized with RSV infection by 24 months of age using their medical records. Results Forty-eight infants were antenatally diagnosed as having CCLD. Of the 48 infants, four (8.3%) were hospitalized with RSV infection by 24 months of age. Conclusions Infants with CCLD have increased risk of severe RSV infection. [ABSTRACT FROM AUTHOR]

An editorial is presented on the Treatment for congenital diaphragmatic hernia. Topics discussed include Modern treatment of Congenital diaphragmatic hernia (CDH) has steadily progressed by improved understanding and better management of deranged cardiopulmonary physiology and recognition of the role of delayed surgical repair; and the improvement of survival rate(s) of CDH is attributed to increasing prenatal diagnosis (%), emergent intubation at birth, gentle ventilation.

Aim Fetal borderline ventriculomegaly represents a frequent dilemma in perinatal management. The present study aimed to evaluate the clinical significance of fetal borderline ventriculomegaly in a low-risk Japanese population and to identify the risk factors for associated anomalies. Methods Data of cases of fetal borderline ventriculomegaly detected at 26−28 weeks of gestation by routine ultrasonographic screening of low-risk singleton pregnancies between 2006 and 2012 were retrospectively collected. Ventricular width, in utero progression, associated anomalies, chromosomal abnormalities, and perinatal and postnatal outcomes were assessed. The ventricular width, in utero progression and other perinatal characteristics were compared between the isolated and non-isolated groups. Results Among the total 6020 singleton low-risk pregnancies, we noted that 42 had borderline ventriculomegaly. Six (14%) of these cases had other defects by subsequent detailed examination. Ventriculomegaly resolved or regressed in 35 (83%) and progressed in four (10%) cases, of which three were associated with other anomalies. The median ventricular width was 12.8 mm (range, 10.0-14.7) in the six non-isolated cases and 10.5 mm (range, 10.0-13.3) in the 36 isolated cases; the differences were statistically significant. A ventricular width of 12 mm or more and in utero progression were more frequently observed in non-isolated cases than in isolated cases. Conclusion Fetal borderline ventriculomegaly frequently resolves in utero. A ventricular diameter of more than 12 mm and in utero progression are risk factors for additional anomalies. After the initial diagnosis of borderline ventriculomegaly, the pregnancy should be carefully followed up to determine whether the ventricle size is resolved, remains stable or increases. [ABSTRACT FROM AUTHOR]

Aim Second-trimester maternal serum screening ( MSS) is the predominant form of prenatal screening in Japan. We hypothesize that patient education and physician knowledge of Down syndrome ( DS) screening are insufficient to provide adequate information regarding prenatal screening in Japan. Material and Methods In-person or telephone interviews with medical personnel were conducted at 25 medical facilities utilizing Afp4 ( Esoterix Genetic Laboratories, LLC, a wholly-owned subsidiary of Laboratory Corporation of America Holdings) second trimester screening. We explored how medical facilities provided information about the MSS process to pregnant women. Results Before prenatal testing, 60% of medical facilities spent an average of less than 5 min per patient explaining the MSS process. The option of amniocentesis for chromosomal aneuploidy was explained at nearly all facilities, but only 60% explained the risk of amniocentesis. Ultrasound examination for open neural tube defects was explained only at half the facilities. Only five of 25 (20%) medical practitioners explained the possibility of having congenital disorders fetus. Conclusion This study revealed that most obstetricians in Japan do not provide their patients with sufficient information about MSS. [ABSTRACT FROM AUTHOR]

Aim To establish reference values for the nuchal translucency ( NT) thickness in Japanese fetuses. Material and Methods Ultrasonographic measurements of the crown-rump length ( CRL) and NT were performed from 11 to 13 + 6 weeks of gestation in consecutive Japanese fetuses examined during prenatal visits between February 2011 and January 2012. The median, 5th and 95th percentiles of the NT thickness with 5 mm intervals of the CRL were confirmed. Results A total of 970 cases were enrolled in the study. The median NT thickness for a CRL between 45 and 80 mm ranged from 1.2 mm to 1.9 mm, and the 95th percentile of these values ranged from 2.1 mm to 3.2 mm, respectively. Conclusion The reference values for the NT thickness in Japanese fetuses were determined. These values should be useful for fetal biometry, morphological assessment and first trimester screening for chromosomal abnormalities in Japan. [ABSTRACT FROM AUTHOR]

Background During the last decade, new supportive modalities and new therapeutic strategies to treat congenital diaphragmatic hernia ( CDH) have been introduced. In Japan, the large number of hospitals prevents centralizing infants with CDH in tertiary centers. The aim of this study was to evaluate the correlations between the number of CDH patients, survival rates, and the current strategies employed to treat CDH at the individual hospitals. Methods Eighty-three hospitals with 674 CDH cases were analyzed using questionnaires. We classified the hospitals into three groups according to the number of CDH patients treated: Group 1 ( G1; more than 21 patients), Group 2 ( G2; 11-20 patients), and Group 3 ( G3; fewer than 10 patients). Results The median number of CDH patients in G1, G2, and G3 were 28, 14, and 4, respectively. The overall survival rate was 74.5%. When only the isolated CDH cases with a prenatal diagnosis were included, the overall survival rate was 79.3%. The survival rate of isolated CDH cases with a prenatal diagnosis was significantly higher in G1 than that in G2 or G3 (87.2% vs 75.2% vs 74.3%; P < 0.001). There were no differences in perinatal therapeutic strategies among the three groups. Conclusions We concluded that it might therefore be important to centralize infants with CDH, especially those with isolated CDH with a prenatal diagnosis, to tertiary centers in Japan in order to improve the survival rates. [ABSTRACT FROM AUTHOR]

Background: The aim of this retrospective study was to evaluate the influence of prenatal diagnosis on perinatal outcomes of congenital heart disease (CHD) over a 17 year period at a single center. Methods: The perinatal outcome of CHD in 146 patients diagnosed on fetal echocardiography between 1994 and 2010 were reviewed. The characteristics of 193 neonatal inpatients with CHD treated at the authors' department between 2001 and 2010 were also analyzed; among the inpatients, 61 were diagnosed before birth (prenatal group) and 132 were diagnosed after birth (postnatal group). Results: Among the 146 patients prenatally diagnosed with CHD, the prenatal mortality, including abortion and stillbirth, decreased from 1994 to 2010. Among the 193 neonatal inpatients, the prenatal group had lower gestational age and bodyweight than the postnatal group. Further, the prenatal group had lower blood pH at admission, but no patient in that group experienced ductal shock, although six patients in the postnatal group did. The average dose of prostaglandin E1 used in duct-dependent CHD was significantly lower in the prenatal group than in the postnatal group (3.4 vs. 4.6 ng/kg per min; P = 0.015). Conclusions: Prenatal diagnosis of CHD enables planned labor, prevents ductal shock, and reduces prostaglandin E1 side-effects and medical expenditure. [ABSTRACT FROM AUTHOR]

Aim: We investigated trends in early-onset group B streptococcal disease (EOD) after the introduction of culture-based screening in Japan. Material and Methods: A retrospective cohort study examined EOD trends in 9506 pregnancies and 10 715 neonates at our center from 2002 to 2009. Results: EOD occurred in four neonates (4/7332: 0.55/1000 live births). The EOD incidence among infants born to women positive for GBS by screening was 0.90 cases per 1000 live births (1/1107). In contrast, the EOD incidence among infants negative by GBS screening was 0.48 cases per 1000 live births (3/6225). Thus, of the four affected neonates, three had mothers who tested negative on antepartum GBS screening. Two neonates had symptoms of infection during labor and intrapartum antibiotic agents were administered. The other two neonates received no antibiotics because deliveries were uneventful and they were negative on GBS screening. Conclusion: The incidence of EOD is 0.90 cases per 1000 live births among GBS-positive women and 0.48 cases per 1000 live births among GBS-negative women. The results of our study implied that EOD can develop regardless of GBS screening and intrapartum clinical course, although the method of sample collection, indications for antibiotic prophylaxis, and the antibiotics regimen should be considered. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the methods of screening and prenatal diagnosis of vasa previa. Material and Methods: We reviewed cases of vasa previa in our hospital between January 2002 and December 2007. During this period, we visualized the site of cord insertion using transabdominal ultrasonography and observed the internal os using gray-scale transvaginal ultrasonography. A diagnosis of vasa previa was confirmed by transvaginal color Doppler imaging. Results: We encountered 10 cases of vasa previa among 5131 deliveries. All cases had one or more known risk factors. In all of the four cases that underwent screening in the second trimester (i.e. between 20 and 25 weeks of gestation), the diagnosis was correct. Routine ultrasonography detected in only three of the other six cases of vasa previa that were referred to our hospital after 26 weeks of gestation. Of the other three cases referred after 26 weeks of gestation, in two cases vasa previa was detected by detailed examination using color Doppler transvaginal ultrasonography after fetal heart rate monitoring detected the presence of non-reassuring fetal status; in the remaining case, we were unable to make an antenatal diagnosis. Non-reassuring fetal status was seen on fetal heart rate monitoring in four of the five detected cases complicated by preterm labor. Conclusion: We consider that the best timing of antenatal screening for vasa previa is the second trimester. Non-reassuring fetal heart rate pattern without other possible causes warrants detailed examination of vasa previa. [ABSTRACT FROM AUTHOR]

Clinical guidelines for obstetrical practice were first published by the Japan Society of Obstetrics and Gynecology (JSOG) and the Japan Association of Obstetricians and Gynecologists (JAOG) in 2008, and a revised version was published in 2011. The aims of this publication include the determination of current standard care practices for pregnant women in Japan, the widespread use of standard care practices, the enhancement of safety in obstetrical practice, the reduction in burdens associated with medico-legal and medico-economical problems, and a better understanding between pregnant women and maternity-service providers. These guidelines include a total of 87 Clinical Questions followed by several Answers (CQ&A), a Discussion, a List of References, and some Tables and Figures covering common problems and questions encountered in obstetrical practice. Each answer with a recommendation level of A, B or C has been prepared based principally on 'evidence' or a consensus among Japanese obstetricians in situations where 'evidence' is weak or lacking. Answers with a recommendation level of A or B represent current standard care practices in Japan. All 87 CQ&A are presented herein to promote a better understanding of the current standard care practices for pregnant women in Japan. [ABSTRACT FROM AUTHOR]

Aim: To determine the current status of fetal CHD screening in our region and to establish a CHD screening system in Japan. Material and Methods: Subjects were 168 fetuses prenatally-diagnosed with CHD at four referral centers in Japan from 2003 to 2007. Subjects were divided into two groups: group A (n = 84) included cases without extracardiac sonographic abnormalities and known risk factors for CHD and group B (n = 84) included thosewith extracardiac sonographic abnormalities or risk factors. The diagnostics and outcomes between the groups were analyzed. Results: There were more cases of single ventricle and restrictive ductus arteriosus and fewer cases of ventricular septal defect and double outlet right ventricle in groupA than in group B (P < 0.05). In group A, the most frequent referral reason was an abnormal four-chamber view. In group B, 37 cases had chromosomal anomalies. The mortality rates in group B were higher than those in group A (P < 0.05). There were no differences in mortality rates between fetuses without chromosomal anomalies in group B and group A. Conclusion: Prenatally-diagnosed CHD were mostly limited to those cases with obvious abnormalities in the four-chamber view or those with chromosomal anomalies. Prenatal detection of CHD is useful for the prediction of outcomes. [ABSTRACT FROM AUTHOR]

Objective: To clarify the effect of starvation due to hyperemesis gravidarum on the screening of gestational diabetes mellitus (GDM).Methods: A retrospective study was undertaken of pregnant women who delivered at Tsukuba University Hospital, Japan, between October 1, 2010, and September 30, 2013. GDM screening was performed in the first trimester using the random blood glucose test with a cutoff value of 5.2mmol/L and in the second trimester using a 50-g glucose challenge test with a cutoff value of 7.8mmol/L. If the screening was positive, a 75-g oral glucose tolerance test was performed for a definite diagnosis.Results: Among 2112 eligible women, 33 (1.6%) required hospitalization for hyperemesis; the remaining 2079 women formed the control group. In the first trimester, the positive GDM screening rate was significantly higher in the hyperemesis group than in the control group (13 [39.4%] vs 115 [5.5%]; P<0.001). Additionally, the positive predictive value was significantly lower in the hyperemesis group (23.1% vs 73.9%; P<0.001). In the second trimester, no significant differences were observed between groups.Conclusion: Hyperemesis gravidarum affects the positive GDM screening rate in the first trimester. [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]

Abstract: Objective: To identify adequate weight gain ranges during pregnancy in Japanese women. Method: Obstetric records from 2001 to 2002 for 46,659 term, singleton, vaginally delivered live births was used to estimate IUGR and macrosomia risk. Total maternal weight gain was grouped according to gestational age-specific percentile values of weight gain as follows: “very low” (under the 25th), “low” (25th to 49th), “moderate” (50th to 74th), “high” (75th to 89th), and “very high” (90th and over). Results: About 6% of infants were identified as having IUGR and 0.9% as macrosomia. IUGR risk was elevated with low weight gains. Macrosomia risk was related to high weight gains and previous spontaneous abortions. Conclusion: Achieving weight gains between the 50th and 75th percentiles for gestational age was considered adequate for optimal fetal growth in Japanese pregnant women. [Copyright &y& Elsevier]

Lenz microphthalmia syndrome comprises microphthalmia-anophthalmia with mental retardation, malformed ears and skeletal anomalies, and is inherited in an X-linked recessive pattern. In 2004, it was reported that the missense mutation ( BCL-6 co-repressor gene [ BCOR] c. 254C>T, p. P85L) in a single family with Lenz microphthalmia syndrome co-segregated with the disease phenotype. We report a case of prenatal diagnosis for X-linked recessive Lenz microphthalmia syndrome with the mutation. A 32-year-old gravida 5, para 2 Japanese woman was referred to Nagoya City University Hospital at 15 weeks of gestation. After genetic counseling and informed consent, amniocentesis was performed for fetal karyotyping, which was 46, XY. Using the extracted DNA from cultured amniotic cells, fetal search for BCOR c. 254C>T mutation was undertaken. The couple requested medical termination of pregnancy, and the postabortion examination confirmed the diagnosis. This is the third report of a BCOR mutation, associated with X-linked syndromic microphthalmia, and most importantly, it is always the same mutation. The prenatal genetic diagnosis of the Lenz microphthalmia syndrome allowed time for parental counseling and delivery planning. [ABSTRACT FROM AUTHOR]

To support people with Down syndrome (DS), it is essential to know and predict the number of live births of children with this condition. In this study, we estimated DS live birth rates on the basis of maternal age distribution and numbers of births in the general population, the maternal-age specific chance for a live birth of a child with DS, and the prenatal diagnosis/termination rate. The total number of live births in Japan decreased to less than 1 million in 2016 and the percentage of women aged 35 years old or over giving birth has increased by sixfold. Prenatal genetic testing in Japan has gradually become more widespread, and 20% of all cases of DS were diagnosed prenatally in 2016. Meanwhile, the annual projected number of DS live births has remained steady at around 2,200 (22 per 10,000 births). In 2016, it was estimated that 70% of all DS babies were born to women of advanced maternal age (AMA). Given that Japan is facing a decreasing birth rate and an aging population, adoption of the practice of prenatal genetic testing for AMA has balanced the number of DS births over the last 7 years from 2010., (© 2019 Wiley Periodicals, Inc.)

The article discusses a study on congenital cystic lung disease among infants delivered at Keio University Hospital in Tokyo, Japan, which was diagnosed through fetal ultrasonography. The researchers evaluate retrospectively the infants who have congenital cystic lung disease in utero. The study revealed a cystic lesion with progressive regression in 10 infants and lung hypoplasia developed.

A letter to the editor is presented in response to the article "Survey of prenatal testing for genetic disorders," by T. Nobuzane and colleagues in the 2015 issue.

Reports on the detection of aneuploidy with fetal nuchal translucency and maternal serum markers in Japanese women. Total number of women diagnosed with nuchal translucency; Comparison of the risk for aneuploidies with fetal nuchal translucency and positive maternal serum markers.