Aiko Sasaki

Prenatal genetic testing in Japan has undergone major changes over the past 2 decades. Maternal serum screening (MSS), amniocentesis (AC), and chorionic villus sampling (CVS) have been the principal tools used to identify fetal chromosomal abnormalities. Recently, non-invasive prenatal testing (NIPT) has reshaped clinical decision-making. However, updated national-level data capturing trends in conventional prenatal testing methods are limited. We aimed to assess the current landscape of prenatal genetic testing in Japan. To update the national data, we compiled test volumes from five major high-volume laboratories that analysed prenatal genetic tests and conducted a supplemental nationwide questionnaire-based survey on ultrasound (US)-only screening between 2020 and 2023. Over this period, MSS declined from 34,887 cases in 2018 to 25,553 in 2023, AC from 16,454 in 2014 to 5620 in 2023, and CVS from 2149 in 2015 to 1167 in 2023, whereas US-only screening increased slightly to >10,000 cases annually. The chromosomal abnormality detection rate among AC cases increased from 8% during 2006–2014 to 20.0% in 2023, with trisomy 21 comprising 43.6% of the cases. During the same period, the proportion of mothers aged ≥35 years increased from 14.0% in 2003 to 30.4% in 2023, whereas the proportion of national live births decreased by 35.3%. Thus, declining test volumes cannot be attributed solely to demographic changes but also reflect the influence of NIPT uptake, improved pretest risk stratification, and changing reproductive decision-making supported by expanding genetic counselling. This study provides foundational data for future prenatal genetic testing practices and policies in Japan.

Introduction Neonatal haemochromatosis, considered to be a gestational alloimmune liver disease (NH-GALD), is a rare but serious disease that results in fulminant hepatic failure. The recurrence rate of NH-GALD in a subsequent infant of a mother with an affected infant is 70%–90%. Recently, antenatal maternal high-dose intravenous immunoglobulin (IVIG) therapy has been reported as being effective for preventing recurrence of NH-GALD in a subsequent infant. However, no clinical trial has been conducted to date. Methods and analysis This is a multicentre open-label, single-arm study of antenatal maternal high-dose IVIG therapy in pregnant women with a history of documented NH in a previous offspring. The objective of this study is to evaluate the efficacy and safety of antenatal maternal high-dose IVIG therapy in preventing or reducing the severity of alloimmune injury to the fetal liver. Ethics and dissemination The clinical trial is being performed in accordance with the Declaration of Helsinki. The trial protocol was approved by the Clinical Research Review Board at four hospitals. Before enrolment, written informed consent would be obtained from eligible pregnant women. The results are expected to be published in a scientific journal. Protocol version 28 October 2024, V.8.0. Trial registration number jRCT1091220353.

Aim: Women's clothing during pregnancy may influence perinatal outcomes. A preliminary study suggested that midwives' advice to avoid wearing tight clothing during pregnancy may reduce the risk of preterm delivery. We examined the effects of such advice to pregnant women on the risk of preterm birth and health status during pregnancy.Methods: An open-label evaluator-blinded randomized controlled trial was conducted at the National Centre for Child Health and Development in Tokyo, Japan. Normal pregnant women were randomly assigned to receive constrictive clothing elimination care or standard care at 20 weeks gestation. The control group was issued leaflets concerning anemia prevention at entry and skin care at 30 weeks' gestation, along with a brief explanation and answers to questions by midwives as standard care. The intervention group received advice from midwives concerning avoiding constrictive clothing in addition to standard care. The primary outcome was the incidence of preterm birth (<37 weeks). The secondary outcomes were 12 indicators related to preterm delivery or health status.Results: Among 624 randomly assigned women, 599 (intervention group, n = 306; control group, n = 293) completed the study between February 2015 and August 2016. The incidence of preterm birth in the intervention and control groups was 4.2% (13/306) and 5.1% (15/293), respectively (p = 0.614). There were no significant differences regarding any secondary outcomes, including obstetric outcomes and physical/mental indicators, during pregnancy.Conclusions: Advice from midwives to avoid constrictive clothing during pregnancy did not influence the incidence of preterm birth or maternal health status.

We investigated folic acid (FA) intake and disturbing factors in pregnant women who visited our center in 2017. Among 1531 pregnant women, 45.1% of women initiated FA supplementation before pregnancy. The risk of failure of supplementation was significantly lower among women of ≥35 (adjusted odds ratio [aOR] 0.43) and 30-34 years of age (aOR: 0.59) in comparison to women of <30 years of age, and among those conceived with timing/AIH (aOR 0.47) and IVF/ICSI (aOR 0.32) in comparison to those conceived naturally. The risk among those with 1 (aOR 1.44) or ≥2 previous deliveries (aOR 2.75) was significantly higher in comparison to nulliparous women. Young, multiparous women, and those with natural conception should be targeted to promote pre-conceptional FA intake.

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