Neonatal transfer and duration of hospitalization of newborns as potential risk factors for impaired mother-infant bonding: The Japan Environment and Children's Study.

BACKGROUND: Currently, there is no consensus regarding the relationship between neonatal transfer and duration of hospitalization in cases of impaired mother-infant bonding (MIB). This study aimed to determine whether neonatal transfer and duration of hospitalization of newborns increase the risk for impaired MIB. METHODS: The MIB Scale was used to assess impaired MIB 1 year after delivery, using data from the Japan Environment and Children's Study. A score ≥ 5 points indicated impaired MIB. Multiple logistic regression analyses were performed to estimate the association between neonatal transfer and duration of hospitalization of newborns with the risk of impaired MIB. RESULTS: A total of 66,402 pregnant women were included in the study. The overall incidence rate of impaired MIB was 11.2 %. The mean duration of hospitalization of newborns was 7.1 ± 6.4 days. After adjusting for potential confounders, neonatal transfer (adjusted odd ratio (OR): 1.13 [95 % confidence interval (CI)), 1.01-1.27]) and duration of hospitalization of newborns (adjusted OR 1.007; 95 % CI 1.003-1.010) were associated with impaired MIB. The area under the receiver operating characteristic curve for the duration of hospitalization of newborns for impaired MIB was 0.53. LIMITATIONS: Maternal childhood abuse and neglect history were not evaluated, and information regarding whether the infants were admitted to the neonatal intensive care unit was unavailable. CONCLUSIONS: Japanese women whose newborns underwent neonatal transfer should be followed up for at least 1 year after delivery, regardless of the duration of hospitalization of newborns.

Opinions on research involving human embryo models by researchers and the general public.

Rules and ethical considerations regarding research on embryo models have been debated across numerous countries. In this paper, we provide insights from our attitude survey conducted among Japanese researchers, including members of the Japanese Society for Regenerative Medicine, and among the general public residing in Japan, the US, the UK, Canada, and Australia. Our survey revealed that many researchers expressed the need for clear guidelines for embryo model research. Furthermore, a minority but significant portion of the general public in each country expressed opposition to research on embryo models but did not oppose research involving real embryos.

Association of maternal leukocyte, monocyte, and neutrophil counts with hypertensive disorders of pregnancy: the Japan Environment and Children's Study (JECS).

Hypertensive disorders of pregnancy (HDP) increase the risk of preterm births and cesarean delivery. This study aimed to investigate whether maternal blood leukocyte, monocyte, or neutrophil counts in the first trimester are related to the development of HDP. Data were collected from the Japan Environment and Children's Study, a large birth cohort study (n = 38,194) that recruited pregnant women in 15 Regional Centers across Japan (from January 2011 to March 2014). The odds ratios (ORs) for mild/severe HDP according to the cut-off value of leukocyte/neutrophil/monocyte counts by the receiver operating characteristic curve showed high ORs. Furthermore, pregnant women with the highest quartiles of leukocyte and monocyte counts had higher adjusted ORs (aORs) for mild (leukocyte: aOR = 1.27, 95% confidence interval [CI]: 1.02-1.58; monocyte: aOR = 1.30, 95% CI 1.04-1.63) and severe HDP (leukocyte: aOR = 1.51, 95% CI 1.08-2.13; monocyte: aOR = 1.44, 95% CI 1.03-2.01) compared with those with the lowest quartiles of those counts. In addition, pregnant women with the highest neutrophil counts had higher aOR for mild HDP (aOR = 1.26, 95% CI 1.02-1.56) compared with those with the lowest count. In conclusion, high leukocyte and monocyte counts in the first trimester are associated with the development of HDP. Thus, they may be used to predict subsequent HDP.

Association between filaggrin gene mutations and the clinical features of molluscum contagiosum: The Yamanashi Adjunct Study of the Japan Environment and Children's Study.

Previous studies have reported swimming, atopic dermatitis, and filaggrin (FLG) gene mutations as risk factors for molluscum contagiosum (MC) infection. FLG gene mutations impair skin barrier function. The aim of this study was to determine the impact of FLG mutations on the incidence and clinical features of MC. We used data from 2036 children who participated in the Yamanashi Adjunct Study of the Japan Environment and Children's Study, a prospective, birth cohort study. A questionnaire for caregivers (when children were 4 and 8 years of age) asked about clinical features including previous MC incidence and treatment, number of MC lesions at first visit, and time to resolution. Participants underwent genotyping to detect six FLG mutations that are common in the Japanese population. A logistic regression model was used to analyze the association between MC incidence and FLG mutations, adjusted for potential confounders. The cumulative incidence of MC at age 8 years was 47.1%. Among participants with a history of MC, 67.6% had undergone curettage. FLG mutation was a significant risk factor for MC incidence (adjusted odds ratio [aOR] 1.69, 95% confidence interval [CI] 1.18-2.42). Swimming and atopic dermatitis were also significant risk factors for MC. There was no significant association between FLG mutation and the number of MC lesions at the first visit or the time to resolution of lesions. FLG mutation is a risk factor for MC incidence; however, FLG mutations do not affect the number of MC lesions at presentation or the time to resolution.

Infantile peanut introduction and peanut allergy in regions with a low prevalence of peanut allergy: the Japan Environment and Children's Study (JECS).

BACKGROUND: In regions with a high prevalence of peanut allergy (PA), there is a consensus that the introduction of peanuts in early infancy is preventive against the development of PA. However, few studies have investigated whether the introduction of peanuts to infants is associated with PA in regions with a low prevalence of PA, including Japan. METHODS: We used data from 74,240 mother-child pairs who participated in the Japan Environment and Children's Study, a prospective birth cohort recruited between January 2011 and March 2014. A logistic regression model was used to analyze the association between infantile peanut introduction and PA at the age of 4 years with non-infantile peanut introduction as the reference group, adjusted for potential confounders. RESULTS: The percentage of infantile peanut introduction was 4.9% (n=3294) and 286 (0.4%) participants had allergic symptoms to peanuts at 4 years of age. Of all participants, 129 (0.2%) had PA at 4 years of age, which was defined as allergic symptoms and sensitization to peanuts. Those with infantile peanut introduction had a lower prevalence of PA than those without infantile peanut introduction, although this did not reach statistical significance (adjusted odds ratio: 0.53, 95% confidence interval, 0.17-1.68). Sensitivity analysis using IgE-mediated symptoms caused by peanuts as the outcome showed a similar result in relation to infantile peanut introduction. CONCLUSIONS: In countries with a low prevalence of PA, the effect of infantile peanut introduction on PA prevention was unclear.

Obesity as a potential risk factor for stillbirth: The Japan Environment and Children's Study.

The relationship between high body mass index (BMI) >25 kg/m2 and risk for stillbirth in the Japanese population remains unclear. This study aimed to estimate the impact of maternal obesity on the risk of stillbirth in a Japanese population. This prospective cohort study used data from the Japan Environment and Children's Study, which recruited pregnant individuals between 2011 and 2014. A total of 93,772 fetuses were considered eligible for inclusion in this study. Stillbirth (fetal death before or during labor at ≥22 completed weeks of gestation) rates were compared among four pre-pregnancy BMI groups: underweight (<18.5 kg/m2), reference (18.5 to <25.0 kg/m2), overweight (25.0 to <30.0 kg/m2), and obese (≥30.0 kg/m2). The association between pre-pregnancy BMI and the risk of stillbirth was estimated using multiple logistic regression analyses. The overall stillbirth incidence was 0.33% (305/93,722). Compared with the reference group, the risk of stillbirth was significantly higher in the overweight group (adjusted odds ratio [aOR]: 1.55; 95% confidence interval [CI]: 1.08-2.23) and the obese group (aOR: 2.60; 95% CI: 1.59-4.24). The overall incidence of early stillbirth (i.e., <28 weeks) was 0.17% (155/93,722). Similarly, after adjusting for potential confounding factors, the risk of early stillbirth was significantly higher in the obese group (aOR: 4.33; 95% CI: 2.44-7.70). Increased maternal BMI was associated with an increased risk of stillbirth in the Japanese population. Therefore, counselling women planning for pregnancy on the importance of an appropriate pre-pregnancy BMI to minimize the risk of stillbirth is important.

Maternal dietary fiber intake during pregnancy and child development: the Japan Environment and Children's Study.

Background: Animal studies have shown that maternal low-fiber diets during pregnancy may impair brain development and function in offspring, but this has not been validated by epidemiological studies. The aim of this study was to investigate the link between maternal dietary fiber intake during pregnancy and neurodevelopmental delay in offspring using a large birth cohort. Methods: A total of 76,207 mother-infant pairs were analyzed using data from the Japan Environment and Children's Study, a nationwide prospective cohort study. Maternal dietary fiber intake was estimated using the food frequency questionnaire in mid-pregnancy. Maternal dietary fiber intake was adjusted for energy and classified into quintiles. Developmental delay was assessed in five domains using the Japanese version of the Ages and Stages Questionnaire, Third Edition at the age of 3 years. The logistic regression analysis was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) for the link between dietary fiber intake during pregnancy and developmental delay at the age of 3 years. Results: The lowest intake group of total dietary fiber had a higher risk of delayed communication [adjusted OR (aOR), 1.51; 95% CI, 1.32-1.74], fine motor (aOR, 1.45; 95% CI, 1.32-1.61), problem-solving (aOR, 1.46; 95% CI, 1.32-1.61), and personal-social skills (aOR, 1.30; 95% CI, 1.12-1.50) than did the highest intake group. An analysis that excluded the effects of insufficient folic acid intake during pregnancy also showed a similar trend. Conclusion: This study showed that maternal dietary fiber deficiency during pregnancy might influence an increased risk of neurodevelopmental delay in offspring.

A nationwide, prospective, cohort study on exogenous oxytocin and delays in early child development: the Japan environment and children's study.

Although it remains debatable, exogenous oxytocin, commonly used for labour induction and augmentation, reportedly increases risks of neurodevelopment delay, attention-deficit/hyperactivity disorder, and autism spectrum disorder among children prenatally exposed to exogenous oxytocin. However, only few studies have objectively examined exogenous oxytocin's impact on early childhood development through scoring evaluations. This study investigated the association between exogenous oxytocin exposure and neurodevelopment in 3-year-old children using the Ages and Stages Questionnaires, Third Edition. In this nationwide prospective cohort study, we extracted data from 104,062 foetal records regarding exogenous oxytocin use during labour from the Japan Environment and Children's Study. Participants completed questionnaires throughout the pregnancy and postpartum periods. Outcomes comprised the developmental status less than each cut-off value for the five domains of the Ages and Stages Questionnaire, Third Edition. We conducted multivariable logistic regression analyses on the data of 55,400 children after controlling for confounders. Among the 55,400 included women, 19.0% (n = 10,506) used exogenous oxytocin during labour and 81.0% (n = 44,894) did not. Children exposed to exogenous oxytocin showed no significantly increased risk of developmental delay in any domain (communication: odds ratio [OR] 1.04, 95% confidence interval [CI] 0.92-1.16; gross motor: OR 0.97, 95% CI 0.87-1.08; fine motor: OR 1.00, 95% CI 0.92-1.09; problem-solving: OR 1.02, 95% CI 0.94-1.11; personal-social: OR 0.91, 95% CI 0.80-1.03).   Conclusion: Exogenous oxytocin for labour induction did not adversely affect early childhood development. Further studies accounting for the degree of exogenous oxytocin exposure are required to confirm these results. What is Known: • In developed countries, labour is induced in 20-25% of all pregnancies, for which oxytocin is commonly used. • Studies have associated risks of neurodevelopment delay, attention-deficit/hyperactivity disorder, and autism spectrum disorder with exposure to exogenous oxytocin. What is New: • Evaluation with the Ages and Stages Questionnaire, Third Edition, revealed that exogenous oxytocin use did not adversely affect early childhood development. • This prospective study reinforced the lack of evidence of an association between exogenous oxytocin use and early childhood development after adjustment for confounding and rigorous bias elimination.

Attitudes towards human fetal tissue research: Survey of researchers and the public in Japan.

Introduction: The rules for human fetal tissue (HFT) research in Japan are unclear. Methods: In this paper, we conducted a web survey to examine the attitudes of Japanese researchers (n=535) and the public (n=3,000) toward HFT research. Results: The results demonstrated that 5.8% of researchers and 18.8% of the public explicitly opposed HFT research, and 71.8% of the researchers thought that the rules for HFT research need to be clarified. Even among researchers who intended to consider conducting HFT research, 74.2% responded that the rules should be clarified. Although different from attitudes to make decisions regarding HFT donation, being non-religious and in their reproductive age among women in the public group were factors for accepting attitudes toward HFT research. Conclusion: To establish the rules, it is necessary to develop a system that can adequately protect vulnerable women who are asked to provide HFT.

Interpregnancy weight change as a potential risk factor for large-for-gestational-age infants: the Japan Environment and Children's Study.

OBJECTIVE: This study aimed to estimate the impact of interpregnancy weight change from the first to the second pregnancy on the risk of infants being large for gestational age (LGA). METHODS: This nationwide prospective birth cohort analysis included 3245 women who delivered their first two live singletons between 2011 and 2014. Interpregnancy weight change was calculated as the difference between the prepregnancy body mass index (BMI) of the first and second pregnancies. LGA infants were compared among three interpregnancy weight change groups: weight loss (a BMI loss >1 unit), weight gain (a BMI gain >1 unit), and stable weight (BMI maintained within - 1 to <1 unit). Interpregnancy weight change was assessed in mothers with a BMI <25 and ≥25 kg/m2, and adjusted odds ratios (ORs) were calculated for LGA infants by multiple logistic regression. RESULTS: The incidence of LGA infants was 8.6% (279 out of 3245). Compared with the stable weight group, interpregnancy weight gain was associated with an increased risk of infants being LGA (adjusted OR: 1.69, 95% confidence interval: 1.21-2.36) in the normal BMI (<25 kg/m2) group. In contrast, in the overweight/obese BMI (≥25 kg/m2) group, interpregnancy BMI was not a significant risk factor for LGA infants. CONCLUSIONS: Accurate risk stratification using interpregnancy BMI could assist the clinical management of women with a normal BMI who are at risk of delivering LGA infants.

Survey of Japanese researchers and the public regarding the culture of human embryos in vitro beyond 14 days.

The International Society for Stem Cell Research (ISSCR) has eliminated its prohibition on research involving the culturing of human embryos beyond 14 days within the updated 2021 guidelines. We conducted a survey of Japanese researchers working in stem cell- or embryo-related research (n = 535) and the public (n = 3,000) about their attitudes toward the 14-day rule. Among the researchers, 46.2% agreed that embryos could be cultured beyond 14 days, a result that was slightly lower among the public (37.9%). Among those that disagreed with embryo culturing beyond 14 days, 9.5% of researchers and 5.1% of the public agreed with culturing embryos within 14 days. Among the public, higher comprehension levels correlated with both agreement and disagreement with the culture of embryos beyond 14 days compared with "cannot judge." Further research and pubic discourse are necessary in order to better understand the factors informing participant decisions regarding the 14-day rule.

Multiple pregnancy as a potential risk factor for postpartum depression: The Japan Environment and Children's Study.

BACKGROUND: Postpartum depression (PPD) results in adverse consequences for both mother and infant. However, the association between multiple pregnancy and PPD is unknown because of the difference in the estimated prevalence rate of PPD based on country, ethnicity, and study type. Thus, this study aimed to determine whether Japanese women with multiple pregnancy were at a high risk of developing PPD at 1 and 6 months postpartum. METHODS: In this nationwide prospective cohort study (the Japan Environment and Children's Study), conducted between January 2011 and March 2014, 77,419 pregnant women were enrolled. PPD was assessed using the Edinburgh Postnatal Depression Scale (EPDS) 1 and 6 months postpartum. A score of ≥13 points implied "positive" for PPD. Multiple logistic regression analyses estimated the association between multiple pregnancy and PPD risk. RESULTS: Overall, 77,419 pregnancies (singleton, n = 76,738; twins, n = 676; triplets, n = 5) were included; 3.6 % and 2.9 % of pregnant women had PPD at 1 and 6 months postpartum, respectively. Compared with singleton pregnancy, multiple pregnancy was not associated with PPD at 1 month, but at 6 months postpartum (adjusted odd ratios: 0.968 [95 % confidence interval {CI}, 0.633-1.481] and 1.554 [95 % CI, 1.046-2.308], respectively). LIMITATIONS: 1) Some potential PPD risk factors could not be evaluated, 2) PPD was not diagnosed by psychiatrists, and 3) depressive symptoms at 6 months postpartum were considered PPD; however, definitions may vary. CONCLUSIONS: Japanese women with multiple pregnancy may be regarded as a target group for follow-up and postpartum depression screening for at least 6 months during the initial postpartum period.

Appropriate procedures to increase the adherence of children to blood collection: A cross-sectional study.

Background and Aim: Venipuncture for blood collection elicits fear and pain in children. We investigated factors that affect satisfaction with health checkups that included blood collection in healthy 7-8-year-old children who underwent blood collection with topical anesthesia. Method: Two studies, one questionnaire survey, and the other structured interviews were conducted to gather insights and understand the emotions of 492 and 20 children, respectively. Results: We found that the following six points can be applied to encourage children to assess their experience of blood collection positively: (1) prior information using a pamphlet; (2) telling the children that the volume of blood drawn will be small; (3) carefully explaining the risk and benefit of topical anesthesia; (4) conducting the blood collection process swiftly; (5) praising and thanking the children's effort and cooperation; and (6) explaining the results of the research to the children if their blood is going to be used for research. Conclusion: The findings indicate that with appropriate measures to reduce pain and fear, children's initial negative feelings toward blood collection can be replaced by positive feelings after the procedure.

Comparison of the 2021 International Society for Stem Cell Research (ISSCR) guidelines for "laboratory-based human stem cell research, embryo research, and related research activities" and the corresponding Japanese regulations.

This paper presents a comparison of the 2021 guidelines for stem cell research and clinical translation outlined by the International Society for Stem Cell Research (ISSCR) with the current regulations in Japan regarding the performance of such research. This paper provides a convenient English-language summary of the Japanese regulations, and illustrates the difference between the ISSCR guidelines and Japanese regulations regarding the conditions of implementation of study activities using human embryos or stem cells, for researchers outside Japan. The regulations governing the performance of research activities using human embryos or stem cells in Japan are relatively complex and comprise a range of laws and guidelines; the specific rules applied depend on the characteristics of each study. Therefore, even similar research activities may differ in terms of not only the guidelines or laws implemented, but also the procedures required. Such situations may confuse researchers.

Factors of parental COVID-19 vaccine hesitancy: A cross sectional study in Japan.

The eligibility of COVID-19 vaccines has been expanded to children aged 12 and above in several countries including Japan, and there is a plan to further lower the age. This study aimed to assess factors related to parental COVID-19 vaccine hesitancy. A nationwide internet-based cross-sectional study was conducted between May 25 and June 3, 2021 in Japan. The target population was parents of children aged 3-14 years who resided in Japan, and agreed to answer the online questionnaire. Parental COVID-19 vaccine hesitancy (their intention to vaccinate their child) and related factors were analyzed using logistic regression models. Interaction effects of gender of parents and their level of social relationship satisfaction related to parental vaccine hesitancy was tested using log likelihood ratio test (LRT). Social media as the most trusted information source increased parental vaccine hesitancy compared to those who trusted official information (Adjusted Odds Ratio: aOR 2.80, 95% CI 1.53-5.12). Being a mother and low perceived risk of infection also increased parental vaccine hesitancy compared to father (aOR 2.43, 95% CI 1.57-3.74) and those with higher perceived risk of infection (aOR 1.55, 95% CI 1.04-2.32) respectively. People with lower satisfaction to social relationships tended to be more hesitant to vaccinate their child among mothers in contrast to fathers who showed constant intention to vaccinate their child regardless of the level of satisfaction to social relationship (LRT p = 0.021). Our findings suggest that dissemination of targeted information about COVID-19 vaccine by considering means of communication, gender and people who are isolated during measures of social distancing may help to increase parental vaccine acceptance.

Clinical Application of In Vitro Fertilization and the Establishment of the Japan Society of Fertilization and Implantation.

The first Japanese in vitro fertilization (IVF) baby was born in 1983. The author considered the processes,how clinical application of IVF started, focusing on the establishment of the Japan Society of Fertilization and Implantation (JSFI), and the movement of the Japan Society of Fertility and Sterility (JSFS), and the Microsurgery Study Group (MSG). For this purpose, the author mainly reviewed the relevant papers from professional journals. Fundamental studies of IVF were reported before clinical application in JSFS established in 1956 for studying infertility treatment. In 1982, while clinical-application was argumentative topic in JSFS, JSFI was established by obstetricians and gynecologists who supported the clinical application. The establishment of JSFI was told as a go sign for the clinical application. Also, one of the purposes of JSFI was said to be making a consensus for clinical application. It was however, not achieved at least with the civic groups such as the DNA Problem Study Group. MSG was established in 1979 for studying microsurgery of the fallopian tubes, which is practiced to the fallopian tube infertility like IVF. Those who criticized the clinical application of IVF had an expectation to the obstetricians and gynecologists who studied this surgery. However, this surgery was ineffective, especially for the treatment of severe diseases of the fallopian tubes. Also, main members of JSFI and MSG were duplicated. Therefore, MSG had limitations against the movement toward clinical application of IVF characterized by the establishment of JSFI.