Mother-child correlation of kidney function: data from the Yamanashi Adjunct Study of Japan Environment and Children's Study (JECS).

BACKGROUND: Individual variation in kidney function can be affected by both congenital and acquired factors, and kidney function in children is possibly correlated with that in their mothers. However, the mother-child correlation in kidney function remains directly unconfirmed. METHODS: We conducted a cross-sectional study of 655 healthy pairs of 7- or 8-year-old children and their mothers as an adjunct study of a nationwide epidemiological study (Japan Environment and Children's Study). RESULTS: Both serum creatinine level (all children, r = 0.324, p < 0.001; girls, r = 0.365, p < 0.001; boys, r = 0.278, p < 0.001) and estimated glomerular filtration rate (eGFR) (r = 0.274, p < 0.001; r = 0.352, p < 0.001; r = 0.195, p < 0.001, respectively) in children were weakly associated with their maternal values. In the single linear regression analyses, maternal values of serum creatinine and eGFR were significantly associated with the children's values. Moreover, several body composition values in children, such as weight-SDS, fat (%), and predicted muscle weight, were also significantly associated with kidney function values in children. In the multiple linear regression analysis for serum creatinine levels in children, in which weight-SDS and predicted muscle weight in children were selected as adjustment factors, maternal serum creatinine level showed a significant positive association (B = 0.214, p < 0.001 in the adjusted model). Moreover, in the multiple linear regression analysis for eGFR value in children, in which fat (%) and predicted muscle weight in children were selected as adjustment factors, maternal eGFR values showed a significant positive association (B = 0.319, p < 0.001). CONCLUSIONS: We directly confirmed mother-child correlations in both serum creatinine levels and eGFR values, particularly in girls. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information.

Maternal protein intake in early pregnancy and child development at age 3 years.

BACKGROUND: The current study aimed to assess the association between low maternal protein intake during pregnancy and child developmental delay at age 3 years. METHODS: This research used data obtained from the Japan Environment and Children's Study. In total, we analyzed 77,237 mother-child pairs. Dietary intake was assessed using the Food Frequency Questionnaire. Developmental outcomes at age 3 years were evaluated with the Japanese version of the Ages and Stages Questionnaire, Third Edition. A multivariate logistic regression analysis was performed to assess the association between maternal protein intake during pregnancy and child development delays at age 3 years. RESULTS: Based on the protein-to-total energy intake ratio during early pregnancy, the participants were categorized into three groups: <9.39% (>2 standard deviation below the mean), the severely low protein (SLP) group; 9.39-<13%, the low protein group; and ≥13%, the normal protein group. After adjusting for potential confounding factors, SLP intake was found to be significantly correlated with a higher risk of developmental delay according to the communication, fine motor and problem-solving skill domains. CONCLUSIONS: SLP intake caused by inadequate diet during early pregnancy was associated with a higher risk of child developmental delay at age 3 years. IMPACT: Animal studies have shown that maternal protein restriction during pregnancy and lactation causes abnormal brain development among offspring. Birth cohort studies to date have not assessed the effects of maternal low protein exposure during pregnancy on child development. Severely low protein intake during early pregnancy was associated with a higher risk of child developmental delay at age 3 years. Since nutritional imbalance in early pregnancy affects not only fetal growth but also postnatal neurodevelopment, nutritional management before pregnancy is considered important.

Association of influenza vaccination or influenza virus infection history with subsequent infection risk among children: The Japan Environment and Children's Study (JECS).

We measured the association between history of influenza vaccination by age 2 years and influenza virus (IFV) infection at ages 3 and 4 years by relative risk reduction. We also examined the association between history of IFV infection by age 2 years and recurrent IFV infection at age 3 years. This study included 73,666 children from a large Japanese birth cohort. Among children vaccinated never, once or twice when aged under 2 years, 16.0%, 10.8% and 11.3%, respectively, had been infected with IFV by age 3 years, and 19.2%, 14.5% and 16.0%, respectively, by age 4 years. Compared with no history of influenza vaccination, vaccination at ages 1 and/or 2 years reduced the risk of IFV infection at age 3 by 30%-32% and at age 4 by 17%-24%. The relative risk of recurrent IFV infection at ages 3 and 4 years increased in proportion to the number of prior infections by age 2. One-season-prior influenza vaccination history reduced the IFV infection risk at age 3 years by 25%-42%. Influenza vaccination most effectively protected children at age 3 who lacked older sibling(s) and did not attend nursery school. One-season-prior IFV infection increased the relative risk of recurrent infection at age 3 years (1.72-3.33). In conclusion, influenza vaccination-induced protection may partly extend to the next season. Owing to the relative risk reduction by influenza vaccination and the increased relative risk of IFV infection from prior-season infection, annual influenza vaccination is recommended.

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.

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.

Risk of low birthweight associated with the timing and frequency of antenatal care visits in Lao PDR: a retrospective cohort study.

BACKGROUND: Antenatal care (ANC) plays an important role in preventing low birthweight (LBW). Whereas the government of Lao People's Democratic Republic (Lao PDR) has committed to increasing the usage of ANC, little attention has been given to the early initiation of ANC. The present study assessed the influence of delayed and fewer ANC visits on LBW in the country. METHODS: This is a retrospective cohort study conducted at Salavan Provincial Hospital. Study participants were all pregnant women who gave birth at the hospital between 1 August 2016 and 31 July 31 2017. Data were collected from medical records. Logistic regression analyses were performed to quantify the relationship between ANC visits and LBW. We also investigated factors associated with inadequate ANC visits: first ANC visit after the first trimester or < 4 ANC visits. RESULTS: The mean birth weight was 2808.7 g [standard deviation: SD 455.6]. Among 1804 participants, 350 (19.4%) had babies with LBW, and 147 (8.2%) had inadequate ANC visits. In multivariate analyses, compared to participants with adequate ANC visits, those with ≥ 4 ANC visits and the first ANC visit after the second trimester, those with < 4 ANC visits, and those with no ANC visits had higher odds ratios (ORs) of LBW: 3.77 (95% confidence interval: CI = 1.66-8.57), 2.39 (95% CI = 1.18-4.83) and 2.22 (95% CI = 1.08-4.56), respectively. Younger maternal age (OR 1.42; 95% CI = 1.07-1.89), government subsidisation (OR 2.69; 95% CI = 1.97-3.68) and ethnic minority (OR 1.88; 95% CI = 1.50-2.34) were associated with increased risk of insufficient number of ANC visits after adjusting for covariates. CONCLUSIONS: Frequent and early initiation of ANC was associated with a reduction in LBW in Lao PDR. Encouraging childbearing-aged women to receive sufficient ANC at proper timing may lead to a reduction in LBW and improvement in short- and long-term health outcomes of neonates. Special attention will be needed for ethnic minorities and women in lower socioeconomic classes.

'Caregivers' awareness matters': Call for a child-centred approach to early detection of autism spectrum disorder through well-child visits in Japan.

BACKGROUND: Early detection of autism spectrum disorder (ASD) is essential to provide children with timely treatment and support. Evidence-based screening measures make it possible to identify children with suspected ASD at an early stage. Although Japan has a universal healthcare system that covers well-child visits, detection rates of developmental disorders, including ASD, at 18 months vary widely between municipalities (0.2%-48.0%). The reasons for this high level of variation are poorly understood. The present study aims to describe the barriers and facilitators of incorporating ASD identification during well-child visits in Japan. METHODS: This is a qualitative study that conducts semi-structured in-depth interviews in two municipalities of Yamanashi Prefecture. We recruited all public health nurses (n = 17) and paediatricians (n = 11) involved in the well-child visit in each municipality and caregivers of children who also participated in the visits during the study period (n = 21). RESULTS: We identified four themes characterizing the process of ASD identification in the target municipalities: (1) Identification of children with ASD is driven by caregivers' sense of concern, acceptance and awareness. (2) Multidisciplinary cooperation and shared decision-making is limited. (3) Skills and training for developmental disabilities screening are underdeveloped. (4) Caregivers' expectations shape the interaction in important ways. CONCLUSIONS: Non-standardization of screening methods, limited knowledge and skills on screening and child development among healthcare providers and poor coordination among healthcare providers and caregivers are the main barriers to effective early detection of ASD through well-child visits. The findings suggest the importance of promoting a child-centred care approach through the application of evidence-based screening measures and effective information sharing.

Effect of birth season on allergic rhinitis and cedar pollinosis considering allergen and vitamin D exposure: The Japan Environment and Children's study (JECS).

BACKGROUND: The relationship between the season of birth, allergen sensitization, and allergic rhinitis have been inconsistent, and there are no studies that simultaneously consider vitamin D and allergen exposure. This study aimed to determine the associations between the season of birth, house dust mite (HDM) and Japanese cedar pollen (JCP) sensitization, and allergic rhinitis and pollinosis, while taking vitamin D levels and allergen exposure into account. METHODS: This study included 4323 participants in the Sub-Cohort Study of the Japan Environment and Children's Study. A logistic regression model was used to analyze the association between the season of birth and sensitization to JCP or HDM (judged by specific immunoglobulin E) at age 2 and allergic rhinitis or pollinosis at age 3, adjusted for HDM or JCP exposure and vitamin D levels with potential confounders. RESULTS: Participants born in spring or summer were more likely to have pollinosis than were those born in winter (adjusted odds ratio [aOR]: 2.08, 95% confidence interval [CI]: 1.13-3.82 for spring; aOR: 1.89, 95% CI: 1.03-3.47 for summer). Participants born in summer were more likely to have HDM sensitization than were those born in winter (Der p 1, aOR: 1.53, 95% CI: 1.10-2.15; Der f 1, aOR: 1.44, 95% CI: 1.03-2.01). Exposure to JCP and HDM were associated with pollinosis and HDM sensitization, respectively. CONCLUSIONS: Spring and summer births were associated with the development of pollinosis, and summer birth was associated with HDM sensitization, even when vitamin D and allergen exposure were considered. Further studies on mechanisms other than vitamin D and allergen exposure are required.

Relationship between floating toes condition and lower limb muscle weight in 8-year-old children: the Yamanashi adjunct study of the Japan Environment and Children's Study (JECS-Y).

[Purpose] Floating toe is a condition in which the toes make insufficient contact with the ground. Weak muscle strength is reportedly one cause of floating toe. However, little evidence exists regarding the relationship between foot muscle strength and floating toe. Here we examined the relationship between foot muscle strength and floating toe by investigating the children' lower extremity muscle mass and floating toe conditions. [Participants and Methods] This cohort study enrolled 118 8-year-old children (62 females, 56 males) with recorded footprints and muscle mass evaluations using dual-energy X-ray absorptiometry. We calculated the floating toe score using the footprint. We measured the muscle weights and the muscle weights divided by the lengths of the lower limbs separately on the left and right sides using dual-energy X-ray absorptiometry. [Results] No significant correlations were observed between the floating toe score and muscle weights or muscle weights divided by lower-limb lengths for either gender or side. [Conclusion] In this study, no significant correlation was found between floating toe degree and lower limb muscle mass, suggesting that lower limb muscle strength is not the primary cause of floating toe, at least in children.

Prenatal Negative Life Events and Childhood Allergies: The Japan Environment and Children's Study (JECS).

BACKGROUND: It is inconclusive whether prenatal negative life events are a risk for the development of allergic diseases in children or whether social capital modifies the association. The objective of this study was to examine whether women's experiences of such events during pregnancy were associated with the development of allergic diseases in their offspring at 3 years old and whether social capital moderated this association. METHODS: We used data from 81,337 mother-child pairs who participated in the Japan Environment and Children's Study. This is a prospective birth cohort recruited between January 2011 and March 2014. We examined the associations between prenatal maternal negative life events (e.g., bereavement, financial, and marital problems) during pregnancy and allergic diseases (asthma, eczema, and food allergies) in children after adjustment for covariates using multivariate logistic regression. We also examined interactions between these life events and social capital, measured as two items, social cohesion and social support. RESULTS: Prenatal negative life events were significantly associated with doctor-diagnosed asthma at 3 years old with a dose-response relationship (one life event vs. none: adjusted odds ratio 1.13, 95% confidence interval [CI]: 1.07-1.20; two life events vs. none: adjusted odds ratio 1.24, 95% CI: 1.13-1.36; three or more life events vs. none: adjusted odds ratio 1.26, 95% CI: 1.10-1.46; p for trend <0.01). Similar results were observed for eczema and food allergies. There were no interactions between life events and social capital. CONCLUSION: Prenatal negative life events may be a risk factor for allergies in children. There was no modification of the effect of these events by social capital.

Association between Household Income and Allergy Development in Children: The Japan Environment and Children's Study.

BACKGROUND: Socioeconomic status has been found to be associated with allergic diseases in children, but results are inconsistent. This study aimed to assess the association between household income and the development of allergic disease in children at 3 years old. METHODS: We used data from 72,180 participants from the Japan Environment and Children's Study, which is a prospective birth cohort study with participants recruited from January 2011 to March 2014. We examined the associations between household income and allergic diseases (asthma, eczema, and food allergies) in children, adjusting for covariates using multivariate logistic regression. RESULTS: The percentages of doctor-diagnosed allergies at 3 years old were 7.5% for asthma, 7.2% for eczema, and 6.2% for food allergies. Children from households with an annual income of <2 million yen (approx. 18,000 USD) had a significantly higher risk of doctor-diagnosed asthma and eczema than those from households with an income of 4-6 million yen. The adjusted odds ratios (aORs) were 1.17 (95% confidence interval [CI] 1.03-1.34) and 1.21 (95% CI 1.06-1.39). Children from households with an income of >6 million yen tended to have an increased risk of food allergies (aOR 1.07, 95% CI 0.98-1.15). CONCLUSION: Low household income was a risk for doctor-diagnosed asthma and eczema, suggesting that public health professionals should recognize low-income groups as vulnerable populations for these conditions.

Prenatal occupational disinfectant exposure and childhood allergies: the Japan Environment and Children's study.

BACKGROUND: Disinfectants are widely used in the medical field, particularly recently because of the coronavirus pandemic, which has led to an increase in their use by both medical professionals and the general population. The objective of this study was to examine whether occupational disinfectant use during pregnancy was associated with the development of allergic disease in offspring at 3 years. METHODS: We used data from 78 915 mother/child pairs who participated in the Japan Environment and Children's Study, which is a prospective birth cohort recruited between January 2011 and March 2014. We examined the associations between maternal disinfectant use during pregnancy and allergic diseases (asthma, eczema and food allergies) in children after adjustment for covariates including maternal postnatal return to work when the child was 1 year old by multivariate logistic regression. RESULTS: Compared with those who never used disinfectants, participants who used disinfectant every day had a significantly higher risk of asthma in their offspring (adjusted OR 1.18, 95% CI 1.05 to 1.33 for 1-6 times a week; adjusted OR 1.26, 95% CI 1.05 to 1.52 for every day). The associations between disinfectant exposure and eczema were similar to those of asthma (adjusted OR 1.16, 95% CI 1.02 to 1.31 for 1-6 times a week; adjusted OR 1.29, 95% CI 1.06 to 1.57 for every day). We found a significant exposure-dependent relationship (p for trend <0.01). There were no significant associations between disinfectant use and food allergies. CONCLUSION: Disinfectant use by pregnant women may be a risk factor for asthma and eczema in offspring. As disinfectants are an effective tool in the prevention of infectious diseases, replication of this study and further research into the mechanisms are warranted.

Mother's iodine exposure and infants' hypothyroidism: the Japan Environment and Children's Study (JECS).

In this study, we aimed to determine the association of neonatal/post-neonatal hypothyroidism with mother's iodine exposure, especially povidone iodine disinfection, and hysterosalpingography. Participants were mother-child pairs in a Japanese birth cohort (n = 100,286). Risk factors of hypothyroidism were supplement intake, seaweed intake, other daily iodine intake, povidone iodine disinfection at delivery, and maternal history of hysterosalpingography, thyroid disease (Graves' disease and Hashimoto's thyroiditis), and medication (thiamazole and levothyroxine). Congenital hypothyroidism (CH) at age 1 year was assessed using a questionnaire. Transient hypothyroidism was defined as elevated thyroid stimulating hormone level at birth and absence of CH at age 1 year. The incidence of CH at age 1 year per 100 children was 1.1 for those born at 22-30 weeks' gestation, 0.17 following povidone iodine disinfection, and 0.07, 0.95, 0.81, 1.17, and 1.15 with a maternal history of hysterosalpingography, Graves' disease, Hashimoto's thyroiditis, thiamazole use, and levothyroxine use, respectively. Odds ratios (95% confidence intervals) of CH at age 1 year for povidone iodine disinfection, hysterosalpingography history, maternal Graves' disease, and maternal Hashimoto's thyroiditis were 1.13 (0.71-1.79), 0.47 (0.07-3.36), 7.06 (3.70-13.5), and 5.93 (2.90-12.1), respectively. For transient hypothyroidism for povidone iodine disinfection and hysterosalpingography history, these values were 1.99 (1.51-2.62) and 0.63 (0.20-1.96), respectively. Maternal thyroid disease greatly increased neonatal/post-neonatal hypothyroidism risk. Povidone iodine disinfection may increase transient hypothyroidism risk but not the risk at 1 year of age. Hysterosalpingography does not increase hypothyroidism risk from birth to age 1 year.

Association of egg protein levels in dust with allergy status and related factors.

BACKGROUND: Levels of peanut protein in dust have been reported to be associated with sensitization and allergy to it, so controlling food protein in dust may help prevent food allergy. However, studies of factors associated with egg protein levels in dust are scarce. This study aimed to determine the factors contributing to egg protein levels in dust. METHODS: This cross-sectional study included 159 participants in the Sub-Cohort Study of the Japan Environment and Children's Study in Yamanashi Prefecture at a 6 year follow up. House dust at 6 years was collected and egg protein concentrations were measured for whole egg protein. Household factors, including the maternal frequency of egg consumption, were assessed by questionnaires. A linear regression model was used to analyze the effect of household environmental factors on egg protein in dust. RESULTS: In multivariate analysis, frequent maternal egg consumption (≥5 times a week) was associated with higher egg protein concentrations in house dust (ß = 0.96, P = 0.01). The egg protein load was significantly associated with a higher number of cohabitants (≥5, ß = 0.85, P = 0.02) in addition to frequent maternal egg consumption. Among the participants, 140 (88.1%) had no egg allergy, 15 (9.4%) were egg tolerant, and 4 (2.5%) had an egg allergy at 6 years old. There was no significant association between the current egg allergy status and egg protein concentrations in dust. CONCLUSIONS: The frequency of maternal egg consumption and the number of inhabitants are contributing factors to egg protein levels in dust.

A cross-sectional study on the correlations between floating toe, plantar arch posture, and body composition in 8-year-old children.

BACKGROUND: Floating toe (FT): inadequately in contact with the ground and flexible flat foot (FFF) are frequently seen in children. According to some reports, inadequate foot muscle strength may cause FT or FFF.Therefore, a relationship may exist between arch formation, FT, and pedal muscle strength. This study aimed to evaluate the correlation of FT with plantar arch posture and body composition, including overall muscle mass. METHODS: We conducted our own cohort study in addition to the Japan Environment and Children's Study conducted by the Ministry of the Environment, Japan. Out of 705 eight-year-old children participating in this adjunct study, 578 with recorded footprints were included. Body composition (body weight, body fat percentage, and predicted muscle mass) was assessed using body composition analyzer. Presence of FT or FFF was evaluated using foot pressure plate. We calculated the FT score (small FT score indicates insufficient ground contact of the toes) and the Chippaux-Smirak Index (CSI) using images of the plantar footprint. RESULTS: The FT score (an indicator of FT) showed no significant correlation with CSI (an indicator of plantar arch posture). Moreover, no significant correlations between the predicted muscle mass, FT score, and CSI were observed. CONCLUSIONS: This is the first report that assessed the relationship of FT with plantar arch posture and body composition in children. This study indicated that muscle strength might not be a major factor for FT and FFF development in children.

Gestational body weight gain and risk of low birth weight or macrosomia in women of Japan: a nationwide cohort study.

OBJECTIVE: Both maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) influence maternal and pediatric outcomes. We sought to clarify the impact of prepregnancy BMI-specific GWG and its patterns on the risk of low birth weight (LBW) or macrosomia using data from a large nationwide study in Japan. METHODS: This cohort study (n = 98,052) used data from the Japan Environment and Children's Study (JECS). The outcome variables in this study were LBW and macrosomia. We stratified the subjects into groups according to prepregnancy BMI. RESULTS: GWG from pre-pregnancy to the first trimester had a small effect on the risk of LBW and macrosomia. From the first to second trimesters, insufficient GWG was associated with the risk of LBW, and from the second trimester to delivery, a GWG of less than 2 kg was associated with the risk of LBW. These associations were commonly observed in all prepregnancy BMI categories. Irrespective of the GWG from pre-pregnancy to the first trimester, GWG from the first to second trimesters affects LBW and/or macrosomia. Irrespective of the GWG from the first to second trimesters, GWG from the second trimester to delivery affects LBW and/or macrosomia. LBW or macrosomia was associated with the prevalence of a sustained low or high BMI percentile until three years of age, respectively. CONCLUSIONS: The present large national cohort study indicates that the risk of LBW or macrosomia is associated with GWG in women in Japan; the significance of this risk depends on the GWG patterns.

Association between gestational hair dye use and allergies at 3 years old: the Japan environment and Children's study.

BACKGROUND: Hair dye use frequently induces allergic contact dermatitis, and on rare occasions induces immunoglobulin E-mediated immediate urticaria, anaphylaxis, and asthma. The effects of hair dye use during pregnancy on offspring have been studied for carcinogenicity, but not for development of allergies. This study aimed to assess the association between hair dye use during pregnancy and allergic disease in children at 3 years old. METHODS: Data of 77,303 participants from the Japan Environment and Children's Study, which is a prospective birth cohort recruited from January 2011 to March 2014, were used. We examined the associations between using hair dye during pregnancy and allergic diseases (food allergy, asthma, atopic dermatitis and allergic rhinitis) in children after adjustment for covariates by multivariable logistic regression. RESULTS: Among mothers who were exposed to hair dye during pregnancy, 50.0% were exposed in hair salons, 21.3% had home use, and 9.5% had occupational exposure. The percentages of doctor-diagnosed allergies at 3 years old were 6.3% for food allergies, 7.7% for asthma, 7.3% for atopic dermatitis, and 4.6% for allergic rhinitis. In univariable analyses, hair dye use at home and occupational exposure was significantly associated with asthma respectively (odds ratio [OR] 1.15, 95% CI 1.07-1.24 for at home; OR 1.18, 95% CI 1.08-1.28 for occupational exposure). Hair dye use at home were significantly associated with doctor-diagnosed allergic rhinitis at 3 years old (OR 1.12, 95% CI 1.02-1.22). After adjustment for covariates, these associations for asthma decreased and were no longer significant (aOR 1.06, 95% CI 0.98-1.14 for at home; aOR 1.09, 95% CI 1.00-1.20 for occupational exposure, p = 0.057), also for allergic rhinitis (aOR 1.07, 95% CI 0.97-1.19). Doctor-diagnosed allergic rhinitis at 3 years old was significantly associated with hair dye use at home in the most frequent use group (aOR for quite often versus never 1.78, 95% CI 1.22-2.60). CONCLUSION: Both home and occupation use of hair dye during pregnancy showed a trend of increased odds of allergic rhinitis and asthma in offspring at 3 years. However, the only association that reached significance was in frequency of use analyses between the highest frequency of home hair dye users and allergic rhinitis.

Effectiveness of self-managed continuous monitoring for maintaining high-quality early essential newborn care compared to supervision visit in Lao PDR: a cluster randomised controlled trial.

BACKGROUND: Thousands of neonatal deaths are expected to be averted by introducing the Early Essential Newborn Care (EENC) in the Western Pacific Region. In Lao People's Democratic Republic (Lao PDR), the government adopted the EENC programme and expanded it to district hospitals. With the expansion, maintaining the quality of EENC has become difficult for the government. METHODS: A cluster randomised controlled trial with four strata based on province and history of EENC coaching was implemented to evaluate the effectiveness of self-managed continuous monitoring compared with supervisory visit in Lao PDR between 20 July 2017 and 2 April 2019. Health workers who were routinely involved in maternity care were recruited from 15 district hospitals in Huaphanh (HP) and Xiangkhouang (XK) provinces. The primary endpoint was the score on the determinants of EENC performance measured by the Theory of Planned Behaviour (TPB). Secondary endpoints were set as the knowledge and skill scores. A linear mixed-effects model was applied to test the effects of intervention over time on the endpoints. RESULTS: Among 198 recruited health workers, 46 (23.2%) did not complete the final evaluation. TPB scores were 180.9 [Standard Deviation: SD 38.6] and 182.5 [SD 37.7] at baseline and 192.3 [SD 30.1] and 192.3 [SD 28.4] at the final evaluation in the intervention and control groups, respectively. There was no significant difference in changes between the groups in the adjusted model (2.4, p = 0.650). Interviews with participants revealed that district hospitals in HP regularly conducted peer reviews and feedback meetings, while few hospitals did in XK. Accordingly, in stratified analyses, the TPB score in the intervention group significantly increased in HP (15.5, p = 0.017) but largely declined in XK (- 17.7, p = 0.047) compared to the control group after adjusting for covariates. Skill scores declined sharper in the intervention group in XK (- 8.78, p = 0.026), particularly in the practice of managing nonbreathing babies. CONCLUSIONS: The study indicates that self-managed continuous monitoring is effective in improving behaviour among district health workers; however, additional measures are necessary to support its proper implementation. To maintain resuscitation skills, repeated practice is necessary. TRIAL REGISTRATION: This trial was registered at UMIN Clinical Trials Registry on 15/6/2017. Registration number is UMIN000027794 .

Association between preterm birth and maternal allergy considering IgE level.

BACKGROUND: The aim of this study was to explore the association between maternal allergies and preterm birth by different total immunoglobulin E (IgE) levels. METHODS: Data of 81 791 pregnant women from the Japan Environment and Children's Study, a prospective birth cohort, were used. Maternal allergic diseases, including a history of bronchial asthma (BA), atopic dermatitis (AD), and allergic rhinitis (AR), were obtained by self-administered questionnaires. Total serum IgE levels were measured at the first trimester and obstetrical outcomes from medical records transcripts were analyzed. The association between maternal allergic disease and obstetric outcome, including threatened abortion, preterm labor, early preterm birth (22-33 weeks), and late preterm birth (34-36 weeks), were examined by logistic regression. Subgroup analyses were performed by IgE level. RESULTS: Maternal BA and AR were associated with an increased risk of threatened abortion and preterm labor, but high total IgE level was associated with a decreased risk of preterm labor. There was little difference in associations between allergic disease and threatened abortion and preterm labor by total IgE levels. Although there was no significant association between allergic disease and preterm birth, if total IgE was high, AR was significantly associated with a decreased risk of early preterm birth (adjusted odds ratio, 0.60; 95% confidence interval 0.43-0.86). There was significant evidence for differences associated with total IgE levels (P-values for the interaction of the effects of AD and AR on early preterm birth were 0.039 and 0.015, respectively). CONCLUSIONS: The effect of allergy on preterm birth might differ depending on the total IgE level.

Mechanisms of aggregation and fibril formation of the amyloidogenic N-terminal fragment of apolipoprotein A-I.

The N-terminal (1-83) fragment of the major constituent of plasma high-density lipoprotein, apolipoprotein A-I (apoA-I), strongly tends to form amyloid fibrils, leading to systemic amyloidosis. Here, using a series of deletion variants, we examined the roles of two major amyloidogenic segments (residues 14-22 and 50-58) in the aggregation and fibril formation of an amyloidogenic G26R variant of the apoA-I 1-83 fragment (apoA-I 1-83/G26R). Thioflavin T fluorescence assays and atomic force microscopy revealed that elimination of residues 14-22 completely inhibits fibril formation of apoA-I 1-83/G26R, whereas Δ32-40 and Δ50-58 variants formed fibrils with markedly reduced nucleation and fibril growth rates. CD measurements revealed structural transitions from random coil to ß-sheet structures in all deletion variants except for the Δ14-22 variant, indicating that residues 14-22 are critical for the ß-transition and fibril formation. Thermodynamic analysis of the kinetics of fibril formation by apoA-I 1-83/G26R indicated that both nucleation and fibril growth are enthalpically unfavorable, whereas entropically, nucleation is favorable, but fibril growth is unfavorable. Interestingly, the nucleation of the Δ50-58 variant was entropically unfavorable, indicating that residues 50-58 entropically promote the nucleation step in fibril formation of apoA-I 1-83/G26R. Moreover, a residue-level structural investigation of apoA-I 1-83/G26R fibrils with site-specific pyrene labeling indicated that the two amyloidogenic segments are in close proximity to form an amyloid core structure, whereas the N- and C-terminal tail regions are excluded from the amyloid core. These results provide critical insights into the aggregation mechanism and fibril structure of the amyloidogenic N-terminal fragment of apoA-I.