Nasopharyngeal airway long noncoding RNAs of infants with bronchiolitis and subsequent risk of developing childhood asthma.

BACKGROUND: Severe bronchiolitis (ie, bronchiolitis requiring hospitalization) during infancy is a major risk factor for developing childhood asthma. However, the biological mechanisms linking these 2 conditions remain unclear. OBJECTIVE: We sought to investigate the longitudinal relationship between nasopharyngeal airway long noncoding RNA (lncRNA) in infants with severe bronchiolitis and subsequent asthma development. METHODS: In this multicenter prospective cohort study of infants with severe bronchiolitis, we performed RNA sequencing of nasopharyngeal airway lncRNAs at index hospitalization. First, we identified differentially expressed lncRNAs (DE-lncRNAs) associated with asthma development by age 6 years. Second, we investigated the associations of DE-lncRNAs with asthma-related clinical characteristics. Third, to characterize the function of DE-lncRNAs, we performed pathway analysis for mRNA targeted by DE-lncRNAs. Finally, we examined the associations of DE-lncRNAs with nasal cytokines at index hospitalization. RESULTS: Among 343 infants with severe bronchiolitis (median age, 3 months), we identified 190 DE-lncRNAs (false-discovery rate [FDR] < 0.05) associated with asthma development (eg, LINC02145, RAMP2-AS1, and PVT1). These DE-lncRNAs were associated with asthma-related clinical characteristics (FDR < 0.05), for example, respiratory syncytial virus or rhinovirus infection, infant eczema, and IgE sensitization. Furthermore, DE-lncRNAs were characterized by asthma-related pathways, including mitogen-activated protein kinase, FcɛR, and phosphatidylinositol 3-kinase (PI3K)-protein kinase B signaling pathways (FDR < 0.05). These DE-lncRNAs were also associated with nasal cytokines (eg, IL-1ß, IL-4, and IL-13; FDR < 0.05). CONCLUSIONS: In a multicenter cohort study of infants with severe bronchiolitis, we identified nasopharyngeal airway lncRNAs associated with childhood asthma development, characterized by asthma-related clinical characteristics, asthma-related pathways, and nasal cytokines. Our approach identifies lncRNAs underlying the bronchiolitis-asthma link and facilitates the early identification of infants at high risk of subsequent asthma development.

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.

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.

Nasopharyngeal lipidomic endotypes of infants with bronchiolitis and risk of childhood asthma: a multicentre prospective study.

BACKGROUND: Bronchiolitis is the leading cause of hospitalisation of US infants and an important risk factor for childhood asthma. Recent evidence suggests that bronchiolitis is clinically heterogeneous. We sought to derive bronchiolitis endotypes by integrating clinical, virus and lipidomics data and to examine their relationship with subsequent asthma risk. METHODS: This is a multicentre prospective cohort study of infants (age <12 months) hospitalised for bronchiolitis. We identified endotypes by applying clustering approaches to clinical, virus and nasopharyngeal airway lipidomic data measured at hospitalisation. We then determined their longitudinal association with the risk for developing asthma by age 6 years by fitting a mixed-effects logistic regression model. To account for multiple comparisons of the lipidomics data, we computed the false discovery rate (FDR). To understand the underlying biological mechanism of the endotypes, we also applied pathway analyses to the lipidomics data. RESULTS: Of 917 infants with bronchiolitis (median age, 3 months), we identified clinically and biologically meaningful lipidomic endotypes: (A) cinicalclassiclipidmixed (n=263), (B) clinicalseverelipidsphingolipids-high (n=281), (C) clinicalmoderatelipidphospholipids-high (n=212) and (D) clinicalatopiclipidsphingolipids-low (n=161). Endotype A infants were characterised by 'classic' clinical presentation of bronchiolitis. Profile D infants were characterised by a higher proportion of parental asthma, IgE sensitisation and rhinovirus infection and low sphingolipids (eg, sphingomyelins, ceramides). Compared with endotype A, profile D infants had a significantly higher risk of asthma (22% vs 50%; unadjusted OR, 3.60; 95% CI 2.31 to 5.62; p<0.001). Additionally, endotype D had a significantly lower abundance of polyunsaturated fatty acids (eg, docosahexaenoic acid; FDR=0.01). The pathway analysis revealed that sphingolipid metabolism pathway was differentially expressed in endotype D (FDR=0.048). CONCLUSIONS: In this multicentre prospective cohort study of infants with bronchiolitis, integrated clustering of clinical, virus and lipidomic data identified clinically and biologically distinct endotypes that have a significantly differential risk for developing asthma.Delete.

Proteomics endotyping of infants with severe bronchiolitis and risk of childhood asthma.

BACKGROUND: Bronchiolitis is the leading cause of hospitalization in U.S. infants and a major risk factor for childhood asthma. Growing evidence supports clinical heterogeneity within bronchiolitis. We aimed to identify endotypes of infant bronchiolitis by integrating clinical, virus, and serum proteome data, and examine their relationships with asthma development. METHODS: This is a multicenter prospective cohort study of infants hospitalized for physician-diagnosis of bronchiolitis. We identified bronchiolitis endotypes by applying unsupervised machine learning (clustering) approaches to integrated clinical, virus (respiratory syncytial virus [RSV], rhinovirus [RV]), and serum proteome data measured at hospitalization. We then examined their longitudinal association with the risk for developing asthma by age 6 years. RESULTS: In 140 infants hospitalized with bronchiolitis, we identified three endotypes: (1) clinicalatopic virusRV proteomeNFκB-dysregulated , (2) clinicalnon-atopic virusRSV/RV proteomeTNF-dysregulated , and (3) clinicalclassic virusRSV proteomeNFκB/TNF-regulated endotypes. Endotype 1 infants were characterized by high proportion of IgE sensitization and RV infection. These endotype 1 infants also had dysregulated NFκB pathways (FDR < 0.001) and significantly higher risks for developing asthma (53% vs. 22%; adjOR 4.04; 95% CI, 1.49-11.0; p = 0.006), compared with endotype 3 (clinically resembling "classic" bronchiolitis). Likewise, endotype 2 infants were characterized by low proportion of IgE sensitization and high proportion of RSV or RV infection. These endotype 2 infants had dysregulated tumor necrosis factor (TNF)-mediated signaling pathway (FDR <0.001) and significantly higher risks for developing asthma (44% vs. 22%; adjOR 2.71; 95% CI, 1.03-7.11, p = 0.04). CONCLUSION: In this multicenter cohort, integrated clustering of clinical, virus, and proteome data identified biologically distinct endotypes of bronchiolitis that have differential risks of asthma development.

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.

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.

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.

Prevalence of and factors associated with unplanned pregnancy among women in Koshu, Japan: cross-sectional evidence from Project Koshu, 2011-2016.

BACKGROUND: Unplanned pregnancy is a public health issue with adverse consequences for maternal and neonatal health. In Japan, the prevalence of unplanned pregnancy was 46.2% in 2002. However, few studies have investigated this topic, and there is little recent data from Japan. We described and examined the prevalence and determinants of unplanned pregnancy among rural women in Japan from 2011 to 2016. METHODS: We used cross-sectional data from a community-based cohort study (Project Koshu). Data were collected from 2011 to 2016 via a self-report questionnaire included in the Maternal and Child Health Handbook of Japan. Pregnancy intention was measured as a binary variable (planned or unplanned). Univariate and multivariate logistic regression analyses were performed to examine factors associated with unplanned pregnancy, with results reported as odds ratios (ORs) and 95% confidence intervals (CIs). We conducted sensitivity analyses with different definitions of pregnancy intention to assess the robustness of the results. The significance level was set at 5%. RESULTS: Of the 932 participants (mean ± standard deviation age at baseline: 31.3 ± 5.2 years), 382 (41%) pregnancies were reported as unplanned. The multivariate analyses showed that maternal age (+ 1 year: OR = 0.94, 95% CI: 0.92-0.97, p <  0.001), 'other' family structure (OR = 2.76, 95% CI: 1.12-6.76, p = 0.03), three or more pregnancies (OR = 2.26, 95% CI: 1.66-3.08, p <  0.001), current smoking (OR = 2.60, 95% CI: 1.26-5.35, p = 0.01), balanced diet (OR = 0.62, 95% CI: 0.47-0.83, p <  0.001) and current depression (OR = 1.63, 95% CI: 1.24-2.16, p <  0.001) were strongly associated with unplanned pregnancy. These associations were consistent across definitions of pregnancy intention, supporting the robustness of our results. CONCLUSIONS: The prevalence of unplanned pregnancy in the study population was high (41%). Risk factors for unplanned pregnancy were age, number of pregnancies, smoking, having a balanced diet and current depression. These results suggest greater efforts are needed to enhance sex education for young people, improve access to family planning services and provide comprehensive health care for high-risk women to help reduce unplanned pregnancies.

[Association between time-appropriate vaccinations in early childhood and individual and community-level factors in Japan].

Objective　Recently, in Japan, the compulsory vaccinations administered during early childhood have been becoming increasingly varied. As a result, the vaccination schedule has become complicated. In this study, we aimed to identify the association of time-appropriate vaccination during early childhood (dependent variable) with individual-level factors including socioeconomic status and having a family doctor. We also studied the association of time-appropriate vaccination with community-level factors including the number of pediatricians in a community.Methods　Multilevel logistic regression models were used for analysis. Time-appropriate BCG, DPT, and measles vaccinations were the dependent variables. Individual-level data were obtained through a survey of parents of 18-month-old children as part of the final evaluation of "Healthy Parents and Children 21"; community-level data were obtained through a survey of municipalities as part of the aforementioned final evaluation as well as through a national survey. There were 23,583 parents in 430 municipalities who were eligible for analysis.Results　Time-appropriate vaccination of infants was carried out by 88.3% of parents. The results of the multilevel logistic regression showed that time-appropriate vaccination was significantly lower for those who did not have a family doctor (adjusted odds ratio [AOR], 0.45; 95% confidence interval [CI], 0.36-0.55), the fourth or later birth order (0.23; 0.19-0.28), mothers aged less than 19 years at childbirth (0.17; 0.13-0.24), full-time working mothers (0.52; 0.47-0.58), and those under very difficult economic conditions (0.66; 0.57-0.77). Among community-level factors, only use of vaccination data by a municipality had a significantly negative association with the dependent variable.Conclusion　Not having a family doctor, the mother's young age, late birth order, poor economic status, and full-time working mothers were risk factors associated with delayed vaccinations. It is necessary to improve environments that promote infants having a family doctor as well as to promote special approaches toward families at risk for delayed vaccinations.