Association of a low chest-to-head circumference ratio with breech or transverse lie: the Japan Environment and Children's Study.

OBJECTIVE: We examined whether the chest-to-head circumference ratio at birth was associated with breech presentation and transverse lie. We also described the obstetric management of such pregnancies in the Japan Environment and Children's Study (JECS). METHODS: We performed a cross-sectional evaluation of data collected between January 2011 and March 2014 in a nationwide prospective birth cohort study, the JECS. We analyzed 83,822 non-anomalous singletons born at 34-41 weeks' gestation to mothers with no history of previous cesareans or uterine surgery. We defined low, normal (reference group), and high chest-to-head circumference ratios as <10th percentile, 10th to 90th percentiles, and >90th percentile, respectively. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for breech presentation and transverse lie. The timing and mode of delivery of such pregnancies were examined. RESULTS: Breech presentation was recorded in 2.6% and transverse lie in 0.2%. A low chest-to-head circumference ratio was associated with increased rate of breech presentation (5.2%; adjusted OR 2.36, 95% CI: 2.10-2.65) and transverse lie (0.3%; adjusted OR 2.33, 95% CI: 1.50-3.60), whereas a high ratio was linked to reduced breech presentation (1.1%; adjusted OR 0.51, 95% CI: 0.39-0.66). Subgroup analysis of children delivered by cesarean (n = 7971) showed a similar association, albeit with slightly reduced strength for breech presentation. Eighty-three percent of breech births and 46.3% of transverse lie births occurred at 37-38 weeks' gestation. Cesarean section was performed in 96.8% of breech presentations and 63.4% of transverse-lie ones. CONCLUSIONS: These findings imply that the fetal chest-to-head circumference ratio may influence presentation at birth.

[Development and Assessment of a New Oral Selenium Fast-disintegrating Tablets].

Selenium is an essential trace element and its deficiency causes myositis, myocardial damage, and other symptoms. Patients receiving long-term intravenous nutrition or tube-feeding in particular are deficient in essential trace elements, including selenium, and require regular supplementation. In Japan, injectable selenium-containing products are listed on the National Health Insurance drug price list, and oral solutions are prepared and used in hospitals. However, these formulations have problems related to preservation and require complicated administration procedures. In this study, we developed a new fast-disintegrating tablet formulation of selenium, using SmartEx® (D-mannitol·low substituted hydroxypropylcellulose (L-HPC)·fully hydrolyzed polyvinyl alcohol (PVA) mixture) as a coprocessing additive, that can be administered orally or by feeding tube. The tablet formulation had excellent disintegrable capability, sufficient hardness, and did not cause tube blockage when administered in the simple suspension method. In addition, the tablet formulation showed no changes in properties in an accelerated test without packaging for 42 d, indicating that it could be stored for a long period. Fast-disintegrating tablets prepared with SmartEx® are expected to improve the adherence and quality of life of patients who require selenium supplementation.

Association between eating habits during adolescence and gestational diabetes: data from the Japan environment and children's study.

Purpose: It is difficult to change pre-pregnancy eating habits, yet establishing healthy eating habits before pregnancy is important for preventing gestational diabetes mellitus (GDM). This study aimed to examine whether the weight-loss behavior of avoiding between-meal and midnight snacking in teenagers is associated with a reduction in the risk of subsequent GDM. Methods: We used a dataset (jecs-an-20,180,131) from a nationwide, prospective birth cohort study, the Japan Environment and Children's Study (JECS). We included 89,227 (85.7% of the total) mother-infant pairs with live births. Participants in their second or third trimester were asked to report their weight-loss behavior during their teenage years. The prevalence of GDM was investigated. Differences in maternal characteristics were examined using chi-square tests. Crude and adjusted logistic regression models were constructed to assess the associations of various maternal characteristics with the weight-loss behavior of avoiding between-meal and midnight snacking during teenage years. Results: A total of 2,066 (2.3%) participants had GDM. Weight-loss behavior in teenagers was associated with a decreased risk of GDM. Among participants with normal weight or overweight prior to pregnancy, the adjusted odds ratios were 0.79 (95% confidence interval, 0.70-0.89) and 0.82 (95% confidence interval, 0.69-0.98), respectively. Conclusions: The results suggest that teenage weight-loss behaviors, such as avoiding between-meal and midnight snacking, are associated with a decreased risk of developing GDM. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01294-2.

Association between maternal cholesterol level during pregnancy and placental weight and birthweight ratio: data from the Japan Environment and Children's Study.

BACKGROUND: Placental weight to birthweight ratio (PW/BW ratio), or its inverse, is used as an indicator of placental efficiency. Past studies have shown an association between an abnormal PW/BW ratio and adverse intrauterine environment, however, no previous studies have examined the effect of abnormal lipid levels during pregnancy on PW/BW ratio. We aimed to evaluate the association between maternal cholesterol levels during pregnancy and placental weight to birthweight ratio (PW/BW ratio). METHODS: This study was a secondary analysis using the data from the Japan Environment and Children's Study (JECS). 81 781 singletons and their mothers were included in the analysis. Maternal serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels during pregnancy were obtained from participants. Associations between maternal lipid levels and placental weight and PW/BW ratio were assessed by regression analysis using restricted cubic splines. RESULTS: Dose-response relationships were observed between maternal lipid level during pregnancy and placental weight and PW/BW ratio. High TC and LDL-C levels were associated with heavy placental weight and high PW/BW ratio, i.e., inappropriately heavy placenta for birthweight. Low HDL-C level was also associated with inappropriately heavy placenta. Low TC and LDL-C levels were associated with low placental weight and low PW/BW ratio, i.e., inappropriately light placenta for birthweight. High HDL-C was not associated with PW/BW ratio. These findings were independent of pre-pregnancy body mass index and gestational weight gain. CONCLUSIONS: Abnormal lipid levels such as elevated TC and LDL-C, and low HDL-C level, during pregnancy were associated with inappropriately heavy placental weight.

Comprehensive Analysis of the Expression and Functions of Pattern Recognition Receptors in Differentiated Cytotrophoblasts Derived from Term Human Placentas.

Pregnant women are exposed to various microbes, some of which can harm the mother and/or fetus and can lead to life-long morbidity and even death. The syncytiotrophoblast (STB) covers the placental villi and comes into direct contact with pathogens contained in the maternal blood and plays a key role in placental host defense. However, the precise mechanisms whereby the STB recognizes and responds to pathogenic microbes remain unclear. In this study, we comprehensively analyzed the expression of functional pattern recognition receptors, which are responsible for tissue defense against pathogens, in a primary STB model differentiated from highly purified human term cytotrophoblasts (CTBs). Screening for mRNA expression and multiplex cytokine/chemokine production demonstrated that differentiated CTBs (dCTBs) predominantly expressed dsRNA receptors, including TLR3, MDA5, and RIG-I. We confirmed that term human placentas also expressed TLR3. Transcriptome analysis revealed common and unique responses of dCTBs to a synthetic dsRNA (polyinosinic-polycytidylic acid) compared with human peripheral mononuclear cells. Moreover, polyinosinic-polycytidylic acid induced the release of type I and type III IFNs (IFN-ß, IFN-λ1, IFN-λ2, IFN-λ3), as well as mRNA expression of IFN-stimulated genes (IFIT1, MX1, and OAS1). dCTBs underwent apoptosis via the mitochondrial pathway in response to dsRNA stimulation. These results suggest that dsRNA receptors expressed on the STB are key players in antiviral defense in the placenta. Elucidation of the underpinnings of these defense processes can help us better understand the pathophysiology of viral infections during pregnancy.

Influence of chest/head circumference ratio at birth on obstetric and neonatal outcomes: The Japan environment and children's study.

OBJECTIVES: Some newborns that are not small-for-gestational-age (non-SGA, birthweight ≥10th percentile for a given gestational age) may have pathologic growth restrictions. This study examined the association of adverse obstetric and neonatal outcomes with chest/head circumference ratio at birth in non-SGA and SGA newborns. METHODS: This study was a cross-sectional evaluation of data from a nationwide prospective birth cohort study, the Japan Environment and Children's Study. We analyzed 93 690 non-anomalous singletons born at 34-41 gestational weeks. We defined low, normal, and high chest/head circumference ratio as <10th percentile, 10th-90th percentile, and >90th percentile, respectively, according to the internally constructed chest/head circumference percentile chart. Modified Poisson regression was used to estimate adjusted prevalence ratios (aPR) for the outcomes studied. RESULTS: Compared with non-SGA newborns with a normal ratio, those with a low ratio had an increased occurrence of low birthweight (1.75, 1.58-1.94 [aPR, 95% confidence interval]), cesarean delivery (1.34, 1.29-1.38), Apgar score <7 at 5 min (1.57, 1.14-2.17), respiratory complications (1.20, 1.04-1.39), and prolonged hospitalization (1.36, 1.30-1.42). In contrast, the high-ratio group had a lower rate of low birthweight (0.71, 0.59-0.86), cesarean delivery (0.82, 0.77-0.87), and prolonged hospitalization (0.83, 0.78-0.89). In SGA newborns, a low ratio was associated with increased aPRs for low birthweight, cesarean delivery, hypoglycemia, and prolonged hospitalization, whereas a high ratio showed no such association. CONCLUSIONS: Findings indicate that the chest/head circumference ratio at birth influence obstetric and neonatal outcomes regardless of the birthweight status.

Overlap of Thrombotic Microangiopathy and Mesangial Proliferative Glomerulonephritis Caused by Combination Therapy with Atezolizumab and Bevacizumab.

Vascular endothelial growth factor inhibitors and checkpoint inhibitors are effective treatments for solid tumors. These new classes of anti-cancer agents frequently cause kidney-related side effects. Although their anti-cancer effects may be enhanced when used in combination, the severity of their kidney-related side effects is unknown. We herein report the first case of thrombotic microangiopathy and mesangial proliferative glomerulonephritis caused by combined treatment with atezolizumab and bevacizumab in a 74-year-old man with hepatocellular carcinoma. The combination therapy was discontinued and replaced with intravenous methylprednisolone followed by oral prednisolone. Subsequently, the urinary protein excretion levels declined.

Epidemiology conduction of paediatric rheumatic diseases based on the registry database of the Pediatric Rheumatology Association of Japan.

OBJECTIVES: Although epidemiological surveys of paediatric rheumatic diseases in Japan have been conducted, they were single surveys with no continuity. This is the first report of the Pediatric Rheumatology Association of Japan registry database, which was established to continuously collect data for paediatric rheumatic diseases. METHODS: Pediatric Rheumatology International Collaborate Unit Registry version 2 (PRICUREv2) is a registry database established by the Pediatric Rheumatology Association of Japan. The registry data were analysed for the age of onset, time to diagnosis, sex differences, seasonality, and other factors. RESULTS: Our data showed the same trend regarding rates of paediatric rheumatic diseases reported in Japan and other countries. The age of onset was lower in juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis and higher in systemic lupus erythematosus and Sjögren's syndrome. The time to diagnosis was relatively short in JIA and systemic lupus erythematosus but longer in juvenile dermatomyositis and Sjögren's syndrome. Rheumatoid factor-positive polyarticular JIA showed a seasonality cluster with regard to onset. CONCLUSION: PRICUREv2 aided the retrieval and evaluation of current epidemiological information on patients with paediatric rheumatic diseases. It is expected that the data collection will be continued and will be useful for expanding research in Japan.

Safety and feasibility of autologous cord blood infusion for improving motor function in young children with cerebral palsy in Japan: A single-center study.

INTRODUCTION: Cerebral palsy (CP) is the most prevalent motor disorder of childhood. It typically results from in utero or perinatal brain injury. Recently, it has been reported that autologous cord blood (ACB) infusion for children with CP improved gross motor function and brain connectivity, but unfortunately, it has never been tried in Japan. We conducted a pilot study of the infusing of ACB, which was delivered from private bank, in the children with CP to assess the safety and feasibility to the procedure as well as any effect in improving neurological function. METHODS: After demonstrating the induction of tissue regeneration in animal model studies conducted a single-arm pilot study of intravenous ACB infusion in 6 young Japanese children with CP (ages 1-6 years). Primary outcomes were safety assessed by vital signs, clinical symptoms, and blood and urinary examinations at baseline and 1 weeks, 1, 2 and 3 years after treatment. In addition, motor function evaluations, neurodevelopmental examinations, magnetic resonance imaging, and electroencephalography (EEG) were performed at the same time. RESULTS: Infusion was generally well-tolerated, although one patient experienced microhematuria 1 year after treatment and another one patient experienced febrile convulsion once 9 months after treatment. These events were transient, no relapse was seen during observation study. All patients improved a median of 6.8 points on the 1-year Gross Motor Functional Measure-66 (GMFM-66) scores, greater than predicted by age and severity. Furthermore, the 2-year and 3-year GMFM-66 scores were also greater than expected (median 6.2 points and 5.5 points, respectively). Overall scales and language-social scales of the developmental quotient (DQ) improved in 3 of 6 patients, who had greater changes in their GMFM-66 scores than the other cases after treatment. There were no significant correlations among the GMFM-66 scores, DQ, and infusion cell counts. CONCLUSION: ACB infusion was safe and feasible for clinical use in patients with CP. However, much more clinical study with larger numbers of patients and in-depth studies of treatment mechanism of CP are needed.

Association between the ratio of placental weight to birthweight and the risk of neurodevelopmental delay in 3-year-Olds: The Japan environment and Children's study.

INTRODUCTION: The ratio of placental weight to birthweight (PW/BW ratio) is well known as a simple indicator of the prenatal intrauterine environment and placental functioning. We assessed the impact of PW/BW ratio on the risk of neurodevelopmental delay in 3-year-olds. METHODS: We used data of 71 205 mother-child pairs enrolled in the Japan Environment and Children's Study. Low PW/BW ratio was defined as a PW/BW ratio below the 10th percentile of the study population, high PW/BW ratio was defined as above the 90th percentile, and normal PW/BW ratio was defined as between the low and high PW/BW ratio. Neurodevelopment was assessed using the Japanese translation of the Ages and Stages Questionnaires, third edition. Associations between PW/BW ratio and risk of developmental delay were examined using multivariable models. RESULTS: Compared with boys in the normal PW/BW group, boys in the high PW/BW group had higher risk for developmental delays in all domains except fine motor skills (communication: adjusted risk ratio [aRR], 1.17; 95% confidence interval [CI], 1.04-1.33; gross motor skills: aRR, 1.28; 95% CI, 1.13-1.46; problem solving: aRR, 1.20; 95% CI, 1.09-1.31; personal-social: aRR, 1.26; 95% CI, 1.10-1.43), and boys in the low PW/BW group also had higher risk for developmental delays in some domains. For girls, there was almost no association between PW/BW ratio and developmental delay. DISCUSSION: An unbalanced PW/BW ratio, especially high PW/BW ratio, might indicate intrauterine suboptimality, which affects child neurodevelopment in a sex-specific manner.

Gestational weight gain mediates the effects of energy intake on birth weight among singleton pregnancies in the Japan Environment and Children's Study.

BACKGROUND: Extra energy intake is commonly recommended for pregnant women to support fetal growth. However, relevant data regarding variations in energy intake and expenditure, body mass index and gestational weight gain (GWG) are frequently not considered. This study aimed to investigate how energy intake during pregnancy and gestational weight gain (GWG) are associated with birth weight. METHODS: Early pregnant women were recruited into a Japanese nationwide prospective birth cohort study between 2011 and 2014. We analysed data of 89,817 mother-child pairs of live-born non-anomalous singletons after excluding births before 28 weeks or after 42 weeks. Energy intake during pregnancy was estimated from self-administered food frequency questionnaires (FFQ) and was stratified into low, medium, and high. Participants completed the FFQ in mid-pregnancy (mean 27.9 weeks) by recalling food consumption at the beginning of pregnancy. Effects of energy intake on birth weight and mediation by GWG were estimated using the Karlson-Holm-Breen method; the method separates the impact of confounding in the comparison of conditional and unconditional parameter estimates in nonlinear probability models. Relative risks and risk differences for abnormal birth size were calculated. RESULTS: Mean daily energy intake, GWG, and birth weight were 1682.1 (533.6) kcal, 10.3 (4.0) kg, and 3032.3 (401.4) g, respectively. 6767 and 9010 women had small-for-gestational-age and large-for-gestational-age infants, respectively. Relative to low energy intake, moderate and high intakes increased adjusted birth weights by 13 g and 24 g, respectively: 58 and 69% of these effects, respectively, were mediated by GWG. Compared with the moderate energy intake group, the low energy intake group had seven more women per 1000 women with a small-for-gestational-age birth, whereas the high energy intake group had eight more women per 1000 women with a large-for-gestational-age birth. CONCLUSION: GWG mediates the effect of energy intake on birth weight. All pregnant women should be given adequate nutritional guidance for optimal GWG and fetal growth.

Protease-digested egg-white products induce oral tolerance in mice but elicit little IgE production upon epicutaneous exposure.

BACKGROUND: Early food introduction induces tolerance, but epicutaneous exposure, especially via eczema lesions, promotes IgE sensitization. Aiming for safe and effective primary prevention of egg allergy, we examined several protease-digested egg-white (EW) products for three properties: 1) induction of oral tolerance that prevents IgE sensitization, 2) weak IgE binding that can prevent allergic reactions even in IgE-sensitized mice, and 3) minimal epicutaneous IgE sensitization even when in contact with inflamed skin. METHODS: Heated EW was digested with several proteases under optimal conditions. First, three-week-old BALB/c female mice were intragastrically administered EW or each protease-digested EW product, followed by intraperitoneal ovalbumin (OVA) or ovomucoid (OVM) injection with alum. Serum OVA- and OVM-specific IgE titers were measured. Second, six-week-old mice were sensitized with OVA/OVM, and the rectal temperature was measured after intraperitoneal administration of EW or each protease-digested EW. Third, EW or each protease-digested EW product was applied to the tape-stripped skin for 3 days/week for 3 weeks. Serum OVA- and OVM-specific IgE titers were measured. RESULTS: Orally administered pepsin-digested EW product (PDEW) and Thermoase PC10F-digested EW product (TDEW) significantly suppressed OVA-/OVM-specific IgE production. Neither product elicited a body temperature decline (anaphylaxis) in OVA-/OVM-sensitized mice. Serum OVA-/OVM-specific IgE levels were significantly lower in mice epicutaneously exposed to PDEW or TDEW than in EW-exposed mice. CONCLUSIONS: Two protease-digested EWs showed potential as optimal EW products for early introduction for primary prevention of egg allergy.

Exogenous oxytocin used to induce labor has no long-term adverse effect on maternal-infant bonding: Findings from the Japan Environment and Children's Study.

BACKGROUND: This study investigated the association between exogenous oxytocin use for labor induction and adverse maternal-infant bonding (MIB). METHODS: Data on 19 700 mother-infant pairs were collected, in which the infants were live-birth singletons, born in cephalic position and at >37 weeks of gestation; the drug used to induce labor was noted. Between 2011 and 2014, Japanese pregnant women were enrolled in a nationwide prospective birth cohort study, the Japan Environment and Children's Study. The Japanese version of the Mother-to-infant Bonding Scale (MIBS-J) was administered and demographic information was collected through medical record transcripts. MIBS-J scores were obtained at one month, six months, and one year after delivery. We estimated the risk of adverse MIB between use of oxytocin and other methods for labor induction using multiple linear regression analyses; interaction and mediation analyses to assess the relationship among MIBS-J scores also followed. RESULTS: Exogenous oxytocin was used during labor on 15 252 (77.4%) participants. After adjusting for confounders, there were no significant differences in adverse MIB between groups for which exogenous oxytocin was used and not used for labor induction. LIMITATION: The MIBS-J scores at one and six months were compiled using five instead of 10 questions. Moreover, detailed information was unavailable; for example, the questionnaire did not ask for the dosage and timing of the drugs used to induce labor. CONCLUSIONS: Exogenous oxytocin is a safe and vital drug to induce labor, and has been shown in this study to have no significant impact on long-term adverse MIB.

Early neurodevelopmental problems and risk for avoidant/restrictive food intake disorder (ARFID) in 4-7-year-old children: A Japanese birth cohort study.

Background: An overrepresentation of neurodevelopmental problems (NDPs) has been observed in individuals with avoidant/restrictive food intake disorder (ARFID). Previous studies on the association between ARFID and NDPs have been limited by cross-sectional data from clinical samples of small size. This study aimed to extend previous research by using prospectively collected data in a non-clinical child cohort. We examined the occurrence of early NDPs in 4-7-year-old children with suspected ARFID and how predictive early NDPs are of ARFID. Methods: Data were collected via parent-report a sub-sample of the Japan Environment and Children's Study (JECS) including 3728 children born 2011-2014 in Kochi prefecture. NDPs were assessed biannually between 0.5 and 3 years of age with the Ages and Stages Questionnaire-3, at age 2.5 years with the ESSENCE-Q, and at age 1 and 3 years via parent-reported clinical diagnoses. ARFID was identified cross-sectionally (at age 4-7 years) using a newly developed screening tool. Logistic regressions were used to test association of (1) a composite early NDP risk score, (2) specific early NDPs, and (3) neurodevelopmental trajectories over time with ARFID. Results: Children in the highest risk percentiles of the NDP risk score had roughly three times higher odds of having suspected ARFID; the absolute risk of later ARFID for children above the 90th percentile was 3.1%. Early NDPs (excluding early feeding problems) were more predictive of later ARFID than were early feeding problems. Specific NDPs predictive of ARFID were problems with general development, communication/language, attention/concentration, social interaction, and sleep. Neurodevelopmental trajectories of children with and without suspected ARFID started to divert after age 1 year. Conclusions: The results mirror the previously observed overrepresentation of NDPs in ARFID populations. In this non-clinical child cohort, early feeding problems were common and rarely developed into ARFID; however, our findings imply that they should be monitored closely in children with high NDP risk to prevent ARFID.

Association between nausea and vomiting of pregnancy and postpartum depression: the Japan Environment and Children's Study.

OBJECTIVE: Postpartum depression (PPD) is a global emotional distress that affects women and their offspring regardless of their culture. The association between nausea and vomiting of pregnancy (NVP) and PPD has been widely described only for the severe form of NVP. We aimed to assess the relationship between PPD and NVP with regards to its severity. METHODS: Data from the Japan Environment and Children's Study (JECS), a birth cohort study, were analyzed. PPD was assessed using the Edinburgh Postnatal Depression Scale (EPDS). Multiple logistic regression models were performed to assess the association between NVP and PPD. RESULTS: Out of the 80,396 women included in the study 14% had PPD. Among them 4,640 (42.1%) had mild NVP; 3,295 (29.9%) had moderate NVP whereas 1,481 (13.4%) had severe NVP. All forms of NVP were associated with PPD and the association gradually increased with the severity of NVP symptoms with odd ratio (OR): 1.26; 95% confidence interval (CI): 1.18-1.35 for mild, OR: 1.28; 95% CI: 1.19-1.38 for moderate and OR: 1.54; 95% CI: 1.42-1.68 for severe NVP. CONCLUSION: Japanese women with NVP were more susceptible to develop PPD and the more severe the NVP symptoms were, the greater the risk of PPD. Thus, close monitoring of NVP-affected women is recommended.

Development of a parent-reported screening tool for avoidant/restrictive food intake disorder (ARFID): Initial validation and prevalence in 4-7-year-old Japanese children.

The prevalence of avoidant/restrictive food intake disorder (ARFID) in the general child population is still largely unknown and validated screening instruments are lacking. The aims of this study were (1) to investigate the prevalence of children screening positive for ARFID in a Japanese birth cohort using a newly developed parent-reported screening tool, (2) to estimate the prevalence of children with ARFID experiencing physical versus psychosocial consequences of their eating pattern, and (3) to provide preliminary evidence for the validity of the new screening tool. Data were collected from 3728 4-7-year-old children born between 2011 and 2014 in Kochi prefecture, Japan (response rate was 56.5%); a sub-sample of the Japan Environment and Children's Study (JECS). Parents completed a questionnaire including the ARFID screener and several other measures to assess convergent validity. The point prevalence of children screening positive for ARFID was 1.3%; half of them met criteria for ARFID based on psychosocial impairment alone, while the other half met diagnostic criteria relating to physical impairment (and additional psychosocial impairment in many cases). Sensory sensitivity to food characteristics (63%) and/or lack of interest in eating (51%) were the most prevalent drivers of food avoidance. Children screening positive for ARFID were lighter in weight and shorter in height, they showed more problem behaviors related to mealtimes and nutritional intake, and they were more often selective eaters and more responsive to satiety, which together provides preliminary support for the validity of the new screening tool. This is the largest screening study to date of ARFID in children up to 7 years. Future studies should examine the diagnostic validity of the new ARFID screener using clinically ascertained cases. Further research on ARFID prevalence in the general population is needed.

Breastfeeding and risk of febrile seizures in the first 3 years of life: The Japan Environment and Children's Study.

OBJECTIVE: Our study was conducted to examine the association between breastfeeding and febrile seizures (FS) in the first 3 years of life. METHODS: We analyzed the dataset of the Japan Environment and Children's Study (JECS), which is a birth cohort study undertaken to elucidate the influence of environmental factors on children's health during the fetal period and early childhood. Information on feeding duration and feeding pattern, as well as information on febrile seizures, were obtained from questionnaires sent to mothers/caregivers. We categorized a child as having experienced FS if the child was reported as having been diagnosed with FS in the first 3 years. Modified Poisson regression with a robust error variance was used to estimate the effect of duration of breastfeeding and the risk of FS. RESULTS: Of the 84,321 children included in the analysis, 6264 (7.4%) were reported to have experienced FS at least once in the first 3 years of life. Multivariate analyses showed that the risk of FS during the first 3 years of life tended to decrease as the duration of breastfeeding increased. Male sex and frequent fever episodes were also associated with an increased risk of FS. CONCLUSIONS: Continued breastfeeding until 2 years of age, the most susceptible age for FS, had a small but protective effect on FS.

Dose-response relationships between maternal urinary cotinine and placental weight and ratio of placental weight to birth weight: The Japan Environment and Children's Study.

INTRODUCTION: Studies on the relationship between maternal self-reported smoking status and placental weight report inconsistent results. This study examined the relationships between maternal urinary cotinine concentration and placental weight and the ratio of placental weight to birth weight (PW/BW ratio). The study also examined the relationship between maternal smoking status, as determined by cotinine concentration, with placental weight and with PW/BW ratio, stratified by sex of offspring. METHODS: Our analysis used information of 91,049 mother-child pairs enrolled in the Japan Environment and Children's Study. Maternal urinary cotinine concentration was quantified (during the second or third trimester) with high-performance liquid chromatography-tandem mass spectrometry. Using restricted cubic splines, placental weight and PW/BW ratio were plotted against natural log-transformed cotinine concentration. Taking cotinine levels of <0.17 ng/mL, 0.17 to <21.5 ng/mL (natural log-transformed values, -1.77 to 3.07), and ≥21.5 ng/mL as indicative of non-smokers, passive smokers, and active smokers, respectively, the relationships between maternal smoking status and placental weight and PW/BW ratio were examined, adjusting for confounders. RESULTS: Placental weight and PW/BW ratio increased with increasing cotinine concentration. After cotinine reached a certain concentration, the placental weight decreased in male offspring whereas it plateaued in female offspring. Compared with not smoking, active smoking during pregnancy significantly increased placental weight and PW/BW ratio. CONCLUSION: Placental weight responded as an inverted U-shape whereas the PW/BW ratio followed a J-shape with increasing maternal urinary cotinine concentration measured during pregnancy, suggesting exposure to tobacco smoke induces a disproportionate reduction in fetal growth. The effect of tobacco smoke on placental growth varied by sex of offspring.

Cancer After Pediatric Kidney Transplantation: A Long-term Single-center Experience in Japan.

BACKGROUND: The cancer incidence, types, and risk factors after pediatric kidney transplantation (KT) have been reported in the United States, Canada, Europe, Australia, and New Zealand. However, no information is available about cancer in pediatric KT recipients in Asian countries. METHODS: Children aged <20 y who underwent initial KT from 1983 to 2016 were analyzed. We compared the cancer incidence with that in the general Japanese population using standardized incidence ratio and examined posttransplant cancer risk using Cox proportional hazards models. RESULTS: A total of 356 children (median age, 11.7 y; interquartile range, 5.0-17.6) received KT with a follow-up period of 4466 person-years. The median age of cancer onset was 18.5 y (interquartile range, 8.0-32.3), and 13 cancers occurred in 12 patients (3.4%). Two patients died from cancer. The most common cancers were posttransplant lymphoproliferative disorders (PTLDs) (38.5%). The median time to PTLD and non-PTLD diagnosis after KT was 0.6 and 16.4 y, respectively. There was no occurrence of skin cancer. The posttransplant cancer incidence was 9.9 times higher than that in the general age-matched population (standardized incidence ratio = 9.9; 95% confidence interval, 4.80-18.39). The cumulative cancer incidence was 5.3% in 20 y after KT, which is lower than that reported in previous studies. We could not identify any risk factors for all cancer after KT in all patients, whereas subgroup analysis in 264 patients with available data of recipient Epstein-Barr virus serological status showed that recipient Epstein-Barr virus-negative serology was an independent risk factor for cancer development. CONCLUSIONS: The incidence of cancer is higher in Japanese pediatric KT recipients than in the general population. The cumulative incidence of cancer after KT was lower in our population than that previously reported. This may be because there was no skin cancer observed in the Japanese pediatric KT recipients in our study.