Sex steroid hormones and allergic diseases in children: a pilot birth cohort study in the Japan Environment and Children's Study cohort.

BACKGROUND: Numerous studies suggest that sex steroids might play a role in sex disparity observed in allergic diseases in adults. However, whether sex hormones influence allergic diseases in children remains unclear. The aim of the present study was to examine the association of sex steroid hormones with allergic disease in Japanese children. METHODS: The present cross-sectional study included 145 6-year-old children participating in a pilot birth cohort study in the Japan Environment and Children's Study. Data on allergic diseases were obtained from questionnaires, and serum levels of sex steroid hormones and allergen-specific IgE were measured. Logistic regression was performed to evaluate the association of sex hormones with allergic diseases. RESULTS: After adjusted sex, amount of body fat at 6 years, parental history of allergic disease, and exposure to tobacco smoke, serum dehydroepiandrosterone sulfate level was significantly associated with reduced odds of any allergic disease (adjusted odds ratio, 0.58; 95% confidence interval, 0.36-0.93; P = 0.024) and serum follicle-stimulating hormone level was significantly associated with increased odds of any allergic disease (adjusted odds ratio, 2.04; 95% confidence interval, 1.01-4.11, P = 0.046). Dehydroepiandrosterone sulfate level showed a significant association with number of allergic diseases. CONCLUSIONS: The current study findings suggest that sex hormones may play an important role in the development of allergic diseases in prepubertal children.

Relationship between the Mediterranean Diet Score in Pregnancy and the Incidence of Asthma at 4 Years of Age: The Japan Environment and Children's Study.

Several scoring methods for the Mediterranean diet, which is considered as a healthy diet, are available, but studies that have compared more than one of these scores are rare. In addition, the applicability of Mediterranean diet scoring has not been sufficiently examined outside of Mediterranean regions. We collected data on the Mediterranean diet during pregnancy and the incidence of type 1 allergies in offspring from the Japan Environment and Children's Study. Using multiple Mediterranean diet scoring methods, we analyzed the effect of adherence to the Mediterranean diet in pregnancy on the allergies of the offspring. Overall, 46,532 pairs of mothers and children were analyzed. In Japan, a high adherence to the Mediterranean diet during pregnancy was associated with a lower incidence of asthma in the offspring (odds ratio: 0.896, 95% confidence interval: 0.835, 0.962). Furthermore, we found that the selection of the Mediterranean diet scoring method and the setting of the reference value significantly altered the results. Our findings suggest that an appropriate selection of scoring methods and a reference value for food items are important to analyze the effects of adherence to the Mediterranean diet inside and outside of Mediterranean regions.

Change over time in internal cerebral vein pulsation in premature infants at risk of intraventricular hemorrhage.

BACKGROUND: Prolonged continuation of augmented internal cerebral vein (ICV) pulsation may be related to the development of premature intraventricular hemorrhage (IVH). However, the characteristics of ICV flow patterns in premature infants are unclear. AIM: To investigate the changes over time in ICV pulsation in premature infants at risk of IVH. STUDY DESIGN: A 5-year retrospective observational study of a single-center trial. SUBJECTS: In total, 112 very-low-birth-weight infants with gestational age of ≤32 weeks. OUTCOME MEASURES: ICV flow was measured every 12 h until 96 h after birth and thereafter on days 7, 14, and 28. The ICV pulsation index (ICVPI), which is a ratio of the minimum/maximum speed of ICV flow, was calculated. We recorded longitudinal ICVPI change and compared ICVPI among three groups classified according to gestational age. RESULTS: ICVPI started declining after day 1 and reached the minimum median value in 49-60 h after birth (1.0 during 0-36 h, 0.9 during 37-72 h, and 1.0 after 73-84 h). ICVPI was significantly lower during 25-96 h than during 0-24 h and on days 7, 14, and 28. ICVPI in the 23-25-week group was significantly lower between 13-24 h and day 14 than that in the 29-32-week group, and the same was observed for the 26-28-week group between 13-24 h and 49-60 h. CONCLUSIONS: ICV pulsation was affected by time after birth and gestational age, and this ICVPI fluctuation may reflect a postnatal circulatory adaptation.

Coronary Vasospasm in a Patient With Argininosuccinic Aciduria.

A 39-year-old male was referred for treatment of hypertension. He had been treated for argininosuccinic aciduria since 8 months of age. Therapeutic drugs, including l-arginine, sodium phenylbutyrate, and antiepileptic drugs, had been prescribed. A detailed medical history revealed that he complained of chest discomfort under psychologic stress. A 12-lead electrocardiogram showed abnormal q waves in lead III and aVF. Transthoracic echocardiography showed hypokinesia of the left ventricular posterior wall. The patient was diagnosed with myocardial infarction because of coronary vasospastic angina by intracoronary acetylcholine provocation test. Argininosuccinic aciduria is a genetic disorder of the urea cycle caused by a deficiency of argininosuccinate lyase. Reduction of the enzymatic activity leads to a decrease in nitric oxide production, even if arginine is supplemented. Our case report supports the significance of endothelial function in the pathogenesis of coronary vasospasm.

Elective Cesarean Section during Preterm Prevents Pulmonary Hypoplasia Development in Potter Sequence.

Potter syndrome, first reported in 1946 by Edith Potter, refers to fatal cases of bilateral renal aplasia with pulmonary hypoplasia, peculiar facial features, and limb deformities. Presently, patients with oligohydramnios showing similar pathological manifestations due to oligohydramnios caused by conditions other than bilateral renal aplasia have been reported, and are known as the Potter sequence. There are limited studies and unclear guidelines on the safest delivery time and detailed postpartum management for patients with the Potter sequence. We experienced a case of Potter sequence, in which the patient was born by elective cesarean section at gestational age (GA) of 34 weeks. Fetal ultrasound at GA of 26 weeks 4 days showed oligohydramnios, multilocular cystic lesions in the left kidney, and an absent right kidney. Prenatal fetal MRI at GA of 33 weeks and 3 days showed pulmonary hypoplasia, and the ratio of fetal lung volume (FLV) to fetal body weight (FBW) was 0.0135 ml/g. We suspected that the fetal lung could not grow because of persistent oligohydramnios, which leads to a further decline in the ratio of FLV to FBW during pregnancy. We performed a cesarean section at GA of 34 weeks to prevent the exacerbation of the imbalance between lung volume and physique. We struggled to keep her condition stabilized with strict management of her respiratory condition, dialysis, and nutrition. She was discharged from the hospital at 169 days of age. Elective caesarean section in the term of premature birth prevented the progression of pulmonary hypoplasia and made it possible to save her life. Potter sequence is still relatively unknown, and it is necessary for more studies to be conducted in the future.

Impaired Height Growth Associated with Vitamin D Deficiency in Young Children from the Japan Environment and Children's Study.

Vitamin D is essential for calcium absorption and bone homeostasis. Although short-stature children were reported to have low vitamin D concentrations, there is no clear evidence of a link between vitamin D and height growth in young children not limited to those with short stature. We collected height and weight data at 2 and 4 years of age, serum vitamin D concentrations at 4 years, and questionnaire results on sun exposure from the Japan Environment and Children's Study (JECS). We then analyzed the relationship between vitamin D deficiency and height growth. We also analyzed the correlation between serum vitamin D concentration and sun exposure. Overall, 3624 participants from JECS were analyzed. We identified cases of subclinical vitamin D deficiency and insufficiency. We further found that definitive vitamin D deficiency (<10 ng/mL) impaired height growth by 0.6 cm per year even in young children not limited to those with short stature. Furthermore, we clarified that children with vitamin D deficiency had reduced outdoor activity, especially during winter. In children with either short or normal stature, definitive vitamin D deficiency was associated with height growth decline, and reduction in outdoor activity, especially during winter, was a risk factor for vitamin D deficiency.

Changes in Internal Cerebral Vein Pulsation and Intraventricular Hemorrhage in Extremely Preterm Infants.

OBJECTIVES: This study aimed to investigate the relationship between internal cerebral vein (ICV) pulsation and intraventricular hemorrhage (IVH) and to identify the cut-off values that predict IVH. We hypothesized that the severity of ICV flow pulsations was related to IVH severity. STUDY DESIGN: In this prospective observational study, ICV flow was measured in 61 extremely preterm infants using ultrasonography at every 12 hours until 96 hours after birth and on days 7, 14, and 28. The ICV pulsation index (ICVPI = minimum/maximum ICV speed) was calculated and compared among the groups determined by Papile's IVH classification. The ICVPI cut-off values for IVH were determined by receiver operating characteristic curve analysis. RESULTS: Compared with those in the no IVH (NIVH) group (n = 51), the ICVPI median values in the severe IVH (SIVH; grades 3 and 4) group (n = 5) were lower at 25 to 96 hours and on day 7, whereas those in the mild IVH (MIVH; grades 1 and 2) group (n = 5) were lower at 37 to 60 hours. All SIVH events were initially detected within 60 hours after birth. The ICVPI cut-off values for SIVH were 0.92 at 13 to 24 hours, 0.42 at 25 to 36 hours, 0.58 at 37 to 48 hours, and 0.55 at 49 to 60 hours. Infants whose ICVPI values were below the cut-off value ≥3 times between 13 and 60 hours had a significantly higher SIVH incidence than those whose ICVPI values were below the cut-off value ≤2 times (57.1 vs. 1.9%, p < 0.001). CONCLUSION: Our results indicate that SIVH had sustained pronounced internal cerebral vein pulsations and that the ICVPI values may help predict SIVH. Further research on strategies to decrease venous pressure for IVH prevention is needed. KEY POINTS: · IVH preterm infants had sustained ICV pulsations.. · ICV flow in SIVH pulsated stronger.. · ICVPI fluctuation implies postnatal adaptation.. · We newly defined ICVPI to predict SIVH..

Fluctuations of aeroallergen-specific immunoglobulins and children's allergic profiles: Japan Environment & Children's Study of a pilot cohort.

BACKGROUND: Allergen-specific immunoglobulins have a crucial role in allergic diseases. Most wheeze episodes develop before school age, and allergic rhinitis later develops during early elementary school years. However, the clinical background and cytokine/chemokine profiles associated with changes in immunoglobulins during early school-age are poorly understood. METHODS: This study used blood samples from children participating in the JECS Pilot Study. We examined nineteen kinds of aeroallergen-specific immunoglobulins (IgE, IgG1, IgG4, and IgA) levels in patients at age 6 and age 8. Fluctuations of Der f 1- and Cry j 1-specific immunoglobulins levels during the two periods were compared to assess the frequency of allergic statuses and clusters of cytokine/chemokine profiles. RESULTS: The medians of aeroallergen-specific IgE levels did not fluctuate, and almost all IgG1 and IgG4 decreased. In IgA, four (e.g., Der f 1) increased, whereas the other four (e.g., Cry j 1) decreased. The ratio of the Der f 1-specific IgG1 level at age 8 to that at age 6 was higher in children with poor asthma control than in children with better asthma control. Moreover, the cytokine/chemokine cluster with relatively lower IL-33 and higher CXCL7/NAP2 was associated with lower Der f 1- and Cry j 1-specific IgG4 levels, but not IgE levels. CONCLUSIONS: The cluster of cytokine/chemokine profiles characterized by lower IL-33 and higher CXCL7/NAP2 was associated with the maintenance of aeroallergen-specific IgG4 levels. This result provides a basis for considering the control of aeroallergen-specific immunoglobulins.

Procalcitonin is associated with postnatal respiratory condition severity in preterm neonate.

INTRODUCTION: Postnatal respiratory failure is common in preterm neonates and is difficult to distinguish from early-onset neonatal bacterial infection by clinical symptoms. Similar to C-reactive protein (CRP), procalcitonin (PCT) is used as a marker of bacterial infection. Recently, it has been reported that the serum PCT levels increase because of respiratory failure immediately after birth. However, there is insufficient information concerning the relationship between biological inflammation markers, such as PCT and CRP, and postnatal respiratory condition severity. METHODS: Preterm neonates were classified according to the received respiratory management as follows: nonrespiratory support (NRS), respiratory support (RS), surfactant administration therapy (STA), and STA with nitric oxide inhalation therapy (NO). The median serum PCT and CRP levels at 12-36 h postnatally were compared among the four groups. Additionally, the median serum PCT and CRP levels in the STA group were compared by STA timing and STA number. RESULTS: The PCT levels for the NRS, RS, STA, and NO groups were 1.04, 6.46, 12.93, and 86.79 µg/L, respectively; the CRP levels were 0.40, 0.80, 1.10, and 16.40 mg/L, respectively. The PCT levels were significantly lower among neonates receiving STA in the birth subgroup (4.82 µg/L) than among those receiving STA in the admission subgroup (14.71 µg/L). The PCT levels were significantly higher among the STA multiple-dose subgroup (24.87 µg/L) than among the STA single-dose subgroup (12.47 µg/L). No significant differences in the CRP levels were observed. CONCLUSION: The serum PCT levels in preterm neonates were associated with postnatal respiratory condition severity.

Female-dominant estrogen production in healthy children before adrenarche.

OBJECTIVE: Ultra-sensitive hormone assays have detected slight sex differences in blood estradiol (E2) levels in young children before adrenarche. However, the origin of circulating E2 in these individuals remains unknown. This study aimed to clarify how E2 is produced in young girls before adrenarche. DESIGN: This is a satellite project of the Japan Environment and Children's Study organized by the National Institute for Environmental Studies. METHODS: We collected blood samples from healthy 6-year-old Japanese children (79 boys and 71 girls). Hormone measurements and data analysis were performed in the National Institute for Environmental Studies and the Medical Support Center of the Japan Environment and Children's Study, respectively. RESULTS: E2 and follicle stimulating hormone (FSH) levels were significantly higher in girls than in boys, while dehydroepiandrosterone sulfate (DHEA-S) and testosterone levels were comparable between the two groups. Girls showed significantly higher E2/testosterone ratios than boys. In children of both sexes, a correlation was observed between E2 and testosterone levels and between testosterone and DHEA-S levels. Moreover, E2 levels were correlated with FSH levels only in girls. CONCLUSIONS: The results indicate that in 6-year-old girls, circulating E2 is produced primarily in the ovary from adrenal steroids through FSH-induced aromatase upregulation. This study provides evidence that female-dominant E2 production starts several months or years before adrenarche. The biological significance of E2 biosynthesis in these young children needs to be clarified in future studies.

Measles antibody seropositivity among children with allergic diseases: A cross-sectional study in the Japan Environment & Children's Pilot Study.

BACKGROUND: The relationship between allergic individuals and their responsiveness to routine vaccines has rarely been investigated. This study examined whether the seroprevalence of measles antibody differed between children with and without allergic diseases in the general pediatric population. METHODS: The cross-sectional study was performed within a prospective general birth cohort (a pilot study of the Japan Environment & Children's Pilot Study [JECS]) of children aged 8 years. The clinical history of allergic diseases, measles, and the concentration of measles immunoglobulin G titers in serum enzyme immunoassay were examined. Fisher's exact tests were used to assess the relationships between the allergic characteristics of the children and their measles antibody positivity rates. RESULTS: This study included 162 children. Any allergic disease was reported in 75 (46.3%). The measles antibody positivity rate was 94.7% among children with any allergic diseases and 92.0% among children without allergic diseases. Our results revealed no differences in measles antibody seropositivity between children with allergies and controls. CONCLUSIONS: Children with allergies mount and maintain a comparable immune response to the measles vaccine.

Comparison of Simultaneous Quantitative Analysis of Methylmercury and Inorganic Mercury in Cord Blood Using LC-ICP-MS and LC-CVAFS: The Pilot Study of the Japan Environment and Children's Study.

Prenatal exposure to methylmercury (MeHg) affects child development after birth. However, many epidemiological studies have evaluated total mercury levels without analyzing speciation. Biomonitoring of MeHg and inorganic mercury (IHg) is essential to reveal each exposure level. In this study, we compared a high-throughput analysis for mercury speciation in blood using liquid chromatography-inductively coupled plasma-mass spectrometry (LC-ICP-MS) and liquid chromatography-cold vapor atomic fluorescence spectrometry (LC-CVAFS). The validated LC-ICP-MS method was applied to 101 maternal blood and 366 cord blood samples in the pilot study of the Japan Environment and Children's Study (JECS). The accuracy of the LC-CVAFS method ranged 90-115% determined by reference material analysis. To evaluate the reliability of 366 cord blood samples, fifty cord blood samples were randomly selected and analyzed using LC-CVAFS. The median (5th-95th percentile) concentrations of MeHg and IHg were 5.4 (1.9-15) and 0.33 (0.12-0.86) ng/mL, respectively, in maternal blood, and 6.3 (2.5-15) and 0.21 (0.08-0.49) ng/mL, respectively, in cord blood. Inter-laboratory comparison showed a relatively good agreement between LC-ICP-MS and LC-CVAFS. The median cord blood:maternal blood ratios of MeHg and IHg were 1.3 and 0.5, respectively. By analyzing speciation, we could focus on the health effects of each chemical form.

A missense variant in NUF2, a component of the kinetochore NDC80 complex, causes impaired chromosome segregation and aneuploidy associated with microcephaly and short stature.

Mutations in proteins involved in cell division and chromosome segregation, such as microtubule-regulating, centrosomal and kinetochore proteins, are associated with microcephaly and/or short stature. In particular, the kinetochore plays an essential role in mitosis and cell division by mediating connections between chromosomal DNA and spindle microtubules. To date, only a few genes encoding proteins of the kinetochore complex have been identified as causes of syndromes that include microcephaly. We report a male patient with a rare de novo missense variant in NUF2, after trio whole-exome sequencing analysis. The patient presented with microcephaly and short stature, with additional features, such as bilateral vocal cord paralysis, micrognathia and atrial septal defect. NUF2 encodes a subunit of the NDC80 complex in the outer kinetochore, important for correct microtubule binding and spindle assembly checkpoint. The mutated residue is buried at the calponin homology (CH) domain at the N-terminus of NUF2, which interacts with the N-terminus of NDC80. The variant caused the loss of hydrophobic interactions in the core of the CH domain of NUF2, thereby impairing the stability of NDC80-NUF2. Analysis using a patient-derived lymphoblastoid cell line revealed markedly reduced protein levels of both NUF2 and NDC80, aneuploidy, increased micronuclei formation and spindle abnormality. Our findings suggest that NUF2 may be the first member of the NDC80 complex to be associated with a human disorder.

SGLT2 inhibition alleviated hyperglycemia, glucose intolerance, and dumping syndrome-like symptoms in a patient with glycogen storage disease type Ia: a case report.

BACKGROUND: Glycogen storage disease (GSD) type Ia is a glycogenesis disorder with long-term complications such as hepatomegaly and renal dysfunction and is caused by congenital loss of glucose-6-phosphatase (G6Pase) expression. G6Pase is essential for the final step of gluconeogenesis and glycogenolysis, and its deficiency causes clinical hypoglycemia in the fasting state during infancy. Contrastingly, patients also show blood glucose trends and glucose intolerance similar to those in type II diabetes. Owing to the contrasting presentation of hypoglycemia with glucose intolerance, glucose control in patients remains a challenge, requiring management of both fasting hypoglycemia and post-prandial hyperglycemia. CASE PRESENTATION: The patient was a 45-year old Asian (Japanese) woman who showed disease onset at 3 years of age, when hypoglycemia and hepatomegaly were observed, and GDS type Ia was diagnosed by the lack of G6Pase activity. Over the past 45 years, she presented hyperglycemia and dumping syndrome like symptoms (a feeling of fullness, even after eating just a small amount, abdominal cramping, nausea, sweating, flushing, or light-headedness and rapid heartbeat) at 2 hours after food intake. Her liver and kidney dysfunction also worsened over time. Treatment with exercise combined with a sodium-glucose co-transporter 2 inhibitor and an alpha glucosidase inhibitor alleviated her glucose intolerance and dumping syndrome-like symptoms, without increasing hypoglycemic events. CONCLUSION: This case suggests SGLT2 inhibitor as a promising candidate for treating glucose intolerance in GSD type Ia without worsening of hypoglycemia.

The Predictive Value of Procalcitonin and High-Sensitivity C-Reactive Protein for Early Bacterial Infections in Preterm Neonates.

INTRODUCTION: Evidence on the reliability of using procalcitonin (PCT) and high-sensitivity C-reactive protein (hs-CRP) as diagnostic markers for early-onset neonatal bacterial infections is still insufficient because of their physiological elevation during the early neonatal period. This study aimed to assess the respiratory influence of serum PCT and hs-CRP levels and evaluate their predictive value for bacterial infections during the first 72 h of life in preterm neonates. METHODS: The preterm neonates enrolled in this single-center retrospective cohort study were categorized into 3 groups: reference, infection-unlikely respiratory failure, and probable bacterial infection; their serum PCT and hs-CRP levels were assessed. Subsequently, age-specific 95th percentile curves were plotted and the median and cutoff PCT and hs-CRP levels for predicting bacterial infections at birth and 7-18, 19-36, and 37-72 h after birth were determined. Moreover, the analysis of PCT and hs-CRP with a neonatal sequential organ failure assessment (nSOFA) score was performed in very low birth weight neonates. RESULTS: Serum PCT levels were influenced by respiratory failure. A significant difference was found in the median PCT and hs-CRP levels among the 3 groups at each time point. PCT sensitivities for predicting bacterial infection were slightly higher than those of hs-CRP in each time frame during the first 72 h of life. In both PCT and hs-CRP, there was no significant difference between infants with nSOFA scores of >4 and those with nSOFA scores of ≤4. DISCUSSION/CONCLUSION: Age-specific evaluation showed that PCT has better predictive value than hs-CRP for early-onset bacterial infections in preterm neonates.

Reversal of blood flow in deep cerebral vein in preterm intraventricular hemorrhage: two case reports.

BACKGROUND: Intraventricular hemorrhage during the early stage is a major complication in very low birth weight infants. Elevation of venous pressure is one of the contributing factors. The internal cerebral vein receives most of the venous flow from the subependymal germinal matrix, the most common site of origin of intraventricular hemorrhage. Recently, it has been reported that pulsatile or partially interrupted internal cerebral vein waveforms might also be risk factors for intraventricular hemorrhage in extremely low birth weight infants. Here, we report two cases of partially reversed internal cerebral vein flow with intraventricular hemorrhage. There are no published reports documenting this unique flow pattern. CASE PRESENTATION: Between 2013 and 2020, we had in our neonatal intensive care unit two cases of very low birth weight infants (27 and 25 weeks of gestational age) who showed a partially reversed internal cerebral vein waveform pattern, which was recognized as a new blood flow pattern. Their internal cerebral vein flow patterns were continuously flat early after birth. They showed an intraventricular hemorrhage on the unilateral side with partially interrupted internal cerebral vein flow at 31 and 41 hours after birth (27- and 25-week-old neonates, respectively). Consecutively, their internal cerebral vein flow changed to a partially reversed pattern with intraventricular hemorrhage on the contralateral side at 43 and 87 hours after birth (27- and 25-week-old neonates, respectively). Their flow patterns improved by day 7. These partially reversed patterns were equivalent to triphasic venous flow, and the reverse flow corresponded to A- and V-waves. CONCLUSION: In the two cases, the internal cerebral vein flow patterns were normal and flat before intraventricular hemorrhage and changed to a severe flow pattern (partially interrupted or reversed flow) at the same time as the detection of intraventricular hemorrhage. After the development of intraventricular hemorrhage, they improved. These cases indicate that a partially reversed or interrupted internal cerebral vein flow pattern may be derived from central venous pressure elevation and related to intraventricular hemorrhage in very low birth weight infants, however, it is difficult to determine when this flow pattern occurs in relation to intraventricular hemorrhage.

Associations of dog and cat ownership with wheezing and asthma in children: Pilot study of the Japan Environment and children's study.

OBJECTIVES: No previous study has used repeated measures data to examine the associations of dog/cat ownership with wheezing and asthma prevalence among children. This prospective study used repeated measurers analysis to determine whether dog/cat ownership in childhood is an independent risk factor for wheezing and asthma, after adjustment for gestational, socio-economical, and demographical confounders confounders, in Japan. METHODS: We conducted a multicenter pilot study of the Japan Environment and Children's Study (JECS) during 2009-2010. Among 440 newborn infants enrolled, 410 (52.8% males) were evaluated for dog/cat ownership in the home and history of wheezing and asthma in five follow-up questionnaire surveys (until age 6 years). Dog/cat ownership during follow-up period was categorized into four groups: 7.6% were long-term dog/cat owners, 5.9% were toddler-age owners, 5.9% were preschool-age owners, and 80.7% were never owners. RESULTS: The prevalence of wheezing during follow-up period increased from 20.8% to 35.4% and the prevalence of asthma increased from 1.3% to 16.3%. A fitted logistic generalized estimating equation models including important confounders showed no significant associations of the interaction between dog and/or cat ownership and follow-up time with the risks of wheezing and asthma. However, the risks of wheezing and asthma were slightly lower for long-term and toddler-age dog/cat owners than for preschool-age and never owners. CONCLUSIONS: The present findings suggest that dog and cat ownership from toddler-age does not increase the risks of wheezing and asthma compared with never owners among Japanese children.

New reference ranges of procalcitonin excluding respiratory failure in neonates.

BACKGROUND: Existing reference data on serum procalcitonin (PCT) in neonates include the effects of respiratory disorders commonly occurring during birth. We aimed to determine new 95% reference intervals in neonates after excluding the influence of respiratory failure at birth, and to investigate the effects of gestational age (GA) and respiratory condition at birth on postnatal transient serum PCT elevation. METHODS: Samples were obtained from term and preterm neonates during the first 3 days of life. Neonates were classified into reference, respiratory failure, and bacterial infection groups. In the reference group, the correlation between PCT level and GA was investigated. RESULTS: The median PCT level within the 95% range 12-36 h after birth was 1.05 ng/mL (0.14-4.39) in term neonates (143 samples) and 1.01 ng/mL (0.15-4.44) in preterm neonates (95 samples). There was no correlation between GA and serum PCT level during 1-48 h after birth. There was a significant difference in median serum PCT level during 12-36 h after birth between the respiratory failure (9.56 ng/mL) and bacterial infection (49.82 ng/mL) groups in preterm neonates but no difference between term neonates (respiratory failure 6.83 ng/mL, and bacterial infection 7.43 ng/mL). CONCLUSIONS: Respiratory failure is the main effector for the transient elevation in serum PCT levels at 3 days of life. After excluding the influence of respiratory failure, the chronological pattern and range were very similar between term and preterm neonates. Procalcitonin can be useful for clinicians in distinguishing bacterial infection from respiratory failure, aiding decisions on appropriate antibiotic use.

Exploratory analysis of plasma cytokine/chemokine levels in 6-year-old children from a birth cohort study.

This study aimed to reveal a new dimension of allergy profiles in the general population by using machine learning to explore complex relationships among various cytokines/chemokines and allergic diseases (asthma and atopic dermatitis; AD). We examined the symptoms related to asthma and AD and the plasma levels of 72 cytokines/chemokines obtained from a general population of 161 children at 6 years of age who participated in a pilot birth cohort study of the Japan Environment and Children's Study (JECS). The children whose signs and symptoms fulfilled the criteria of AD, which are mostly based on questionnaire including past symptoms, tended to have higher levels of the two chemokine ligands, CCL17 and CCL27, which are used for diagnosis of AD. On the other hand, another AD-related chemokine CCL22 level in plasma was higher only in children with visible flexural eczema, which is one of AD diagnostic criteria but was judged on the same day of blood examination unlike other criteria. Here, we also developed an innovative method of machine learning for elucidating the complex cytokine/chemokine milieu related to symptoms of allergic diseases by using clustering analysis based on the random forest dissimilarity measure that relies on artificial intelligence (AI) technique. To our surprise, the majority of children showing at least any asthma-related symptoms during the last month were divided by AI into the two clusters, either cluster-2 having elevated levels of IL-33 (related to eosinophil activation) or cluster-3 having elevated levels of CXCL7/NAP2 (related to neutrophil activation), among the total three clusters. Future studies will clarify better approach for allergic diseases by endotype classification.