Distinct motifs in the E protein are required for SARS-CoV-2 virus particle formation and lysosomal deacidification in host cells.

IMPORTANCE: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), has caused a global public health crisis. The E protein, a structural protein found in this virus particle, is also known to be a viroporin. As such, it forms oligomeric ion channels or pores in the host cell membrane. However, the relationship between these two functions is poorly understood. In this study, we showed that the roles of E protein in virus particle and viroporin formation are distinct. This study contributes to the development of drugs that inhibit SARS-CoV-2 virus particle formation. Additionally, we designed a highly sensitive and high-throughput virus-like particle detection system using the HiBiT tag, which is a useful tool for studying the release of SARS-CoV-2.

Nut consumption during pregnancy is associated with decreased risk of peer problems in 5-year-old Japanese children.

OBJECTIVES: Nuts are nutrient-dense foods rich in unsaturated fatty acids, protein, dietary fiber, vitamins, and minerals. The present prebirth cohort study examined the association between maternal nut intake during pregnancy and the risk of childhood behavioral problems in 5-year-old Japanese children. METHODS: Study subjects were 1199 mother-child pairs. Dietary intake was assessed using a diet history questionnaire. Emotional problems, conduct problems, hyperactivity problems, peer problems, and low prosocial behavior were assessed using the parent-reported version of the Strengths and Difficulties Questionnaire. Adjustments were made for a priori-selected nondietary confounders and potentially related dietary factors. RESULTS: Compared with mothers who had not eaten nuts during pregnancy, mothers who had eaten nuts had a significantly reduced risk of peer problems in children; the adjusted odds ratio was 0.64 (95% confidence interval: 0.42-0.97). There were no measurable associations between maternal consumption of nuts during pregnancy and the risk of childhood emotional problems, conduct problems, hyperactivity problems, and low prosocial behavior. CONCLUSIONS: Maternal consumption of nuts during pregnancy may be associated with a decreased risk of peer problems in 5-year-old children.

Reaction of size-selected iron-oxide cluster cations with methane: a model study of rapid methane loss in Mars' atmosphere.

We report gas-phase reactions of free iron-oxide clusters, FenOm+, and their Ar adducts with methane in the context of chemical processes in Mars' atmosphere. Methane activation was observed to produce FenOmCH2+/FenOmCD2+ and FenOmC+, where the reactivity exhibited size and composition dependence. For example, the rate coefficients of methane activation for Fe3O+ and Fe4O+ were estimated to be 1 × 10-13 and 3 × 10-13 cm3 s-1, respectively. Based on these reaction rate coefficients, the presence of iron-oxide clusters/particles with a density as low as 107 cm-3 in Mars' atmosphere would explain the rapid loss of methane observed recently by the Curiosity rover.

Maternal fat intake in pregnancy and risk of depressive symptoms in Japanese adolescents: the Kyushu Okinawa Maternal and Child Health Study.

The current prebirth cohort study investigated the association between maternal intake of specific types of fatty acids during pregnancy and adolescent depressive symptoms based on the Center for Epidemiologic Studies Depression Scale. Subjects were 873 mother-child pairs. Dietary intake during the preceding month was assessed using a self-administered diet history questionnaire. The risk of depressive symptoms was 23.3% among the 873 adolescents at 13 years of age. Higher maternal saturated fatty acid intake during pregnancy was independently associated with a reduced risk of depressive symptoms in adolescents. Maternal intake of total fat, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid and cholesterol during pregnancy was not significantly related to depressive symptoms in adolescents. Higher maternal intake of saturated fatty acids during pregnancy may be inversely associated with adolescent depressive symptoms.

Flavivirus recruits the valosin-containing protein-NPL4 complex to induce stress granule disassembly for efficient viral genome replication.

Flaviviruses are human pathogens that can cause severe diseases, such as dengue fever and Japanese encephalitis, which can lead to death. Valosin-containing protein (VCP)/p97, a cellular ATPase associated with diverse cellular activities (AAA-ATPase), is reported to have multiple roles in flavivirus replication. Nevertheless, the importance of each role still has not been addressed. In this study, the functions of 17 VCP mutants that are reportedly unable to interact with the VCP cofactors were validated using the short-interfering RNA rescue experiments. Our findings of this study suggested that VCP exerts its functions in replication of the Japanese encephalitis virus by interacting with the VCP cofactor nuclear protein localization 4 (NPL4). We show that the depletion of NPL4 impaired the early stage of viral genome replication. In addition, we demonstrate that the direct interaction between NPL4 and viral nonstructural protein (NS4B) is critical for the translocation of NS4B to the sites of viral replication. Finally, we found that Japanese encephalitis virus and dengue virus promoted stress granule formation only in VCP inhibitor-treated cells and the expression of NS4B or VCP attenuated stress granule formation mediated by protein kinase R, which is generally known to be activated by type I interferon and viral genome RNA. These results suggest that the NS4B-mediated recruitment of VCP to the virus replication site inhibits cellular stress responses and consequently facilitates viral protein synthesis in the flavivirus-infected cells.

Photodestruction Action Spectroscopy of Silver Cluster Anions, AgN- (N = 3-19), with a Linear Ion Trap: Observation of Bound Excited States above the Photodetachment Threshold.

Electron detachment thresholds of metal cluster anions, MN-, are a few electron volts. The excess electron is therefore detached by visible or ultraviolet light, which also creates low-lying bound electronic states, MN-*; i.e., MN-* energetically overlaps with the continuum, MN + e-. Here, we perform action spectroscopy of photodestruction, leading either to photodetachment or to photofragmentation, for size-selected silver cluster anions, AgN- (N = 3-19), to unveil such bound electronic states embedded in the continuum. The experiment takes advantage of a linear ion trap that enables us to measure photodestruction spectra with high quality at well-defined temperatures, where bound excited states, AgN-*, are clearly identified above their vertical detachment energies. Structural optimization of AgN- (N = 3-19) is conducted by using density functional theory (DFT), which is followed by calculations of vertical excitation energies by time-dependent DFT to assign the observed bound states. Spectral evolution observed as a function of cluster size is also discussed, where the optimized geometries are found to be closely related to the observed spectral profiles. A plasmonic band consisting of nearly degenerate individual excitations is observed for N = 19.

Sex differences in the association between smoking exposure and prevalence of wheeze and asthma in 3-year-old children.

OBJECTIVE: We examined independent and joint associations between prenatal and postnatal smoking exposure and the prevalence of wheeze and asthma among 3-year-old Japanese children. Sex differences were also investigated. METHODS: Smoking exposure, allergic symptoms, and potential confounding factor data were collected using a self-administered questionnaire. Wheeze was defined on the basis of the International Study of Asthma and Allergies in Childhood criteria. Physician-diagnosed asthma was considered to be present if a physician had diagnosed the child with asthma any time before the survey was administered. RESULTS: There were 6402 pediatric participants in this study. Maternal smoking throughout pregnancy and household smoking exposure during the first year of life were associated with an increased prevalence of wheeze among girls but not boys (adjusted odds ratio (OR) [95% CI] = 2.00 [1.13-3.42] and 1.34 [1.07-1.68], respectively). Girls exposed to both prenatal maternal smoking and postnatal household smoking exposure had a significantly higher prevalence of wheeze and physician-diagnosed asthma compared with girls without these exposures (adjusted OR [95% CI] = 2.06 [1.39-3.01] and 1.86 [1.01-3.26], respectively). No association was observed between perinatal smoking exposure and the prevalence of wheeze or asthma among boys. Significant interactions between sex and smoking exposure affecting wheeze and asthma were also found (p for interaction = 0.0003 and 0.01, respectively). CONCLUSION: We found a positive association between perinatal smoking exposure and the prevalence of wheeze and asthma only among girls. Effects of perinatal smoking exposure on wheeze and asthma might be sex specific. Further research is required.

Pre- and postnatal maternal hair dye use and risk of wheeze and asthma in 5-year-old Japanese children: the Kyushu Okinawa Maternal and Child Health Study.

The present study investigated the association between pre- and postnatal maternal hair dye use and the risk of wheeze and asthma in Japanese children aged 5 years. Study participants were 1199 mother-child pairs. Information on the variables under study was obtained using repeated questionnaires completed by parents. Prenatal maternal hair dye use was associated with an increased risk of current wheeze and ever doctor-diagnosed asthma; the adjusted odds ratios (ORs) (95% confidence intervals [CIs]) were 1.44 (1.02-2.02) and 1.51 (1.00-2.25), respectively. Postnatal maternal hair dye use was related to the risk of doctor-diagnosed asthma; the adjusted OR (95% CI) was 1.58 (1.03-2.40). Children who were exposed to maternal hair dye use both prenatally and postnatally had an increased risk of childhood current wheeze and ever doctor-diagnosed asthma; the adjusted ORs (95% CIs) were 1.59 (1.03-2.42) and 1.76 (1.06-2.88), respectively. Our findings suggest that perinatal maternal hair dye use is associated with the risk of wheeze and asthma in children.

Endoplasmic Reticulum-Associated Degradation Controls Virus Protein Homeostasis, Which Is Required for Flavivirus Propagation.

Many positive-stranded RNA viruses encode polyproteins from which viral proteins are generated by processing the polyproteins. This system produces an equal amount of each viral protein, though the required amounts for each protein are not the same. In this study, we found the extra membrane-anchored nonstructural (NS) proteins of Japanese encephalitis virus and dengue virus are rapidly and selectively degraded by the endoplasmic reticulum-associated degradation (ERAD) pathway. Our gene targeting study revealed that ERAD involving Derlin2 and SEL1L, but not Derlin1, is required for the viral genome replication. Derlin2 is predominantly localized in the convoluted membrane (CM) of the viral replication organelle, and viral NS proteins are degraded in the CM. Hence, these results suggest that viral protein homeostasis is regulated by Derlin2-mediated ERAD in the CM, and this process is critical for the propagation of these viruses. IMPORTANCE The results of this study reveal the cellular ERAD system controls the amount of each viral protein in virus-infected cells and that this "viral protein homeostasis" is critical for viral propagation. Furthermore, we clarified that the "convoluted membrane (CM)," which was previously considered a structure with unknown function, serves as a kind of waste dump where viral protein degradation occurs. We also found that the Derlin2/SEL1L/HRD1-specific pathway is involved in this process, whereas the Derlin1-mediated pathway is not. This novel ERAD-mediated fine-tuning system for the stoichiometries of polyprotein-derived viral proteins may represent a common feature among polyprotein-encoding viruses.

Perinatal maternal depressive symptoms and risk of behavioral problems at five years.

BACKGROUND: Evidence on the association between perinatal maternal depression and children's behavioral development is limited. We investigated the association between maternal depressive symptoms during pregnancy and postpartum and the risk of childhood behavioral problems using data from a birth cohort study. METHODS: Study subjects were 1199 mother-child pairs. Maternal depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale during pregnancy and the Edinburgh Postnatal Depression Scale at 4 months postpartum. Children's behavioral development at 5 years of age was assessed with the Strengths and Difficulties Questionnaire. RESULTS: Compared with children whose mothers did not experience depressive symptoms during pregnancy, those whose mothers did experience depressive symptoms during pregnancy had increased risk of emotional symptoms, conduct problems, hyperactivity, peer problems, and low prosocial behavior. Maternal depressive symptoms at around 4 months postpartum were associated with increased risk of childhood emotional problems. Compared with children whose mothers did not experience depressive symptoms during the perinatal period, those whose mothers did experience depressive symptoms both during pregnancy and postpartum had a fivefold increased risk of childhood emotional symptoms and a threefold increased risk of peer problems. CONCLUSIONS: Our findings suggest that perinatal maternal depression is associated with behavioral problems in children. IMPACT: Several epidemiological studies in Western countries have examined the association between perinatal maternal depression and children's behavioral development, yet the results are conflicting and inconclusive. There is limited evidence on this topic in Asia. In our study using data from a prospective pregnancy birth cohort, maternal depressive symptoms around 4 months postpartum were associated with an increased risk of emotional symptoms in children aged 5 years. Children whose mothers had exhibited depressive symptoms both during pregnancy and postpartum had a fivefold increased risk of childhood emotional symptoms and a threefold increased risk of peer problems.

Expression of Zinc-Finger Antiviral Protein in hCMEC/D3 Human Cerebral Microvascular Endothelial Cells: Effect of a Toll-Like Receptor 3 Agonist.

INTRODUCTION: Invasion of viruses into the brain causes viral encephalitis, which can be fatal and causes permanent brain damage. The blood-brain barrier (BBB) protects the brain by excluding harmful substances and microbes. Brain microvascular endothelial cells are important components of the BBB; however, the mechanisms of antiviral reactions in these cells have not been fully elucidated. Zinc-finger antiviral protein (ZAP) is a molecule that restricts the infection of various viruses, and there are 2 major isoforms: ZAPL and ZAPS. Toll-like receptor 3 (TLR3), a pattern-recognition receptor against viral double-stranded RNA, is implicated in antiviral innate immune reactions. The aim of this study was to investigate the expression of ZAP in cultured hCMEC/D3 human brain microvascular endothelial cells treated with an authentic TLR3 agonist polyinosinic-polycytidylic acid (poly IC). METHODS: hCMEC/D3 cells were cultured and treated with poly IC. Expression of ZAPL and ZAPS mRNA was investigated using quantitative reverse transcription-polymerase chain reaction, and protein expression of these molecules was examined using western blotting. The role of nuclear factor-κB (NF-κB) was examined using the NF-κB inhibitor, SN50. The roles of interferon (IFN)-ß, IFN regulatory factor 3 (IRF3), tripartite motif protein 25 (TRIM25), and retinoic acid-inducible gene-I (RIG-I) in poly IC-induced ZAPS expression were examined using RNA interference. Propagation of Japanese encephalitis virus (JEV) was examined using a focus-forming assay. RESULTS: ZAPS mRNA and protein expression was upregulated by poly IC, whereas the change of ZAPL mRNA and protein levels was minimal. Knockdown of IRF3 or TRIM25 decreased the poly IC-induced upregulation of ZAPS, whereas knockdown of IFN-ß or RIG-I did not affect ZAPS upregulation. SN50 did not affect ZAPS expression. Knockdown of ZAP enhanced JEV propagation. CONCLUSION: ZAPL and ZAPS were expressed in hCMEC/D3 cells, and ZAPS expression was upregulated by poly IC. IRF3 and TRIM25 are involved in poly IC-induced upregulation of ZAPS. ZAP may contribute to antiviral reactions in brain microvascular endothelial cells and protect the brain from invading viruses such as JEV.

Tryptophan intake is related to a lower prevalence of depressive symptoms during pregnancy in Japan: baseline data from the Kyushu Okinawa Maternal and Child Health Study.

OBJECTIVE: Tryptophan is an essential amino acid wholly derived from diet. While the majority of tryptophan is degraded through the kynurenine pathway into neuroactive metabolites like quinolinic acid and kynurenic acid, a small proportion of ingested tryptophan is metabolized into the neurotransmitter serotonin. The current cross-sectional study in Japan examined the association between tryptophan intake and depressive symptoms during pregnancy. METHODS: Study subjects were 1744 pregnant women. Dietary intake during the preceding month was assessed using a self-administered diet history questionnaire. Depressive symptoms were defined as a score ≥ 16 on the Center for Epidemiologic Studies Depression Scale. Adjustment was made for age, gestation, region of residence, number of children, family structure, history of depression, family history of depression, smoking, secondhand smoke exposure at home and at work, employment, household income, education, body mass index, and intake of saturated fatty acids, eicosapentaenoic acid plus docosahexaenoic acid, calcium, vitamin D, and isoflavones. RESULTS: The prevalence of depressive symptoms during pregnancy was 19.2%. After adjustment for confounding factors, higher tryptophan intake was independently inversely associated with the prevalence of depressive symptoms during pregnancy: the adjusted prevalence ratios (95% confidence intervals) for depressive symptoms during pregnancy in the first, second, third, and fourth quartiles of tryptophan intake were 1 (reference), 0.99 (0.76-1.28), 0.94 (0.71-1.25), and 0.64 (0.44-0.93), respectively (p for trend = 0.04). CONCLUSIONS: Higher estimated tryptophan intake was cross-sectionally independently associated with a lower prevalence of depressive symptoms during pregnancy in Japanese women.

Correction: Electron counting in cationic and anionic silver clusters doped with a 3d transition-metal atom: endo- vs. exohedral geometry.

Correction for 'Electron counting in cationic and anionic silver clusters doped with a 3d transition-metal atom: endo- vs. exohedral geometry' by Kento Minamikawa et al., Phys. Chem. Chem. Phys., 2022, DOI: 10.1039/d1cp04197e.

Electron counting in cationic and anionic silver clusters doped with a 3d transition-metal atom: endo- vs. exohedral geometry.

Electron counting is a concept that often governs properties of molecules, clusters, and complexes. Here we explore silver clusters doped with a transition-metal atom, where it has been an issue whether or not 3d electrons delocalize to participate in electron counting. The experiment is performed on AgNM+/- (M = Sc-Ni) clusters to examine their stability through chemical reactivity, enabling systematic control of the number of valence electrons by the cluster size, the charge state, and the transition-metal element across the periodic table. It is revealed for 18-valence-electron clusters that 3d electrons participate in electron counting to show exceptional stability only when the transition-metal atom is endohedrally doped, except for Cr and Mn doping that forces 3d electrons to localize. We thus present new entries for superatomic metal clusters as well as a geometric factor that regulates the behavior of 3d electrons in the nanoscale regime.

Exploring s-d, s-f, and d-f Electron Interactions in AgnCe+ and AgnSm+ by Chemical Reaction toward O2.

We investigate gas-phase reactions of free AgnCe+ and AgnSm+ clusters with oxygen molecules to explore s-d, s-f, and d-f electron interactions in the finite size regime; a Ce atom has a 5d electron as well as a 4f electron, whereas a Sm atom has six 4f electrons without 5d electrons. In the reaction of AgnCe+ (n = 3-20), the Ce atom located on the cluster surface provides an active site except for n = 15 and 16, as inferred from the composition of the reaction products with oxygen bound to the Ce atom as well as from their relatively high reactivity. The extremely low reactivity for n = 15 and 16 is due to encapsulation of the Ce atom by Ag atoms. The minimum reactivity observed at n = 16 suggests that a closed electronic shell with 18 valence electrons is formed with a delocalized Ce 5d electron, while the localized Ce 4f electron does not contribute to the shell closure. As for AgnSm+ (n = 1-18), encapsulation of the Sm atom was observed for n ≥ 15. The lower reactivity at n = 17 than at n = 16 and 18 implies that an 18-valence-electron shell closure is formed with s electrons from Ag and Sm atoms; Sm 4f electrons are not involved in the shell closure as in the case of AgnCe+. The present results suggest that the 4f electrons tend to localize on the lanthanoid atom, whereas the 5d electron delocalizes to contribute to the electron shell closure.

Maternal metal intake during pregnancy and childhood behavioral problems in Japan: the Kyushu Okinawa Maternal and Child Health Study.

OBJECTIVES: Lower maternal metal intake during pregnancy might affect childhood development. The current prebirth cohort study investigated the relationship between maternal intake of zinc, magnesium, iron, copper, and manganese during pregnancy and behavioral problems in Japanese children aged five years. METHODS: Subjects were 1199 mother-child pairs. Dietary intake during the preceding month was assessed using a diet history questionnaire. Emotional, conduct, hyperactivity, and peer problems and low prosocial behavior were assessed using the Strengths and Difficulties Questionnaire. Maternal age, gestation at baseline, region of residence, number of children, maternal and paternal education, household income, maternal depressive symptoms during pregnancy, maternal alcohol intake during pregnancy, maternal smoking during pregnancy, child's birth weight, child's sex, breastfeeding duration, smoking in the household during the first year of life, and some dietary confounders that were associated with outcomes under study in this population were adjusted for. RESULTS: Compared with maternal magnesium intake during pregnancy in the first quartile, magnesium intake in the second, third, and fourth quartiles was independently inversely related to childhood hyperactivity problems, but not to emotional, conduct, or peer problems or low prosocial behavior: the adjusted odds ratio between extreme quartiles was 0.48 (95% confidence interval: 0.23-0.99, P for trend = 0.04). No evident associations were observed between maternal intake of zinc, iron, copper, or manganese during pregnancy and childhood emotional, conduct, hyperactivity, or peer problems or low prosocial behavior. CONCLUSIONS: The present study suggests that higher maternal magnesium intake during pregnancy is inversely associated with hyperactivity problems in Japanese children.

Reaction of nitric oxide molecules on transition-metal-doped silver cluster cations: size- and dopant-dependent reaction pathways.

We report size- and dopant-dependent reaction pathways as well as reactivity of gas-phase free AgnM+ (M = Sc-Ni) clusters interacting with NO. The reactivity of AgnM+, except for M = Cr and Mn, exhibits a minimum at a specific size, where the cluster cation possesses 18 or 20 valence electrons consisting of Ag 5s and dopant's 3d and 4s. The product ions range from NO adducts, AgnM(NO)m+, and oxygen adducts, AgnMOm+, to NO2 adducts, AgnM(NO2)m+. At small sizes, AgnMOm+ are the major products for M = Sc-V, whereas AgnM(NO)m+ dominate the products for M = Cr-Ni in striking contrast. In both cases, these reaction products are reminiscent of those from an atomic transition metal. However, the reaction pathways are different at least for M = Sc and Ti; kinetics measurements reveal that the present oxygen adducts are formed via NO adducts, while, for example, Ti+ is known to produce TiO+ directly by reaction with a single NO molecule. At larger sizes, on the other hand, AgnM(NO2)m+ are dominantly produced regardless of the dopant element because the dopant atom is encapsulated by the Ag host; the NO2 formation on the cluster is similar to that reported for undoped Agn+.

Calcium intake during pregnancy is associated with decreased risk of emotional and hyperactivity problems in five-year-old Japanese children.

Background: Recently, more attention has been paid to behavioral problems in children. However, for the most part, risk factors for these problems have yet to be determined.Objective: The current prebirth cohort study investigated the relationship between maternal calcium consumption during pregnancy and behavioral problems in five-year-old Japanese children.Methods: Subjects were 1199 mother-child pairs. Dietary intake during the preceding month was assessed using a self-administered diet history questionnaire. Emotional problems, conduct problems, hyperactivity problems, and peer problems were assessed using the Strengths and Difficulties Questionnaire. Logistic regression analysis was conducted to estimate odds ratios (ORs) and 95% confidence intervals (CIs).Results: Compared with the lowest quartile of maternal calcium intake, the highest was significantly associated with decreased risk of childhood emotional problems: the adjusted OR (95% CIs) was 0.46 (0.27-0.79, P for trend = 0.01). Higher maternal calcium intake during pregnancy was also independently associated with decreased risk of childhood hyperactivity problems; the adjusted ORs (95% CIs) in the first, second, third, and fourth quartiles of maternal calcium intake during pregnancy were 1 (reference), 0.52 (0.31-0.84), 0.58 (0.35-0.93), and 0.60 (0.37-0.97), respectively (P for trend = 0.046). No such inverse associations were observed for childhood conduct problems or peer problems; the adjusted ORs (95% CIs) in the highest quartile of maternal calcium intake were 0.97 (0.64-1.47) for conduct problems and 1.11 (0.61-2.01) for peer problems.Conclusions: Maternal calcium intake during pregnancy may decrease the risk of childhood emotional and hyperactivity problems.

Maternal Use of Induction Heating Cookers During Pregnancy and Birth Outcomes: The Kyushu Okinawa Maternal and Child Health Study.

The effects of exposure to intermediate-frequency electromagnetic fields (IF-EMFs) during pregnancy on birth outcomes are uncertain. We investigated the association between the use of induction heating (IH) cookers, which are major sources of IF-EMFs, during pregnancy and preterm birth (PTB), low birth weight (LBW), small-for-gestational-age (SGA), and birth weight, using data from a prebirth cohort study in Japan. Study participants were 1,565 mothers with singleton pregnancies and the babies born from these pregnancies. We collected the data presented here using self-administered questionnaires. An adjustment was made for maternal age, region of residence, number of children, family structure, maternal education, maternal employment, maternal alcohol intake, smoking during pregnancy, maternal body mass index, baby's sex, and gestational age at birth. IH cooker use during pregnancy was independently associated with a reduced risk of PTB: the adjusted odds ratio was 0.28 (95% confidence interval: 0.07-0.78). IH cooker use during pregnancy was not associated with LBW, SGA, or birth weight. This is the first study to show that IH cooker use during pregnancy is independently inversely associated with PTB.

Maternal caffeine intake during pregnancy and risk of food allergy in young Japanese children.

AIM: To examine the association between maternal caffeine intake during pregnancy and the development of food allergy in young Japanese children up to 3 years of age. METHODS: The study involved 1522 mother-child pairs. Data on maternal caffeine intake during pregnancy were assessed with a validated diet history questionnaire. Food allergy was defined by a self-reported claim of having a physicians' diagnosis of food allergy or of having an acute reaction to a food. RESULTS: Compared with the lowest tertile of maternal caffeine intake during pregnancy, the second tertile, but not the highest tertile, was significantly associated with an increased risk of food allergy. Further adjustment on suspicion or diagnosis of atopic eczema at around 4 months postpartum in a follow-up survey did not substantially change the association between maternal caffeine intake during pregnancy and the risk of food allergy in children: further adjusted hazard ratios (95% confidence intervals) for the second (T2), the highest tertiles (T3) and the second and the highest tertiles combined (T2 + T3) were 1.46 (1.10-1.96), 1.16 (0.85-1.56) and 1.31 (1.01-1.70), respectively. CONCLUSIONS: Our findings suggest that maternal caffeine intake during pregnancy may be positively associated with the risk of food allergy in children.