Functional AGXT2 SNP rs180749 variant and depressive symptoms: Baseline data from the Aidai Cohort Study in Japan.

No study has shown the relationship between alanine-glyoxylate aminotransferase 2 (AGXT2) single nucleotide polymorphisms (SNPs) and depressive symptoms. The present case-control study examined this relationship in Japanese adults. Cases and control participants were selected from those who participated in the baseline survey of the Aidai Cohort Study, which is an ongoing cohort study. Cases comprised 280 participants with depressive symptoms based on a Center for Epidemiologic Studies Depression Scale (CES-D) score ≥ 16. Control participants comprised 2034 participants without depressive symptoms based on the CES-D who had not been diagnosed by a physician as having depression or who had not been currently taking medication for depression. Adjustment was made for age, sex, smoking status, alcohol consumption, leisure time physical activity, education, body mass index, hypertension, dyslipidemia, and diabetes mellitus. Compared with the GG genotype of rs180749, both the GA and AA genotypes were significantly positively associated with the risk of depressive symptoms assessed by the CES-D: the adjusted odds ratios for the GA and AA genotypes were 2.83 (95% confidence interval [CI] 1.23-8.24) and 3.10 (95% CI 1.37-8.92), respectively. The TGC haplotype of rs37370, rs180749, and rs16899974 was significantly inversely related to depressive symptoms (crude OR 0.67; 95% CI 0.49-0.90), whereas the TAC haplotype was significantly positively associated with depressive symptoms (crude OR 1.24; 95% CI 1.01-1.52). This is the first study to show significant associations between AGXT2 SNP rs180749, the TGC haplotype, and the TAC haplotype and depressive symptoms.

Asymmetric Brominative Dearomatization of 2-Naphthols Using a Cinchona Alkaloid-Based Organocatalyst.

A cinchona alkaloid-based organocatalyst enables asymmetric brominative dearomatization of 2-naphthols, providing the corresponding bromonaphthalenones with high enantioselectivities. The first metal-free reaction can accommodate a variety of functional groups and give useful frameworks bearing a Br-containing tetrasubstituted stereogenic center.

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.

Coffee and caffeine intake reduces risk of ulcerative colitis: a case-control study in Japan.

BACKGROUND AND AIM: Although diet is one of the potential environmental factors affecting ulcerative colitis (UC), evidence is not sufficient to draw definitive conclusions. This Japanese case-control study examined the association between the consumption of coffee, other caffeine-containing beverages and food, and total caffeine and the risk of UC. METHODS: The study involved 384 UC cases and 665 control subjects. Intake of coffee, decaffeinated coffee, black tea, green tea, oolong tea, carbonated soft drinks, and chocolate snacks was measured with a semiquantitative food-frequency questionnaire. Adjustments were made for sex, age, pack-years of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, body mass index, and intake of vitamin C, retinol, and total energy. RESULTS: Higher consumption of coffee and carbonated soft drinks was associated with a reduced risk of UC with a significant dose-response relationship (P for trend for coffee and carbonated soft drinks were <0.0001 and 0.01, respectively), whereas higher consumption of chocolate snacks was significantly associated with an increased risk of UC. No association was observed between consumption of decaffeinated coffee, black tea, green tea, or oolong tea and the risk of UC. Total caffeine intake was inversely associated with the risk of UC; the adjusted odds ratio between extreme quartiles was 0.44 (95% confidence interval: 0.29-0.67; P for trend <0.0001). CONCLUSIONS: We confirmed that intake of coffee and caffeine is also associated with a reduced risk of UC in Japan where people consume relatively low quantities of coffee compared with Western countries.

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.

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.

Influence of Multimodal Emotional Stimulations on Brain Activity: An Electroencephalographic Study.

This study aimed to reveal the influence of emotional valence and sensory modality on neural activity in response to multimodal emotional stimuli using scalp EEG. In this study, 20 healthy participants completed the emotional multimodal stimulation experiment for three stimulus modalities (audio, visual, and audio-visual), all of which are from the same video source with two emotional components (pleasure or unpleasure), and EEG data were collected using six experimental conditions and one resting state. We analyzed power spectral density (PSD) and event-related potential (ERP) components in response to multimodal emotional stimuli, for spectral and temporal analysis. PSD results showed that the single modality (audio only/visual only) emotional stimulation PSD differed from multi-modality (audio-visual) in a wide brain and band range due to the changes in modality and not from the changes in emotional degree. The most pronounced N200-to-P300 potential shifts occurred in monomodal rather than multimodal emotional stimulations. This study suggests that emotional saliency and sensory processing efficiency perform a significant role in shaping neural activity during multimodal emotional stimulation, with the sensory modality being more influential in PSD. These findings contribute to our understanding of the neural mechanisms involved in multimodal emotional stimulation.

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.

Easily Switchable 18π-, 19π-, and 20π-Conjugation of Diazaporphyrin Double-Pincer Bispalladium Complexes.

NiII 3,7,13,17-tetrapyridyl-5,15-diazaporphyrin serves as a double tridentate ligand to PdII ions to provide a pincer-type bispalladium complex. Electrochemical analysis revealed that the bispalladium complex shows excellent ability to accept electrons and reversible redox properties due to the coordination of the two cationic PdII centers to the meso-nitrogen atoms. We isolated and characterized one- and two-electron reduction species of the bispalladium complex. The 20π antiaromatic nature of the two-electron reduction species was confirmed by 1 H NMR spectroscopy, UV/Vis-near-IR (NIR) absorption spectra, and density functional theory (DFT) calculations. X-ray diffraction revealed highly twisted structures for the bispalladium complexes regardless of the oxidation state.

IL12B rs6887695 polymorphism and interaction with alcohol intake in the risk of ulcerative colitis in Japan.

BACKGROUND: The interleukin (IL)-23/Th17 pathway plays a critical role in ulcerative colitis (UC). The IL-12p40 subunit, which is shared by IL-23 and IL-12, is encoded by the IL12B gene. The current case-control study investigated the association between IL12B SNP rs6887695 and the UC risk. METHODS: There were 384 cases within 4 years of UC diagnosis and 661 controls who were enrolled. Adjustments were made for sex, age, pack-years of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, and body mass index. RESULTS: Subjects with the GG IL12B SNP rs6887695 genotype had a significantly increased risk of UC compared with those with the CC genotype (adjusted odds ratio [AOR], 1.60; 95% confidence interval [CI], 1.08-2.36). This positive association was also significant using the additive and recessive models (AOR, 1.25; 95% CI, 1.03-1.52; AOR, 1.50; 95% CI, 1.08-2.09, respectively). An independent inverse relationship was observed between ever alcohol consumption and the UC risk in those with the CC genotype while no significant association was found in those with at least one G allele (P for interaction = 0.0008). CONCLUSIONS: IL12B SNP rs6887695 was significantly associated with UC. The influence of alcohol consumption might rely on rs6887695.

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.

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.

Active and passive smoking and risk of ulcerative colitis: A case-control study in Japan.

BACKGROUND AND AIM: Although an inverse relationship between current smoking and the development of ulcerative colitis (UC) has been shown in North America and Europe, evidence is limited in Asian countries, where the incidence of UC is rapidly increasing. This Japanese case-control study examined the association between active and passive smoking and risk of UC. METHODS: A self-administered questionnaire was used to obtain information on smoking and potential confounding factors in 384 cases with a diagnosis of UC within the past 4 years and 665 controls. RESULTS: Compared with having never smoked, having ever smoked was associated with an increased risk of UC (adjusted odds ratio [OR] = 1.70, 95% confidence interval [CI]: 1.23-2.37). No association was observed between current smoking and risk of UC, but former smokers had a significant elevation in risk (adjusted OR = 2.40, 95% CI: 1.67-3.45). There was a positive dose-response relationship with pack-years smoked (P for trend = 0.006). Among never smokers, passive smoking exposure at home was significantly associated with an increased risk of UC (adjusted OR = 1.90, 95% CI: 1.30-2.79). A significant dose-response gradient was also observed between pack-years of passive smoking at home and risk of UC (P for trend = 0.0003). CONCLUSIONS: We confirmed that former smoking elevated the risk of UC, whereas an inverse association between current smoking and the risk of UC did not reach a statistically significant level. Passive smoking may be associated with an increased risk of UC.

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.

Enthalpically and Entropically Favorable Self-Assembly: Synthesis of C4h -Symmetric Tetraazatetrathia[8]circulenes by Regioselective Introduction of Pyridine Rings.

Self-assembly of π-conjugated molecules in solution generally occurs owing to either an enthalpic or an entropic gain; however, designing π-conjugated systems that simultaneously exhibit enthalpically and entropically favorable self-assembly behavior is challenging. Herein, the self-assembly behavior of tetraazatetrathia[8]circulenes is disclosed, which is driven by both enthalpy and entropy. Single-crystal X-ray diffraction analysis demonstrated that molecules of these tetraazatetrathia[8]circulenes form face-to-face stacked dimers with a 1D columnar structure owing to the circularly arranged dipole moments. Importantly, concentration- and temperature-dependent 1 H NMR spectra revealed that the formation of self-assemblies of tetraazatetrathia[8]circulenes in chloroform and methanol is favored by both enthalpic and entropic factors. The unique association behavior is due to the presence of sp2 -hybridized nitrogen atoms, which weakly coordinate to the hydrogen atoms of these solvents and reduce the π-electron density of the circulene cores.

Quadruply BN-Fused Tetrathia[8]circulenes with Flexible Frameworks: Synthesis, Structures and Properties.

Quadruply BN-fused tetrathia[8]circulenes were synthesized through four-fold electrophilic borylation. The single-crystal X-ray diffraction analysis revealed that the BN-fused tetrathia[8]circulene with peripheral phenyl groups exhibits crystal polymorphism, in which the circulene core adopts both planar and saddle conformations in the solid state. The experimental and theoretical studies revealed that the weaker aromaticity of azaborine compared with benzene renders the flexibility of the BN-fused tetrathia[8]circulenes.

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.

Hypertension and dyslipidemia are risk factors for herpes zoster in patients with rheumatoid arthritis: a retrospective analysis using a medical information database.

This study used data from a large-scale multicenter medical information database in Japan to estimate the incidence rate of herpes zoster (HZ) and to examine the relationship between hypertension, dyslipidemia, and diabetes mellitus (DM), and the risk of HZ among patients with rheumatoid arthritis (RA). The research dataset consisted of 221,196 records of potential target patients with RA extracted between April 1, 2008 and August 31, 2017 from the Medical Data Vision database. To assess the association between hypertension, dyslipidemia, and DM and the risk of HZ, a case-control study was set up. Records of 101,498 study subjects met the inclusion criteria. During the observation period, 2566 patients developed HZ and the overall incidence rate was 5.2 (95% confidence interval: 5.0-5.4 per 1000 patient-years). Hypertension, dyslipidemia, and DM were significantly associated with an increased risk of HZ after adjustment for sex, age, hospital size, and use of anti-rheumatic drugs. When mutual adjustment was made for hypertension, dyslipidemia, and DM, the positive associations between hypertension and dyslipidemia and the risk of HZ remained significant; however, the positive association with DM completely disappeared. RA patients with hypertension or dyslipidemia may be at higher risk of HZ.

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.