Maternal and Cord Blood 25-Hydroxyvitamin D3 Are Associated with Increased Cord Blood and Naive and Activated Regulatory T Cells: The Barwon Infant Study.

Vitamin D has shown immune-modulatory effects but mostly in in vitro and animal studies. Regulatory T cells (Treg) are important for a balanced immune system. The relationship between vitamin D on the number of circulating neonatal Treg is unclear. We sought to investigate the association between maternal and neonatal vitamin D metabolites and cord blood (CB) Treg subsets. In a cohort of Australian infants (n = 1074), recruited using an unselected antenatal sampling frame, 158 mother-infant pairs had data on the following: 1) 25-hydroxyvitamin D3 (25(OH)D3) measures in both maternal peripheral blood (28- to 32-wk gestation) and infant CB; 2) proportions (percentage of CD4+ T cells) of CB Treg subsets (CD4+CD45RA+ FOXP3low naive Treg, and CD4+CD45RA- FOXP3high activated Treg [aTreg]); and 3) possible confounders, including maternal personal UV radiation. Multiple regression analyses were used. The median 25(OH)D3 was 85.4 and 50.7 nmol/l for maternal and CB samples, respectively. Higher maternal 25(OH)D3 levels were associated with increased CB naive Treg (relative adjusted mean difference [AMD] per 25 nmol/l increase: 5%; 95% confidence interval [CI]: 1-9%), and aTreg (AMD per 25 nmol/l increase: 17%; 95% CI: 6-28%). Furthermore, a positive association between CB 25(OH)D3 levels and CB aTreg (AMD per 25 nmol/l increase: 29%; 95% CI: 13-48%) was also evident. These results persisted after adjustment for other factors such as maternal personal UV radiation and season of birth. 25(OH)D3, may play a role in the adaptive neonatal immune system via induction of FOXP3+ Tregs. Further studies of immune priming actions of antenatal 25(OH)D3 are warranted.

Burden of infection in Australian infants.

AIM: To determine the incidence, risk factors and health service utilisation for infection in the first 12 months of life in a population-derived Australian pre-birth cohort. METHODS: The Barwon Infant Study is a population-derived pre-birth cohort with antenatal recruitment (n = 1074) based in Geelong, Victoria, Australia. Infection data were collected by parent report, and general practitioner and hospital records at 1, 3, 6, 9 and 12 months of age. We calculated the incidence of infection, attendance at a health service with infection and used multiple negative binomial regression to investigate the effects of a range of exposures on incidence of infection. RESULTS: In the first 12 months of life, infections of the upper and lower respiratory tract (henceforth 'respiratory infections'), conjunctivitis and gastroenteritis occurred at a rate of 0.35, 0.04 and 0.04 episodes per child-month, respectively. A total of 482 (72.4%) infants attended a general practitioner with an infection and 69 (10.4%) infants attended the emergency department. Maternal antibiotic exposure in pregnancy and having older siblings were associated with respiratory infection. Childcare attendance by 12 months of age was associated with respiratory infections and gastroenteritis. Breastfeeding, even if less than 4 weeks in total, was associated with reduced respiratory infection. CONCLUSION: Infection, especially of the respiratory tract, is a common cause of morbidity in Australian infants. Several potentially modifiable risk factors were identified, particularly for respiratory infections. Most infections were managed by general practitioners and 1 in 10 infants attended an emergency department with infection in the first year of life.

Methylation of the LEP gene promoter in blood at 12 months and BMI at 4 years of age-a population-based cohort study.

Increasing evidence links epigenetic variation to anthropometric and metabolic measures. Leptin signalling regulates appetite and energy expenditure, and in pregnancy is important for nutrient supply to the foetus. Maternal metabolic health and foetal growth are linked to infant blood leptin gene (LEP) methylation, which has been cross-sectionally associated with adolescent obesity. Despite this, few studies have explored the relationship between infant LEP methylation and childhood anthropometry, or the impact of genetic variation on these relationships. Using a prospective birth cohort, we investigated whether blood LEP promoter methylation at birth and 12 months predicts weight and adiposity at 4-years. Locus-specific methylation data was analysed by partial correlation tests and multivariable linear regression. There was weak evidence of an association of birth LEP methylation with anthropometry measures at 4 years. Methylation at a specific site (cg19594666) at 12 months was inversely associated with 4-year weight (r = -0.11, p = 0.02) and body-mass index (BMI) (r = -0.13, p = 0.007), which persisted following adjustment for weight at birth and at 12 months. Neither association was influenced by genotype. We report the first evidence of an association between LEP methylation in infancy and childhood weight. Replication in additional cohorts is required to determine if this relationship persists.

Pre-school child blood lead levels in a population-derived Australian birth cohort: the Barwon Infant Study.

OBJECTIVES: To investigate blood lead levels in an Australian birth cohort of children; to identify factors associated with higher lead levels. DESIGN, SETTING: Cross-sectional study within the Barwon Infant Study, a population birth cohort study in the Barwon region of Victoria (1074 infants, recruited June 2010 - June 2013). Data were adjusted for non-participation and attrition by propensity weighting. PARTICIPANTS: Blood lead was measured in 523 of 708 children appraised in the Barwon Infant Study pre-school review (mean age, 4.2 years; SD, 0.3 years). MAIN OUTCOME MEASURE: Blood lead concentration in whole blood (µg/dL). RESULTS: The median blood lead level was 0.8 µg/dL (range, 0.2-3.7 µg/dL); the geometric mean blood lead level after propensity weighting was 0.97 µg/dL (95% CI, 0.92-1.02 µg/dL). Children in houses 50 or more years old had higher blood lead levels (adjusted mean difference [AMD], 0.13 natural log units; 95% CI, 0.02-0.24 natural log units; P = 0.020), as did children of families with lower household income (per $10 000, AMD, -0.035 natural log units; 95% CI, -0.056 to -0.013 natural log units; P = 0.002) and those living closer to Point Henry (inverse square distance relationship; P = 0.002). Associations between hygiene factors and lead levels were evident only for children living in older homes. CONCLUSION: Blood lead levels in our pre-school children were lower than in previous Australian surveys and recent surveys in areas at risk of higher exposure, and no children had levels above 5 µg/dL. Our findings support advice to manage risks related to exposure to historical lead, especially in older houses.

Higher Sun Exposure is Associated With Lower Risk of Pediatric Inflammatory Bowel Disease: A Matched Case-control Study.

OBJECTIVES: The incidence of pediatric inflammatory bowel disease (IBD) is increasing worldwide. Ecological studies show higher incidence in regions at higher latitude or lower ambient ultraviolet radiation; individual-level associations with sun exposure have not been assessed. METHODS: We recruited children (0-17 years) with IBD from 2 large hospitals in Melbourne, Australia. Control participants were recruited from the day surgery unit of one of the same hospitals. Questionnaires provided data on demographics, past sun exposure, the likelihood of sunburn (skin sensitivity) or tanning following sun exposure, use of sun protection, physical activity, and parental smoking and education. Grandparent ancestry was used to determine participant ethnicity. Cases and controls were matched on age and sex. We used conditional logistic regression to test the association between being an IBD case and past sun exposure at different ages, adjusted for a range of other factors. RESULTS: After matching, n = 99 cases and n = 396 controls were included in the analysis. In multivariable analysis, for each 10 min increment in leisure-time sun exposure in summer or winter there was a linear 6% reduction in the odds of having IBD (P = 0.002). Results were similar in sensitivity analyses including only the most recently diagnosed cases, only Caucasian cases and controls, only those with symptom onset within the year before study entry, or additionally adjusted for age or physical activity. CONCLUSIONS: Higher sun exposure in the previous summer or winter was associated with a reduced risk of having IBD. There are plausible pathways that could mediate this effect.

High incidence of respiratory disease in Australian infants despite low rate of maternal cigarette smoking.

AIM: The burden of wheezing illnesses in Australian infants has not been documented since the success of initiatives to reduce maternal cigarette smoking. We aimed to determine the incidence of wheeze and related health-care utilisation during the first year of life among a contemporary Australian birth cohort. METHODS: A birth cohort of 1074 infants was assembled between 2010 and 2013. Parents completed questionnaires periodically. Several non-exclusive infant respiratory disease phenotypes were defined, including any wheeze, wheeze with shortness of breath and recurrent wheeze. Skin prick testing was performed to determine atopic wheeze. Health-care utilisation for respiratory disease was determined from questionnaires and hospital medical records. RESULTS: Retention to 1 year was 840/1074 (83%). The incidence of any wheeze was 51.8% (95% confidence interval (CI) 48.3-55.2%), wheeze with shortness of breath 20.6% (95% CI 17.9-23.5), recurrent wheeze 19.4% (95% CI 16.8-22.2) and atopic wheeze 6% (95% CI 4.6-7.8). Respiratory illness resulted in primary health-care utilisation in 82.2% (95% CI 79.3-84.8) of participants and hospital presentation in 8.8% (95% CI 7.2-10.6). Maternal smoking during pregnancy was uncommon (15.7%) and was not associated with wheeze or health resource utilisation. Male gender, familial atopy and asthma and smaller household size were associated with a higher incidence of wheeze. CONCLUSIONS: The incidence of wheezing illness among Australian infants remains high despite relatively low rates of maternal smoking during pregnancy. The majority of the health-care burden is borne by primary health-care services. Further research is required to inform novel prevention strategies.

Prevalence of clinic-defined food allergy in early adolescence: The SchoolNuts study.

BACKGROUND: Rising rates of food-induced anaphylaxis have recently been shown in the adolescent age group, following earlier descriptions of a rise in children younger than 5 years. However, few population-based studies have examined the prevalence of food allergy in adolescence using objective measures such as oral food challenge (OFC). OBJECTIVE: We sought to determine the prevalence of food allergy among a population-based sample of 10- to 14-year-old adolescents using clinical evaluation including OFC to confirm the diagnosis. METHODS: Schools were randomly selected from greater metropolitan Melbourne, Australia. Students aged 10 to 14 years, and their parents, were asked to complete a questionnaire regarding the adolescent's food allergy or food-related reactions. Clinic evaluation, which consisted of skin prick tests and OFC where eligible, was undertaken if students were suspected to have current food allergy from parent response. Among 9816 students assessed, 5016 had complete parent response and clinic evaluation when eligible. An additional 4800 students had student questionnaires only. RESULTS: The prevalence of clinic-defined current food allergy based on history, sensitization data, and OFC results was 4.5% (95% CI, 3.9-5.1), with the most common food triggers being peanut, 2.7% (95% CI, 2.3-3.2), and tree nut, 2.3% (95% CI, 1.9-2.8). Among the additional group of 4800 adolescents who had only self-reported food allergy status available, the prevalence of self-reported current food allergy was 5.5% (95% CI, 4.9-6.2), with peanut, 2.8% (95% CI, 2.3-3.3), and tree nut, 2.3% (95% CI, 1.9-2.8), the most common. CONCLUSIONS: Approximately 1 in 20 10- to 14-year-old school students in Melbourne has current food allergy. This high prevalence suggests that the previously reported rise in food-induced anaphylaxis in this age group may reflect an increasing prevalence of food allergy rather than simply increased reporting of anaphylaxis.

Language and social-emotional and behavioural wellbeing from 4 to 7 years: a community-based study.

Language disorder (LD) and social-emotional and behavioural (SEB) difficulties are common childhood problems that often co-occur. While there is clear evidence of these associations from clinical samples, less is known about community samples. This paper examines these associations in children aged 4-7 years from a community-based longitudinal study. 771 families provided questionnaire and assessment data at 4, 5 and 7 years. Parent-reported SEB difficulties were measured at each point (SDQ). Child language was directly assessed at 4 (CELF-P2), 5 and 7 years (CELF-4). Linear regression analysis was used to compare cross-sectional differences in mean SDQ scores between children with and without LD at each time point. Linear regression was then used to examine how patterns of language development (language disordered at three time points; never disordered; disordered at one or two time points, i.e. 'unstable' group) related to SEB difficulties at each age, adjusted for potential confounders, as in the previous analyses. Higher hyperactivity/inattention scores were associated with LD at each age. In fully adjusted models, there was little difference in mean emotional symptoms scores between children with and without LD. The 'never' LD group had lower mean SDQ scores at each time point than the 'unstable' group. Findings highlight that children with persistent LD from preschool to early primary school may be more likely to have concomitant SEB difficulties, particularly behavioural difficulties. Those with unstable LD may also have co-occurring SEB difficulties, showing a need for education and health professionals to monitor early language and SEB development.

Who to Refer for Speech Therapy at 4 Years of Age Versus Who to "Watch and Wait"?

OBJECTIVE: To examine predictors of speech disorder resolution versus persistence at age 7 years in children with speech errors at age 4 years. STUDY DESIGN: Participants were drawn from a longitudinal, community cohort. Assessment at age 4 years (N?=?1494) identified children with speech errors. Reassessment at age 7 years allowed categorization into resolved or persistent categories. Logistic regression examined predictors of speech outcome, including family history, sex, socioeconomic status, nonverbal intelligence, and speech error type (delay vs disorder). RESULTS: At age 7 years, persistent errors were seen in over 40% of children who had errors at age 4 years. Speech symptomatology was the only significant predictor of outcome (P?=?.02). Children with disordered errors at age 4 years were twice as likely to have poor speech outcomes at age 7 years compared with those with delayed errors. CONCLUSIONS: Children with speech delay at age 4 years seem more likely to resolve, and this might justify a "watch and wait" approach. In contrast, those with speech disorder at age 4 years appear to be at greater risk for persistent difficulties, and could be prioritized for therapy to offset long-term impacts.

The influence of sun exposure in childhood and adolescence on atopic disease at adolescence.

BACKGROUND: It has been postulated that ultraviolet ray exposure in childhood might influence the development of allergic disease. We examined whether reported sun exposure during childhood or in adolescence is related to the occurrence of atopy or allergic disease. METHODS: Population-based longitudinal cohort study with sixteen-year follow-up (N = 415). Subjects were recruited at birth as part of an infant health study. The reported daily duration of sun exposure in the summer months was recorded at 8 and 16 yrs of age. Allergen sensitization and the presence of eczema, asthma, and rye grass positive rhinitis were recorded at age 16. RESULTS: Reported sun exposures of more than 4 h per day during summer holidays in adolescence were associated with reduced eczema and rhinitis but not inhalant allergen sensitization or asthma risk. Thus, higher sun exposure during summer holidays and summer weekends in adolescence was associated with significantly reduced eczema (test of trend p-value = 0.001 summer holidays; test of trend p-value = 0.003 summer weekends) and rye grass positive rhinitis (test of trend p-value = 0.03 summer holidays; test of trend p-value = 0.02 summer weekends). Sun exposure at adolescence or age 8 was not related to inhalant allergen sensitization. There was no association between serum 25(OH)D levels at adolescence with either inhalant allergen sensitization or allergic disease and adjustment for serum 25(OH)D levels did not alter these findings. CONCLUSIONS: Increased sun exposure during summer holidays in adolescence was associated with reduced eczema and rhinitis risk, independently of measured vitamin D levels but no difference in inhalant allergen sensitization or asthma. The beneficial effects of sun exposure on allergic disease may operate independently from vitamin D or an effect on allergen sensitization.

Obesity and asthma at school entry: co-morbidities and temporal trends.

AIM: A decline in asthma prevalence from 2000 to 2005 was reported previously. The objective is to examine the temporal trends for the prevalence of obesity and other childhood disorders and consider the extent to which associations between asthma and other co-morbidities can be accounted for by body mass index. METHODS: Serial cross-sectional surveys of primary school entrants (n = 18,999) in the Australian Capital Territory between 2001 and 2005 were used. Asthma, recent respiratory symptoms and diabetes data were extracted from parental reports. Anthropometric measurements were obtained from health assessments by school nurses. Child obesity was defined using the age and sex-specific Cole criteria. Time trends for the prevalence of obesity and other disorders, and the association between 'current asthma' and co-morbidities were analysed using multiple logistic regression and other analyses. RESULTS: Obesity prevalence was 5.24% in 2001 decreasing to 3.60% in 2005 (test of linear trend P = 0.02). Overweight (adjusted odds ratio (AOR) 1.30 (95% confidence interval (CI) 1.16, 1.46), P < 0.001) and obese (AOR 1.36 (95% CI 1.13, 1.62), P = 0.001) children were more likely to report 'asthma ever'. Children with diabetes (AOR 9.35 (95% CI 3.11, 28.12, P < 0.001)) and attention deficit (AOR 3.39 (95% CI 2.04, 5.64), P < 0.001) were more likely to report 'current asthma'. CONCLUSIONS: The pattern of association with co-morbidities was different for asthma and obesity. The temporal decline/plateau effect in 'current asthma' could not be explained by concurrent body mass index changes. The decline in obesity was largely driven by the 2005 findings. Longer term trends need to be evaluated further.

Infant anthropometry, early life infection, and subsequent risk of type 1 diabetes mellitus: a prospective birth cohort study.

BACKGROUND: Higher birthweight is associated with increased type 1 diabetes mellitus (T1DM) risk, but the contribution of higher adiposity or lean mass is unclear. In this Tasmanian infant cohort, early upper respiratory infection has been associated with higher asthma risk. PATIENTS AND METHODS: Eligible infants represented one-fifth of live births in Tasmania, 1988-1995. Hospital interview data (day 6) were obtained on 96.3% (10 628/11 040), home (5 wk) visit data (38 d) on 92.9% (9876/10 628) of those, then a phone (12 wk) interview (87 d). Tricep and subscapular skinfold measures and upper arm circumference were recorded at the first two interviews. T1DM cases (n = 26) arising from the age of 16 or under in Tasmania from 1988 to 2006 were ascertained. RESULTS: Higher birthweight [adjusted odds ratio (AOR) 2.82 (95% CI 1.31-6.09)], lean mid-upper arm circumference [AOR 1.76 (95% CI 1.16-2.66)], not skinfold measures, were associated with T1DM risk. Children with an early upper respiratory tract infection by 5-wk visit [AOR 2.74 (95% CI 1.19-6.32)] or ear infection by 12-wk interview [AOR 3.44 (95% CI 1.00-11.79)] were also at higher risk. Putative markers of altered microbial exposure such as resident density were not associated with T1DM risk but the effect of increasing birth order on T1DM risk differed for older (AOR 0.41, p = 0.02) than young mother (AOR 2.45, p = 0.01); difference in effect, p = 0.001. CONCLUSION: In this cohort, early upper respiratory tract infection was associated with T1DM risk, as had been previously found for asthma, consistent with immunoinflammatory upregulation. Using the detailed anthropometric measures available, the link between higher birthweight and T1DM did not appear to reflect increased adiposity.

Importance of accounting for sibling age when examining the association between family size and early childhood cognition, language and emotional behaviour: a birth cohort study.

OBJECTIVES: Larger sibships are associated with poorer cognitive and language outcomes but have different impacts on child emotional development. Previous studies have not taken into account sibling age, nor have impacts across multiple neurodevelopmental domains been considered in the same participant group. This study investigated the influence of family size indicators on early childhood cognitive, language and emotional-behavioural development. The effect of sibling age was considered by evaluating these relationships separately for different sibling age categories. DESIGN: Prospective birth cohort study. SETTING: Participants in the Barwon Infant Study were recruited from two major hospitals in the Barwon region of Victoria, Australia, between 2010 and 2013 (n=1074 children). PARTICIPANTS: The 755 children with any neurodevelopmental data at age 2-3 years excluding twins and those with an acquired neurodisability. OUTCOME MEASURES: Cognitive and language development was assessed using the Bayley Scales of Infant and Toddler Development, Third Edition, and emotional-behavioural development was measured with the Child Behaviour Checklist for Ages 1½-5. RESULTS: Greater household size was associated with a reduced cognitive development score (adjusted mean difference (AMD) -0.66 per extra household member; 95% CI -0.96 to -0.37; p<0.001) without age-specific differences. However, poorer expressive language was only observed for exposure to siblings between 2-6 and 6-10 years older. Having siblings 2-6 years older was associated with less internalising behaviour (AMD -2.1 per sibling; 95% CI -3.1 to -1.0; p<0.001). These associations persisted after multiple comparison adjustment. CONCLUSIONS: The influence of siblings on early childhood development varies substantially by sibling age and the neurodevelopmental outcome under study. Although family size alone appears important for cognitive development, age-specific findings emphasise the importance of sibling interaction in early childhood expressive language development and emotional behaviour.

HIF3A cord blood methylation and systolic blood pressure at 4 years - a population-based cohort study.

Methylation levels at the hypoxia-inducible factor 3α gene (HIF3A) in blood have been linked to body mass index (BMI) in adults. Despite evidence implicating HIF3A in angiogenesis and metabolism, no studies have examined links between HIF3A methylation in early life and cardiovascular health. Here, we investigated the relationship between HIF3A methylation in blood at birth and 12 months of age with cardiovascular measures at 4 years. We also examined influences of prenatal exposures, birth outcomes, and genetic variation. Methylation of two HIF3A promoter regions in cord blood was measured using Sequenom EpiTYPER mass-spectrometry. The first promoter region was also measured in 12-month blood. Four-year cardiovascular measures included blood pressure, pulse wave velocity, and aortic and carotid intima-media thickness. Associations were tested using partial correlation tests and linear regression modelling. Methylation of the first HIF3A promoter in cord and 12-month blood was not associated with four-year measures. There was modest evidence of an association between DNA methylation at the second HIF3A promoter in cord blood and four-year systolic blood pressure (n = 353, r = 0.12, p = 0.03). In sex-stratified analysis, methylation of the second promoter was modestly associated with systolic and diastolic blood pressure (r = 0.16, p = 0.03 for both) in males only. In conclusion, HIF3A methylation at birth shows some evidence of an association with later blood pressure in childhood. Further work should determine whether this relationship persists into later childhood, and should assess potential functional links between HIF3A methylation and cardiovascular health more generally.

Predictors with regard to ingestion, inhalation and dermal absorption of estimated phthalate daily intakes in pregnant women: The Barwon infant study.

Human exposure to phthalate chemicals, used in consumer product plastics, occurs throughout the day. Phthalate levels in pregnant women are associated with offspring health effects including obesity and neurodevelopmental problems. Knowledge of predictors of exposure is necessary in order to effectively reduce phthalate exposure. The present study aims to identify predictors of phthalate levels in Australian pregnant women from the Barwon Infant study birth cohort. Maternal urine samples from 841 women were analyzed for phthalate metabolites. Maternal diet and food preparation practices, use of volatile household products, household characteristics and personal care product use were assessed with questionnaires. All maternal urine contained phthalate metabolites. Maternal prenatal high-fat milk consumption was associated with higher benzyl butyl phthalate (BBzP) (p < 0.001), and bis(2-ethylhexyl) phthalate (DEHP) (p = 0.0023). Higher phthalate levels were associated with consumption of tinned food (fish and tomatoes). Diethyl phthalate (DEP) levels were significantly higher when women reported using air freshener (35% increase, p = 0.01), aerosols (40% increase, p = 0.005), hair treatment chemicals (28% increase, p = 0.031), and chlorine (34% increase, p = 0.009) compared to no use. Maternal phthalate levels did not vary by reported plastic avoidance during pregnancy. The study showed that phthalate exposure is ubiquitous and increased by multiple factors. Future intervention studies to reduce phthalate levels among pregnant women will need to take into account the variety of sources identified in this study.

Gut microbiota composition during infancy and subsequent behavioural outcomes.

BACKGROUND: Despite intense interest in the relationship between gut microbiota and brain development, longitudinal data from human studies are lacking. This study aimed to investigate the relationship between the composition of gut microbiota during infancy and subsequent behavioural outcomes. METHODS: A subcohort of 201 children with behavioural outcome measures was identified within a longitudinal, Australian birth-cohort study. The faecal microbiota were analysed at 1, 6, and 12 months of age. Behavioural outcomes were measured at 2 years of age. FINDINGS: In an unselected birth cohort, we found a clear association between decreased normalised abundance of Prevotella in faecal samples collected at 12 months of age and increased behavioural problems at 2 years, in particular Internalizing Problem scores. This association appeared independent of multiple potentially confounding variables, including maternal mental health. Recent exposure to antibiotics was the best predictor of decreased Prevotella. INTERPRETATION: Our findings demonstrate a strong association between the composition of the gut microbiota in infancy and subsequent behavioural outcomes; and support the importance of responsible use of antibiotics during early life. FUNDING: This study was funded by the National Health and Medical Research Council of Australia (1082307, 1147980, 1129813), The Murdoch Children's Research Institute, Barwon Health, Deakin University, Perpetual Trustees, and The Shepherd Foundation. The funders had no involvement in the data collection, analysis or interpretation, trial design, recruitment or any other aspect pertinent to the study.

Prenatal phthalate exposure, oxidative stress-related genetic vulnerability and early life neurodevelopment: A birth cohort study.

Prenatal phthalate chemicals may have adverse effects on brain development by various mechanisms including oxidant damage. However, birth cohort findings have been conflicting. This study aimed to (i) investigate the interplay between maternal prenatal phthalate levels, infant genetic vulnerability to oxidative stress, and child neurodevelopment and (ii) examine combined putative oxidant exposures. In a population-based birth cohort of 1064 women with prenatal recruitment in Victoria, Australia, maternal urine was collected at 36 weeks of pregnancy and phthalate metabolite concentrations measured. An unweighted genetic score for oxidative stress was made using a candidate gene approach. Cognition was assessed using the BAYLEY-III at two years (n = 678). Parents completed questionnaires for doctor diagnosed autism spectrum disorder (ASD) (1.4 %), ASD traits (4.9 %) and child inattention/hyperactivity (n = 791). Analyses included multiple linear and logistic regression. Higher prenatal phthalate levels and a higher oxidative stress genetic score were each associated with subsequent ASD. Several oxidative stress-related SNPs modified the association between prenatal phthalates and ASD and other outcomes. Consistent patterns were evident across gene score-phthalate combinations for cognition, ASD, ASD traits and inattention/hyperactivity. Other putative oxidant factors such as prenatal smoking further increased risk. Prenatal phthalate levels and infant oxidative stress-related genetic vulnerability are associated with adverse neurodevelopment. Combined exposures are important. Current recommendations and regulation on maternal phthalate exposure during pregnancy require re-evaluation.

Maternal carriage of Prevotella during pregnancy associates with protection against food allergy in the offspring.

In mice, the maternal microbiome influences fetal immune development and postnatal allergic outcomes. Westernized populations have high rates of allergic disease and low rates of gastrointestinal carriage of Prevotella, a commensal bacterial genus that produces short chain fatty acids and endotoxins, each of which may promote the development of fetal immune tolerance. In this study, we use a prebirth cohort (n = 1064 mothers) to conduct a nested case-cohort study comparing 58 mothers of babies with clinically proven food IgE mediated food allergy with 258 randomly selected mothers. Analysis of the V4 region of the 16S rRNA gene in fecal samples shows maternal carriage of Prevotella copri during pregnancy strongly predicts the absence of food allergy in the offspring. This association was confirmed using targeted qPCR and was independent of infant carriage of P. copri. Larger household size, which is a well-established protective factor for allergic disease, strongly predicts maternal carriage of P. copri.

The interaction between early life upper respiratory tract infection and birth during the pollen season on rye-sensitized hay fever and ryegrass sensitization--a birth cohort study.

Studies on early life viral respiratory infection and subsequent atopic disease in childhood have conflicting findings. Animal models show that viral respiratory infection in conjunction with allergen presentation can enhance sensitization. This prospective study assesses the influence of an upper respiratory tract infection (URI) in the first month of life and the season of birth on the development of hay fever and ryegrass allergen sensitization in childhood. From a Tasmanian cohort born during 1988 and 1989, a group of 498 children were followed up at 8 yr and another different group of 415 children were followed up at 16 yr. The ryegrass pollen season in Tasmania occurs in November and December. Forty-four (9.6%) children in Follow-up sample 1 and 47 (12.5%) children in Follow-up sample 2 were born in the pollen season. The parental report of an early upper respiratory tract infection (EURI) was documented prospectively by a home interview at 1 month of age (median age 5.1 wk). Sensitization to ryegrass and house dust mite (HDM) was determined at 8 yr of age by skin prick testing and at 16 yr by ImmunoCap. Ryegrass sensitized hay fever was defined as a positive response to a question on hay fever plus the presence of ryegrass allergy. For children tested at age 8 and born in the pollen season, a EURI by postnatal interview was associated with an increased risk of ryegrass sensitization (OR 5.80 95% CI 1.07, 31.31) but not for children with a EURI born outside the pollen season (OR 0.62 95% CI 0.35, 1.08). Similarly, EURI was significantly associated with early onset (< or = 8 yr) ryegrass sensitized hay fever for children born in the pollen season (AOR 4.78 95% CI 1.17, 19.47) but was not associated with early onset ryegrass sensitized hay fever for children born outside the pollen season (AOR 0.76 95% CI 0.43, 1.33). These findings suggest that early life viral URI interacts with ryegrass allergen exposure in the development of ryegrass allergen sensitization and ryegrass sensitized hay fever symptoms.

A case-sibling assessment of the association between skin pigmentation and other vitamin D-related factors and type 1 diabetes mellitus.

Fair skin pigmentation has been associated with a higher risk of type 1 diabetes mellitus (T1DM). The aim is to compare children with T1DM directly to a sibling in relation to their skin pigmentation in sun-exposed and unexposed sites, past sun exposure and methylation of the VDR gene promoter. The sample consisted of children with T1DM attending a diabetes outpatient clinic and siblings (total n=42). Cutaneous melanin density was estimated using a spectrophotometer. Parental report on past sun exposure was obtained. DNA methylation analysis of the VDR gene promoter was conducted. Matched data analysis was performed comparing each case directly to their sibling. Cases were significantly more likely to have lighter skin pigmentation at the upper arm (AOR 0.69 [95% CI: 0.52, 0.90]; P=0.01). Low infant sun exposure was imprecisely associated with a two-fold increase in T1DM risk (AOR 2.43 [95% CI: 0.91, 6.51]; P=0.08 for under 1 h of winter sun exposure per leisure day). The VDR gene promoter was completely unmethylated in both cases and siblings. The previously demonstrated association between light skin pigmentation and T1DM risk was evident even in this comparison across sibling pairs. Further work on past UVR exposure and related factors such as skin pigmentation is required.