Publications by authors named "Anne-Louise Ponsonby"

235 Publications

Exposure to adversity and inflammatory outcomes in mid and late childhood.

Brain Behav Immun Health 2020 Dec 28;9:100146. Epub 2020 Sep 28.

Murdoch Children's Research Institute, Melbourne, Australia.

Background: We aimed to estimate the association between exposure to adversity and inflammatory markers in mid (4 years) and late (11-12 years) childhood, and whether effects differ by type and timing of exposure.

Methods: : Barwon Infant Study (BIS; N = 510 analyzed) and Longitudinal Study of Australian Children (LSAC; N = 1156 analyzed). : Adversity indicators assessed from 0 to 4 (BIS) and 0-11 years (LSAC): parent legal problems, mental illness and substance abuse, anger in parenting responses, separation/divorce, unsafe neighborhood, and family member death; a count of adversities; and, in LSAC only, early (0-3), middle (4-7), or later (10-11) initial exposure. Inflammation quantified by high sensitivity C-reactive protein (hsCRP, Log (ug/ml)) and glycoprotein acetyls (GlycA, Log (umol/L)). Linear regression was used to estimate relative change in inflammatory markers, adjusted for sociodemographic characteristics, with exposure to adversity. Outcomes were log-transformed.

Results: Evidence of an association between adversity and hsCRP was weak and inconsistent (e.g., 3+ versus no adversity: BIS: 12% higher, 95%CI -49.4, 147.8; LSAC 4.6% lower, 95%CI: -36.6, 48.3). A small positive association between adversity and GlycA levels was observed at both 4 years (e.g., 3+ versus no adversity: 3.3% higher, 95%CI -3.0, 9.9) and 11-12 years (3.2% higher, 95%CI 0.8, 5.8). In LSAC, we did not find evidence that inflammatory outcomes differed by initial timing of adversity exposure.

Conclusions: Small positive associations between adversity and inflammation were consistently observed for GlycA, across two cohorts with differing ages. Further work is needed to understand mechanisms, clinical relevance, and to identify opportunities for early intervention.
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http://dx.doi.org/10.1016/j.bbih.2020.100146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474172PMC
December 2020

Physical activity and adiposity in preschool children: The Barwon Infant Study.

Pediatr Obes 2021 Sep 29:e12853. Epub 2021 Sep 29.

School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia.

Background: The association between physical activity and adiposity in preschool-aged children is unclear.

Objective: To assess the cross-sectional association between objectively measured physical activity and body fat in preschool-aged children.

Methods: In the preschool review in an Australian birth cohort study (n = 1074), mean duration and time accumulated in ≥1-min bouts of physical activity at light-intensity (LPA), moderate- to vigorous-intensity (MVPA) and light- to vigorous-intensity (LMVPA) were computed from accelerometer (ActiGraph GT3X+) data. Percent body fat was assessed by bioelectrical impedance. Associations between physical activity and percent body fat were examined by multiple regression, adjusted for accelerometer wear time, MVPA (in analyses of LPA), maternal body mass index (BMI) and maternal education.

Results: A total of 450 participants (n = 450) had valid data. There was evidence of associations between physical activity and adiposity: each additional hour of LVPA was associated with 0.6% (CI -0.2%, 1.3%) higher body fat; ≥1-min bouts of LPA was associated with 1.0% (CI 0.1%, 1.9%) higher body fat; each additional hour of MVPA was associated with -0.8% (CI -1.6%, -0.1%) less body fat; and ≥1-min bouts of MVPA was associated with -1.3% (CI -2.5%, -0.1%) body fat.

Conclusions: Among a cohort of preschool-aged children, there was evidence that more intensive physical activity assessed by an accelerometer is associated with reduced body fat.
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http://dx.doi.org/10.1111/ijpo.12853DOI Listing
September 2021

The newborn metabolome: associations with gestational diabetes, sex, gestation, birth mode, and birth weight.

Pediatr Res 2021 Sep 15. Epub 2021 Sep 15.

Murdoch Children's Research Institute, Parkville, VIC, Australia.

Background: Pathways towards many adult-onset conditions begin early in life, even in utero. Maternal health in pregnancy influences this process, but little is known how it affects neonatal metabolism. We investigated associations between pregnancy and birth factors and cord blood metabolomic profile in a large, population-derived cohort.

Methods: Metabolites were measured using nuclear magnetic resonance in maternal (28 weeks gestation) and cord serum from 912 mother-child pairs in the Barwon Infant Study pre-birth cohort. Associations between maternal (metabolites, age, BMI, smoking), pregnancy (pre-eclampsia, gestational diabetes (GDM)), and birth characteristics (delivery mode, gestational age, weight, infant sex) with 72 cord blood metabolites were examined by linear regression.

Results: Delivery mode, sex, gestational age, and birth weight were associated with specific metabolite levels in cord blood, including amino acids, fatty acids, and cholesterols. GDM was associated with higher cord blood levels of acetoacetate and 3-hydroxybutyrate.

Conclusions: Neonatal factors, particularly delivery mode, were associated with many cord blood metabolite differences, including those implicated in later risk of cardiometabolic disease. Associations between GDM and higher offspring ketone levels at birth are consistent with maternal ketosis in diabetic pregnancies. Further work is needed to determine whether these neonatal metabolome differences associate with later health outcomes.

Impact: Variations in blood metabolomic profile have been linked to health status in adults and children, but corresponding data in neonates are scarce. We report evidence that pregnancy complications, mode of delivery, and offspring characteristics, including sex, are independently associated with a range of circulating metabolites at birth, including ketone bodies, amino acids, cholesterols, and inflammatory markers. Independent of birth weight, exposure to gestational diabetes is associated with higher cord blood ketone bodies and citrate. These findings suggest that pregnancy complications, mode of delivery, gestational age, and measures of growth influence metabolic pathways prior to birth, potentially impacting later health and development.
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http://dx.doi.org/10.1038/s41390-021-01672-7DOI Listing
September 2021

Common maternal infections during pregnancy and childhood leukaemia in the offspring: findings from six international birth cohorts.

Int J Epidemiol 2021 Sep 14. Epub 2021 Sep 14.

Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, UK.

Background: Previous epidemiological studies have found positive associations between maternal infections and childhood leukaemia; however, evidence from prospective cohort studies is scarce. We aimed to examine the associations using large-scale prospective data.

Methods: Data were pooled from six population-based birth cohorts in Australia, Denmark, Israel, Norway, the UK and the USA (recruitment 1950s-2000s). Primary outcomes were any childhood leukaemia and acute lymphoblastic leukaemia (ALL); secondary outcomes were acute myeloid leukaemia (AML) and any childhood cancer. Exposures included maternal self-reported infections [influenza-like illness, common cold, any respiratory tract infection, vaginal thrush, vaginal infections and urinary tract infection (including cystitis)] and infection-associated symptoms (fever and diarrhoea) during pregnancy. Covariate-adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated using multilevel Cox models.

Results: Among 312 879 children with a median follow-up of 13.6 years, 167 leukaemias, including 129 ALL and 33 AML, were identified. Maternal urinary tract infection was associated with increased risk of any leukaemia [HR (95% CI) 1.68 (1.10-2.58)] and subtypes ALL [1.49 (0.87-2.56)] and AML [2.70 ([0.93-7.86)], but not with any cancer [1.13 (0.85-1.51)]. Respiratory tract infection was associated with increased risk of any leukaemia [1.57 (1.06-2.34)], ALL [1.43 (0.94-2.19)], AML [2.37 (1.10-5.12)] and any cancer [1.33 (1.09-1.63)]; influenza-like illness showed a similar pattern but with less precise estimates. There was no evidence of a link between other infections and any outcomes.

Conclusions: Urinary tract and respiratory tract infections during pregnancy may be associated with childhood leukaemia, but the absolute risk is small given the rarity of the outcome.
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http://dx.doi.org/10.1093/ije/dyab199DOI Listing
September 2021

Omega-3 Index, fish consumption, use of fish oil supplements and first clinical diagnosis of central nervous system demyelination.

Mult Scler Relat Disord 2021 Oct 10;55:103210. Epub 2021 Aug 10.

Curtin School of Population Health, Curtin University, Perth, WA, Australia. Electronic address:

Higher intakes of omega-3 polyunsaturated fatty acids (n3PUFAs) have been associated with lower MS risk. We aimed to test associations between the Omega-3 Index, blood levels of n3PUFAs, fish oil supplement use, and fish consumption with a first clinical diagnosis of CNS demyelination (FCD). Cases (n = 250) had a higher Omega-3 Index compared with a matched group of controls (n = 471) (average treatment effect (ATE)=0.31, p = 0.047, based on augmented inverse probability weighting). A higher percentage of cases than controls used fish oil supplements (cases=17% vs. controls=10%). We found that Omega-3 Index increased as time between FCD and study interview increased (e.g., at or below median (112 days), based on ATE, mean=5.30, 95% CI 5.08, 5.53; above median, mean=5.90, 95% CI 5.51, 6.30). Fish oil supplement use increased in a similar manner (at or below median (112 days), based on ATE, proportion=0.12, 95% CI 0.06, 0.18; above the median, proportion=0.21, 95% CI 0.14, 0.28). Our results suggest a behaviour change post FCD with increased use of fish oil supplements.
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http://dx.doi.org/10.1016/j.msard.2021.103210DOI Listing
October 2021

The maternal gut microbiome during pregnancy and offspring allergy and asthma.

J Allergy Clin Immunol 2021 Sep 24;148(3):669-678. Epub 2021 Jul 24.

Institute for Physical and Mental Health and Clinical Transformation, Deakin University, Geelong, Australia; Child Health Research Unit, Barwon Health, Geelong, Australia; the Centre For Food Allergy Research, Murdoch Children's Research Institute, Parkville. Electronic address:

Environmental exposures during pregnancy that alter both the maternal gut microbiome and the infant's risk of allergic disease and asthma include a traditional farm environment and consumption of unpasteurized cow's milk, antibiotic use, dietary fiber, and psychosocial stress. Multiple mechanisms acting in concert may underpin these associations and prime the infant to acquire immune competence and homeostasis following exposure to the extrauterine environment. Cellular and metabolic products of the maternal gut microbiome can promote the expression of microbial pattern recognition receptors, as well as thymic and bone marrow hematopoiesis relevant to regulatory immunity. At birth, transmission of maternally derived bacteria likely leverages this in utero programming to accelerate postnatal transition from a T2- to T1- and T17-dominant immune phenotype and maturation of regulatory immune mechanisms, which in turn reduce the child's risk of allergic disease and asthma. Although our understanding of these phenomena is rapidly evolving, the field is relatively nascent, and we are yet to translate existing knowledge into interventions that substantially reduce disease risk in humans. Here, we review evidence that the maternal gut microbiome impacts the offspring's risk of allergic disease and asthma, discuss challenges and future directions for the field, and propose the hypothesis that maternal carriage of Prevotella copri during pregnancy decreases the offspring's risk of allergic disease via production of succinate, which in turn promotes bone marrow myelopoiesis of dendritic cell precursors in the fetus.
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http://dx.doi.org/10.1016/j.jaci.2021.07.011DOI Listing
September 2021

Prevention of infant eczema by neonatal bacille Calmette-Guérin vaccination: The MIS BAIR randomized controlled trial.

Allergy 2021 Jul 26. Epub 2021 Jul 26.

Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia.

Background: Bacille Calmette-Guérin (BCG) vaccine could play a role in counteracting the rising prevalence of atopic diseases, through its beneficial off-target effects. We aimed to determine whether neonatal BCG vaccination reduces the incidence of eczema in infants.

Methods: Randomized controlled trial with 1272 infants allocated to receive BCG-Denmark or no BCG at birth. The primary outcome was the 12-month incidence of eczema based on 3-monthly questionnaires. Eczema was also assessed at a 12-month clinic visit. ClinicalTrial.gov: NCT01906853.

Results: The 12-month eczema incidence was 32.2% in the BCG group compared with 36.6% in the control group (adjusted risk difference (aRD) -4.3%, 95% CI -9.9% to 1.3%, multiple imputation model). In addition, comparing infants in the BCG group with the control group, 15.7% vs. 19.2% had eczema lesions at the 12-month visit (aRD -3.5%, 95% CI -8.0% to 1.0%); 35.7% vs. 39.0% reported using topical steroids (aRD -3.3, 95% CI -9.2 to 2.7); and 7.3% vs. 10.2% had severe eczema scores (aRD -3.0%, 95% CI -8.8% to 2.7%). In 344 high-risk infants (two atopic parents), the 12-month eczema incidence was 35.3% in the BCG group compared with 46.8% in the control group (aRD -11.5%, 95% CI -21.9% to -1.2%; number needed to treat 8.7, 95% CI 4.6 to 83.3).

Conclusion: There is insufficient evidence to recommend neonatal BCG vaccination in all infants for the prevention of eczema in the first year of life; however, a modest beneficial effect was observed among high-risk infants. A single dose of BCG-Denmark soon after birth could reduce the incidence of eczema in infants with two atopic parents.
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http://dx.doi.org/10.1111/all.15022DOI Listing
July 2021

Neonatal Bacille Calmette-Guérin Vaccination and Infections in the First Year of Life: The MIS BAIR Randomized Controlled Trial.

J Infect Dis 2021 Oct;224(7):1115-1127

Infectious Diseases; Clinical Epidemiology and Biostatistics Unit; Population Allergy, Murdoch Children's Research Institute, Parkville, Victoria, Australia.

Background: Bacille Calmette-Guérin (BCG) vaccination has beneficial off-target effects that may include protecting against non-mycobacterial infectious diseases. We aimed to determine whether neonatal BCG vaccination reduces lower respiratory tract infections (LRTI) in infants in the Melbourne Infant Study: BCG for Allergy and Infection Reduction (MIS BAIR) trial.

Methods: In this investigator-blinded trial, neonates in Australia were randomized to receive BCG-Denmark vaccination or no BCG at birth. Episodes of LRTI were determined by symptoms reported in parent-completed, 3-month questionnaires over the first year of life. Data were analyzed by intention-to-treat using binary regression.

Results: A total of 1272 neonates were randomized to the BCG vaccination (n = 637) or control (n = 635) group. The proportion of participants with an episode of LRTI in the first year of life among BCG-vaccinated infants was 54.8% compared to 58.0% in the control group, resulting in a risk difference of -3.2 (95% confidence interval, -9.0 to 2.6) after multiple imputation. There was no interaction observed between the primary outcome and sex, maternal BCG, or the other prespecified effect modifiers.

Conclusions: Based on the findings of this trial, there is insufficient evidence to support the use of neonatal BCG vaccination to prevent LRTI in the first year of life in high-income settings.
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http://dx.doi.org/10.1093/infdis/jiab306DOI Listing
October 2021

Maternal prenatal gut microbiota composition predicts child behaviour.

EBioMedicine 2021 Jun 5;68:103400. Epub 2021 Jun 5.

Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, Barwon Health, Geelong, VIC, 3220, Australia; Murdoch Children's Research Institute, Parkville, Victoria, 3052, Australia; Barwon Health, Geelong, Victoria 3220, Australia. Electronic address:

Background: Murine studies demonstrate that maternal prenatal gut microbiota influences brain development and behaviour of offspring. No human study has related maternal gut microbiota to behavioural outcomes during early life. This study aimed to evaluate relationships between the prenatal faecal microbiota, prenatal diet and childhood behaviour.

Methods: A sub-cohort of 213 mothers and 215 children were selected from a longitudinal pre-birth cohort. Maternal prenatal exposure measures collected during the third trimester included the faecal microbiota (generated using 16S rRNA amplicon sequencing), and dietary intake. The behavioural outcome used the Childhood Behaviour Checklist at age two. Models were adjusted for prenatal diet, smoking, perceived stress, maternal age and sample batch.

Findings: We found evidence that the alpha diversity of the maternal faecal microbiota during the third trimester of pregnancy predicts child internalising behaviour at two years of age (-2·74, (-4·71, -0·78), p = 0·01 (Wald test), R=0·07). Taxa from butyrate-producing families, Lachnospiraceae and Ruminococcaceae, were more abundant in mothers of children with normative behaviour. A healthy prenatal diet indirectly related to decreased child internalising behaviours via higher alpha diversity of maternal faecal microbiota.

Interpretation: These findings support animal studies showing that the composition of maternal prenatal gut microbiota is related to offspring brain development and behaviour. Our findings highlight the need to evaluate potential impacts of the prenatal gut microbiota on early life brain development.

Funding: This study was funded by the National Health and Medical Research Council of Australia (1082307, 1147980), Murdoch Children's Research Institute, Barwon Health and Deakin University.
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http://dx.doi.org/10.1016/j.ebiom.2021.103400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190443PMC
June 2021

Infant pacifier sanitization and risk of challenge-proven food allergy: A cohort study.

J Allergy Clin Immunol 2021 05 30;147(5):1823-1829.e11. Epub 2021 Mar 30.

Murdoch Children's Research Institute, Parkville, Australia; Allergy and Lung Health Unit, School of Population and Global Health, University of Melbourne, Parkville, Australia; Neuroepidemiology Research Group, Florey Institute for Neuroscience and Mental Health, Parkville, Australia. Electronic address:

Background: Environmental microbial exposure plays a role in immune system development and susceptibility to food allergy.

Objective: We sought to investigate whether infant pacifier use during the first postnatal year, with further consideration of sanitization, alters the risk of food allergy by age 1 year.

Methods: The birth cohort recruited pregnant mothers at under 28 weeks' gestation in southeast Australia, with 894 families followed up when infants turned 1 year. Infants were excluded if born under 32 weeks, with a serious illness, major congenital malformation, or genetic disease. Questionnaire data, collected at recruitment and infant ages 1, 6, and 12 months, included pacifier use and pacifier sanitization (defined as the joint exposure of a pacifier and cleaning methods). Challenge-proven food allergy was assessed at 12 months.

Results: Any pacifier use at 6 months was associated with food allergy (adjusted odds ratio, 1.94; 95% CI, 1.04-3.61), but not pacifier use at other ages. This overall association was driven by the joint exposure of pacifier-antiseptic use (adjusted odds ratio, 4.83; 95% CI, 1.10-21.18) compared with no pacifier use. Using pacifiers without antiseptic at 6 months was not associated with food allergy. Among pacifier users, antiseptic cleaning was still associated with food allergy (adjusted odds ratio, 3.56; 95% CI, 1.18-10.77) compared with no antiseptic use. Furthermore, persistent and repeated antiseptic use over the first 6 months was associated with higher food allergy risk (P = .029).

Conclusions: This is the first report of a pacifier-antiseptic combination being associated with a higher risk of subsequent food allergy. Future work should investigate underlying biological pathways.
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http://dx.doi.org/10.1016/j.jaci.2021.01.032DOI Listing
May 2021

The incidence of acute respiratory infection in Indonesian infants and association with vitamin D deficiency.

PLoS One 2021 23;16(3):e0248722. Epub 2021 Mar 23.

Department of Paediatrics, Murdoch Children's Research Institute, Royal Children's Hospital, University of Melbourne, Melbourne, Australia.

Background: Vitamin D deficiency has been associated with acute respiratory infection (ARI) in early life, but this has not been evaluated in Indonesia. We aimed to determine the incidence of ARI in Indonesian infants, and to evaluate the association with vitamin D deficiency.

Methods: From 23 December 2015 to 31 December 2017, we conducted a community-based prospective cohort study in Yogyakarta province. We enrolled 422 pregnant women and followed their infants from birth until 12 months of age for ARI episodes. Vitamin D status was measured at birth and at age six months. We performed Cox proportional hazard regression analysis to evaluate the association between vitamin D deficiency and pneumonia incidence.

Results: At study completion, 95% (400/422) of infants retained with a total of 412 child years of observation (CYO). The incidence of all ARI and of WHO-defined pneumonia was 3.89 (95% CI 3.70-4.08) and 0.25 (95% CI 0.21-0.30) episodes per CYO respectively. Vitamin D deficiency at birth was common (90%, 308/344) and associated with more frequent episodes of ARI non-pneumonia (adjusted odds ratio 4.48, 95% CI:1.04-19.34). Vitamin D status at birth or six months was not associated with subsequent pneumonia incidence, but greater maternal sun exposure during pregnancy was associated with a trend to less frequent ARI and pneumonia in infants.

Conclusion: ARI, pneumonia, and vitamin D deficiency at birth were common in Indonesian infants. Minimising vitamin D deficiency at birth such as by supplementation of mothers or safe sun exposure during pregnancy has the potential to reduce ARI incidence in infants in this setting.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248722PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987198PMC
October 2021

Children of Asian ethnicity in Australia have higher risk of food allergy and early-onset eczema than those in Singapore.

Allergy 2021 10 7;76(10):3171-3182. Epub 2021 Apr 7.

Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore City, Singapore.

Background: In Western countries, Asian children have higher food allergy risk than Caucasian children. The early-life environmental exposures for this discrepancy are unclear. We aimed to compare prevalence of food allergy and associated risk factors between Asian children in Singapore and Australia.

Methods: We studied children in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort (n = 878) and children of Asian ancestry in the HealthNuts cohort (n = 314). Food allergy was defined as a positive SPT ≥3 mm to egg or peanut AND either a convincing history of IgE-mediated reaction at 18 months (GUSTO) or a positive oral food challenge at 14-18 months (HealthNuts). Eczema was defined as parent-reported doctor diagnosis.

Results: Food allergy prevalence was 1.1% in Singapore and 15.0% in Australia (P<0.001). Egg introduction was more often delayed (>10 months) in Singapore (63.5%) than Australia (16.3%; P<0.001). Prevalence of early-onset eczema (<6 months) was lower in Singapore (8.4%) than Australia (30.5%) (P<0.001). Children with early-onset eczema were more likely to have food allergy than those without eczema in Australia [aOR 5.11 (2.34-11.14); P<0.001] and Singapore [aOR4.00 (0.62-25.8); P = 0.145].

Conclusions: Among Asian children, prevalence of early-onset eczema and food allergy was higher in Australia than Singapore. Further research with larger sample sizes and harmonized definitions of food allergy between cohorts is required to confirm and extend these findings. Research on environmental factors influencing eczema onset in Australia and Singapore may aid understanding of food allergy pathogenesis in different parts of the world.
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http://dx.doi.org/10.1111/all.14823DOI Listing
October 2021

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.

BMJ Open 2021 03 19;11(3):e041984. Epub 2021 Mar 19.

Murdoch Children's Research Institute,Royal Children's Hospital, University of Melbourne, Parkville, Victoria, Australia

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.
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http://dx.doi.org/10.1136/bmjopen-2020-041984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986776PMC
March 2021

Reflection on modern methods: building causal evidence within high-dimensional molecular epidemiological studies of moderate size.

Int J Epidemiol 2021 07;50(3):1016-1029

This commentary provides a practical perspective on epidemiological analysis within a single high-dimensional study of moderate size to consider a causal question. In this setting, non-causal confounding is important. This occurs when a factor is a determinant of outcome and the underlying association between exposure and the factor is non-causal. That is, the association arises due to chance, confounding or other bias rather than reflecting that exposure and the factor are causally related. In particular, the influence of technical processing factors must be accounted for by pre-processing measures to remove artefact or to control for these factors such as batch run. Work steps include the evaluation of alternative non-causal explanations for observed exposure-disease associations and strategies to obtain the highest level of causal inference possible within the study. A systematic approach is required to work through a question set and obtain insights on not only the exposure-disease association but also the multifactorial causal structure of the underlying data where possible. The appropriate inclusion of molecular findings will enhance the quest to better understand multifactorial disease causation in modern observational epidemiological studies.
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http://dx.doi.org/10.1093/ije/dyaa174DOI Listing
July 2021

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

J Immunol 2021 02 11;206(4):874-882. Epub 2021 Jan 11.

Murdoch Children's Research Institute, Royal Children's Hospital, University of Melbourne, Parkville, Victoria 3052, Australia;

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 ( = 1074), recruited using an unselected antenatal sampling frame, 158 mother-infant pairs had data on the following: 1) 25-hydroxyvitamin D (25(OH)D) 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 (CD4CD45RA FOXP3 naive Treg, and CD4CD45RA FOXP3 activated Treg [aTreg]); and 3) possible confounders, including maternal personal UV radiation. Multiple regression analyses were used. The median 25(OH)D was 85.4 and 50.7 nmol/l for maternal and CB samples, respectively. Higher maternal 25(OH)D 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)D 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)D 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)D are warranted.
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http://dx.doi.org/10.4049/jimmunol.2000515DOI Listing
February 2021

Objectively measured physical activity and all cause mortality: A systematic review and meta-analysis.

Prev Med 2021 02 7;143:106356. Epub 2020 Dec 7.

Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, UK; Murdoch Children's Research Institute, Melbourne, Australia. Electronic address:

Current physical activity recommendations have been based on evidence from systematic reviews of questionnaire-based data. Questionnaire-based physical activity data are subject to both random and non-random error. If the estimated association between physical activity and health outcomes was different when a more accurate, objective measure was used, this would have important health policy implications for physical activity. We conducted a systematic review and meta-analysis of published cohort studies that investigated the association between an objective measure of physical activity and all cause mortality. We searched PubMed, Scopus, Embase, Cochrane library, and SPORTDiscus for prospective cohort studies that examined the association between objectively measured (accelerometer, pedometer, or doubly labeled water method) physical activity and mortality in adults aged≥18 years, of either sex. Summary hazard ratios and 95% confidence interval [CI]s were computed using random-effects models. Thirty-three articles from 15 cohort studies were identified that together ascertained 3903 deaths. The mean years of follow-up ranged from 2.3-14.2 years. Individuals in the highest category of light, moderate-to-vigorous, and total physical activity had 40% (95%CI 20% to 55%), 56% (95%CI 41% to 67%), and 67% (95%CI 57% to 75%), respectively, lower risk for mortality compared to individuals in the lowest category of light, moderate-to-vigorous, and total physical activity. The summary hazard ratio for objectively measured physical activity and all cause mortality is lower than previously estimated from questionnaire based studies. Current recommendations for physical activity that are based on subjective measurement may underestimate the true reduction in mortality risk associated with physical activity.
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http://dx.doi.org/10.1016/j.ypmed.2020.106356DOI Listing
February 2021

The prevalence and determinants of vitamin D deficiency in Indonesian infants at birth and six months of age.

PLoS One 2020 5;15(10):e0239603. Epub 2020 Oct 5.

Department of Paediatrics and Murdoch Childrens Research Institute, Royal Children's Hospital, University of Melbourne, Melbourne, Victoria, Australia.

Background: Vitamin D deficiency in infants has been associated with an increased risk of a number of diseases but there are limited data on the prevalence and determinants of vitamin D deficiency from tropical settings with high infant morbidity and mortality.

Objective: To determine the prevalence and determinants of vitamin D deficiency in infants at birth and at six months of age in Yogyakarta province, Indonesia.

Design: Serum vitamin D of eligible infants was measured in cord blood at birth and at six months of age. Factors associated with vitamin D deficiency (serum 25-hydroxyvitamin D <50 nmol/L) were collected prospectively monthly from birth and concentrations measured by liquid chromatography-tandem mass spectrometry. Independent risk factors were identified by multiple logistic regression.

Results: Between December 2015 to December 2017, 350 maternal-newborn participants were recruited and followed up. Vitamin D deficiency was detected in 90% (308/344) of cord blood samples and 13% (33/255) of venous blood samples at six months. Longer time outdoors (≥2 hours per day) and maternal multivitamin intake containing vitamin D during pregnancy were protective against vitamin D deficiency at birth (AOR: 0.10, 95% CI: 0.01-0.90 and AOR: 0.21, 95% CI: 0.06-0.68, respectively). Risk factors for vitamin D deficiency at six months included lower cumulative skin-sun exposure score (AOR: 1.12, 95% CI: 1.04-1.20), severe vitamin D deficiency at birth (AOR: 7.73, 95% CI: 1.20-49.60) and exclusive breastfeeding (AOR: 2.64, 95% CI: 1.07-6.49) until six months. Among exclusively breast fed (EBF) infants, a higher skin-sun exposure score was associated with reduced vitamin D deficiency risk.

Conclusion: In equatorial regions, the role of 'safe' morning sun exposure in infants and mothers in populations with medium to dark brown skin pigmentation and effective interventions to prevent vitamin D deficiency in newborns and EBF infants, need further consideration and evaluation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239603PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7535980PMC
November 2020

Burden of infection in Australian infants.

J Paediatr Child Health 2021 02 23;57(2):204-211. Epub 2020 Sep 23.

Population Health and Infection and Immunity Themes, Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia.

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.
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http://dx.doi.org/10.1111/jpc.15174DOI Listing
February 2021

The Interplay Between Eczema and Breastfeeding Practices May Hide Breastfeeding's Protective Effect on Childhood Asthma.

J Allergy Clin Immunol Pract 2021 02 16;9(2):862-871.e5. Epub 2020 Sep 16.

Murdoch Children's Research Institute, Parkville, VIC, Australia; Department of Pediatrics, University of Melbourne, Parkville, VIC, Australia.

Background: Longer duration of breastfeeding may be protective against asthma. However, early manifestations of allergic disease, such as eczema, are risk factors for asthma and can influence the duration of breastfeeding, and hence, may bias observable associations.

Objective: To examine the relationship between breastfeeding ever and duration and the development of asthma and allergic asthma phenotypes, stratified by a diagnosis of eczema during or after the breastfeeding period.

Methods: A total of 3663 children participated in the 6-year-old follow-up of the HealthNuts study, a population-based, longitudinal study of allergic diseases in Australia. At age 1 year, breastfeeding and eczema data were collected and at age 6 years, information on wheeze, medication use, and parental report of doctor-diagnosed asthma were obtained, both via questionnaire. Skin prick test responses to food and aeroallergens at age 6 years further distinguished asthmatic children into allergic and nonallergic phenotypes.

Results: Breastfeeding initiation was not associated with current asthma at age 6 years (adjusted odds ratio, 0.76; 95% CI, 0.45-1.29) when compared with never breastfeeding. Results were similar for length of exclusiveness and overall duration of breastfeeding, and allergic and nonallergic asthma phenotypes. However, increased duration of breastfeeding among children without eczema in infancy was associated with reduced odds of asthma (per month increase, adjusted odds ratio, 0.98; 95% CI, 0.95-1.0; P = .05), which equates to 0.86 (95% CI, 0.74-1.0) reduced odds of asthma for a 6-month increase in breastfeeding. This association was not apparent in children who were diagnosed with eczema during breastfeeding (adjusted odds ratio, 1.03; 95% CI, 0.98-1.08; P = .3).

Conclusions: Longer duration of breastfeeding was associated with a reduced odds of asthma among children without eczema in the first year of life; this association was masked before stratification by eczema in infancy. Future studies examining breastfeeding practices and the risk of allergic outcomes in later childhood need to consider the presence of early-life allergic manifestations impacting on breastfeeding behavior.
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http://dx.doi.org/10.1016/j.jaip.2020.09.006DOI Listing
February 2021

Community-Based Adverse Food Reactions and Anaphylaxis in Children with IgE-Mediated Food Allergy at Age 6 Years: A Population-Based Study.

J Allergy Clin Immunol Pract 2020 Nov - Dec;8(10):3515-3524. Epub 2020 Jul 21.

Murdoch Children's Research Institute, Melbourne, VIC, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, VIC, Australia; Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia. Electronic address:

Background: Few studies have investigated adverse food reactions among food-allergic children in a population-based sample, which is critical for the development of evidence-based management strategies.

Objective: We aimed to evaluate the frequency, characteristics, and risk factors for adverse food reactions, including anaphylaxis, among food-allergic 6-year-old-children using the population-based HealthNuts study.

Methods: The HealthNuts study of 5276 infants (1-year-old) followed them up at age 6 years (84.4% participated). A total of 260 children with IgE-mediated food allergy who completed a questionnaire detailing recent adverse food reactions were included in this analysis.

Results: Among food-allergic children, 44.6% (95% CI, 38.6%-50.8%) reported an adverse food reaction in the last 12 months and 10.8% (95% CI, 7.5%-15.2%) reported an anaphylactic reaction, although only half of these were recognized as anaphylaxis by parents. Adrenaline autoinjectors were used in 25% (4 of 16) of recognized anaphylaxis episodes. Nut allergy was associated with a reduced risk of having an adverse reaction (adjusted odds ratio, 0.3; 95% CI, 0.1-0.7). There were trends that adverse reactions were more likely in children with at least 1 parent born in Asia compared with both parents born in Australia (adjusted odds ratio, 1.9; 95% CI, 0.9-3.9), and in children with 3 or more food allergies compared with children with a single food allergy (adjusted odds ratio, 1.8; 95% CI, 0.9-3.5).

Conclusions: Adverse food reactions occurred in almost half of all food-allergic 6-year-old children and anaphylaxis occurred in 1 in 10 children over a 12-month period. Anaphylaxis was poorly recognized and adrenaline autoinjectors were not used appropriately. Improved regular education on the prevention, recognition, and management of adverse food reactions is urgently needed.
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http://dx.doi.org/10.1016/j.jaip.2020.07.008DOI Listing
May 2021

High Prudent diet factor score predicts lower relapse hazard in early multiple sclerosis.

Mult Scler 2021 06 23;27(7):1112-1124. Epub 2020 Jul 23.

Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.

Background: Dietary patterns and their association with subsequent clinical course have not been well studied in early multiple sclerosis (MS).

Objectives: To describe dietary patterns in people in 5 years following first clinical demyelination and assess associations with MS conversion and relapse.

Methods: This study included baseline food frequency questionnaire dietary intake (entry to the Ausimmune Study) and 5-year follow-up; iterated principal factor analysis was applied. MS conversion and relapse risks were assessed by Cox proportional hazards models, adjusted for age, sex, study site, education, body mass index (BMI), smoking and omega-3 supplement use.

Results: In cases with a first clinical diagnosis of central nervous system (CNS) demyelination, we identified three major dietary patterns, 'Prudent', 'High-Vegetable' and 'Mixed', explaining 43%, 37% and 24% of diet variance in dietary intake, respectively. Fruits, vegetables, fish, wholegrains and nuts loaded highly on the Prudent pattern, starchy vegetables and legumes on the High-Vegetable pattern, and meats and alcohol on the Mixed pattern. Diet factor scores were not associated with MS conversion risk. Those with baseline Prudent scores above the median had significantly lower relapse risk (adjusted hazard ratio = 0.54, 95% confidence interval (CI) 0.37, 0.81) with some evidence of a plateau effect.

Conclusion: Prudent diet factor score above the median was prospectively associated with lower relapse risk in the 5 years following the first clinical demyelinating event.
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http://dx.doi.org/10.1177/1352458520943087DOI Listing
June 2021

No cashew allergy in infants introduced to cashew by age 1 year.

J Allergy Clin Immunol 2021 01 18;147(1):383-384. Epub 2020 Jul 18.

Murdoch Children's Research Institute, Parkville, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Australia; Department of Allergy and Immunology, Royal Children's Hospital, Parkville, Australia. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2020.07.003DOI Listing
January 2021

Associations between grass pollen exposures and in early life with food allergy in 12-month-old infants.

Int J Environ Health Res 2020 Jul 17:1-11. Epub 2020 Jul 17.

School of Psychology and Public Health, La Trobe University, Melbourne, Australia.

Birth during pollen seasons may influence food allergy risk but no study has assessed pollen exposure. Using the HealthNuts population-based cohort of 5276 infants, we assessed grass pollen exposures, and up to the first 6 months of life, on hen's egg, sesame and peanut allergy outcomes at 12 months. Cumulative pollen exposure in the first 7 days of life increased risk of peanut sensitization aMOR (adjusted multinomial odds ratio) = 1.21 (95% CI: 1.01-1.44). Exposure between first 4-6 months of life increased risk of hen's egg aMOR = 1.02 (95% CI: 1.004-1.04) and sensitization to all foods aMOR = 1.02 (95% CI: 1.003-1.04). Grass pollen exposure was associated with food challenge diagnosed food allergy, but only among infants with a maternal history of food allergy. Exposure to grass pollen in the period and infancy may be important but more studies are needed to replicate these findings.
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http://dx.doi.org/10.1080/09603123.2020.1793920DOI Listing
July 2020

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

Epigenetics 2020 12 27;15(12):1361-1369. Epub 2020 Jun 27.

Murdoch Children's Research Institute , Parkville, Australia.

Methylation levels at the hypoxia-inducible factor 3α gene () in blood have been linked to body mass index (BMI) in adults. Despite evidence implicating in angiogenesis and metabolism, no studies have examined links between methylation in early life and cardiovascular health. Here, we investigated the relationship between 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 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 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 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, 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 methylation and cardiovascular health more generally.
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http://dx.doi.org/10.1080/15592294.2020.1781027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678916PMC
December 2020

Plasma metabolomic profiles associated with infant food allergy with further consideration of other early life factors.

Prostaglandins Leukot Essent Fatty Acids 2020 08 25;159:102099. Epub 2020 May 25.

Murdoch Children's Research Institute, Royal Children's Hospital, University of Melbourne, Parkville, VIC, Australia; Florey Institute for Neuroscience and Mental Health, Parkville, VIC, Australia. Electronic address:

Background: Fatty acids have been implicated in early life immune development. Food allergy provides a clear phenotype of early allergic disease. Fish oil and vitamin D have immune-modulating properties. We aimed to identify the metabolomic profile of (i) infant food allergy and (ii) factors linked to food allergy in past studies such as fish oil supplementation and serum 25OHD3 levels in early life.

Methods: NMR was used to quantify 73 metabolites in plasma of 1 year old infants from the Barwon Infant Study (n=485). Logistic regression models were used to examine associations between infant metabolome and food allergy in infants. Linear regression models were used to describe associations between maternal fish oil supplementation and 25OHD3 levels with infant metabolites.

Results: A higher linoleic acid: total fatty acid (FA) ratio and phenylalanine level were associated with higher odds of food allergy. Antenatal fish oil supplementation was positively associated with docosahexaenoic acid (DHA) and omega-3 related metabolite levels. Postnatal 25OHD3 levels at 1 year of age were positively associated with several FA measures and creatinine and inversely with the saturated FA: total FA ratio. Only the postnatal 25OHD3 patterns persisted after adjustment for multiple comparisons.

Conclusions: Infants with food allergy had altered fatty acid profiles at one year. Fish oil supplementation in pregnancy was associated with higher DHA and omega-3 related metabolites at 1 year of age. Associations were modest and the most robustly altered metabolomic profiles were with postnatal 25OHD3 levels.
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http://dx.doi.org/10.1016/j.plefa.2020.102099DOI Listing
August 2020

The ENDpoiNTs Project: Novel Testing Strategies for Endocrine Disruptors Linked to Developmental Neurotoxicity.

Int J Mol Sci 2020 Jun 1;21(11). Epub 2020 Jun 1.

Evolutionary Biology Centre, Uppsala University, 75236 Uppsala, Sweden.

Ubiquitous exposure to endocrine-disrupting chemicals (EDCs) has caused serious concerns about the ability of these chemicals to affect neurodevelopment, among others. Since endocrine disruption (ED)-induced developmental neurotoxicity (DNT) is hardly covered by the chemical testing tools that are currently in regulatory use, the Horizon 2020 research and innovation action ENDpoiNTs has been launched to fill the scientific and methodological gaps related to the assessment of this type of chemical toxicity. The ENDpoiNTs project will generate new knowledge about ED-induced DNT and aims to develop and improve in vitro, in vivo, and in silico models pertaining to ED-linked DNT outcomes for chemical testing. This will be achieved by establishing correlative and causal links between known and novel neurodevelopmental endpoints and endocrine pathways through integration of molecular, cellular, and organismal data from in vitro and in vivo models. Based on this knowledge, the project aims to provide adverse outcome pathways (AOPs) for ED-induced DNT and to develop and integrate new testing tools with high relevance for human health into European and international regulatory frameworks.
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http://dx.doi.org/10.3390/ijms21113978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312023PMC
June 2020

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

Neurotoxicology 2020 09 30;80:20-28. Epub 2020 May 30.

Murdoch Children's Research Institute, Royal Children's Hospital Melbourne, University of Melbourne, Victoria, Australia; School of Medicine, Deakin University, Victoria, Australia; Barwon Health, Victoria, Australia.

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.
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http://dx.doi.org/10.1016/j.neuro.2020.05.006DOI Listing
September 2020

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

Environ Int 2020 06 28;139:105700. Epub 2020 Apr 28.

Murdoch Children's Research Institute, Royal Children's Hospital, University of Melbourne, Melbourne, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia. Electronic address:

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.
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http://dx.doi.org/10.1016/j.envint.2020.105700DOI Listing
June 2020

Perinatal photoperiod and childhood cancer: pooled results from 182,856 individuals in the international childhood cancer cohort consortium (I4C).

Chronobiol Int 2020 07 1;37(7):1034-1047. Epub 2020 Apr 1.

Institute and Policlinic for Occupational Medicine, Environmental Medicine and Prevention Research, University Hospital of Cologne , Cologne, Germany.

Experimental evidence suggests that perinatal light imprinting of circadian clocks and systems may affect downstream physiology and cancer risk in later life. For humans, the predominant circadian stimulus is the daily light-dark cycle. Herein, we explore associations between perinatal photoperiod characteristics (photoperiod: duration of daylight as determined by time-of-year and location) and childhood cancer risk. We use pooled data on 182,856 mothers and babies from prospective birth cohorts in six countries (Australia, Denmark, Israel, Norway, UK, USA) within the International Childhood Cancer Cohort Consortium (I4C). Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In line with predicted differential dose-responses, restricted cubic splines indicate a potential non-linear, non-monotonic relationship between perinatal mean daily photoperiod (0-24 h) and childhood cancer risk. In a restricted analysis of 154,121 individuals who experienced third trimester photoperiods exclusively within the 8-16-h range, the relative risk of developing childhood cancer decreased by 9% with every hour increase in third trimester mean daily photoperiod [HR: 0.91 (95%CIs: 0.84-0.99)]. In conclusion, in this first study of perinatal photoperiod and childhood cancer, we detected an inverse ["protective"] linear association between third trimester mean daily photoperiod and childhood cancer risk in the 8-16-h set of the total study population. Limited statistical power impeded the investigation of risks with individuals exposed to more extreme photoperiods. Future studies are needed to confirm differential photoperiod-associated risks and further investigations into the hypothesized circadian imprinting mechanism are warranted.
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http://dx.doi.org/10.1080/07420528.2020.1740724DOI Listing
July 2020

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

Nat Commun 2020 03 24;11(1):1452. Epub 2020 Mar 24.

The Murdoch Children's Research Institute, Parkville, Victoria, 3052, Australia.

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.
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http://dx.doi.org/10.1038/s41467-020-14552-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093478PMC
March 2020
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