Suzanne Meldrum

Postnatal Fish Oil Supplementation in High-Risk Infants to Prevent Allergy: Randomized Controlled Trial

BACKGROUND AND OBJECTIVE: Relative deficiency of dietary omega 3 polyunsaturated fatty acids (n-3 PUFA) has been implicated in the rising allergy prevalence in Westernized countries. Fish oil supplementation may provide an intervention strategy for primary allergy prevention. The objective of this study was to assess the effect of fish oil n-3 PUFA supplementation from birth to 6 months of age on infant allergic disease. METHODS: In a double-blind randomized controlled trial, 420 infants at high atopic risk received a daily supplement of fish oil containing 280 mg docosahexaenoic acid and 110 mg eicosapentaenoic acid or a control (olive oil), from birth to age 6 months. PUFA levels were measured in 6-month-old infants’ erythrocytes and plasma and their mothers’ breast milk. Eczema, food allergy, asthma and sensitization were assessed in 323 infants for whom clinical follow-up was completed at 12 months of age. RESULTS: At 6 months of age, infant docosahexaenoic acid and eicosapentaenoic acid levels were significantly higher (both P < .05) and erythrocyte arachidonic acid levels were lower (P = .003) in the fish oil group. Although n-3 PUFA levels at 6 months were associated with lower risk of eczema (P = .033) and recurrent wheeze (P = .027), the association with eczema was not significant after multiple comparisons and there was no effect of the intervention per se on the primary study outcomes. Specifically, between-group comparisons revealed no differences in the occurrence of allergic outcomes including sensitization, eczema, asthma, or food allergy. CONCLUSIONS: Postnatal fish oil supplementation improved infant n-3 status but did not prevent childhood allergic disease.

Fish oil supplementation in early infancy modulates developing infant immune responses

Maternal fish oil supplementation during pregnancy has been associated with altered infant immune responses and a reduced risk of infant sensitization and eczema.

The relationship between maternal folate status in pregnancy, cord blood folate levels, and allergic outcomes in early childhood

To cite this article: Dunstan JA, West C, McCarthy S, Metcalfe J, Meldrum S, Oddy WH, Tulic MK, D’Vaz N, Prescott SL. The relationship between maternal folate status in pregnancy, cord blood folate levels, and allergic outcomes in early childhood. Allergy 2012; 67: 50–57.

Effects of high-dose fish oil supplementation during early infancy on neurodevelopment and language: a randomised controlled trial.

n-3 Long-chain PUFA (LC-PUFA) intake during infancy is important for neurodevelopment; however, previous studies of n-3 LC-PUFA supplementation have been inconclusive possibly due to an insufficient dose and limited methods of assessment. The present study aimed to evaluate the effects of direct supplementation with high-dose fish oil (FO) on infant neurodevelopmental outcomes and language. In the present randomised, double-blind, placebo-controlled trial, 420 healthy term infants were assigned to receive a DHA-enriched FO supplement (containing at least 250 mg DHA/d and 60 mg EPA/d) or a placebo (olive oil) from birth to 6 months. Assessment occurred at 18 months via the Bayley Scales of Infant and Toddler Development (3rd edition; BSID-III) and the Child Behavior Checklist. Language assessment occurred at 12 and 18 months via the Macarthur-Bates Communicative Development Inventory. The FO group had significantly higher erythrocyte DHA (P = 0·03) and plasma phospholipid DHA (P = 0·01) levels at 6 months of age relative to placebo. In a small subset analysis (about 40% of the total population), children in the FO group had significantly higher percentile ranks of both later developing gestures at 12 and 18 months (P = 0·007; P = 0·002, respectively) and the total number of gestures (P = 0·023; P = 0·006, respectively). There was no significant difference between the groups in the standard or composite scores of the BSID-III. The results suggest that improved postnatal n-3 LC-PUFA intake in the first 6 months of life using high-dose infant FO supplementation was not beneficial to global infant neurodevelopment. However, some indication of benefits to early communicative development was observed.

Associations between maternal antioxidant intakes in pregnancy and infant allergic outcomes.

Antioxidant intakes in pregnancy may influence fetal immune programming and the risk of allergic disease. We investigated associations between maternal intakes of β-carotene, vitamin C, vitamin E, copper and zinc, and infant allergic outcomes. Antioxidant intakes of pregnant women (n = 420) assessed prospectively by a food frequency questionnaire, were examined in relation to allergic outcomes at 1 year of age (n = 300). The main relationships with allergic outcomes were seen with dietary vitamin C and copper. Specifically, higher maternal dietary vitamin C intake was associated with a reduced risk of any diagnosed infant allergic disease and wheeze. After adjustment for potential confounders the relationship with wheeze remained statistically significant. There was also an inverse linear relationship between vitamin C and food allergy. Higher dietary copper intake was associated with reduced risk of eczema, wheeze and any allergic disease. The relationship with wheeze and any allergic disease remained statistically significant in multivariate analysis, and there was also an inverse linear relationship between copper and food allergy. However, these relationships were only seen for nutrients present in food. There were no relationships between β-carotene, vitamin E or zinc and any allergic outcomes. In summary, this study suggests that maternal diet of fresh foods rich in vitamin C is associated with reduced risk of infant wheeze, and that copper intake is associated with reduced risk of several allergic outcomes.

25-hydroxyvitamin D3 status is associated with developing adaptive and innate immune responses in the first 6 months of life

Vitamin D (25[OH]D3) status in early life has been linked to the risk of allergic disease in multiple observational studies. While immunomodulating properties are well recognized, there are few longitudinal studies of 25(OH)D3 status, immune function and allergic disease in infants.

Allergic disease in the first year of life is associated with differences in subsequent neurodevelopment and behaviour

BACKGROUND Recent trials suggest a link between neuropsychological function, atopy and allergic disease particularly in early childhood; however the nature of this association remains unclear. AIMS To investigate the relationship between early allergic disease and sensitisation at 12 months of age and neurodevelopmental outcomes at 18 months. STUDY DESIGN Linear or binary logistic regression analysis was used to determine whether allergic diseases or sensitization at 12 months of age was a significant predictor of neurodevelopmental test scores at the 18 months. SUBJECTS Infants with a maternal history of allergic disease (n=324). OUTCOME MEASURES Allergic outcomes at 12 months of age included allergen sensitisation, eczema, IgE-mediated and food allergy, and neurodevelopmental outcomes at 18 included the Bayley Scales of Infant Toddler Development III Edition, the Achenbach Child Behaviour Checklist and the Macarthur Scales of Infant Toddler Development. RESULTS Children with any diagnosed allergic disease at 12 months had evidence of reduced motor scores (p=.016), and this was most apparent for a diagnosis of eczema (p=.007). Non-IgE mediated food allergy was significantly positively associated with problem Internalising Behaviours (p=.010), along with a trend for effects on the Social-Emotional composite score for IgE-Mediated food allergies (p=.052). Allergic sensitisation was not independently associated with any effects on neurodevelopmental outcomes. CONCLUSION This study provides evidence that an allergic phenotype in infancy is associated with effects on neurodevelopment. Further research is required to investigate the nature of this relationship.

Autism spectrum disorder in children born preterm—role of exposure to perinatal inflammation

Autism Spectrum Disorder (ASD) is the collective term for neurodevelopmental disorders characterized by qualitative impairments in social interaction, communication, and a restricted range of activities and interests. Many countries, including Australia, have reported a dramatic increase in the number of diagnoses over the past three decades, with current prevalence of ASD at 1 in every 110 individuals (~1%). The potential role for an immune-mediated mechanism in ASD has been implicated by several studies, and some evidence suggests a potential link between prenatal infection-driven inflammation and subsequent development of ASD. Furthermore, a modest number of contemporary studies have reported a markedly increased prevalence of ASD in children born preterm, who are at highest risk of exposure to perinatal inflammation. However, the mechanisms that underpin the susceptibility to infection-driven inflammation during pregnancy and risk of preterm birth, and how these intersect with the subsequent development of ASD in the offspring, is not understood. This review aims to summarize and discuss the potential mechanisms and evidence for the role of prenatal infection on the central nervous system, and how it may increase the susceptibility for ASD pathogenesis in children born preterm.

Voice abnormalities at school age in children born extremely preterm

BACKGROUND AND OBJECTIVES: Voice abnormality is a frequent finding in school age children born at <25 weeks’ gestation in Western Australia. The objective of this study was to determine the frequency of voice abnormality, voice-related quality of life, and demographic and intubation factors in this population. METHODS: Survivors <25 weeks’ gestational age in Western Australia born from 1996 to 2004 were included. Voice assessments (auditory perceptual assessment scale and Pediatric Voice Handicap Index) were carried out by speech pathologists. Intubation history was obtained by retrospective chart review. RESULTS: Of 251 NICU admissions, 154 (61%) survived. Exclusions were based on severe disability (11) or distant residence (13). Of 70 assessed, 67 completed assessments, 4 (6%) were in the normal range and 39 (58%) showed moderate-severe hoarseness. Simultaneous modeling of demographic and intubation characteristics showed an increased odds of moderate-severe voice disorder for children who had more than 5 intubations (odds ratio 6.96, 95% confidence interval 2.07–23.40, P = .002) and for girls relative to boys (odds ratio 3.46, 95% confidence interval 1.12–10.62, P = .030). Tube size and duration of intubation were not significant in the multivariable model. Median scores of parent-reported voice quality of life on the Pediatric Voice Handicap Index were markedly different for preterm (22) and term (3) groups, P < .001. CONCLUSIONS: Voice disorders in this population were much more frequent than expected. Further studies are required to assess voice across a broader range of gestational ages, and to investigate voice-protective strategies in infants requiring multiple episodes of intubation.

The Infant Fish Oil Supplementation Study (IFOS): Design and research protocol of a double-blind, randomised controlled n−3 LCPUFA intervention trial in term infants

STUDY DESIGN The Infant Fish Oil Supplementation Study is a double-blind randomised controlled trial investigating whether the incidence of allergic disease can be reduced and developmental outcomes enhanced through supplementation with omega-3 fatty acids. Infants at high risk of developing allergic disease will be randomised to receive either fish oil or olive oil supplements until 6 months of age and followed up at six postnatal clinic visits to assess allergy outcomes and infant neurodevelopment. INTERVENTION Study groups to consist of a treatment group allocated to receive 650 mg of fish oil daily (250-280 mg docosahexaenoic acid and at least 60 mg eicosapentaenoic acid and a placebo group (olive oil) from birth to 6 months of age. OUTCOMES Allergy outcomes will be assessed by clinical history, clinical assessments and allergen skin prick tests at the 12, 30 and 60 month visits. Neurodevelopmental assessments to be conducted at 18 months, and language questionnaires at 12, 18 and 30 months. Samples will be collected from mothers antenatally, from infants at birth, and at clinic visits from 6 months onwards for immunological assessments. Fatty acid composition to be measured in erythrocytes and plasma (at birth and after the supplementation period) to assess the effect of the intervention on fatty acid status. Information on medical history, diet and other lifestyle factors at an antenatal clinic visit and postnatal clinic visits will also be collected. CONCLUSION This study is designed to examine clinically relevant effects of a novel, non-invasive and potentially low cost approach to reduce the incidence of allergic disease and facilitate neurodevelopment during early childhood.