Maternal fish oil supplementation in pregnancy: A 12 year follow-up of a randomised controlled test

A number of trials have been undertaken to assess whether the intake of omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) during pregnancy can influence the neurological development of the offspring, yet no consensus from these trials has been reached. We aimed to investigate the long-term effects (12 years) of fish oil supplementation in pregnancy on neurodevelopment, including cognition, language and fine motor skills. In a follow up of a previously published randomised controlled trial of 98 pregnant women, their children were assessed at 12 years of age using a battery of neurodevelopmental assessments. Fifty participants were assessed at 12 years, with 25 participant’s mothers receiving fish oil supplementation, and 25 receiving control capsules. There were no significant differences for any of the assessment measures completed. Our data indicate that fish oil supplementation during pregnancy does not influence the cognition, language or fine motor skills of children in late primary school (12 years of age)

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Achieving definitive results in long-chain polyunsaturated fatty acid supplementation trials of term infants: factors for consideration

Numerous randomized controlled trials (RCTs) have been undertaken to determine whether supplementation with long-chain polyunsaturated fatty acids (LCPUFAs) in infancy would improve the developmental outcomes of term infants. The results of such trials have been thoroughly reviewed with no definitive conclusion as to the efficacy of LCPUFA supplementation. A number of reasons for the lack of conclusive findings in this area have been proposed. This review examines such factors with the aim of determining whether an optimal method of investigation for RCTs of LCPUFA supplementation in term infants can be ascertained from previous research. While more research is required to completely inform a method that is likely to achieve definitive results, the findings of this literature review indicate future trials should investigate the effects of sex, genetic polymorphisms, the specific effects of LCPUFAs, and the optimal tests for neurodevelopmental assessment. The current literature indicates a docosahexaenoic acid dose of 0.32%, supplementation from birth to 12months, and a total sample size of at least 286 (143 per group) should be included in the methodology of future trials

Voice problems in school-aged children following very preterm birth

Background and objective Very preterm children may be at risk of voice abnormalities (dysphonia). Risk factors previously identified in extremely preterm children include female gender, multiple intubations, complicated intubation and very low birth weight. This study sought to identify the prevalence of dysphonia in very preterm children, at school age. Methods Children born between 23 and 32 weeks’ gestation were included in this prospective observational study. Participants were randomly selected from a sample stratified by gestational age and number of intubations, and were aged between 5 and 12 years at the time of assessment. Clinical voice assessments were conducted by a speech pathologist, and a diagnosis of dysphonia was made based on the presence and severity of disturbance to the voice. Retrospective chart review identified medical and demographic characteristics. Results 178 participants were assessed. The prevalence of dysphonia in this cohort was 61%. 31% presenting with significant dysphonia, that is, voice disturbance of greater than mild in severity. Female gender (p=0.009), gestational age (p=0.031) and duration of intubation (p=0.021) were significantly associated with dysphonia although some preterm children with dysphonia were never intubated. Conclusions Significant voice abnormalities were observed in children born at up to 32 weeks’ gestation, with intubation a major contributing factor

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

Autism Spectrum Disorder (ASD) is the collective term for neurodevelopmental disorders characterised by qualitative impairments in social interaction and 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, and recent reports suggest a prevalence of ASD of 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, 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 summarise and evaluate 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

Teachers’ experiences of inclusion of children with developmental disabilities across the early years of school

This study reports data from teachers in regular school classrooms on their experiences of inclusion for 143 young children with disabilities. The children were recruited from early intervention programs and their experiences in regular schools were tracked across three years, from a Preparatory year to Year 2 of school. Across the three years, the children’s teachers rated the child’s placement in their classroom as appropriate and that resources and supports available to support inclusion were generally adequate. Teachers perceived a range of benefits for the child, peers, and themselves. However, teachers also identified significant challenges including time pressures and increased responsibilities; and various behavioural and developmental concerns that impacted on all children’s learning in the classroom. The various challenges deserve continued attention for successful inclusive practice