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.

BACKGROUND: Maternal fish oil supplementation during pregnancy has been associated with altered infant immune responses and a reduced risk of infant sensitization and eczema. OBJECTIVE: To examine the effect of early postnatal fish oil supplementation on infant cellular immune function at 6 months of age in the context of allergic disease. METHODS: In a double-blind randomized controlled trial (ACTRN12606000281594), 420 infants of high atopic risk received fish oil [containing 280 mg docosahexaenoic acid (DHA) and 110 mg eicosapentanoic acid (EPA)] or control oil daily from birth to 6 months. One hundred and twenty infants had blood collected at 6 months of age. Fatty acid levels, induced cytokine responses, T cell subsets and monocyte HLA-DR expression were assessed at 6 months of age. Infant allergies were assessed at 6 and 12 months of age. RESULTS: DHA and EPA levels were significantly higher in the fish oil group and erythrocyte arachidonic acid (AA) levels were lower (all P < 0.05). Infants in the fish oil group had significantly lower IL-13 responses (P = 0.036) to house dust mite (HDM) and higher IFNγ (P = 0.035) and TNF (P = 0.017) responses to phytohaemaglutinin (PHA). Infants with relatively high DHA levels had lower Th2 responses to allergens including lower IL-13 to ß-lactoglobulin (BLG) (P = 0.020), and lower IL-5 to BLG (P = 0.045). CONCLUSIONS AND CLINICAL RELEVANCE: Postnatal fish oil supplementation increased infant n-3 polyunsaturated fatty acid (PUFA) levels and associated with lowered allergen-specific Th2 responses and elevated polyclonal Th1 responses. Our results add to existing evidence of n-3 PUFA having immunomodulatory properties that are potentially allergy-protective.

Determinants of DHA levels in early infancy: differential effects of breast milk and direct fish oil supplementation.

INTRODUCTION: Although omega (n)-3 long-chain polyunsaturated fatty acids (LCPUFA), particularly docosahexaenoic acid (DHA), intakes are important during infancy, the optimal method of increasing infant status remains unclear. We hypothesized that high-dose infant fish oil supplementation would have greater relative effects upon n-3 LCPUFA status at six months of age than breast milk fatty acids. PATIENTS AND METHODS: Infants (n=420) were supplemented daily from birth to six months with fish oil or placebo. In a subset of infants, LCPUFA levels were measured in cord blood, breast milk and in infant blood at 6 months. RESULTS: DHA levels increased in the fish oil group relative to placebo (p<05). Breast milk DHA was the strongest predictor of infant erythrocyte DHA levels (p=<001). This remained significant after adjustment for cord blood DHA, supplementation group and adherence. CONCLUSION: In this cohort, breast milk DHA was a greater determinant of infant erythrocyte n-3 LCPUFA status, than direct supplementation with fish oil.

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.

The effect of 50 Hz external electrical interference on implanted cardiac pacemakers.

The effects of injected 50 Hz alternating current on the function of cardiac pacemakers has been observed in 18 patients with implanted unipolar VVI units. Current, in the range 0-600 microA was applied via electrodes attached to the patients' upper body and feet and fed from a specially designed current injection unit at the bedside. Most implanted pacemakers reverted to interference mode in the current range 29-250 microA. At current levels just below the reversion current all units developed irregular and inappropriate pacing. This current level was pacemaker dependent and varied in the range 27-246 microA. The total reversion current depended on the location of the injecting electrodes and on the patients' posture. The sensitivity of the units to injected interference was increased by deep inspiration. Temporary pacing catheters fitted to an additional ten patients were used to monitor the interference voltage which would be sensed by an implanted unit. This voltage was similarly dependent on patient posture and on deep respiration. Current injection has proved to be a safe, controllable and reproducible method of testing the sensitivity of implanted pacemakers to 50 Hz external interference.

The effect of power frequency high intensity electric fields on implanted cardiac pacemakers.

Thirty-five patients fitted with 16 different pacemaker models (from 6 manufacturers) were exposed to 50 Hz electric fields up to a maximum of 20 kV/m. Four different response patterns were encountered: (1) normal sensing and pacing in all Medtronic and some Vitatron units; (2) reversion to the fixed (interference) rate in all Telectronics, all Pacesetter, some Vitatron and CPI units; (3) slow and irregular pacing in one CPI and in all Cordis units; (4) mixed behavior over a critical range of field strengths in which slow and irregular pacing preceded reversion to fixed-rate, in some Telectronics and Pacesetter units. The field strengths required to induce such behavior varied from unit to unit and from model to model, with Telectronics being the most sensitive. In general, the interference threshold depended on the magnitude and distribution of induced body current relative to the pacemaker as well as field strength and thus varied with patient height, build and posture. While only a small proportion of pacemaker patients are likely to encounter electric fields strong enough to interfere with pacemaker behavior, this possible hazard should be recognized.

Effects of high-intensity power-frequency electric fields on implanted modern multiprogrammable cardiac pacemakers.

The effect on an implanted, multiprogrammable pacemaker of power-frequency (50 Hz) electric fields up to an intensity (unperturbed value measured at 1.7 m) of 20 kV/m were assessed in ten paced patients. Radiotelemetric monitoring of the electrocardiogram allowed supervision of the electrocardiogram throughout exposure to the alternating electric field. Displacement body currents of up to 300µA were achieved depending on the position and height of the patient. None of the pacemakers was inhibited, triggered or reverted to fixed rate operation during the exposure. The programmable functions, programmability or output characteristics were not affected. Small changes in cardiac rate and rhythm elicited the correct pacemaker responses. Unlike earlier models of pacemaker, this modern implanted pacemaker, which represents `the state of the art', is not affected by 50 Hz electric fields likely to be encountered when standing underneath power lines.