<b>BACKGROUND: </b>Reduced intake of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) may be a contributing factor to the increasing prevalence of wheezing disorders. We assessed the effect of supplementation with n-3 LCPUFAs in pregnant women on the risk of persistent wheeze and asthma in their offspring.<b>METHODS: </b>We randomly assigned 736 pregnant women at 24 weeks of gestation to receive 2.4 g of n-3 LCPUFA (fish oil) or placebo (olive oil) per day. Their children formed the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) cohort and were followed prospectively with extensive clinical phenotyping. Neither the investigators nor the participants were aware of group assignments during follow-up for the first 3 years of the children's lives, after which there was a 2-year follow-up period during which only the investigators were unaware of group assignments. The primary end point was persistent wheeze or asthma, and the secondary end points included lower respiratory tract infections, asthma exacerbations, eczema, and allergic sensitization.<b>RESULTS: </b>A total of 695 children were included in the trial, and 95.5% completed the 3-year, double-blind follow-up period. The risk of persistent wheeze or asthma in the treatment group was 16.9%, versus 23.7% in the control group (hazard ratio, 0.69; 95% confidence interval [CI], 0.49 to 0.97; P=0.035), corresponding to a relative reduction of 30.7%. Prespecified subgroup analyses suggested that the effect was strongest in the children of women whose blood levels of eicosapentaenoic acid and docosahexaenoic acid were in the lowest third of the trial population at randomization: 17.5% versus 34.1% (hazard ratio, 0.46; 95% CI, 0.25 to 0.83; P=0.011). Analyses of secondary end points showed that supplementation with n-3 LCPUFA was associated with a reduced risk of infections of the lower respiratory tract (31.7% vs. 39.1%; hazard ratio, 0.75; 95% CI, 0.58 to 0.98; P=0.033), but there was no statistically significant association between supplementation and asthma exacerbations, eczema, or allergic sensitization.<b>CONCLUSIONS: </b>Supplementation with n-3 LCPUFA in the third trimester of pregnancy reduced the absolute risk of persistent wheeze or asthma and infections of the lower respiratory tract in offspring by approximately 7 percentage points, or one third. (Funded by the Lundbeck Foundation and others; ClinicalTrials.gov number, NCT00798226 .).
BACKGROUND: Long-term follow-up was completed in 84 mother-infant pairs of 118 women who completed a randomized controlled trial of prenatal supplementation with EPA- or DHA-rich fish oil or soy oil placebo. The goal of this study was to determine whether prenatal omega-3 fatty acid supplementation protects offspring against development of early childhood allergies.
METHODS AND FINDINGS: Assessment of childhood allergic/atopic disease among offspring at age 36 months was performed by maternal interview using the National Health Interview Survey (NHIS) questions for childhood digestive allergies, wheezing, eczema or skin allergy, and respiratory allergy. Multiple logistic regressions examined the association between prenatal supplementation and childhood outcomes, adjusted for covariates. Eczema was reported in 26/84 (31%) of offspring at age 36 months, and was significantly more prevalent in the omega-3 supplementation groups vs. placebo: EPA 13/31 (41.9%); DHA 10/26 (38.5%); placebo 3/27 (11.1%), p=0.019. Compared to placebo, EPA and DHA were associated with ≥5 times risk of offspring eczema [odds ratios (ORs): EPA 5.8 (95% CI 1.4-23.3); DHA 5.0 (95% CI 1.2-21.0)]. After adjusting for other potential risk factors (race, birth weight, vaginal/Cesarean delivery, and maternal eczema) the magnitudes of association for omega-3 supplementation increased: EPA OR 8.1 (95% CI 1.4-45.6); DHA OR 9.6 (95% CI 1.6-58.5). Maternal eczema was also significantly associated with offspring eczema in the adjusted model: OR 10.8 (95% CI 2.1-54.3).
CONCLUSION: Contrary to our hypothesis, acids supplementation compared to soy oil was associated with a substantial increase in risk of childhood eczema. This association was not observed on childhood respiratory or digestive outcomes. It is unclear if these findings were driven by unfavorable effects of omega-3s, or whether there may have been unanticipated protective effects of the soy-based placebo with regards to eczema.
ANTECEDENTES: Existe un creciente interés en el papel potencial de los anti-inflamatorios n-3 ácidos grasos poliinsaturados (AGPI n-3) en la prevención de la enfermedad alérgica.
OBJETIVO: Nuestro objetivo era determinar si los suplementos de la dieta materna con n-3 PUFAs durante el embarazo puede modificar la respuesta inmune en los bebés.
MÉTODOS: En un estudio aleatorizado, controlado con 98 mujeres atópicas, embarazadas recibieron aceite de pescado (3,7 g AGPI n-3 por dia) o placebo de 20 semanas de gestación hasta el parto. Neonatales niveles de ácidos grasos poliinsaturados y la respuesta inmunológica a los alérgenos se midieron en el nacimiento.
Resultados: Ochenta y tres mujeres completaron el estudio. Administración de suplementos de aceite pescado (n = 40) logró proporciones significativamente más altos de n-3 PUFAs en recién nacidos membranas de los eritrocitos (media + / - DS, 17,75% + / - 1,85% como porcentaje de ácidos grasos totales) en comparación con el grupo control (n = 43, 13,69% + / - 1,22%, p <.001). Todas las citocinas neonatal (IL-5, IL-13, IL-10, e IFN-gamma) (respuestas a todos los alergenos) tiende a ser menor en el grupo de aceite de pescado (estadísticamente significativa sólo para la IL-10 en respuesta al gato). Aunque este estudio no fue diseñado para analizar los resultados clínicos, hemos observado que los niños en el grupo de aceite de pescado eran 3 veces menos probabilidades de tener una prueba cutánea positiva al huevo a 1 año de vida (odds ratio, 0,34; 95% intervalo de confianza, 0,11 a 1,02, p = 0,055). Aunque no hubo diferencia en la frecuencia de la dermatitis atópica menos 1 año de edad, los bebés en el grupo de aceite de pescado también tenían enfermedad mucho menos grave (odds ratio, 0,09; 95% intervalo de confianza, 0,01 a 0,94, P = 0,045).
CONCLUSIONES: Estos datos sugieren una posible reducción de la alergia infantil posterior después de la suplementación materna con ácidos grasos poliinsaturados. Más detallados estudios de seguimiento se requieren en grandes cohortes para establecer la robustez de estos resultados y determinar su importancia en relación a más largo plazo la modificación de las enfermedades alérgicas en los niños.
BACKGROUND AND OBJECTIVE: Evidence from randomized controlled trials in early infancy suggest that prenatal supplementation with Ω-3 (n-3) long-chain polyunsaturated fatty acids (LCPUFA) reduces the incidence of allergic disease characterized by an immunoglobulin E (IgE) response. We aimed to determine whether protective effects were evident in the 6-year-old offspring of women supplemented with n-3 rich fish oil during pregnancy. METHODS: Six-year follow-up of children [n = 706) with a family history of allergic disease from the Docosahexaenoic Acid to Optimize Mother Infant Outcome (DOMInO) trial. Women were randomly allocated to receive n-3 LCPUFA-rich fish oil capsules (800 mg/d docosahexaenoic acid DHA and 100mg/d eicosapentaenoic acid) or vegetable oil capsules [without n-3 LCPUFA). Allergic disease symptoms including eczema, wheeze, rhinitis, and rhino-conjunctivitis, were assessed using the International Study of Asthma and Allergies in Childhood questionnaire and sensitization to allergens was measured by skin prick test. RESULTS: There was no difference in the percentage of children with any igE-associated allergic disease between the n-3 LCPUFA and control groups (116/367 [31.5%] vs 106/336 [31.5%]; adjusted relative risk, 1.04; 95% confidence interval, 0.82-1.33; P = .73). There was a reduction in the percentage of children sensitized to house dust mite Dermatophagoides farinae (49/367 [13.4%] vs 68/336 [20.3%]; adjusted relative risk, 0.67, 95% confidence interval, 0.44-1.00; P = .0495). CONCLUSIONS: Prenatal n-3 LCPUFA supplementation did not reduce IgE-associated allergic disease at 6 years of age. Secondary outcomes were suggestive of a protective effect of the intervention on the incidence of D. farinae sensitization.
We have previously reported a protective effect of maternal omega-3 long-chain polyunsaturated fatty acids (ω-3 LCPUFA) supplementation in pregnancy and lactation on IgE-associated eczema and food allergy in the infant during the first year of life. Here we investigate whether the effects of the LCPUFA supplementation on IgE-associated diseases last up to 2 yr of age and assess the relationship between plasma proportions of ω-3 PUFAs and the frequency and severity of infant allergic disease. 145 pregnant women, at risk of having an allergic infant, were randomized to daily supplementation with 1.6 g eicosapentaenoic acid (EPA) and 1.1 g docosahexaenoic acid (DHA) or placebo starting in the 25th gestational week and continuing through 3.5 months of breastfeeding. Clinical examinations, skin prick tests and analysis of maternal and infant plasma phospholipid fatty acids and infant specific IgE were performed. No difference in the prevalence of allergic symptoms was found between the intervention groups. The cumulative incidence of IgE-associated disease was lower in the ω-3-supplemented group (6/54, 13%) compared with the placebo group (19/62, 30%, p=0.01). Higher maternal and infant proportions of DHA and EPA were associated with lower prevalence of IgE associated disease (p=0.01-0.05) in a dose-dependent manner. Higher maternal and infant proportions of DHA and EPA were found if the infants presented none, when compared with multiple allergic symptoms, (p<0.05) regardless of sensitization. In summary, the ω-3 supplementation offered no obvious preventive effect on the prevalence of clinical symptoms of allergic disease, but the decrease in cumulative incidence of IgE-associated disease seen during the first year still remained until 2 yr of age. Furthermore, high proportions of DHA and EPA in maternal and infant plasma phospholipids were associated with less IgE-associated disease and a reduced severity of the allergic phenotype.
