Paediatric Acute-onset Neuropsychiatric Syndrome (PANS) and intravenous immunoglobulin (IVIG): comprehensive open-label trial in ten children.

BACKGROUND: Treatment with intravenous immunoglobulin (IVIG) in children with Paediatric Acute-onset Neuropsychiatric Syndrome (PANS) has for many years been used on clinical indications, but the research evidence for its efficacy is insufficient. METHODS: Open-label prospective in-depth trial including ten children (median age 10.3 years) with PANS, who received IVIG treatment 2 g/kg monthly for three months. Primary outcomes were changes in symptom severity and impairment from baseline to first and second follow-up visits one month after first and one month after third treatment, using three investigator-rated scales: Paediatric Acute Neuropsychiatric Symptom (PANS) scale, Clinical Global Impression - Severity and Improvement (CGI-S and CGI-I) scales. Secondary outcomes reported here were changes in Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) scores, and side effects. RESULTS: All ten children received three treatments at one-month intervals according to study plan. From baseline to second follow-up marked reductions were seen in mean total PANS scale scores (p = .005), and CGI-S scores (p = .004). CGI-I ratings showed much to very much global improvement (mean CGI-I 1.8). Nine children had clinical response defined as > 30% reduction in PANS Scale scores. Improvements were also noted for CY-BOCS scores (p = .005), and in school attendance. Three children suffered moderate to severe temporary side effects after the first treatment, and the remaining seven had mild to moderate side effects. Side effects were much less severe after second and third treatments. CONCLUSIONS: Considerable and pervasive improvements in symptoms and clinical impairments were seen in these ten children after three monthly IVIG treatments. Moderate to severe transient side effects occurred in three cases. TRIAL REGISTRATION: EudraCT no. 2019-004758-27, Clinicaltrials.gov no. NCT04609761, 05/10/2020.

High levels of omega-3 fatty acids in milk from omega-3 fatty acid-supplemented mothers are related to less immunoglobulin E-associated disease in infancy.

AIM: We previously reported a protective effect of maternal omega-3 fatty acid supplements on the development of immunoglobulin E (IgE)-associated disease in infancy. This study assessed omega-3 long-chain polyunsaturated fatty acids (LCPUFA) in maternal milk in relation to omega-3 LCPUFA supplementation and the development of allergic disease in their infants. METHODS: This study randomised 95 pregnant women at risk of having an allergic infant, to daily supplements of 2.6 g omega-3 LCPUFA or a placebo of 2.7 g soya bean oil from gestational week 25 until 3 months of lactation. Breast milk samples were collected as colostrum, at one and 3 months. Milk fatty acids were related to allergic outcome in the infants at 24 months. RESULTS: Omega-3 milk fatty acids were higher in women who received omega-3 supplements than the placebo group (p < 0.01). Higher proportions of milk eicosapentaenoic acid and docosahexaenoic acid and a lower arachidonic/eicosapentaenoic acid ratio were associated with an absence of IgE-associated disease in the infants. None of the children developed IgE-associated atopic eczema above a level of 0.83 mol% eicosapentaenoic acid in colostrum. [Correction added on 7 July 2016, after online publication: In the preceding sentence, the correct word should be "above" instead of "below" and this has been amended in this current version.] CONCLUSION: High omega-3 LCPUFA milk levels in mothers who received omega-3 LCPUFA supplements were related to fewer allergies in their children.

Allergic disease in infants up to 2 years of age in relation to plasma omega-3 fatty acids and maternal fish oil supplementation in pregnancy and lactation.

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.

Th1 and Th2 chemokines, vaccine-induced immunity, and allergic disease in infants after maternal ω-3 fatty acid supplementation during pregnancy and lactation.

We investigated whether the previously reported preventive effect of maternal ω-3 fatty acid supplementation on IgE-associated allergic disease in infancy may be mediated by facilitating a balanced circulating Th2/Th1 chemokine profile in the infant. Vaccine-induced immune responses at 2 y of age were also evaluated. Pregnant women, at risk of having an allergic infant, were randomized to daily supplementation with 1.6 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid or placebo from the 25th gestational week through 3.5 mo of breastfeeding. Infant plasma was analyzed for chemokines (cord blood, 3, 12, 24 mo) and anti-tetanus and anti-diphtheria IgG (24 mo). High Th2-associated CC-chemokine ligand 17 (CCL17) levels were associated with infant allergic disease (p < 0.05). In infants without, but not with, maternal history of allergy, the ω-3 supplementation was related to lower CCL17/CXC-chemokine ligand 11 (CXCL11) (Th2/Th1) ratios (p < 0.05). Furthermore, in nonallergic, but not in allergic infants, ω-3 supplementation was linked with higher Th1-associated CXCL11 levels (p < 0.05), as well as increased IgG titers to diphtheria (p = 0.01) and tetanus (p = 0.05) toxins. Thus, the prospect of balancing the infant immune system toward a less Th2-dominated response, by maternal ω-3 fatty acid supplementation, seems to be influenced by allergic status.

Fish oil supplementation in pregnancy and lactation may decrease the risk of infant allergy.

UNLABELLED: Maternal intake of omega-3 (omega-3) polyunsaturated fatty acids (PUFAs) during pregnancy has decreased, possibly contributing to a current increased risk of childhood allergy. AIM: To describe the effects of maternal omega-3 long-chain PUFA supplementation during pregnancy and lactation on the incidence of allergic disease in infancy. METHODS: One hundred and forty-five pregnant women, affected by allergy themselves or having a husband or previous child with allergies, were included in a randomized placebo-controlled trial. Daily maternal supplementation with either 1.6 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid or placebo was given from the 25(th) gestational week to average 3-4 months of breastfeeding. Skin prick tests, detection of circulating specific immunoglobulin E (IgE) antibodies and clinical examinations of the infants were performed. RESULTS: The period prevalence of food allergy was lower in the omega-3 group (1/52, 2%) compared to the placebo group (10/65, 15%, p < 0.05) as well as the incidence of IgE-associated eczema (omega-3 group: 4/52, 8%; placebo group: 15/63, 24%, p < 0.05). CONCLUSION: Maternal omega-3 fatty acid supplementation may decrease the risk of food allergy and IgE-associated eczema during the first year of life in infants with a family history of allergic disease.

The effects of omega-3 fatty acid supplementation in pregnancy on maternal eicosanoid, cytokine, and chemokine secretion.

The incidence of allergic diseases has increased, and a relation between allergy and dietary fatty acids has been proposed. Modulation of the maternal immune function during pregnancy may have an impact on future clinical outcomes in the child. The aim of this study was to determine the effects of omega (omega)-3 long-chain polyunsaturated fatty acids (LCPUFA) supplementation during pregnancy on the plasma fatty acid composition in relation to the maternal immune function. Pregnant women with allergic disease in their immediate family were supplemented daily with 2.7 g omega-3 LCPUFA (n = 70) or 2.8 g soybean oil as placebo (n = 75) from the 25th gestational week. The proportions of eicosapentaenoic acid and docosahexaenoic acid in plasma/serum phospholipids increased in the omega-3-supplemented group, whereas arachidonic acid decreased during intervention. Lipopolysaccharide-induced prostaglandin E2 secretion from whole blood culture supernatants (n = 59) decreased in a majority of the omega-3-supplemented mothers (18 of 28, p = 0.002). The decreased prostaglandin E2 production was more pronounced among nonatopic than atopic mothers. The lipopolysaccharide-induced cytokine and chemokine secretion was not affected. Our results indicate that omega-3 LCPUFA supplementation during the last trimester may dampen certain immune responses involved in allergic inflammation.