Karel Duchén

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

Maternal intake of omega‐3 (ω‐3) polyunsaturated fatty acids (PUFAs) during pregnancy has decreased, possibly contributing to a current increased risk of childhood allergy.

Human milk polyunsaturated long-chain fatty acids and secretory immunoglobulin A antibodies and early childhood allergy

The possible protective effect of breast milk against atopic manifestations in infancy, i.e. atopic eczema and food allergy, has been controversial for the last decades. Besides the methodological problems, differences in the composition of human milk could explain these controversies. The aim of this study was to investigate the composition of polyunsaturated fatty acids (PUFA) and secretory immunoglobulin A (S‐IgA) levels to food proteins (ovalbumin and β‐lactoglobulin) and an inhalant allergen (cat) in milk from mothers of allergic and non‐allergic children. Blood samples were obtained at birth and at 3 months from 120 children. Skin prick tests were performed at 6, 12 and 18 months, and the development of atopic diseases was assessed in the children. Breast milk samples were collected from their mothers at birth and monthly during the lactation period. Milk PUFA composition was measured by gas chromatography, and enzyme‐linked immunosorbent assay (ELISA) was used to measure total S‐IgA, anti‐cat S‐IgA, anti‐ovalbumin S‐IgA, and anti‐β‐lactoglobulin S‐IgA. Allergic disease developed in 44/120 children (22/63 children of allergic mothers and 22/57 children of non‐allergic mothers). Lower levels of eicosapentaenoic acid, C20:5 n‐3 (EPA), docosapentaenoic acid C22:5n‐3 (DPA), and docosatetraenoic acid C22:4 n‐6 (DHA) (p < 0.05 for all) were found in mature milk from mothers of allergic as compared to milk from mothers of non‐allergic children. The total n‐6 : total n‐3 and the arachidonic acid, C20:4 n‐6 (AA) : EPA ratios were significantly lower in transitional and mature milk from mothers of allergic children, as compared to milk from mothers of non‐allergic children. The PUFA levels in serum of allergic and non‐allergic children were largely similar, except for higher levels of C22:4 n‐6 and C22:5 n‐6 (p < 0.05 for both) and a higher AA : EPA ratio in serum phospholipids in the former group (p < 0.05). Changes in the levels of milk PUFA were reflected in changes in PUFA serum phospholipids, particularly for the n‐6 PUFA. The AA : EPA ratio in maternal milk was related, however, to the AA : EPA only in serum from non‐allergic children, while this was not the case in allergic children. The levels of total S‐IgA, anti‐cat S‐IgA, anti‐ovalbumin S‐IgA, and anti‐β‐lactoglobulin S‐IgA in milk from mothers of allergic, as compared to non‐allergic, children were similar through the first 3 months of lactation. Low levels of n‐3 PUFA in human milk, and particularly a high AA : EPA ratio in maternal milk and serum phospholipids in the infants, were related to the development of symptoms of allergic disease at 18 months of age. The milk PUFA composition influenced the composition of PUFA in serum phospholipids of the children. We also showed that the lower levels of colostral anti‐ovalbumin S‐IgA and lower total S‐IgA in mature milk from atopic mothers did not influence the development of allergic disease in the children up to 18 months of age. The findings indicate that low α‐linolenic acid, C18:3 n‐3 (LNA) and n‐3 long‐chain polyunsaturated fatty acids (LCP) 20–22 carbon chains, but not the levels of S‐IgA antibodies to allergens, are related to the development of atopy in children.

Atopic Sensitization during the First Year of Life in Relation to Long Chain Polyunsaturated Fatty Acid Levels in Human Milk

The levels of the long chain polyunsaturated n-6 and n-3 fatty acides (PUFA) were studied in colostrum and mature milk of 29 atopic and 29 nonatopic mothers and related to sensitization in their babies during the first 12 mo of life. The levels of α-linolenic acid (LNA) were lower (0.96 versus 1.23 weight percentage, p < 0.01) and the levels of dihomo-γ-linoleic acid were higher (0.36 versus 0.31 weight percentage, p < 0.05) in mature milk from mothers of atopic babies (n = 24) compared with mothers of nonatopic babies (n = 34). The total n-3 levels and the ratio of n-6 PUFA/n-3 PUFA were similar in colostrum of all mothers and then decreased significantly in mature milk (p < 0.001), particularly in milk given to atopic babies. The levels of the n-6 fatty acids arachidonic acid, C22:4, and C22:5 n-6 correlated in milk samples from nonatopic mothers (r = 0.61-0.97, p < 0.05 to p < 0.001) but were largely absent in colostrum and mature milk from atopic mothers. In contrast, LNA and eicosapentaenoic levels correlated in colostrum from the atopic mothers (r = 0.61-0.88) regardless of atopic sensitization in the infants, whereas LNA correlated to C20:4 n-3 in colostrum from nonatopic mothers of nonatopic infants. Furthermore, the levels of the n-3 fatty acid C20:4 n-3 correlated significantly to all n-6 fatty acids, except linoleic acid (r = 0.64-0.79, all p < 0.01) in mature milk from nonatopic mothers of nonsensitized children. Low levels of LNA and total n-3 long chain polyunsaturated fatty acids, in mature milk from the mothers, appear to be associated with atopic sensitization early in life, as well as disturbed relationships between the n-3 fatty acid 20:4 and the n-6 fatty acids particularly in mature milk. On the other hand, disturbed relationships within the individual fatty acids in the n-6 series in human milk reflected the atopic status in the mothers. The variations in the lipid composition of human milk could in part explain some of the controversies regarding the protective effects of breast-feeding against allergy.

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.

To cite this article: Furuhjelm C, Warstedt K, Fagerås M, Fälth‐Magnusson K, Larsson J, Fredriksson M, Duchén K. 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. Pediatr Allergy Immunol 2011; 22: 505–514.

Fatty acid composition in colostrum and mature milk from non‐atopic and atopic mothers during the first 6 months of lactation

The fatty acid composition of total lipids was analysed in colostrum and mature human milk samples obtained at 1, 3, 4 and 6 months from 17 non‐atopic and at 1 and 3 months from 17 atopic mothers. The relative levels of linoleic acid and α‐linolenic acid increased up to 3 months after delivery and then declined. In contrast, the levels of their metabolites were higher in colostrum than in mature milk. The levels of dihomo‐γ‐linolenic acid, eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid were all lower in atopic than non‐atopic mothers in milk samples obtained after 1 month of lactation (all p < 0:05). The ratio of total n‐6 to n‐3 long‐chain polyunsaturated fatty acids (LCP) in milk at 1 and 3 months was higher in atopic than non‐atopic mothers (all p < 0:05). Lower levels of the monounsaturated fatty acids (MUFA) were also observed in atopic mothers, as compared to non‐atopic mothers. In the non‐atopic mothers, the levels of individual n‐6 LCP correlated and also correlated with n‐3 LCP in colostrum and early mature milk (r= 0:60‐0.92, all p < 0:01). These correlations within n‐6 and between n‐6 and n‐3 LCP were mostly absent in atopic mothers. The findings suggest that the LCP metabolism in human milk is disturbed in atopic mothers, as indicated by the lower relative levels of some LCP at 1 month, higher ratios of n‐6 to n‐3 LCP and poor correlations between the levels of the various compounds during the first 3 months of lactation.

Exclusive breastfeeding and risk of atopic dermatitis in some 8300 infants

Earlier studies on breastfeeding and atopy in infants have yielded contradictory results. We examined the relationship between exclusive breastfeeding and atopic dermatitis (AD) in a cohort of infants born between 1 October 1997 and 1 October 1999 in south‐east Sweden. We evaluated the risk of AD ‘at least once’ or ‘at least three times’ during the first year of life in relation to duration of exclusive breastfeeding: <4 months (short exclusive breastfeeding; SEBF) vs. ≥4 months. All data were obtained through questionnaires. Of 8346 infants with breastfeeding data, 1943 (23.3%) had suffered from AD during the first year of life. Duration of exclusive breastfeeding was not associated with lower risk of AD (p = 0.868). SEBF did not influence the risk of any AD (OR = 1.03; 95% CI OR = 0.91–1.17; p = 0.614) or AD at least three times (OR = 0.97; 95% CI OR = 0.81–1.16; p = 0.755) during the first year of life. Adjustment for confounders did not change these point estimates. Neither was there any link between SEBF and risk of AD among infants with a family history of atopy [adjusted odds ratio (AOR) = 1.16; 95% CI AOR = 0.90–1.48; p = 0.254]. Furred pets at home were linked to a lower risk of AD both among infants with a family history of atopy (AOR = 0.76; 95% CI AOR = 0.60–0.96; p = 0.021) and among infants with no such history (AOR = 0.79; 95% CI AOR = 0.69–0.90; p < 0.001). Infants with no family history of atopy were less prone to develop AD if parents smoked (AOR = 0.76; 95% CI AOR = 0.61–0.95; p = 0.016). This study indicates that exclusive breastfeeding does not influence the risk of AD during the first year of life, while presence of furred pets at home seems to be negatively associated with AD.

Noonan and cardio-facio-cutaneous syndromes: two clinically and genetically overlapping disorders

Background: Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFC) are related disorders associated with disrupted RAS/RAF/MEK/ERK signalling. NS, characterised by facial dysmorphism, congenital heart defects and short stature, is caused by mutations in the genes PTPN11, SOS1, KRAS and RAF1. CFC is distinguished from NS by the presence of ectodermal abnormalities and more severe mental retardation in addition to the NS phenotype. The genetic aetiology of CFC was recently assigned to four genes: BRAF, KRAS, MEK1 and MEK2. Methods: A comprehensive mutation analysis of BRAF, KRAS, MEK1, MEK2 and SOS1 in 31 unrelated patients without mutations in PTPN11 is presented. Results: Mutations were identified in seven patients with CFC (two in BRAF, one in KRAS, one in MEK1, two in MEK2 and one in SOS1). Two mutations were novel: MEK1 E203Q and MEK2 F57L. The SOS1 E433K mutation, identified in a patient diagnosed with CFC, has previously been reported in patients with NS. In one patient with NS, we also identified a mutation, BRAF K499E, that has previously been reported in patients with CFC. We thus suggest involvement of BRAF in the pathogenesis of NS also. Conclusions: Taken together, our results indicate that the molecular and clinical overlap between CFC and NS is more complex than previously suggested and that the syndromes might even represent allelic disorders. Furthermore, we suggest that the diagnosis should be refined to, for example, NS–PTPN11-associated or CFC–BRAF-associated syndromes after the genetic defect has been established, as this may affect the prognosis and treatment of the patients.

EPA supplementation improves teacher-rated behaviour and oppositional symptoms in children with ADHD.

Aim:  Measure efficacy of eicosapentaenoic acid (EPA) in children with attention deficit hyperactivity disorder (ADHD).

Breastfeeding, very long polyunsaturated fatty acids (PUFA) and IQ at 6 1/2 years of age.

AIM Breastfeeding seems to be favorable for cognitive development. Could levels of polyunsaturated fatty acids (PUFA) explain this? METHODS Pregnant mothers were recruited consecutively at maternity care centres. PUFA were analysed in colostrum and breast milk at 1 and 3 mo. The product-precursor ratios of n-6+n-3 PUFA were examined as measures of activity in respective steps in the fatty acid metabolic chain. Also, the quotient between DHA and AA was analysed. The children were tested with the full WISC-III at 6.5 y. RESULTS First, the influence of length of breastfeeding was analysed by multiple regression together with relevant cofactors (except for PUFA). In the best models, 46% of the variation in total IQ was explained. Length of breastfeeding contributed significantly to total IQ (beta = 0.228, p = 0.021), verbal IQ (beta = 0.204, p = 0.040) and performance IQ (beta = 0.210, p = 0.056). There were no significant single correlations between PUFA and measures of cognitive development. However, in multiple regression analysis of colostrum, significant beta-coefficients were found for steps 4+5 in the fatty acid metabolic chain (beta = 0.559, p = 0.002). If length of breastfeeding and gestation week were added to steps 4+5, this three-factor model could explain 67% of the variation of total IQ. Introducing length of breastfeeding and gestation week together with the quotient DHA/AA (beta = 0.510, p < 0.001) yielded a three-factor model, which explained 76% of the variation in total IQ. CONCLUSION Our findings could be interpreted as supporting the importance of high levels of PUFA for cognitive development. However, the sample is small and the results must be interpreted with caution.

Polyunsaturated n-3 fatty acids and the development of atopic disease

The relationship between polyunsaturated long-chain fatty acids and atopy has been discussed for decades. Higher levels of the essential fatty acids linoleic acid and α-linolenic acid and lower levels of their longer metabolites in plasma phospholipids of atopic as compared to nonatopic individuals have been reported by several, but not all, studies. Largely similar findings have been reported in studies of cell membranes from immunological cells from atopics and nonatopics despite differences in methodology, study groups, and definitions of atopy. An imbalance in the metabolism of the n−6 fatty acids, particularly arachidonic acid and dihomo-γ-linolenic acid, leading to an inappropriate synthesis of prostaglandin (PG) E2 and PGE1 was hypothesized early on but has not been corroborated. The fatty acid composition of human milk is dependent on the time of lactation not only during a breast meal but also the time of the day and the period of lactation. This explains the discrepancies in reported findings regarding the relationship between milk fatty acids and atopic disease in the mother. Prospective studies show disturbances in both the n−6 and n−3 fatty acid composition between milk from atopic and nonatopic mothers. Only the composition of long-chain polyunsaturated n−3 fatty acids was related to atopic development in the children, however. A relationship between lower levels of n−3 fatty acids, particularly eicosapentaenoic acid (20∶5 n−3), and early development of atopic disease is hypothesized.