Long chain polyunsaturated fatty acids in chronic childhood disorders: panacea, promising, or placebo.
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Publications and source records attributed to C Agostoni.
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OBJECTIVE: To determine whether supplementation of infant formula milk with long chain polyunsaturated fatty acids (LCPUFAs) influences blood pressure in later childhood. DESIGN: Follow up of a multicentre, randomised controlled trial. SETTING: Four study centres in Europe. PARTICIPANTS: 147 formula fed children, with a reference group of 88 breastfed children. INTERVENTION: In the original trial newborn infants were randomised to be fed with a formula supplemented with LCPUFAs (n=111) or a formula without LCPUFAs but otherwise nutritionally similar (n=126). In the present follow up study the blood pressure of the children at age 6 years was measured. MAIN OUTCOME MEASURES: Systolic, diastolic, and mean blood pressure. RESULTS: 71 children in the LCPUFA supplementation group (64% of the original group) and 76 children in the non-supplementation group (60%) were enrolled into the follow up study. The LCPUFA group had significantly lower mean blood pressure (mean difference -3.0 mm Hg (95% confidence interval -5.4 mm Hg to -0.5 mm Hg)) and diastolic blood pressure (mean difference -3.6 mm Hg (-6.5 mm Hg to -0.6 mm Hg)) than the non-supplementation group. The diastolic pressure of the breastfed children (n=88 (63%)) was significantly lower than that of the non-supplemented formula group but did not differ from the LCPUFA formula group. CONCLUSIONS: Dietary supplementation with LCPUFAs during infancy is associated with lower blood pressure in later childhood. Blood pressure tends to track from childhood into adult life, so early exposure to dietary LCPUFAs may reduce cardiovascular risk in adulthood.
OBJECTIVE: To investigate the relation between maternal smoking habits, plasma lipids and milk fatty acid (FA) content and composition. DESIGN: Breastfeeding mothers who gave birth to healthy, full-term infants were recruited. Mothers were interviewed on smoking habits, being defined smokers (S) when usually smoking at least five cigarettes per day before pregnancy. SETTING: Department of Pediatrics, San Paolo Hospital, Milan, Italy. SUBJECTS: In total, 92 mothers: 61 non-S (NS) and 31 S. INTERVENTIONS: Pooled hindmilk was collected at the first raise of milk (colostrum stage), 1, 3 and 6 months, and total lipid (TL) content and fatty acid (FA) composition were evaluated. Maternal dietary habits were assessed by a food-frequency questionnaire. Two subsamples (16 NS, 6 S) were investigated after delivery and at 3 months for serum lipids and FA status. At 6 months after delivery, the number of mothers still breastfeeding decreased to 30. Variables were compared using nonparametric tests. RESULTS: In smoking mothers serum levels of triglycerides, cholesterol and low-density lipoproteins were higher, while those of high-density lipoproteins were lower. TL content in breast milk was similar in the two groups just after delivery but higher in milk from NS at 1 month. TL content and FA absolute amounts of linoleic, arachidonic, alpha-linolenic and docosahexaenoic (DHA) acid in breast milk were lower in S vs NS 1 month after delivery. Also 3 months after delivery, the breast milk of smoking mothers contained less DHA than the breast milk of nonsmoking mothers. CONCLUSIONS: Maternal cigarette smoking in early pregnancy is associated with higher plasma lipid levels and lower milk TL and DHA content in the first months of lactation.
UNLABELLED: Fats are the only dietary agents possibly modulating the individual membrane composition, which otherwise is "genetically" determined. In infancy, human milk represents the first natural source of fats. Although the fat intake of breastfed infants is quantitatively and qualitatively unique, it is not known to what extent their varying requirements are met by the fat composition in the milk of their mothers. CONCLUSION: The fat composition of arbitrarily chosen human milk is not always the best standard for that in infant formula.
AIM: To assess and compare the rates of initiation and duration of breastfeeding in Italy in 1995 and 1999, and to examine the adherence to the ten steps to successful breastfeeding recommended by WHO. METHODS: Two cohorts of mothers who delivered healthy infants in November 1995 (n = 1601) or November 1999 (n = 2450) were interviewed by telephone within 4 wk of delivery and when their infant were 3, 6, 9 and 12 mo of age. Type of breastfeeding was classified according to the WHO definitions. Adherence to the WHO ten steps was evaluated as experienced by the mothers. RESULTS: Initiation and duration of breastfeeding increased during the 1995-1999 period (p < 0.0001). The rate of breastfeeding at birth, at discharge and when the infants were 3, 6, 9 and 12 mo of age was 85%, 83%, 42%, 19%, 10% and 4%, in 1995 and 91%, 89%, 66%, 47%, 25% and 12% in 1999. The rate of exclusive breastfeeding was higher in 1999 than 1995 at birth (39% vs 30%, p < 0.0001) and at discharge (77% vs 70%, p < 0.0001), but overall no longer duration was observed in 1999. At 4 and 6 mo of age the rate of exclusive breastfeeding was 25% and 8% in 1995 and 31% and 5% in 1999. The adherence to each WHO step was higher in 1999 than in 1995 (p < 0.05) but concomitant adherence was low (<3%). CONCLUSION: Although an increase in initiation and duration of breastfeeding occurred in Italy during the 1995-1999 period, the duration of breastfeeding and exclusive breastfeeding is currently unsatisfactory, as is adherence to the ten steps specified by WHO. Promotion of breastfeeding and education and improvement in adherence to the WHO recommendations are still needed in Italy.
AIM: To investigate whether those who were exposed to high levels of the dioxin TCDD 25 years ago in Seveso, northern Italy still have higher than the expected levels of dioxins in their fat stores, and to investigate the concentrations of dioxins in the breast milk of mothers in Seveso and in two other regions in Italy. The load of vertically transmitted dioxins to the next generation, if being breastfed, was also investigated. METHODS: As there may be a synergistic effect of mixtures of organic chlorines, the concentrations of pesticides such as DDTs and PCBs have also been studied in the same human milk samples. Breast milk from 12 mothers from Seveso, Central Milan and a Lombardian village was collected for analysis during the first week and 1 and 3 mo after delivery. Individual samples were used for the analysis of pesticides and PCBs, whereas dioxins were analysed in pooled samples from all 12 mothers on each occasion. RESULTS: In human milk from Seveso, the TCDD concentration in fat calculated on a fresh weight basis was more than twice as high as the level in the other two regions, whereas the concentrations of investigated other toxins were lower in Seveso possible due to induction of the enzyme cytochrome P4501A, which means that the total level of dioxins was the same in all three locations. The congener profile, measured as mean toxic equivalency (TEQ) values, was the same in the Italian samples as previously reported from Stockholm. The calculations are based on the most recent WHO TCDD equivalency factors (TEF). The DDE concentration was higher in the samples from Milan than in the samples from the other two Italian regions, which may be due to the fact that, to a greater extent than in the other regions, Milanese food is imported from countries where DDT is still used as a pesticide. CONCLUSION: Twenty-five years after the dioxin catastrophe, human milk from mothers in Seveso has concentrations of the highly toxic dioxin congener TCDD that are more than twice as high as those in central Milan and a Lombardian village. This means that breastfed infants in Seveso still store an appreciable amount of TCDD in their body fat. The health consequences of this fact remain to be elucidated. The effect of the high load of DDTs in central Milan also has to be considered
AIM: to determine the rates of initiation and duration of breastfeeding in Italy in 1995 and 1999, and to examine the adherence to the ten steps to successful breastfeeding recommended by WHO. METHODS: Two cohorts of mothers who delivered healthy infants in November 1995 (n = 2400) or November 1999 (n = 3500) were interviewed by telephone within 4 wk of delivery when their infants were 3 months of age. Type of breastfeeding was classified according to the WHO definitions. Adherence to the WHO ten steps was evaluated. RESULTS: Initiation and duration of breastfeeding increased during the 1995-1999 period (p < 0.0001). The rate of breastfeeding at discharge and when the infants where 3 months of age was 83% and 42% in 1995, and 89% and 66% in 1999. The rate of exclusive/predominant breastfeeding at discharge was higher in 1999 than 1995 (78% vs 72%). CONCLUSION: An increase in initiation and duration of breastfeeding through the first 3 months of age occurred in Italy during the 1995-1999 period, but both breastfeeding duration and observance of the WHO's ten steps are not completely satisfactory yet.
Blood fatty acid status and visual function of 20 treated hyperphenylalaninemic (HPA) children, randomly allocated into two groups to receive supplementation of either long chain polyunsaturated fatty acids (LCPUFA), including docosahexaenoic acid (DHA), or placebo for 12 months, have been investigated three years after the end of the treatment. Although in the LCPUFA group blood DHA levels and P100 wave latency improved at the end of supplementation, they had returned to baseline after three years.
Infant formulas on the market today should be aimed at providing the best alternative to breast milk for infants of those women who are unable to continue breastfeeding until 6 months of age and substituting ideally for human milk after 6 months of age approaching the structural and functional effects observed in breastfed infants. The aim is to mimic the functional outcome of the breastfed infant (e.g. growth and development), and not to copy the composition of human milk. For this purpose, the following compounds have been added to formulas and are reviewed: long-chain polyunsaturated fatty acids (LCPUFA) for brain composition and neurodevelopment, probiotics and prebiotics for the fecal flora and the local intestinal defense, and nucleotides for promoting the immune response. Changes in protein quantity and quality allow to balance the blood amino acid pattern (possibly relevant to the early stages of brain development for the neurotransmitter function) and reducing the protein intake could be important for the prevention of later overweight. Hydrolysed proteins are important in the prevention of atopic disorders. Many trials have been published so far with short-term assessments, most of them with positive findings. However, we need more data on the long-term follow-up of infants who were fed the new formulas. Such data will allow to look at neural performance, prevention of overweight and obesity, and effects on the immune-allergic pattern.
UNLABELLED: The aim of this study was to determine whether any relationship exists between the severity of mutation of the phenylalanine hydroxylase (PAH) gene and the plasma concentrations of phenylalanine (Phe) and tyrosine (Tyr) under fasting and semifasting conditions among heterozygotes in a matched case-control study. Parents of patients affected by PAH deficiency (n = 25) detected through the Italian Neonatal Screening Program and referred from January 1994 to June 2000, and parents of healthy children were investigated. In total, 68 subjects without any disease, 34 hyperphenylalaninaemia (HPA) heterozygous parents and 34 age- and gender-matched controls, were recruited. Plasma concentrations of Phe and Tyr in fasting and semifasting (1600 mg Phe oral load) conditions were the main outcome measures. DNA analysis for PAH mutations was performed in all 68 subjects. Compared with controls, heterozygotes showed higher fasting and semifasting Phe concentrations (p < 0.0001), lower semifasting Tyr concentrations (p = 0.015), lower Tyr variations (p = 0.003) and a higher Phe/Tyr ratio (p < 0.0001) in switching from fasting to semifasting conditions. Heterozygotes carrying a severe mutation showed semifasting plasma Tyr concentrations lower than controls (p = 0.019) but not significantly different from Tyr levels found in non-severe carriers (p = 0.197). The Tyr variations were minor in severe carriers than controls (p < 0.001) and non-severe carriers too, although with lower significance (p = 0.089). In six carriers of A403V mutation, parents of mild hyperphenylalaninaemics on an unrestricted diet, significant differences in variations from fasting to semifasting conditions were found compared with parents of patients on a diet. CONCLUSION: Although the great heterogeneity of PAH mutations limits any general conclusion, the results suggest that monitoring plasma Tyr variations may be more sensitive than plasma Phe in assessing the severity of PAH mutations in HPA heterozygotes.
Since dietary fats may affect brain composition and function in early life, we evaluated developmental indices at 1 year of age in relation to the duration of breast-feeding and the milk fat composition in a breast-fed population. A blinded monitor administered the Bayley test (2nd edition) to 1-year-old subjects born at term and exclusively breast-fed for at least 3 months. Weaning foods were introduced from the 5th month onward. Mothers' milk lipid composition (fat [wt/dL], fatty acid [wt/dL], FA% [% of total fatty acids]) was determined at 0, 1, 3, 6, 9, and 12 months. Statistics used were Student's t-test, Pearson's r, and multiple regression. Forty-four infants out of 95 recruited at birth met inclusion criteria. There was a progressive reduction of the number of breast-fed babies to 29 (6 mo), 17 (9 mo), and 10 (12 mo). Breast-feeding for 6 months or longer gave a 6.6-point advantage (95% confidence interval, -0.6, 13.8; P = 0.07 for the Bayley psychomotor developmental index (PDI) and 2.0 for the Bayley mental developmental index (MDI) (95% confidence interval, -3.2, 7.3; NS) compared with the 15 subjects breast-fed for fewer than 6 months. Among the milk lipid factors, the fat weight (mg/dL) at 6 months showed the highest association with the MDI (r = 0.55, P = 0.002). Thus, prolonged breast-feeding during the weaning process may result in a better developmental performance at 12 months, possibly due to the supply of fats contributing energy and/or affecting brain composition.
We assessed the total fat content and fatty acid concentrations in colostrum and throughout a nursing period of 12 months in a group of mothers recruited after delivery of full-term infants. Pooled human milk (hindmilk) was collected from all feedings over 24 hours at the following times: 1st day of nursing (colostrum), and at 1, 3, 6, 9, and 12 months. Total fat was quantified by a microgravimetric method. Fatty acids were analyzed by means of capillary gas chromatography. Comparisons were made with analysis of variance for repeated measures. Ten mothers completed the follow-up 12-month nursing period. We found that the total lipid content of hindmilk (mg/dL) rises more than 3-fold from the colostrum up to the 3rd month, and then more slowly up to the 12th month. Total saturated fatty acids progressively increase and total monounsaturated FA progressively decrease. Among long-chain polyunsaturated fatty acids, we found that the concentrations (mg/dL) of C20:4 and C22:6 remain stable from colostrum up to the 12th month of nursing, while their percentage levels are highest in colostrum and decrease afterwards in association with the increase in total fats. The C18:2n6 and C18:3n3 amounts progressively increase, following the trend of total fats. These data indicate that the secretion of arachidonic acid and docosahexaenoic acid during lactation remains constant, in spite of changes in total fat and in the linoleic acid and alpha-linolenic acid contents of milk.
To evaluate the prevalence of breast-feeding in Italy and to describe the social and environmental factors associated with its practice, 1601 mothers were systematically recruited as representative of deliveries across all regions of Italy during November 1995. They were interviewed in March, June, and September of 1996. Interviews were conducted by telephone using a standardized questionnaire designed for computer scanning. The results indicated that 85% of mothers breast-fed their infants. The rates of breast-feeding at 3, 6, and 9 months were, respectively, 51%, 32%, and 19%. Among the 830 lactating mothers at 3 months, 72% practiced breast-feeding "on demand." Pediatricians, midwives, and gynecologists were the main sources of information about breast-feeding, but 43% of the mothers did not receive any information. Media (radio, TV) were mentioned as sources of information by only 2% of the mothers. Maternal factors significantly associated with breast-feeding and its duration were: a) having been breast-fed as infants, b) being nonsmokers, and c) being given information about lactation at the time of discharge from their hospital ward. Maternal characteristics (age, weight, and height), parental socioeconomic indicators (profession and education), and neonatal care (rooming-in practice) were not significantly associated with breast-feeding. Our results show that in Italy a fairly high percentage of mothers start breast-feeding and that both maternal factors (history and habits) and good information may support its duration.
The associations of breastfeeding duration and milk fat composition with the developmental outcome at 1 year of age were measured within 44 infants exclusively breastfed for 3 months, out of 95 recruited at birth. Pooled breast milk (hindmilk) of the mothers was analysed at colostrum, 1, 3, 6, 9, and 12 months for total fat and fatty acid content. Infants were examined at 12 months by means of the Bayley test. There was a progressive reduction of the number of breastfed babies after the introduction of solids to 29 (6 months), 17 (9 months) and 10 (12 months). After adjusting for major confounders, infants breastfed for 6 months or longer showed a trend to have an advantage at the Bayley psychomotor developmental index compared to those breastfed >3 and <6 months (95% CI for difference: - 0.6, 13.8; P= 0.07) while the Bayley mental developmental index (MDI) was just 2.1 points higher. Among the milk fat components considered for each time-point, the total fat content at 6 months showed the strongest association with the MDI at 12 months (r=0.59, P=0.001). Prolonging breastfeeding during the weaning process may result in a better developmental performance at 12 months, possibly due to the supply of fats affecting brain composition.
Hyperphenylalaninemic (HPA) children display low levels of long-chain polyunsaturated fatty acids (LCPUFA), particularly docosahexaenoic acid (DHA), in circulating lipids and erythrocytes. We have investigated the effects on the blood fatty acid status and lipid picture of a balanced supplementation with LCPUFA in HPA children through a double-blind, placebo-controlled trial. A total of 20 well-controlled HPA, school-age children were randomized to receive through a 12-month trial fat capsules supplying either 26% fatty acid as LCPUFA (including 4.6%gamma -linolenic acid, 7.4% arachidonic acid, AA, 5.5% eicosapentaenoic acid and 8% DHA) or placebo (olive oil). The study supplementation was administered in order to provide 0.3-0.5% of the individual daily energy requirements as LCPUFA. Reference data were obtained from healthy children of comparable age. Among HPA children (whose DHA status was poor at baseline), those supplemented with LCPUFA showed an increase of around 100% in the baseline DHA levels in plasma phospholipids and erythrocytes. No changes of AA levels were observed. Blood lipid levels did not significantly change. A balanced supplementation with LCPUFA in treated HPA children may improve the DHA status without adversely affecting the AA status.
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Several recent studies document a beneficial effect of breast-feeding on later neurodevelopmental outcomes. The mechanisms involved are still in need of elucidation, but evidence is accruing that the fatty acid (FA) composition of human milk plays a role. The composition of body fats, from circulating erythrocyte lipids to brain phospholipids, is linked in infants to the early feeding mode and which FA predominates among circulating lipids influences visual and neurodevelopmental performance test scores. In these studies, greater differences were found between breast-fed and standard formula-fed infants, the latter showing low tissue long-chain polyunsaturated fatty acids (LCPUFA: arachidonic acid, AA, 20:4n-6; eicosapentaenoic acid, EPA, 20:5n-3; docosahexaenoic acid, DHA, 22:6n-3) accretion and lower visual and neurodevelopmental test scores. Human milk contains LCPUFA, while most available formulas, especially those intended for full-term infants, do not. With the progressive introduction of solid foods, the question arises whether a specific or "ideal" dietary lipid mixture can be found to meet growth requirements and ensure a lipid balance adequate for the early and effective preventive purposes. These complementary aspects are challenges for the paediatric nutrition researcher today.
UNLABELLED: This paper reports on the conclusions of a workshop on the role of long chain polyunsaturated fatty acids (LC-PUFA) in maternal and child health. The attending investigators involved in the majority of randomized trials examining LC-PUFA status and functional outcomes summarize the current knowledge in the field and make recommendations for dietary practice. Only studies published in full or in abstract form were used as our working knowledge base. CONCLUSIONS: For healthy infants we recommend and strongly support breastfeeding as the preferred method of feeding, which supplies preformed LC-PUFA. Infant formulas for term infants should contain at least 0.2% of total fatty acids as docosahexaenoic acid (DHA) and 0.35% as arachidonic acid (AA). Since preterm infants are born with much less total body DHA and AA, we suggest that preterm infant formulas should include at least 0.35% DHA and 0.4% AA. Higher levels might confer additional benefits and should be further investigated because optimal dietary intakes for term and preterm infants remain to be defined. For pregnant and lactating women we consider it premature to recommend specific LC-PUFA intakes. However, it seems prudent for pregnant and lactating women to include some food sources of DHA in their diet in view of their assumed increase in LC-PUFA demand and the relationship between maternal and foetal DHA status.