Altered materno-fetal transfer of 13C-polyunsaturated fatty acids in obese pregnant women.

BACKGROUND & AIMS: Maternal obesity at conception is considered a major predictor of offspring obesity. This could by driven at least in part by an altered placental fat transfer. However, the pathophysiological mechanisms involved are not fully understood. We investigated the in vivo materno-fetal transfer of fatty acids (FAs) in obese pregnant women using stable isotopes. METHODS: Ten obese and ten normo-weight pregnant women (control) received orally a bolus of 13C-labeled FAs 12 h before elective caesarean section: oleic acid (13C-OA), linoleic acid (13C-LA) and docosahexaenoic acid (13C-DHA). Maternal blood samples were collected at -12 (basal), -8, -4, -2, 0 h relative to the time of cesarean section. At the time of birth, arterial and venous cord bloods as well as placental tissue were collected. FAs composition was determined by gas-liquid chromatography and isotopic enrichment by gas chromatography-combustion-isotope ratio mass spectrometry. RESULTS: Maternal plasma insulin and placental weight tended to higher values in obese pregnant women although they did not present serum hyperlipidemia. Higher concentrations of 13C-LA and 13C-DHA were found in non-esterified FAs fraction in maternal plasma of obese mothers. The ratio of placental uptake for 13C-LA and 13C-DHA was lower in obese women compared to normal weight pointing toward a limited capacity of FA placental transfer, especially of essential FAs. Maternal insulin was associated to this lower placenta/maternal plasma ratio for both 13C-LA (R = -0.563, P = 0.012) and 13C-DHA (R = -0.478, P = 0.033). In addition, the ratio cord/maternal plasma of 13C-LA was significantly lower in obese women compared to controls. CONCLUSIONS: In conclusion, obese mothers without hyperlipidemia showed a reduced materno-fetal transfer of polyunsaturated FAs which could affect fetal development. This affect dietary recommendation for obese pregnant women. TRIAL REGISTRY NUMBER: ISRCTN69794527.

Associations between fatty acids and low-grade inflammation in children from the LISAplus birth cohort study.

BACKGROUND/OBJECTIVES: Assessing fatty acid (FA) composition in relation to inflammatory markers can shed light on the role of different FA and their metabolism in low-grade inflammation. Existing exploratory studies in children are scarce, and findings inconsistent. We hence aim to analyse associations of FA with common inflammatory markers, high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6), in 10-year-old children. SUBJECTS/METHODS: Complete data were available for 958 participants from the 10-year follow-up of the LISAplus (Influence of Lifestyle-Related Factors on the Immune System and the Development of Allergies in Childhood plus the Influence of Traffic Emissions and Genetics) birth cohort study. FA composition was assessed in serum glycerophospholipids. Hs-CRP and IL-6 were categorised into three levels. Associations of FA with inflammatory markers were assessed using multinomial logistic regression, adjusting for potential confounders. Additionally, sex-stratified analyses were carried out. RESULTS: FA exposures associated with significantly higher low-grade inflammation, as indicated by higher hs-CRP or IL-6 levels, included: palmitic acid (PA) (IL-6: P<0.001, 95% confidence interval: 1.30; 2.43), arachidonic acid (AA) (hs-CRP: P=0.002, 1.07; 1.31), n-6 highly unsaturated FA (HUFA) (hs-CRP: P=0.002, 1.06; 1.27), ratio of AA to linoleic acid (AA/LA) (hs-CRP: P<0.001, 1.16; 1.62) and total saturated FA (SFA) (IL-6: P<0.001, 1.77; 3.15). FA exposures associated with reduced levels of inflammatory markers included LA (hs-CRP: P=0.001, 0.84; 0.96; IL-6: P<0.001, 0.69; 0.90) and total polyunsaturated FA (PUFA) (IL-6: P<0.001, 0.57; 0.78). CONCLUSIONS: These findings suggest that higher SFA and minor n-6 HUFA, namely PA and AA, are associated with increased low-grade inflammation in children, whereas the major dietary n-6 PUFA and total PUFA are associated with reduced inflammation. Elevated desaturase activity, estimated by the ratio AA/LA, may be associated with higher inflammation, particularly in boys.

Maternal plasma polyunsaturated fatty acid levels during pregnancy and childhood lipid and insulin levels.

BACKGROUND AND AIMS: Maternal polyunsaturated fatty acid (PUFA) levels are associated with cord blood lipid and insulin levels. Not much is known about the influence of maternal PUFAs during pregnancy on long-term offspring lipid and insulin metabolism. We examined the associations of maternal plasma n-3 and n-6 PUFA levels during pregnancy with childhood lipid and insulin levels. METHODS AND RESULTS: In a population-based prospective cohort study, among 3230 mothers and their children, we measured maternal second trimester n-3 and n-6 PUFA plasma levels. At the median age of 6.0 years (95% range, 5.6-7.9), we measured childhood total-cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglyceride, insulin and c-peptide levels. Higher maternal total n-3 PUFA levels, and specifically DHA levels, were associated with higher childhood total-cholesterol, HDL-cholesterol and insulin levels (p-values <0.05), but not with LDL-cholesterol and triglycerides. Maternal total n-6 PUFA levels were not associated with childhood outcomes, but higher levels of the individual n-6 PUFAs, EDA and DGLA were associated with a lower childhood HDL-cholesterol, and higher AA levels with higher childhood total-cholesterol and HDL-cholesterol levels (all p-values <0.05). A higher maternal n-6/n-3 PUFA ratio was only associated with lower childhood HDL-cholesterol and insulin levels (p-values <0.05). These associations were not explained by childhood body mass index. CONCLUSIONS: Higher maternal total n-3 PUFAs and specifically DHA levels during pregnancy are associated with higher childhood total-cholesterol, HDL-cholesterol and insulin levels. Only individual maternal n-6 PUFAs, not total maternal n-6 PUFA levels, tended to be associated with childhood lipid and insulin levels.

Effects of a Follow-On Formula Containing Isomaltulose (Palatinose™) on Metabolic Response, Acceptance, Tolerance and Safety in Infants: A Randomized-Controlled Trial.

UNLABELLED: Effects of the dietary glycaemic load on postprandial blood glucose and insulin response might be of importance for fat deposition and risk of obesity. We aimed to investigate the metabolic effects, acceptance and tolerance of a follow-on formula containing the low glycaemic and low insulinaemic carbohydrate isomaltulose replacing high glycaemic maltodextrin. Healthy term infants aged 4 to 8 completed months (n = 50) were randomized to receive the intervention follow-on formula (IF, 2.1g isomaltulose (Palatinose™)/100mL) or an isocaloric conventional formula (CF) providing 2.1g maltodextrin/100mL for four weeks. Plasma insulinaemia 60 min after start of feeding (primary outcome) was not statistically different, while glycaemia adjusted for age and time for drinking/volume of meal 60 min after start of feeding was 122(105,140) mg/dL in IF (median, interquartile range) and 111(100,123) in CF (p = 0.01). Urinary c-peptide:creatinine ratio did not differ (IF:81.5(44.7, 96.0) vs. CF:56.8(37.5, 129),p = 0.43). Urinary c-peptide:creatinine ratio was correlated total intake of energy (R = 0.31,p = 0.045), protein (R = 0.42,p = 0.006) and fat (R = 0.40,p = 0.01) but not with carbohydrate intake (R = 0.22,p = 0.16). Both formulae were well accepted without differences in time of crying, flatulence, stool characteristics and the occurrence of adverse events. The expected lower postprandial plasma insulin and blood glucose level due to replacement of high glycaemic maltodextrin by low glycaemic isomaltulose were not observed in the single time-point blood analysis. In infants aged 4 to 8 completed months fed a liquid formula, peak blood glucose might be reached earlier than 60 min after start of feeding. Non-invasive urinary c-peptide measurements may be a suitable marker of nutritional intake during the previous four days in infants. TRIAL REGISTRATION: ClinicalTrials.gov NCT01627015.

Cord blood n-3 LC-PUFA is associated with adiponectin concentrations at 10 years of age.

An elevated ratio of n-6 to n-3 long-chain (LC-) polyunsaturated fatty acids (PUFA) may be a potential risk factor for obesity development. N-3 LC-PUFA are thought to alter adiponectin concentrations, and thus may have a beneficial effect on weight development. We analysed the association between n-3 LC-PUFA concentrations in cord blood and adiponectin concentrations at 10 years. Fatty acid composition was measured in cord blood and at 10 years of age by gas chromatography, and adiponectin concentrations were measured only at 10 years of age in 237 children from the Munich LISAplus birth cohort study. Linear regression models assessed associations between n-3 LC-PUFA, n-6 LC-PUFA and the n-6/n-3 ratio in cord blood with adiponectin concentrations at 10 years of age. LC-PUFA were presented as percentages and categorized into tertiles. Regression models were adjusted for LC-PUFA percentages at 10 years of age and other potential confounding factors. Cord blood n-3 LC-PUFA tertiles were significantly associated with adiponectin concentrations in an inverse J-shaped relationship [2nd tertile versus 1st tertile: Beta=1.84 (SE=0.65), and 3rd tertile versus 1st tertile: 1.02 (0.68), p-value<0.01 (ANOVA)]. Further, cord blood n-6/n-3 ratios were significantly associated with adiponectin concentrations [2nd tertile versus 1st tertile: 0.14 (0.67), and 3rd tertile versus 1st tertile: -1.37 (0.68), p-value=0.03 (ANOVA)]. The cord blood n-6 LC-PUFA tertiles were not associated with adiponectin concentrations. Our results suggest that a higher n-3 LC-PUFA concentrations and a lower n-6/n-3 ratio in cord blood are associated with higher adiponectin concentrations at 10 years of age.

The placental exposome: placental determinants of fetal adiposity and postnatal body composition.

Offspring of obese and diabetic mothers are at increased risk of being born with excess adiposity as a consequence of their intrauterine environment. Excessive fetal fat accretion reflects additional placental nutrient transfer, suggesting an effect of the maternal environment on placental function. High plasma levels of particular nutrients in obese and diabetic mothers are likely to be the important drivers of nutrient transfer to the fetus, resulting in excess fat accretion. However, not all offspring of obese and diabetic mothers are born large for gestational age and the explanation may involve the regulation of placental nutrient transfer required for fetal growth. The placenta integrates maternal and fetal signals across gestation in order to determine nutrient transfer rate. Understanding the nature of these signals and placental responses to them is key to understanding the pathology of both fetal growth restriction and macrosomia. The overall effects of the maternal environment on the placenta are the product of its exposures throughout gestation, the 'placental exposome'. Understanding these environmental influences is important as exposures early in gestation, for instance causing changes in the function of genes involved in nutrient transfer, may determine how the placenta will respond to exposures later in gestation, such as to raised maternal plasma glucose or lipid concentrations. Longitudinal studies are required which allow investigation of the influences on the placenta across gestation. These studies need to make full use of developing technologies characterising placental function, fetal growth and body composition. Understanding these processes will assist in the development of preventive strategies and treatments to optimise prenatal growth in those pregnancies at risk of either excess or insufficient nutrient supply and could also reduce the risk of chronic disease in later life.

Mc2 receptor knockdown modulates differentiation and lipid composition in adipocytes.

The melanocortin system is involved in central and peripheral regulation of energy homeostasis. In adipocytes, the melanocortin 2 receptor (MC2R) transmits ACTH-dependent signaling and its expression rises substantially during adipocyte differentiation. An in vitro system of retrovirally expressed shRNA directed against Mc2r mRNA in 3T3-L1 cells was established and effects of Mc2r knockdown (kd) in comparison to cells expressing non-targeting shRNA (control) were explored in differentiated adipocytes. Morphology, gene expression, lipolysis and fatty acid composition were analyzed. While gross morphology was unchanged extractable amount of lipids was reduced to 70-80% in kd cell lines (p<0.01). Moreover, expression changes of Pparγ2, aP2, and Pref1 indicated reduced differentiation in Mc2r kd cells. Intriguingly, not only ACTH, but also norepinephrine stimulated lipolysis were substantially reduced demonstrating functional significance of MC2R for general lipolysis pathway. Analysis of fatty acid composition in triglyceride and phospholipid fractions showed a lowered ratio of C16:1/C16:0 and C18:1/C18:0, but increased concentrations of arachidonic acid upon Mc2r knockdown. Reduction of mono-unsaturated fatty acids (MUFAs) was associated with lower expression of stearoyl-Coenzyme A desaturase 1 and 2 in kd cells (21 ± 8% vs. 100 ± 13%, p=0.01 and 32 ± 3% vs. 100 ± 15%, p=0.046). Conversely, high doses of ACTH resulted in gene expression changes, mirroring Mc2r knockdown (higher Pparγ2, Scd1, Hsl expression). MC2R plays an important role for regular lipolytic function and lipid composition in 3T3-L1 adipocytes. Of interest, desaturase expression was reduced and MUFA content accordingly altered in kd cells.

Genetic variations in polyunsaturated fatty acid metabolism--implications for child health?

Sufficient nutritional supply with polyunsaturated fatty acids (PUFAs) has long been considered as beneficial for child health, especially in regard to neuronal development and allergic diseases. In recent years, genetic association studies showed that in addition to nutritional influences, the genetic background is highly important for PUFA composition in human tissues. Specifically, polymorphisms in the fatty acid desaturase genes or FADS determine the efficiency of how PUFAs are processed endogenously. Recent gene-nutrition interaction studies suggest that these polymorphisms modulate the effect of nutritional fatty acid intake on complex phenotypes such as cognitive outcomes and asthma risk in children. These early results may provide the basis for future well-specified dietary recommendations to achieve optimal health benefit for all children. This article presents results from recent gene-nutrition interaction studies, discusses its implications for child health, and gives an outlook how this association might translate into clinical practice in the future.

Effect of protein intake and weight gain velocity on body fat mass at 6 months of age: the EU Childhood Obesity Programme.

INTRODUCTION: Higher protein intake during the first year of life is associated with increased weight gain velocity and body mass index (BMI). However, the relationship of protein intake and weight gain velocity with body composition is unclear. OBJECTIVE: To assess if the increases in weight gain velocity and BMI induced by protein intake early in life are related to an increase in fat or fat-free mass. MATERIALS AND METHODS: In all, 41 infants randomized at birth to a higher or lower protein content formula (HP=17 and LP=24, respectively) and 25 breastfed infants were included. Anthropometric measures were assessed at baseline, 6, 12 and 24 months, and fat-free mass (FFM) and fat mass (FM) were assessed by isotope dilution at 6 months. RESULTS: Weight gain velocity (g per month) during the first 6 months of life was significantly higher among HP infants (807.8 (±93.8) vs 724.2 (±110.0) (P=0.015)). Weight gain velocity strongly correlated with FM z-score (r=0.564, P<0.001) but showed no association with FFM z-scores. FFM showed no association with BMI. Nevertheless, FM strongly correlated with BMI at 6, 12 and 24 months (r=0.475, P<0.001; r=0.332, P=0.007 and r=0.247, P=0.051, respectively). FFM and FM z-scores did not differ significantly between HP and LP infants (0.32±1.75 vs -0.31±1.17 and 0.54±2.81 vs -0.02±1.65, respectively). CONCLUSION: Our findings support the hypothesis that higher protein intakes early in life are associated with faster weight gain and in turn to higher adiposity. This mechanism could be a determinant factor for later obesity risk.

Inverse association between trans isomeric and long-chain polyunsaturated fatty acids in pregnant women and their newborns: data from three European countries.

BACKGROUND: trans unsaturated fatty acids are thought to interfere with essential fatty acid metabolism. To extend our knowledge of this phenomenon, we investigated the relationship between trans isomeric and long-chain polyunsaturated fatty acids (LCPUFA) in mothers during pregnancy and in their infants at birth. METHODS: Fatty acid composition of erythrocyte phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was determined in Spanish (n = 120), German (n = 78) and Hungarian (n = 43) women at the 20th and 30th week of gestation, at delivery and in their newborns. RESULTS: At the 20th week of gestation, the sum of trans fatty acids in PE was significantly (p < 0.01) lower in Hungarian [0.73 (0.51), % wt/wt, median (IQR)] than in Spanish [1.42 (1.36)] and German [1.30 (1.21)] women. Docosahexaenoic acid (DHA) values in PE were significantly (p < 0.01) higher in Hungarian [5.65 (2.09)] than in Spanish [4.37 (2.60)] or German [4.39 (3.3.2)] women. The sum of trans fatty acids significantly inversely correlated to DHA in PCs in Spanish (r = -0.37, p < 0.001), German (n = -0.77, p < 0.001) and Hungarian (r = -0.35, p < 0.05) women, and in PEs in Spanish (r = -0.67, p < 0.001) and German (r = -0.71, p < 0.001), but not in Hungarian (r = -0.02) women. Significant inverse correlations were seen between trans fatty acids and DHA in PEs at the 30th week of gestation (n = 241, r = -0.52, p < 0.001), at delivery (n = 241, r = -0.40, p < 0.001) and in cord lipids (n = 218, r = -0.28, p < 0.001). CONCLUSION: Because humans cannot synthesize trans isomeric fatty acids, the data obtained in the present study support the concept that high maternal trans isomeric fatty acid intake may interfere with the availability of LCPUFA both for the mother and the fetus.

[Infant feeding practice and later obesity risk. Indications for early metabolic programming]. / Frühkindliche Ernährung und späteres Adipositasrisiko. Hinweise auf frühe metabolische Programmierung.

Metabolic factors acting during limited and sensitive time periods of pre- and postnatal development can induce lasting effects on health and disease risk in later life up to old age, including later obesity risk, which is referred to as early metabolic programming of long-term health. Three meta-analyses of observational studies found that obesity risk at school age was reduced with early breastfeeding compared to formula feeding. We assumed that breastfeeding protects against later obesity by reducing the occurrence of high weight gain in infancy and that one causative factor is the lower protein content of human milk compared to usual infant formulas (the "early protein hypothesis"). We are testing this hypothesis in the European Childhood Obesity Project, a double-blind, randomized clinical trial enrolling 1,678 infants in five countries (Belgium, Germany, Italy, Poland, Spain). We have randomized healthy infants born at term to receive for the first year infant formula and follow-on formula with higher or lower protein contents, respectively. The follow-up data obtained at age 2 years indicates that feeding formula with reduced protein content normalizes early growth relative to a breastfed reference group and the current WHO growth standard, which may furnish a significant long-term protection against later obesity. We conclude that infant feeding practice has a high potential for long-term health effects. The results obtained should stimulate the review of recommendations and policies for infant formula composition.

[(13)C]Methionine breath test as a marker for hepatic mitochondrial function in HIV-infected patients.

Metabolic disturbances such as dyslipidemia, lipodystrophy syndrome, visceral obesity, hyperlactatemia, diabetes mellitus, and hepatic steatosis have been recognized as serious complications in long-term antiretroviral-treated HIV-infected patients. The oxidative capacity of liver mitochondria plays a central role in their pathogenesis and can be analyzed using the [(13)C]methionine breath test. We analyzed hepatic mitochondrial function using the [(13)C]methionine breath test in antiretrovirally treated and untreated HIV-infected patients as well as HIV-negative controls. Patients with hepatic steatosis, hypertriglyceridemia, lipohypertrophy, and older age showed reduced methionine metabolism. Hepatic mitochondrial function is impaired in antiretroviral-treated HIV-infected patients with disturbances of lipid metabolism.

Perfluorooctane sulphonate (PFOS) and perfluorooctanoic acid (PFOA) in human breast milk: results of a pilot study.

Perfluorinated compounds (PFC) are a large group of chemicals produced for several decades and widely used for many industrial and consumer applications. Because of their global occurrence in different environmental media, their persistence and their potential to bioaccumulate in organisms they are of toxicological and public concern. In the present study, perfluorooctane sulphonate (PFOS) and perfluorooctanoic acid (PFOA) were quantified in 70 breast milk samples. Samples were obtained from Leipzig, Germany (38 archived samples), Munich, Germany (19 fresh samples) and Gyor, Hungary (13 frozen samples). PFOS could be quantified in all 70 samples. The concentration in samples from Germany ranged between 28 and 309 ng/l (median: 119 ng/l). Samples from Hungary showed significantly higher PFOS concentrations (median 330 ng/l, range 96-639 ng/l). In only 11 of 70 samples (16%) PFOA reached the LOQ (200 ng/l); values ranged from 201 to 460 ng/l. If only those samples with PFOA values above the LOQ were considered, we found a significant correlation between the PFOS and PFOA concentrations (r=0.75, p=0.008). Based on the results of the German sample, we estimated an intake of 0.10 microg PFOS/day (using median) or 0.27 PFOS microg/day (using maximum value) via breast milk for an infant of 5 kg bodyweight. Our data suggest that fully breastfed infants are unlikely to exceed the recommended tolerable daily intake of PFC. However, more target-oriented studies are needed to identify the amount and time-trend of PFOS and PFOA in maternal blood during pregnancy, after delivery, as well as in the growing infant and in its diet (e.g., breast milk and formula).

Dietary long-chain polyunsaturated fatty acid supplementation in infants with phenylketonuria: a randomized controlled trial.

BACKGROUND: Pre- and postnatal tissue accretion of long-chain polyunsaturated fatty acids (LCPUFA) has been related to visual and cognitive development in healthy children in several studies. Children with phenylketonuria (PKU) consume diets with very low contents of preformed LCPUFA. We studied prospectively the LCPUFA status in infants with PKU without or with LCPUFA supplementation during the first year of life. SUBJECTS AND METHODS: Infants with PKU were enrolled at diagnosis (<4 weeks of age) and randomized double blind to phenylalanine-free amino acid supplements without LCPUFA (n = 11) or with both arachidonic (AA, 0.46 wt%) and docosahexaenoic acids (DHA, 0.27 wt%) (n = 10). At enrolment and again at 1, 2, 3, 4, 6, 9 and 12 months, plasma phospholipid fatty acids were measured and dietary intakes were calculated from dietary protocols. RESULTS: Unsupplemented patients showed a marked LCPUFA depletion to levels clearly below those observed in healthy breast-fed infants. In contrast, supplemented infants had stable and higher LCPUFA levels than unsupplemented infants, reaching significant differences for AA values at 3, 4 and 6 months, and for DHA values at 1, 3, 4, 6, 9 and 12 months. Plasma phospholipid levels correlated closely with estimated dietary intakes of preformed LCPUFA. CONCLUSION: Low LCPUFA intakes with PKU diets induce marked depletion of AA and particularly of DHA in the first year of life. Thus endogenous synthesis of LCPUFA from precursors supplied by diet seems unable to compensate for low LCPUFA intakes. LCPUFA supplementation of PKU diets during the first year of life effectively enhances LCPUFA status to levels comparable to those of healthy breast-fed infants.

n6/n3 hypothesis and allergies: biologically plausible, but not confirmed.

The dietary intake of certain fatty acids might contribute to the development of atopic diseases like allergic rhinitis and asthma. We investigated the association between the ratio of n-6 and n-3 fatty acids in serum phospholipids and hay fever or allergic sensitisation in adults. Data from a population based cross-sectional study on respiratory health including measurement of fatty acids in serum phospholipids of 740 adults between 20 and 64 years of age were analysed. We could not find any significant association between n6/n3-ratio of fatty acids in serum phospholipids and hay fever or allergic sensitisation neither in the total population nor in the sub-population stratified by sex. Since no previous study on fatty acid intake confirmed the n6/n3-ratio hypothesis and this study did not find any association between the n6/n3-ratio in serum-phospholipids and hay fever or allergic sensitization, we conclude that the n6/n3- ratio hypothesis is not confirmed although biological plausible.

Analysis of FA contents in individual lipid fractions from human placental tissue.

Data on FA contents in the human placenta are limited. Different methods have been used for the FA analysis, and only percentage results have been presented. We developed and evaluated a method for the determination of FA concentrations in placental tissue. Lipids were extracted from placental tissue with a chloroform/methanol mixture; and phospholipids (PL), nonesterified FA (NEFA), TG, and cholesterol esters (CE) were isolated by TLC. Individual lipid fractions were derivatized with methanolic hydrochloric acid, and the FAME were quantified by GC with FID. The CV of intra-assay (n = 8) of absolute concentrations were evaluated for FA showing a tissue content > 0.01 mg/g. CV ranges were 4.6-11.0% for PL, 6.4-9.3% for NEFA, 6.1-8.9% for TG, and 11.4-16.3% for CE. The relative FA composition across a term placenta indicated no differences between samples of central and peripheral locations of maternal and fetal site (CV 0.5-9.9%), whereas the absolute FA concentrations were only reproducible in the PL fraction (CV 7.0-12.8%). The method shows a reasonably high precision that is well suited for physiological and nutritional studies.

[13C]linoleic acid oxidation and transfer into milk in stunted lactating women with contrasting body mass indexes.

BACKGROUND: The fat concentration of human milk is associated with maternal adiposity, but there is no clear understanding of the mechanisms controlling milk fat concentration. OBJECTIVE: We evaluated the effect of postpartum body mass index (BMI; in kg/m(2)) on the metabolic distribution of an oral dose of [13C]linoleic acid in lactating women. DESIGN: Ten lactating women stratified by BMI (either <22.5 or >23.5) at 5 mo postpartum received orally 2.5 mg [13C]linoleic acid/kg body wt. Exhaled air, milk, and plasma samples were collected in relation to tracer administration. Linoleic acid was determined by gas chromatography. Dietary intake, serum, milk composition, [13C]linoleic acid enrichment in milk and plasma, and exhaled 13CO2 (by isotope ratio mass spectrometry) were assessed. RESULTS: Women with a higher BMI exhaled more 13CO2 than did women with a lower BMI (22.8 +/- 9.4% compared with 8.6 +/- 3.5% of dose, P < 0.03). Cumulated 72-h transfer of [13C]linoleic acid to milk was not significantly different between groups (14.8 +/- 6.5% compared with 17.7 +/- 6.7% of dose). Within the first 9 h after dose administration, 51.6 +/- 4.9% of the total isotope transfer into milk had passed in women with a higher BMI, but only 24.0 +/- 15.3% had passed in those with a lower BMI (P = 0.02). CONCLUSIONS: Women with a lower BMI, who were reputed as having less body fat, oxidized and secreted into milk less dietary linoleic acid within 12 h after tracer administration than did women with a higher BMI. In both groups, a large proportion of [13C]linoleic was retained in the maternal compartment, most likely fat tissue, in a slow turnover pool, and released slowly in later hours.

Polyunsaturated fatty acid supply with human milk.

Polyunsaturated fatty acids in human milk may derive from diet, liberation from maternal body stores, or endogenous synthesis from precursor fatty acids. The contribution of each of these sources has not been studied in detail. Although maternal diet is a key factor affecting human milk composition, other factors such as gestational age, stage of lactation, nutritional status, and genetic background are known to influence the fat content and fatty acid composition in human milk. Both linoleic and alpha-linolenic acids, the essential fatty acids, are present in human milk, as are several other n-6 and n-3 longer chain polyunsaturated fatty acids that are required for optimal growth and development of infants. The fatty acid profile of human milk from lactating women of different countries is remarkably stable, but there is variability in some of the components, such as docosahexaenoic acid, which is mainly due to differences in dietary habits. Tracer techniques with stable isotopes have been valuable in assessing the kinetics of fatty acid metabolism during lactation and in determining the origin of fatty acids in human milk. Based on these studies, the major part of polyunsaturated fatty acids in human milk seems not to be provided directly from the diet but from maternal tissue stores.

Evaluation of two commercial enzyme immunoassays, testing immunoglobulin G (IgG) and IgA responses, for diagnosis of Helicobacter pylori infection in children.

Serological testing to diagnose Helicobacter pylori infection in children is still controversial, although commonly used in clinical practice. We compared the immunoglobulin G (IgG) and IgA results of two commercially available enzyme immunoassays (EIAs) (Pyloriset IgG and IgA and Enzygnost II IgG and IgA) for 175 children with abdominal symptoms divided into three age groups (0 to < or =6 years, n = 47; >6 to < or =12 years, n = 77; >12 years, n = 51). A child was considered H. pylori infected if at least two of three tests (histology, rapid urease test, 13C-urea breath test) or culture were positive and noninfected if all results were concordantly negative. Of 175 children, 93 (53%) were H. pylori negative and 82 were H. pylori positive. With the recommended cutoff values, the overall specificity was excellent for all four EIAs (95.7 to 97.8%) regardless of age. Sensitivity varied markedly between tests and was 92.7, 70.7, 47.5, and 24.4% for Enzygnost II IgG, Pyloriset IgG, Enzygnost II IgA, and Pyloriset IgA, respectively. Sensitivity was low in the youngest age group (25 to 33.3%), except for Enzygnost II IgG (91.6%). Receiver-operating curve analyses revealed that lower cutoff values would improve the accuracy of all of the tests except Enzygnost II IgG. Measurement of specific IgA, in addition to IgG, antibodies hardly improved the sensitivity. The specificity of commercial serological tests is high in children when the cutoff values obtained from adults are used. In contrast, sensitivity is variable, with a strong age dependence in some, but not all, tests. We speculate that young children may have a different immune response to H. pylori, with preferable responses to certain antigens, as well as lower titers than adults. The Pyloriset test may fail to recognize these specific antibodies.

Influence of formulas with borage oil or borage oil plus fish oil on the arachidonic acid status in premature infants.

Several studies have reported that feeding gamma-linolenic acid (GLA) has resulted in no increase in arachidonic acid (AA) in newborns. This result was ascribed to the eicosapentaenoic acid (EPA)-rich fish oil used in these formulas. Docosahexaenoic acid (DHA) sources with only minor amounts of EPA are now available, thus the addition of GLA to infant formulas might be considered an alternative to AA supplementation. Sixty-six premature infants were randomized to feeding one of four formulas [ST: no GLA, no long-chain polyunsaturated fatty acids; BO: 0.6% GLA (borage oil); BO + FOLOW: 0.6% GLA, 0.3% DHA, 0.06% EPA; BO + FOHIGH: 0.6% GLA, 0.3% DHA, 0.2% EPA] or human milk (HM, nonrandomized) for 4 wk. Anthropometric measures and blood samples were obtained at study entry and after 14 and 28 d. There were no significant differences between groups in anthropometric measures, tocopherol, and retinol status at any of the studied time points. The AA content of plasma phospholipids was similar between groups at study start and decreased significantly until day 28 in all formulafed groups, but not in the breast-fed infants [ST: 6.6 +/- 0.2%, BO: 6.9 +/- 0.3%, BO + FOLOW: 6.9 +/- 0.4%, BO + FOHIGH: 6.7 +/- 0.2%, HM: 8.6 +/- 0.5%, where values are reported as mean +/- standard error; all formulas significantly different (P< 0.05) from HM]. There was no significant influence of GLA or fish oil addition to the diet. GLA had only a very limited effect on AA status which was too small to obtain satisfactory concentrations (concentrations similar to breast-fed babies) under the circumstances tested. The effect of GLA on AA is independent of the EPA and DHA content in the diet within the dose ranges studied.