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1.
Br J Nutr ; 122(s1): S22-S30, 2019 09.
Article in English | MEDLINE | ID: mdl-31638498

ABSTRACT

In humans, maximum brain development occurs between the third trimester of gestation and 2 years of life. Nutrition during these critical windows of rapid brain development might be essential for later cognitive functioning and behaviour. In the last few years, trends on protein recommendations during infancy and childhood have tended to be lower than that in the past. It remains to be demonstrated that lower protein intakes among healthy infants, a part of being able to reduce obesity risk, is safe in terms of mental performance achievement. Secondary analyses of the EU CHOP, a clinical trial in which infants from five European countries were randomised to be fed a higher or a lower protein content formula during the 1st year of life. Children were assessed at the age of 8 years with a neuropsychological battery of tests that included assessments of memory (visual and verbal), attention (visual, selective, focused and sustained), visual-perceptual integration, processing speed, visual-motor coordination, verbal fluency and comprehension, impulsivity/inhibition, flexibility/shifting, working memory, reasoning, visual-spatial skills and decision making. Internalising, externalising and total behaviour problems were assessed using the Child Behaviour Checklist 4-18. Adjusted analyses considering factors that could influence neurodevelopment, such as parental education level, maternal smoking, child's gestational age at birth and head circumference, showed no differences between feeding groups in any of the assessed neuropsychological domains and behaviour. In summary, herewith we report on the safety of lower protein content in infant formulae (closer to the content of human milk) according to long-term mental performance.


Subject(s)
Dietary Proteins/administration & dosage , Infant Formula/chemistry , Mental Processes/physiology , Attention , Child , Child Behavior , Cognition/physiology , Dietary Proteins/analysis , European Union , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Language Development , Male , Memory , Neuropsychological Tests , Psychomotor Performance
2.
BJOG ; 126(8): 984-995, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30786138

ABSTRACT

OBJECTIVE: To assess the separate and combined associations of maternal pre-pregnancy body mass index (BMI) and gestational weight gain with the risks of pregnancy complications and their population impact. DESIGN: Individual participant data meta-analysis of 39 cohorts. SETTING: Europe, North America, and Oceania. POPULATION: 265 270 births. METHODS: Information on maternal pre-pregnancy BMI, gestational weight gain, and pregnancy complications was obtained. Multilevel binary logistic regression models were used. MAIN OUTCOME MEASURES: Gestational hypertension, pre-eclampsia, gestational diabetes, preterm birth, small and large for gestational age at birth. RESULTS: Higher maternal pre-pregnancy BMI and gestational weight gain were, across their full ranges, associated with higher risks of gestational hypertensive disorders, gestational diabetes, and large for gestational age at birth. Preterm birth risk was higher at lower and higher BMI and weight gain. Compared with normal weight mothers with medium gestational weight gain, obese mothers with high gestational weight gain had the highest risk of any pregnancy complication (odds ratio 2.51, 95% CI 2.31- 2.74). We estimated that 23.9% of any pregnancy complication was attributable to maternal overweight/obesity and 31.6% of large for gestational age infants was attributable to excessive gestational weight gain. CONCLUSIONS: Maternal pre-pregnancy BMI and gestational weight gain are, across their full ranges, associated with risks of pregnancy complications. Obese mothers with high gestational weight gain are at the highest risk of pregnancy complications. Promoting a healthy pre-pregnancy BMI and gestational weight gain may reduce the burden of pregnancy complications and ultimately the risk of maternal and neonatal morbidity. TWEETABLE ABSTRACT: Promoting a healthy body mass index and gestational weight gain might reduce the population burden of pregnancy complications.


Subject(s)
Body Mass Index , Gestational Weight Gain/physiology , Overweight/complications , Pregnancy Complications/etiology , Adult , Australia/epidemiology , Birth Weight , Cohort Studies , Europe/epidemiology , Female , Gestational Age , Humans , Infant, Newborn , North America/epidemiology , Odds Ratio , Pregnancy , Pregnancy Complications/epidemiology , Risk Factors
3.
Int J Obes (Lond) ; 41(1): 159-169, 2017 01.
Article in English | MEDLINE | ID: mdl-27569686

ABSTRACT

BACKGROUND/OBJECTIVES: Elevated prepregnancy body mass index (pBMI) and excess gestational weight gain (GWG) constitute important prenatal exposures that may program adiposity and disease risk in offspring. The objective of this study is to investigate the influence of pBMI and GWG on the maternal metabolomic profile across pregnancy, and to identify associations with birth weight. SUBJECTS/METHODS: This is a longitudinal prospective study of 167 nondiabetic women carrying a singleton pregnancy. Women were recruited between March 2011 and December 2013 from antenatal clinics affiliated to the University of California, Irvine, Medical Center. Seven women were excluded from analyses because of a diagnosis of diabetes during pregnancy. A total of 254 plasma metabolites known to be related to obesity in nonpregnant populations were analyzed in each trimester using targeted metabolomics. The effects of pBMI and GWG on metabolites were tested through linear regression and principle component analysis, adjusting for maternal sociodemographic factors, diet, and insulin resistance. A Bonferroni correction was applied for multiple comparison testing. RESULTS: pBMI was significantly associated with 40 metabolites. Nonesterified fatty acids (NEFA) showed a strong positive association with pBMI, with specificity for mono-unsaturated and omega-6 NEFA. Among phospholipids, sphingomyelins with two double bonds and phosphatidylcholines containing 20:3 fatty acid chain, indicative of omega-6 NEFA, were positively associated with pBMI. Few associations between GWG, quality and quantity of the diet, insulin resistance and the maternal metabolome throughout gestation were detected. NEFA levels in the first and, to a lesser degree, in the second trimester were positively associated with birth weight percentiles. CONCLUSIONS: Preconception obesity appears to have a stronger influence on the maternal metabolic milieu than gestational factors such as weight gain, dietary intake and insulin resistance, highlighting the critical importance of preconception health. NEFA in general, as well as monounsaturated and omega-6 fatty acid species in particular, represent key metabolites for a potential mechanism of intergenerational transfer of obesity risk.


Subject(s)
Birth Weight/physiology , Body Mass Index , Metabolomics , Pregnant Women , Adult , California , Female , Humans , Infant, Newborn , Longitudinal Studies , Male , Pregnancy , Prospective Studies , Risk Factors , Weight Gain
4.
Nutr Metab Cardiovasc Dis ; 27(1): 78-85, 2017 01.
Article in English | MEDLINE | ID: mdl-27919543

ABSTRACT

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.


Subject(s)
Cholesterol, HDL/blood , Fatty Acids, Omega-3/blood , Fatty Acids, Omega-6/blood , Insulin/blood , Mothers , Adolescent , Adult , Age Factors , Biomarkers/blood , Body Mass Index , C-Peptide/blood , Child , Child Nutritional Physiological Phenomena , Docosahexaenoic Acids/blood , Eicosapentaenoic Acid/blood , Female , Humans , Infant, Newborn , Life Style , Maternal Nutritional Physiological Phenomena , Nutritional Status , Pregnancy , Prenatal Exposure Delayed Effects , Prospective Studies , Young Adult
5.
Matern Child Health J ; 21(7): 1563-1572, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28188472

ABSTRACT

Background Maternal postpartum depression (PPD) could affect children's emotional development, increasing later risk of child psychological problems. The aim of our study was to assess the association between child's emotional and behavioural problems and mother's PPD, considering maternal current mental health problems (CMP). Methods This is a secondary analysis from the EU-Childhood Obesity Project (NCT00338689). Women completed the Edinburgh Postnatal Depression Scale (EPDS) at, 2, 3 and 6 months after delivery and the General Health Questionnaire (GHQ-12) to assess CMP once the children reached the age of 8 years. EPDS scores > 10 were defined as PPD and GHQ-12 scores > 2 were defined as CMP. The psychological problems of the children at the age of eight were collected by mothers through the Child's Behaviour Checklist (CBCL). Results 473, 474 and 459 mothers filled in GHQ-12 and CBCL tests at 8 years and EPDS at 2, 3 and 6 months, respectively. Anxiety and depression was significantly increased by maternal EPDS. Children whose mothers had both PPD and CMP exhibited the highest levels of psychological problems, followed by those whose mothers who had only CMP and only PPD. PPD and CMP had a significant effect on child's total psychological problems (p = 0.033, p < 0.001, respectively). Children whose mothers had PPD did not differ from children whose mothers did not have any depression. Conclusions Maternal postpartum depression and current mental health problems, separately and synergistically, increase children's psychological problems at 8 years.


Subject(s)
Anxiety/complications , Child Behavior Disorders/epidemiology , Child of Impaired Parents , Depression, Postpartum/psychology , Emotions , Mothers/psychology , Anxiety/psychology , Child , Depression , Depression, Postpartum/diagnosis , Depression, Postpartum/epidemiology , Female , Humans , Mental Health , Mother-Child Relations , Pregnancy , Problem Behavior , Psychiatric Status Rating Scales , Surveys and Questionnaires , Time Factors
6.
Crit Rev Food Sci Nutr ; 56(1): 82-91, 2016.
Article in English | MEDLINE | ID: mdl-24628089

ABSTRACT

Pregnancy is a complex period of human growth, development, and imprinting. Nutrition and metabolism play a crucial role for the health and well-being of both mother and fetus, as well as for the long-term health of the offspring. Nevertheless, several biological and physiological mechanisms related to nutritive requirements together with their transfer and utilization across the placenta are still poorly understood. In February 2009, the Child Health Foundation invited leading experts of this field to a workshop to critically review and discuss current knowledge, with the aim to highlight priorities for future research. This paper summarizes our main conclusions with regards to maternal preconceptional body mass index, gestational weight gain, placental and fetal requirements in relation to adverse pregnancy and long-term outcomes of the fetus (nutritional programming). We conclude that there is an urgent need to develop further human investigations aimed at better understanding of the basis of biochemical mechanisms and pathophysiological events related to maternal-fetal nutrition and offspring health. An improved knowledge would help to optimize nutritional recommendations for pregnancy.


Subject(s)
Global Health , Infant Nutrition Disorders/prevention & control , Maternal Nutritional Physiological Phenomena , Models, Biological , Nutrition Policy , Patient Compliance , Pregnancy Complications/prevention & control , Adult , Child Development , Female , Fetal Development , Humans , Infant Nutrition Disorders/epidemiology , Infant, Newborn , Nutritional Status , Pregnancy , Pregnancy Complications/epidemiology , Pregnancy Outcome , Risk , Weight Gain
7.
Nutr Metab Cardiovasc Dis ; 26(9): 786-96, 2016 09.
Article in English | MEDLINE | ID: mdl-27146364

ABSTRACT

BACKGROUND AND AIMS: Moderately reduced maternal nutrient availability during pregnancy has adverse effects on the fetuses' growth and metabolism during and after pregnancy. The aim of this study was to explore effects of maternal nutrition restriction (MNR) on key metabolites of the fetal energy metabolism, particularly amino acids (AA), nonesterified fatty acids (NEFA), acylcarnitines and phospholipids. These effects may reflect mechanisms relating MNR to later adverse outcomes. METHODS AND RESULTS: Plasma and liver samples of fetal baboons, whose mothers were fed ad libitum (CTR) or MNR (70% of CTR), were collected at 0.5 and 0.9 gestation (G - term 184 days). Metabolites were measured with liquid chromatography coupled to mass spectrometry. In both, CTR and MNR, fetal metabolic profiles changed markedly between 0.5G and 0.9G. Fetal liver glucose concentrations were strongly increased. Hepatic levels of NEFA, sphingomyelins, and alkyl-linked phospholipids increased while plasma NEFA and acyl-linked phospholipids levels decreased with progression of gestation. At 0.5G, MNR fetal plasma levels of short- and medium-chain acylcarnitines were elevated, but did no longer differ between groups at 0.9G. At 0.9G, plasma levels of methionine and threonine as well as hepatic threonine levels were lower in the MNR group. CONCLUSION: Small differences in the concentrations of plasma and liver metabolites between MNR and CTR fetuses reflect good adaptation to MNR. Fetal liver metabolic profiles changed markedly between the two gestation stages, reflecting enhanced liver glucose and lipid levels with advancing gestation. Decreased concentrations of AA suggest an up-regulation of gluconeogenesis in MNR.


Subject(s)
Caloric Restriction , Fetus/metabolism , Liver/metabolism , Malnutrition/metabolism , Maternal Nutritional Physiological Phenomena , Metabolome , Adaptation, Physiological , Animals , Biomarkers/blood , Carnitine/analogs & derivatives , Carnitine/blood , Chromatography, Liquid , Disease Models, Animal , Fatty Acids, Nonesterified/blood , Female , Gestational Age , Gluconeogenesis , Humans , Malnutrition/physiopathology , Mass Spectrometry , Metabolomics/methods , Papio , Phospholipids/blood , Pregnancy
8.
Nutr Metab Cardiovasc Dis ; 26(9): 824-32, 2016 09.
Article in English | MEDLINE | ID: mdl-27212617

ABSTRACT

BACKGROUND AND AIMS: The double-blind randomized European Childhood Obesity Project (CHOP) demonstrated that reduced protein content in infant formula leads to a lower body mass index (BMI) up to six years of age. Here we aimed at assessing pre-peritoneal fat, a marker of visceral fat, in children participating in the CHOP trial. METHODS AND RESULTS: Healthy term formula-fed infants in five European countries were randomized either to higher (n = 550) or lower (n = 540) protein formulas in the first year of life. Infants who were exclusively breastfed for at least three months (n = 588) were enrolled as an observational (non randomized) group. At age 5 years, subcutaneous fat (SC) and pre-peritoneal fat (PP) were measured by ultrasound in a subgroup of 275 children. The PP fat layer was thicker in the higher compared to the lower protein group (adjusted estimated difference: 0.058 cm, 95%CI 0.002; 0.115; p = 0.043), while SC fat was not different. Girls showed a thicker SC fat layer than boys. CONCLUSIONS: Higher protein intake in formula-fed infants appears to enhance pre-peritoneal fat tissue accumulation at the age of 5 years, but not of subcutaneous fat, which may trigger adverse metabolic and health consequences.


Subject(s)
Adiposity , Diet, Protein-Restricted , Dietary Proteins/adverse effects , Infant Formula/adverse effects , Intra-Abdominal Fat/physiopathology , Pediatric Obesity/prevention & control , Subcutaneous Fat/physiopathology , Age Factors , Child Development , Child, Preschool , Dietary Proteins/administration & dosage , Double-Blind Method , Europe , Female , Humans , Infant , Infant Nutritional Physiological Phenomena , Infant, Newborn , Intra-Abdominal Fat/diagnostic imaging , Male , Nutritional Status , Pediatric Obesity/diagnosis , Pediatric Obesity/etiology , Pediatric Obesity/physiopathology , Peritoneum , Subcutaneous Fat/diagnostic imaging , Time Factors , Ultrasonography
9.
BMC Public Health ; 16: 93, 2016 Jan 30.
Article in English | MEDLINE | ID: mdl-26829928

ABSTRACT

BACKGROUND: Obesity is growing at an alarming rate in Latin America. Lifestyle behaviours such as physical activity and dietary intake have been largely associated with obesity in many countries; however studies that combine nutrition and physical activity assessment in representative samples of Latin American countries are lacking. The aim of this study is to present the design rationale of the Latin American Study of Nutrition and Health/Estudio Latinoamericano de Nutrición y Salud (ELANS) with a particular focus on its quality control procedures and recruitment processes. METHODS/DESIGN: The ELANS is a multicenter cross-sectional nutrition and health surveillance study of a nationally representative sample of urban populations from eight Latin American countries (Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Perú and Venezuela). A standard study protocol was designed to evaluate the nutritional intakes, physical activity levels, and anthropometric measurements of 9000 enrolled participants. The study was based on a complex, multistage sample design and the sample was stratified by gender, age (15 to 65 years old) and socioeconomic level. A small-scale pilot study was performed in each country to test the procedures and tools. DISCUSSION: This study will provide valuable information and a unique dataset regarding Latin America that will enable cross-country comparisons of nutritional statuses that focus on energy and macro- and micronutrient intakes, food patterns, and energy expenditure. TRIAL REGISTRATION: Clinical Trials NCT02226627.


Subject(s)
Diet/ethnology , Feeding Behavior/ethnology , Nutrition Surveys/statistics & numerical data , Nutritional Status/ethnology , Adult , Aged , Argentina/epidemiology , Brazil/epidemiology , Chile/epidemiology , Cross-Sectional Studies , Eating/ethnology , Ecuador/epidemiology , Female , Health Status , Humans , Latin America/epidemiology , Male , Middle Aged , Nutrition Surveys/standards , Peru/epidemiology , Pilot Projects , Venezuela/epidemiology
10.
Gesundheitswesen ; 78(11): 695-707, 2016 Nov.
Article in German | MEDLINE | ID: mdl-26335658

ABSTRACT

Aim: 20 years after establishment of the National Breastfeeding Committee, the present work, based on published data on breastfeeding, is aimed at providing insight into the development of breastfeeding behaviour in Germany. Methods: To identify relevant publications, a comprehensive literature search was conducted in PubMed and Web of Science using the search terms "breast feeding" or "breastfeeding" in combination with "Germany". The publication period was limited to the period 1995-2014. Results: A total of 35 studies with data on breastfeeding for the birth cohorts of 1990-2012 were identified. Most of the data had been collected in regional or local surveys, often retrospectively. About 60% of the studies had been conducted with the primary aim of collecting data on breastfeeding or infant nutrition. Over the past 2 decades, breastfeeding rates were always relatively high at the beginning (72-97%). However, they declined significantly within the first 2 months, and by the age of 6 months, only about 50% of infants were still breastfed. Conclusion: Breastfeeding support and early assistance should be offered to a greater extent in order to achieve sustainable improvement of breastfeeding frequency and duration in Germany. Regarding the quality of data collected on breastfeeding, it seems crucial to implement standardised approaches to monitor breastfeeding in Germany.


Subject(s)
Breast Feeding/statistics & numerical data , Breast Feeding/trends , Maternal Behavior , Adolescent , Adult , Age Distribution , Female , Germany/epidemiology , Humans , Infant, Newborn , Middle Aged , Young Adult
11.
Mol Genet Metab ; 110 Suppl: S44-8, 2013.
Article in English | MEDLINE | ID: mdl-24071437

ABSTRACT

OBJECTIVES: A controlled long-term study was performed to assess the neurological and neuropsychological performance in adult patients with early-treated phenylketonuria (PKU). METHODS: We investigated 57 patients with early-treated classical PKU aged 19 to 41 years (mean age 31 years) and 46 matched healthy controls, matched for age and socioeconomic status. Patients and controls were assessed for their intelligence quotient (IQ), and attention and information-processing abilities. Magnetic resonance imaging (MRI) of the brain was performed in all patients. Neuropsychological assessments and MRI were repeated at a five-year-follow-up. RESULTS: In the five-year interval IQ, information processing and attention of patients and controls remained constant. At both assessment times the IQ scores were significantly lower in patients compared to controls. Older adult patients (>32 years) showed poorer information processing and attention at both assessment times compared to young adult patients (<32 years) and controls. IQ, information processing and attention showed no correlation to imaging results but were significantly correlated to blood phenylalanine (Phe) levels in patients' childhood and adolescence, and Phe levels had been higher in the adolescent years of older adult patients. CONCLUSIONS: Cognitive performance in adult patients with early-treated PKU does not seem to be subject to deterioration observable in a five-year interval. Neuropsychological assessment in adults with PKU revealed neurocognitive impairment particularly in older adult patients. This seems to refer to an early relaxation of diet that was recommended when the older patients were adolescents. Results indicate a benefit of dietary control during adolescence in PKU.


Subject(s)
Brain/physiopathology , Cognition , Phenylalanine/blood , Phenylketonurias/psychology , Adolescent , Adult , Age Factors , Case-Control Studies , Child , Female , Humans , Intelligence , Intelligence Tests , Magnetic Resonance Imaging , Male , Neuropsychological Tests , Phenylketonurias/diet therapy , Young Adult
12.
Ann Nutr Metab ; 63(4): 311-22, 2013.
Article in English | MEDLINE | ID: mdl-24514069

ABSTRACT

Diet and physical activity before and during pregnancy affect short- and long-term health of mother and child. The energy needs at the end of pregnancy increase only by about 10% compared to nonpregnant women. An excessive energy intake is undesirable since maternal overweight and excessive weight gain can increase the risks for a high birth weight and later child overweight and diabetes. Maternal weight at the beginning of pregnancy is especially important for pregnancy outcome and child health. Women should strive to achieve normal weight already before pregnancy. Regular physical activity can contribute to a healthy weight and to the health of pregnant women. The need for certain nutrients increases more than energy requirements. Before and during pregnancy, foods with a high content of essential nutrients should be preferentially selected. Supplements should include folic acid and iodine, iron (in case of suboptimal iron stores), the ω-3 fatty acid docosahexaenoic acid (in case of infrequent consumption of ocean fish) and vitamin D (in case of decreased sun exposure and decreased endogenous vitamin D synthesis). Pregnant women should not smoke and not stay in rooms where others smoke or have smoked before (passive smoking). Alcohol consumption should be avoided, since alcohol can harm unborn children.


Subject(s)
Diet/standards , Life Style , Maternal Nutritional Physiological Phenomena , Nutrition Policy , Body Weight , Dietary Supplements , Female , Folic Acid/administration & dosage , Germany , Humans , Iodine/administration & dosage , Iron, Dietary/administration & dosage , Meta-Analysis as Topic , Nutritional Requirements , Nutritional Status , Observational Studies as Topic , Pregnancy , Pregnancy Outcome
13.
Rev Gastroenterol Mex (Engl Ed) ; 88(1): 57-70, 2023.
Article in English | MEDLINE | ID: mdl-36737343

ABSTRACT

Complementary feeding (CF) is defined as the feeding of infants that complements breastfeeding, or alternatively, feeding with a breast milk substitute, and is a process that is more than simply a guide as to what and how to introduce foods. The information provided by healthcare professionals must be up-to-date and evidence-based. Most of the recommendations that appear in the different international guidelines and position papers are widely applicable, but some must be regionalized or adapted to fit the conditions and reality of each geographic zone. The Nutrition Working Group of the Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition (LASPGHAN) summoned a group of experts from each of the society's member countries, to develop a consensus on CF, incorporating, whenever possible, local information adapted to the reality of the region. The aim of the present document is to show the results of that endeavor. Utilizing the Delphi method, a total of 34 statements on relevant aspects of CF were evaluated, discussed, and voted upon.


Subject(s)
Gastroenterology , Infant , Child , Female , Humans , Cocos , Consensus , Latin America , Infant Nutritional Physiological Phenomena
14.
Biochim Biophys Acta ; 1812(6): 691-8, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21362473

ABSTRACT

Dysmorphic features, multisystem disease, and central nervous system involvement are common symptoms in congenital disorders of glycosylation, including several recently discovered Golgi-related glycosylation defects. In search for discriminative features, we assessed eleven children suspected with a Golgi-related inborn error of glycosylation. We evaluated all genetically unsolved patients, diagnosed with a type 2 transferrin isofocusing pattern in the period of 1999-2009. By combining biochemical results with characteristic clinical symptoms, we used a diagnostic flow chart to approach the underlying defect in patients with congenital disorders of glycosylation-IIx. According to specific symptoms and laboratory results, we initiated additional, targeted biochemical and genetic studies. We found a distinctive spectrum of congenital disorders of glycosylation type 2-associated anomalies including sudden hearing loss, brain malformations, wrinkled skin, and epilepsy in combination with skeletal dysplasia, dilated cardiomyopathy, sudden cardiac arrest, abnormal copper and iron metabolism, and endocrine abnormalities in our patients. One patient with severe cortical malformations and mild skin abnormalities was diagnosed with a known genetic syndrome, due to an ATP6V0A2 defect. Here, we present unique congenital disorders of glycosylation type 2-associated anomalies, including both ATPase-related and unrelated cutis laxa and sensorineural hearing loss, a recently recognized symptom of congenital disorders of glycosylation. Based on our findings, we recommend clinicians to consider congenital disorders of glycosylation in patients with cardiac rhythm disorders, spondylodysplasia and biochemical abnormalities of the copper and iron metabolism even in absence of intellectual disability.


Subject(s)
Congenital Disorders of Glycosylation/diagnosis , Transferrin/analysis , Adolescent , Congenital Disorders of Glycosylation/genetics , Female , Glycosylation , Humans , Infant , Infant, Newborn , Isoelectric Focusing , Male
15.
Int J Obes (Lond) ; 36(4): 548-53, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22310472

ABSTRACT

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.


Subject(s)
Adipose Tissue , Breast Feeding , Dietary Proteins/administration & dosage , Infant Formula , Obesity/epidemiology , Weight Gain , Body Mass Index , Body Water , Body Weight , Cohort Studies , Double-Blind Method , Energy Intake , European Union , Female , Germany/epidemiology , Humans , Infant , Male , Obesity/prevention & control , Pregnancy , Spain/epidemiology
16.
Allergy ; 67(1): 83-90, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21933193

ABSTRACT

BACKGROUND: The protective effect of breastfeeding (BF) on the development of asthma has been widely recognized, even if not all results have been consistent. Gene variants of the FADS gene cluster have a major impact on fatty acid composition in blood and in breast milk. Therefore, we evaluated the influence of the FADS1 FADS2 gene cluster polymorphisms on the association between BF and asthma. METHODS: The analysis was based on data (N=2245) from two German prospective birth cohort studies. Information on asthma and BF during the first 6 months was collected using questionnaires completed by the parents. Logistic regression modelling was used to analyse the association between exclusive BF and ever having asthma stratified by genotype. RESULTS: In the stratified analyses, BF for 3 or 4 months after birth had a protective effect for heterozygous and homozygous carriers of the minor allele (adjusted odds ratio between 0.37 (95% CI: 0.18-0.80) and 0.42 (95% CI: 0.20-0.88). Interaction terms of BF with genotype were significant and ranged from -1.17 (P-value: 0.015) to -1.33 (0.0066). Moreover, heterozygous and homozygous carriers of the minor allele who were exclusively breastfed for 5 or 6 months after birth had a reduced risk of asthma [0.32 (0.18-0.57) to 0.47 (0.27-0.81)] in the stratified analyses. For individuals carrying the homozygous major allele, BF showed no significant effect on the development of asthma. CONCLUSIONS: The association between exclusive BF and asthma is modified by the genetic variants of FADS genotypes in children.


Subject(s)
Asthma/genetics , Breast Feeding , Fatty Acid Desaturases/genetics , Multigene Family , Asthma/epidemiology , Child , Child, Preschool , Delta-5 Fatty Acid Desaturase , Female , Genotype , Humans , Infant , Infant, Newborn , Male , Polymorphism, Single Nucleotide , Prevalence , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
17.
Horm Metab Res ; 44(9): 670-5, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22723268

ABSTRACT

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.


Subject(s)
Adipocytes/cytology , Adipocytes/metabolism , Cell Differentiation , Lipids/chemistry , Receptor, Melanocortin, Type 2/genetics , 3T3-L1 Cells , Adipocytes/chemistry , Animals , Gene Expression , Gene Knockdown Techniques , Lipid Metabolism , Lipolysis , Mice , Receptor, Melanocortin, Type 2/metabolism , Signal Transduction
18.
Clin Exp Allergy ; 41(12): 1757-66, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21793953

ABSTRACT

BACKGROUND: The association between dietary fatty acid intake and the development of atopic diseases has been inconsistent. This could be due to inter-individual genetic differences in fatty acid metabolism. OBJECTIVE: The aim of the current study was to assess the influence of FADS1 FADS2 gene cluster polymorphisms on the association between dietary fatty acid intake and atopic diseases and allergic sensitization in 10-year-old children. METHODS: The analysis was based on data from two German prospective birth cohort studies. Data on margarine and fatty acid intake were collected using a food frequency questionnaire. Information on atopic diseases was collected using a questionnaire completed by the parents. Specific IgE against common food and inhalant allergens were measured. Six variants of the FADS1 FADS2 gene cluster (rs174545, rs174546, rs174556, rs174561, rs174575 and rs3834458) were tested. Logistic regression modelling, adjusted for gender, age, maternal education level and study centre, was used to analyse the association between fatty acid intake and atopic diseases stratified by genotype. RESULTS: No significant association was found between the six FADS single nucleotide polymorphisms (SNPs) and allergic diseases or atopic sensitization. The total n-3/total n-6 ratio was positive associated with an increased risk of hayfever in homozygous major allele carriers ranging from an adjusted odds ratios of 1.25 (95%-CI: 1.00-1.57) to 1.31 (95%-CI: 1.01-1.69) across the six tested SNPs although this association was not significant anymore after correcting for multiple testing. Daily margarine intake was significantly associated with asthma [1.17 (1.03-1.34) to 1.22 (1.06-1.40)] in individuals carrying the homozygous major allele. This association was also significant after correcting for multiple testing. CONCLUSIONS & CLINICAL RELEVANCE: The association between dietary intake of fatty acids and allergic diseases might be modulated by FADS gene variants in children.


Subject(s)
Fatty Acid Desaturases/genetics , Fatty Acids/metabolism , Hypersensitivity/genetics , Hypersensitivity/metabolism , Polymorphism, Single Nucleotide , Alleles , Cohort Studies , Delta-5 Fatty Acid Desaturase , Female , Genotype , Humans , Infant , Infant, Newborn , Male , Margarine
19.
Ann Nutr Metab ; 59(2-4): 107-16, 2011.
Article in English | MEDLINE | ID: mdl-22142767

ABSTRACT

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.


Subject(s)
Arachidonic Acid/blood , Dietary Supplements , Docosahexaenoic Acids/blood , Fatty Acids, Essential/blood , Trans Fatty Acids/blood , Arachidonic Acid/administration & dosage , Docosahexaenoic Acids/administration & dosage , Double-Blind Method , Erythrocytes/chemistry , Fatty Acids, Essential/administration & dosage , Female , Germany , Gestational Age , Humans , Hungary , Infant, Newborn , Isomerism , Maternal Nutritional Physiological Phenomena , Phosphatidylcholines/analysis , Phosphatidylethanolamines/analysis , Pregnancy , Spain , Trans Fatty Acids/administration & dosage
20.
Article in German | MEDLINE | ID: mdl-21347765

ABSTRACT

The high prevalence of childhood obesity necessitates broadly effective prevention measures. A behavioral program for children in daycare settings was developed, and its effects were assessed in a 2-year cluster randomized controlled trial. A total of 64 daycare settings were cluster randomized in a 2:1 ratio to intervention and control in order to assess the effects of the program. Samples of 1318 and 1340 children were assessed after 5.7±2.6 and 17.6±2.3 months. Main outcome measures were prevalence of high fruit and vegetable consumption and of low consumption of high caloric drinks at home assessed by parental questionnaires. TigerKids achieved a significantly higher prevalence of high home consumption of fruits (66.6 vs. 55.7%, p<0.0001) and vegetables (42.7 vs. 33.6%, p=0.001) as well as a lower frequency of high consumption of energy rich beverages (47.7 vs. 60.4%, p<0.0001). The TigerKids group tended to show a lower prevalence of overweight (13.9 vs. 18.0%, p=0.05) and obesity (3.4 vs. 5.4%, p=0.07) in the first year. TigerKids is a low cost program applied in daycare settings which achieves significant behavioral changes in the home environment.


Subject(s)
Health Promotion/statistics & numerical data , Obesity/epidemiology , Obesity/prevention & control , Adolescent , Child , Child, Preschool , Female , Germany/epidemiology , Humans , Male , Prevalence , Treatment Outcome
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