R. Hankard

Longitudinal evaluation and risk factors of lipodystrophy and associated metabolic changes in HIV-infected children

Objective:To assess the rate of progression of lipodystrophy and the associated metabolic disturbances over a 2-year period in children and to assess risk factors associated with lipodystrophy and metabolic disturbances. Design:Multicenter 2-year prospective study with a standardized evaluation. Methods:One hundred thirty children (median age = 10 years, 64 boys and 66 girls) receiving antiretroviral therapy were recruited in 3 pediatric clinics. Lipodystrophy was defined based on 4 skinfold thickness measurements. Fasting lipids and glucose profile were measured in all children. Results:The proportion of children presenting with lipodystrophy was 24.6%. Nineteen percent of children had high-density lipoprotein values less than 1 mmol/L. Twenty-two percent and 15% of children had values greater than 2 standard deviations for age and gender for cholesterol and triglycerides, respectively. A total of 13.2% showed insulin resistance. A total of 42.7% showed at least 1 of these biologic disturbances. Prospective follow-up showed no progression at all over 2 years, except for a doubling of the number of children with insulin resistance. In multivariate analyses, ethnicity, previous severe clinical condition, duration of HIV infection, and nucleoside reverse transcriptase inhibitor treatment were significantly associated with lipodystrophy. Tanner stage V of puberty, severe clinical symptoms and protease inhibitor treatment were independently associated with the risk of metabolic disturbances. Conclusions:Puberty seems to be the time when HIV-infected children taking potent antiretroviral therapy are more likely to develop lipodystrophy and metabolic complications, especially in children with a severe underlying HIV infection. Once developed, lipodystrophy and metabolic changes seem to be extremely stable with time.

Decreased Full Breastfeeding, Altered Practices, Perceptions, and Infant Weight Change of Prepregnant Obese Women: A Need for Extra Support

OBJECTIVE. The purpose of this work was to compare breastfeeding practices, perceptions, and infant weight change of prepregnant obese versus normal-weight mothers in the first 3 months postpartum. PATIENTS AND METHODS. For the prospective case-control study, obese mothers (prepregnant BMI ≥ 30 kg/m2) were matched with normal-weight mothers (18.5 ≤ prepregnant BMI < 25 kg/m2) according to initial infant feeding, parity, maternal age, ethnicity, and education. Participants completed an oral questionnaire in the hospital and a telephone interview at 1 and 3 months postpartum. RESULTS. Of 1432 mothers who had given birth at a university hospital in France, 10% were obese. Breastfeeding initiation was lower for obese (48%) versus normal-weight (64%) mothers. A total of 111 of 141 obese mothers were paired with 111 normal-weight mothers. Infant birth weight was similar for newborns of obese and normal-weight mothers. Among mothers who initiated breastfeeding, infant weight gain from 0 to 1 month was lower in breastfed infants of obese mothers compared to normal-weight mothers. Obese mothers were less likely to maintain full breastfeeding at 1 month and 3 months. The percentage of mothers breastfeeding to any extent did not differ between obese and reference women. Obese mothers more often felt uncomfortable breastfeeding in public at 3 months. Fewer obese mothers perceived that their milk supply was sufficient at 1 month and 3 months. Despite greater breastfeeding difficulties, obese mothers were less likely to seek support for breastfeeding in the first 3 months postpartum. CONCLUSIONS. Pediatricians and health professionals should recognize that obese mothers have different breastfeeding practices and perceptions. Extra support and intervention are needed among obese mothers during prenatal and early postnatal periods so that their children can benefit from breastfeeding.

Vitamin D: Still a topical matter in children and adolescents. A position paper by the Committee on Nutrition of the French Society of Paediatrics

The aims of the present position paper by the Committee on Nutrition of the French Society of Paediatrics were to summarize the recently published data on vitamin D in infants, children and adolescents, i.e., on metabolism, physiological effects, and requirements and to make recommendations on supplementation after careful review of the evidence. Scientific evidence indicates that calcium and vitamin D play key roles in bone health. The current evidence, limited to observational studies, however, does not support other benefits for vitamin D. More targeted research should continue, especially interventional studies. In the absence of any underlying risk of vitamin D deficiency, the recommendations are as follows: pregnant women: a single dose of 80,000 to 100,000 IU at the beginning of the 7th month of pregnancy; breastfed infants: 1000 to 1200 IU/day; children less than 18 months of age, receiving milk supplemented with vitamin D: an additional daily dose of 600 to 800 IU; children less than 18 months of age receiving milk not supplemented with vitamin D: daily dose of 1000 to 1200 IU; children from 18 months to 5 years of age: 2 doses of 80,000 to 100,000 IU every winter (November and February). In the presence of an underlying risk of vitamin D deficiency (dark skin; lack of exposure of the skin to ultraviolet B [UVB] radiation from sunshine in summer; skin disease responsible for decreased exposure of the skin to UVB radiation from sunshine in summer; wearing skin-covering clothes in summer; intestinal malabsorption or maldigestion; cholestasis; renal insufficiency; nephrotic syndrome; drugs [rifampicin; antiepileptic treatment: phenobarbital, phenytoin]; obesity; vegan diet), it may be justified to start vitamin D supplementation in winter in children 5 to 10 years of age as well as to maintain supplementation of vitamin D every 3 months all year long in children 1 to 10 years of age and in adolescents. In some pathological conditions, doses of vitamin D can be increased. If necessary, the determination of 25(OH) vitamin D serum concentration will help determine the level of vitamin D supplementation.

Role of Glutamine as a Glucose Precursor in Fasting Humans

Recently, significant incorporation of labeled carbon into plasma glucose was documented during infusion of 14C-labeled glutamine in postabsorptive humans. Such labeling of plasma glucose can occur as a result of two different processes: either 1) through incorporation of glutamine carbon into glucose via glutamine entering Krebs cycle at a-ketoglutarate or 2) through simple fixation of labeled CO2 resulting from oxidation of labeled glutamine. Therefore, these studies were designed to determine 1) whether glutamine contributes carbon to gluconeogenesis other than through mere CO2 fixation, and, if so, 2) whether the apparent transfer of carbon from glutamine to glucose increases with fasting. Eight healthy adults were studied on two consecutive days: once after an overnight (18-h) fast and again on the second day of fasting (42-h fast). On each study day, subjects received a simultaneous 5-h infusion of D-[6,6-2H2]glucose, l-[3,4-13C2]glutamine, and l-[l-14C]leucine. Apparent rates of incorporation of glutamine carbon into glucose were estimated from the appearance of 13C into plasma glucose; glucose and glutamine production rates (appearance rate [-RJ) were determined from plasma [2H2]glucose and [13C2]glutamine enrichments, respectively. The appearance of 14C into plasma glucose was used to correct the measured rates of carbon transfer from glutamine to glucose as a result of CO2 fixation. We observed that of the apparent contribution of labeled glutamine to gluconeogenesis, only 4% occurred as a result of fixation of labeled CO2, while 96% seemed to occur through other routes. We also observed that between 18 and 42 h of fasting, 1) the relative contribution of protein breakdown to glutamine production was enhanced, while that of de novo synthesis declined; 2) the apparent contribution of glutamine to glucose production rose from 8 ± 1 to 16 ± 3% of overall glucose Ra; and 3) the relative apparent contribution of glutamine to gluconeogenesis remained constant. From the current data, it cannot be ascertained to what extent the apparent carbon transfer from glutamine to glucose represents a true contribution of glutamine to gluconeogenesis or mere carbon exchange between the trichloroacetic acid cycle and the gluconeogenic pathway. These findings are nevertheless compatible with a role of glutamine as a significant precursor of glucose in fasting humans.

Cohort Profile: The EDEN mother-child cohort on the prenatal and early postnatal determinants of child health and development

The overall objective of the EDEN study was to examine the relations and potential interactions between maternal exposures and health status during pregnancy, fetal development, health status of the infant at birth and the childs health and development.

Oral glutamine slows down whole body protein breakdown in Duchenne muscular dystrophy.

We determined whether glutamine has a protein anabolic effect in six 8-13-y-old boys with Duchenne muscular dystrophy. Children received a 5-h i.v. infusion of L-[1-13C]leucine and L-[2-15N]glutamine in the postabsorptive state on two consecutive days while drinking: 1) flavored water on one day, and 2) the same drink mixed with L-glutamine (800 μmol·kg-1·h-1), the other day. Oral glutamine administration was associated with an 8% decrease in leucine release from protein breakdown, from 116 ± 5 to 107 ± 6μmol·kg-1h-1 (p < 0.01), and a 35% decrease in leucine oxidation rate from 23 ± 2 to 15 ± 2μmol·kg-1·-1 (p < 0.01), resulting in no change in the nonoxidative leucine disposal, an index of protein synthesis. Whole body glutamine exchange in plasma doubled from 321 ± 22 to 623 ± 24 μmol·kg-1·h-1,p < 0.01, but glutamine from protein degradation and glutamine de novo synthesis both decreased (91 ± 4 versus 84± 5 μmol·kg-1·-1, p < 0.01, and 230 ± 21 versus 163 ± 25μmol·kg-1·h-1, p = 0.02, respectively). These data suggest that acute oral glutamine administration might have a protein-sparing effect in children with Duchenne muscular dystrophy, decreasing estimates of whole body protein degradation and glutamine de novo synthesis, therefore sparing nitrogen precursors.

Determinants of early ponderal and statural growth in full-term infants in the EDEN mother-child cohort study

BACKGROUND Growth velocity in the first months of postnatal life has been associated with later overweight and obesity. OBJECTIVE We analyzed prenatal and postnatal factors in association with weight, length, and growth velocities in the first 3 mo of life. DESIGN We estimated weight, length, and instantaneous weight- and length-growth velocities (in g/d and mm/d) in 1418 term infants at 1 and 3 mo of age and evaluated the following potential determinants: maternal prepregnancy body mass index (BMI), 1-h plasma glucose concentrations during pregnancy, smoking, socioeconomic status, parity, paternal BMI, parental heights, and infant feeding, gestational age, and sex. RESULTS Maternal obesity and plasma glucose concentrations were associated with the weights and lengths of offspring at birth but not at 1 and 3 mo after birth. In contrast, there was no association between paternal BMI and anthropometric measures of offspring at birth, but by 3 mo of age infants of obese fathers had significantly higher weights and weight-growth velocities than did infants of fathers with a normal BMI. Maternal weight gain was a significant predictor of weight at birth and 3 mo of age. Exclusively breastfed infants had a slower weight-growth velocity as early as 1 mo of age compared with exclusively formula-fed infants. CONCLUSIONS In the first 3 mo of life, the positive associations between maternal obesity, plasma glucose concentrations, and infant anthropometric measures at birth seem to progressively fade away, whereas the emerging association with paternal BMI may indicate an early postnatal influence of paternal genetics. Among the determinants we evaluated, some are potentially modifiable, such as maternal gestational weight gain and infant feeding. The identification of optimal patterns of growth remains crucial before providing any clinical recommendations.

[Breast feeding: health benefits for child and mother].

The prevalence of breastfeeding in France is one of the lowest in Europe: 65% of infants born in France in 2010 were breastfed when leaving the maternity ward. Exclusive breastfeeding allows normal growth until at least 6 months of age, and can be prolonged until the age of 2 years or more, provided that complementary feeding is started after 6 months. Breast milk contains hormones, growth factors, cytokines, immunocompetent cells, etc., and has many biological properties. The composition of breast milk is influenced by gestational and postnatal age, as well as by the moment of the feed. Breastfeeding is associated with slightly enhanced performance on tests of cognitive development. Exclusive breastfeeding for at least 3 months is associated with a lower incidence and severity of diarrhoea, otitis media and respiratory infection. Exclusive breastfeeding for at least 4 months is associated with a lower incidence of allergic disease (asthma, atopic dermatitis) during the first 2 to 3 years of life in at-risk infants (infants with at least one first-degree relative presenting with allergy). Breastfeeding is also associated with a lower incidence of obesity during childhood and adolescence, as well as with a lower blood pressure and cholesterolemia in adulthood. However, no beneficial effect of breastfeeding on cardiovascular morbidity and mortality has been shown. Maternal infection with hepatitis B and C virus is not a contraindication to breastfeeding, as opposed to HIV infection and galactosemia. A supplementation with vitamin D and K is necessary in the breastfed infant. Very few medications contraindicate breastfeeding. Premature babies can be breastfed and/or receive mothers milk and/or bank milk, provided they receive energy, protein and mineral supplements. Return to prepregnancy weight is earlier in breastfeeding mothers during the 6 months following delivery. Breastfeeding is also associated with a decreased risk of breast and ovarian cancer in the premenopausal period, and of osteoporosis in the postmenopausal period.

Glutamine metabolism in children with short-bowel syndrome: a stable isotope study.

ABSTRACT: Because glutamine is thought to be a major fuel for developing gut, we tested the hypothesis that extensive small-bowel resection alters whole-body glutamine metabolism in vivo. Eleven infants and children who had undergone extensive small intestinal resection (residual bowel length: 35 ± 13 cm; mean ± SD) and four control infants received 4-h primed, continuous i.v. infusions of l-[1-13C]leucine and L-[2-15N]glutamine in the postabsorptive state. The appearance rates of glutamine and leucine into plasma were determined from stable isotope enrichments in plasma at steady state. We observed the following: 1) Regardless of intestinal status, leucine and glutamine fluxes were higher in infants than values previously reported for adults. 2) Small-bowel resection was associated with a reduction in glutamine appearance rate (568 ± 124 μmol kg lean body mass-1 h-1 in short-bowel syndrome infants versus 816 ± 149 μmol kg lean body mass-1 h-1 in control infants; p < 0.05). 3) In contrast, leucine appearance rate was unaltered in short-bowel syndrome patients. The findings suggest that the small intestine plays a prominent role in glutamine metabolism in human infants.

Infant feeding patterns over the first year of life: influence of family characteristics

Background/Objectives:Early eating patterns and behaviors can determine later eating habits and food preferences and they have been related to the development of childhood overweight and obesity. We aimed to identify patterns of feeding in the first year of life and to examine their associations with family characteristics.Subjects/Methods:Our analysis included 1004 infants from the EDEN mother-child cohort. Feeding practices were assessed through maternal self-report at birth, 4, 8 and 12 months. Principal component analysis was applied to derive patterns from breastfeeding duration, age at complementary food (CF) introduction and type of food used at 1 year. Associations between patterns and family characteristics were analyzed by linear regressions.Results:The main source of variability in infant feeding was characterized by a pattern labeled ‘late CF introduction and use of ready-prepared baby foods’. Older, more educated, primiparous women with high monthly income ranked high on this pattern. The second pattern, labeled ‘longer breastfeeding, late CF introduction and use of home-made foods’ was the closest to infant feeding guidelines. Mothers ranking high on this pattern were older and more educated. The third pattern, labeled ‘use of adults’ foods’ suggests a less age-specific diet for the infants. Mothers ranking high on this pattern were often younger and multiparous. Recruitment center was related to all patterns.Conclusions:Not only maternal education level and age, but also parity and region are important contributors to the variability in patterns. Further studies are needed to describe associations between these patterns and infant growth and later food preferences.