Kathy Kennedy

How much loss to follow-up is acceptable in long-term randomised trials and prospective studies?

to test early nutritional interventions and prospective observational cohorts. RCTs are generally accepted as methodologically the best approach for informing health policy. They can equalise unknown as well as known confounding factors and so can demonstrate causation; they permit estimation of effect size and so can be used to assess likely economic

Promotion of Faster Weight Gain in Infants Born Small for Gestational Age Is There an Adverse Effect on Later Blood Pressure

Background— Being born small for gestational age is associated with later risk factors for cardiovascular disease, such as high blood pressure. Promotion of postnatal growth has been proposed to ameliorate these effects. There is evidence in animals and infants born prematurely, however, that promotion of growth by increased postnatal nutrition increases rather than decreases later cardiovascular risk. We report the long-term impact of growth promotion in term infants born small for gestational age (birth weight <10th percentile). Methods and Results— Blood pressure was measured at 6 to 8 years in 153 of 299 (51%) of a cohort of children born small for gestational age and randomly assigned at birth to receive either a standard or a nutrient-enriched formula. The enriched formula contained 28% more protein than standard formula and promoted weight gain. Diastolic and mean (but not systolic) blood pressure was significantly lower in children assigned to standard compared with nutrient-enriched formula (unadjusted mean difference for diastolic blood pressure, −3.2 mm Hg; 95% CI, −5.8 to −0.5; P=0.02) independent of potential confounding factors (adjusted difference, −3.5 mm Hg; P=0.01). In observational analyses, faster weight gain in infancy was associated with higher later blood pressure. Conclusions— In the present randomized study targeted to investigate the effect of early nutrition on long-term cardiovascular health, we found that a nutrient-enriched diet increased later blood pressure. These findings support an adverse effect of relative “overnutrition” in infancy on long-term cardiovascular disease risk, have implications for the early origins of cardiovascular disease hypothesis, and do not support the promotion of faster weight gain in infants born small for gestational age.

Nutrition in infancy and long-term risk of obesity: evidence from 2 randomized controlled trials

BACKGROUND Growth acceleration as a consequence of relative overnutrition in infancy has been suggested to increase the risk of later obesity. However, few studies have investigated this association by using an experimental study design. OBJECTIVE We investigated the effect of early growth promotion on later body composition in 2 studies of infants born small for gestational age (weight <10th percentile in study 1 and <20th percentile in study 2). DESIGN We reviewed a subset of children (n = 153 of 299 in study 1 and 90 of 246 in study 2) randomly assigned at birth to receive either a control formula or a nutrient-enriched formula (which contained 28-43% more protein and 6-12% more energy than the control formula) at 5-8 y of age. Fat mass was measured by using bioelectric impedance analysis in study 1 and deuterium dilution in study 2. RESULTS Fat mass was lower in children assigned to receive the control formula than in children assigned to receive the nutrient-enriched formula in both trials [mean (95% CI) difference for fat mass after adjustment for sex: study 1: -38% (-67%, -10%), P = 0.009; study 2: -18% (-36%, -0.3%), P = 0.04]. In nonrandomized analyses, faster weight gain in infancy was associated with greater fat mass in childhood. CONCLUSIONS In 2 prospective randomized trials, we showed that a nutrient-enriched diet in infancy increased fat mass later in childhood. These experimental data support a causal link between faster early weight gain and a later risk of obesity, have important implications for the management of infants born small for gestational age, and suggest that the primary prevention of obesity could begin in infancy.

Dual-Energy X-ray Aborptiometry Assessment in Children and Adolescents with Diseases that May Affect the Skeleton: The 2007 ISCD Pediatric Official Positions

The Task Force focusing on the use of dual energy X-ray absorptiometry (DXA) in children and adolescents with diseases that may affect the skeleton reviewed over 300 articles to establish the basis for the Official Positions. A significant number of studies used DXA-based outcome measures to assess the effects of specific interventions and charted the natural history of incremental changes in bone size and mass in specific disease states in children. However, the utility of DXA in clinical practice has not been evaluated systematically, in large part due to the lack of a workable definition for childhood osteoporosis. Thus, in combination with the Official Positions addressing the diagnosis of osteoporosis in children, and the reporting of DXA results in children, this document presents clear guidelines from which clinicians and researchers alike can work. This report delineates a set of disorders in which it is appropriate to use DXA as part of the comprehensive assessment of skeletal health in children and adolescents, and provides guidance concerning the initiation of assessment and the frequency of monitoring. Importantly, this document also highlights significant gaps in our knowledge, emphasizing areas for future research.

Pediatric reference data for lean tissue properties: density and hydration from age 5 to 20 y

BACKGROUND Hydrometry and densitometry are widely used to assess pediatric body composition due to their ease of application. The accuracy of these techniques depends on the validity of age- and sex-specific constant values for lean tissue hydration or density. Empirical data on these constants, and their variability between individuals, are lacking. OBJECTIVES The objectives were to measure lean tissue hydration and density in a large sample of children and adolescents and to derive prediction equations. DESIGN Body composition was measured in 533 healthy individuals (91% white) aged 4-23 y by using the 4-component model. Age- and sex-specific median values for hydration and density were obtained by using the LMS (lambda, mu, sigma) method. Regression analysis was used to generate prediction equations on the basis of age, sex, and body mass index SD score (BMI SDS). Values were compared with those in previously published predictions. RESULTS Age-associated changes in density and hydration differed between the sexes. Compared with our empirical values, use of published values resulted in a mean bias of 2.1% fat (P < 0.0001). Age, sex, and BMI SDS were all significant predictors of lean tissue hydration and density. With adjustment for age and sex, hydration was higher, and density lower, in higher-BMI SDS individuals. CONCLUSIONS The chemical maturation of lean tissue is not a linear process and proceeds differently in males and females. Previously published reference values are inaccurate and induce clinically significant bias in percentage fat. New empirical reference values are provided for use in pediatric hydrometry and densitometry. Further research that extends to cover nonwhite ethnic groups is needed.

Body-composition reference data for simple and reference techniques and a 4-component model: a new UK reference child

BACKGROUND A routine pediatric clinical assessment of body composition is increasingly recommended but has long been hampered by the following 2 factors: a lack of appropriate techniques and a lack of reference data with which to interpret individual measurements. Several techniques have become available, but reference data are needed. OBJECTIVE We aimed to provide body-composition reference data for use in clinical practice and research. DESIGN Body composition was measured by using a gold standard 4-component model, along with various widely used reference and bedside methods, in a large, representative sample of British children aged from 4 to ≥20 y. Measurements were made of anthropometric variables (weight, height, 4 skinfold thicknesses, and waist girth), dual-energy X-ray absorptiometry, body density, bioelectrical impedance, and total body water, and 4-component fat and fat-free masses were calculated. Reference charts and SD scores (SDSs) were constructed for each outcome by using the lambda-mu-sigma method. The same outcomes were generated for the fat-free mass index and fat mass index. RESULTS Body-composition growth charts and SDSs for 5-20 y were based on a final sample of 533 individuals. Correlations between SDSs by using different techniques were ≥0.68 for adiposity outcomes and ≥0.80 for fat-free mass outcomes. CONCLUSIONS These comprehensive reference data for pediatric body composition can be used across a variety of techniques. Together with advances in measurement technologies, the data should greatly enhance the ability of clinicians to assess and monitor body composition in routine clinical practice and should facilitate the use of body-composition measurements in research studies.

Sex-specific differences in essential fatty acid metabolism

Sex hormones may influence the enzymatic synthesis of long-chain polyunsaturated fatty acids (LC-PUFAs), which may lead to sex-specific differences in LC-PUFA status. Isotope studies with U-(13)C α-linolenic acid (ALA) have shown a considerably higher conversion rate of ALA to n-3 (omega-3) LC-PUFAs in women than in men. A review of the literature generally suggested that there was a higher contribution of arachidonic acid (AA) and docosahexaenoic acid (DHA) in blood lipids in women than in men; however, sex-specific differences were not seen in every study. The fatty acid composition of plasma phospholipids was recently reported separately for a large group of women and men (n > 3000) living in 15 regions of Europe. The contributions of saturated and monounsaturated fatty acids were higher, whereas those of AA and DHA were lower in men than in women; however, sex explained only ≈ 2% of the variability of plasma phospholipid DHA values. Results reported from a limited number of randomized controlled trials of perinatal LC-PUFA supplementation have, on occasion, shown sex-specific differences in some outcomes; however, the heterogeneity both in the interventions and outcomes measured made it difficult to draw conclusions on the direction or the extent of the effects. Data summarized in the current review highlight the importance of planning a subgroup analysis by sex in perinatal LC-PUFA supplementation trials.

Postnatal growth in preterm infants and later health outcomes: a systematic review

In preterm infants, poor postnatal growth is associated with adverse neurocognitive outcomes; conversely, rapid postnatal growth is supposedly harmful for future development of metabolic diseases.

10-year Cognition in Preterms After Random Assignment to Fatty Acid Supplementation in Infancy

OBJECTIVE: To test the hypothesis that long-chain polyunsaturated fatty acid (LCPUFA) supplementation in infancy would improve cognition into later childhood (after 9 years) at both general and specific levels. METHODS: A comprehensive cognitive battery was completed by 107 formerly preterm infants (mean age: 128 months). As infants, they had been assigned randomly to receive LCPUFA-supplemented (N = 50) or control (N = 57) formula, between birth and 9 months; the docosahexaenoic acid level (DHA) in the supplemented formulas was 0.5%. In addition to randomized comparisons, we planned supplementary analyses to examine the effects of both gender and feeding group (those receiving some maternal breast milk versus those receiving none). RESULTS: There were no significant differences between randomized diet groups on any cognitive measure. There was significant interaction between gender and supplementation; girls only showed beneficial effects of LCPUFAs on literacy. Significant interaction also occurred between feeding group and supplementation; increases of 0.7 SD in verbal IQ, full-scale IQ, and memory scores were found for the LCPUFA group, but only for infants who received only formula and no maternal breast milk. CONCLUSIONS: The results of this post–9-year cognitive follow-up study in a randomized trial of LCPUFA-supplemented formula for preterm infants suggest no overall group effects but indicate that gender-specific and diet-specific effects may exist. The data provide some evidence that LCPUFAs are a key factor in the cognitive benefits of breast milk. Caution is advised in data interpretation because of the small groups used.

Milk composition of insulin-dependent diabetic women

The macronutrient, trace mineral, and immunological contents of milk of five moderately controlled, insulin-dependent diabetic women were studied at 3 months postpartum. Concentrations of total nitrogen, lactose, fat, and energy were not distinguishable from those in milk of nondiabetic women. Glucose concentrations in milk from diabetic women were significantly higher (p less than 0.001) and more variable. The macro- and trace minerals (Ca, P, Mg, K, Zn, Cu, and Fe) were within normal ranges with the exception of Na which was higher in milk from the diabetic women (p less than 0.05). The concentrations of lactoferrin and secretory IgA were not statistically different from reference norms. Milk composition of five insulin-dependent diabetic women was not distinguishable from that of the reference population, with the exceptions of Na and glucose concentrations, which were slightly elevated.