Z score prediction model for assessment of bone mineral content in pediatric diseases.

The objective of this study was to develop an anthropometry-based prediction model for the assessment of bone mineral content (BMC) in children. Dual-energy X-ray absorptiometry (DXA) was used to measure whole-body BMC in a heterogeneous cohort of 982 healthy children, aged 5-18 years, from three ethnic groups (407 European- American [EA], 285 black, and 290 Mexican-American [MA]). The best model was based on log transformations of BMC and height, adjusted for age, gender, and ethnicity. The mean +/- SD for the measured/predicted in ratio was 1.000 +/- 0.017 for the calibration population. The model was verified in a second independent group of 588 healthy children (measured/predicted In ratio = 1.000 +/- 0.018). For clinical use, the ratio values were converted to a standardized Z score scale. The whole-body BMC status of 106 children with various diseases (42 cystic fibrosis [CF], 29 juvenile dermatomyositis [JDM], 15 liver disease [LD], 6 Rett syndrome [RS], and 14 human immunodeficiency virus [HIV]) was evaluated. Thirty-nine patients had Z scores less than -1.5, which suggest low bone mineral mass. Furthermore, 22 of these patients had severe abnormalities as indicated by Z scores less than -2.5. These preliminary findings indicate that the prediction model should prove useful in determining potential bone mineral deficits in individual pediatric patients.

Basal and postprandial metabolic rates in lactating and nonlactating women.

Basal and postprandial metabolic rates were determined by indirect calorimetry in lactating, nonlactating postpartum, and nulliparous women who received a controlled diet of protein at 1.0 g.kg-1.d-1 and energy that approximated usual intake levels on the basis of diet records. Milk production was measured by the test-weighing procedure and by milk expression. Basal metabolic rates (BMRs) were similar among all groups of women. No relationships were detected between BMRs and postpartum time in lactating women. In contrast, postprandial metabolic rates (PMRs) increased (P less than 0.01) in lactating compared with nonlactating women. Milk nitrogen concentrations but not energy showed a linear relationship with PMR (r = 0.86, P less than 0.001). The energy cost of milk production was estimated to be 125% of the energy output in milk. Thus, increased energy needs during lactation are associated not only with milk production but also with elevated PMRs. This increase was met by an increase in dietary energy intakes of 50% above the intakes of nonlactating counterparts.

Dietary protein and nitrogen balance in lactating and nonlactating women.

Adaptive responses of body protein metabolism to dietary protein intakes of 1.0 g.kg body wt-1.d-1 were determined by nitrogen balance and urinary 3-methylhistidine excretion in lactating and nonlactating women. Despite higher energy intakes (p less than 0.04), lactating women had lower nitrogen balances compared with nonlactating postpartum and nulliparous women (p less than 0.001). Nitrogen losses in milk did not account entirely for these differences. Nitrogen balance showed linear (p less than 0.04) and quadratic (p less than 0.03) trends over time postpartum among the lactating women. Urinary 3-methylhistidine excretion also was reduced (p less than 0.05) in lactating compared with nonlactating women. These observations suggest that protein intakes of 1.0 g.kg body wt-1.d-1 in lactating women are associated with adaptive responses that promote the conservation of skeletal muscle protein stores and that currently recommended dietary protein allowances may be insufficient to meet the nutritional needs of well-nourished lactating women.

Lean body mass of well-nourished women is preserved during lactation.

To determine whether the lean body mass of well-nourished women was mobilized to support milk protein output during lactation, the body composition of 10 lactating and 10 nonlactating women was examined longitudinally at 6-wk intervals between 6 and 24 wk postpartum and at 52 wk postpartum, and that of 10 nulliparous women was examined at equivalent intervals, by using clinical anthropometry and whole-body potassium counting. Milk production was determined at 6-wk intervals during the period of exclusive breast-feeding (6-24 wk postpartum) by the test-weighing procedure. Milk composition was determined by chemical analysis. Dietary intakes were determined at 6-wk intervals between 6 and 24 wk postpartum from 3-d food records with use of a nutrient database. Lean body mass was maintained in women who exclusively breast-fed their infants during the first 6 mo postpartum while consuming dietary protein in amounts that exceeded those of their nonlactating counterparts by 55%. The high protein intakes were sustained throughout lactation despite a progressive reduction by 32% of milk protein output. Lean body mass was preserved throughout lactation in well-nourished women, suggesting that the metabolic needs of milk protein production were met solely by higher protein intakes of the lactating women.

Whole-body protein turnover in the fed state is reduced in response to dietary protein restriction in lactating women.

We examined the adaptive responses of body protein metabolism in the fed state to dietary protein restriction in lactating women to determine whether rates of body protein degradation and synthesis were lower than those of nonlactating women. Thirteen healthy women (five lactating, four nonlactating postpartum, four nulliparous) aged 28-32 y were given protein intakes of 1.5, 0.4, and 1.0 g.kg-1.d-1 over three consecutive 3-d periods, respectively. At the end of each period, while in the fed state, subjects received orally a single bolus dose of [1-13C]leucine. A 24-h urine collection was obtained simultaneously. Whole-body protein metabolism was characterized by using the end product model based on nitrogen excretion and leucine catabolism. Nitrogen flux and rates of protein degradation and synthesis in the fed state were significantly lower at a dietary protein intake of 1.0 g.kg-1.d-1 in lactating women than in their nonlactating postpartum counterparts. Net protein retention in the fed state was significantly higher at a dietary protein intake of 1.0 g.kg-1.d-1 in lactating than in nonlactatating postpartum and nulliparous women because of the relatively greater reduction in protein degradation than in protein synthesis. These studies suggest that lactating women rapidly adapt to dietary protein restriction by down-regulating protein metabolism, and that 13C-labeled amino acid tracers in combination with urinary nitrogen excretion serve as useful metabolic markers for the adequacy of the dietary protein content of lactating women.

Relationship of plasma leucine and alpha-ketoisocaproate during a L-[1-13C]leucine infusion in man: a method for measuring human intracellular leucine tracer enrichment.

The keto analog of leucine, alpha-ketoisocaproate (KIC), is formed intracellularly from leucine and is released, in part, into the systemic circulation. Therefore. KIC can be used to estimate intracellular leucine tracer enrichment in man during labeled-leucine tracer experiments without requiring tissue biopsy samples. This approach was studied in young, healthy, male adults maintained on different dietary protein intakes from generous (1.5 g kg-1d-1) to deficient (0.0 g kg-1d-1) for 5-7 day periods. At the end of each dietary period, the volunteers were given a primed, continuous infusion of L-[1-13C]leucine either after an overnight fast (postabsorptive state) or while being fed hourly aliquots of the same diet. The plasma concentrations of all 3 branched-chain amino and keto acid pairs were measured from early morning blood samples taken from 4 subjects at 4 different levels of protein intake. Leucine concentration showed a weak correlation, and valine concentration showed a strong correlation with protein intake; isoleucine and the 3 keto acids did not. However, each branched-chain amino acid concentration was strongly correlated with its corresponding keto acid concentration. In plasma samples obtained during the L-[1-13C]leucine infusions, the ratio of [1-13C]KIC to [1-13C]leucine enrichment ratio remained relatively constant (77 +/- 1% over the wide range of dietary protein intakes and for both the fed and postabsorptive states. For the tissues from which the plasma KIC originates, the rate of plasma leucine into cells will account for approximately 77% of the intracellular leucine flux with the remaining 23% coming primarily from leucine release via protein breakdown. The constant nature of the plasma KIC to leucine 13C enrichment ratio implies that relative changes in leucine kinetics will appear the same under many dietary circumstances regardless of whether plasma leucine or KIC enrichments are used for the calculations.

Whole-body protein metabolism in lactating and nonlactating women.

The adaptive responses of body protein metabolism to lactation were characterized in women at 1, 5, and 12 mo postpartum and in nulliparous controls during a controlled diet of measured protein and energy intakes by nitrogen balance, a constant infusion of [13C]bicarbonate, and a primed constant infusion of [1-13C]leucine and [alpha-15N]-lysine. Dietary energy intakes in the lactating women were 27% greater than those in the nulliparous controls. Despite these differences, lactating women had significantly lower nitrogen balances compared with the nonlactating women (-4.0 +/- 37.8 vs. +44.7 +/- 30.8 mg.kg-1.day-1). No significant differences in amino acid flux, oxidation, or incorporation into protein were detected during fasting conditions in the two groups of women. However, significantly positive associations were noted between dietary intakes and the variables of protein metabolism in the lactating women. A more complete understanding of the mechanisms that regulate the disposition of dietary nutrients into maternal body stores or milk production will enhance the determination of nutrient requirements in lactating women.

Disposition of olsalazine and metabolites in breast milk.

This study examined the disposition of olsalazine and its metabolites into breast milk after the ingestion of a single dose of 500 mg olsalazine. Blood and serum samples were obtained for 48 hours after the ingestion of 500 mg olsalazine in a 39-year-old lactating woman. Blood samples were obtained at .0, .5, 1, 2, 4,6, 24.5, 26, and 48 hours. Maternal milk samples were obtained at .0, .5, 2, 4, 6, 14, 24, 28, 36, and 48 hours. Olsalazine and olsalazine-S underwent high-pressure liquid chromatography analysis, and 5-ASA and Ac 5-ASA underwent fluorometric detection. Acetylated-5-ASA achieved concentrations of .8, .86, and 1.24 mumol/L in breast milk at 10, 14, and 24 hours, respectively. Olsalazine, olsalazine-S, and 5-ASA were undetectable in the breast milk for 48 hours after drug administration. Clinically significant drug exposure in the breast-fed infant is unlikely after a maternal single dose of olsalazine. Idiosyncratic hypersensitivity, however, remains a possibility even if the infant is exposed to only minute quantities.

Relationships among lactation performance, maternal diet, and body protein metabolism in humans.

The relationships between lactation performance and maternal diet and body protein metabolism were determined at 1, 5, and 12 months postpartum in lactating women who consumed a controlled diet of measured protein and energy. Milk production was measured by the 24-h test weighing procedure. Maternal body protein metabolism was evaluated by nitrogen balance and a primed, constant infusion of [1-13C]leucine and [alpha-15N]lysine. Milk production was associated positively with lysine flux (P less than 0.05, r = 0.59), leucine incorporation into body protein (P less than 0.05, r = 0.58), nitrogen intakes (P less than 0.05, r = 0.56), and energy intakes (P less than 0.01, r = 0.69). When adjusted for postpartum time, significant associations between total nitrogen concentrations in milk and nitrogen balance also were present (P less than 0.05, r = 0.77). These observations document associations among lactation performance, maternal diet, and the metabolic responses of body protein stores in well-nourished women and suggest strategies for the improvement of milk production in settings where nutrient insufficiency and malnutrition prevail.

Complications of essential amino acid hyperalimentation in children with acute renal failure.

The metabolic effects of intravenous hyperalimentation, using an essential amino acid (EAA) and glucose solution, were evaluated in 2 children with acute renal failure. Hyperammonemia and hyperchloremic metabolic acidosis associated with elevated plasma methionine and depressed plasma citrulline, ornithine, arginine, and histidine levels complicated the nutritional therapy. Initial infusion of a complete amino acid (CAA) solution was not associated with these aberrations and reintroduction of a CAA solution after the EAA trial resulted in a progressive amelioration of or complete recovery from these metabolic disturbances. It is likely that the hyperammonemia was due to an arginine deficiency, while excess methionine and presumably sulfate production may have contributed to the hyperchloremic metabolic acidosis in these two children.

Altered energy balance may account for growth failure in Rett syndrome.

To determine whether alterations in energy balance account for growth failure in Rett syndrome, we measured dietary energy intakes, fecal fat losses, activity patterns, and sleeping as well as quietly and actively awake metabolic rates in Rett syndrome girls and healthy controls. Dietary energy intakes and fecal fat losses did not differ between the groups. Metabolic rates while sleeping and quietly awake were 23% lower (P < .05) in Rett syndrome girls than in controls; metabolic rates while actively awake did not differ between the groups. However, because of the 2.4-fold greater time (P < .001) spent in involuntary motor movement, energy expenditure associated with activity was twofold greater (P < .05) in Rett syndrome girls than in controls. Although total daily energy expenditure of the two groups did not differ significantly, energy balance was less positive in the Rett syndrome girls than in the controls. This small difference in energy balance, if sustained over months to years, is sufficient to account for growth failure in Rett syndrome girls.

Organ growth in Rett syndrome: a postmortem examination analysis.

Rett syndrome is a disorder of unknown etiology in females that manifests as severe mental and motor retardation during the first years of life. A postnatal pattern of altered growth is its earliest clinical expression. Head growth decelerates during the first year of age and is followed by a decline in somatic (height/weight) growth. The decreased occipitofrontal circumference (OFC) is reflected in decreased brain size, and measurements of the dendrites of cortical neurons suggest that a developmental and growth arrest have occurred. To further document growth in Rett syndrome, measurements of organ weights, as recorded in 39 postmortem examination studies were compared with normal organ weights for females of comparable age and height. These organ weights suggest that the pattern of growth failure in Rett syndrome, as compared with other forms of mental handicap, such as Down syndrome and Turner's syndrome, may be unique. In Rett syndrome the rate of brain growth, as derived from OFC, decelerates after birth. The increment in normal brain weight after 4 years of age, the age of the first postmortem examinations, is not observed in the Rett brain. The heart, kidneys, liver, and spleen grow at the normally defined rate until 8-12 years of age, when their growth rate decelerates, but their growth continues achieving organ weights that are appropriate for the height of the female. Adrenal weights are normal. These observations suggest that despite a generalized decreased growth in Rett syndrome the brain may be preferentially affected in this syndrome.

Lactational performance of adolescent mothers shows preliminary differences from that of adult women.

PURPOSE: The purposes of this study were to characterize milk production, milk composition, and the lactational behavior of adolescent mothers, and to compare their lactational performance with that of adult females. METHODS: Twenty-two lactating mothers, 11 adolescents and 11 adults, were studied at 6-week intervals between 6 and 24 weeks postpartum. Milk production was determined by the test-weighing procedure. Milk nutrient composition was determined by standard chemical analyses. Frequency and duration of nursing and the use of supplemental formula and complementary foods were recorded. RESULTS: The amount of milk adolescents produced at 6, 12, 18, and 24 weeks postpartum ranged from 37-54% less (P < .05) than that of the adults and resulted in a 45% weaning rate at 18 weeks postpartum in the younger group. Milk nutrient concentrations were not significantly different between groups, with the exception of significantly higher sodium concentrations during early lactation in the adolescents' milk. Lactational behavior differed significantly between the adolescent and adult groups; however, with the exception of the lower frequency of daytime nursing and the tendency toward the early introduction of supplemental formula in the adolescent group, these behavioral differences were the result of the racial and ethnic differences between the two groups. The differences in lactational behavior did not contribute to the differences in milk production between the adolescents and adult mothers. CONCLUSIONS: This preliminary study suggests that milk production was reduced in adolescent mothers compared with adult females. Although behavioral strategies that increase the frequency of daytime nursing and reduce the frequency of supplemental feedings may enhance the milk production of adolescent mothers, other biological factors may account for their poorer lactational performance.

PIP: In a comparative study of the lactational performance of 11 adolescent and 11 adult breast-feeding mothers from the US, adolescents were found to produce significantly less milk and lactate for a significantly shorter period of time than their adult counterparts. All subjects were assessed at 6-24 weeks postpartum. The adolescents produced 37% and 54% less milk at 6 and 24 weeks postpartum, respectively, than adult women. These differences in milk production were significant even when adjusted for differences in the frequency and duration of breast feeding episodes and use of supplementary feeds. The amount of dietary energy the infants of adolescents received from human milk alone was clearly inadequate, at every time point, to support normal growth rates. In both groups, the average frequency of nursing episodes during the first 12 weeks postpartum was 7 or more per 24 hours (consistent with current recommendations for adequate lactation); adolescents, however, spent significantly less time nursing and provided greater quantities of supplementary feeds. While all adult women breast-fed throughout the study period, 20% of adolescents had stopped breast feeding by 12 weeks, 50% weaned by 18 weeks, and 64% had discontinued breast feeding by 24 weeks. Unexpectedly, the energy, lactose, fat, total nitrogen, protein nitrogen, nonprotein nitrogen, sodium, potassium, calcium, and phosphorous concentrations showed little difference between the two age groups. The absence of data from the first 6 weeks of life makes it impossible to rule out a role for early formula supplementation in the decreased milk production of adolescents. It is believed,however, that adolescents may be biologically incapable of producing a full complement of milk because of their developmental immaturity.

Nutritional management of inflammatory bowel disease.

Malnutrition and growth failure are frequent complications of inflammatory bowel disease in childhood owing to inadequate dietary nutrient intakes, excessive intestinal losses, malabsorption, and increased nutrient requirements. Aggressive nutritional therapy is indicated for primary and supportive management of disease activity, drug nutrient interactives, individual nutrient abnormalities, and the overall complications of inflammatory bowel disease, malnutrition, and growth failure. The prevention of nutritional disorders in inflammatory bowel disease is accomplished by monitoring anthropometric and biochemical indices and by instituting appropriate enteral or parenteral nutritional therapy when indicated.

Special properties of human milk.

Human milk is a highly complex fluid with a nutrient balance and an array of functional properties that may promote a level of metabolic efficiency that is not attainable when a cow milk-based formula is fed. This is not a novel idea. Mitchell in 1933 proposed that the level of efficiency of energy use is determined by the nutrient "balance" in the diet. Nonetheless, difficulties remain in the attempt to reconcile the low levels of intake with established estimates of energy needs. If the amount of energy that appears necessary for growth and maintenance of a 4-month-old infant is compared with that from his or her intake of an exclusive human milk diet, the infant should have little or no energy left for activity. Do metabolic economies contribute to more efficient uses of energy for growth and maintenance in breastfed infants? Are there differences in body composition? Does more efficient use of energy occur as a result of a decrease in clinical and subclinical infections? Is efficient energy utilization accomplished by significant curtailment in activity? If an excess level of energy is consumed by bottlefed infants, what are the positive or negative short-term or long-term consequences? These questions are the focus of research in numerous laboratories. Field and clinical studies of breastfed infants and in vitro studies of human milk offer unique opportunities to understand basic mechanisms of human adaptations to nutrient intake and environmental challenges.

Massive upper gastrointestinal hemorrhage in an infant following cardiac surgery.

This is a case of massive upper gastrointestinal hemorrhage and hematoma formation in a 32-day-old infant following uneventful repair of congenital heart disease. Stress ulcers and gastrointestinal hemorrhage are rare complications of cardiac surgery in the young. Conservative management often fails and early surgery can be lifesaving. The etiology of this problem remains unknown and more work is needed so that effective preventive measures can be developed.

Intestinal button implantation for obstipation and fecal impaction in children.

Chronic obstipation and fecal impaction in children can be difficult management problems for pediatricians. We describe a novel approach to the management of obstipation and fecal impaction: the implantation of the button gastrostomy device in the appendiceal stump or the terminal ileum. We report the procedure in two children. One child had pseudoobstruction syndrome complicated by recurrent obstipation; the other had cystic fibrosis complicated by recurrent obstruction from meconium ileus equivalent. Both children received a polyethylene glycol/electrolyte solution, with or without pancreatic enzymes, which was administered through the button. The children have remained essentially asymptomatic for at least 10 months. We believe that this is the first report of the use of a button gastrostomy device to successfully manage chronic obstipation and recurrent fecal impaction in children.

Clinical severity and quality of life in children and adolescents with Rett syndrome.

OBJECTIVE: The clinical features and genetics of Rett syndrome (RTT) have been well studied, but examination of quality of life (QOL) is limited. This study describes the impact of clinical severity on QOL among female children and adolescents with classic RTT. METHODS: Cross-sectional and longitudinal analyses were conducted on data collected from an NIH-sponsored RTT natural history study. More than 200 participants from 5 to 18 years of age with classic RTT finished their 2-year follow-up at the time of analysis. Regression models after adjustment for their MECP2 mutation type and age at enrollment were used to examine the association between clinical status and QOL. RESULTS: Severe clinical impairment was highly associated with poor physical QOL, but worse motor function and earlier age at onset of RTT stereotypies were associated with better psychosocial QOL; conversely, better motor function was associated with poorer psychosocial QOL. CONCLUSIONS: Standard psychosocial QOL assessment for children and adolescents with RTT differs significantly with regard to their motor function severity. As clinical trials in RTT emerge, the Child Health Questionnaire 50 may represent one of the important outcome measures.

Epilepsy and the natural history of Rett syndrome.

BACKGROUND: Rett syndrome (RTT) is a neurodevelopmental disorder primarily seen in females, most with a mutation in MECP2. Epilepsy has been reported in 50%-80%. Previous reports were based on small sample sizes or parent-completed questionnaires, or failed to consider the impact of specific MECP2 mutations. METHODS: The Rare Disease Consortium Research Network for RTT is an NIH-funded project to characterize the clinical spectrum and natural history of RTT in advance of clinical trials. Evaluations include clinical status (classic vs atypical RTT), MECP2 mutations, clinical severity, and presence, frequency, and treatment of seizures. RESULTS: Enrollment as of June 2008 is 602; 528 (88%) meet clinical criteria for classic RTT. Of these, 493 (93%) have MECP2 mutations. Age range was 8 months to 64 years. A total of 360 (60%) were reported to have seizures, including 315 (60%) classic and 45 (61%) atypical RTT. Physician assessment of the 602 indicated that 48% had seizures. There was no significant difference in seizure occurrence by race/ethnicity. A significant age impact for seizures was seen and seizures were infrequent before age 2 years. MECP2 mutations most frequently associated with epilepsy were T158M (74%) and R106W (78%), and less frequently R255X and R306C (both 49%). Individuals with seizures had greater overall clinical severity, and greater impairment of ambulation, hand use, and communication. DISCUSSION: Seizures are common in Rett syndrome, have an age-related onset and occurrence, vary by mutation, and are associated with greater clinical severity. This information represents a key consideration for designing clinical trials.