Lewis A. Barness

Obesity: Genetic, molecular, and environmental aspects†

Obesity has emerged as one of the most serious public health concerns in the 21st century. Obese children tend to become obese adults. The dramatic rise in pediatric obesity closely parallels the rapid increase in the prevalence of adult obesity. As overweight children become adults they face the multitude of health problems associated with obesity at younger ages. The morbidity and mortality associated with obesity continue to increase. Obesity is one of the leading causes of preventable death. Complications of obesity include cardiovascular risks, hypertension, dyslipidemia, endothelial dysfunction, type 2 diabetes mellitus and impaired glucose tolerance, acanthosis nigricans, hepatic steatosis, premature puberty, hypogonadism and polycystic ovary syndrome, obstructive sleep disorder, orthopedic complications, cholelithiasis and pseudotumor cerebri. Genetic and molecular and environmental factors play an important role in the assessment and management of obesity.

Dietary nucleotide effects upon murine natural killer cell activity and macrophage activation

Weanling mice fed chow or chow plus water supplemented with 3.5 mg of nucleotides per 100 ml of water for 6 weeks exhibited increased natural killer cell (NK) activity and lower macrophage activation compared to mice fed chow plus nonsupplemented water. In a dose-response study, NK activity, macrophage activation and spleen weight (as a percentage of body weight) were higher in mice fed up to 0.035% w/w nucleotides, however macrophage activation was decreased by feeding over 0.35% w/w compared to those receiving basal purified diet (BPD). Nucleotides in human milk may affect the immune response in breast-fed infants.

Hazards of mattresses, beds and bedding in deaths of infants

Of 52 infants who had died suddenly and were referred to autopsy, nine had lain on adult water beds for the first time: five had died as a result of accidents: two had died on water beds; two were in beds with widely spaced slats; and one had died as a result of strangulation. Three deaths were due to overlying. Three other infants had been placed on sheepskin rugs for the first time and were found dead shortly thereafter. These infants ranged in age from 2 to 9 months, except for a severely mentally retarded nine-year-old with spastic paraplegia. We believe that a general warning should be issued concerning water beds and that soft bedding should not be used for infants. Infants should not be placed unattended or left to sleep on water beds: only beds recommended for infants should be used. Overlying of a young infant is most likely to occur on a water bed. or if the parent is obese or has consumed alcohol.

Effect of Docosahexaenoic Acid Content of Maternal Diet on Auditory Brainstem Conduction Times in Rat Pups

Previous studies of dietary docosahexaenoic acid (DHA; 22:6n–3) effects on neurodevelopment have focused mainly on effects on the visual system; these studies may be confounded by effects on the retina rather than on neural pathways. Auditory brainstem conduction times (ABCTs) provide an alternate measure of central neural development. We conducted a dose-response study in which ABCTs were measured in pups whose dams were fed diets containing one of three levels of DHA (2, 4 or 6% of total fatty acids) from a single cell oil. Diets were fed during pregnancy and lactation, and pups were randomly cross-fostered on postnatal day 3 to minimize litter effects. ABCTs showed a dose-response effect, with higher levels of dietary DHA being associated with longer conduction times on postnatal day 31 (p < 0.05). Higher dietary DHA was reflected in pup cerebrums collected on postnatal days 3 and 31, and levels of arachidonic acid (AA, 20:4n–6) were inversely related to levels of DHA. This study demonstrated that the auditory brainstem response is sensitive for identifying effects of diet on neurodevelopment, and that supplementing the maternal diet with high levels of DHA may negatively impact development of the central auditory system of offspring.

SAFETY CONSIDERATIONS WITH HIGH ASCORBIC ACID DOSAGE

When a new drug is found effective in the prevention or treatment of a disease, before use is recommended the toxicity of thc drug must be weighed against its beneficial effects, When the substance in question is a foodstuff, and especially a vitamin, it becomes difficult to clearly separate need, effect, and emotion. That any necessary substance, including water, can be toxic if taken in sufficient quantities is a truism. A level of intake of vitamin C must exist that is toxic to everyone and, at lesser levels, to many, a phenomenon related to biological variability of humans. The concept that humans have the capacity to regulate their intake of foods and toxic substances is outmoded. It is even excessive to claim that physicians, informed as they are, know their needs any better, whether of food or surgery,l than do laymen. Since properties other than the commonly acknowledged one of preventing scurvy have been attributed to large doses of vitamin C, and since a continuum of actions of ascorbate have been discussed for many years, definition of the toxic effects of vitamin C becomes important. Toxic effects of ascorbic acid that have been reported include acidosis, oxaluria, renal stones, glycosuria, renal tubular disease, gastrointestinal disturbances, sensitivity reactions, conditioned need, prothrombin and cholesterol disturbances, vitamin B, destruction, fatigue and sterility; additionally, ascorbate ingestion has been noted to interfere with results of certain laboratory determinations. Probably the two most frightening claims about the possible toxicity of ascorbic acid concern the development of acidosis, and the production of oxaluria.

The Effects of Dietary Nucleotides on Intestinal Blood Flow in Preterm Infants

Nucleotides (NT) are reported to affect development of the immune and gastrointestinal systems, and they are currently added to most term infant formulas. In the present study, dietary NT effects on superior mesenteric artery blood flow were investigated. Formula-fed preterm infants were studied once with a 20 kcal/oz. term infant formula containing 80.6 mg/L of NT (NT+), and once with the same formula with no added NT (NT−) (n = 20, gestational age 28.0 ± 2.2 wk). A reference group of preterm infants fed human milk was also studied (n = 20, gestational age 29.0 ± 1.6 wk). Superior mesenteric artery blood flow velocities (BFV) were measured by Doppler ultrasound 15 min before and 30, 60, and 90 min after the start of the feed. BFV rose in all infants from baseline to 30 min after feed initiation, and progressively declined thereafter in infants fed NT− or human milk. However, NT+ feedings were associated with a minimal change in BFV between 60 and 90 min. As a result, the difference in blood flow velocities between baseline and 90 min was significantly greater with the NT+versus the NT− feedings for the mean, peak systolic, and end diastolic velocities (p = 0.03, 0.05, and 0.03, respectively). BFV after the NT− and human milk feedings were similar. These data suggest that orally administered NT are associated with effects on the intestinal vasculature.

Festschrift for Dr. John M. Opitz: Pathogenesis of cardiac conduction disorders in children genetic and histopathologic aspects

Fetal dysrhythmias are usually transient. Abnormal fetal rates and rhythms during labor are “functional.” Fetal dysrhythmias may be associated with congenital heart disease and fetal hydrops. Bradycardia is usually related to fetal distress; supraventricular tachycardia, atrial flutter, and atrial fibrillation may be associated with severe congestive heart failure. Ventricular fibrillation is rare in the fetus and infant and is usually associated with myocardial necrosis with perimembranous septal defect; the nonbranching atrioventricular (AV) bundle may have an aberrant position and result in cardiac arrhythmia. Wolff–Parkinson–White syndrome with conduction abnormalities and left ventricular hypertrophy (LVH) is due to an accessory pathway that bypasses the AV sulcus and results in faster conduction. Carnitine deficiency may be primary or secondary and may result in cardiac arrhythmia. Histiocytoid cardiomyopathy is characterized by cardiomegaly, incessant ventricular tachycardia, and frequently sudden death. Arrhythmogenic right ventricular dysplasia (ARVD) results in ventricular tachycardia and left bundle branch block. Noncompaction of the left ventricle predisposes to potentially fatal arrhythmias. Long Q‐T syndromes (LQTS) are a heterogeneous group of disorders with many genetic mutations. Brugada syndrome is an autosomal dominant trait with right bundle branch block and ST elevation. Barth syndrome is an X‐linked disorder with dilated cardiomyopathy, cyclic neutropenia and skeletal myopathy. Hypertrophic cardiomyopathy in infancy may be related to metabolic diseases, particularly glycogen storage diseases; the familial form predisposes to sudden death. Arrhythmias following cardiac surgery may occur after closure of a ventricular septal defect (VSD) or damage to the conduction system.

History of pediatric nutrition and fluid therapy.

This is the seventh article in our series on the history of pediatric specialties. Drs. Kleinman and Barness describe the history of artificial feeding, discoveries of micronutrients, definition of nutritional requirements and the affirmation of human breast milk as the ideal infant feeding. Dr. Finberg describes the studies of electrolyte metabolism and effective fluid therapy, which has resulted in a dramatic reduction in the mortality of diarrheal disease. These are great stories of major contributions from Pediatrics.

Obesity in children.

The alarming increase in obesity in children has become a major health problem in the increased incidence of type 2 diabetes as well as other complications including cardiovascular diseases, hepatic disorders, skeletal abnormalities, malignancies and in particular psychological disorders. Mechanisms of appetite and energy metabolism are mediated through hormones leptin and ghrelin, and neuropeptide-Y neurons as well as genetic factors. Control of obesity is largely through appetite control and physical exercise.

Nonmalformative cardiovascular pathology in infants and children.

CARDIOMYOPATHY IN CHILDREN The cardiomyopathies are a group of disorders of the myocardium that are associated with a decrease in cardiac function. The original classification by the World Health Organization (WHO) divided congestive cardiomyopathy into two categories: (1) primary, or idiopathic; and (2) secondary, or related to an underlying definable systemic disorder [1], and of three functional types: (1) dilated or congestive; (2) obstructive, as in hypertrophic cardiomyopathy; and (3) restrictive, as in infiltrative disorders such as the storage diseases. A revised classification added two additional categories: arrhythmogenic right ventricular cardiomyopathy and unclassified cardiomyopathies. In addition, specific cardiomyopathies include such categories as metabolic cardiomyopathies, general systemic diseases such as connective tissue disorders, neuromuscular disorders, and immunological diseases.