Increases in physical fitness during childhood improve cardiovascular health during adolescence: the Muscatine Study.

Longitudinal studies from childhood through adolescence have the potential of defining maturational changes in cardiovascular risk factors and may provide insight into the prediction of future cardiovascular disease. We assessed aerobic fitness, muscular strength, vigorous and sedentary activity, maturation, blood pressure, lipids, and body composition in 125 healthy children for a period of five years (mean baseline age, 10.5 years). All subjects were in pre- or early-puberty at baseline. After adjusting for age and gender and considering the confounding effects of growth and maturation, we examined whether changes in fitness and activity during the first four years of our study could predict cardiovascular health outcomes at year-five of our study. Change in muscular strength explained 4 % of the variability in year-five systolic blood pressure. Change in aerobic fitness explained 11 % of year-five total cholesterol to high density lipoprotein ratio and 5 % of year-five low density lipoprotein cholesterol. Changes in aerobic fitness and muscular strength explained 15 % of the variability in year-five adiposity and 15 % of the variability in year-five abdominal adiposity. Childhood health promotion programs that specifically target increases in physical fitness may help to reduce the increasing prevalence of adolescent obesity.

Usefulness of the Framingham risk score and body mass index to predict early coronary artery calcium in young adults (Muscatine Study).

The value of a coronary artery disease prediction algorithm, the Framingham risk score (score), for detecting coronary artery calcium (CAC) was examined in 385 men and 472 women, aged 29 to 43 years. Scores were compared in subjects with and without CAC and were also used to predict presence of CAC. Receiver-operating characteristic curves were computed to compare different prediction models. The score model was compared with age only, natural logarithm of body mass index (lnBMI) only, and score plus lnBMI models. CAC was detected in 30% of men and 16% of women. The mean score was significantly higher in men and women with CAC. For every 2-point increase in the score, the odds of CAC increased by 30% in women and 20% in men. Significant associations between CAC status and risk factors were observed for age in women, and high- density lipoprotein cholesterol and blood pressure in men and women. The area under the receiver-operating characteristic curve for the score was 0.67 and 0.57 for women and men, respectively. When lnBMI was added to the score model, the area increased to 0.76 in women (lnBMI p <0.0001, score p <0.005). For men, the area increased from 0.57 to 0.67, and the score was no longer significant (p >0.60) in the model with lnBMI (p <0.0001). Score predicts CAC in asymptomatic young adults. Inclusion of lnBMI in the score model adds significantly to the prediction of CAC in women and men. The lnBMI model has a greater predictive value than the score in this young population.

Goal orientation and ratings of perceived exertion in graded exercise testing of adolescents.

This study examined the relationship between adolescents' goal orientation in sport and their ratings of perceived exertion (RPE) during a graded exercise test. Subjects (N = 114; 56 boys) were randomly selected adolescents (ages 11 to 15 years) who were part of a 5-year longitudinal study of cardiac growth. RPE was measured during each of three submaximal stages throughout the graded exercise test and again during the maximal stage. A series of regression analyses showed that RPE for female subjects was significantly predicted by Task Orientation, Perceived Ability, and Intensity of Leisure Activity at Stage 1, Task Orientation and Perceived Ability at Stage 2, and by Intensity of Leisure Activity at Stage 3. Examination of the beta weights indicated that lower RPE for the girls was related to higher Task Orientation and lower Perceived Ability and more experience with higher Intensity of Leisure Activity. Results are discussed in light of the literature pertaining to goal orientation and ratings of perceived exertion.

Tracking physical fitness and physical activity from childhood to adolescence: the muscatine study.

PURPOSE: Physical fitness and physical activity tracking data enhance our understanding as to when children settle into their long-term exercise and fitness patterns and, therefore. provide insight as to when programs focusing on preventing sedentary adults behaviors should be initiated. METHODS: In this paper, the tracking of physical fitness and physical activity was examined in a 5-yr population-based study of children and adolescents in Muscatine, IA. Study subjects (N = 126) were pre- or early-pubescent at baseline (mean age boys 10.8 yr and girls 10.3 yr). Physical fitness was measured using direct determination of oxygen uptake and maximal voluntary isometric contraction while physical activity was assessed via questionnaire. RESULTS: Boys classified as sedentary based on initial measurements of TV viewing and video game playing were 2.2 times more likely than their peers to also be classified as sedentary at follow-up. Tracking of most physical fitness and physical activity variables was moderate to high, indicating some predictability of early measurements for later values. Sedentary behavior tracked better in boys, whereas vigorous activity tended to track better in girls. CONCLUSION: These observations suggest that preventive efforts focused on maintaining physical fitness and physical activity through puberty will have favorable health benefits in later years.

Predicting heart growth during puberty: The Muscatine Study.

OBJECTIVES: During childhood, heart growth is closely associated with somatic growth including increases in body weight, fat-free body mass (FFM), and height. However, with age, greater variability in heart size in relationship to body size is observed, presumably attributable to the increased effect of cardiac workload. At this time, little is known as to what functional attributes (eg, aerobic fitness) contribute to cardiac workload and the relative contribution of these attributes to heart growth during childhood and adolescence. In this article, we report cross-sectional and longitudinal relationships among aerobic fitness, body size, blood pressure (BP), and left ventricular mass (LVM) through puberty including the predictors of heart growth during puberty and the tracking of LVM from pre-puberty to late and post-puberty. Describing the predictors of heart size and heart growth and establishing the likelihood that a large heart, relative to peers, may (or may not) remain a large heart should aid pediatricians in discerning between normal developmental increases in LVM and increases in LVM suggestive of excessive heart growth (left ventricular hypertrophy). METHODOLOGY: Using a repeated-measures design, we assessed aerobic fitness, FFM, fatness, weight, height, sexual maturation, resting BP, peak exercise BP, and LVM in 125 healthy children (mean baseline age: 10.5 years) for a period of 5 years. All subjects were either in prepuberty or early puberty at the beginning of the study. At follow-up, 110 subjects attempted all research procedures (87% of the initial cohort). Using anthropometry and bioelectrical impedance, we measured FFM, fatness, weight, and height quarterly (once every 3 months) for a total of 20 examinations. Resting BP and LVM (2-dimensional echocardiography) were also assessed quarterly. Aerobic fitness, peak exercise BP, and sexual maturation (staging of secondary sex characteristics and, for boys, serum testosterone) were measured annually (5 examinations). The same field staff conducted all examinations. Statistical methods included Spearman rank correlation coefficients (r(s)) calculated to estimate how well the year 5 LVM was predicted by LVM at earlier years. We also categorized the LVM data into tertiles and reported the percentage who remained in the extreme tertiles in year 5, given they began in that tertile in year 1. Gender-specific stepwise multivariate analysis was used to evaluate predictors of follow-up LVM and predictors of changes in LVM. The latter model examined whether the variability in the changes in LVM, as quantified by subject-specific slopes, could be explained by changes in predictor variables, also quantified by subject-specific slopes. RESULTS: At baseline and at follow-up, boys tended to be taller, leaner, more aerobically fit, and had greater LVM than girls. Rate of change for these variables was also greater in boys than girls. For example, LVM increased 62% in boys and 48% in girls. At year 5, subjects had advanced at least 1 stage in genital or breast development and over 80% of the subjects were in late- or post-puberty. Significant and strong tracking of heart size (r(s) =.65-.87) was observed. The likelihood that a subject would be in an extreme tertile for heart size at follow-up was approximately doubled if he or she started there at baseline. In boys, baseline FFM explained 54% of the variability in follow-up LVM. Change in aerobic fitness and change in FFM explained 55% of the variability in change in LVM. In girls, baseline aerobic fitness and fatness explained 45% of the variability in follow-up LVM. Because FFM did not enter in this model, we constructed an alternative model in which baseline aerobic fitness adjusted for FFM was entered. Using this approach, 43% of the variability in follow-up LVM was explained by baseline FFM, fatness, and adjusted aerobic fitness. Change in FFM explained 58% of the variability in change in LVM. (ABSTRACT TRUNCATED)

Increased carotid intimal-medial thickness and coronary calcification are related in young and middle-aged adults. The Muscatine study.

BACKGROUND: Increased carotid intimal-medial thickness (IMT) and coronary artery calcification (CAC) are used as 2 markers of early atherosclerosis. Our objectives were to assess whether increased IMT and CAC are related and to determine the relationship between cardiovascular risk factors and carotid IMT in young adults. METHODS AND RESULTS: A sample of 182 men and 136 women aged 33 to 42 years living in Muscatine, Iowa, underwent B-mode carotid ultrasound to determine the mean of 12 measurements of maximal carotid IMT. CAC was defined as calcification in the proximal coronary arteries in >/=3 contiguous pixels with a density of >/=130 HU. The mean IMT was 0.788 mm (SD 0.127) for men and 0.720 mm (SD 0.105) for women. CAC was present in 27% of men and 14% of women and was significantly associated with IMT in men (P<0.025) and women (P<0.005). With multivariate analysis, after adjustment for age, significant risk factors for carotid IMT were LDL cholesterol (P<0.001) and pack-years of smoking (P<0.05) in men and LDL cholesterol (P<0.001) and systolic blood pressure (P<0.01) in women. These risk factors remained significant after CAC was included in the multivariate model. CONCLUSIONS: There is an association between increased carotid IMT and CAC and between cardiovascular risk factors and increased IMT in young adults. Carotid IMT may provide information in addition to CAC that can be used to identify young adults with premature atherosclerosis.

Longitudinal analysis of scaling VO2 for differences in body size during puberty: the Muscatine Study.

PURPOSE: The purpose of this study was to determine an appropriate method to "normalize" oxygen uptake (VO2) for body size in children and adolescents. METHODS: We examined allometric scaling factors for a cohort of 126 children (mean age at baseline = 10.3 yr) participating in a 5-yr follow-up study. Each year for 5 yr we measured peak VO2, submaximal VO2, body mass, height, body composition, and sexual maturation. We sorted the 5-yr data set by sexual maturation and gender and then used the generalized estimating equation method to estimate regression parameters that described the influence of log transformed body mass on log transformed VO2. All analyses were repeated using log transformed fat-free body mass (FFM) in lieu of log transformed body mass. RESULTS: Models using FFM appeared better at eliminating the effect of body size on VO2. In boys a univariate model with a FFM exponent of 0.91 and in girls a univariate model with a FFM exponent of 0.87 satisfactorily normalized peak VO2. However, we could not identify a common body size exponent for both boys and girls. CONCLUSIONS: Results support the use of allometric scaling of VO2 as a function of FFM for maturing boys and girls but indicate that the effects of maturation on the relationship between VO2 and body size differ between boys and girls.

Three-year follow-up of changes in aerobic fitness during puberty: the Muscatine Study.

To assess the tracking of aerobic fitness during puberty and its relationship to changes in body composition and indexes of growth, the authors of this study measured body fat, echocardiographic left ventricular mass (LVM), fat-free mass (FFM), height, physical activity, resting blood pressure, sexual maturation, and maximal aerobic fitness (VO2peak) in 123 children (ages 7-12 years). Measures were repeated 3 years later. Tracking was assessed by Spearman rank correlation coefficients between baseline and follow-up data. Predictors of changing aerobic fitness were examined using stepwise regression. Significant tracking of aerobic fitness was observed with correlations ranging from .70-.75. Increased FFM and increased LVM explained 51% of the variability in improved aerobic fitness (ml.min-1) in boys. Increased FFM and increased height explained 26% of the variability in improved aerobic fitness (ml.min-1) in girls. During puberty, children who gain the greatest amount of lean tissue (including cardiac) experience the greatest improvements in aerobic fitness (ml.min-1). Measures of aerobic fitness prior to and during early puberty tend to predict aerobic fitness during puberty.

Coronary risk factors measured in childhood and young adult life are associated with coronary artery calcification in young adults: the Muscatine Study.

OBJECTIVES: This study was designed to estimate the prevalence of coronary artery calcification in young adult men and women and to examine the association between the presence of coronary artery calcification and coronary risk factors measured in childhood and young adult life. BACKGROUND: Electron beam computed tomography is a sensitive, noninvasive method for detecting coronary artery calcification, a marker of the atherosclerotic process. Coronary artery calcification is associated with coronary risk factors in older adults. METHODS: Subjects (197 men, 187 women) had coronary risk factors measured in childhood (mean age 15 years) and twice during young adult life (mean ages 27 and 33 years). Each underwent an electron beam computed tomographic study at their second young adult examination. RESULTS: The prevalence of coronary artery calcification was 31% in men and 10% in women. Increased body size, increased blood pressure and decreased high density lipoprotein (HDL) cholesterol levels were the coronary risk factors that showed the strongest association with coronary artery calcification. Significant odds ratios for coronary artery calcification, using standardized risk factor measurements at a mean age of 33 years in men and women, respectively, were 6.4 and 13.6 for the highest decile of body mass index, 6.4 and 6.4 for the highest decile of systolic blood pressure and 4.3 and 4.7 for the lowest decile of HDL cholesterol. CONCLUSIONS: Coronary artery calcification is more prevalent in men in this young adult population. Coronary risk factors measured in children and young adults are associated with the early development of coronary artery calcification. Increased body mass index measured during childhood and young adult life and increased blood pressure and decreased HDL cholesterol levels measured during young adult life are associated with the presence of coronary artery calcification in young adults.

The stability of children's physical activity as measured by accelerometry and self-report.

The Computer Science Application (CSA) accelerometer uses integrated circuitry and memory to provide a continuous recording of minute-by-minute movement counts. It has been previously validated as an objective monitor of children's physical activity in field and laboratory settings. Our purpose was to derive accelerometry summary variables reflective of different physical activity intensity levels, evaluate the stability of these summary variables, and define the number of days needed to adequately measure usual physical activity. A secondary study purpose was to compare three self-report questionnaires to accelerometry. Thirty children (7-15 yr) wore accelerometers for 12 h.d-1 for 6 d. Daily summary variables of average movement count (total physical activity) and daily frequency of sedentary through vigorous activity were constructed. Intraclass correlation coefficients (R) and 95% confidence intervals (CI) were used to analyze the data. Accelerometry stability using 1 monitored day to represent usual physical activity was R = 0.42-0.47. When 6 d were used, stability increased to R = 0.81-0.84. Acceptable intraclass correlations and CI were achieved with 4 d of monitoring (R = 0.75-0.78, CI = 0.60-0.88). The self-report questionnaires were poorly to moderately correlated to accelerometry variables (r = -0.03-0.51). Data indicate that in field settings: 1) accelerometry can be used to assess the intensity of children's activity and 2) 4 or more days of activity monitoring are needed to achieve satisfactory reliability.

Predictors of left ventricular mass and resting blood pressure in children: the Muscatine Study.

The objective of this study was to determine predictors of left ventricular mass (LVM) and resting systolic blood pressure (SBP) in preteenage children. Subjects consisted of 124 children (7.9-12 yr) from Muscatine, Iowa. Methods consisted of echocardiographic examinations, random-zero SBP, hormone determination of serum androgens, physician's examination for Tanner stage, anthropometry, maximal bicycle ergometry, hand grip dynamometry, and a physical activity survey. Least square's regression analysis quantified the percentage of explained variability in LVM and resting SBP attributable to the predictor variables. All models were adjusted for body composition. In boys, 72% of the variability in LVM was explained by fat-free body mass (FFM), sum of skinfolds, and peak SBP. In girls, FFM and peak SBP explained 69% of the variability in LVM. Peak SBP was also a significant predictor of resting SBP in boys and girls. Study results indicated that physical fitness and physical activity are not significant predictors of LVM nor resting SBP; however, after adjusting for body composition, peak SBP was an independent predictor of LVM and resting SBP. This result suggests that peak SBP may aid in the prediction of subsequent hypertension and its complications such as left ventricular hypertrophy.

Acyanotic congenital heart disease. Atrial and ventricular septal defects, atrioventricular canal, patent ductus arteriosus, pulmonic stenosis.

This article discusses the four common congenital heart lesions associated with communications between the systemic circulation and the pulmonary circulation, as well as valvular pulmonic stenosis with intact ventricular septum. The incidence and description of each specific anatomical malformation is presented. The clinical findings on physical examination, electrocardiography, chest radiograph, and echocardiography are delineated for each defect. Emphasis is placed on the medical and surgical management and the long-term outcome of such management.

Factors affecting left ventricular mass in childhood: the Muscatine Study.

OBJECTIVE: To examine the contribution of age, body size, and blood pressure to left ventricular mass (LVM) in childhood and develop a population-based reference of normative LVM data. METHODS: Age, sex, height, weight, and auscultatory systolic and diastolic blood pressures were measured and an echocardiogram was performed to estimate LVM in 904 normal children, aged 6 to 16 years, in Muscatine, IA. Pearson product-moment correlation coefficients were determined to describe the degree of linear association between LVM and age, body size, and blood pressure. Age-sex-, weight-sex-, and height-sex-specific Z scores were determined for LVM, age, weight, height, and blood pressure. Sex-specific LVM prediction equations were derived using weighted-least-squares regression analysis. RESULTS: A strong positive linear association of LVM with age, weight, height, Quetelet index, and systolic and diastolic blood pressure was demonstrated. Z scores for eight different LVM quintile patterns revealed that age, height, weight, and blood pressure each exert an independent influence on LVM in children. Sex-specific predicted M-mode LVM and upper limits of the 90% prediction intervals based on age and height are presented. CONCLUSION: Since age, height, weight, and blood pressure may each exert an independent influence on LVM in children, each factor must be considered when interpreting LVM in childhood. While age, sex, and height are unalterable, both weight and blood pressure can be modified. Thus the pathologic contribution of excess weight and blood pressure ought not be masked by statistical adjustments in reference values for LVM. Sex-specific values of LVM and the 90% and 95% prediction intervals of LVM that do not factor out the effects of obesity or blood pressure are presented. These provide the upper-limit reference values of LVM for the evaluation of children in whom increased LVM is suspected.

Childhood predictors for high adult blood pressure. The Muscatine Study.

In adult populations, elevated blood pressure is related to the development of stroke, renal disease, and occlusive atherosclerosis. The significance of blood pressure levels in childhood, unless extremely elevated, has not been related to disease outcomes. In a study carried out in Muscatine, Iowa, the risk of high blood pressure in young adult life was evaluated based on the observations of blood pressure and other factors made during the school-aged years. Subjects, 2445 in number, were first observed at ages 7 through 18 years and again between 20 and 30 years. During childhood, measurements of blood pressure, height, and weight were made on alternate years. At adult ages, the same measurements were again made and a health questionnaire was administered. Adult blood pressure was correlated with childhood blood pressure, body size, and change in ponderosity from childhood to adult life. Adult ponderosity was related to childhood ponderosity, and those who were most obese as adults showed the greatest increase in weight from their childhood years. These observations suggest that strategies to prevent the acquisition of excess ponderosity during childhood may be useful in preventing adult hypertension.

Comparative hemodynamic depression of halothane versus isoflurane in neonates and infants: an echocardiographic study.

The purpose of this study was to measure and compare the relationship of cardiovascular depression and dose during equal potent levels of halothane and isoflurane anesthesia in neonates (n = 19) (16.7 +/- 6.9 days) and infants (n = 54) (6.1 +/- 3.1 mo). Seventy-three children had heart rate, arterial blood pressure, and pulsed Doppler pulmonary blood flow velocity as well as two-dimensional echocardiographic assessments of left ventricular area and length recorded just before anesthesia induction. Anesthesia was induced by inhalation of increasing inspired concentrations of halothane or isoflurane in oxygen using a pediatric circle system and mask. During controlled ventilation, halothane and isoflurane concentrations were adjusted to maintain 1.0 MAC and then 1.5 MAC (corrected for age), and echocardiographic and hemodynamic measurements were repeated. A final cardiovascular measurement was recorded after intravenous administration of 0.02 mg/kg of atropine. All measurements were completed before tracheal intubation and the start of elective surgery. In neonates, 1.0 MAC concentrations of halothane and isoflurane decreased cardiac output (74% +/- 16%), stroke volume (75% +/- 15%), and ejection fraction (76% +/- 15%) similarly from awake levels. Decreases in cardiac output, stroke volume, and ejection fraction with halothane and isoflurane were significantly larger at 1.5 MAC (approximately 35% decreases from awake values) than at 1.0 MAC. Heart rate decreased significantly during 1.5 MAC halothane anesthesia (94% +/- 4%) but remained unchanged during isoflurane anesthesia. In infants, 1.0 MAC halothane and isoflurane decreased cardiac output (83% +/- 12%), stroke volume (78% +/- 12%), and ejection fraction (74% +/- 12%) when compared with awake measures.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart rate monitoring of physical activity in children and adolescents: the Muscatine Study.

To assess the usefulness of whole-day heart rate monitoring as a quantitative measure of physical activity in children, the activity of 76 children and adolescents (ages 6 to 17 years), randomly selected from a school population, was measured during a typical summer day using a light-weight, nonrestrictive heart rate telemetry unit. A 12-hour recall and a simple self-rating of usual activity questionnaire were also administered on the same day. An additional 12-hour recall questionnaire was administered on another day. Within 1 month of the heart rate monitoring, the skinfold measures, peak aerobic capacity, and sexual maturation were assessed. Data analysis indicated that activity as measured by telemetry was related to questionnaire recall on the monitored day (r = .50), nonmonitored day (r = .32), and self-rating (r = .35); level of activity as measured by telemetry was related to peak aerobic capacity in girls (r = .36) but not in boys (r = -.06); body fat was related inversely to activity (r = -.32); and prepubescent children were more active than post- and pubescent children (P less than .003). No difference was found in activity level between boys and girls (P greater than .05). This study suggests that for children whole-day heart rate monitoring is an objective, nonobtrusive method for measuring physical activity; and maturation, but not gender, is an influential mediating factor for activity.

Childhood predictors of high blood pressure.

Longitudinal studies in children have tracked blood pressure through childhood and from childhood into adult life. However, many children do not maintain their rank during these periods of observation. Several of the factors contributing to maintenance of rank order are reviewed, such as initial level of blood pressure, body size, sexual maturation, and family history of high blood pressure. Children with initially high level of blood pressure are more likely to become adults with high blood pressure, particularly if they are obese as children or become obese as young adults, and if they have a positive family history for hypertension.

Childhood predictors of future blood pressure.

Blood pressure in infants and children is much lower than that in adults. It is suspected that children whose blood pressures are greatest for their age or body size may be destined for future hypertension. However, it is apparent that some children with lower blood pressures are also destined for hypertension as adults. Children with a family history of hypertension demonstrate greater blood pressure and heart rate responses to mental challenge. These responses are enhanced when a high salt diet is consumed. Increased maximal exercise systolic blood pressure and increased left ventricular wall mass in childhood add significantly to the prediction of future high blood pressure. In addition, the acquisition of excess weight for height from childhood to young adult life adds to the prediction of future blood pressure elevations. Both children and adults who are obese have significantly higher blood pressures than those who are lean. Approximately 34% of the variability in body mass index is explained by genotype differences at a single recessive locus, 41% by genotype differences at polygenic loci, and 25% by nongenetic factors. Thus, the genetic influence of obesity may be an important factor responsible for elevated blood pressure in both children and adults.

Hemodynamic responses to nitrous oxide during inhalation anesthesia in pediatric patients.

STUDY OBJECTIVE: To measure the hemodynamic changes produced by nitrous oxide (N2O) during halothane and isoflurane anesthesia in infants and children. DESIGN: A repeated measures design in two groups of infants and small children. SETTING: Operating rooms at a university hospital. PATIENTS: Nineteen healthy unmedicated infants and small children (mean age 12 months) who required elective surgery. INTERVENTIONS: Prior to anesthesia induction, cardiovascular measurements were recorded using pulsed Doppler and two-dimensional echocardiography. Following anesthesia induction with halothane (n = 10) or isoflurane (n = 9) in oxygen (O2) and air, anesthetic measures were stabilized at 1.0 minimum alveolar concentration (MAC) and cardiovascular measures were repeated. After 30% N2O was added to the 1.0 MAC anesthetic concentration, a third set of cardiovascular measurements was recorded. A final cardiovascular data set was measured 5 minutes following an increase in N2O concentration to 60%. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure (MAP), cardiac index (CI), stroke volume (SV), and ejection fraction (EF) decreased similarly and significantly at 1.0 MAC halothane and isoflurane. Heart rate (HR) increased during isoflurane anesthesia but decreased during halothane anesthesia. The addition of N2O resulted in a decrease in HR, CI, and MAP when compared to 1.0 MAC levels of halothane or isoflurane; however, SV and EF were not significantly changed from levels measured during 1.0 MAC halothane or isoflurane. CONCLUSIONS: The addition of N2O to halothane and isoflurane anesthesia in infants and children decreased HR. This decrease led to a decrease in cardiac output (CO). Unlike with adults, N2O did not produce cardiovascular signs of sympathetic stimulation in infants and children.