CHAPTER 7 GROWTH AND DEVELOPMENT IN THE NORMAL INFANT AND CHILD
Principles and Practice of Endocrinology and Metabolism
CHAPTER 7 GROWTH AND DEVELOPMENT IN THE NORMAL INFANT AND CHILD
GILBERT P. AUGUST
Height and Weight
Body Mass Index
Growth Hormone and Insulin-Like Growth Factors
Adrenocorticotropic Hormone and Adrenocortical Steroids
Thyroid-Stimulating Hormone and Thyroid Hormones
Luteinizing Hormone, Follicle-Stimulating Hormone, and the Sex Steroids
Renin and Aldosterone
The pediatric population is composed of continually changing individuals. Thus, a knowledge of normal developmental changes is required for the clinician to recognize deviant growth and development and abnormalities in the hormonal milieu.
HEIGHT AND WEIGHT
Height and weight standards derived from one ethnic group cannot always be applied to other ethnic groups. Furthermore, use of current standards is important, because growth data obtained from a previous generation may not apply to the present generation. The National Health Survey collected growth and anthropometric data on American children from 1963 to 1974 (Table 7-1).1,2,3,4,5,6,7,8 and 9 These data provide standards that can be correlated with sex, race, and socioeconomic status. The growth charts distributed by pharmaceutical companies are derived from these National Health Survey data. Because the growth standards of American white and black children do not differ significantly, a single growth standard can be used. Significant differences do exist, however, in the growth standards of American children of Asian descent.7
TABLE 7-1. Height and Weight of Children, Body Proportions, and Error of Prediction of Adult Height (United States)
Figure 7-1, Figure 7-2, Figure 7-3 and Figure 7-4 show the current growth data from the National Health Survey. In Table 7-1, the mean heights, mean weights, and standard deviations (SDs) for children 2 to 18 years of age are detailed. The standard deviation is useful in evaluating extreme deviations in growth (e.g., heights and weights below the standard curves).10 Children whose heights or weights are below the standard curves constitute a significant proportion of the population, because the commonly used growth charts provide data from only the 5th through the 95th percentiles.
FIGURE 7-1. Length and weight of boys. Birth to 36 months of age. Centers for Disease Control and Prevention, National Center for Health Statistics. CDC growth charts: United States. Full size charts are available on the internet at http://www.cdc.gov/nchs/about/major/nhanes/growthcharts/charts.htm May 30, 2000.
FIGURE 7-2. Height and weight of boys. 2 to 20 years of age. Centers for Disease Control and Prevention, National Center for Health Statistics. CDC growth charts: United States. Full size charts are available on the internet at http://www.cdc.gov/nchs/about/major/nhanes/growthcharts/charts.htm May 30, 2000.
FIGURE 7-3. Length and weight of girls. Birth to 36 months of age. Centers for Disease Control and Prevention, National Center for Health Statistics. CDC growth charts: United States. Full size charts are available on the internet at http://www.cdc.gov/nchs/about/major/nhanes/growthcharts/charts.htm May30, 2000.
FIGURE 7-4. Height and weight of girls. 2 to 20 years of age. Centers for Disease Control and Prevention, National Center for Health Statistics. CDC growth charts: United States. Full size charts are available on the internet at http://www.cdc.gov/nchs/about/major/nhanes/growthcharts/charts.htm May 30, 2000.
For children aged 2 to 18 years, growth curves for as low as 2 SD below the mean are available. These curves are more in keeping with the usual definition of “normal” as comprising 95% of the population. Only 2.5% of children would be considered as “short” by these standards (Fig. 7-1, Fig. 7-2, Fig. 7-3 and Fig. 7-4).
The National Center for Health Statistics has revised the current growth charts to reflect a more contemporaneous standard. The new charts contain data from the 3rd to 97th percentiles. The new growth charts are available on the internet at http://www.cdc.gov/growthcharts.
Socioeconomic status was found to play a small but significant adverse role in the growth of children with very low family incomes.6
Beyond age 2 to 3 years, children grow throughout childhood until puberty along a particular height percentile channel that is determined by genetic factors. The normal pubertal growth spurt is reflected by an upward shift in height percentile. As growth decelerates later in puberty with impending epiphyseal closure, a shift downward in height percentile occurs, so that adult height more closely approximates the prepubertal percentile ranking. The reason for these shifts lies in the cross-sectional character of the standard growth charts. Cross-sectional data mask normal longitudinal growth patterns. The growth charts derived from studies in Britain have superim-posed longitudinal growth lines that represent temporal variations in the onset of puberty.11 Similar data are available for North American children.12
A shift in height percentile can also occur during infancy when growth velocities are adjusted in children whose birth lengths are either “too long” or “too short” in comparison with their parents’ heights. The shift upward in percentile generally takes place within the first 6 months of life and is usually completed by 12 months of age. The shift downward in percentile begins later, generally after 3 months of age, and is completed by 18 months of age.13
The influence of midparental stature on the interpretation of a child’s growth status is considered to be of such importance by some workers that conversion graphs and adjustment formulas have been developed. Tanner and coworkers14 developed such curves for British children, and adjustment tables are now available for American children.15 Parental heights can also be used to predict target adult height.16 This can be valuable when the effects of a treatment are analyzed.
The standard growth charts derived from the National Health Survey data are not as applicable for tracking the growth of premature infants or children small for gestational age. However, growth standards are available for such children through 4 years of age.17,18 These growth charts must be adjusted for the degree of low birth weight.19 Further, infants small for gestational age may not truly “catch up” when their heights are compared with those of their siblings.20,21
Whenever sufficient data exist to construct growth charts for children with constitutional diseases, those standards should be used for comparison of current growth status and for expected adult height. Such growth standards are available for children with achondroplasia, Down syndrome, diastrophic dysplasia, Duchenne muscular dystrophy, Klinefelter syndrome, Noonan syndrome, pseudoachondroplasia, Russell-Silver syndrome, spondyloepiphyseal dysplasia, and William syndrome.22 Similar information is available for children with gonadal dysgenesis.23,24
Careful attention to detail is important to produce accurate height measurements that can be used to track a child’s growth (Fig. 7-5). Length should be measured on a horizontal board with the head held firmly against the upright at one end and the length determined by sliding the movable upright against the child’s heels. Length should be determined until 3 years of age. The growth curve from birth until 3 years of age is standardized on length. Height must be measured using a wall-mounted instrument or tape. This permits the child to stand fully upright. The feet should be together, the back and heels should be pressed against the wall or vertical part of the measuring instrument, and the head should be held in the Frankfort horizontal plane with upward pressure exerted under the child’s mastoid process to hold the correct position and to measure maximal height. The measurement of height is taken by sliding a right-angle block downward until it touches the child’s head; the height can then be read from the vertically mounted rule. Accurate, reproducible height measurements cannot be obtained from the commonly used height-measuring devices attached to weighing scales. The importance of adhering to the correct technique is documented in the National Health Survey data.1,2,3,4,5 and 6
FIGURE 7-5. Technique of accurate measurement of standing height.
The standard growth charts with their height percentiles are growth attainment charts, which represent how much height the child has attained by a particular age. A concept that is often more useful, especially when evaluating the longitudinal growth of an individual child, is growth velocity, which depicts growth during a given period. The difference in height at the beginning and end of a given period of time is annualized and then expressed as centimeters per year.11,12 The X-axis on a growth velocity chart is the chronologic age; the Y-axis is the growth velocity in centimeters per year. These charts take into consideration the variability in height velocity caused by the normal variability in age of onset of puberty.
An advantage of height velocity charts is their ability to demonstrate more quickly an aberration of growth or the effects of treatment. Short-term growth velocity data, however, may be subject to error because of marked seasonal variation; children generally grow faster in the spring through early summer.24
The growth velocity charts clearly demonstrate that a child’s growth rate is most rapid during infancy and puberty and is relatively stable during the elementary school years.
Although these charts present height velocity percentiles ranging from the 3rd to 97th percentiles, these may not represent the biologic normal range. Longitudinal growth that is consistently below the 10th percentile may not be sufficient to maintain a child in a single height attainment percentile; instead, that child may demonstrate a downward shift in height percentile.25
Skinfold thickness is used as a measure of total body fat.26 In research studies, more than one site needs to be measured, but for clinical use, the more readily accessible triceps skin-fold is commonly used. The National Health Survey used a carefully standardized technique to measure the triceps skin-fold. The Lange caliper (Fig. 7-6) was used on a skinfold parallel to the long axis of the arm over the triceps muscle halfway between the elbow and acromial process of the scapula; care was taken to apply the caliper so that the pressure plates remained parallel to each other. Table 7-2 presents the normal values.27,28 and 29
FIGURE 7-6. Measurement of skinfold thickness with the Lange caliper.
TABLE 7-2. Percentiles for Triceps Skinfold Thickness (in Millimeters) by Year of Age27,28
BODY MASS INDEX
Body mass index (BMI) is another convenient measure of body fat. It is derived by calculating the weight in kilograms divided by the the height in meters squared. Population ranges for American children are now available according to ethnic group for ages 5 to 17 years.30 The 15th, 50th, and 85th percentiles for each ethnic group appear in Table 7-3. The BMI will assume greater applicability once the new BMI curves are available from the National Center for Health Statistics. For adults, grade 1 obesity is defined as a BMI of over 25 and grade 2 obesity as a BMI over 30. Similar cutoff levels have been suggested for late adolescence. These BMI values are close to the 80th and 95th percentiles, respectively, on the National Center for Health Statistics charts.31
TABLE 7-3. Body Mass Index Centiles for Children 5–17 Years of Age
The concept of bone age is based on the skeletal changes that occur with the physical growth and maturation of the child. These skeletal changes include the calcification, growth, and shaping of the epiphyseal centers of the bones and their eventual fusion with the diaphyses. The fact that these changes occur in a regular sequence in the different bones as determined by the radiographic examination of normally developing children permits one to estimate a bone age for a particular child. Any of a number of techniques can be used, as well as any part of the skeleton. The most popular method in the United States compares a single anteroposterior radiograph of the left hand and wrist with the series of standard films in the atlas compiled by Greulich and Pyle.32 In Europe, the Tanner method is used to calculate the bone age of the left hand and wrist by using maturity indicators for each bone, so that a composite score is derived.33 The Tanner-Whitehouse method has been standardized for American children aged 8 to 16 years.34
As with any other laboratory test, there is a mean population bone age that corresponds to the particular best fit in the Greulich and Pyle atlas and a standard deviation or range of expected values. The normal range of expected bone ages for a child younger than 1 year of age is ±3 to 6 months; for a child of 6 to 11 years of age, the range is ±2 years; and for a child of 12 to 14 years of age, the range is ±2 years.35
The National Health Survey compared the bone ages of contemporary children with those derived from the original study of Greulich and Pyle between 1917 and 1942. The original study population was composed of upper-middle-class children in Cleveland. In children aged 6 to 11 years, good congruence was seen except that contemporary 10- and 11-year-old children showed a significant retardation in bone age of 0.2 to 0.65 years.36
The assumption that bone age advances 1 year for each calendar year may not be correct; bone age advances more rapidly than chronologic age during the onset of puberty and during peak height velocity of puberty. At these times, the average advancement in bone age over chronologic age is 1.73 years, with a range of 0.8 to 2.8 years.37 Bone age advancement should not be attributed falsely to therapeutic intervention. These results serve as another example of the difference between normal longitudinal growth of a single child and the cross-sectional standards that are usually available for tracking a child’s growth and development.37
The determination of bone age can be useful if one remains aware of its limitations. The particular standard used must be verified for the population being studied. The person interpreting the bone age radiograph must be consistent. Separate male and female standards exist, and there is a range of normal (see Chap. 18 and Chap. 217).
One of the most common applications of a bone age determination is the prediction of eventual adult height. Bayley and Pinneau38 published prediction tables based on the percentage of adult height attained at various bone ages. The tables were further refined by separating the children whose bone ages were>1 year advanced or retarded compared with chronologic age. Separate prediction tables are provided for these children as well as for males and females.
More mathematically refined systems have been proposed that use regression formulas with the addition of variables such as weight, midparental stature, growth velocity, and menarcheal status. The Roche-Wainer-Thissen (RWT) method uses the child’s recumbent length rather than standing height and is standardized for American children.39 The Tanner-Whitehouse system (TW2 Mark 2) is standardized for British children.33 It includes a larger number of children at the extremes of the standardizing group and thus tries to counter one criticism of height prediction methods—that they are most accurate for the prediction of the final adult height of normal children whose bone ages are not significantly retarded. In addition, the TW2 Mark 2 system no longer takes into account midparental stature in the prediction regression formulas, as did the previous formulas.
Regardless of which system is used for the prediction of adult height, the prediction always has an error. For the RWT method, the ±90% confidence range for a prediction is given in Table 7-1. For the TW2 Mark 2 system, the error is stated as a residual standard deviation. For comparison purposes, in Table 7-1, the residual standard deviation has been multiplied by 1.645 to provide the 90% confidence range for a predicted adult height. To obtain a 95% confidence range, the residual standard deviation is multiplied by ±1.96. For normal children, these two methods are comparable and appear more accurate than the older Bailey and Pinneau tables39; the stated error in the latter method is 5.1 cm for ±2 SD. In a comparative study of the three methods that examined Finnish children, the RWT method was slightly more accurate.40,41
The important issue is not how well the various height prediction systems work in normal children but rather how well they work in children with abnormal growth patterns. In children with familial tall stature, the Tanner method was slightly more accurate than the other two methods.41 Both the RWT and Tanner methods, however, overestimated adult height in children with precocious puberty or gonadal dysgenesis; the Bailey and Pinneau tables were more accurate in these conditions. The overestimation for children with precocious puberty ranged from 30 cm at 5 years of age to just 5 cm at 13 years of age. The overestimation of adult height was 10 cm at the earlier ages in children with gonadal dysgenesis. The greater accuracy of height prediction with increasing age of the patient also holds true for children with constitutional tall stature.42 In addition, the RWT and Tanner methods both overestimated the adult heights of children with primordial short stature.41
These studies used the older Tanner methods. Tanner and coworkers33 point out several limitations to the accuracy of their new formulas that should apply to other height prediction systems. Although the formulas take into account several variables, some unpredictability still exists, as reflected in the residual standard deviation. Tanner and co-workers33 point out that no particular reason exists that the equations should be valid in cases of precocious puberty or achondroplasia.
In part, the error in height prediction, measured by whatever means, may be due to the variability in total height gained during puberty. In a review43 of four studies of American children, from the onset of puberty, girls had an average gain in height of 25.4 to 31 cm, and boys had an average gain in height of 28.2 to 31 cm. The standard deviations ranged from 4 to 6.8 cm for girls and 4.3 to 5.5 cm for boys. Thus, although considerable height was gained during puberty, considerable variability was seen as well. Similar results were reported in European studies.43 Confounding this further is the inverse relationship between height obtained during puberty and the age of onset of puberty.44 This phenomenon may be related to the shortened duration of puberty, at least in girls, with the later onset of puberty.45
Finally, an additional caution arises from a study that compared the final adult height achieved by short children with normal bone ages and by short children with significantly retarded bone ages with predictions of the children’s height using the Bailey and Pinneau tables.46 Although only 1 of 17 children with normal bone age had an overpredicted adult height, 5 of 10 children with a retarded bone age had an over-prediction of their adult height—they failed to reach an adult height within 5.1 cm of the predicted height.46 This is the group of children for whom the physician is most often called on to use height prediction tables and provide reassurance to the patient and family.
A comparison of predicted adult height, based on bone age and current height, with the predicted genetic target adult height based on parental heights is often useful.16 This is of importance when determining if the child’s current height is inconsistent with genetic potential or when one is evaluating the effects of a therapeutic intervention.
Significant racial differences exist in regard to body proportions. The sitting/standing height ratio was determined during the National Health Survey.4,5 These data are presented in Table 7-1. Careful attention to detail is required. Height measurement using a wall-mounted instrument is required. Sitting height is measured on a sitting height table, with the child sitting erect in a standardized manner and with the head held in the Frankfort plane4,5 (Fig. 7-7).
FIGURE 7-7. Technique of accurate measurement of sitting height.
Table 7-4 presents the normal standards for penile and testicular size.47,48 and 49 Penile length is a stretched length; traction is applied to the penis and the rule is applied firmly to the root of the penis. Too often, the suprapubic fat pad is not compressed enough so that one obtains a penile length that is artifactually too short (see Chap. 93).
TABLE 7-4. Penile and Testicular Size During Childhood
The pediatric patient undergoes continuous change that is reflected not only in growth rates but also in the secretory activity of the endocrine system. The perinatal period is one of rapid change in the endocrine system when the child is adjusting to extrauterine life (Table 7-6). This is further complicated by the differences that may exist in hormonal levels in the full-term versus preterm infant. This section outlines some of these hormonal variations. As a general rule, one can divide the analysis of hormonal secretory activity into the following developmental periods: fetal, perinatal, childhood, and pubertal.50,51
TABLE 7-6. Blood Concentrations of Gonadotropins, Gonadal Steroids, Renin, and Aldosterone in Infancy and Childhood
GROWTH HORMONE AND INSULIN-LIKE GROWTH FACTORS
Immunoreactive growth hormone is found in human anterior pituitary glands as early as the seventh week of gestation.49 Pituitary growth hormone increases from 0.44µg per gland at 10 to 14 weeks of gestation to a mean of 675µg per gland at term. However, pituitary growth hormone level is fairly constant after 25 weeks of gestation. Growth hormone is also detectable in fetal serum in high concentration. These high concentrations of growth hormone may be a reflection of hypothalamic-pituitary neuroendocrine immaturity. At 10 to 14 weeks of gestation, the mean growth hormone level in fetal serum is 65 ng/mL, and it rises rapidly to a peak fetal concentration of 132 ng/mL at 20 to 25 weeks of gestation. Thereafter, serum growth hormone declines to 35 ng/mL at 35 to 40 weeks of gestation.
The postulated immature neuroendocrine control of growth hormone secretion persists into the neonatal period. Growth hormone is not suppressed by glucose until 1 month of age, and the normal sleep-induced rise in serum growth hormone levels does not appear until 3 months of age.51
Insulin-like growth factor-I (IGF-I) plasma concentrations show a marked age-related pattern. The normal ranges, as reported by the Quest Diagnostic Nichols Institute, are shown in Figure 7-8 and Figure 7-9. The range is large, and a marked overlap of values is seen when one compares the lower range of normal with values typically associated with growth hormone deficiency. Plasma IGF-I levels increase with age; during puberty concentrations are reached that would be associated with acromegaly if encountered in an adult. After puberty, the levels decline to the normal adult range. Females generally have IGF-I levels ~20% higher than those of males. The normal level of IGF-I may correlate better with the child’s physiologic development. Such a relation is seen during puberty (see Fig. 7-9). For prepubertal boys, a similar relation with bone age may be valid as well.52,53 Insulin-like growth factor–binding protein-3 (IGFBP-3) has been suggested as another serum protein reflective of growth hormone secretion and function.54 In a manner similar to IGF-I, normal values for IGFBP-3 vary according to age and stage of puberty (Fig. 7-10).
FIGURE 7-8. Variation of insulin-like growth factor-I with age and sex. (Data derived from the normal values provided by Quest Diagnostic Nichols Institute, San Juan Capistrano, California.)
FIGURE 7-9. Variation of insulin-like growth factor-I with stage of puberty and sex. (Data derived from the normal values provided by Quest Diagnostic Nichols Institute, San Juan Capistrano, California.)
FIGURE 7-10. Variation of insulin-like growth factor–binding protein-3 with age. (Data derived from the normal values provided by Quest Diagnostic Nichols Institute, San Juan Capistrano, California.)
Measurement of insulin-like growth factor–binding protein-2 (IGFBP-2) has been proposed as another aid in the diagnosis of growth hormone deficiency55 (see Table 7-5). Interestingly, IGFBP-2 is increased in growth hormone deficiency, rather than being decreased as is the case with both IGF-I and IGFBP-3.
TABLE 7-5. Normal Values for Insulin-Like Binding Protein-2 (IGFBP-2)
ADRENOCORTICOTROPIC HORMONE AND ADRENOCORTICAL STEROIDS
Adrenocorticotropic hormone (ACTH) is detectable in fetal serum as early as 10 to 14 weeks of gestation. The concentration of ACTH declines toward term, falling from 249 pg/mL ± 65 SE (standard error) to 143 pg/mL ± 9 SE at term. By 1 week of age, the serum ACTH levels are similar to those found in older children. The pattern of adrenal corticosteroids secreted varies from those found in older children. This is due to the presence of a fetal zone in the adrenal gland that constitutes 70% to 85% of the total weight of the adrenal gland at term. In both full-term and premature infants, the fetal zone undergoes rapid involution after birth, so that it constitutes just 10% of the adrenal gland by 4 to 5 months of age.56 Plasma concentrations of adrenal steroids are shown in Figure 7-11.
FIGURE 7-11. Variation of selected adrenal steroids with age and onset of puberty. (DHEA, dehydroepiandrosterone.) (Data derived from the normal values provided by Endocrine Sciences, Calabasas Hills, California.)
THYROID-STIMULATING HORMONE AND THYROID HORMONES
As with the previously discussed hormone systems, thyroid function varies greatly depending on gestational age and perinatal circumstances (see Chap. 47). Thyroid-stimulating hormone (TSH) is detected in fetal serum as early as 10 weeks of gestation; however, the levels are low—only 2.4µU/mL ± 0.14 SE at 10 to 20 weeks of gestation. This increases to 9.6µU/mL ± 0.93 SE at 25 to 30 weeks of gestation. The increase in TSH is accompanied by increases in mean free thyroxine (T4) and total T4 serum concentrations. Free T4 increases from 1.8 ng/dL at 10 to 20 weeks of gestation, to 2.6 ng/dL at 22 weeks, to 3 ng/dL at 30 weeks, and to 4 ng/dL at term. The rise in mean T4-binding globulin during this period helps to produce an increase in serum T4 levels, which rise from 3µg/dL at 20 weeks of gestation to 9.4µg/dL (range, 5.7–15.6) at 30 weeks of gestation. Without any further rise in T4-binding globulin, the fetal T4 rises to 10.1µg/mL at 35 weeks of gestation (range, 6.1–16.8) and to 10.9µg/dL by term (range, 6.6–18.1).57,58 Between 30 and 40 weeks of gestation, some further maturation seems to take place of the hypothalamic systems responsible for the feedback inhibition of TSH by circulating thyroid hormones. This is suggested by the fall in serum TSH concentration to 8.9µU/mL ± 0.93 SE at term as the serum free T4 rises.59 New second- and third-generation TSH assays have been introduced, and the absolute values listed should be viewed relative to the newer assays.
The perinatal period is associated with marked changes in thyroid hormone levels. Within a half hour of birth, the serum TSH level rises to a mean of slightly over 18µU/mL and then rapidly returns to normal within a day. The rise in serum TSH is paralleled within 24 hours by rises in serum T4 and triiodothyronine (T3) levels; T3 levels then decline in a few days, and T4 levels decline in a few weeks. Similar but less marked changes are seen in premature infants.59 The rise in serum T3 is not completely dependent on the rise in TSH but rather is also due to a change in the peripheral conversion of T4 to T3, as opposed to reverse T3, which occurs in the prenatal period59 (see Chap. 15, Chap. 33 and Chap. 47). The changes in thyroid hormone levels during the neonatal period in premature infants is also dependent on the degree of prematurity and the infant’s health status.60
LUTEINIZING HORMONE, FOLLICLE-STIMULATING HORMONE, AND THE SEX STEROIDS
As early as the 10th week of gestation, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are found in fetal pituitary glands. Serum LH and FSH levels in the fetus are high, well within the adult castrate range. Higher fetal serum FSH levels are found in females. Toward term, serum LH and FSH levels decline to the low levels typically found at term, but shortly after birth, serum levels of LH and FSH rise again, with LH levels higher in the male and FSH levels higher in the female. Serum LH and FSH levels may not decline to the concentrations deemed typical of childhood for 6 to 12 months (Table 7-6; see also Chap. 16 and Chap. 91). Marked differences appear to exist in the patterns of immunoreactive LH and FSH as compared with bioactive LH and FSH. The ratios also appear to vary with age and stage of development.61,62 and 63
The fetal serum estradiol level does not differ in males and females, but males have higher serum levels of testosterone before the 20th week of gestation, corresponding to the period of development of the male external genitalia. The serum testosterone level ranges from 100 to 600 ng/dL.64 The fetal serum testosterone level declines toward term, but in cord blood, it remains higher in males than in females. Coincident with the postnatal surge of LH, serum testosterone levels in males rise again to mid-pubertal levels, remaining higher than concentrations thought appropriate for childhood until 4 to 9 months of age.65,66,67 and 68 The normal concentrations of these hormones and some other adrenal hormones are presented in Table 7-6 and Figure 7-11.
Although the serum androstenedione level is in the typical prepubertal range by 1 year of age, it begins to rise again before any manifestations of puberty. Androstenedione begins to rise at 8 years of age in boys and at 7 years of age in girls.
A similar pattern can be seen for dehydroepiandrosterone and for dehydroepiandrosterone sulfate. The rise in these hormones starts at 7 years of age in boys and at 6 years of age in girls. Similar to other adrenal androgens, dehydroepiandrosterone sulfate also manifests serum concentrations that vary with the child’s age. In premature infants, the mean serum concentration is 263µg/dL ± 40.1 SD; in full-term infants, 58.9µg/dL ± 4.5 SD; in male children 1 to 6 years of age, 15.4µg/dL ± 6.8 SD; in female children 1 to 6 years of age, 24.7µg/dL ± 11.1 SD; in male children 6 to 8 years of age, 18.8µg/dL ± 4.1 SD; in female children 6 to 8 years of age, 30.4µg/dL ± 7.6 SD; in male children 8 to 10 years of age, 58.6µg/dL ± 10.1 SD; and in female children 8 to 10 years of age, 117.3µg/dL ± 41.7 SD69 (see Chap. 91 and Chap. 92).
RENIN AND ALDOSTERONE
The plasma concentrations of renin and aldosterone are markedly elevated in the newborn and decline slowly to accepted normal levels70 (see Table 7-6).
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