Growth of Hyperactive Children Treated With Methylphenidate James H.
Satterfield, MD; Dennis
P.
Cantwell, MD;
Ann
Schell, PhD; Thomas Blaschke, MS
\s=b\ This is a study of the growth of 72 hyperactive boys treated continuously with methylphenidate hydrochloride. Major findings were that methylphenidate produces an adverse effect on growth in height and in weight in the first year of treatment, but not in the second year; the first year height deficit is offset in the second year by a greater-than-expected growth rate. No clinical predictors of growth deficits were found; growth in height deficits are not related to total dosage or summer drug holidays, but weight deficits may be related to these factors. Side effects did not correlate with dosage. The temporary growth deficits of the first year are of such minor magnitude as to have little clinical significance. (Arch Gen Psychiatry 36:212-217, 1979)
article
prospective study of weight and hyperactive boys treated for one hyperactive boys treated for two years with methylphenidate hydrochloride.
Thisheight gainreports in year and 48
a
a
All children who were referred to Gateways Hospital Hyperki¬ netic Children's Clinic, Los Angeles, from September 1973 through December 1974 and who met the following selection criteria were admitted to this study. Subjects had to be boys between the ages of 6 and 12. They had to be attending school, have normal vision and hearing, and be of normal intelligence on the Wechsler Intel,:gence Scale for Children (full scale IQ of 80 or above). All subjects were hyperactive by behavioral criteria that required evidence of a chronic symptom pattern of hyperexcitability, impulsivity, and poor attention span, as reported by parents and teachers. Because our subjects were children, informed consent was obtained from the child's parents after the procedures of the study had been fully explained. Details of behavioral, psychiatric, psychological, neurological, and psychosocial studies in these children have been reported elsewhere.' In general, this was a group of nonpsychotic, nonbrain damaged boys of normal intelligence. Their baseline factor scores on the Connors Teacher Rating Scale were similar to those in three other independent studies of hyperactive children.'
Methylphenidate
Treatment
Medication was started at low doses (5 to 10 mg twice a day) and increased at weekly intervals until good clinical response was noted. Most patients took their medication in divided doses (morning and noon) on five weekdays. However, a few required a midafternoon dose, while several others required medication seven
Accepted for publication Sept 5, 1978. From Gateways Hospital (Dr Satterfield and Mr Blaschke), Department of Psychiatry, University of California, Los Angeles (Drs Satterfield and Cantwell), and the Department of Psychology, Occidental College, Los Angeles (Dr Schell). Reprint requests to Gateways Hospital, 1891 Effie St, Los Angeles, CA Satterfield).
Tables 1 and 2.
Twenty percent of the subjects had received stimulant drugs for varying periods of time prior to entering the study. However, during the first year, this subgroup did not show height or weight deficits that differed from the other 80% who had not received prior medication. Neither group showed growth deficits in the second year. These two groups were therefore combined for subsequent data analyses.
group of 72
SUBJECTS AND METHODS Selection Criteria and Patient Population
90026 (Dr
days a week. Our treatment philosophy was oriented to providing a drug-free holiday during the summer. Many children, however, required continuous medication during the summer, though usual¬ ly at somewhat lower dosages. All of these varied patterns of treatment were considered when the average daily dosage in milligrams per kilogram of body weight per day was computed for each individual child over the entire period. Medication dosages at various times for various groups during years 1 and 2 are shown in
Height and Weight Measurements height and weight measurements were
Patients' obtained before treatment and at monthly intervals thereafter in most cases. Thus, there were up to 12 measurements during each year of treatment for both height and weight. All weight and height measurements were obtained by a member of the research team on a pediatrie scale, with the child's shoes removed and his pockets emptied. Although these measurements were carefully done, there is always some inherent error in any such measurement. There¬ fore, to reduce the amount of error present in any single measure, all of the monthly measurements were used to determine growth velocities and total year's growth. This was done by fitting a regression line to each of the three time periods that were expected to have different rates of growth (before, during, and after summer). Thus, for each child, monthly height and weight measurements were used to derive a trisegmental line for the regression of height and weight on age (Fig 1). The intersection of the regression line with the appropriate time periods (12 and 24 months) was used as the best estimate of the child's height and weight at those points in time, rather than the individual observed measures at those same points (Pig 1). For a few subjects, this procedure could not be followed, as there were not enough monthly measurements during all three periods to derive a trisegmental regression line. For those cases, single measures of height and weight obtained at the appropriate points in time were used. All correlations between single measures and growth values at the same points in time taken from the regres¬ sion lines exceeded .95, so very little error should have been incurred from this occasional direct use of individual growth measures. That the data fit these trisegmental regression lines quite well is indicated by the fact that the r2 values in predicting height and weight from age in year 1 and year 2 ranged from .80 to .90. Initial
height and weight measures were utilized to obtain a percentile rank based on the Iowa growth percentile tables for normal children.2 Using these same tables, this percentile rank predicted height and weight at years 1 and 2 for each child. The initial values subtracted from the predicted values at end of year 1 were then used to compute expected gains during year 1.
Downloaded From: http://archpsyc.jamanetwork.com/ by a University of Ottawa User on 04/17/2016
Table 1. Initial
Height
Weight
and
Height, Group Total Summer medi¬ cation No summer medication "First year
mean
During
Year 1 for All
Subjects
First Year
Presummer
Summer
Postsummer
SD
Drug Dosage, mg/Day*
Mean
.49
.30
SD .37
Mean
.47
SD .33
Mean
24.2
SD .35
Mean
7.7
.53
SD .42
29.1
5.9
26.8
.62
.41
.53
.31
.51
.42
.70
.48
29.8
8.9
22.2
.37
.25
.45
.15
.00
.40
.32
Mean 132.2
SD
Mean
10.8
29.5
31
131.2
11.0
41
132.9
10.6
on
Information
Drug Dosage, mg/kg/Day
Weight, kg
cm
No. of Patients 72
dosage
Dosage
Initial
Initial Patient
and
drug days.
Table 2. Initial
Height
and
Weight
and
Dosage
Information for
Subjects Continuing
Two Years
Drug Dosage, mg/kg/Day Initial No. of Patients Total group Summer medication second year No summer medication second year Both summer medication Neither summer medication
48 24 24
Height,
Mean 132.6 129.3 135.8 129.6
deficits. in Medication
That the majority of patients took their prescribed dosage of medication is indicated by the results of our monthly urinalysis for ritalinic acid, a major metabolite of methylphenidate. By this objective laboratory method we were able to validate drug compliance in 93% of our patients. Details of this method have been reported elsewhere.1 It should be noted that validation of drug compliance by urinalysis was attempted monthly. In the 93% of children for whom we were able to repeatedly validate drug compliance by this procedure, we assume that parental reports of consistent use of medication between monthly visits were also valid. This assump¬ tion is consistent with other indirect evidence of drug compliance: parental reports of their weekly checks on administration of medication at school and changes in monthly teacher rating scales, which have been reported elsewhere.'
Statistical
SD
Analysis
All statistical tests reported are either two-tailed t tests Pearson correlation coefficients. RESULTS Presummer, Summer, and Postsummer Velocities
or
Weight and height gain velocities (centimeter or kilo¬ gram gain per month values) were studied for three time periods during the first year: presummer, summer, and postsummer. The actual length of these periods for each subject varied, depending on the time of year the subject entered the study. All subjects began treatment before the summer period. Therefore, this presummer period was the first treatment period in all cases. The mean time for the before, during, and after summer periods was 4.49, 3.15, and 4.36 months, respectively. Deficits (expressed in percent) were defined as expected growth velocity minus
Weight, kg
Mean 29.2
9.8
9.7 8.8 12.7
28.2 30.3 28.4 293
133.6
Expected gains for year 2 were similarly computed (predicted height and weight at end of year 2 minus predicted height and weight at end of year 1. Growth deficits were computed by two methods: predicted growth minus observed growth equals deficit, in kilograms or centimeters, and predicted growth minus observed growth, divided by predicted growth, times 100 equals percent
Compliance
Initial
cm
First Year
Second Year
SD 5.6 5.8
Mean
.52 65
SD .38 .48
Mean .59
5.4 6.2 5.4
.40 .76 .38
.17 .52 .13
.37 .83 .36
SD .44
.52
.52 .19
observed velocity, divided by expected velocity, times 100. For the purpose of this analysis, the summer medication and the no summer medication groups were studied sepa¬ rately in each of the three time periods. Summer Medication Group.—Thirty-one children received medication for the summer period. The height and weight deficits during the three time periods are shown in Fig 2. The mean weight and height deficits in the presummer period were both statistically significant. In the summer period, only the height deficit, actually a height surplus, was significantly different from zero. In the postsummer period, neither the height nor the weight deficit was
significant.
No Summer Medication Group.—Forty-one children did not receive medication during the summer of treatment year 1. The height and weight deficits during the three time periods are shown in Fig 2. In the presummer period,
weight deficit was significant. Summer weight height deficits were not significant. In the postsum¬ mer period, only the height deficit was significant. Total Growth During the First Year For the 72 subjects studied during year 1, the mean observed weight gain was 0.85 kg less and the mean height gain was 1.03 cm less than the predicted year's growth (Fig 3). As can be seen in Fig 3, there was a trend for the 12-month weight deficits to be greater and height deficits
only
the
and
to be smaller in the group that had continued medication during the summer, but these differences did not reach
statistical
significance. Not surprisingly, those subjects taking summer medication received a greater daily aver¬ age dosage for the year (Table 1). Second Year's Growth To compare the effect of stimulant medication
on
growth during treatment year 2 with its effect on growth during treatment year 1, we studied those 48 patients who were treated with methylphenidate both years (Fig 4). Dosages for these subjects are reported in Table 2.
Downloaded From: http://archpsyc.jamanetwork.com/ by a University of Ottawa User on 04/17/2016
Fig 1.—Trisegmental regression line for one individual subject. Observed weight measurements are re¬ gressed on age in months, for three time periods: presummer, summer, and postsummer months. This re¬ sults in three straight lines with different slopes, reflecting different rates of growth.
37
36
34
MONTHS
0
1
2
3
4
S
-«-PRESUMMER-»—«- SUMMER
6 -»—
8
12
10
POSTSUMMER
Fig 2.—Growth rate deficit in per¬ cent of expected growth rate during presummer, summer, and postsum¬
mer months for children who con¬ tinued medication during summer months (summer medication group)
and children who medication during
discontinued
summer
(no
medication group) (aster¬ isk indicates < .05, double aster¬ isk, P< .01).
summer
PRESUMMER
SUMMER
Second Year vs First Year Growth.—During treatment 1, the mean observed weight gain of these 48 patients was 0.72 kg less and the mean height gain was 0.52 cm less than the predicted year's growth (Fig 4). During treatment year two, the mean observed weight gain was 0.31 kg less and the mean observed height gain was 0.42 cm more than the expected year's growth. These second-year growth values were not significantly different from the expected values. Accumulated height and weight deficits were measured over both years. Only the cumulative weight deficit was significant. In the second year, 24 subjects took medication during the summer months and 24 did not. Fourteen of the 24 subjects receiving summer medication in the second year also took summer medication in the first year. The 24 children who continued their medication in the summer of year two had a weight gain that was 0.67 kg less and a height gain that was 0.36 cm more than expected year
SUMMER
MEDICATION = 31
POSTSUMMER
GROUP
PRESUMMER NO
SUMMER
SUMMER
POSTSUMMER
MEDICATION =
GROUP
41
The 24 children who discontinued medication for months had a weight gain that was 0.25 kg more and height gain that was 0.49 cm more than expected (Fig 5). These gains were not significantly greater than the expected gains. This trend for the no summer medica¬ tion group to have a smaller weight deficit than the summer medication group during treatment year two was
(Fig 5). the
summer
marginally statistically significant.
Continuous Medication Effect
on
Growth
To examine the effects of remaining on the medication regimen for the entire 24 months, we compared 14 patients who received medication during both summers and 18 patients who did not receive medication during either summer. The average daily dosage for those subjects receiving medication during both summers was signifi¬ cantly greater than the dosage for those subjects receiving no medication during both summers (P < .01) (Table 2).
Downloaded From: http://archpsyc.jamanetwork.com/ by a University of Ottawa User on 04/17/2016
40'
S
-
me
weight
W&
HEIGHT
íí WEIGHT ;
30-M
=48
30· i¿
***
20
20·
.
*
L·:·:·:·:·;
w
S 10'
10-1
o oc
¬
=
o
o
0
:
ÉÉÉÉI
O
COMBINED GROUPS Ns72 SUMMER
^
30
$:^i
WEIGHT
YEARS
20-
m&
HEIGHT
Fig 4.—Year 1, year 2, and accumulated (year 1 plus year 2) growth deficits in percent of expected growth in those 48 subjects who
Satterfield, MD; Dennis
P.
Cantwell, MD;
Ann
Schell, PhD; Thomas Blaschke, MS
\s=b\ This is a study of the growth of 72 hyperactive boys treated continuously with methylphenidate hydrochloride. Major findings were that methylphenidate produces an adverse effect on growth in height and in weight in the first year of treatment, but not in the second year; the first year height deficit is offset in the second year by a greater-than-expected growth rate. No clinical predictors of growth deficits were found; growth in height deficits are not related to total dosage or summer drug holidays, but weight deficits may be related to these factors. Side effects did not correlate with dosage. The temporary growth deficits of the first year are of such minor magnitude as to have little clinical significance. (Arch Gen Psychiatry 36:212-217, 1979)
article
prospective study of weight and hyperactive boys treated for one hyperactive boys treated for two years with methylphenidate hydrochloride.
Thisheight gainreports in year and 48
a
a
All children who were referred to Gateways Hospital Hyperki¬ netic Children's Clinic, Los Angeles, from September 1973 through December 1974 and who met the following selection criteria were admitted to this study. Subjects had to be boys between the ages of 6 and 12. They had to be attending school, have normal vision and hearing, and be of normal intelligence on the Wechsler Intel,:gence Scale for Children (full scale IQ of 80 or above). All subjects were hyperactive by behavioral criteria that required evidence of a chronic symptom pattern of hyperexcitability, impulsivity, and poor attention span, as reported by parents and teachers. Because our subjects were children, informed consent was obtained from the child's parents after the procedures of the study had been fully explained. Details of behavioral, psychiatric, psychological, neurological, and psychosocial studies in these children have been reported elsewhere.' In general, this was a group of nonpsychotic, nonbrain damaged boys of normal intelligence. Their baseline factor scores on the Connors Teacher Rating Scale were similar to those in three other independent studies of hyperactive children.'
Methylphenidate
Treatment
Medication was started at low doses (5 to 10 mg twice a day) and increased at weekly intervals until good clinical response was noted. Most patients took their medication in divided doses (morning and noon) on five weekdays. However, a few required a midafternoon dose, while several others required medication seven
Accepted for publication Sept 5, 1978. From Gateways Hospital (Dr Satterfield and Mr Blaschke), Department of Psychiatry, University of California, Los Angeles (Drs Satterfield and Cantwell), and the Department of Psychology, Occidental College, Los Angeles (Dr Schell). Reprint requests to Gateways Hospital, 1891 Effie St, Los Angeles, CA Satterfield).
Tables 1 and 2.
Twenty percent of the subjects had received stimulant drugs for varying periods of time prior to entering the study. However, during the first year, this subgroup did not show height or weight deficits that differed from the other 80% who had not received prior medication. Neither group showed growth deficits in the second year. These two groups were therefore combined for subsequent data analyses.
group of 72
SUBJECTS AND METHODS Selection Criteria and Patient Population
90026 (Dr
days a week. Our treatment philosophy was oriented to providing a drug-free holiday during the summer. Many children, however, required continuous medication during the summer, though usual¬ ly at somewhat lower dosages. All of these varied patterns of treatment were considered when the average daily dosage in milligrams per kilogram of body weight per day was computed for each individual child over the entire period. Medication dosages at various times for various groups during years 1 and 2 are shown in
Height and Weight Measurements height and weight measurements were
Patients' obtained before treatment and at monthly intervals thereafter in most cases. Thus, there were up to 12 measurements during each year of treatment for both height and weight. All weight and height measurements were obtained by a member of the research team on a pediatrie scale, with the child's shoes removed and his pockets emptied. Although these measurements were carefully done, there is always some inherent error in any such measurement. There¬ fore, to reduce the amount of error present in any single measure, all of the monthly measurements were used to determine growth velocities and total year's growth. This was done by fitting a regression line to each of the three time periods that were expected to have different rates of growth (before, during, and after summer). Thus, for each child, monthly height and weight measurements were used to derive a trisegmental line for the regression of height and weight on age (Fig 1). The intersection of the regression line with the appropriate time periods (12 and 24 months) was used as the best estimate of the child's height and weight at those points in time, rather than the individual observed measures at those same points (Pig 1). For a few subjects, this procedure could not be followed, as there were not enough monthly measurements during all three periods to derive a trisegmental regression line. For those cases, single measures of height and weight obtained at the appropriate points in time were used. All correlations between single measures and growth values at the same points in time taken from the regres¬ sion lines exceeded .95, so very little error should have been incurred from this occasional direct use of individual growth measures. That the data fit these trisegmental regression lines quite well is indicated by the fact that the r2 values in predicting height and weight from age in year 1 and year 2 ranged from .80 to .90. Initial
height and weight measures were utilized to obtain a percentile rank based on the Iowa growth percentile tables for normal children.2 Using these same tables, this percentile rank predicted height and weight at years 1 and 2 for each child. The initial values subtracted from the predicted values at end of year 1 were then used to compute expected gains during year 1.
Downloaded From: http://archpsyc.jamanetwork.com/ by a University of Ottawa User on 04/17/2016
Table 1. Initial
Height
Weight
and
Height, Group Total Summer medi¬ cation No summer medication "First year
mean
During
Year 1 for All
Subjects
First Year
Presummer
Summer
Postsummer
SD
Drug Dosage, mg/Day*
Mean
.49
.30
SD .37
Mean
.47
SD .33
Mean
24.2
SD .35
Mean
7.7
.53
SD .42
29.1
5.9
26.8
.62
.41
.53
.31
.51
.42
.70
.48
29.8
8.9
22.2
.37
.25
.45
.15
.00
.40
.32
Mean 132.2
SD
Mean
10.8
29.5
31
131.2
11.0
41
132.9
10.6
on
Information
Drug Dosage, mg/kg/Day
Weight, kg
cm
No. of Patients 72
dosage
Dosage
Initial
Initial Patient
and
drug days.
Table 2. Initial
Height
and
Weight
and
Dosage
Information for
Subjects Continuing
Two Years
Drug Dosage, mg/kg/Day Initial No. of Patients Total group Summer medication second year No summer medication second year Both summer medication Neither summer medication
48 24 24
Height,
Mean 132.6 129.3 135.8 129.6
deficits. in Medication
That the majority of patients took their prescribed dosage of medication is indicated by the results of our monthly urinalysis for ritalinic acid, a major metabolite of methylphenidate. By this objective laboratory method we were able to validate drug compliance in 93% of our patients. Details of this method have been reported elsewhere.1 It should be noted that validation of drug compliance by urinalysis was attempted monthly. In the 93% of children for whom we were able to repeatedly validate drug compliance by this procedure, we assume that parental reports of consistent use of medication between monthly visits were also valid. This assump¬ tion is consistent with other indirect evidence of drug compliance: parental reports of their weekly checks on administration of medication at school and changes in monthly teacher rating scales, which have been reported elsewhere.'
Statistical
SD
Analysis
All statistical tests reported are either two-tailed t tests Pearson correlation coefficients. RESULTS Presummer, Summer, and Postsummer Velocities
or
Weight and height gain velocities (centimeter or kilo¬ gram gain per month values) were studied for three time periods during the first year: presummer, summer, and postsummer. The actual length of these periods for each subject varied, depending on the time of year the subject entered the study. All subjects began treatment before the summer period. Therefore, this presummer period was the first treatment period in all cases. The mean time for the before, during, and after summer periods was 4.49, 3.15, and 4.36 months, respectively. Deficits (expressed in percent) were defined as expected growth velocity minus
Weight, kg
Mean 29.2
9.8
9.7 8.8 12.7
28.2 30.3 28.4 293
133.6
Expected gains for year 2 were similarly computed (predicted height and weight at end of year 2 minus predicted height and weight at end of year 1. Growth deficits were computed by two methods: predicted growth minus observed growth equals deficit, in kilograms or centimeters, and predicted growth minus observed growth, divided by predicted growth, times 100 equals percent
Compliance
Initial
cm
First Year
Second Year
SD 5.6 5.8
Mean
.52 65
SD .38 .48
Mean .59
5.4 6.2 5.4
.40 .76 .38
.17 .52 .13
.37 .83 .36
SD .44
.52
.52 .19
observed velocity, divided by expected velocity, times 100. For the purpose of this analysis, the summer medication and the no summer medication groups were studied sepa¬ rately in each of the three time periods. Summer Medication Group.—Thirty-one children received medication for the summer period. The height and weight deficits during the three time periods are shown in Fig 2. The mean weight and height deficits in the presummer period were both statistically significant. In the summer period, only the height deficit, actually a height surplus, was significantly different from zero. In the postsummer period, neither the height nor the weight deficit was
significant.
No Summer Medication Group.—Forty-one children did not receive medication during the summer of treatment year 1. The height and weight deficits during the three time periods are shown in Fig 2. In the presummer period,
weight deficit was significant. Summer weight height deficits were not significant. In the postsum¬ mer period, only the height deficit was significant. Total Growth During the First Year For the 72 subjects studied during year 1, the mean observed weight gain was 0.85 kg less and the mean height gain was 1.03 cm less than the predicted year's growth (Fig 3). As can be seen in Fig 3, there was a trend for the 12-month weight deficits to be greater and height deficits
only
the
and
to be smaller in the group that had continued medication during the summer, but these differences did not reach
statistical
significance. Not surprisingly, those subjects taking summer medication received a greater daily aver¬ age dosage for the year (Table 1). Second Year's Growth To compare the effect of stimulant medication
on
growth during treatment year 2 with its effect on growth during treatment year 1, we studied those 48 patients who were treated with methylphenidate both years (Fig 4). Dosages for these subjects are reported in Table 2.
Downloaded From: http://archpsyc.jamanetwork.com/ by a University of Ottawa User on 04/17/2016
Fig 1.—Trisegmental regression line for one individual subject. Observed weight measurements are re¬ gressed on age in months, for three time periods: presummer, summer, and postsummer months. This re¬ sults in three straight lines with different slopes, reflecting different rates of growth.
37
36
34
MONTHS
0
1
2
3
4
S
-«-PRESUMMER-»—«- SUMMER
6 -»—
8
12
10
POSTSUMMER
Fig 2.—Growth rate deficit in per¬ cent of expected growth rate during presummer, summer, and postsum¬
mer months for children who con¬ tinued medication during summer months (summer medication group)
and children who medication during
discontinued
summer
(no
medication group) (aster¬ isk indicates < .05, double aster¬ isk, P< .01).
summer
PRESUMMER
SUMMER
Second Year vs First Year Growth.—During treatment 1, the mean observed weight gain of these 48 patients was 0.72 kg less and the mean height gain was 0.52 cm less than the predicted year's growth (Fig 4). During treatment year two, the mean observed weight gain was 0.31 kg less and the mean observed height gain was 0.42 cm more than the expected year's growth. These second-year growth values were not significantly different from the expected values. Accumulated height and weight deficits were measured over both years. Only the cumulative weight deficit was significant. In the second year, 24 subjects took medication during the summer months and 24 did not. Fourteen of the 24 subjects receiving summer medication in the second year also took summer medication in the first year. The 24 children who continued their medication in the summer of year two had a weight gain that was 0.67 kg less and a height gain that was 0.36 cm more than expected year
SUMMER
MEDICATION = 31
POSTSUMMER
GROUP
PRESUMMER NO
SUMMER
SUMMER
POSTSUMMER
MEDICATION =
GROUP
41
The 24 children who discontinued medication for months had a weight gain that was 0.25 kg more and height gain that was 0.49 cm more than expected (Fig 5). These gains were not significantly greater than the expected gains. This trend for the no summer medica¬ tion group to have a smaller weight deficit than the summer medication group during treatment year two was
(Fig 5). the
summer
marginally statistically significant.
Continuous Medication Effect
on
Growth
To examine the effects of remaining on the medication regimen for the entire 24 months, we compared 14 patients who received medication during both summers and 18 patients who did not receive medication during either summer. The average daily dosage for those subjects receiving medication during both summers was signifi¬ cantly greater than the dosage for those subjects receiving no medication during both summers (P < .01) (Table 2).
Downloaded From: http://archpsyc.jamanetwork.com/ by a University of Ottawa User on 04/17/2016
40'
S
-
me
weight
W&
HEIGHT
íí WEIGHT ;
30-M
=48
30· i¿
***
20
20·
.
*
L·:·:·:·:·;
w
S 10'
10-1
o oc
¬
=
o
o
0
:
ÉÉÉÉI
O
COMBINED GROUPS Ns72 SUMMER
^
30
$:^i
WEIGHT
YEARS
20-
m&
HEIGHT
Fig 4.—Year 1, year 2, and accumulated (year 1 plus year 2) growth deficits in percent of expected growth in those 48 subjects who
