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Growth and body composition of preterm, small-for-gestational-age infants at a postmenstrual age of 37–40 weeks
Early Human Development, 33 (1993)11I- I3 I 0 1993 Elsevier Scientific Publishers Ireland Ltd. All rights reserved
II7 0378-3782/93/$06.00
EHD 01409
Growth and body composition of preterm, small-for-gestational-age infants at a postmenstrual age of 37-40 weeks Kuo-Inn Tsou Yau and Mei-Hwei Chang Department
of Pediatrics,
(Received
1 September
College of Medicine, 1992; revision
National
received
Taiwan University,
25 January
Taipei (Taiwan,
1993; accepted
9 March
ROC)
1993)
Summary
In order to understand the nutritional status of preterm, small-for-gestational-age (SGA) infants in the early postnatal period, the growth and body composition of preterm, SGA infants was followed prospectively from birth to the postmenstrual age of 37-40 weeks. The infants were stratified into different groups by gestational age, clinical condition and body proportionality. In each subgroup, the growth and changes in body composition of SGA infants were compared with appropriate-forgestational-age (AGA) infants of a comparable postmenstrual age. At birth, the SGA infants of both the 3 l-33 and 34-36 week gestational-age groups were smaller than AGA infants in all body measurements, including arm area (AA), arm muscle area (AMA) and arm fat area (AFA). When the preterm SGA infants had grown to the postmenstrual age of 37-40 weeks, the amount of fat they had accumulated was as much as, or more than that in term AGA infants. Yet, they had less muscle mass and their body weight, body length and head circumference were less than those in term AGA infants. This pattern of growth and the changes in body composition had been persistently observed in SGA infants of different gestational-age groups, different clinical status and different body proportionality. Differences between postnatal enteral nutrition and placental nutrition, or different energy utilization, in preterm SGA infants are hypothesized to account for these observations. The growth of less mature (31-33 weeks gestation) SGA infants and those preterm SGA infants with an eventful clinical course was suboptimal as compared with other SGA infants in the same subgroup. In this study, the weight to length ratio (WLR) was used to define the status of nutrition in preterm SGA infants: WLR % 2 S.D. or > 2 S.D. off the reference mean. Infants in both groups showed some catch-up Correspondence to: Kuo-Inn Tsou Yau, Department Taipei, Taiwan IO 016, ROC.
of Pediatrics,
National
Taiwan
University
Hospital.
118
growth in body weight. Yet, at near-term their body weight were still more than 2 SD. below the mean of term AGA. In each gestational-age group, the growth of these two body-proportionality groups did not differ from each other except for the low WLR group of 34-36 weeks gestation which had a significantly lower body weight and skinfold thickness than the group with a normal WLR. Multiple regression analysis revealed that skinfold measurements of preterm SGA infants at birth is the best factor for determining the body weight gain at near-term. After use of the skinfold thickness was set aside, WLR became the most important factor. The results of this study highlight the importance of evaluating the body composition of growing preterm SGA infants to assess their nutritional status. Key words: small-for-gestational-age growth
infants; preterm infants; body composition;
Introduction To meet the nutritional requirements of small-for-gestational-age infants (SGA infants; infants who weigh less than the 10th percentile for gestational age) [l] is a challenge to neonatologist, not only because of their prematurity, but also because of their deviation from normal growth. The growth of either premature or SGA infants is usually assessed by the changes in body weight (BW), body length (BL) or head circumference (HC) [2-71. In recent years, measurements of skinfold thickness, mid-arm circumference (MAC) and indices for assessing body proportionality have been used to evaluate the presence of impaired fetal nutrition [8,9] and also to assess the nutritional status of postnatal growth [lo]. The majority of studies on the growth of SGA infants have been done either on term SGA infants [3-51 or in a mixed group including both AGA and SGA infants [2,6]. There are very few longitudinal studies which have evaluated both the growth and the changes in body composition of preterm SGA infants as they grow to nearterm [ 111. Appropriate-for-gestational-age (AGA) preterm infants have been noted to accumulate a higher amount of fat postnatally than neonates of the same postmenstrual age when they were given formula feedings designed to mimic intrauterine growth rates [ 121.Therefore, it would be interesting to know the postnatal changes in body composition of preterm SGA infants. Our study longitudinally followed the changes in body composition of preterm SGA infants from birth to a postmenstrual age at 37-40 weeks and compared their body compositions with those of AGA infants of a similar postmenstrual age at birth. In addition, the postnatal growth and changes in body composition of preterm SGA infants was assessed by the severity of postnatal illnesses and the type of growth retardation. Factors which correlated best with body-weight deviation at near-term of these preterm SGA infants were also analyzed. Subjects and Methods Thirty-eight SGA infants with a gestational age of less than 37 weeks (gestational age: 3 l-36 weeks; birth body weight: 1034-2110 g) and 193 AGA infants (gestation-
119
al age: 31-40 weeks; birth body weight: 1242-3858 g) admitted to the neonatal unit of the National Taiwan University Hospital without the following problems were enrolled in this study prospectively. Criteria for exclusion were congenital anomalies, chromosomal abnormalities or intrauterine infection. The SGA infants were stratified by degree of prematurity into two gestational-age groups: 31-33 weeks (918 cases), and 34-36 weeks (20 cases). For the purpose of comparison, the AGA infants were stratified into three groups: 31-33 weeks (22 cases), 34-36 weeks (42 cases) and 37-40 weeks (129 cases). Gestational age was determined from the last menstrual period of the mother and confirmed postnatally by the Ballard score [ 131. Whenever there was a discrepancy of more than two weeks between these two methods, the latter was used. SGA was defined as an infant with a birth weight below the 10th percentile for his gestational age, based on the weight criteria established for Chinese fetuses [14]. All 193 AGA infants were healthy in the immediate neonatal period. In each gestational-age group of SGA infants, those who had sepsis, a high grade of intraventricular hemorrhage (Grade III or IV by Papile’s criteria [ 15]), needed respiratory therapy for more than 3 days for pulmonary disease or whose enteral feedings progressed with difficulty were grouped together as Group II, (nine cases in the 31-33 weeks gestational-age group, six cases in the 34-36 weeks gestational-age group). Those infants with a relatively uneventful clinical course for whom enteral feedings were started within one week of birth and progressed smoothly were grouped together as Group I (nine cases in the 31-33 weeks gestational-age group, 14 cases in the 34-36 weeks gestational-age group). SGA infants are heterogenous; some are malnourished, some are just small for their gestational age. The ponderal index (PI; BW/BL3 (g/cm3) x 100) has usually been used to assess the nutritional status of intrauterine growth [8] and its impact on the postnatal growth of SGA infants [3,10]. Recently, PI has been observed to not be reliable in the detection of symptomatic newborns with abnormal fetal growth [16-181. The simple weight-to-length ratio (WLR; BW/BL, g/cm) has been demonstrated to have the closest correlation with skinfold measurements by Wolf et al. [ 171, Sumners et al. [ 181, and by ourselves in a previous study [ 191. Therefore, WLR was used to assess the state of nutrition in our study infants. The SGA infants were classified into two groups: those having a low WLR (LWLR group, the WLR was 2 S.D. below the WLR of AGA infants of a similar postmenstrual age) and those having a normal WLR (NWLR group; the WLR was within 2 S.D. of that of AGA infants of a similar postmenstrual age). Study infants with a birth body weight of less than 1800 g were usually cared for and nursed in an incubator with the temperature set within the range for a neutral thermal environment. Usually, after their admission to the neonatal unit, the infants received an intravenous infusion of a glucose solution which was started at a rate of 80- 100 ml/kg per day and was increased by lo-20 ml/kg per day, until 150- 160 ml/kg per day was reached, as determined by the amount of urine output and the status of hydration. Infants were usually fed 12-48 h after birth for those weighing less than 1500 g, and 4-24 h for those weighing more than 1500 g at birth. Enteral feedings began with sterile water, then glucose water; milk feedings were started with a premature infant formula at a concentration of 40 kcal/lOO ml with the milk con-
120
centration increased gradually to 80 kcal/lOO ml in 7-10 days. The goal of enteral feeding was to provide a daily caloric intake of 120 kcal/kg; this was usually achieved at l-2 weeks old for infants who weighed less than 1500 g, and at 5-7 days old for those weighing more than 1500 g. For sick infants and infants who weighed less than 1800 g, partial parenteral nutrition was supplied until they could obtain adequate calories enterally. Amino acid supplement was started at 0.5 g/kg per day on the third day of life and increased gradually up to 2.0-2.5 g/kg per day, as required. Lipid supplement was usually given 5-7 days after birth at 0.5 g/kg per day, then increased gradually up to 2.0 g/kg per day, as required. As the amount of the enteral feedings increased, parenteral nutrition was decreased. Our aim was to supply a caloric intake of 90-l 10 kcal/kg per day (enteral plus supplementary parenteral nutrition). The study infants were fed with a premature formula until their body weight reached 1800 g, then the formula was changed to that used for full-term infants. The premature infant formula contains approximately 80 kcal, 2.2 g protein and 4.3 g fat per 100 ml. The formula for full-term infants contains approximately 67 kcal, 1.5 g protein and 3.6 g fat per 100 ml. Each study case. was followed prospectively during the infant’s hospital stay, and then at the outpatient clinic. Informed consent for study was obtained from at least one of the parents of each patient. The following measurements were obtained weekly during hospitalization and at each outpatient visit: BW, BL, HC, MAC, skinfold thickness (T - SF, sum of the measurements obtained at the tricepital and the subscapular areas of the left side). Details of the measurements are described elsewhere [20]. The skinfold thickness was measured in duplicate with a Holtain skinfold caliper (Holtain Ltd, Bryberian, UK; pressure 10 g/mm2) using the technique describe by Brans [21]. Then WLR, body mass index (BMI; BW/BL2, g/cm2), PI and MAC/HC were calculated from the above measurements. Changes in the body composition of preterm SGA infants were evaluated when they had grown to a postmenstrual age of 37-40 weeks by the following parameters: arm area (AA;MAC2/4r), arm muscle area (AMA; (MAC - TSF x 7r)2/47r)and arm fat area (AFA; AA - AMA) [22,23]. The same measurements in term AGA infants at birth were used as the control. The body weight growth index [6] (BWGI, study weight minus reference mean body weight for the same postmenstrual age, then divided by the S.D. of the reference mean body weight) was used to display the amount of deviation in the body weight from the reference value for the same postmenstrual age. All measured variables were expressed as mean f S.D. Student’s test was used to compare the difference between the two groups for each nonparametric variable. The stepwise multiple regression test was used to correlate the BWGI at a postmenstrual age of 37-40 weeks with variables which showed a significant correlation with it by the linear regression test. P < 0.05 was taken as significant. Results Comparison
between the two groups of SGA infants
SGA infants of 31-33 weeks gestation were fed later, needed a longer time to reach an enteral feeding of 100 ml/kg per day and regained their birth weight later
121 TABLE I Clinical characteristics of SGA infants at birth.
(16 cases)
34-36 weeks (19 cases)
32.4 zt 0.8 1327 ztz 168 5.7 f 5.0 16.3 zt 13.4
34.7 1679 2.2 6.6
3 1-33 weeks
Characteristic
Gestational age (weeks) Brith body weight (g) Age feeding started (days) Age fed 100 ml/kg per d enterally (days) Age fed 100 kcal/kg enterally (days) Duration of PN (days) Weight loss (%) Age of maximal weight loss Age regained birth weight (days)
19.4 f
14.2
12.4 f 9.4 * 4.3 f
16.2 4.9 2.1
12.1 ??
5.5
f 0.8* zt l99* f 1.9* f 4.6*
10.9 f
9.2t
4.7 f 10.0 6.1 zt 4.9 2.1 3.8 f 7.5 f
4.18
*P < 0.001.
tP < 0.05
than SGA infants in the 34-36 weeks gestation group (P < 0.05) (Table I). They had lower measurements for BW, BL, HC and MAC; yet the BWGI and T - SF measured at birth did not differ statistically from SGA infants with a longer gestation (Table II). Their WLR and BMI were also significantly less than those of the 34-36 weeks gestation group (Table III). The weekly enteral intakes of protein and TABLE II Anthropometric measurements of study cases and AGA infants at birth. Age and group
BW (g)
BWGI
31-33 Weeks SGA infants (18 cases) AGA infants (22 cases)
1302p*
(199) 1768 (248)
-3.8 (1.5) -0.3 (0.1)
38.5* (2.4) 42.9 (2.2)
34-36 Weeks SGA infants (20 cases) AGA infants (42 cases)
1679 (199) 2276 (257)
-2.9 (1.7) -0.6 (0.5)
41.5 (2.3) 44.8 (2.1)
MAC (cm)
T-SF (cm)
29.6 (1.0)
6.4* (0.5) 7.6 (0.8)
5.4 (0.9) 6.9 (1.1)
29.4 (1.4) 31.5 (1.2)
7.0 (0.4) 8.3 (0.7)
6.1 (1.1) 7.7 (1.1)
27.2*
(2.1)
tMean (SD) as compared with AGA infants in the same gestational-age group: P < 0.01. As compared with SGA infants in the 34-36 weeks gestation group: *P < 0.01. BWGI: body weight growth index, (study weight-reference mean weight for the same postmenstrual age)/SD for the reference mean weight, BL: body length; HC: head circumference; MAC: mid-arm circumference; T-SF: sum of the skinfold thickness measured at the tricepital and subscapular areas.
122 TABLE III Ratios or indices for body proportionality Age and group 31-33 Weeks SGA infants (18 cases) AGA infants (22 cases) 34-36 Weeks SGA infants (20 cases) AGA infants (42 cases)
at birth.
WLR (g/cm)
BMI (g/cm’)
ricrn3 x 100)
34.o*q (3.8) 41.1 (4.2)
0.89*x (0.10) 0.96 (0.07)
2.35 (0.36) 2.24 (0.17)
0.233; (0.019) 0.260 (0.03)
40.2* (3.5) 51.0 (6.6)
0.972 (0.08) 1.14 (0.15)
2.34t
0.237* (0.014) 0.260 (0.02)
MACIHC
(0.26) 2.55 (0.39)
As compared with AGA infants in the same gestational-age group: *P < 0.01, tP < 0.05. As compared with SGA infants in the 34-36 weeks gestation group: $P < 0.01. WLR: weight-to-length ratio, body weight/body length; BMI: body mass index, body weight/body length2; PI: ponderal index, body weight/body length3 x 100, MACYHC: mid-arm circumference/head circumference.
calories at 2,4 and 6 weeks old were not different from those of infants in the 34-36 weeks group gestation (Table IV). When these two groups of SGA infants had grown to the postmenstrual age of 37-40 weeks, the SGA infants in the 3 l-33 weeks gestation had significantly lower body weight and body length than SGA infants of 34-36 weeks gestation (Table V). They also had a lower T - SF and MAC, yet this difference was not statistically significant (P = 0.23 and 0.174, respectively). Infants in these two groups did not differ in AA, AMA and AFA (Figs. 1 and 2). Comparison between SGA infants and AGA infants
At birth, the anthropometric measurements of SGA infants in either gestationalage group were much less than those of AGA infants of a similar gestational age (P TABLE IV Average protein and caloric intakes while on full enteral feeding in each gestational-age group. SGA infants
Two weeks old
Four weeks old
Six weeks old
At near-term
Proteina
Calorieb
Protein
Calorie
Protein
Calorie
Protein
Calorie
118 (17) 8 135 (23) 15
3.5 (0.7) 16 3.7 (0.8) 13
134 (27) 16 146 (25) 13
3.6 (0.9) IO 2.9 (0.4) 8
130 (25) 10 129 (20) 8
3.8 (0.7) 17 3.4 (0.8) 20
143 (26) 17 138 (25) 20
31-33 Weeks 3.4 (0.06) Case no. 8 34-36 Weeks 3.5 (0.7) Case no. 15 ‘As g/kg per day. bAs kcal/kg per day.
123
< 0.01) (Table II). The body weight of most of the study cases were more than two S.D. below the mean. They also had a lower AA, AMA and AFA than the AGA infants (Figs. 1 and 2). When the growth and body composition of the preterm SGA infants at a postmenstrual age of 37-40 weeks were compared with those of term AGA infants measured at birth (Table V), the SGA infants still weighed less, and were shorter than the AGA infants. They also had a smaller head and arm size, yet their skinfolds were much thicker than that of AGA infants of a similar gestational age. This was reflected as a significantly higher AFA and a lower AMA in SGA infants in the 34-36 weeks gestation group (Fig. 2); no significant difference in AFA and a lower AMA were notes in SGA infants in the 31-33 weeks gestation group (Fig. 1), as compared with the term AGA infants. Comparison between different clinical groups of SGA infants
In both gestational-age groups, infants in Group II regained their birth weight at a similar postnatal age as infants in Group I (12.3 f 6.5 vs. 13.3 f 5.6 day for infants in the 31-33 weeks gestation group; 8.9 f 3.0 vs. 6.8 f 4.6 days for infants in the 34-36 weeks gestation group), although they achieved total enteral feeding later than the infants in Group I (24.2 f 16.8 vs. 2.0 f 3.7 days for infants in the 31-33 weeks gestation group; 11.9 f 14.3 vs. 0.5 f 3.5 days for infants in the 34-36 weeks gestation group). These two groups of infants did not differ in any of the antropometric measurements at birth. When they had grown to the postmenstrual age of 37-40 weeks, the body weight of SGA infants in subgroup II of the 34-36 weeks gestational-age group deviated from the reference weight significantly more than infants in Group I (Table VI). Subgroup II infants in the
TABLE V Comparison of body anthropometrics of study cases in both gestational-age groups at the postmenstrual age of 37-40 weeks with measurements of AGA infants born at 37-40 weeks, Age and
BW
group
(9)
31-33 Weeks SGA infants (17 cases) AGA infants (129cases) 34-36 Weeks SGA infants (20 cases) AGA infants (129 cases)
2222t
(430) 3153 (305) 2564 (566) 3153 (305)
BWGI
BL
HC
MAC
(cm)
(cm)
(cm)
T-SF (mm)
-2.2 (0.8) -0.1 (0.6)
44.6$ (2.0) 49.1 (1.5)
32.4 (1.6) 33.8 (1.1)
8.3 (0.8) 9.6 (0.8)
10.4 (3.3) 8.4 (1.5)
-1.6 (1.3) -0.1
46.7 (2.7) 49.1 (1.5)
33.1* (1.6) 33.8 (1.1)
8.6 (1.1) 9.6 (0.8)
11.4 (4.2) 8.4 (1.5)
W5)
As compared with AGA infants in the same gestational-age group: *P < 0.05; for the rest, P < 0.01. As compared with SGA infants of 34-36 weeks gestation: tP < 0.05, $P < 0.01.
124
31-33 group differ 1 and
weeks gestational-age group had a significantly higher AMA than the subI infants (366 & 55 vs. 316 f 35 mm2, P < 0.05) (Fig. 1); the AFA did not statistically from the subgroup I infants in either gestational age group (Figs. 2).
Comparison between SGA infants of different WLR groups
Among the SGA infants in the 31-33 weeks gestation group, nine infants (50%) belonged to the LWLR group; and in the 34-36 weeks gestation group, there were 11 cases (55%). Only three SGA infants had a PI of more than 2 SD. from the mean for AGA infants of the same gestational age. For infants in the 34-36 weeks gestation group, the LWLR group had a significantly lower BWGI and T - SF than the NWLR group, both at birth and at a postmenstrual age of 37-40 weeks (Table VII). They did not differ in MAC, AA, AMA or AFA. For infants in the 31-33 weeks gestation group, infants in both subgroups did not differ in any of the measurements at birth or at a postmenstrual age of 37-40 weeks (Table VIII). ’ In both gestational-age groups, infants in both the LWLR and NWLR subgroups showed some postnatal catch-up growth in body weight. Yet at near-term the BWGI
mm2 1,000
600
AMA Fig. 1. Body composition of SGA postmenstrual age of 37-40 weeks measured at birth were used as the *P < 0.05 as compared with SGA
AFA
AMA
AFA
infants in the 31-33 weeks gestation group at birth (A) and at a (B). Parameters of AGA infants of a comparable postmenstrual age control. AA: arm area, AMA: arm muscle area, AFA: arm fat area. infants; +P < 0.05 as compared with SGA infants in Group I.
125
mm2
800
I *
600
(B) 1T
(A)
T---.....------...
AA
AMA
*
_......
l-
AFA
AA
AMA
AFA
Fig. 2. Body composition of SGA infants in the 34-36 weeks gestation group at birth (A) and at a postmenstrual age of 37-40 weeks (B). Parameters of AGA infants of a comparable postmenstrual age measured at birth were used as the control. *P < 0.05 as compared with SGA infants; +P < 0.05 as compared with SGA infants in Group I.
TABLE
VI
Growth
of SGA infants
SGA infants
at a postmenstrual
BW
age of 37-40
weeks according
BWGI
(g) 31-33 Weeks Group I (9 cases) Group II (9 cases) 34-36 Weeks Group I (14 cases) Group II (6 cases)
to their clinical
status
HC
MAC
T-SF
(cm)
(cm)
(cm)
2285
-1.9
45.0
32.6
8.2
11.2
(515) 2087
(0.9) -2.6
(2.0) 43.6
(1.6) 31.9
(1.0) 8.2
(4.0) 9.1
(365)
(0.8)
(2.6)
(1.8)
(0.8)
(2.1)
2601
-1.5
46.6
33.4
8.8
12.3
(614) 2476
(1.4) -4.4*
(2.8) 47.0
(1.5) 32.4
(1.2) 8.3
(4.6) 10.3
(475)
(2.5)
(2.8)
(1.7)
(0.7)
(3.3)
*P < 0.05 as compared
with infants
in subgroup
I in the 34-36
weeks gestation
group
126
TABLE VII Growth and body composition in the 34-36 weeks-gestation group for SGA infants in different WLR subgroups. SGA infants
BWGI
T-SF (mm)
MAC (cm)
AA (mm*)
AMA (mm*)
AFA (mm2)
-4.5; (2.0) -2.3 (1.1)
4.9* (0.4) 6.4 (1.0)
6.6 (0.3) 7.1 (0.4)
347 (37) 398 (44)
266 (29) 295 (36)
103 (19)
;i28)
539 (100)
,“;a,)
7:)
349 (96) 350 (61)
;3; 292 (128)
At birth
LWLR (6 cases) NWLR (14 cases) At a postmenstrual
LWLR (6 cases) NWLR (13 cases)
age of 37-40 weeki
-2.52 (0.5) -1.1 (1.4)
Fly:) 13.2 (4.5)
*P < 0.05 as compared with the NWLR group of the same age; LWLR: group of low WLR, WLR > 2 SD. ok the reference mean; NWLR: group of normal WLR, WLR I 2 SD. off the reference mean; AA: arm area; AMA: arm muscle area; AFA: arm fat area.
was still more than 1 S.D. below the mean of term AGA infants at birth and the MAC, AA and AMA were still much lower than those of AGA infants. Except for the LWLR subgroup in the 34-36 weeks gestation group, T-SF was higher than that for AGA infants. The AFA was as great as, or higher than that for AGA infants in the NWLR group in the 34-36 weeks gestation group). Multiple regression analysis
Multiple regression analysis was performed to seek the factors which had the strongest correlation with the BWGI of the study cases when they had grown to the TABLE VIII Growth and body composition in the 31-33 weeks-gestation group for SGA infants in different WLR subgroups. SGA infants
BWGI
T-SF (mm)
MAC (cm)
AA (mm*)
AMA (mm*)
AFA (mm*)
6.4 (0.4)
318 (53) 327 (43)
235 (40) 245 (42)
83 (16) 82 (17)
8.0 (0.6) 8.2 (0.9)
517 (81) 545 (119)
327 (42) 359 (71)
190 (69) 186 (54)
At birth
LWLR (9 cases) NWLR (7 cases) At a postmenstrual
LWLR (8 cases) NWLR (6 cases)
-4.4 (1.8) -3.8 (0.9) age of 37-40
-2.3 (0.8) -2.2 (0.5)
;u48) 5.4 (1.1) weeks
10.4 (3.6) 9.5 (2.2)
127 TABLE IX Stepwise multiple regression test: BWGI at a postmenstrual age of 37-40 weeks as the dependent variable Variables
Partial correlation
Independent variables T-SF= 0.76 WLRa 0.69 BWGI’ 0.64 MACa 0.60 Age fed 100 kcal/kg per day -0.49 Age regained birth weight -0.46 Age fed 100 ml/kg per day -0.40 Gestational age 0.40 Percentage of weight loss -0.36 PIa -0.36 BMIa 0.34
F at step 0
F at final step Including T-SF
excluding T-SF
20.96 13.58 10.36 8.47
20.96 0.88 6.52 0.66
-
4.72
1.45
1.33
4.02
8.19
0.09
2.92 2.89
0.29 0.09
0.68 6.85
2.30 2.25 2.02
0.21 1.38 0.96
4.78 5.25 0.36
13.58 0.61 0.21
aObtained from measurements done at birth.
postmenstrual age of 37-40 weeks. Eleven independent variables were included in this test: gestational age, BWGI at birth, age at which they were fed 100 ml/kg per day, age at which they were fed 100 kcal/kg per day, percentage of weight loss, age at which birth weight was regained, WLR, BMI, PI, T-SF and MAC. The test results revealed that the sum of the skinfold thickness measured at the tricepital and the subscapular areas, age at which birth weight was regained and BWGI at birth were the factors which had the strongest correlation with the degree of body weight deviation from the mean birth body weight at near-term (Table IX). Since the measurement of skinfold thickness is cumbersome and is not included in routine nursery measurements, the multiple regression analysis was rerun after skinfold thickness was eliminated. In that case, WLR, PI, percentage of weight loss in the first 1 or 2 weeks and gestational age became the determining factors. Discussion This prospective study revealed that at postmenstrual age of 37-40 weeks, the amount of fat accumulated by preterm SGA infants was as much as, or more than that of term AGA infants, while other body growth factors such as body weight, body length and head size were still behind those with full intrauterine growth. The SGA infants also had less arm muscle mass than AGA infants. This pattern of
128
changes in body composition has been persistently observed in SGA infants in different gestational-age groups, and of different clinical status. Body fat stores reflect caloric reserve, and arm muscle mass reflects protein reserve [22,23], therefore the result of this study implies that preterm SGA infants retain excess calories as fat, yet have an inadequate protein reserve. In a previous report, a higher amount of fat accumulation was noted in formulafed, very-low-birth-weight AGA infants at around the postnatal age of 21 days [12]. It was assumed that the increased accretion of fat by these AGA infants was caused by a higher calorie reserve (67.8 kcal/kg per day, with a daily caloric intake of 150 kcal/kg) than the fetal caloric accretion 1241.In this study the initial weight loss and age-to-regain-birth-weight of preterm SGA infants were comparable with those reported by others [2,25]. In the immediate neonatal period, the average enteral intake of protein was 3.5 g/kg per day; and of calories was 135 kcalfkg per day. Based on values for fetal oxygen consumption and the composition of new tissue deposited, Sparks et al. estimated the total caloric requirement of the human fetus at term to be approximately 96 kcal/kg per day [24]. Since enteral intake cannot be absorbed completely in immature infants [12,26], the enteral caloric requirement obtained from the above estimation would be 120 kcal/kg per day (96 kcal/kg per day + 0.8; retaining 80% of the energy intake). SGA infants often require an increased caloric intake for growth 1271.Therefore, in this study, none of the preterm SGA infants in either gestation-age group had an excess caloric intake. Their protein intake was also adequate, according to the recommendations for low birth-weight infants [27]. There is only one other report where the composition of the weight gain in preterm SGA infants has been studied [ 111. These infants were found to have significantly lower protein and fat depositions than AGA infants of a similar birth weight and postnatal age. Yet, when compared with fetuses of a similar postmenstrual age, the SGA infants of 33.1 ( f 0.3) weeks gestation had deposited more fat [ 111,as observed in the present study. Body composition and the weight gain of full-term infants has been shown to change markedly after birth with an increase in the fat content [27]. This may imply that enteral nutrition differs from placental nutrition, no matter how sophisticated the design of the infant formula used; or it may be due to the effects of the extrauterine environment on body composition: different metabolic demands, hormonal changes, etc. Whether these postnatal changes in body composition (increased fat stores) in either AGA or SGA infants simply reflects altered nutritional supplementation, as is the case in fullterm infants [ 171, or is the result of differences in energy utilization needs further investigation. In addition, it is also very important to study the consequences of in later life this change in body composition of preterm SGA infants. When compared with preterm AGA infants of a similar gestational age, the early postnatal growth rate of preterm SGA infants has been reported to be higher [2,11,28]. Yet, as their growth reaches near term, the body dimensions of preterm SGA infants are reportedly either below the mean [7] or the 10th percentile [ 1I] compared with intrauterine growth curves. The results of this study confirm this observation. This study also demonstrates the poorer catch-up growth in body weight and body length in more immature SGA infants in the early postnatal period, as noted
129
in immature AGA infants [2,29]. This may be related to their limited metabolic and digestive tolerances, or their complex medical status. Only one study reports a significant influence from illness on the growth outcome of very low-birth-weight infants reflected in terms of age-to-lowest-weight, percent weight loss, age-to-initial-sustained-weight gain and age-to-regain-birth weight, [30]. In the present study, we observed that ill, preterm SGA infants received enteral feedings of 100 ml/kg per day at an older age, and required a longer duration of parenteral nutrition than those with an uneventful course. Yet, the age-to-regainbirth-weight did not differ between these two groups of infants. Furthermore, at a postmenstrual age of 37-40 weeks, the growth (body weight, body length and head circumference) and body composition (arm muscle area and arm fat area) of ill SGA infants did not differ significantly from those of SGA infants with an uneventful clinical course. This implies that aggressive nutritional management, including different methods of enteral feeding and parenteral nutritional supplementation, may improve the quality of nutritional care in ill preterm newborns; therefore, their growth and body composition can be comparable with infants with an uneventful clinical course. SGA infants have long been recognized to be a heterogeneous group, and they were classified in this study into two groups according to the relationship between their body weight and body length: the proportioned, symmetric or nonwasted group; and the disproportioned, asymmetric or wasted group [3,10]. The asymmetric term SGA infants were observed to experience catch-up growth in weight during the first few months after birth [3,10]. Very few studies had related the postnatal growth of preterm SGA infants to the status of nutrition at birth. In this study, WLR was used to define the status of nutrition in preterm SGA infants. It was demonstrated that asymmetric infants did not differ much from symmetric infants in the 31-33 weeks gestation group, either at birth or at a postmenstrual age of 37-40 weeks. However, among the more mature SGA infants, asymmetric infants had a significantly lower skinfold thickness than symmetric infants, at birth. Which suggests that placental malnutrition may have occured during the latter period of gestation. When this group of preterm SGA infants had grown to near-term, their skinfold thickness and AFA were not much different from those of term AGA infants. In this study, further analysis by the multiple regression test revealed that preterm SGA infants with higher skinfold measurements at birth had less body weight deviation from the mean when they had grown to near-term. Skinfold measurements have been used widely to indicate the calorie reserve stored in the form of fat in adults, children and neonates [31,32]. Body fat stores, after liver weight, is the parameter mostly affected by intrauterine malnutrition [33]. Thus, SGA infants with higher skinfold measurements are likely to be less severely affected by intrauterine nutrient deprivation. Therefore, they may gain more weight than infants with lower skinfold measurements. The simple weight-to-length ratio has been found to correlate positively with skinfold measurements in neonates [17,18]. It has been suggested that weight-to-length ratio may be the best morphometric measure of the nutritional component of intrauterine growth [ 171.This study confirms this; in addition to the skinfold measure-
130
ment, the weight-to-length ratio correlated best with the near-term weight gain of preterm SGA infants. References 1 Battaglia, F.C. and Lubchenco, L.O. (1977): A practical classification of newborn infants by weight and gestational age. J. Pediatr., 71, 159-163. Fenton, T.R., McMillan, D.D. and Sauve, R.S. (1990): Nutrition and growth analysis of very low birth weight infants. Pediatrics, 86, 378-383. Davies, D.P., Platts, P., Pritchard, J.M. and Wilkinson, P.W. (1979): Nutritional status of light-fordate infants at birth and its influence on early postnatal growth. Arch. Dis. Child., 54, 703-706. Fitzhardinge, P.M. and Steven, E.M. (1972): The small-for-date infant. 1. Later growth patterns. Pediatrics, 49, 67 I-68 1. Fancourt, R., Campbell, S., Harvey, D. and Norman, A.P. (1976): Follow-up study of small-fordates babies. Br. Med. J., 1, 1435-1437. Kamiski, W., Blair, C. and Vitucci, J.S. (1987): The illusion of catch-up growth in premature infants: use of the growth index and age correction. Am. J. Dis. Child., 141, 520-526. Pena, I.C., Teberg, A.J. and Finello, K.M. (1988): The premature small-for-gestational-age infant during the first year of life. J. Pediatr., 113, 1066-1073. Miller H.C. and Hassanein K. (1971): Diagnosis of impaired fetal growth in newborn infants. Pediatrics, 48, 511-522. Georgieff, M.K., Sasanow S.R., Mammel, M.C. and Perira, G.R. (1986): Mid-arm circumference/head ratios for identification of symptomatic LGA, AGA and SGA newborn infants. J. Pediatr., 109, 316-321. 10 Villar, J., Smerigho, V., Martorell, R.. Brown, C.H. and Klein, R.E. (1984): Heterogeneous growth and mental development of intrauterine growth-retarded infants during the first 3 years of life. Pediatrics, 74, 783-791. 11 Chessex, P., Reichman, B., Verellen, G., Putet, G., Smith, J.M., Heim, T. and Sawyer, P.R. (1984): Metabolic consequences of intrauterine growth retardation in very low birth weight infants. Pediatr. Res., 18, 709-713. 12 Reichman, B., Chessex, P., Putet, G., Smith, J.M., Heim, T. and Sawyer, P.R. (1981): Diet, fat accretion, and growth in premature infants. N. Engl. J. Med., 305, 1495-1500. 13 Ballard, J.L., Khoury, J.C., Wedig, K., Wang, L., Eilers-Walsman, B.W. and Lipp, R. (1991): New Ballard score, expanded to include extremely premature infants. J. Pediatr., 119, 417-423. 14 Hsieh, T.T., Hsu, J.J., Chen, C.J., Chiu, T.H., Liou, J.D., Hsieh, C.C., Lo, L.M., Kuo, D.M. and Soong, Y.K. (1991): Analysis of birth weight and gestational age in Taiwan. J. Formosan Med. Assoc., 90, 382-387. 15 Papile, L., Burstein, J., Burstein, R. and Koffler, H. (1978): Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weight less than 1500 g. J. Pediatr., 92, 529-534.14. 16 Georgieff, M.K., Sasanow, S.R., Chockahngarm, U.M. and Periera, G.R. (1988): A comparison of the mid-arm circumference/head circumference ratio and ponderal index for the evaluation of newborn infants after abnormal intrauterine growth. Acta. Paediatr. Stand., 77, 214-219. 17 Wolfe, H.M., Brans, Y.W., Gross, T.L., Bhatia, P.K. and Sokol, R. J. (1990): Correlation of commonly used measures of intrauterine growth with estimated neonatal body fat. Biol. Neonate, 57, 167-171. 18 Sumners, J.E., Findlly, G.M. and Ferguson, K.A. (1990): Evaluation methods for intrauterine growth using neonatal fat stores instead of birth weight as outcome measures: fetal and neonatal measurements correlated with neonatal skinfold thickness. J. Clin. Ultrasound, 18, 9- 14. 19 Yau, K.I. and Chang, M.H. (1993): Weight to length ration - a good parameter for nutritional status in preterm and full-term newborns. Acta Pediatr., in press. 20 Yau, K.I. (1987): Assessment of neonatal body composition from arm circumference and skinfold thickness measurement. Acta Pediatr. Sinica, 28, 157-163.
131 21 22 23 24 25 26 21 28 29 30
31
32 33
Brans, Y. W., Sumners, J.E., Dweck, H.S. and Cassady, G. (1974): A noninvasive approach to body composition in the neonate: dynamic skinfold measurements. Pediatr. Res., 8, 215-222. Frisancho, A.R. (1974): Triceps skinfold and upper arm muscle size norms for assessment of nutritional status. Am. J. Clin. Nutr., 27, 1052-1057. Frisancho, A.R. (1981): New norms of upper limb fat and muscle areas for assessment of nutritional status. Am. J. Clin. Nutr., 34, 2540-2545. Sparks, J.W., Girard, J.R. and Battaglia, F.C. (1980): An estimate of the caloric requirements of the human fetus. Biol. Neonate, 38, 113-l 19. Shaffer, S.G., Quimiro, C.L. and Anderson, J.V. (1987): Postnatal weight changes in low birth weight infants. Pediatrics, 79, 702-705. Brooke, O.G., Alvear, J. and Arnold, M. (1979): Energy retension, energy expenditure, and growth in healthy immature infants. Pediatr. Res., 13, 215-220. Committee on Nutrition, American Academy of Pediatrics. (1985): Nutritional needs of low-birthweight infants. Pediatrics, 75, 976-986. Fomon, S.J. (1967): Body composition of the male reference infant during the first year of life. Pediatrics, 40, 863-870. Gill, A., Yu, V.Y.H., Bajuk, B. and Astbury, J. (1986): Postnatal growth in infants born before 30 weeks gestation. Arch. Dis. Child., 61, 549-553. Rickard, K.A., Brady, M.S., Moye, L., Schreiner, R.L., Gresham, E.L. and Lemons, J.A. (1982): Nutritional outcome of 207 very-low-birth-weight infants in an intensive care unti. J. Am. Diet. Assoc., 81, 674-682. Frisancho, A.R. and Gam, S.M. (1971): Skin-fold thickness and muscle size: implication for developmental status and nutritional evaluation of children from Honduras. Am. J. Chn. Nutr., 24, 541-546. Zerfas, A.J., Shorr, I.J. and Neumann, C.G. (1977): Office assessment of nutritional status. Pediatr. Clin. North. Am., 24, 253-272. Myers, R.E., Hill, D.E. and Cheek, D.B. (1971): Fetal growth retardation produced by experimental placental insufficiency in the rhesus monkey. I. Body weight organ size. Biol. Neonate, 18,379-381.
II7 0378-3782/93/$06.00
EHD 01409
Growth and body composition of preterm, small-for-gestational-age infants at a postmenstrual age of 37-40 weeks Kuo-Inn Tsou Yau and Mei-Hwei Chang Department
of Pediatrics,
(Received
1 September
College of Medicine, 1992; revision
National
received
Taiwan University,
25 January
Taipei (Taiwan,
1993; accepted
9 March
ROC)
1993)
Summary
In order to understand the nutritional status of preterm, small-for-gestational-age (SGA) infants in the early postnatal period, the growth and body composition of preterm, SGA infants was followed prospectively from birth to the postmenstrual age of 37-40 weeks. The infants were stratified into different groups by gestational age, clinical condition and body proportionality. In each subgroup, the growth and changes in body composition of SGA infants were compared with appropriate-forgestational-age (AGA) infants of a comparable postmenstrual age. At birth, the SGA infants of both the 3 l-33 and 34-36 week gestational-age groups were smaller than AGA infants in all body measurements, including arm area (AA), arm muscle area (AMA) and arm fat area (AFA). When the preterm SGA infants had grown to the postmenstrual age of 37-40 weeks, the amount of fat they had accumulated was as much as, or more than that in term AGA infants. Yet, they had less muscle mass and their body weight, body length and head circumference were less than those in term AGA infants. This pattern of growth and the changes in body composition had been persistently observed in SGA infants of different gestational-age groups, different clinical status and different body proportionality. Differences between postnatal enteral nutrition and placental nutrition, or different energy utilization, in preterm SGA infants are hypothesized to account for these observations. The growth of less mature (31-33 weeks gestation) SGA infants and those preterm SGA infants with an eventful clinical course was suboptimal as compared with other SGA infants in the same subgroup. In this study, the weight to length ratio (WLR) was used to define the status of nutrition in preterm SGA infants: WLR % 2 S.D. or > 2 S.D. off the reference mean. Infants in both groups showed some catch-up Correspondence to: Kuo-Inn Tsou Yau, Department Taipei, Taiwan IO 016, ROC.
of Pediatrics,
National
Taiwan
University
Hospital.
118
growth in body weight. Yet, at near-term their body weight were still more than 2 SD. below the mean of term AGA. In each gestational-age group, the growth of these two body-proportionality groups did not differ from each other except for the low WLR group of 34-36 weeks gestation which had a significantly lower body weight and skinfold thickness than the group with a normal WLR. Multiple regression analysis revealed that skinfold measurements of preterm SGA infants at birth is the best factor for determining the body weight gain at near-term. After use of the skinfold thickness was set aside, WLR became the most important factor. The results of this study highlight the importance of evaluating the body composition of growing preterm SGA infants to assess their nutritional status. Key words: small-for-gestational-age growth
infants; preterm infants; body composition;
Introduction To meet the nutritional requirements of small-for-gestational-age infants (SGA infants; infants who weigh less than the 10th percentile for gestational age) [l] is a challenge to neonatologist, not only because of their prematurity, but also because of their deviation from normal growth. The growth of either premature or SGA infants is usually assessed by the changes in body weight (BW), body length (BL) or head circumference (HC) [2-71. In recent years, measurements of skinfold thickness, mid-arm circumference (MAC) and indices for assessing body proportionality have been used to evaluate the presence of impaired fetal nutrition [8,9] and also to assess the nutritional status of postnatal growth [lo]. The majority of studies on the growth of SGA infants have been done either on term SGA infants [3-51 or in a mixed group including both AGA and SGA infants [2,6]. There are very few longitudinal studies which have evaluated both the growth and the changes in body composition of preterm SGA infants as they grow to nearterm [ 111. Appropriate-for-gestational-age (AGA) preterm infants have been noted to accumulate a higher amount of fat postnatally than neonates of the same postmenstrual age when they were given formula feedings designed to mimic intrauterine growth rates [ 121.Therefore, it would be interesting to know the postnatal changes in body composition of preterm SGA infants. Our study longitudinally followed the changes in body composition of preterm SGA infants from birth to a postmenstrual age at 37-40 weeks and compared their body compositions with those of AGA infants of a similar postmenstrual age at birth. In addition, the postnatal growth and changes in body composition of preterm SGA infants was assessed by the severity of postnatal illnesses and the type of growth retardation. Factors which correlated best with body-weight deviation at near-term of these preterm SGA infants were also analyzed. Subjects and Methods Thirty-eight SGA infants with a gestational age of less than 37 weeks (gestational age: 3 l-36 weeks; birth body weight: 1034-2110 g) and 193 AGA infants (gestation-
119
al age: 31-40 weeks; birth body weight: 1242-3858 g) admitted to the neonatal unit of the National Taiwan University Hospital without the following problems were enrolled in this study prospectively. Criteria for exclusion were congenital anomalies, chromosomal abnormalities or intrauterine infection. The SGA infants were stratified by degree of prematurity into two gestational-age groups: 31-33 weeks (918 cases), and 34-36 weeks (20 cases). For the purpose of comparison, the AGA infants were stratified into three groups: 31-33 weeks (22 cases), 34-36 weeks (42 cases) and 37-40 weeks (129 cases). Gestational age was determined from the last menstrual period of the mother and confirmed postnatally by the Ballard score [ 131. Whenever there was a discrepancy of more than two weeks between these two methods, the latter was used. SGA was defined as an infant with a birth weight below the 10th percentile for his gestational age, based on the weight criteria established for Chinese fetuses [14]. All 193 AGA infants were healthy in the immediate neonatal period. In each gestational-age group of SGA infants, those who had sepsis, a high grade of intraventricular hemorrhage (Grade III or IV by Papile’s criteria [ 15]), needed respiratory therapy for more than 3 days for pulmonary disease or whose enteral feedings progressed with difficulty were grouped together as Group II, (nine cases in the 31-33 weeks gestational-age group, six cases in the 34-36 weeks gestational-age group). Those infants with a relatively uneventful clinical course for whom enteral feedings were started within one week of birth and progressed smoothly were grouped together as Group I (nine cases in the 31-33 weeks gestational-age group, 14 cases in the 34-36 weeks gestational-age group). SGA infants are heterogenous; some are malnourished, some are just small for their gestational age. The ponderal index (PI; BW/BL3 (g/cm3) x 100) has usually been used to assess the nutritional status of intrauterine growth [8] and its impact on the postnatal growth of SGA infants [3,10]. Recently, PI has been observed to not be reliable in the detection of symptomatic newborns with abnormal fetal growth [16-181. The simple weight-to-length ratio (WLR; BW/BL, g/cm) has been demonstrated to have the closest correlation with skinfold measurements by Wolf et al. [ 171, Sumners et al. [ 181, and by ourselves in a previous study [ 191. Therefore, WLR was used to assess the state of nutrition in our study infants. The SGA infants were classified into two groups: those having a low WLR (LWLR group, the WLR was 2 S.D. below the WLR of AGA infants of a similar postmenstrual age) and those having a normal WLR (NWLR group; the WLR was within 2 S.D. of that of AGA infants of a similar postmenstrual age). Study infants with a birth body weight of less than 1800 g were usually cared for and nursed in an incubator with the temperature set within the range for a neutral thermal environment. Usually, after their admission to the neonatal unit, the infants received an intravenous infusion of a glucose solution which was started at a rate of 80- 100 ml/kg per day and was increased by lo-20 ml/kg per day, until 150- 160 ml/kg per day was reached, as determined by the amount of urine output and the status of hydration. Infants were usually fed 12-48 h after birth for those weighing less than 1500 g, and 4-24 h for those weighing more than 1500 g at birth. Enteral feedings began with sterile water, then glucose water; milk feedings were started with a premature infant formula at a concentration of 40 kcal/lOO ml with the milk con-
120
centration increased gradually to 80 kcal/lOO ml in 7-10 days. The goal of enteral feeding was to provide a daily caloric intake of 120 kcal/kg; this was usually achieved at l-2 weeks old for infants who weighed less than 1500 g, and at 5-7 days old for those weighing more than 1500 g. For sick infants and infants who weighed less than 1800 g, partial parenteral nutrition was supplied until they could obtain adequate calories enterally. Amino acid supplement was started at 0.5 g/kg per day on the third day of life and increased gradually up to 2.0-2.5 g/kg per day, as required. Lipid supplement was usually given 5-7 days after birth at 0.5 g/kg per day, then increased gradually up to 2.0 g/kg per day, as required. As the amount of the enteral feedings increased, parenteral nutrition was decreased. Our aim was to supply a caloric intake of 90-l 10 kcal/kg per day (enteral plus supplementary parenteral nutrition). The study infants were fed with a premature formula until their body weight reached 1800 g, then the formula was changed to that used for full-term infants. The premature infant formula contains approximately 80 kcal, 2.2 g protein and 4.3 g fat per 100 ml. The formula for full-term infants contains approximately 67 kcal, 1.5 g protein and 3.6 g fat per 100 ml. Each study case. was followed prospectively during the infant’s hospital stay, and then at the outpatient clinic. Informed consent for study was obtained from at least one of the parents of each patient. The following measurements were obtained weekly during hospitalization and at each outpatient visit: BW, BL, HC, MAC, skinfold thickness (T - SF, sum of the measurements obtained at the tricepital and the subscapular areas of the left side). Details of the measurements are described elsewhere [20]. The skinfold thickness was measured in duplicate with a Holtain skinfold caliper (Holtain Ltd, Bryberian, UK; pressure 10 g/mm2) using the technique describe by Brans [21]. Then WLR, body mass index (BMI; BW/BL2, g/cm2), PI and MAC/HC were calculated from the above measurements. Changes in the body composition of preterm SGA infants were evaluated when they had grown to a postmenstrual age of 37-40 weeks by the following parameters: arm area (AA;MAC2/4r), arm muscle area (AMA; (MAC - TSF x 7r)2/47r)and arm fat area (AFA; AA - AMA) [22,23]. The same measurements in term AGA infants at birth were used as the control. The body weight growth index [6] (BWGI, study weight minus reference mean body weight for the same postmenstrual age, then divided by the S.D. of the reference mean body weight) was used to display the amount of deviation in the body weight from the reference value for the same postmenstrual age. All measured variables were expressed as mean f S.D. Student’s test was used to compare the difference between the two groups for each nonparametric variable. The stepwise multiple regression test was used to correlate the BWGI at a postmenstrual age of 37-40 weeks with variables which showed a significant correlation with it by the linear regression test. P < 0.05 was taken as significant. Results Comparison
between the two groups of SGA infants
SGA infants of 31-33 weeks gestation were fed later, needed a longer time to reach an enteral feeding of 100 ml/kg per day and regained their birth weight later
121 TABLE I Clinical characteristics of SGA infants at birth.
(16 cases)
34-36 weeks (19 cases)
32.4 zt 0.8 1327 ztz 168 5.7 f 5.0 16.3 zt 13.4
34.7 1679 2.2 6.6
3 1-33 weeks
Characteristic
Gestational age (weeks) Brith body weight (g) Age feeding started (days) Age fed 100 ml/kg per d enterally (days) Age fed 100 kcal/kg enterally (days) Duration of PN (days) Weight loss (%) Age of maximal weight loss Age regained birth weight (days)
19.4 f
14.2
12.4 f 9.4 * 4.3 f
16.2 4.9 2.1
12.1 ??
5.5
f 0.8* zt l99* f 1.9* f 4.6*
10.9 f
9.2t
4.7 f 10.0 6.1 zt 4.9 2.1 3.8 f 7.5 f
4.18
*P < 0.001.
tP < 0.05
than SGA infants in the 34-36 weeks gestation group (P < 0.05) (Table I). They had lower measurements for BW, BL, HC and MAC; yet the BWGI and T - SF measured at birth did not differ statistically from SGA infants with a longer gestation (Table II). Their WLR and BMI were also significantly less than those of the 34-36 weeks gestation group (Table III). The weekly enteral intakes of protein and TABLE II Anthropometric measurements of study cases and AGA infants at birth. Age and group
BW (g)
BWGI
31-33 Weeks SGA infants (18 cases) AGA infants (22 cases)
1302p*
(199) 1768 (248)
-3.8 (1.5) -0.3 (0.1)
38.5* (2.4) 42.9 (2.2)
34-36 Weeks SGA infants (20 cases) AGA infants (42 cases)
1679 (199) 2276 (257)
-2.9 (1.7) -0.6 (0.5)
41.5 (2.3) 44.8 (2.1)
MAC (cm)
T-SF (cm)
29.6 (1.0)
6.4* (0.5) 7.6 (0.8)
5.4 (0.9) 6.9 (1.1)
29.4 (1.4) 31.5 (1.2)
7.0 (0.4) 8.3 (0.7)
6.1 (1.1) 7.7 (1.1)
27.2*
(2.1)
tMean (SD) as compared with AGA infants in the same gestational-age group: P < 0.01. As compared with SGA infants in the 34-36 weeks gestation group: *P < 0.01. BWGI: body weight growth index, (study weight-reference mean weight for the same postmenstrual age)/SD for the reference mean weight, BL: body length; HC: head circumference; MAC: mid-arm circumference; T-SF: sum of the skinfold thickness measured at the tricepital and subscapular areas.
122 TABLE III Ratios or indices for body proportionality Age and group 31-33 Weeks SGA infants (18 cases) AGA infants (22 cases) 34-36 Weeks SGA infants (20 cases) AGA infants (42 cases)
at birth.
WLR (g/cm)
BMI (g/cm’)
ricrn3 x 100)
34.o*q (3.8) 41.1 (4.2)
0.89*x (0.10) 0.96 (0.07)
2.35 (0.36) 2.24 (0.17)
0.233; (0.019) 0.260 (0.03)
40.2* (3.5) 51.0 (6.6)
0.972 (0.08) 1.14 (0.15)
2.34t
0.237* (0.014) 0.260 (0.02)
MACIHC
(0.26) 2.55 (0.39)
As compared with AGA infants in the same gestational-age group: *P < 0.01, tP < 0.05. As compared with SGA infants in the 34-36 weeks gestation group: $P < 0.01. WLR: weight-to-length ratio, body weight/body length; BMI: body mass index, body weight/body length2; PI: ponderal index, body weight/body length3 x 100, MACYHC: mid-arm circumference/head circumference.
calories at 2,4 and 6 weeks old were not different from those of infants in the 34-36 weeks group gestation (Table IV). When these two groups of SGA infants had grown to the postmenstrual age of 37-40 weeks, the SGA infants in the 3 l-33 weeks gestation had significantly lower body weight and body length than SGA infants of 34-36 weeks gestation (Table V). They also had a lower T - SF and MAC, yet this difference was not statistically significant (P = 0.23 and 0.174, respectively). Infants in these two groups did not differ in AA, AMA and AFA (Figs. 1 and 2). Comparison between SGA infants and AGA infants
At birth, the anthropometric measurements of SGA infants in either gestationalage group were much less than those of AGA infants of a similar gestational age (P TABLE IV Average protein and caloric intakes while on full enteral feeding in each gestational-age group. SGA infants
Two weeks old
Four weeks old
Six weeks old
At near-term
Proteina
Calorieb
Protein
Calorie
Protein
Calorie
Protein
Calorie
118 (17) 8 135 (23) 15
3.5 (0.7) 16 3.7 (0.8) 13
134 (27) 16 146 (25) 13
3.6 (0.9) IO 2.9 (0.4) 8
130 (25) 10 129 (20) 8
3.8 (0.7) 17 3.4 (0.8) 20
143 (26) 17 138 (25) 20
31-33 Weeks 3.4 (0.06) Case no. 8 34-36 Weeks 3.5 (0.7) Case no. 15 ‘As g/kg per day. bAs kcal/kg per day.
123
< 0.01) (Table II). The body weight of most of the study cases were more than two S.D. below the mean. They also had a lower AA, AMA and AFA than the AGA infants (Figs. 1 and 2). When the growth and body composition of the preterm SGA infants at a postmenstrual age of 37-40 weeks were compared with those of term AGA infants measured at birth (Table V), the SGA infants still weighed less, and were shorter than the AGA infants. They also had a smaller head and arm size, yet their skinfolds were much thicker than that of AGA infants of a similar gestational age. This was reflected as a significantly higher AFA and a lower AMA in SGA infants in the 34-36 weeks gestation group (Fig. 2); no significant difference in AFA and a lower AMA were notes in SGA infants in the 31-33 weeks gestation group (Fig. 1), as compared with the term AGA infants. Comparison between different clinical groups of SGA infants
In both gestational-age groups, infants in Group II regained their birth weight at a similar postnatal age as infants in Group I (12.3 f 6.5 vs. 13.3 f 5.6 day for infants in the 31-33 weeks gestation group; 8.9 f 3.0 vs. 6.8 f 4.6 days for infants in the 34-36 weeks gestation group), although they achieved total enteral feeding later than the infants in Group I (24.2 f 16.8 vs. 2.0 f 3.7 days for infants in the 31-33 weeks gestation group; 11.9 f 14.3 vs. 0.5 f 3.5 days for infants in the 34-36 weeks gestation group). These two groups of infants did not differ in any of the antropometric measurements at birth. When they had grown to the postmenstrual age of 37-40 weeks, the body weight of SGA infants in subgroup II of the 34-36 weeks gestational-age group deviated from the reference weight significantly more than infants in Group I (Table VI). Subgroup II infants in the
TABLE V Comparison of body anthropometrics of study cases in both gestational-age groups at the postmenstrual age of 37-40 weeks with measurements of AGA infants born at 37-40 weeks, Age and
BW
group
(9)
31-33 Weeks SGA infants (17 cases) AGA infants (129cases) 34-36 Weeks SGA infants (20 cases) AGA infants (129 cases)
2222t
(430) 3153 (305) 2564 (566) 3153 (305)
BWGI
BL
HC
MAC
(cm)
(cm)
(cm)
T-SF (mm)
-2.2 (0.8) -0.1 (0.6)
44.6$ (2.0) 49.1 (1.5)
32.4 (1.6) 33.8 (1.1)
8.3 (0.8) 9.6 (0.8)
10.4 (3.3) 8.4 (1.5)
-1.6 (1.3) -0.1
46.7 (2.7) 49.1 (1.5)
33.1* (1.6) 33.8 (1.1)
8.6 (1.1) 9.6 (0.8)
11.4 (4.2) 8.4 (1.5)
W5)
As compared with AGA infants in the same gestational-age group: *P < 0.05; for the rest, P < 0.01. As compared with SGA infants of 34-36 weeks gestation: tP < 0.05, $P < 0.01.
124
31-33 group differ 1 and
weeks gestational-age group had a significantly higher AMA than the subI infants (366 & 55 vs. 316 f 35 mm2, P < 0.05) (Fig. 1); the AFA did not statistically from the subgroup I infants in either gestational age group (Figs. 2).
Comparison between SGA infants of different WLR groups
Among the SGA infants in the 31-33 weeks gestation group, nine infants (50%) belonged to the LWLR group; and in the 34-36 weeks gestation group, there were 11 cases (55%). Only three SGA infants had a PI of more than 2 SD. from the mean for AGA infants of the same gestational age. For infants in the 34-36 weeks gestation group, the LWLR group had a significantly lower BWGI and T - SF than the NWLR group, both at birth and at a postmenstrual age of 37-40 weeks (Table VII). They did not differ in MAC, AA, AMA or AFA. For infants in the 31-33 weeks gestation group, infants in both subgroups did not differ in any of the measurements at birth or at a postmenstrual age of 37-40 weeks (Table VIII). ’ In both gestational-age groups, infants in both the LWLR and NWLR subgroups showed some postnatal catch-up growth in body weight. Yet at near-term the BWGI
mm2 1,000
600
AMA Fig. 1. Body composition of SGA postmenstrual age of 37-40 weeks measured at birth were used as the *P < 0.05 as compared with SGA
AFA
AMA
AFA
infants in the 31-33 weeks gestation group at birth (A) and at a (B). Parameters of AGA infants of a comparable postmenstrual age control. AA: arm area, AMA: arm muscle area, AFA: arm fat area. infants; +P < 0.05 as compared with SGA infants in Group I.
125
mm2
800
I *
600
(B) 1T
(A)
T---.....------...
AA
AMA
*
_......
l-
AFA
AA
AMA
AFA
Fig. 2. Body composition of SGA infants in the 34-36 weeks gestation group at birth (A) and at a postmenstrual age of 37-40 weeks (B). Parameters of AGA infants of a comparable postmenstrual age measured at birth were used as the control. *P < 0.05 as compared with SGA infants; +P < 0.05 as compared with SGA infants in Group I.
TABLE
VI
Growth
of SGA infants
SGA infants
at a postmenstrual
BW
age of 37-40
weeks according
BWGI
(g) 31-33 Weeks Group I (9 cases) Group II (9 cases) 34-36 Weeks Group I (14 cases) Group II (6 cases)
to their clinical
status
HC
MAC
T-SF
(cm)
(cm)
(cm)
2285
-1.9
45.0
32.6
8.2
11.2
(515) 2087
(0.9) -2.6
(2.0) 43.6
(1.6) 31.9
(1.0) 8.2
(4.0) 9.1
(365)
(0.8)
(2.6)
(1.8)
(0.8)
(2.1)
2601
-1.5
46.6
33.4
8.8
12.3
(614) 2476
(1.4) -4.4*
(2.8) 47.0
(1.5) 32.4
(1.2) 8.3
(4.6) 10.3
(475)
(2.5)
(2.8)
(1.7)
(0.7)
(3.3)
*P < 0.05 as compared
with infants
in subgroup
I in the 34-36
weeks gestation
group
126
TABLE VII Growth and body composition in the 34-36 weeks-gestation group for SGA infants in different WLR subgroups. SGA infants
BWGI
T-SF (mm)
MAC (cm)
AA (mm*)
AMA (mm*)
AFA (mm2)
-4.5; (2.0) -2.3 (1.1)
4.9* (0.4) 6.4 (1.0)
6.6 (0.3) 7.1 (0.4)
347 (37) 398 (44)
266 (29) 295 (36)
103 (19)
;i28)
539 (100)
,“;a,)
7:)
349 (96) 350 (61)
;3; 292 (128)
At birth
LWLR (6 cases) NWLR (14 cases) At a postmenstrual
LWLR (6 cases) NWLR (13 cases)
age of 37-40 weeki
-2.52 (0.5) -1.1 (1.4)
Fly:) 13.2 (4.5)
*P < 0.05 as compared with the NWLR group of the same age; LWLR: group of low WLR, WLR > 2 SD. ok the reference mean; NWLR: group of normal WLR, WLR I 2 SD. off the reference mean; AA: arm area; AMA: arm muscle area; AFA: arm fat area.
was still more than 1 S.D. below the mean of term AGA infants at birth and the MAC, AA and AMA were still much lower than those of AGA infants. Except for the LWLR subgroup in the 34-36 weeks gestation group, T-SF was higher than that for AGA infants. The AFA was as great as, or higher than that for AGA infants in the NWLR group in the 34-36 weeks gestation group). Multiple regression analysis
Multiple regression analysis was performed to seek the factors which had the strongest correlation with the BWGI of the study cases when they had grown to the TABLE VIII Growth and body composition in the 31-33 weeks-gestation group for SGA infants in different WLR subgroups. SGA infants
BWGI
T-SF (mm)
MAC (cm)
AA (mm*)
AMA (mm*)
AFA (mm*)
6.4 (0.4)
318 (53) 327 (43)
235 (40) 245 (42)
83 (16) 82 (17)
8.0 (0.6) 8.2 (0.9)
517 (81) 545 (119)
327 (42) 359 (71)
190 (69) 186 (54)
At birth
LWLR (9 cases) NWLR (7 cases) At a postmenstrual
LWLR (8 cases) NWLR (6 cases)
-4.4 (1.8) -3.8 (0.9) age of 37-40
-2.3 (0.8) -2.2 (0.5)
;u48) 5.4 (1.1) weeks
10.4 (3.6) 9.5 (2.2)
127 TABLE IX Stepwise multiple regression test: BWGI at a postmenstrual age of 37-40 weeks as the dependent variable Variables
Partial correlation
Independent variables T-SF= 0.76 WLRa 0.69 BWGI’ 0.64 MACa 0.60 Age fed 100 kcal/kg per day -0.49 Age regained birth weight -0.46 Age fed 100 ml/kg per day -0.40 Gestational age 0.40 Percentage of weight loss -0.36 PIa -0.36 BMIa 0.34
F at step 0
F at final step Including T-SF
excluding T-SF
20.96 13.58 10.36 8.47
20.96 0.88 6.52 0.66
-
4.72
1.45
1.33
4.02
8.19
0.09
2.92 2.89
0.29 0.09
0.68 6.85
2.30 2.25 2.02
0.21 1.38 0.96
4.78 5.25 0.36
13.58 0.61 0.21
aObtained from measurements done at birth.
postmenstrual age of 37-40 weeks. Eleven independent variables were included in this test: gestational age, BWGI at birth, age at which they were fed 100 ml/kg per day, age at which they were fed 100 kcal/kg per day, percentage of weight loss, age at which birth weight was regained, WLR, BMI, PI, T-SF and MAC. The test results revealed that the sum of the skinfold thickness measured at the tricepital and the subscapular areas, age at which birth weight was regained and BWGI at birth were the factors which had the strongest correlation with the degree of body weight deviation from the mean birth body weight at near-term (Table IX). Since the measurement of skinfold thickness is cumbersome and is not included in routine nursery measurements, the multiple regression analysis was rerun after skinfold thickness was eliminated. In that case, WLR, PI, percentage of weight loss in the first 1 or 2 weeks and gestational age became the determining factors. Discussion This prospective study revealed that at postmenstrual age of 37-40 weeks, the amount of fat accumulated by preterm SGA infants was as much as, or more than that of term AGA infants, while other body growth factors such as body weight, body length and head size were still behind those with full intrauterine growth. The SGA infants also had less arm muscle mass than AGA infants. This pattern of
128
changes in body composition has been persistently observed in SGA infants in different gestational-age groups, and of different clinical status. Body fat stores reflect caloric reserve, and arm muscle mass reflects protein reserve [22,23], therefore the result of this study implies that preterm SGA infants retain excess calories as fat, yet have an inadequate protein reserve. In a previous report, a higher amount of fat accumulation was noted in formulafed, very-low-birth-weight AGA infants at around the postnatal age of 21 days [12]. It was assumed that the increased accretion of fat by these AGA infants was caused by a higher calorie reserve (67.8 kcal/kg per day, with a daily caloric intake of 150 kcal/kg) than the fetal caloric accretion 1241.In this study the initial weight loss and age-to-regain-birth-weight of preterm SGA infants were comparable with those reported by others [2,25]. In the immediate neonatal period, the average enteral intake of protein was 3.5 g/kg per day; and of calories was 135 kcalfkg per day. Based on values for fetal oxygen consumption and the composition of new tissue deposited, Sparks et al. estimated the total caloric requirement of the human fetus at term to be approximately 96 kcal/kg per day [24]. Since enteral intake cannot be absorbed completely in immature infants [12,26], the enteral caloric requirement obtained from the above estimation would be 120 kcal/kg per day (96 kcal/kg per day + 0.8; retaining 80% of the energy intake). SGA infants often require an increased caloric intake for growth 1271.Therefore, in this study, none of the preterm SGA infants in either gestation-age group had an excess caloric intake. Their protein intake was also adequate, according to the recommendations for low birth-weight infants [27]. There is only one other report where the composition of the weight gain in preterm SGA infants has been studied [ 111. These infants were found to have significantly lower protein and fat depositions than AGA infants of a similar birth weight and postnatal age. Yet, when compared with fetuses of a similar postmenstrual age, the SGA infants of 33.1 ( f 0.3) weeks gestation had deposited more fat [ 111,as observed in the present study. Body composition and the weight gain of full-term infants has been shown to change markedly after birth with an increase in the fat content [27]. This may imply that enteral nutrition differs from placental nutrition, no matter how sophisticated the design of the infant formula used; or it may be due to the effects of the extrauterine environment on body composition: different metabolic demands, hormonal changes, etc. Whether these postnatal changes in body composition (increased fat stores) in either AGA or SGA infants simply reflects altered nutritional supplementation, as is the case in fullterm infants [ 171, or is the result of differences in energy utilization needs further investigation. In addition, it is also very important to study the consequences of in later life this change in body composition of preterm SGA infants. When compared with preterm AGA infants of a similar gestational age, the early postnatal growth rate of preterm SGA infants has been reported to be higher [2,11,28]. Yet, as their growth reaches near term, the body dimensions of preterm SGA infants are reportedly either below the mean [7] or the 10th percentile [ 1I] compared with intrauterine growth curves. The results of this study confirm this observation. This study also demonstrates the poorer catch-up growth in body weight and body length in more immature SGA infants in the early postnatal period, as noted
129
in immature AGA infants [2,29]. This may be related to their limited metabolic and digestive tolerances, or their complex medical status. Only one study reports a significant influence from illness on the growth outcome of very low-birth-weight infants reflected in terms of age-to-lowest-weight, percent weight loss, age-to-initial-sustained-weight gain and age-to-regain-birth weight, [30]. In the present study, we observed that ill, preterm SGA infants received enteral feedings of 100 ml/kg per day at an older age, and required a longer duration of parenteral nutrition than those with an uneventful course. Yet, the age-to-regainbirth-weight did not differ between these two groups of infants. Furthermore, at a postmenstrual age of 37-40 weeks, the growth (body weight, body length and head circumference) and body composition (arm muscle area and arm fat area) of ill SGA infants did not differ significantly from those of SGA infants with an uneventful clinical course. This implies that aggressive nutritional management, including different methods of enteral feeding and parenteral nutritional supplementation, may improve the quality of nutritional care in ill preterm newborns; therefore, their growth and body composition can be comparable with infants with an uneventful clinical course. SGA infants have long been recognized to be a heterogeneous group, and they were classified in this study into two groups according to the relationship between their body weight and body length: the proportioned, symmetric or nonwasted group; and the disproportioned, asymmetric or wasted group [3,10]. The asymmetric term SGA infants were observed to experience catch-up growth in weight during the first few months after birth [3,10]. Very few studies had related the postnatal growth of preterm SGA infants to the status of nutrition at birth. In this study, WLR was used to define the status of nutrition in preterm SGA infants. It was demonstrated that asymmetric infants did not differ much from symmetric infants in the 31-33 weeks gestation group, either at birth or at a postmenstrual age of 37-40 weeks. However, among the more mature SGA infants, asymmetric infants had a significantly lower skinfold thickness than symmetric infants, at birth. Which suggests that placental malnutrition may have occured during the latter period of gestation. When this group of preterm SGA infants had grown to near-term, their skinfold thickness and AFA were not much different from those of term AGA infants. In this study, further analysis by the multiple regression test revealed that preterm SGA infants with higher skinfold measurements at birth had less body weight deviation from the mean when they had grown to near-term. Skinfold measurements have been used widely to indicate the calorie reserve stored in the form of fat in adults, children and neonates [31,32]. Body fat stores, after liver weight, is the parameter mostly affected by intrauterine malnutrition [33]. Thus, SGA infants with higher skinfold measurements are likely to be less severely affected by intrauterine nutrient deprivation. Therefore, they may gain more weight than infants with lower skinfold measurements. The simple weight-to-length ratio has been found to correlate positively with skinfold measurements in neonates [17,18]. It has been suggested that weight-to-length ratio may be the best morphometric measure of the nutritional component of intrauterine growth [ 171.This study confirms this; in addition to the skinfold measure-
130
ment, the weight-to-length ratio correlated best with the near-term weight gain of preterm SGA infants. References 1 Battaglia, F.C. and Lubchenco, L.O. (1977): A practical classification of newborn infants by weight and gestational age. J. Pediatr., 71, 159-163. Fenton, T.R., McMillan, D.D. and Sauve, R.S. (1990): Nutrition and growth analysis of very low birth weight infants. Pediatrics, 86, 378-383. Davies, D.P., Platts, P., Pritchard, J.M. and Wilkinson, P.W. (1979): Nutritional status of light-fordate infants at birth and its influence on early postnatal growth. Arch. Dis. Child., 54, 703-706. Fitzhardinge, P.M. and Steven, E.M. (1972): The small-for-date infant. 1. Later growth patterns. Pediatrics, 49, 67 I-68 1. Fancourt, R., Campbell, S., Harvey, D. and Norman, A.P. (1976): Follow-up study of small-fordates babies. Br. Med. J., 1, 1435-1437. Kamiski, W., Blair, C. and Vitucci, J.S. (1987): The illusion of catch-up growth in premature infants: use of the growth index and age correction. Am. J. Dis. Child., 141, 520-526. Pena, I.C., Teberg, A.J. and Finello, K.M. (1988): The premature small-for-gestational-age infant during the first year of life. J. Pediatr., 113, 1066-1073. Miller H.C. and Hassanein K. (1971): Diagnosis of impaired fetal growth in newborn infants. Pediatrics, 48, 511-522. Georgieff, M.K., Sasanow S.R., Mammel, M.C. and Perira, G.R. (1986): Mid-arm circumference/head ratios for identification of symptomatic LGA, AGA and SGA newborn infants. J. Pediatr., 109, 316-321. 10 Villar, J., Smerigho, V., Martorell, R.. Brown, C.H. and Klein, R.E. (1984): Heterogeneous growth and mental development of intrauterine growth-retarded infants during the first 3 years of life. Pediatrics, 74, 783-791. 11 Chessex, P., Reichman, B., Verellen, G., Putet, G., Smith, J.M., Heim, T. and Sawyer, P.R. (1984): Metabolic consequences of intrauterine growth retardation in very low birth weight infants. Pediatr. Res., 18, 709-713. 12 Reichman, B., Chessex, P., Putet, G., Smith, J.M., Heim, T. and Sawyer, P.R. (1981): Diet, fat accretion, and growth in premature infants. N. Engl. J. Med., 305, 1495-1500. 13 Ballard, J.L., Khoury, J.C., Wedig, K., Wang, L., Eilers-Walsman, B.W. and Lipp, R. (1991): New Ballard score, expanded to include extremely premature infants. J. Pediatr., 119, 417-423. 14 Hsieh, T.T., Hsu, J.J., Chen, C.J., Chiu, T.H., Liou, J.D., Hsieh, C.C., Lo, L.M., Kuo, D.M. and Soong, Y.K. (1991): Analysis of birth weight and gestational age in Taiwan. J. Formosan Med. Assoc., 90, 382-387. 15 Papile, L., Burstein, J., Burstein, R. and Koffler, H. (1978): Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weight less than 1500 g. J. Pediatr., 92, 529-534.14. 16 Georgieff, M.K., Sasanow, S.R., Chockahngarm, U.M. and Periera, G.R. (1988): A comparison of the mid-arm circumference/head circumference ratio and ponderal index for the evaluation of newborn infants after abnormal intrauterine growth. Acta. Paediatr. Stand., 77, 214-219. 17 Wolfe, H.M., Brans, Y.W., Gross, T.L., Bhatia, P.K. and Sokol, R. J. (1990): Correlation of commonly used measures of intrauterine growth with estimated neonatal body fat. Biol. Neonate, 57, 167-171. 18 Sumners, J.E., Findlly, G.M. and Ferguson, K.A. (1990): Evaluation methods for intrauterine growth using neonatal fat stores instead of birth weight as outcome measures: fetal and neonatal measurements correlated with neonatal skinfold thickness. J. Clin. Ultrasound, 18, 9- 14. 19 Yau, K.I. and Chang, M.H. (1993): Weight to length ration - a good parameter for nutritional status in preterm and full-term newborns. Acta Pediatr., in press. 20 Yau, K.I. (1987): Assessment of neonatal body composition from arm circumference and skinfold thickness measurement. Acta Pediatr. Sinica, 28, 157-163.
131 21 22 23 24 25 26 21 28 29 30
31
32 33
Brans, Y. W., Sumners, J.E., Dweck, H.S. and Cassady, G. (1974): A noninvasive approach to body composition in the neonate: dynamic skinfold measurements. Pediatr. Res., 8, 215-222. Frisancho, A.R. (1974): Triceps skinfold and upper arm muscle size norms for assessment of nutritional status. Am. J. Clin. Nutr., 27, 1052-1057. Frisancho, A.R. (1981): New norms of upper limb fat and muscle areas for assessment of nutritional status. Am. J. Clin. Nutr., 34, 2540-2545. Sparks, J.W., Girard, J.R. and Battaglia, F.C. (1980): An estimate of the caloric requirements of the human fetus. Biol. Neonate, 38, 113-l 19. Shaffer, S.G., Quimiro, C.L. and Anderson, J.V. (1987): Postnatal weight changes in low birth weight infants. Pediatrics, 79, 702-705. Brooke, O.G., Alvear, J. and Arnold, M. (1979): Energy retension, energy expenditure, and growth in healthy immature infants. Pediatr. Res., 13, 215-220. Committee on Nutrition, American Academy of Pediatrics. (1985): Nutritional needs of low-birthweight infants. Pediatrics, 75, 976-986. Fomon, S.J. (1967): Body composition of the male reference infant during the first year of life. Pediatrics, 40, 863-870. Gill, A., Yu, V.Y.H., Bajuk, B. and Astbury, J. (1986): Postnatal growth in infants born before 30 weeks gestation. Arch. Dis. Child., 61, 549-553. Rickard, K.A., Brady, M.S., Moye, L., Schreiner, R.L., Gresham, E.L. and Lemons, J.A. (1982): Nutritional outcome of 207 very-low-birth-weight infants in an intensive care unti. J. Am. Diet. Assoc., 81, 674-682. Frisancho, A.R. and Gam, S.M. (1971): Skin-fold thickness and muscle size: implication for developmental status and nutritional evaluation of children from Honduras. Am. J. Chn. Nutr., 24, 541-546. Zerfas, A.J., Shorr, I.J. and Neumann, C.G. (1977): Office assessment of nutritional status. Pediatr. Clin. North. Am., 24, 253-272. Myers, R.E., Hill, D.E. and Cheek, D.B. (1971): Fetal growth retardation produced by experimental placental insufficiency in the rhesus monkey. I. Body weight organ size. Biol. Neonate, 18,379-381.