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Original Studies |
Department of Neonatology (A.L., S.G., O.C., B.L.S.), INSERM U-403 (A.L., P.D.D.), Human’s Nutrition Research Center (A.L., P.D.D., B.L.S.), and Department of Radiology (P.B.), Hôpital Edouard Herriot, Lyon, France
Address all correspondence and requests for reprints to: Alexandre Lapillonne, M.D., Department of Neonatology, Hôpital Edouard Herriot, 69437 Lyon Cedex 03, France.
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Abstract |
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WbBMC was not correlated with gestational age, but was well correlated with birth weight (r = 0.73; P = 0.0001) and also with fat mass (r = 0.87; P = 0.0001) and lean mass (r = 0.42; P = 0.008). The z-scores ± SD adjusted for weight for WbBMC and fat mass were significantly increased (1.3 ± 0.9 and 2.6 ± 1.3, respectively (P < 0.0001), but were not significantly influenced either by in utero growth or by the type of the diabetes mellitus of the mother.
Bone mineralization and fat mass studied by whole body dual x-ray absorptiometry are increased at birth in these infants compared with reference curves.
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Introduction |
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Dual x-ray absorptiometry (DXA) is generally accepted as an accurate and precise noninvasive technique to assess bone mineralization in vivo in adults as well as in children (2, 3, 4, 5, 6, 7, 8, 9). Because DXA is safe, quick, and requires little cooperation from the subject, this method has been acceptable in neonatology practice (10, 11, 12, 13, 14, 15, 16). The validation of DXA in subjects with low body mass has supported its use to study the bone mineral content and the body composition in neonates (10, 16, 17, 18).
Using DXA to determine the bone mass of the entire skeleton in IDM, we sought to confirm the report of decreased bone mass obtained by SPA of the distal radius. Other objectives were to assess the influence of the type of diabetes mellitus of the mothers on the mineralization of their infants and to study the body composition (e.g. fat mass and lean mass) of IDM at birth.
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Subjects and Methods |
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Forty singleton IDM, admitted to the Department of Neonatology of the Edouard Herriot hospital (Lyon, France), were prospectively included in this study. Newborns were eligible for this study if they had a birth weight above 2000 g; a birth weight below 2000 g precluded the use of DXA with a good accuracy (10, 15). Infants with genetic abnormalities or malformations and whose mothers had additional metabolic abnormalities or diseases that may have influenced their growth in utero were not eligible. Gestational age was determined using the date of the last period and was confirmed by early echogram. Infants were classified as large for gestational age (LGA) if their birth weight was above the mean + 2 SD of the curves described by Usher and McLean (19) and as appropriate for gestational age (AGA) if their birth weight was between the mean - 2 SD and the mean + 2 SD.
Twenty-five infants (62%) were born in our perinatal center. For the other 15 infants no precise information about the mothers’ glucose control during pregnancy was available. Thus, we decided to divide the 40 infants into 4 groups according to the type of diabetes mellitus of the mothers according to the classification of White (20), which emphasizes that the age of onset of diabetes, its duration, and the severity and degree of maternal disease all influence fetal survival.
Bone chemistry indexes
Serum calcium, phosphorus, and alkaline phosphatase were measured at birth and at 3 days of life with a Hitachi 747 analyzer (Hitachi, Tokyo, Japan). Serum 25-hydroxyvitamin D was measured at 3 days of life with a modified competitive protein binding assay (Buehlmann Laboratories, Schoenenbuch, Switzerland).
DXA protocol
All children were measured by DXA during their first 48 h under medical surveillance (Hologic QDR 1000W, Pediatric Software 5.47, Hologic, Waltham, MA). This apparatus uses a single beam configuration, and its principles have been previously described (10, 14, 15, 18). With this equipment mean coefficients of variation were below 5%, and mean accuracy was between -3 to +4% for fat mass, lean mass, and whole body bone mineral content (WbBMC) measurements (10, 15, 18).
Spontaneous sleep was obtained in all cases in the supine position without sedation. Room temperature was between 24–25 C, and a radiant source of heat was placed above the infant. The average duration of each measurement was 10 min. Results were compared with body composition reference curves previously obtained (10, 15).
The use of DXA for such infants was approved by the ethics committee of Lyon (CPPRB Lyon A). All parents were informed of the nature of the study and gave informed consent.
Statistical methods
Based on previous studies of WbBMC in term infants (15) and imposing a 0.05 level of significance and a 0.90 power of the test, a minimum sample size of 35 infants should allow identification of minimal detectable differences of 15 g.
Statistical analysis was performed using StatView 4.02 (Abacus Concepts, Berkeley, CA) on a Macintosh LC 475 computer (Apple Computer, Les Ulis, France). Normally distributed data were analyzed using the bilateral t test for comparison of two groups. Nonnormally distributed data were analyzed statistically using the Mann-Whitney nonparametric test for comparison of two groups. The ANOVA for one factor was used to study multiple variables. Correlations were performed between continuous variables, with computation of the coefficient of determination.
We have previously demonstrated that WbBMC, fat mass, and lean mass assessed by DXA at birth are well correlated with gestational age, but even more closely with birth weight (15). Therefore, the interpretation of body composition data in neonates should take into account the birth weight rather than the gestational age. On the basis of a comparison of observed WbBMC, fat mass, and lean mass in IDM with the normative curves for weight, z-scores adjusted for weight (z-score/W) were calculated. Each z-score/W was calculated for the precise weight of each infant at the time of DXA assessment (21). A univariate nonparametric test was used to assess the difference between z-scores and zero.
P values were considered as significant when inferior or equal to 0.05. Results are expressed as the mean ± SD and range.
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Results |
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The main characteristics of the infants at birth according to
their gestational age and their in utero growth are reported
in Table 1
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Individual WbBMC values for the 40 IDM are reported according to
birth weight in Fig. 1, whereas mean
values according to gestational age and in utero growth are
reported in Table 2.
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. For the 40 IDM, the
WbBMC was well correlated with fat mass (r = 0.87;
P = 0.0001) and lean mass (r = 0.42;
P = 0.008). For the 18 AGA IDM, WbBMC was correlated
with birth weight, birth length, and gestational age, as previously
reported in control AGA infants (Table 3); however, coefficients of
correlation in IDM were lower than those reported in control AGA
infants (r = 0.86, 0.67, and 0.68, respectively) (15).
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Body composition
The body composition results in IDM (e.g. fat mass and
lean mass) are also reported in Table 2
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Correlation between fat mass or lean mass and gestational age or growth
parameters are reported in Table 3. For the 18 AGA IDM, fat mass was
significantly correlated with birth weight and birth length, but not
with gestational age, whereas fat mass in control AGA infants is known
to be correlated with all of these parameters (r = 0.91, 0.66, and
0.66, respectively) (15).
The mean fat z-score/W ± SD was positive (2.6 ± 1.3) and significantly different from zero (P < 0.0001). The fat z-score/W was not significantly influenced by in utero growth (2.6 ± 1.4 for AGA vs. 2.6 ± 1.2 for LGA; P = 0.786).
The mean lean z-score/W ± SD was negative (-1.4 ± 2.1) and significantly different from zero (P < 0.0001). The lean z-score/W was significantly influenced by in utero growth (-0.5 ± 0.8 for AGA vs. -2.1 ± 2.5 for LGA; P = 0.0375).
Influence of the type of diabetes of the mothers on the body composition of their infants
No significant differences in gestational age, birth weight, or
birth length existed among the four groups of White’s classification
(Table 4). The results of body
composition assessed by DXA showed no significant influence of White’s
classification on WbBMC, fat mass, or lean mass expressed as absolute
values (Table 4) or expressed as z-scores (Table 5).
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None of the patients had biological abnormalities at birth. At 3 days of life, mean serum calcium ± SD was 2.26 ± 0.25 mmol/L (range, 1.23–2.71), mean serum phosphorus ± SD was 2.16 ± 0.37 mmol/L (range, 1.45–2.9), and mean serum 25-hydroxyvitamin D ± SD was 25.7 ± 11.7 ng/mL (range, 9–50). Two infants had asymptomatic hypocalcemia below 2 mmol/L (1.23 and 1.90 mmol/L) at 3 days of age.
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Discussion |
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Using whole body DXA assessment, we could not confirm that a decreased bone mass is correlated with a poorer maternal glycemic control. In contrast to the findings of Mimouni et al. (1), LGA IDM in our study, who usually represent the infants born after poor maternal glycemic control during pregnancy, have no significant decrease in WbBMC. Finally, we did not observe any significant differences in WbBMC among the four groups of infants according to White’s classification.
Our findings are in keeping with the known role of insulin on bone formation. As IDM are hyperinsulinemic, especially the LGA infants (23, 24, 25), the increase in fetal mineralization found in our study could be explained by the effect of insulin on bone formation. Indeed, insulin, which is the most important systemic hormone modulating normal skeletal growth, does not regulate bone resorption, but causes a marked stimulation of bone matrix synthesis and cartilage formation (26, 27). Insulin also increases insulin-like growth factor I (IGF-I) production by the liver; as it is well known that IGF-I enhances bone collagen and matrix synthesis and stimulates the replication of cells of the osteoblast lineage (28), some of the effects observed in IDM, therefore, may have been mediated by IGF-I. The correlation between WbBMC and growth parameters, fat mass, and lean mass and the absence of correlation with gestational age support the hypothesis that the mineralization of IDM is directly dependent on growth in utero.
It has been previously demonstrated that LGA infants and IDM have a significantly greater body fat mass, assessed by skinfold thickness, than controls in both absolute values and percentages of body weight (23, 24). Macrosomia in IDM is presumed to be the result of fetal hyperinsulinism secondary to maternal and fetal hyperglycemia during pregnancy (25, 29, 30, 31). The degree of macrosomia in IDM is correlated with cord serum total insulin concentrations (32).
In our study, more than half of the IDM were LGA and presented macrosomia, a rate comparable with those recently reported in other centers (33). Fat mass assessed by DXA was higher than that in control subjects with comparable birth weight. Consequently, the lean mass was lower than that in weight-matched control subjects.
Brans et al. found skinfold thickness values more frequently in excess of the normal range in the IDM of the higher White’s diabetic class (24). On the contrary, Ballard et al. found no correlation between White’s classification and fetal growth category (33). In our study, we did not observe any significant differences in fat mass among the four groups according to White’s diabetic class. The higher fat mass observed in IDM, therefore, may be related to glycemic control during pregnancy rather than to White’s diabetic class.
Bone mineralization, studied by whole body DXA, is not impaired in IDM. On the contrary, bone mass of the total skeleton is increased compared with that in control infants. There is no evidence of an influence of the mother’s White’s diabetic class on the mineralization of her newborn. Assessment of body composition by DXA confirms the increase in fat mass in IDM.
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Acknowledgments |
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Received May 20, 1997.
Revised July 3, 1997.
Revised July 28, 1997.
Accepted August 20, 1997.
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References |
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