© 1990 S. Karger AG. Basel 0006-3126/90/0584-0188S2.75/0
Biol Neonate 1990:58:188—191
Hypersomatotropism in the Dysmature Infant at Term and Preterm Birth1* F. de Zegher3, J. Kimpen a , J. Rausb, M. Vanderschueren-Lodeweyckxa 3 Department of Pediatrics, University of Leuven; bDr Willems Institute. University Campus. Diepenbeek, Belgium
Key Words. Growth hormone • Dysmaturity • Fetus
Introduction Growth hormone (GH) serum concentra tions are markedly elevated in the human fetus, decrease with advancing gestational age and present at all ages a striking interin dividual variation [1, 2], The regulation of GH secretion in the human fetus is poorly understood. Administration of somatostatin to the pregnant woman results in a decrease in fetal serum GH concentration [3], Prena
1 This work was supported by the Belgian NFWGO 3.0047.89.
tal administration of glucocorticoids to the prospective mother also results in a reduc tion of the GH levels in fetal serum at pre mature birth [4], Fetal hypothyroidism is known to be associated with decreased se rum GH concentration at birth [5]. In con trast, spontaneously increased serum levels of GH have recently been reported in lategestational fetal lambs of twin and 'out-ofseason' pregnancies, two conditions com monly associated with dysmaturity in the ovine fetus [6]. We extended this study to the human and report the effect of dysmaturity on cord serum GH concentration at term and preterm birth.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/31/2018 1:29:25 PM
Abstract. Growth hormone (GH) concentrations were measured in cord serum of small (< 2 .4 kg), appropriate (3.4 ± 0.1 kg) and large (>4.4 kg) infants born at term (38-42 weeks), and in cord serum of prematurely born twins (28-36 weeks) which were either appropriate (> P10) or small (< P10) for gestational age. Cord serum GH levels were found to be significantly elevated in small for gestational age infants, both at term and preterm birth. In view of the insulin-antagonizing action of fetal GH, these results further support a homeostatic function for GH in the late-gestational human fetus.
Hypersomatotropism in the Dysmature Infant at Birth
189
Materials and Methods GH concentrations were measured in 193 serum samples by a standardized double antibody RIA [7] with an intraassay variation of 3%; all samples of compared groups were analyzed in the same assays.
Preterm Birth Study Mixed cord serum samples were obtained at pre mature birth in our hospital. The study was designed to exclude the interference of maternal factors and the potential influence of fetal lung maturation-therapy (glucocorticoids and thyroid-stimulating hormone-releasing hormone). Therefore, only prematurely born twins (28-36 weeks gestation) were included in the study. Two groups were considered. In one group, the birthweight of both twins was above P10 for gesta tional age (concordant twins). In the second group, one of each pair of twins had a birthweight above P 10 for gestational age, whereas the other twin had a birthweight below P10 for gestational age (discordant twins).
Results The results of the term birth study are summarized in figure 1. Cord serum GH con centrations of large infants (mean ± SE; 16.7 ± 1.0 ng/ml; n = 70) and of appropriate
Fig. 1. Cord serum GH concentrations in large (> 4 .4 kg), appropriate (3.4 ± 0.1 kg) and small (< 2 .4 kg) infants at term birth (38-42 weeks gesta tion). Results are expressed as mean ± SEM. *** p < 0.001
infants (16.5 ± 1.2 ng/ml; n = 49) were simi lar (p= 0.91). In small infants, GH levels were elevated (24.2 ± 1.8 ng/ml; n = 42) compared to the GH concentrations of both appropriate and large infants (p < 0.001). The results obtained in the preterm twins are summa rized in figure 2. Whereas serum GH concen trations in concordant twins were similar (p = 0.50), GH levels were significantly different in discordant twins (p = 0.007), being ele vated in the dysmature infants.
Discussion The data indicate that serum GH concen trations are elevated in the growth-retarded human conceptus at preterm and term birth. The mechanisms underlying this rise in cir culating GH are at present unclear. Among the mechanisms potentially involved are in creased pituitary responsiveness to GH-re-
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/31/2018 1:29:25 PM
Term Birth Study Mixed cord serum samples were donated by the regional cord serum bank (Dr Willems Institute. Uni versity Campus. Diepenbeek, Belgium) where sam ples from 11 maternity hospitals in North-Eastern Belgium are collected. Contamination with maternal serum had been carefully excluded by IgA measure ment [8], All samples were obtained from full-term neonates (38-42 weeks gestation) and were further selected exclusively on the basis of the birthweight of the infant. Three birthweight groups were examined: less than 2.4 kg (small), 3.4 ± 0.1 kg (appropriate) and more than 4.4 kg (large). These groups were cho sen as they represent the lower 3%, the mean and the upper 3% of term birthweights in Belgium. No other clinical information concerning the newborns was made available. Unpaired t tests were used for statis tical comparisons.
de Zegher/Kimpen/Raus/Vanderschueren-Lodeweyckx
190
p = 0 007
Concordant Twins >P10
>P10
Discordant Twins >P10
leasing hormone [6, 9] and decreased inhibi tory feedback by circulating insulin-like growth factor-l (IGF-1) [10]. Increased serum levels of GH have also been documented in the human and the ovine fetus under circumstances of acidosis and hypoxia [11. 12], in fetuses of under nourished ewes [13. 14], in ovine fetuses undergoing surgery [12] and in ovine fetuses in conditions associated with growth retar dation [6]. Thus, fetal serum GH levels are elevated under nutritional, metabolic and surgical stress circumstances. In the human, the increase in GH levels associated with fetal growth retardation appears to persist for at least 3 days after birth [9]. The stress-related increase in fetal-circu lating GH is likely to be of physiological sig nificance: GH is known to have insulinantagonizing actions on fetal carbohydrate [15] and lipid [16] metabolism, and GH receptors may be present in the placenta
Biol Neonate 1990:58:188—191
Hypersomatotropism in the Dysmature Infant at Term and Preterm Birth1* F. de Zegher3, J. Kimpen a , J. Rausb, M. Vanderschueren-Lodeweyckxa 3 Department of Pediatrics, University of Leuven; bDr Willems Institute. University Campus. Diepenbeek, Belgium
Key Words. Growth hormone • Dysmaturity • Fetus
Introduction Growth hormone (GH) serum concentra tions are markedly elevated in the human fetus, decrease with advancing gestational age and present at all ages a striking interin dividual variation [1, 2], The regulation of GH secretion in the human fetus is poorly understood. Administration of somatostatin to the pregnant woman results in a decrease in fetal serum GH concentration [3], Prena
1 This work was supported by the Belgian NFWGO 3.0047.89.
tal administration of glucocorticoids to the prospective mother also results in a reduc tion of the GH levels in fetal serum at pre mature birth [4], Fetal hypothyroidism is known to be associated with decreased se rum GH concentration at birth [5]. In con trast, spontaneously increased serum levels of GH have recently been reported in lategestational fetal lambs of twin and 'out-ofseason' pregnancies, two conditions com monly associated with dysmaturity in the ovine fetus [6]. We extended this study to the human and report the effect of dysmaturity on cord serum GH concentration at term and preterm birth.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/31/2018 1:29:25 PM
Abstract. Growth hormone (GH) concentrations were measured in cord serum of small (< 2 .4 kg), appropriate (3.4 ± 0.1 kg) and large (>4.4 kg) infants born at term (38-42 weeks), and in cord serum of prematurely born twins (28-36 weeks) which were either appropriate (> P10) or small (< P10) for gestational age. Cord serum GH levels were found to be significantly elevated in small for gestational age infants, both at term and preterm birth. In view of the insulin-antagonizing action of fetal GH, these results further support a homeostatic function for GH in the late-gestational human fetus.
Hypersomatotropism in the Dysmature Infant at Birth
189
Materials and Methods GH concentrations were measured in 193 serum samples by a standardized double antibody RIA [7] with an intraassay variation of 3%; all samples of compared groups were analyzed in the same assays.
Preterm Birth Study Mixed cord serum samples were obtained at pre mature birth in our hospital. The study was designed to exclude the interference of maternal factors and the potential influence of fetal lung maturation-therapy (glucocorticoids and thyroid-stimulating hormone-releasing hormone). Therefore, only prematurely born twins (28-36 weeks gestation) were included in the study. Two groups were considered. In one group, the birthweight of both twins was above P10 for gesta tional age (concordant twins). In the second group, one of each pair of twins had a birthweight above P 10 for gestational age, whereas the other twin had a birthweight below P10 for gestational age (discordant twins).
Results The results of the term birth study are summarized in figure 1. Cord serum GH con centrations of large infants (mean ± SE; 16.7 ± 1.0 ng/ml; n = 70) and of appropriate
Fig. 1. Cord serum GH concentrations in large (> 4 .4 kg), appropriate (3.4 ± 0.1 kg) and small (< 2 .4 kg) infants at term birth (38-42 weeks gesta tion). Results are expressed as mean ± SEM. *** p < 0.001
infants (16.5 ± 1.2 ng/ml; n = 49) were simi lar (p= 0.91). In small infants, GH levels were elevated (24.2 ± 1.8 ng/ml; n = 42) compared to the GH concentrations of both appropriate and large infants (p < 0.001). The results obtained in the preterm twins are summa rized in figure 2. Whereas serum GH concen trations in concordant twins were similar (p = 0.50), GH levels were significantly different in discordant twins (p = 0.007), being ele vated in the dysmature infants.
Discussion The data indicate that serum GH concen trations are elevated in the growth-retarded human conceptus at preterm and term birth. The mechanisms underlying this rise in cir culating GH are at present unclear. Among the mechanisms potentially involved are in creased pituitary responsiveness to GH-re-
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/31/2018 1:29:25 PM
Term Birth Study Mixed cord serum samples were donated by the regional cord serum bank (Dr Willems Institute. Uni versity Campus. Diepenbeek, Belgium) where sam ples from 11 maternity hospitals in North-Eastern Belgium are collected. Contamination with maternal serum had been carefully excluded by IgA measure ment [8], All samples were obtained from full-term neonates (38-42 weeks gestation) and were further selected exclusively on the basis of the birthweight of the infant. Three birthweight groups were examined: less than 2.4 kg (small), 3.4 ± 0.1 kg (appropriate) and more than 4.4 kg (large). These groups were cho sen as they represent the lower 3%, the mean and the upper 3% of term birthweights in Belgium. No other clinical information concerning the newborns was made available. Unpaired t tests were used for statis tical comparisons.
de Zegher/Kimpen/Raus/Vanderschueren-Lodeweyckx
190
p = 0 007
Concordant Twins >P10
>P10
Discordant Twins >P10
leasing hormone [6, 9] and decreased inhibi tory feedback by circulating insulin-like growth factor-l (IGF-1) [10]. Increased serum levels of GH have also been documented in the human and the ovine fetus under circumstances of acidosis and hypoxia [11. 12], in fetuses of under nourished ewes [13. 14], in ovine fetuses undergoing surgery [12] and in ovine fetuses in conditions associated with growth retar dation [6]. Thus, fetal serum GH levels are elevated under nutritional, metabolic and surgical stress circumstances. In the human, the increase in GH levels associated with fetal growth retardation appears to persist for at least 3 days after birth [9]. The stress-related increase in fetal-circu lating GH is likely to be of physiological sig nificance: GH is known to have insulinantagonizing actions on fetal carbohydrate [15] and lipid [16] metabolism, and GH receptors may be present in the placenta
