Maternal Hypoxia as a Model for Intrauterine Growth Retardation: Effects on Insulin-Like Growth Factors and Their Binding Proteins

Tapanainen, Päivi; Bang, Peter; Wilson, Kristin; Unterman, Terry G.; Vreman, Hendrik J.; Rosenfeld, Ron G.

doi:10.1203/00006450-199408000-00004

Cited by 94 publications

(66 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…High IGFBP-1 levels are also found in conditions such as prolonged fasting, anorexia nervosa (37), and fetal hypoxemia (38). The high IGFBP-1 levels in our study were not caused by fasting as all our preterm infants were continuously fed and never showed low glucose levels.…”

Section: Discussionsupporting

confidence: 58%

Effect of Dexamethasone Treatment on Serum GH, IGF-I, and the Binding Proteins IGFBP-1 and -3 in Ventilated Very Preterm Infants

Huysman

Hokken-Koelega

Hop³

et al. 2003

Pediatr Res

View full text Add to dashboard Cite

Very preterm infants developing bronchopulmonary dysplasia frequently show a compromised growth in the neonatal period especially when steroids are given to facilitate weaning from the ventilator. The aim of this study was to evaluate the short-term effect of dexamethasone (DEXA) on the GH-IGF axis in ventilated very preterm infants developing bronchopulmonary dysplasia. We studied 10 very preterm artificially ventilated infants with bronchopulmonary dysplasia [median (range) gestational age 27.5 wk (25.9 -32.0 wk), median (range) birth weight 970 g (610 -2150 g)] immediately before and 2 d after the start of DEXA treatment. On both days of study, serum GH profiles were obtained, and serum IGF-I and IGF binding protein (IGFBP) -1 and -3 levels were measured. The ventilation score and the nutritional intake were calculated. Before the start of DEXA treatment, the median serum mean GH level was 12.0 g/L (6 -28.4 g/L), whereas 2 d after the start of DEXA treatment the median serum mean GH level declined significantly to a value of 4.4 g/L (1.7-11.9 g/L). During DEXA treatment, mean, baseline, and maximal GH levels (Pulsar analysis) were significantly lower compared with pretreatment levels (p Ͻ 0.01, p Ͻ 0.01, and p Ͻ 0.05, respectively). Serum IGF-I and IGFBP-3 levels did not decline during DEXA. Serum IGFBP-1 levels were significantly lower compared with pretreatment levels (p Ͻ 0.01). Serum GH levels during DEXA treatment were correlated with neither the time interval between the administration of DEXA and the second GH profile nor the cumulative DEXA dose administered. Ventilation score and nutritional intake did not significantly correlate with serum GH, IGF-I, or IGFBP-1 or -3 levels, either before or after the start of DEXA. Two days of DEXA treatment in very preterm ventilated infants has a suppressive effect on serum GH levels, without an acute decline in serum IGF-I levels. A concomitant decrease in serum IGFBP-1 levels was found. Very preterm infants developing BPD, with a persistent need for artificial ventilation and oxygenation, frequently show a very compromised growth in the neonatal period (1, 2). Their growth will be further attenuated when DEXA treatment is given after conservative treatment, including increased ventilation settings and fluid restriction, has failed to wean them from the ventilator (3-5). The hormonal mechanisms underlying this early postnatal growth retardation and the role of glucocorticosteroids have not been elucidated. DEXA has a catabolic effect by increasing protein breakdown and alters skeletal metabolism by inhibition of intestinal calcium absorption, stimulation of renal calcium excretion, and suppression of collagen turnover in preterm infants (6 -8).Glucocorticosteroids have been suggested to have a suppressive effect on the pituitary GH secretion with attenuation of the spontaneous GH secretion and decreased GH responses to various stimuli (9 -11). A direct antagonizing effect of DEXA on the epiphyseal cartilage to the action of GH has been reported, probably by inhi...

show abstract

Section: Discussionsupporting

confidence: 58%

Effect of Dexamethasone Treatment on Serum GH, IGF-I, and the Binding Proteins IGFBP-1 and -3 in Ventilated Very Preterm Infants

Huysman

Hokken-Koelega

Hop³

et al. 2003

Pediatr Res

View full text Add to dashboard Cite

show abstract

“…Pregnancy at high altitude may also alter the fetal plasma concentrations of binding proteins and the sensitivity of fetal tissues to these hormones and/or factors. The sparse available data suggest that up-regulation of IGF-binding proteins by chronic hypoxia may provide a mechanism operating in the human fetus to restrict IGF-mediated growth in utero (62,63). In addition, human fetal growth may be regulated directly by the availability of oxygen.…”

Section: Discussionmentioning

confidence: 99%

Effects of Altitude versus Economic Status on Birth Weight and Body Shape at Birth

et al. 2001

View full text Add to dashboard Cite

“…Significant increases in fetal hepatic IGFBP-1 and -2 have been observed in animal models of IUGR, late in pregnancy, and these increases are postulated to exert an inhibitory effect on the growth promoting action of IGF-I during fetal life (7). Additionally, several studies report increases in IGFBP-4, and decreases in IGFBP-3 in IUGR fetal circulation (8,9).…”

mentioning

confidence: 99%

Altered Placental and Fetal Expression of IGFs and IGF-Binding Proteins Associated With Intrauterine Growth Restriction in Fetal Sheep During Early and Mid-Pregnancy

et al. 2006

View full text Add to dashboard Cite

ABSTRACT:The insulin-like growth factors (IGFs) are postulated to be altered in association with the development of intrauterine growth restriction (IUGR). The present studies examined placental and fetal hepatic mRNA concentration of components of the IGF system at two time points (55 and 90 d gestational age, dGA; Term 147 dGA) in a hyperthermia (HT)-induced sheep model of placental insufficiency-IUGR. Maternal plasma insulin and IGF-I were constant at 55 and 90 dGA and were unaffected by treatment. Umbilical vein insulin concentrations tended to be reduced at 90 dGA following HT exposure. Caruncle IGF-I mRNA was increased at 90 dGA in HT placentae (p Ͻ 0.05), while cotyledon concentrations were constant over gestation and unaltered by treatment. In control cotyledons, IGF-II mRNA concentration increased (p Ͻ 0.01) and IGFBP-3 decreased between 55 and 90 dGA (p Ͻ 0.01). Cotyledon IGF-II and caruncle IGFBP-4 mRNA were elevated at 55 dGA in HT placentae compared with control (p Ͻ 0.01 and p Ͻ 0.05 respectively). Fetal hepatic IGF-I, IGFBP-2, -3 and -4 concentrations rose over gestation (p Ͻ 0.05), but there were no treatment effects. These data suggest that changes in placental IGF expression in early and mid gestation may predispose the pregnancy to placental insufficiency, resulting in inadequate substrate supply to the developing fetus later in gestation.

show abstract

Maternal Hypoxia as a Model for Intrauterine Growth Retardation: Effects on Insulin-Like Growth Factors and Their Binding Proteins

Cited by 94 publications

References 26 publications

Effect of Dexamethasone Treatment on Serum GH, IGF-I, and the Binding Proteins IGFBP-1 and -3 in Ventilated Very Preterm Infants

Effect of Dexamethasone Treatment on Serum GH, IGF-I, and the Binding Proteins IGFBP-1 and -3 in Ventilated Very Preterm Infants

Effects of Altitude versus Economic Status on Birth Weight and Body Shape at Birth

Altered Placental and Fetal Expression of IGFs and IGF-Binding Proteins Associated With Intrauterine Growth Restriction in Fetal Sheep During Early and Mid-Pregnancy

Contact Info

Product

Resources

About