Insulin-like growth factor 1 has multisystem effects on foetal and preterm infant development

Abstract

Poor postnatal growth after preterm birth does not match the normal rapid growth in utero and is associated with preterm morbidities. Insulin-like growth factor 1 (IGF-1) axis is the major hormonal mediator of growth in utero, and levels of IGF-1 are often very low after preterm birth. We reviewed the role of IGF-1 in foetal development and the corresponding preterm perinatal period to highlight the potential clinical importance of IGF-1 deficiency in preterm morbidities.

Conclusion: There is a rationale for clinical trials to evaluate the potential benefits of IGF-1 replacement in very preterm infants.

Keywords: Development; Foetus; Insulin-like growth factor 1; Metabolism; Preterm infant.

Figure 1

Mean foetal blood IGF‐1 concentrations (samples obtained by cordocentesis from normal pregnancies measured by RIA) double from 18 to 42 weeks of gestational age (GA) (n = 174) (213, 257). This figure combines data from Lasarre et al. and Bang et al. on IGF1 levels in utero.

Figure 2

(A) Describes the relationship between insulin and the GH/IGF‐1 axis in childhood and in (B) preterm newborn. GH, growth hormone; GHBP, growth hormone‐binding protein; GH receptor, growth hormone receptor; BP1, IGF binding protein 1; IGF‐1, insulin growth factor 1, BPs, IGF binding proteins, ALS, acid labile subunit, IGFR, IGF‐1 receptor.

Figure 3

Effect of IGF‐I inhibition on vascular growth. Mice were perfused with fluorescein dextran at postnatal day 5, eyes were enucleated, and retinas were examined in flat mount. There was significantly retarded vascular growth (perfused vessels seen as bright green) in the retinas of the IGF‐I−/− mice (A) compared with littermate IGF‐I+/+ controls with normal IGF‐I levels (B). The distance from the optic nerve to the vessel front (red arrow) vs optic nerve to periphery (yellow arrow) was 58 ± 4.8% for IGF‐I−/− retinas vs 70.3 ± 5.8% for IGF‐I+/+ controls (p < 0.001), indicating that IGF‐I is critical for normal vascular development and that low IGF‐I in the neonatal period could cause retardation of vascular growth. Figure by Hellström et al., with permission from PNAS (S80).

Figure 4

Normal intrauterine IGF‐1 concentrations obtained from the umbilical cord with cordocentesis over 18–42 weeks of gestational age (GA) (black circles) (n = 174) 23, 60 compared to preterm infants of matched postmenstrual ages (red dots) (S86,S87).

Figure 5

Change in weight SDS with increasing postmenstrual age (PMA) illustrating phases of growth retardation and catch‐up in preterm infants compared to undisturbed intrauterine growth (purple line) (S112). Data from 1942 infants born at GA 23–28 weeks from North America and Sweden. Figure courtesy of Susanna Klevebro.

Figure 6

Developmental processes and growth in normal brain development during gestation and after birth. Figure by Lagercrantz with permission from Cambridge University Press (S121).

Figure 7

HCSDS at PMA 31 weeks correlate significantly with mean serum IGF‐1 levels from birth to PMA 31 weeks among 58 preterm children, Figure by Löfqvist et al. with permission from Pediatrics (S122).