Postnatal Serum Insulin-Like Growth Factor I Deficiency Is Associated With Retinopathy of Prematurity and Other Complications of Premature Birth

Hellström, Ann; Engström, Eva; Hård, Anna‐Lena; Albertsson‐Wikland, Kerstin; Carlsson, Björn; Niklasson, Aimon; Löfqvist, Chatarina; Svensson, Elisabeth; Holm, Sture; Ewald, Uwe; Holmström, Gerd; Smith, Lois E.H.

doi:10.1542/peds.112.5.1016

Cited by 488 publications

(419 citation statements)

References 26 publications

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“…They are also associated with each other, suggesting a possible common pathogenetic mechanism localized in three different areas (4,18). It has recently been hypothesized that, at least for what concerns ROP and necrotizing enterocolitis, a serum IGF-I reduction (common in prematurity) may be involved, particularly in the case of ROP when this decrease was persistent after birth and an imbalance between IGF-I and vascular endothelial growth factor serum concentrations was also present (18).…”

Section: Discussionmentioning

confidence: 99%

“…Because it is known that serum free IGF-I values increase with the gestational age and are lower in infants developing ROP/BPD (18), the data support the idea that the free IGF-I molecules, determined in the BALF, may derive from a local production, and this finding is in agreement with the literature data showing that these molecules may be produced by the alveolar macrophages/monocytes (5,8,13). A limit of this study is the fact that the methods used cannot identify the IGF-I-and PAPP-A-producing cells.…”

Section: Epithelial Lining Fluid Levels Of Free Igf-i Papp-a and mentioning

confidence: 99%

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Epithelial lining fluid free IGF-I-to-PAPP-A ratio is associated with bronchopulmonary dysplasia in preterm infants

Capoluongo

Ameglio

Lulli

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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Preterm newborns developing retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD) show persistently low levels of insulin-like growth factor-I (IGF-I) in sera. They also present higher free IGF-I concentrations in epithelial lining fluids (ELFs) and lung tissues. Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase that dissociates three binding proteins from the active form of IGF-I, namely free IGF-I. The present study analyzes the ELF concentrations of free IGF-I, PAPP-A, and their ratios in preterm newborns developing or not BPD, defined as O2 dependence at 36 wk postmenstrual age. Bronchoalveolar lavage fluids of 41 infants (34 without and 7 with BPD) were analyzed on the 2nd and 4th day after birth. Infants developing BPD showed increased ELF free IGF-I and decreased PAPP-A concentrations on both days 2 and 4 compared with newborns without BPD. A nonsignificant trend between these 2 days was observed for free IGF-I (increasing) and PAPP-A (decreasing). On the same days, the free IGF-I-to-PAPP-A ratio was always significantly higher in patients developing BPD. These differences were more significant than those of IGF-I or PAPP-A when individually evaluated. A multivariate analysis confirmed the significance for free IGF-I on day 4, whereas the ratio was confirmed on both days 2 and 4. The same ratio was significantly correlated with some indexes of disease severity, such as hours of oxygen administration, days of hospitalization, and ROP severity scores. Finally, the ratio between ELF free IGF-I and PAPP-A appears to be a useful marker for lung injury of premature newborns.

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Section: Discussionmentioning

confidence: 99%

Section: Epithelial Lining Fluid Levels Of Free Igf-i Papp-a and mentioning

confidence: 99%

Epithelial lining fluid free IGF-I-to-PAPP-A ratio is associated with bronchopulmonary dysplasia in preterm infants

Capoluongo

Ameglio

Lulli

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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“…Several lines of evidence, including in vitro studies, support the notion that IGF-1 is critical for vessel development (King et al, 1985;Grant et al, 1993). Preterm infants with reduced serum levels of IGF-1 have a higher incidence of development of retinopathy (Hellstrom et al, 2003). Mice null for the IGF-1 gene have retarded retinal vascular growth, compared to wild type controls (Hellstrom et al, 2001).…”

Section: Regulation Of Vegf Expressionmentioning

confidence: 96%

Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

636

527

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Collectively, angiogenic ocular conditions represent the leading cause of irreversible vision loss in developed countries. In the U.S., for example, retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the principal causes of blindness in the infant, working age and elderly populations, respectively. Evidence suggests that vascular endothelial growth factor (VEGF), a 40 kDa dimeric glycoprotein, promotes angiogenesis in each of these conditions, making it a highly significant therapeutic target. However, VEGF is pleiotropic, affecting a broad spectrum of endothelial, neuronal and glial behaviors, and confounding the validity of anti-VEGF strategies, particularly under chronic disease conditions. In fact, among other functions VEGF can influence cell proliferation, cell migration, proteolysis, cell survival and vessel permeability in a wide variety of biological contexts. This article will describe the roles played by VEGF in the pathogenesis of retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. The potential disadvantages of inhibiting VEGF will be discussed, as will the rationales for targeting other VEGF-related modulators of angiogenesis.

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“…The study group comprised 71 preterm infants at baseline. Data regarding the initial IGF-I levels at birth are reported elsewhere (32). The current follow-up study was conducted after the initial study, and all patients were contacted for this follow-up study.…”

Section: Subjectsmentioning

confidence: 99%

Bone and fat mass in relation to postnatal levels of insulin-like growth factors in prematurely born children at 4 y of age

et al. 2014

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Background: Children born prematurely may be at risk of developing osteopenia. This study investigated whether insulin-like growth factors (IGFs) in the early postnatal period influence bone mass and body composition in prematurely born children. Methods: A total of 74 control (gestational age >36 wk; n = 37) and preterm (gestational age <32 wk; n = 37) infants were investigated (mean age ± SD: 4.59 ± 0.31 y). Bone mineral density, body composition, and markers of bone and mineral metabolism were investigated in relation to postnatal IGF levels. results: After adjusting for confounders, we found no differences in bone mass, but significantly less lean mass, increased fat mass, and increased osteocalcin levels in ex-preterm infants. Forward stepwise multiple analysis revealed that higher late postnatal IGF-II levels predict lumbar spine bone mineral content (P < 0.05) and lean mass (P < 0.05). When the birth weight standard deviation score was included in the analysis, higher early postnatal IGF-I levels predicted both lumbar spine bone mineral density and bone mineral content (P < 0.05). Higher early postnatal IGF binding protein-3 (P < 0.01) predicted increased fat mass at 4-y follow-up. conclusion: Ex-preterm children have normal bone mass but different body composition compared with full-term controls. Higher early IGF-I and late postnatal IGF-II concentrations are positive predictors of lumbar spine bone mass. c hildren's bone health is an important issue with lifelong importance. Many factors and medical conditions are associated with an increased risk of a bone mineral disorder and future skeletal problems, including genetics, mechanical loading, activity level, longitudinal growth, puberty, hormones, cytokines, and nutritional status. Peak bone mass is achieved during early adulthood and serves as the "bone bank" for the remainder of life. Bone remodeling, the continuous process of bone formation and resorption, can be assessed and monitored by biochemical markers of bone turnover (1). Many studies have found that ex-preterm infants are shorter, lighter, and have lower bone mass (2-5) than their full-term peers, and ex-preterm infants who are small for gestational age at birth seem to have the most risk (6). However, several studies have found that the bone mass in ex-preterm infants is appropriate for their body size (7,8) and one study proposed that bone mineral density (BMD) in very-low-birth-weight infants is normalized at 2 y of age (9). During adolescence, children who were born prematurely do not have different bone mineral content (BMC ) (10) or BMD (11) (adjusted for height and weight) in comparison with normal-weight children born at full term. Supplementation with early diet benefits short-time growth and BMD. Positive outcomes of an early special diet have been shown on body composition and fat mass during the first 2 y of life, but the long-term effects on BMD and other morbidities are not yet known (12).In full-term newborn infants, umbilical cord serum insulinlike growth factor (IGF)-I and ...

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Postnatal Serum Insulin-Like Growth Factor I Deficiency Is Associated With Retinopathy of Prematurity and Other Complications of Premature Birth

Abstract: These results indicate that persistent low serum concentrations of IGF-I after premature birth are associated with later development of ROP and other complications of prematurity. IGF-I is at least as strong a determinant of risk for ROP as postmenstrual age at birth and birth weight.

Cited by 488 publications

References 26 publications

Epithelial lining fluid free IGF-I-to-PAPP-A ratio is associated with bronchopulmonary dysplasia in preterm infants

Epithelial lining fluid free IGF-I-to-PAPP-A ratio is associated with bronchopulmonary dysplasia in preterm infants

Vascular endothelial growth factor in eye disease

Bone and fat mass in relation to postnatal levels of insulin-like growth factors in prematurely born children at 4 y of age

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