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Insulin-Like Growth Factor-1 and Morbidities of Prematurity: Bronchopulmonary Dysplasia, Retinopathy of Prematurity, Intraventricular Hemorrhage and Necrotizing Enterocolitis

Year 2019, Volume: 17 Issue: 2, 189 - 199, 02.08.2019

Abstract

Insulin-like growth factor-1 (IGF-1) is important for fetal and postnatal development. After premature births, serum IGF-1 concentrations rapidly decrease and can stay at much lower levels than during the intrauterine period. In this study, we aimed to ascertain whether IGF-1 is associated with morbidities of prematurity such as bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), and necrotizing enterocolitis (NEC), and is a useful predictor of these diseases.

METHODS: We enrolled newborn infants born at a postmenstrual age of ≤32 weeks in this prospective observational cohort study. Serum IGF-1 levels were measured serially in blood samples on the 1st, 3rd, 7th, 21st, and 28th day.

RESULTS: A total of 93 infants were enrolled in the study. All these infants had the following characteristics at birth: weight 1236.11±354.06 g, and gestational age 29.43±2.10 weeks. All of the IGF-1 levels were significantly lower in the group which developed BPD or ROP (p<0.001). The patients who developed IVH and NEC also had lower IGF-1 levels.

DISCUSSION and CONCLUSION: Strong correlations have been found between low serum IGF-1 levels during the first four weeks and development of BPD and ROP.

References

  • 1. Netchine I, Azzi S, Le Bouc Y, Savage MO. IGF1 molecular anomalies demonstrate its critical role in fetal, postnatal growth and brain development. Best Pract Res Clin Endocrinol Metab 2011;25:181-90.
  • 2. Ley D, Hansen-Pupp I, Niklasson A, Domellöf M, Friberg LE, Borg J, et al. Longitudinal infusion of a complex of insulin-like growth factor-I and IGF-binding protein-3 in five preterm infants: pharmacokinetics and short-term safety. Pediatr Res 2013;73:68–74.
  • 3. Hansen-Pupp I, Hövel H, Löfqvist C, Hellström-Westas L, Fellman V, Hüppi PS, et al. Circulatory insulin-like growth factor-I and brain volumes in relation to neurodevelopmental outcome in very preterm infants. Pediatr Res 2013;74:564–9.
  • 4. Löfqvist C, Hellgren G, Niklasson A, Engström E, Ley D, Hansen-Pupp I. Low postnatal serum IGF-I levels are associated with bronchopulmonary dysplasia (BPD). ActaPaediatr 2012;101:1211–6.
  • 5. Hansen-Pupp I, Hövel H, Hellström A, Hellström-Westas L, Löfqvist C, Larsson EM, et al. Postnatal decrease in circulating insulin-like growth factor-I and low brain volumes in very preterm infants. J Clin Endocrinol Metab 2011;96:1129–35.
  • 6.Academy A, Ophthalmology P. Screening examination of premature infants for retinopathy of prematurity. Pediatrics 2013;131:189–95.
  • 7. Jobe AH, Bancalari E. Bronchopulmonary Dysplasia. Am J RespirCrit Care Med 2001;163:1723–9.
  • 8.Stoll BJ, Hansen NI, Bell EF, Shankaran S, Laptook AR, Walsh MC, et al. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics 2010;126:443–56.
  • 9. Capoluongo E, Ameglio F, Zuppi C. Insulin-like growth factor-I and complications of prematurity: a focus on bronchopulmonary dysplasia. Clin Chem Lab Med 2008;46:1061–6.
  • 10. Hellström A, Engström E, Hard AL, Albertsson-Wikland K, Carlsson B, Niklasson A, et al. Postnatal Serum Insulin-Like Growth Factor I Deficiency Is Associated With Retinopathy of Prematurity and Other Complications of Premature Birth. Pediatrics 2003;112:1016–20.
  • 11. Chung JK, Hallberg B, Hansen-Pupp I, Graham MA, Fetterly G, Sharma J, et al. Development and verification of a pharmacokinetic model to optimize physiologic replacement of rhIGF-1/rhIGFBP-3 in preterm infants. Pediatr Res 2017;81:504–10.
  • 12. Stahl A, Connor KM, Sapieha P, Chen J, Dennison RJ, Krah NM, et al. The mouse retina as an angiogenesis model. Invest Ophthalmol Vis Sci 2010;51:2813–26.
  • 13. Hellstrom A, Perruzzi C, Ju M, Engstrom E, Hard AL, Liu JL, et al. Low IGF-I suppresses VEGF-survival signaling in retinal endothelial cells: Direct correlation with clinical retinopathy of prematurity. Proc Natl Acad Sci 2001;98:5804–8.
  • 14. Hawkes CP, Grimberg A. Insulin-Like Growth Factor-I is a Marker for the Nutritional State. Pediatr Endocrinol Rev 2015;13:499–511.
  • 15.Hansen-Pupp I, Löfqvist C, Polberger S, Niklasson A, Fellman V, Hellström A, et al. Influence of insulin-like growth factor 1 and nutrition during phases of postnatal growth in very preterm infants. Pediatr Res 2011;69:448–53.
  • 16. Pérez-Muñuzuri A, Fernández-Lorenzo J, Couce-Pico M, Blanco-Teijeiro M, Fraga-Bermúdez J. Serum levels of IGF1 are a useful predictor of retinopathy of prematurity. Acta Paediatr 2010;99:519–25.
  • 17. Cheong JL, Hunt RW, Anderson PJ, Howard K, Thompson DK, Wang HX, et al. Head growth in preterm infants: correlation with magnetic resonance imaging and neurodevelopmental outcome. Pediatrics 2008;12:1534-40.
  • 18. Ozen S, Akisu M, Baka M, Yalaz M, Sozmen EY, Berdeli A, et al. Insulin-like growth factor attenuates apoptosis and mucosal damage in hypoxia/reoxygenation-induced intestinal injury. Biol Neonate 2005;87:91–6.

İnsülin Benzeri Büyüme Faktörü-1 ve Premature Morbiditeleri: Bronkopulmoner Displazi, Premature Retinopatisi, İntraventriküler Kanama ve Nekrotizan Enterokolit

Year 2019, Volume: 17 Issue: 2, 189 - 199, 02.08.2019

Abstract

GİRİŞ ve AMAÇ: İnsulin benzeri büyüme faktörü-1 (IGF-1) fetal ve postnatal dönemde etkili önemli bir büyüme faktörüdür. Prematüre doğum sonrası serum IGF-1 düzeyleri hızlıca düşmekte intrauterin dönemden daha da düşük seviyelerde kalabilmektedir. Bu çalışmada serum IGF-1 düzeylerinin, bronkopulmoner displazi (BPD), prematüre retinopatisi (PR), intraventriküler kanama (İVK) ve nekrotizan enterokolit (NEK) gibi prematüre morbiditeleri ile ilişkisinin olup olmadığı ve morbiditeleri ön görmede belirteç olarak kullanıp kullanılamayacağı araştırılmıştır.
YÖNTEM ve GEREÇLER: Bu ileriye yönelik, gözlemsel çalışmaya, doğum yaşı ≤32 hafta olan prematüre bebekler alındı. Bebeklerin yaşamların 1, 3, 7, 21 ve 28. günlerinde serum IGF-1 düzeyleri ölçüldü. Neonatal morbiditeler açısından izlemleri yapıldı.
BULGULAR: Çalışmaya toplam 93 bebek alındı. Bebeklerin ortalama doğum ağırlığı 1236,11±354,06 gr, ortalama doğum yaşları 29,43±2,10 hafta idi. BPD ve PR gelişen bebeklerin serum IGF-1 değerleri, gelişmeyenlere göre anlamlı olarak düşük saptandı. İVK ve NEK gelişen hastalarda ise IGF-1 düzeyleri açısından gelişmeyenlere göre anlamlı fark saptanmadı.
TARTIŞMA ve SONUÇ: Prematüre bebeklerde BPD ve PR gelişimi ile ilk 4 haftadaki düşük IGF-1 düzeyleri arasında belirgin ilişki mevcuttur.

References

  • 1. Netchine I, Azzi S, Le Bouc Y, Savage MO. IGF1 molecular anomalies demonstrate its critical role in fetal, postnatal growth and brain development. Best Pract Res Clin Endocrinol Metab 2011;25:181-90.
  • 2. Ley D, Hansen-Pupp I, Niklasson A, Domellöf M, Friberg LE, Borg J, et al. Longitudinal infusion of a complex of insulin-like growth factor-I and IGF-binding protein-3 in five preterm infants: pharmacokinetics and short-term safety. Pediatr Res 2013;73:68–74.
  • 3. Hansen-Pupp I, Hövel H, Löfqvist C, Hellström-Westas L, Fellman V, Hüppi PS, et al. Circulatory insulin-like growth factor-I and brain volumes in relation to neurodevelopmental outcome in very preterm infants. Pediatr Res 2013;74:564–9.
  • 4. Löfqvist C, Hellgren G, Niklasson A, Engström E, Ley D, Hansen-Pupp I. Low postnatal serum IGF-I levels are associated with bronchopulmonary dysplasia (BPD). ActaPaediatr 2012;101:1211–6.
  • 5. Hansen-Pupp I, Hövel H, Hellström A, Hellström-Westas L, Löfqvist C, Larsson EM, et al. Postnatal decrease in circulating insulin-like growth factor-I and low brain volumes in very preterm infants. J Clin Endocrinol Metab 2011;96:1129–35.
  • 6.Academy A, Ophthalmology P. Screening examination of premature infants for retinopathy of prematurity. Pediatrics 2013;131:189–95.
  • 7. Jobe AH, Bancalari E. Bronchopulmonary Dysplasia. Am J RespirCrit Care Med 2001;163:1723–9.
  • 8.Stoll BJ, Hansen NI, Bell EF, Shankaran S, Laptook AR, Walsh MC, et al. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics 2010;126:443–56.
  • 9. Capoluongo E, Ameglio F, Zuppi C. Insulin-like growth factor-I and complications of prematurity: a focus on bronchopulmonary dysplasia. Clin Chem Lab Med 2008;46:1061–6.
  • 10. Hellström A, Engström E, Hard AL, Albertsson-Wikland K, Carlsson B, Niklasson A, et al. Postnatal Serum Insulin-Like Growth Factor I Deficiency Is Associated With Retinopathy of Prematurity and Other Complications of Premature Birth. Pediatrics 2003;112:1016–20.
  • 11. Chung JK, Hallberg B, Hansen-Pupp I, Graham MA, Fetterly G, Sharma J, et al. Development and verification of a pharmacokinetic model to optimize physiologic replacement of rhIGF-1/rhIGFBP-3 in preterm infants. Pediatr Res 2017;81:504–10.
  • 12. Stahl A, Connor KM, Sapieha P, Chen J, Dennison RJ, Krah NM, et al. The mouse retina as an angiogenesis model. Invest Ophthalmol Vis Sci 2010;51:2813–26.
  • 13. Hellstrom A, Perruzzi C, Ju M, Engstrom E, Hard AL, Liu JL, et al. Low IGF-I suppresses VEGF-survival signaling in retinal endothelial cells: Direct correlation with clinical retinopathy of prematurity. Proc Natl Acad Sci 2001;98:5804–8.
  • 14. Hawkes CP, Grimberg A. Insulin-Like Growth Factor-I is a Marker for the Nutritional State. Pediatr Endocrinol Rev 2015;13:499–511.
  • 15.Hansen-Pupp I, Löfqvist C, Polberger S, Niklasson A, Fellman V, Hellström A, et al. Influence of insulin-like growth factor 1 and nutrition during phases of postnatal growth in very preterm infants. Pediatr Res 2011;69:448–53.
  • 16. Pérez-Muñuzuri A, Fernández-Lorenzo J, Couce-Pico M, Blanco-Teijeiro M, Fraga-Bermúdez J. Serum levels of IGF1 are a useful predictor of retinopathy of prematurity. Acta Paediatr 2010;99:519–25.
  • 17. Cheong JL, Hunt RW, Anderson PJ, Howard K, Thompson DK, Wang HX, et al. Head growth in preterm infants: correlation with magnetic resonance imaging and neurodevelopmental outcome. Pediatrics 2008;12:1534-40.
  • 18. Ozen S, Akisu M, Baka M, Yalaz M, Sozmen EY, Berdeli A, et al. Insulin-like growth factor attenuates apoptosis and mucosal damage in hypoxia/reoxygenation-induced intestinal injury. Biol Neonate 2005;87:91–6.
There are 18 citations in total.

Details

Primary Language Turkish
Subjects ​Internal Diseases
Journal Section Araştırma
Authors

Bayram Ali Dorum 0000-0002-2823-8454

Nilgün Köksal This is me

Hilal Özkan This is me

Salih Çağrı Çakır This is me

Cansu Yılmaz This is me

Taner Özgür This is me

Ferah Budak This is me

Publication Date August 2, 2019
Published in Issue Year 2019 Volume: 17 Issue: 2

Cite

APA Dorum, B. A., Köksal, N., Özkan, H., Çakır, S. Ç., et al. (2019). İnsülin Benzeri Büyüme Faktörü-1 ve Premature Morbiditeleri: Bronkopulmoner Displazi, Premature Retinopatisi, İntraventriküler Kanama ve Nekrotizan Enterokolit. Güncel Pediatri, 17(2), 189-199.
AMA Dorum BA, Köksal N, Özkan H, Çakır SÇ, Yılmaz C, Özgür T, Budak F. İnsülin Benzeri Büyüme Faktörü-1 ve Premature Morbiditeleri: Bronkopulmoner Displazi, Premature Retinopatisi, İntraventriküler Kanama ve Nekrotizan Enterokolit. Güncel Pediatri. August 2019;17(2):189-199.
Chicago Dorum, Bayram Ali, Nilgün Köksal, Hilal Özkan, Salih Çağrı Çakır, Cansu Yılmaz, Taner Özgür, and Ferah Budak. “İnsülin Benzeri Büyüme Faktörü-1 Ve Premature Morbiditeleri: Bronkopulmoner Displazi, Premature Retinopatisi, İntraventriküler Kanama Ve Nekrotizan Enterokolit”. Güncel Pediatri 17, no. 2 (August 2019): 189-99.
EndNote Dorum BA, Köksal N, Özkan H, Çakır SÇ, Yılmaz C, Özgür T, Budak F (August 1, 2019) İnsülin Benzeri Büyüme Faktörü-1 ve Premature Morbiditeleri: Bronkopulmoner Displazi, Premature Retinopatisi, İntraventriküler Kanama ve Nekrotizan Enterokolit. Güncel Pediatri 17 2 189–199.
IEEE B. A. Dorum, N. Köksal, H. Özkan, S. Ç. Çakır, C. Yılmaz, T. Özgür, and F. Budak, “İnsülin Benzeri Büyüme Faktörü-1 ve Premature Morbiditeleri: Bronkopulmoner Displazi, Premature Retinopatisi, İntraventriküler Kanama ve Nekrotizan Enterokolit”, Güncel Pediatri, vol. 17, no. 2, pp. 189–199, 2019.
ISNAD Dorum, Bayram Ali et al. “İnsülin Benzeri Büyüme Faktörü-1 Ve Premature Morbiditeleri: Bronkopulmoner Displazi, Premature Retinopatisi, İntraventriküler Kanama Ve Nekrotizan Enterokolit”. Güncel Pediatri 17/2 (August 2019), 189-199.
JAMA Dorum BA, Köksal N, Özkan H, Çakır SÇ, Yılmaz C, Özgür T, Budak F. İnsülin Benzeri Büyüme Faktörü-1 ve Premature Morbiditeleri: Bronkopulmoner Displazi, Premature Retinopatisi, İntraventriküler Kanama ve Nekrotizan Enterokolit. Güncel Pediatri. 2019;17:189–199.
MLA Dorum, Bayram Ali et al. “İnsülin Benzeri Büyüme Faktörü-1 Ve Premature Morbiditeleri: Bronkopulmoner Displazi, Premature Retinopatisi, İntraventriküler Kanama Ve Nekrotizan Enterokolit”. Güncel Pediatri, vol. 17, no. 2, 2019, pp. 189-9.
Vancouver Dorum BA, Köksal N, Özkan H, Çakır SÇ, Yılmaz C, Özgür T, Budak F. İnsülin Benzeri Büyüme Faktörü-1 ve Premature Morbiditeleri: Bronkopulmoner Displazi, Premature Retinopatisi, İntraventriküler Kanama ve Nekrotizan Enterokolit. Güncel Pediatri. 2019;17(2):189-9.