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PEDIATRICS Vol. 114 No. 2 August 2004, pp. 491

COMMENTARY

Can We Restore Aspects of the In Utero Environment in Premature Infants to Prevent Disease?

Lois E.H. Smith, MD, PhD

Department of Ophthalmology,
Children’s Hospital,
Harvard Medical School,
Boston, MA 02115

Abbreviations: IGF-1, insulin-like growth factor 1 • ROP, retinopathy of prematurity

The complications of premature birth result from fundamental differences between the in utero and the postbirth environments, some known and most unknown. An increase in oxygen after birth has been a prime focus of interest, but loss of factors normally found in utero may also play a pivotal role. In the study "Postnatal serum insulin-like growth factor I deficiency is associated with retinopathy of prematurity and other complications of premature birth,"¹ we examined the hypothesis that lower insulin-like growth factor 1 (IGF-1) levels after preterm birth are associated with retinopathy of prematurity (ROP). This hypothesis arose from our previous studies in mice and humans showing that IGF-1 deficiency results in abnormal retinal blood vessel development^2–5 (as well as poor development of brain and other tissue). Loss of normal blood vessel growth precipitates ROP. If it were possible to allow blood vessels to grow normally in all premature infants, as they do in utero, then the second damaging neovascular phase of ROP would not occur. We found that low IGF-1 is associated with ROP and with other complications of prematurity. This study does not prove causality, and it may be that low serum IGF-1 levels reflect delayed maturation, illness, or poor nutrition and that other mediators may be central to delayed development of vessels. However, early short-term elevation to in utero levels of IGF-1 may allow faster maturation of the liver and other organs, which will then produce the necessary complement of factors necessary for growth and development, an upward spiral effect. Appropriate nutrition may be a relatively simple way to accomplish this goal because increased protein intake in particular increases IGF-1 levels in premature infants. We hope to encourage a new look at prematurity and ROP in terms of specific deficiencies and restoration to normal levels.

	FOOTNOTES

 
Received for publication Jan 5, 2004; Accepted Feb 2, 2004.

Reprint requests to (L.E.H.S.) Department of Ophthalmology, Children’s Hospital, Harvard Medical School, 300 Longwood Ave, Boston MA 02115. E-mail: lois.smith{at}tch.harvard.edu

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2. Smith LE, Shen W, Perruzzi C, et al. Regulation of vascular endothelial growth factor-dependent retinal neovascularization by insulin-like growth factor-1 receptor. Nat Med.1999; 5 :1390 –1395[CrossRef][Web of Science][Medline]
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4. Hellstrom A, Perruzzi C, Ju M, et al. Low IGF-I suppresses VEGF-survival signaling in retinal endothelial cells: direct correlation with clinical retinopathy of prematurity. Proc Natl Acad Sci U S A.2001; 98 :5804 –5808[Abstract/Free Full Text]
5. Hellstrom A, Carlsson B, Niklasson A, et al. IGF-I is critical for normal vascularization of the human retina. J Clin Endocrinol Metab.2002; 87 :3413 –3416[Abstract/Free Full Text]

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PEDIATRICS (ISSN 1098-4275). ©2004 by the American Academy of Pediatrics

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This Article Extract Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Smith, L. E.H. Search for Related Content PubMed PubMed Citation Articles by Smith, L. E.H. Related Collections Premature & Newborn Social Bookmarking                         What's this?