Published online August 1, 2005
PEDIATRICS Vol. 116 No. 2 August 2005, pp. 516 (doi:10.1542/10.1542/peds.2005-0887)

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Risk Factors for Severe Retinopathy of Prematurity Among Very Preterm Infants: A Unit-Based or Population-Based Approach?

Paolo Manzoni, MD
Daniele Farina, MD
MariaLisa Leonessa, MD
Giovanna Gomirato
Neonatology and Hospital NICU

Riccardo Arisio, MD
Department of Pathology
Azienda Ospedaliera OIRM–Sant’Anna
S. Anna Hospital
10136 Turin, Italy

To the Editor.—

In the interesting article by Darlow et al,1 the authors correctly remark that, although many factors (including prenatal factors) have been suggested to have some causal association with retinopathy of prematurity (ROP), most studies have been unit based or from hospital groupings, rather than being population based, and may have introduced bias into the results. These limits in the available studies may explain the fact that the same prenatal variables are reported as associated to an increased risk of ROP by some single-center, cohort studies and as not associated or even protective in others (eg, the use of antenatal steroids [no association according to refs 2–4; an association with a protective effect based on refs 5 and 6] or the maternal history of preeclampsia [no association according to ref 7; an association with a protective effect based on ref 5]).

Nevertheless, the data from population-based studies such as that by Darlow et al, although methodologically correct and exhaustively clarifying which are the major factors clearly associated with severe ROP, may not be of great help to the neonatologist at a single NICU who has to address the parents’ fears about their preterm infant’s real risk for ROP. Knowing that the younger and the smaller the infant, the greater the risk, might be not enough; an informed parent could reply that this is not any news for him or her. If we want to try quantifying the real risk for the infant to whom we are attending, we must be aware of the current situation of the risk for ROP in our unit or units similar to ours to provide more pertinent information to the parents about their infant’s visual outcome.

This is why the factors that have been found associated with ROP (or, on the contrary, protective) in single-center studies, although probably related to the variability that exists between centers and between different geographic areas, must be taken in consideration and carefully verified in every NICU.

In our third-level unit, located in a high-income Northern Italy urban area and attending >4000 mean births per year, we have been maintaining a detailed database that stores demographic, maternal, clinical, laboratory, and microbiologic data of all infants with a birth weight of <1500 g admitted in the last 8 years (n = 645). We assessed with univariate analysis, and subsequently controlled with multivariate logistic regression, the significance of the risk factors for ROP listed in the literature, both the major ones (prematurity, oxygen use, male gender, and white race) and those occasionally described as associated in studies from single NICUs.

We found that in our unit, vaginal delivery is an independent predictor of severe (requiring urgent ablative surgery) threshold ROP in infants with a birth weight of <1000 g but not in those of >1000 g. Threshold ROP occurred in 40.9% (27 of 66) of the extremely low birth weight infants delivered vaginally and in 17.5% (19 of 108) of those delivered by caesarian section (relative risk: 3.35; 95% confidence interval: 1.230–4.855; P = .008 [univariate analysis] and P = .04 [multivariate logistic regression]). Vaginal delivery was not significantly associated with other major sequelae (intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis).

Possible explanations include a higher frequency, in the caesarian-section group, of mothers affected by preeclampsia and/or undergoing antenatal steroid treatment, although the differences in these 2 variables, if considered separately, were not significant. Whatever may be the reason(s) for these findings, we must keep them in mind when we admit a preterm extremely low birth weight infant and begin giving information to his or her parents, because these data are an expression of the "adjusted" risk for ROP for this infant in our unit.

The prevention of ROP may be achieved by maintaining a focus on research and also in clinical practice. Based on our experience, we greatly benefit from careful consideration of data from large units (such as single-center studies similar to ours) as much as from population-based studies. Increased availability of both types of information should be encouraged for its impact on the daily clinical practice and for better focusing our attention on the infants with a higher risk for ROP in different NICUs.

REFERENCES

1. Darlow B, Hutchinson JL, Henderson-Smart DJ, et al. Prenatal risk factors for severe retinopathy of prematurity among very preterm infants of the Australian and New Zealand Neonatal Network. Pediatrics. 2005;115 :990 –996[Abstract/Free Full Text]
2. Smith LM, Qureshi N, Chao CR. Effects of single and multiple courses of antenatal glucocorticoids in preterm newborns less than 30 weeks’ gestation. J Matern Fetal Med. 2000;9 :131 –135[CrossRef][Medline]
3. Haroon Parupia MF, Dhanireddy R. Association of postnatal dexamethasone use and fungal sepsis in the development of severe retinopathy of prematurity and progression to laser therapy in extremely low-birth-weight infants. J Perinatol. 2001;21 :242 –247[CrossRef][Medline]
4. Garg R, Agthe AG, Donohue PK, Lehmann CU. Hyperglycemia and retinopathy of prematurity in very low birth weight infants. J Perinatol. 2003;23 :186 –194[Medline]
5. Seiberth V, Linderkamp O. Risk factors in retinopathy of prematurity: a multivariate statistical analysis. Ophthalmologica. 2000;214 :131 –135[CrossRef][Web of Science][Medline]
6. Higgins RD, Mendelsohm AL, DeFeo MJ, Ucsel R, Hendricks-Munoz KD. Antenatal dexamethasone and decreased severity of retinopathy of prematurity. Arch Ophthalmol. 1998;116 :601 –605[Abstract/Free Full Text]
7. Mittal M, Dhanireddy R, Higgins RD. Candida sepsis and association with retinopathy of prematurity. Pediatrics. 1998;101 :654 –657[Abstract/Free Full Text]

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PEDIATRICS (ISSN 1098-4275). ©2005 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 Web of Science 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 Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Manzoni, P. Articles by Arisio, R. Search for Related Content PubMed PubMed Citation Articles by Manzoni, P. Articles by Arisio, R. Related Collections Office Practice Related AAP Red Book topics: Yersinia enterocolitica and... Social Bookmarking                         What's this?