Dear Editor,

In their retrospective observational study of 1960 preterm infants over a 7-year period, Aralikatti et al reported an increased risk of developing threshold retinopathy of prematurity (ROP) in Asian and black infants compared to white infants [1]. The proportion of small for gestational age (SGA), by standard growth charts, was also higher in Asian (36.19%) than in white (29.45%) and black infants (27.81%) and the authors speculated that this might explain the increased risk of ROP in Asian infants. They also adjusted for birthweight and gestational age through logistic regression analysis and reported that the results still supported the increased risk of ROP in non-white infants.

SGA, as defined by standard growth standards, is a known risk factor for ROP in the preterm infant [2-5]. When looking for an association between ethnicity and the risk of ROP in a logistic regression model which adjusts for birthweight and gestational age, the model calculates the odds ratio of ROP for each ethnicity by adjusting separately for each unit increment in birthweight and for each unit increment in gestational age, while maintaining the other factor constant. The classification of each infant as SGA or AGA is totally ignored in the model used, as the birthweight and the gestational age of each infant are separately taken into account, without any indication whether each infant's birthweight is appropriate for his/her gestational age or not. We believe that this deficiency in the model they used prevented the authors from reliably studying whether the relationship they found between ethnicity and the risk of ROP was not confounded by growth retardation.

Furthermore, the observed ethnic differences in foetal growth are often physiologic rather than pathologic [6]. Customised birth weight percentiles, by adjusting for the variables found to be associated with normal variation in birth weight, such as maternal height, weight, parity, ethnic origin and the baby's gender, better distinguish growth-restricted from constitutionally small but healthy neonates and have been proven to be superior to standard growth charts in detecting foetal and neonatal complications associated with poor foetal growth [7-8]. Using these customised birth weight percentiles [9], we found that, regardless of gestational age, SGA infants identified exclusively by the customised method, and therefore missed by the standard growth charts, accounted for 50% of all infants diagnosed with ROP in a cohort of 6125 neonates. We also found that, after adjusting for prematurity, SGA infants exclusively identified by the customised method, still had a higher risk of complications, including an increased risk for all grades of ROP, confirming previous reports that morbidities associated with preterm delivery, including ROP [2-5], are compounded by foetal growth restriction [10].

We therefore believe that adding a classification of birthweight as SGA (or not) in their regression model, even using the standard growth charts, was needed, and would have allowed the authors to reliably confirm if the role of ethnicity in the risk of ROP is not confounded by SGA. Better still, using the customised growth percentiles instead of standard growth charts to classify infants' growth in their model would have been more appropriate, as maternal ethnicity is already integrated in the customised classification of the infant's birth weight.

Hassib Narchi, Alyson Skinner

References

1. Aralikatti AKV, Mitr A, Denniston AKO, Haque MS, Ewer AK, Butler L. Is ethnicity a risk factor for severe retinopathy of prematurity? Arch Dis Child Fetal Neonatal Ed 2010;95:F174-F176.

2. Zaw W, Gagnon R, da Silva O. The risks of adverse neonatal outcome among preterm small for gestational age infants according to neonatal versus fetal growth standards. Pediatrics 2003;111 (Part 1):1273-1277.

3. 26. Slidsborg C, Olesen HB, Jensen PK, Jensen H, Nissen KR, Greisen G, Rasmussen S, Fledelius HC, la CM. Treatment for retinopathy of prematurity in Denmark in a ten-year period (1996-2005): is the incidence increasing? Pediatrics 2008; 121:97-105.

4. Allegaert K, Vanhole C, Casteels I, Naulaers G, Debeer A, Cossey V, Devlieger H. Perinatal growth characteristics and associated risk of developing threshold retinopathy of prematurity. J AAPOS 2003;7:34-37.

5. Regev RH, Lusky A, Dolfin T, Litmanovitz I, Arnon S, Reichman B. Excess mortality and morbidity among smallfor- gestational-age premature infants: a population-based study. J Pediatr 2003;143:186-191.

6. Kierans WJ, Joseph KS, Luo ZC, Platt R, Wilkins R, Kramer MS. Does one size fit all? The case for ethnic-specific standards of fetal growth. BMC Pregnancy Childbirth 2008;8:1.

7. Gardosi J. New definition of small for gestational age based on fetal growth potential. Horm Res 2006;65 (Suppl 3):15-18.

8. Reddy UM. Prediction and prevention of recurrent stillbirth. Obstet Gynecol 2007;110:1151-1164

9. Narchi H, Skinner A, Williams B. Small for gestational age neonates- are we missing some by only using standard population growth standards and does it matter? J Matern Fetal Neonatal Med. 2009; 29:1-7.

10. Pallotto EK, Kilbride HW. Perinatal outcome and later implications of intrauterine growth restriction. Clin Obstet Gynecol 2006;49:257-269

Conflict of Interest:

None declared

Dear editor, We read with great interest the recent article by Aralikatti et al.1 The authors conducted a well designed study regarding the effect of ethnicity on developing severe retinopathy of prematurity (ROP). They concluded that asians and black infants have a higher risk of developing threshold ROP compared to white infants. Although ethinicity might be a risk factor, we think that it can hardly be considered as an independent factor. To our knowledge2,3 lower socio-economical status of the black and Asian race in most areas of the world might be the main contributing factor for the increase in severe retinopathy of prematurity incidence requiring treatment. The lower socio-economical status means lower educational level and less reliability on the data collected from the parents with respect to correct gestational age, maternal smoking and nutrition, infant nutrition. The infants born in developing countries carry greater risk of acquiring infectious, inherited and malnutrition diseases. It is well known that these all are risk factors for ROP. In our study a screening was performed on neonates born between 32 and 35 weeks gestation and referred for ROP screening between 1 January 2004 and 31 December 2008. Our unpublished data suggested that, in developing countries attention must be paid to increase awareness among neonatologists and widely used screening criteria for ROP must be revised to decrease the risk of blindness due to ROP in larger babies as it can be treatable to a great extent. From this point of view, some different aspects should be stressed. We think that though ethnicity may be an independent risk factor for developing severe ROP, concomitant attributes of the infants of the black and asian race are the main underlying factors for greater risk for severe ROP.

References 1. Aralikatti AK, Mitra A, Denniston AK et al. Is ethnicity a risk factor for severe retinopathy of prematurity? Arch Dis Child Fetal Neonatal Ed. 2009 Nov 29. (Epub) 2. Silva AM, de Almeida MF, Matsuo T, Soares DA. Risk factors for pre-term birth in Londrina, Parana State, Brazil. Cad Saude Publica. 2009; 25: 2125 -38. 3. Maida JM, Mathers K, Alley CL. Pediatric ophthalmology in the developing world. Curr Opin Ophthalmol 2008; 19(5):403-8.

Conflict of Interest:

None declared