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,

With great interest we read the article by Sehgal et al describing the hemodynamics of surfactant administration in the delivery room. The authors found a low RVO, low LVO, low to normal SVC flow and an increasing RVO:LVO ratio in the first 60 minutes after surfactant administration. Surprisingly, SVC flow is responsible for 62% of RVO in the pre-surfactant measurement and up to 79% of LVO at 1 hour after surfactant. This combined with a large duct and exclusive left-to-right shunting would mean there is very little blood flow to the lower body. However, this was not reflected by the arterial pH. The authors provide hemodynamic explanations, but do not discuss methodological issues surrounding Doppler-derived cardiac output measurements. Delivery room hemodynamics are not extensively studied, but some information is available for healthy term newborns. Agata et al. measured 34 healthy term infants at 1 hour of age and found a LVO of 327 /- 66 ml/kg/min, followed by a decrease.1 Walther et al. showed comparable findings in a group of 32 term infants starting at 30 minutes after birth.2 We re-analysed a previously published cohort of preterm infants who were studied during lung recruitment.3 There were 9 infants who were measured within 1 hour after birth immediately after the change to high frequency ventilation. In this group the median (range) RVO and SVC flow was 325 (251-541) and 74 (48-126) ml/kg/min respectively. The ductal diameter was 2.9 (1.7-3.6) mm with total ductal shunting always left-to-right. We suggest that differences in methodology may explain the differences in findings. Detailed information on where LVO and RVO diameters were determined was not provided. The Pa Vmax is suggestive of an expected RVO of 150-300 ml/kg/min 4 so it is possible that a reduced diameter measurement could explain the low RVO and LVO compared to values found using other referenced methodology.5 Further investigations into whether the low-normal SVC flow is caused by the early surfactant administration and if this coincides with low peripheral blood flow will be required to establish the full picture and potential consequences of these observations.

1. Agata Y, Hiraishi S, Oguchi K, Misawa H, Horiguchi Y, Fujino N, Yashiro K, Shimada N. Changes in left ventricular output from fetal to early neonatal life. J Pediatr. 1991;119(3):441-5

2. Walther FJ, Benders MJ, Leighton JO. Early changes in the neonatal circulatory transition. J Pediatr. 1993;123(4):625-32

3. de Waal K, Evans N, van der Lee J, van Kaam A. Effect of lung recruitment on pulmonary, systemic, and ductal blood flow in preterm infants. J Pediatr. 2009;154(5):651-5

4. Evans N. Support of the preterm circulation: keynote address to the Fifth Evidence vs Experience Conference, Chicago, June 2008. J Perinatol. 2009;29 Suppl 2:S50-7

5. Evans N, Kluckow M. Early determinants of right and left ventricular output in ventilated preterm infants. Arch Dis Child Fetal Neonatal Ed. 1996;74(2):F88-94

Conflict of Interest:

None declared

The case report by R. Negrine and colleagues(1) is of considerable interest. However, testicular trauma following breech delivery is not extremely rare as they suggest. In 1975 I reported 11 cases of scrotal bruising and significant testicular enlargement among 114 consecutively breech-born male infants over a two year period(2). Those affected tended to be large, first-born, singleton and term or post-term infants. One infant with particularly severe damage was found to have soft and hypoplastic testicles at the age of 10 years. It is therefore not improbable that the damage at birth may be another cause of the vanishing testicle and for sterility or gonadal dysfunction. It would be of interest to study the prior incidence of breech delivery in a large series of sterile adult males.

Correspondence to: Professor Peter M. Dunn University of Bristol, Southmead Hospital, Bristol, BS10 5NB p.m.dunn@bristol.ac.uk

References

1. Negrine, R., Easter, W., Fraser, I. and Ellis, S. Neonatal testicular trauma: scrotal rupture. Arch. Dis. Child. Fetal Neonatal Ed., 2010; 95, F.193.

2. Dunn, P.M. Testicular birth trauma. Arch. Dis. Child., 1975; 50, 743.

Conflict of Interest:

None declared

Dear Editor,

It was with great interest that we read the article by Choong et al. - Remifentanil for endotracheal intubation in neonates: a randomised controlled trial. First of all, we would like to congratulate the authors for their relevant RCT. However, there are some aspects that should be pointed out. The premedication protocol for endotracheal intubation of this study includes many classes of drugs besides opioids that might interfere with physiological responses. For instance, the administration of succinylcoline (a short action muscle relaxant) might have biased the results. Indeed, premedication with succinylcoline could be able to influence the evaluation of intubation conditions by intubators. Since both groups received atropine, the pharmacodynamic responses were probably more influenced by this drug than by the opioids themselves. It should have been more appropriate if the comparison had included only the opioids (remifentanil versus fentanyl). Another issue is the evaluation of intubation conditions per se. The use of subjective impression of intubation rather than specific and validated scores1 seems to be not the ideal approach. In addition, the enrollment of six different intubators instead of just one2 could also have influenced this evaluation. The authors did not show any sample size calculation to support one of the outcomes (adverse events) and also one of the main conclusions of this trial. Even though, no differences in adverse events were detected in the comparison between groups. However, the study suggested that remifentanil was more frequently responsible for chest wall rigidity. To date, synthetic opioid administration as a cause of chest wall rigidity in adults has been recently questioned3. The general idea is that the opioids produce transient vocal cord closure rather than chest wall rigidity and this phenomenon could also happen with neonates. In this regard, succinylcoline administration might again avoid this adverse event in the group treated with fentanyl.4 Finally, the experience with remifentanil in neonates is not large enough and the RCTs with this opioid are very important. Indeed, the American Academy of Pediatrics has recently recommended the use of remifentanil as a possible premedication for neonatal endotracheal intubation.5,6 However, further properly designed and larger clinical trials are needed before any conclusion concerning the best opioid recommended for neonatal intubation.

Yerkes Pereira e Silva, MD, PhD; Juliana Marcatto, RN; Rosilu Barbosa, MD, MSc; Ana Cristina Simoes e Silva, MD, PhD

1- Viby-Mogensen J, Engbaek J, Eriksson LI et al. Good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents. Acta Anaesthesiol Scand 1996;40:59-74.

2- E Silva Y, Gomez R, de Oliveira Marcatto J, et al. Morphine versus remifentanil for intubating preterm neonates. Arch Dis Child Fetal Neonatal Ed 2007;18:176-83.

3- Bennett JA, Abrams JT, Van Riper DF, et al. Difficult or impossible ventilation after sufentanil-induced anesthesia is caused primarily by vocal cord closure. Anesthesiology 1997;87:1070-1074.

4- Fahnenstich H, Steffan J, Kau N et al. Fentanyl induced chest wall rigidity and laryngospasm in preterm and term infants. Crit Care Med, 2000;28:836-839.

5- Kumar P, Denson, SE, Mancuso TJ and Committee of Fetus and Newborn, Section on Anesthesiology and Pain Medicine. Pediatrics 2010;125;608-615.

6- Greenwood CS, Colby CE. Pharmacology Review: Premedication for endotracheal intubation of the neonate: What is the evidence? NeoReviews 2009;10:e31-e35

Conflict of Interest:

None declared