The Journal of Pediatrics
Volume 155, Issue 5 , Page 763, November 2009

Indomethacin and retinopathy of prematurity

Department of Pediatrics, Christchurch School of Medicine, University of Otago, Christchurch, Christchurch, New Zealand

Article Outline

 

To the Editor:

Jegatheesan et al,1 in a randomized, controlled trial of higher or lower doses of indomethacin for treatment of a patent ductus arteriosus (PDA) in infants <28 weeks gestation, reported that higher doses were associated with increased risk of moderate or severe retinopathy of prematurity (ROP). I agree with Hammerman,2 who has suggested that the timing of the indomethacin dose might be crucial, with doses given in the early vasoconstrictive phase of ROP being more likely to be detrimental.

In 1986, we carried out a prospective audit of all very low birthweight (birthweight <1500g) infants born in New Zealand and admitted to a neonatal intensive care unit with the aim of ensuring all infants were examined appropriately for acute ROP.3, 4 Sixty-nine of 321 infants (21.5%) examined had acute ROP. With multiple logistic regression analysis, 3 variables were significantly associated with risk of ROP, gestational age (P < .0001), the hospital caring for the infant (P < .01), and treatment with indomethacin (P < .01). These variables remained significant after further adjustment for timing of eye examination.4

In this New Zealand study, the median time of treatment was 6 days of age. Indomethacin was typically given by rapid injection for 15 to 30 seconds. Such injections lead to a sustained reduction in cerebral arterial blood flow velocity,5 and decreased cerebral blood flow might also occur with a slow infusion.6 Recently, Laughon et al7 reported from a large dataset and suggested that treatment of a PDA with indomethacin versus no treatment was associated with decreased mortality but increased severe ROP. Noting great variation in when and how to treat a PDA, they have called for a randomized controlled trial.7 Providing attention is paid to the timing of treatment, ROP will be an important outcome in any such trial.

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References 

  1. Jegatheesan P, Ianus V, Buchh B, Yoon G, Chorne N, Esing A, et al. Increased indomethacin dosing for persistent patent ductus arteriosus in preterm infants: a multicenter, randomized, controlled trial. J Pediatr. 2008;153:183–189
  2. Hammerman C. Indomethacin and retinopathy of prematurity: the hidden paradox. J Pediatr. 2008;153:587–588
  3. Darlow BA. Incidence of retinopathy of prematurity in New Zealand. Arch Dis Child. 1988;63:1083–1086
  4. Darlow BA, Horwood LJ, Clemett RS. Retinopathy of prematurity: risk factors in a prospective population-based study. Paediatr Perinat Epidemiol. 1992;6:62–80
  5. Van Bel F, Van de Bor M, Stijnen T, Baan J, Ruys JH. Cerebral blood flow velocity changes after a single dose of indomethacin: duration of its effects. Pediatrics. 1989;84:802–807
  6. Edwards AD, Wyatt JS, Richardson C, Potter A, Cope M, Delpy DT, et al. Effects of indomethacin on cerebral haemodynamics in very preterm infants. Lancet. 1990;335:1491–1495
  7. Laughon M, Bose C, Clark R. Treatment strategies to prevent or close a patent ductus arteriosus in preterm infants and outcome. J Perinatol. 2007;27:164–170

PII: S0022-3476(09)00544-7

doi:10.1016/j.jpeds.2009.05.038

The Journal of Pediatrics
Volume 155, Issue 5 , Page 763, November 2009

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