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An international replication, and the need for long term follow up studies
  1. Z Vekerdy1,
  2. L Lakatos2,
  3. G Balla3,
  4. G Oroszlan4
  1. 1National Institute for Medical Rehabilitation, Department of Children’s Rehabilitation, Budapest, Hungary
  2. 2Kenezy County Hospital, Debrecen, Bartók, Hungary
  3. 3NICU, University Medical School, Debrecen, Hungary
  4. 4Markusovszky County Hospital, Szombathely, Hungary
  1. Correspondence to:
    Professor Lakatos
    Kenezy County Hospital, Debrecen, Bartók B.u. 2-26., H-4043; lakatosl{at}

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In 1999, a provocative letter was published in your journal1 concerning the use of d-penicillamine (DPA) in the neonatal period. The following statement was written: “Why, then, we wonder, has the demonstration of an effective mode of prevention of retinopathy of prematurity (ROP) in two randomised trials conducted more than 10 years ago in Hungary,2 failed to encourage others to undertake the independent replications needed to verify or refute such a promising approach?”

Now, we (the authors of this article2) greatly appreciate a pilot trial conducted by Christensen et al which has been published in the Journal of Perinatology.3 This work can be considered as the first international replication of our observation and clinical trials.

Christensen et al3 recognised no immediate intolerance of the prepared solution of penicillamine given by nasogastric tube, nor did they observe any evidence of renal, haematological, or hepatic toxicity in five patients approved by the FDA. The authors emphasise that long term adverse effects of DPA administration to preterm babies are possible and they suggest that trials testing enteral 3-mercapto-d-valine (DPA) as a means of reducing ROP should go forward.

We quite agree with this viewpoint and, on the basis of our previous favourable experiences, would like to encourage other neonatal intensive care units to use DPA for the prevention of ROP. Our results suggest that DPA administration in very low birthweight infants has no serious adverse effects during the neonatal period, nor during the short term4 and long term (10–11 years)5 follow up.

Most existing follow up studies have been criticised for the small numbers of infants followed, the short duration of follow up, inconsistencies in reporting and defining disabilities, the absence of control groups, and the number of children who are “lost to follow up”.6 That is why we have decided to conduct a long term follow up study extending over thousands of adults (25–33 years of age) who were treated with DPA around their birth. This may be an enormously difficult task, and we are counting on international support from countries belonging to the European Union.

Finally, we owe a debt of gratitude to the editorial board of Arch Dis Child Fetal Neonatal Ed who contributed to making the publication1 have such a successful effect.


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  • Competing interests: None declared.

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