Correspondence

Correction

Inhaled Nitric Oxide in Preterm Infants — Correction

N Engl J Med 2007; 357:1444-1445October 4, 2007

Article

To the Editor:

My coauthors and I wish to correct data reported in our article on inhaled nitric oxide in preterm infants undergoing mechanical ventilation (July 27, 2006).1 During further data review, we found that one infant in the placebo group in whom bronchopulmonary dysplasia developed was incorrectly categorized as surviving without chronic lung disease. Nine additional infants were part of multiple births and thus received by design the same treatment as the earlier enrolled sibling. Because siblings share both genetic and in utero environmental factors related to the occurrence of chronic lung disease, they represent clustered data. Accordingly, we reanalyzed our data by means of the multiple outputation approach used in the original analysis and obtained a P value of 0.03 (relative benefit of nitric oxide in the overall population, 1.26; 95% confidence interval [CI], 1.02 to 1.55) rather than a P value of 0.04 (relative benefit, 1.23; 95% CI, 1.01 to 1.51), as reported in our article (in the Abstract, Table 2, and the third paragraph of the Results section). Analysis by means of the generalized-estimating-equations method,2 which is also used for analysis of clustered data, gives a P value of 0.03 (relative benefit, 1.45; 95% CI, 1.03 to 2.04). In Table 2, the P value for survival among infants with a birth weight of 500 to 799 g should be 0.07 (relative benefit, 1.26; 95% CI, 0.98 to 1.62) rather than 0.14 (relative benefit, 1.20; 95% CI, 0.94 to 1.54). In the first paragraph of the Results section, the last sentence should read, “The 582 remaining infants had been delivered by 538 mothers (44 infants were assigned to a sibling's treatment).” In the third paragraph of the Results section, the first sentence should read, “In the group that was assigned to receive inhaled nitric oxide, 129 of 294 infants survived to 36 weeks of postmenstrual age without bronchopulmonary dysplasia (43.9 percent), as compared with 105 of 288 infants in the placebo group (36.5 percent).” The second sentence of the sixth paragraph of the Results section (related to data reported in Table 5) should read, “We observed a significant interaction between the age at study entry and treatment (P=0.005),” and the sixth sentence should read, “The effect of inhaled nitric oxide did not differ significantly according to race or ethnic group (P=0.06)” rather than “The effect of inhaled nitric oxide appeared to differ according to race or ethnic group (P=0.05).” These and other minor changes to the tables are listed in the Supplementary Appendix, available with the full text of this letter at www.nejm.org.

Roberta A. Ballard, M.D.
University of California at San Francisco, San Francisco, CA 94143
ballardr@peds.ucsf.edu

Since publication of the article, Dr. Ballard reports having received an honorarium and grant support from IKARIA/Inotherapeutics. No other potential conflict of interest relevant to this letter was reported.

2 References

1. 1

   Ballard RA, Truog WE, Cnaan A, et al. Inhaled nitric oxide in preterm infants undergoing mechanical ventilation. N Engl J Med 2006;355:343-353
   Full Text | Web of Science | Medline

2. 2

   Liang K-Y, Zeger SL. Longitudinal data analysis using generalized linear models. Biometrika 1986;73:13-22
   CrossRef | Web of Science

Citing Articles (6)

Citing Articles

1. 1

   Roberta L. Keller, Roberta A. Ballard. 2012. Bronchopulmonary Dysplasia. , 658-671.
   CrossRef

2. 2

   Susan W. Aucott. (2011) Bronchopulmonary Dysplasia: Development and Progression in the Neonatal Intensive Care Unit. Pediatric Allergy, Immunology, and Pulmonology 24:2, 113-118
   CrossRef

3. 3

   R H Clark, R L Ursprung, M W Walker, D L Ellsbury, A R Spitzer. (2010) The changing pattern of inhaled nitric oxide use in the neonatal intensive care unit. Journal of Perinatology 30:12, 800-804
   CrossRef

4. 4

   M A Posencheg, A J Gow, W E Truog, R A Ballard, A Cnaan, S G Golombek, P L Ballard. (2010) Inhaled nitric oxide in premature infants: effect on tracheal aspirate and plasma nitric oxide metabolites. Journal of Perinatology 30:4, 275-280
   CrossRef

5. 5

   Michele C. Walsh, Anna Maria Hibbs, Camilia R. Martin, Avital Cnaan, Roberta L. Keller, Eric Vittinghoff, Richard J. Martin, William E. Truog, Philip L. Ballard, Arlene Zadell, Sandra R. Wadlinger, Christine E. Coburn, Roberta A. Ballard. (2010) Two-Year Neurodevelopmental Outcomes of Ventilated Preterm Infants Treated with Inhaled Nitric Oxide. The Journal of Pediatrics 156:4, 556-561.e1
   CrossRef

6. 6

   Anna Maria Hibbs, Dennis Black, Lisa Palermo, Avital Cnaan, Xianqun Luan, William E. Truog, Michele C. Walsh, Roberta A. Ballard. (2010) Accounting for Multiple Births in Neonatal and Perinatal Trials: Systematic Review and Case Study. The Journal of Pediatrics 156:2, 202-208
   CrossRef