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In Response to Letter from Altit, Basso, Grandi, and Yang

Journal of Perinatology volume 38, page 768 (2018)Cite this article

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We appreciate the interest in our article on prophylactic indomethacin use in extremely preterm infants referred to a Level IV NICU in a Children’s Hospital from Altit and colleagues. They bring up several issues related to bias in our study and in fact we agree with their concerns. Indeed, we acknowledged these concerns in the limitations section of the paper. Our study was a well-designed observational study [1], and we are aware that bias exists in every type of study, including randomized controlled trials (RCTs). While observational studies have an important role in advancing medical care, a causal relationship cannot be elicited purely from these studies, even those with large sample sizes [1, 2]. We completely agree that our study, despite being a well-designed observational study with a relatively large treatment effect, shares all of the limitations of any observational study and therefore should not, by itself, trigger changes in practice [1, 2]. Our conclusion in the article was that “our findings strongly support the need for a large RCT exploring the effect of prophylactic indomethacin on outcomes of extremely preterm infants to provide definitive evidence for or against the use of prophylactic indomethacin in extremely preterm infants.”

Practitioners base their decision to use or not to use prophylactic indomethacin on landmark studies from the 1990s in babies born at later gestation than in our study. For example, the study by Ment et al. [3] enrolled patients with mean gestational age of 28 weeks, and the study by Schmidt et al. [4] enrolled patients with a mean gestational age of 26 weeks, while in our cohort the median gestational age was 25 weeks with an intraquartile range of 24–26 weeks. The standard of care for periviable infants has also changed dramatically since the 1990s with improvement in survival and outcomes [5]. Our objective was to take advantage of differences in clinical practice among local providers to examine prophylactic indomethacin use in a contemporary cohort of extremely preterm infants with the notion of determining whether there were still benefits to its use in the 21st century. Thus, we agree that our study, while hypothesis generating, should not be used to change practice. Rather, our study is a clear indication for the need of further well-designed and powered RCTs to examine the effects of prophylactic indomethacin in extremely preterm infants to explore the effects of prophylactic indomethacin on survival and outcomes in babies born at <27 weeks gestation in the 21st century.

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References

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  1. Center for Perinatal Research, Research Institute at Nationwide Children’s Hospital, Small Baby ICU, Nationwide Children’s Hospital, Columbus, OH, 43205, USA

    Timothy D. Nelin, Edward G. Shepherd & Leif D. Nelin

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  1. Timothy D. Nelin
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  2. Edward G. Shepherd
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  3. Leif D. Nelin
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Correspondence to Leif D. Nelin.

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Nelin, T.D., Shepherd, E.G. & Nelin, L.D. In Response to Letter from Altit, Basso, Grandi, and Yang. J Perinatol 38, 768 (2018). https://doi.org/10.1038/s41372-018-0070-6

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