Journal of Perinatology | 2019
Response to Dr. Kumar’s letter
Abstract
We would like to thank Dr. Kumar for his comments about our paper. We agree that the non-blinded trials with subjective binary outcomes are more likely at risk for observer bias. As suggested, we will consider using time to start positive pressure ventilation as a continuous variable in future studies. However, finding a difference of few seconds in an initiation of resuscitation is likely be statistically significant but may be clinically insignificant. Moreover, we did not find any differences in the resuscitation efforts, outcomes of resuscitation, Apgar scores, and short-term outcomes with umbilical cord milking (UCM) suggesting this procedure is safe in depressed neonates. The paper referenced by Dr Kumar regrading a potential harmful effect of excessive volume in asphyxiated myocardium is an opinion in a review article, not a conclusion from a human study [1]. As suggested by Dr. Kumar, a study on effects of UCM in depressed neonates using hemodynamic assessment is important. However, we did not find a difference in the use of inotropes with UCM in our cohort of depressed neonates. Recently, two more human studies have shown that the UCM in depressed infants is not only safe, but may also be beneficial [2, 3]. A study by Katheria et al. has shown that the UCM is safe and may decrease the need for resuscitation in term neonates who had acidosis and were depressed at birth [2]. In a more recent randomized clinical trial from India, Mohan et al. reported that the UCM is safe in preterm neonates who are depressed at birth and required resuscitation [3]. The depressed preterm infants who received UCM had a higher mean arterial pressure at 6 and 24 h of life and a higher hemoglobin and ferritin at 6 weeks [3]. Infants with culture positive early onset sepsis were excluded as this a confounding variable for the short term outcomes. We agree about the ethical dilemma of consent processes for the delivery room intervention trials. Our study was not possible without the waiver of informed consent. Multiple randomized clinical trials have shown the safety of UCM in preterm and term infants [4–7]. We and the Institutional Ethics Committee believed that our study fulfilled the requirements for a waiver of informed consent [Combined Federal Regulation, Department of Health and Human Services for the protection of Human Subjects, USA, 45 CFR 46.116 (d)]. The research involved was no more than minimal risk, and the waiver did not adversely affect the rights and welfare of the subjects. The research could not have been practicably carried out without the waiver as we cannot determine which infant will be depressed at birth, and the informed consent was obtained immediately after birth. The sentence “UCM is a novel therapeutic option for infants who are likely to develop mild, moderate, or severe HIE” was not the conclusion of the study. This was a sentence in one paragraph of the discussion section and should be interpreted in context. We agree with Dr. Kumar that our trial succeeds in showing that UCM is feasible in depressed neonates and the results of this trial should be interpreted with caution. We believe that this was also the message and the conclusion of our paper. We suggested a larger clinical trial for long term benefits of UCM in depressed neonates.