In developed countries, where omphalitis has become rare and related mortality nil, benefits of antiseptic use in umbilical cord care have not been demonstrated. We aimed to assess the noninferiority of dry care compared with antiseptics in France where antiseptic use is widespread.
We conducted a noninferiority, cluster-randomized, 2-period crossover trial, in 6 French university maternity units including all infants born after 36 weeks’ gestation. Maternity units were randomly assigned to provide either their usual antiseptic care or a dry care umbilical cord method for a 4-month period, and then units switched to the alternate cord cleansing method for a 4-month period. The primary outcome was neonatal omphalitis, adjudicated by an independent blinded committee based on all available photographs, clinical, and bacteriological data. We used a noninferiority margin of 0.4%. Analysis was performed per protocol and by intention to treat.
Among 8698 participants, omphalitis occurred in 3 of 4293 (0.07%) newborns in the dry care group and in none of the 4404 newborns in the antiseptic care group (crude difference: 0.07; 95% confidence interval: –0.03 to 0.21). Late neonatal infection, parental appreciation of difficulty in care, and time to separation of the cord were not significantly different between the 2 groups.
Dry cord was noninferior to the use of antiseptics in preventing omphalitis in full-term newborns in a developed country. Antiseptic use in umbilical cord care is therefore unnecessary, constraining, and expensive in high-income countries and may be replaced by dry care.
Comments
RE: respons to Drs Klinger and Zayek
To the Editor,
We read with great attention the comment by Drs Klinger and Zayek about our article (1). Interestingly, this question seems relevant in several developed countries. We propose the following clarifications:
First, even if the two Canadian trials found a combined incidence of infection of 0.08% following dry cord care (DCC), Kapellen et al. reported a higher incidence of omphalitis in Germany: 2.1% (7/332 neonates) (2). As recommended by the EMA guidelines on non-inferiority trials, we chose the non-inferiority margin based on a combination of clinical and statistical judgment. The choice of the non-inferiority margin was mostly based on the clinical impression of our team that 0.4% would be an acceptable risk for newborns considering the advantages of DCC compared to antiseptics (3).
Second, our study was planned as a cluster randomized trial. Therefore, stratifying variables (in case one would have decided to use some form of stratification) would have been cluster-level variables, and we may assume there is no evident cluster-level risk factor variables. Moreover, the trial was planned as a cross-over trial. Such a design feature contributes to a better group balance, especially when the number of clusters is small.
Third, the parental concern explaining the higher clinic visit rates for umbilical symptoms in the dry care group was obviously associated with the anxiety generated by this study and the subsequent stress caused by a change to a long-standing traditional practice for both families and caregivers. However, the parental satisfaction was not different in the DCC versus the ATS group (Table 3), and no complaints were reported about exudates or a foul smell. Today, we have generalized DCC use in in our birth center; the initial apprehension of families has disappeared with a rapid return to a usual consultation rate.
Fourth, in the publication by Mullany et al., we agree that the incidence rate ratio of severe omphalitis was 0.25% [95% CI 0·12−0·53] (13 infections/4839 neonates) in chlorhexidine clusters compared with DCC clusters (52 infections/5076 neonates) (4).
Fifth, we performed a secondary investigation of the not statically significant increase in the hospital admission rate by analyzing all the records of the 281 hospitalizations in detail. We observed a marked effect of seasonality on hospitalization rates with a high seasonal peak (December and January) that impacted the repartition of the hospitalizations in this study conducted from March 2011 to January 2012. Viral infections were responsible for these hospitalizations and associated with a high rate in antibiotic treatment prescriptions in a country where overuse of antibiotics is usual whereas vaccination skepticism is growing (5). Because the centers with the higher recruitment during the winter period were randomized in the dry care group, we observed this increase in hospitalization and antibiotics, without any association with umbilical cord pathology.
As suggested by Dr. Klinger, there is an urgent need to update traditional clinical practices and propose evidence-based conclusions. The inevitable limitations in clinical research results must not affect confidence in data when observed in a very large number of patients with an appropriate methodology.
RE: Dry Care Versus Antiseptics for Umbilical Cord Care: A Cluster Randomized Trial
To the Editor,
We read with great interest the study performed by Gras-Le Guen and colleagues1, titled “Dry care versus antiseptics for umbilical cord care: a cluster randomized trial”. We congratulate the authors for performing a well designed cluster analysis that included a large number of patients. In addition, their conclusion is very relevant to the universal prevention of neonatal omphalitis, mainly in the developed world.
Up to now, there have not been well powered randomized clinical trials to reveal the safety of dry cord practice in the developed world. As this study will have impact on the management of umbilical care in developed countries, more clarifications are needed from the authors. First, the choice of a non-inferiority margin of 0.4% is poorly explained2. It could be assumed that the margin was considered as twice the omphalitis occurrence rates of 0.2%. However, two Canadian trials found a combined incidence of 0.08% (1/1291) in the dry cord care group3,4. Even the authors themselves state in their discussion that the prevalence of omphalitis is < 1 in 1000 births in France. Second, except for home delivery, none of the risk factors known to increase the incidence of omphalitis were included, i.e. septic delivery, low birth weight, prolonged rupture of membranes and chorioamnionitis. Third, we are also concerned about the higher clinic visit rates for umbilical cord symptoms (table 3) that were observed in the dry cord care group when compared to the antiseptic group (p=0.052). Parental concerns behind these visits need to be clarified as it gives pediatricians some guidelines for parental education. For instance, several authors commented on Janssen et al’s findings and expressed their concerns with the practice of dry care of the umbilicus as it increases parental complains about cord exudates and foul smelling. Fourth, the rate of severe omphalitis mentioned in the introduction was not 0.25% (13 out of 4930), but instead was 1% (52 out of 4930) in the developing world5. Fifth, the authors state that France would be saving about 10 million dollars a year only by adopting a dry cord care practice. However, if we account for the 1.3% increase in hospital admission per year, then the cost of hospital care for 7800 infants a year should also be included and may completely offset this amount. We also should account for the more frequent clinic visits and higher prescription rates of antibiotics.
Overall, the study of Gras-Le Guen was not associated with any mortality or major morbidity. It strengthens the safety arguments for adopting a dry cord care practice. However, in order to trade our traditional practice with evidence based research, we need to have a better understanding of the strengths as well as the weaknesses or limitations of the research.
References:
1. Gras-Le Guen C, Caille A, Launay E, Boscher C, et al. Dry care versus antiseptics for umbilical care: a cluster randomized trial. Pediatrics. 2017;139(1): e20161857
2. Ricci S. What does 'non-inferior to' really mean? A clinician thinking out loud. Cerebrovasc Dis. 2010;29(6):607-8.
3. Dore S, Buchan D, Coulas S, et al. Alcohol versus natural drying for newborn cord care. J Obstet Gynecol Neonatal Nurs. 1998;27(6):621–627pmid:9836156
4. Janssen PA, Selwood BL, Dobson SR, Peacock D, Thiessen PN. To dye or not to dye: a randomized, clinical trial of a triple dye/alcohol regime versus dry cord care. Pediatrics.2003;111(1):15–20
5. Mullany LC, Darmstadt GL, Khatry SK, Katz J, LeClerq SC, Shrestha S, et al. Topical applications of chlorhexidine to the umbilical cord for prevention of omphalitis and neonatal mortality in southern Nepal: a community-based, cluster-randomised trial. Lancet. 2006 Mar 18;367(9514):910-8.