Articles

BMJ 2012; 344 doi: 10.1136/bmj.e2156 (Published 5 April 2012)

COMMENTARY
For many years, the mainstay of treatment for acute appendicitis has been surgical appendectomy. However, surgery carries risk. Moreover, there are likely times when surgery is not feasible or preferable. In those cases, antibiotics may play a role in the treatment of uncomplicated acute appendicitis. In this study, researchers conducted a meta-analysis of four randomized controlled trials of antibiotics versus appendectomy as first line therapy for uncomplicated acute appendicitis. They found that nearly two-thirds of cases treated with antibiotics resulted in success. The primary outcome of interest, however, was whether using antibiotics as first line therapy resulted in more complications. It did not; in fact, the relative risk of complications was less than one for antibiotic therapy compared with appendectomy. Now it’s important to note that this was a study of adults, and not children. It’s also important to note that these were cases of uncomplicated acute appendicitis, and more concerning cases of appendicitis should go to surgery. No one should read this study and immediately go about changing their practice with respect to treating children with appendicitis. But as we consider how we treat children with appendicitis in the future, especially in resource limited settings, the findings of this study can inform future research and standards of care.

Stroustrup A, Trasande L, Holzman IR.
http://www.jpeds.com/article/S0022-3476(11)00654-8/abstract

COMMENTARY
Transient tachypnea of the newborn is a very common condition that affects neonates and leads to longer hospitalizations and more intensive therapy after birth. This can lead to a disruption of the normal bonding that should occur between mothers and infants right after birth. Unfortunately, there are few therapies that can be used to shorten the time that infants with TTN need monitoring. In this study, the researchers wished to see if fluid restriction might alter the course of TTN. In the past, some have worried that such fluid restriction might have adverse effects in newborns. Therefore, the aims of this study were twofold, to see if fluid restriction would help infants with TTN while also not harming any.

As for the latter, fluid restriction of about 20 mL/kg/day less than that prescribed normally harmed none of the infants in this study. Unfortunately, however, it also did not produce a significant effect overall in reducing the need for respiratory support of hospital costs for caring for infants with TTN. The good news, though, was that in the subset of patients with severe TTN, defined as needing respiratory support for at least 48 hours, there was a significant reduction in the duration of respiratory support. While this study won’t likely lead to an immediate change in practice, it is a small study that could be easily replicated on a larger scale. Such a study may clarity the amount of benefit for children with severe TTN, while also revealing the trends overall to be statistically significant. Anything we could do to improve our management of infants in this time period would be welcomed by mothers and physicians alike.

Lozoff B, Castillo M, Clark KM, Smith JB.
http://archpedi.ama-assn.org/cgi/content/full/166/3/208

COMMENTARY
It has become standard of care, especially in the United States, for iron-fortified formula to be the recommendation for all infants who are not being breastfed. The necessity for iron-supplementation for infants has become so ingrained, that low-iron formula has been effectively removed from the shelves. This is less true in Europe, where iron fortification levels are lower in formula. This shift was based, in part, on the original findings of this randomized controlled trial, where the use of iron-fortified formula significantly reduced the incidence of iron deficiency. However, not all children are iron deficient in infancy. Therefore, any extra iron these children are given will not really provide any benefits, and may produce negative side-effects. The general consensus has been, though, that there was little downside in the fortification, with a significant potential upside.

The ten-year follow up of children in this study showed that those who received the iron-fortified formula had significantly impaired development in a number of areas. Further, this negative effect was most pronounced in children who had high hemoglobin levels as infants when they started the formula. Therefore, it may be that infants who don’t need iron fortification, but still get it, not only derive no benefit from the fortification, but are also harmed developmentally by it. We may need to consider a more nuanced approach to infant formulas, where only children who need iron-fortification receive it. 

Of course, a broader adoption of breastfeeding would make this formula debate less critical, as the iron in breast milk is generally more bioavailable. Infant nutrition continues to be a priority area for EiP and will be featured at the upcoming conference in Madrid.

Melinda Caskey, MD, Bonnie Stephens, MD, Richard Tucker, BA, Betty Vohr, MD
http://pediatrics.aappublications.org/content/128/5/910.full

COMMENTARY
In this highly innovative and important study, researchers used a digital language processor (LENA) to record and code all of the sounds that preterm babies hear and make. They were able to detect adult words, infant vocalizations, and background noise. There are several notable findings. First, there is a paucity of adult language and quite a bit of noise in the babies' environments. Monitors and noise accounted for about ½ of all sounds whereas language accounted for between 2-5%. This of course, stands in marked contrast to the sounds a fetus of the same age would be experiencing in utero-- be it the muffled voices of awake adults or true silence during maternal sleep. Second, there was tremendous variability in the number of adult words detected with a range of 144-26,000 over the 16 hour recording sessions. Based on many studies, including the classic Hart and Risley monograph Meaningful Differences in the Everyday Experiences of Children, we know that the number of words young children hear is critical to their language acquisition, their brain development and their long term function and we see evidence of that here with infant vocalizations increasing with parental vocal interaction. Third, the adult words infants hear increased dramatically when parents were present. The study suggests that the extra uterine environment of NICUs needs to be restructured in many ways. Noise and unnatural stimulation need to be reduced; parental (or other adult) interactions with babies need to be increased. For too long too many of us have not recognized the important and unique non-medical needs of these very young infants.

Verena Schneider-Lindner, MD, MSc; Caroline Quach, MD, MSc; James A. Hanley, PhD; Samy Suissa, PhD
Arch Pediatr Adolesc Med. 2011;165(12):1107-1114. doi:10.1001/archpediatrics.2011.143

COMMENTARY
Community acquired MRSA rates are increasing worldwide.  While these infections are generally limited to skin and soft tissues and are not serious, in some cases they can be invasive with serious and even deadly consequences.  In adults, prior history of antibiotic use has been associated with the development of MRSA but studies in children have been lacking. These authors used a large database and conducted a case control study of prior antibiotic use and subsequent MRSA diagnosis. The results are interesting, informative, and consistent with prior studies. Notably, not only prior use of antibiotic, but class of antibiotic increased the risk.  Case-control studies such as this typically have two potential fatal flaws that could undermine or eliminate their significance. The first is “recall bias” which occurs because cases, when they are the source of information about an exposure, may have spent considerably more effort than controls thinking about what might have caused the condition. Consider the parents of a child with autism. Confronted with their child’s condition, such parents may spend hours—even days pondering all prior potential exposures in utero or in their infant’s post natal environment that may have caused the condition. By comparison, parents of unaffected children will have expended considerably less effort and may therefore overlook prior exposures giving the misleading appearance that cases had a risk factor with greater frequency than controls. Given that parental report was not relied on for prior use of antibiotics, recall bias is not a problem here. The second potential fatal flaw is what is called protopathic bias meaning that cases already were pre-clinically affected at the time of the exposure to the risk factor. For example, suppose one is testing whether non-steroidal anti inflammatories increase the risk of necrotizing fasciitis (NF) in the setting of varicella infection.  It could well be that children who develop NF are taking NSAIDS for pain prior the clinical onset of the condition leading to a false association. Here, the study authors try to control for this by ignoring prescriptions within 30 days of diagnosis. Overall, this study adds yet another reason for clinicians to be cautious in their use of antibiotics.  It also gives them a meaningful rationale to share with parents who may want antibiotics when their child does not need them. Tell them it increases their chances of MRSA! EiP had a session on antimicrobial stewardship at our 2011 conference. Look for it on the website.

Michael Leonardi, MD^a, Kenneth Bromberg, MD^b, Roger Baxter, MD^c, Julie L. Gardner, BS^d,Stephanie Klopfer, PhD^a, Ouzama Nicholson, MD^d, Michael Brockley, BA^e, James Trammel, MS^e, Vicky Leamy, MPH^f, Wendy Williams, MS^d, Barbara Kuter, PhD, MPH^d, Florian Schödel, MD^d
http://pediatrics.aappublications.org/content/128/6/e1387.full

COMMENTARY
The number of vaccines for children has grown considerably and will continue to grow in the future.  For a variety of reasons, parents are increasingly likely to postpone vaccinations, developing in effect their own “schedules.” This reluctance to immunize either according to prescribed schedules or at all is currently being called “vaccine hesitancy.” The primary risk vaccine hesitancy poses is that children spend time at risk (unimmunized) when they could be protected had they received vaccinations in a more timely manner.  For some parents (and indeed for some clinicians) there are questions about whether concomitant administration of vaccines diminishes their efficacy or increases the risk of side-effects.  This important study addresses both concerns. In a large, well-designed randomized controlled trial, there were minimal and clinically insignificant differences in the immune responses when MMR and PCV were administered together or separated by 6 weeks.  Importantly, though 22% of children had fever after vaccination, there was no evidence that concomitant administration increased its frequency.  In fact, given that each vaccination event carries the risk of subsequent fever, one might even hypothesize that two vaccination episodes as would be the case when the vaccines were not delivered concomitantly might increase the overall risk of fever.  Parents can now be reassured that no harm and some benefit can come from simultaneous administration of MMR and PCV. Unfortunately, because the immunogenicity of each vaccine is different, concomitant administration protocols will still need to be evaluated in the future as new vaccines are developed. EiP is planning a session on vaccine hesitancy for the Madrid conference in 2012.