Aly H, et al. Melatonin use for neuroprotection in perinatal asphyxia: a randomized controlled pilot study. J Perinatol. 2015;35(3):186-91. Thirty asphyxiated infants undergoing hypothermia were randomized to melatonin or not, in a study from Egypt. The melatonin was given enterally, and serum concentrations rose in the treated group. There were some potential benefits in the melatonin infants, with less seizures and improved MRI appearance. But this was a very small unblinded study, so a high risk of bias, but very interesting, suggestive results.
Livingston MH, et al. Glycerin Enemas and Suppositories in Premature Infants: A Meta-analysis. Pediatrics. 2015;135(6):1093-106. I must say I have never ordered a glycerin enema for a baby (or for anyone else for that matter), but I have occasionally given a suppository for a baby who has not stooled for a couple of days and appears distended. The three trials included in this meta-analysis are all of routine use of glycerine suppos or enemas. The trials all have some significant limitations, but they show, in general, that there may be a minor effect on the stool pattern, but no other clinical benefits, and there may be an increase in Necrotizing Enterocolitis. The relative risk for NEC was very high at 2.72, but with wide 95% confidence intervals which include the possibility of no effect.
I don’t really understand the rationale behind doing further trials of this subject, even though the authors of this review note that there are 3 that have been or are being done. With the data already in the literature, including the potential for an increase in NEC, I think that routine glycerine suppositories should be avoided, and even occasional intermittent use should be reconsidered or abandoned.
van Pul C, et al. Safe patient monitoring is challenging but still feasible in a neonatal intensive care unit with single family rooms. Acta Paediatrica. 2015;104(6):e247-e54. As many of us are moving toward single patient rooms, a common concern is how to provide alarm surveillance. If a nurse has two patients, as is usual in most places around the world for the more stable NICU patient, and is in a room suctioning a baby, for example, what happens when the other babies ventilator circuit comes apart? The problem is obviously compounded at break times. Many centers have adopted technological solutions which lead to distributed alarms, so the caregivers are supplied with wireless devices that receive alarms, with the primary nurse receiving alarms immediately for her/his patients, and a second nurse receiving the alarm if the first is not able to respond. One thing that I don’t see in the publication is how long it takes on a daily basis to log each primary or secondary nurse or other caregiver to their patient(s). We are expecting a substantial time commitment for that process when we move to our new unit, in about 18 months. This study is reassuring that a workable system can be developed which does not increase the alarm fatigue of the nurses. A system which includes important equipment alarms including the ventilator would be an improvement.
Neonatal Research 
I would like to submit my letter to Editor of Pediatrics on ‘Glycerin Enemas and Suppositories in Premature Infants: A Meta-analysis’
I read with interest the meta-analysis of glycerin suppository and/or enema studies by Livingston et al.( peds.2015-0143). The authors have adequately
acknowledged the major methodological issues with the 3 studies that were included in the meta-analysis (1-3). The study indicates that the evidence for
routine prophylactic glycerine enemas/suppository in preterm infants is inconclusive.
I have major concerns with the conclusion that ‘glycerine enemas/suppository treatment may be associated with increased risk of necrotising enterocolitis
(NEC)’. The NEC incidence in their meta-analysis was 9/93 in treatment group and 3/86 in the control group (RR 2.72[0.76 to 9.81], p=0.13). However in
Haiden et al, (1), all 3 cases of NEC happened in patients with protocol violations (i.e. all 3 NEC cases did not receive any glycerine enema). In light of
the high rate of protocol violation (~25%), it would be more appropriate to include the per-protocol (PP) analysis results of their study in the
meta-analysis (1). In Shinde et al (2), the 2 NEC cases reported in the treatment arm were ‘stage 1’ NEC which is traditionally excluded in most NEC
studies because of its poor specificity. If we consider these factors in the analysis, the results would be as follows:
NEC events (Treatment)
NEC events (Controls)
Haiden et al, (PP analysis) (1)
0/27
0/31
Khadr et al, (2)
4/29
1/25
Shinde et al, (3)
0/21
1/21
Total NEC events
4/77
2/77
This analysis will give a RR 2.00[0.38 to 10.6], p=0.68. This suggests that the use of glycerine enema/suppository has no effect on the incidence of NEC.
Also, NEC was not the primary outcome in any of these studies. The meta-analysis shows primary outcome (time to reach full enteral feeds) was shorter in
the treatment group, though not statistically significant. The studies also did not report any major adverse events related to treatment.
Pietz et al, reported one of the lowest incidence of NEC in very low birth weight infants in United States NICU (4). Their feeding protocol included
regular use of glycerin suppositories if there is no bowel movement for 24 hours. The rationale was to prevent the development of intestinal distension,
with has the potential to alter intestinal blood flow (5,6).
The occasional use of glycerine suppository in preterm infants with feeding intolerance associated with no bowel movements or no rectal gas shadows is very
common in our practice, often with good results. I see no reason to change this practice based on the current available evidence. I think, the news of
further RCT’s in the pipeline is encouraging, and may help to address these issues in a more definitive way.
References
Haiden N, Jilma B, Gerhold B, et al. Small volume enemas do not accelerate meconium evacuation in very low birth weight infants. J Pediatr
Gastroenterol Nutr. 2007;44(2):270–273
Khadr SN, Ibhanesebhor SE, Rennix C, et al. Randomized controlled trial: impact of glycerin suppositories on time to full feeds in preterm infants.
Neonatology. 2011;100(2):169–176
Shinde S, Kabra NS, Sharma SR, Avasthi BS, Ahmed J. Glycerin suppository for promoting feeding tolerance in preterm very low birth weight neonates:
a randomized controlled trial. Indian Pediatr. 2014;51(5): 367–370
Pietz J
, Achanti B,Lilien L,Stepka EC, Mehta SK.Prevention of
necrotizing enterocolitis in preterm infants: a 20-year experience.Pediatrics. 2007
Jan;119(1):e164-70
Meyers RL, Alpan G, Lin E, Clyman RI. Patent ductus arteriosus, indomethacin, and intestinal distension: effects on intestinal blood flow and
oxygen consumption. Pediatr Res. 1991; 29:569–574
W Ruf
, G T Suehiro,A Suehiro, V Pressler, and
J J McNamara.Intestinal blood flow at various intraluminal pressures in the piglet with closed abdomen.
Ann Surg. 1980 Feb; 191(2): 157–163.
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