Journal Club 2011

Acyclovir suppression and neurodevelopment outcome after neonatal HSV

Kimberlin DW et al. NEJM 2011 Oct 6;365:1284

This study reports a potential neurodevelopment benefit for 6 months of AVC suppressive treatment in infants following CNS or SEM disease in the neonatal period. Although numbers were relatively small, infants in the ACV achieved higher Bayley scores compared to infants in the placebo group (88.2 vs. 68.1, p=0.04). Benefit was greatest in infants with previous CNS disease. There was a trend towards neutropenia in the ACV arm but no infant developed any significant infections. Longterm follow-up results of the infants in recruited to trial are eagerly awaited.

Submitted by: Tom Connell 15 Feb 2012

IVIG in neonatal sepsis. Treatment of neonatal sepsis with intravenous immune globulin.

The INIS collaborative group. NEJM 2011 Sep 29;35:1201

This was a large multicentre double blind RCT (3378 babies in the analysis) comparing 2 doses of IVIG 500mg/kg/day with placebo in infants with proven or suspected sepsis. Infants were excluded who had previously received IVIG or who were thought to need IVIG. The primary outcomes were incidence of death or major disability at 2 years and were 39% in both groups. There were no differences in secondary outcomes either (death in the hospital, death by age 2, confirmed sepsis after trial entry, oxygen use on day 28 and major cerebral abnormalities). Subgroup analysis did not change the results.This shows the benefits of a large multicentre trial powered to answer a question which had had variable results in smaller studies. There was no benefit from IVIG in the treatment of neonatal sepsis. However, there remains the possibility that in selected cases it would be of use with different treatment criteria, as patients who were thought to need it were excluded from the trial.

A Cochrane review was published prior to this on this topic in 2010. A subsequent letter in Jan 2012 suggested that the large number of positive cultures with coagulase negative Staph which were included as 'sepsis' but would likely have had a less severe outcome may have decreased any difference found between the 2 groups falsely. The authors responded that this was unlikely as 'In this group, bloodstream sepsis with coagulase-negative staphylococci is associated with markedly independent increase in the risk of cerebral palsy and adverse neurodevelopmental outcome and does not differ substantially from sepsis with other pathogens in these respects.' While this may be debatable, they did a subgroup analysis of 293 patients with Gram negative sepsis and there was no difference between the treatment and placebo groups.

Submitted by: Penelope Bryant 24 Nov 2011, updated 18 Jan 2012

Cord blood vitamin D and RSV.Is there an association between low cord blood vitamin D and subsequent risk of RSV in the first year of life?

Mirjam E. Belderbos, Michiel L. Houben, Berry Wilbrink, Eef Lentjes, Eltje M. Bloemen, Jan L. L. Kimpen, Maroeska Rovers, and Louis Bont. Pediatrics 2011; 127:6 e1513-e1520

In this article Belderbos and colleagues provide preliminary data on a potential association between low cord vitamin D levels and subsequent risk of respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in the first year of life. In their study infants born to mothers with a cord vitamin D level of <50 nmol were six times more likely to develop RSV LRTI in the first year of life compared to infants with a cord vitamin D level > 75 nmol. However the accompanying wide confidence interval (1.6-24.9 reflect the small number of cases that actually developed an RSV related LRTI in their cohort. Although several aspects related to the methodology of the study were questionable the results warrant consideration and could be important if they are replicated in subsequent studies.

Submitted by: Tom Connell 24 Nov 2011