Probiotics for the postoperative management of term neonates after gastrointestinal surgery.

BACKGROUND: The intestinal microflora has an essential role in providing a barrier against colonisation of pathogens, facilitating important metabolic functions, stimulating the development of the immune system, and maintaining intestinal motility. Probiotics are live microorganisms that can be administered to supplement the gut flora. Neonates who have undergone gastrointestinal surgery are particularly susceptible to infectious complications in the postoperative period. This may be partly due to a disruption of the integrity of the gut and its intestinal microflora. There may be a role for probiotics in reducing the incidence of sepsis and improving intestinal motility, thus reducing morbidity and mortality and improving enteral feeding in neonates in the postoperative period. OBJECTIVES: To evaluate the efficacy and safety of administering probiotics after gastrointestinal surgery for the postoperative management of neonates born from 35 weeks of gestation. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and trial registries in August 2023. We checked reference lists of included studies and relevant systematic reviews for additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that investigated the postoperative administration of oral probiotics versus placebo or no treatment in neonates born from 35 weeks of gestation who had one or more gastrointestinal surgical procedures. We applied no restrictions regarding the type or dosage of probiotics or the duration of treatment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods, and we used GRADE to assess the certainty of evidence. MAIN RESULTS: We identified one RCT that recruited 61 neonates with a gestational age of 35 weeks or more. All infants were admitted to a neonatal intensive care unit and had surgery for gastrointestinal pathologies. There may be little or no difference in proven sepsis (positive bacterial culture, local or systemic) between infants who receive probiotics compared with those who receive placebo (odds ratio (OR) 0.64, 95% confidence interval (CI) 0.16 to 2.55; 61 infants; low-certainty evidence). Probiotics compared to placebo may have little or no effect on time to full enteral feeds (mean difference (MD) 0.63 days, 95% CI -4.02 to 5.28; 61 infants; low-certainty evidence). There were no reported deaths prior to discharge from hospital in either study arm. Two weeks after supplementation, the infants who received probiotics had a substantially higher relative abundance of non-pathogenic intestinal microflora (Bifidobacteriaceae) than those who received placebo (MD 38.22, 95% CI 28.40 to 48.04; 39 infants; low-certainty evidence). AUTHORS' CONCLUSIONS: This review provides low-certainty evidence from one small RCT that probiotics compared to placebo have little or no effect on the risk of proven sepsis (positive bacterial culture, local or systemic) or time to full-enteral feeds in neonates who have undergone gastrointestinal surgery. Probiotics may substantially increase the abundance of beneficial bacterial in the intestine of these neonates, but the clinical implications of this finding are unknown. There is a need for adequately powered RCTs to assess the role of probiotics in this population. We identified two ongoing studies. As neither reported the gestational age of prospective study participants, we are unsure if they will be eligible for inclusion in this review.

Antiviral agents for treatment of herpes simplex virus infection in neonates.

BACKGROUND: Herpes simplex virus (HSV) is a rare but serious neonatal pathogen. Prior to the availability of antiviral drugs the mortality associated with all but localised neonatal infection was high, with 85% of infants with disseminated HSV infection and 50% of infants with encephalitis dying by one year of age. The morbidity in the survivors of multiorgan infection was also high, with up to 50% experiencing long-term neurological sequelae. OBJECTIVES: To determine the effect of antiviral agents in the treatment of neonatal HSV infections on mortality, progression of disease and neurodevelopmental sequelae at approximately one year. The secondary objective was to assess the effect of antiviral agents on major complications associated with the use of these agents including nephrotoxicity and bone marrow suppression. SEARCH STRATEGY: Trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2008), MEDLINE (1996 - Nov 2008), EMBASE (1982 - Nov 2008) and reference lists of published trials. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of antiviral therapy in infants less than one month of age with virologically proven HSV infection were included. DATA COLLECTION AND ANALYSIS: Data were extracted and the analyses performed independently by two review authors. Studies were analysed for methodological quality using the criteria of the Cochrane Neonatal Review Group. All data were analysed using RevMan 5.1. When possible, meta-analysis was performed to calculate typical relative risk, typical risk difference, along with their 95% confidence intervals (CI). MAIN RESULTS: Two eligible studies of a total of 273 infants were included. Both studies were randomized controlled trials. One study treated 63 infants with vidarabine or placebo (Whitley 1980) and the other study treated 210 infants with aciclovir or vidarabine (Whitley 1991).In the study comparing vidarabine with placebo (Whitley 1980), infants with all forms of neonatal HSV disease were included [disseminated disease, central nervous system (CNS) disease alone, and skin, eye and mouth (SEM) disease].There was no significant reduction in the risk of mortality when analyzed as an entire group; however, mortality was significantly reduced when data from infants with CNS disease or disseminated disease were combined. There was no difference in the rate of neurological abnormalities in survivors at one year when analyzed as an entire group or by disease category.There was no difference between aciclovir and vidarabine (Whitley 1991) in preventing mortality from neonatal HSV disease, in preventing disease progression, in reducing the incidence of neurological abnormality at one year, or in the incidence of drug-induced renal or bone marrow toxicity. In infants with SEM disease, there was no significant difference in neurological outcome with aciclovir compared vidarabine treatment. Both drugs were well tolerated in the newborn period. AUTHORS' CONCLUSIONS: There is insufficient trial evidence to evaluate the effects of antiviral agents with controls or with each other. The rarity of the condition makes effectively powered clinical trials difficult to perform. The efficacy of newer antiviral agents with better bioavailability (e.g. valaciclovir, valganciclovir) for the treatment of neonatal disease needs to be evaluated in randomised trials. The efficacy of oral formulations need to be evaluated as they may be useful for infants with skin, eye or mouth HSV disease or in the treatment of infants with recurrences after the neonatal period.