Abstract

Insulin is used to treat neonatal hyperglycaemia when blood glucose concentrations are consistently high, and to treat neonatal diabetes. Within this brief report, a review of the existing literature is conducted to determine if intravenous administration of insulin should be proceeded by priming of the intravenous system, adding of albumin, or non-priming to get a stable insulin dose. Within this literature search, we focused on experimental insulin adsorption data (in vitro studies).

Abstract

BACKGROUND Botulism is an acute paralytic illness caused by a neurotoxin produced by Clostridium botulinum. Supportive care, including intensive care, is key, but the role of other medical treatments is unclear. This is an update of a review first published in 2011. OBJECTIVES To assess the effects of medical treatments on mortality, duration of hospitalization, mechanical ventilation, tube or parenteral feeding, and risk of adverse events in botulism. SEARCH METHODS We searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, and Embase on 23 January 2018. We reviewed bibliographies and contacted authors and experts. We searched two clinical trials registers, WHO ICTRP and clinicaltrials.gov, on 21 February 2019. SELECTION CRITERIA Randomized controlled trials (RCTs) and quasi-RCTs examining the medical treatment of any of the four major types of botulism (infant intestinal botulism, food-borne botulism, wound botulism, and adult intestinal toxemia). Potential medical treatments included equine serum trivalent botulism antitoxin, human-derived botulinum immune globulin intravenous (BIG-IV), plasma exchange, 3,4-diaminopyridine, and guanidine. DATA COLLECTION AND ANALYSIS We followed standard Cochrane methodology.Our primary outcome was in-hospital death from any cause occurring within four weeks from randomization or the beginning of treatment. Secondary outcomes were death from any cause occurring within 12 weeks, duration of hospitalization, duration of mechanical ventilation, duration of tube or parenteral feeding, and proportion of participants with adverse events or complications of treatment. MAIN RESULTS A single RCT met the inclusion criteria. Our 2018 search update identified no additional trials. The included trial evaluated BIG-IV for the treatment of infant botulism and included 59 treatment participants and 63 control participants. The control group received a control immune globulin that did not have an effect on botulinum toxin. Participants were followed during the length of their hospitalization to measure the outcomes of interest. There was some violation of intention-to-treat principles, and possibly some between-treatment group imbalances among participants admitted to the intensive care unit and mechanically ventilated, but otherwise the risk of bias was low. There were no deaths in either group, making any treatment effect on mortality inestimable. There was a benefit in the treatment group on mean duration of hospitalization (BIG-IV: 2.60 weeks, 95% confidence interval (CI) 1.95 to 3.25; control: 5.70 weeks, 95% CI 4.40 to 7.00; mean difference (MD) -3.10 weeks, 95% CI -4.52 to -1.68; moderate-certainty evidence); mechanical ventilation (BIG-IV: 1.80 weeks, 95% CI 1.20 to 2.40; control: 4.40 weeks, 95% CI 3.00 to 5.80; MD -2.60 weeks, 95% CI -4.06 to -1.14; low-certainty evidence); and tube or parenteral feeding (BIG-IV: 3.60 weeks, 95% CI 1.70 to 5.50; control: 10.00 weeks, 95% CI 6.85 to 13.15; MD -6.40 weeks, 95% CI -10.00 to -2.80; moderate-certainty evidence), but not on proportion of participants with adverse events or complications (BIG-IV: 63.08%; control: 68.75%; risk ratio 0.92, 95% CI 0.72 to 1.18; absolute risk reduction 0.06, 95% CI 0.22 to -0.11; moderate-certainty evidence). AUTHORS' CONCLUSIONS We found low- and moderate-certainty evidence supporting the use of BIG-IV in infant intestinal botulism. A single RCT demonstrated that BIG-IV probably decreases the duration of hospitalization; may decrease the duration of mechanical ventilation; and probably decreases the duration of tube or parenteral feeding. Adverse events were probably no more frequent with immune globulin than with placebo. Our search did not reveal any evidence examining the use of other medical treatments including serum trivalent botulism antitoxin.

Abstract

BACKGROUND Exchange transfusion and phototherapy have traditionally been used to treat jaundice and avoid the associated neurological complications. Because of the risks and burdens of exchange transfusion, intravenous immunoglobulin (IVIg) has been suggested as an alternative therapy for alloimmune hemolytic disease of the newborn (HDN) to reduce the need for exchange transfusion. OBJECTIVES To assess the effect and complications of IVIg in newborn infants with alloimmune HDN on the need for and number of exchange transfusions. SEARCH METHODS We performed electronic searches of CENTRAL, PubMed, Embase (Ovid), Web of Science, CINAHL (EBSCOhost), Academic Search Premier, and the trial registers ClinicalTrials.gov and controlled-trials.com in May 2017. We also searched reference lists of included and excluded trials and relevant reviews for further relevant studies. SELECTION CRITERIA We considered all randomized and quasi-randomized controlled trials of IVIg in the treatment of alloimmune HDN. Trials must have used predefined criteria for the use of IVIg and exchange transfusion therapy to be included. DATA COLLECTION AND ANALYSIS We used the standard methods of Cochrane and its Neonatal Review Group. We assessed studies for inclusion and two review authors independently assessed quality and extracted data. We discussed any differences of opinion to reach consensus. We contacted investigators for additional or missing information. We calculated risk ratio (RR), risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB) for categorical outcomes. We calculated mean difference (MD) for continuous variables. We used GRADE criteria to assess the risk of bias for major outcomes and to summarize the level of evidence. MAIN RESULTS Nine studies with 658 infants fulfilled the inclusion criteria. Term and preterm infants with Rh or ABO (or both) incompatibility were included. The use of exchange transfusion decreased significantly in the immunoglobulin treated group (typical RR 0.35, 95% CI 0.25 to 0.49; typical RD -0.22, 95% CI -0.27 to -0.16; NNTB 5). The mean number of exchange transfusions per infant was also significantly lower in the immunoglobulin treated group (MD -0.34, 95% CI -0.50 to -0.17). However, sensitivity analysis by risk of bias showed that in the only two studies in which the treatment was masked by use of a placebo and outcome assessment was blinded, the results differed; there was no difference in the need for exchange transfusions (RR 0.98, 95% CI 0.48 to 1.98) or number of exchange transfusions (MD -0.04, 95% CI -0.18 to 0.10). Two studies assessed long-term outcomes and found no cases of kernicterus, deafness or cerebral palsy. AUTHORS' CONCLUSIONS Although overall results show a significant reduction in the need for exchange transfusion in infants treated with IVIg, the applicability of the results is limited because of low to very low quality of evidence. Furthermore, the two studies at lowest risk of bias show no benefit of IVIg in reducing the need for and number of exchange transfusions. Based on these results, we have insufficient confidence in the effect estimate for benefit of IVIg to make even a weak recommendation for the use of IVIg for the treatment of alloimmune HDN. Further studies are needed before the use of IVIg for the treatment of alloimmune HDN can be recommended, and should include blinding of the intervention by use of a placebo as well as sufficient sample size to assess the potential for serious adverse effects.

Abstract

To systematically evaluate the effectiveness of prothrombin complex concentrate (PCC) in neonates and infants, we performed a systematic review and meta-analysis based on current evidence. Quality of studies was assessed by Cochrane Collaboration's risk of bias tool and Newcastle-Ottawa quality assessment scale. For dichotomous data, we obtained the number of events and total number and calculated the relative risk (RR) with 95% confidence intervals (CI). For continuous variables, we obtained mean and standard deviation (SD) values and calculated mean difference (MD) with 95% CI. We identified six trials and two cohort studies. For trials, selection bias and performance bias were high, while detection bias, attrition bias, and reporting bias were relatively low. For cohort studies, selection bias was low. Both individual studies and meta-analysis failed to find any benefit of PCC on mortality. Meta-analysis also failed to show any benefit in reducing intracranial hemorrhage. The effectiveness of PCC on the correction of hemostatic defects was inconsistent among studies. In addition, PCC was not more effective than fresh frozen plasma (FFP) in correcting hemostatic defects. CONCLUSION There is insufficient evidence to allow a recommendation for use of PCC in neonates and infants. What is Known: * Prothrombin Complex Concentrate is becoming increasingly used off-label for treatment of neonates and infants with severe bleeding or risk of severe bleeding. * Some case reports showed PCC seemed to be effective for infants and children with coagulation factor deficiency, but evidence about the effectiveness of PCC to reverse serious Vitamin K Deficiency Bleeding is limited. What is New: * As far as we know, this is the first systematic review that evaluates the effectiveness of PPC in neonates with bleeding or risk of bleeding. * There is insufficient evidence to allow a recommendation for use of PCCs in neonates and infants.

Abstract

BACKGROUND Necrotizing enterocolitis (NEC) is the most common emergency involving the gastrointestinal tract occurring in the neonatal period. There have been published reports that suggest that oral immunoglobulins (Ig)A and IgG produce an immunoprotective effect in the gastrointestinal mucosa. OBJECTIVES To determine the effect of oral immunoglobulin on the incidence of necrotizing enterocolitis and other complications in preterm or low birth weight (or both) neonates. SEARCH METHODS We used the standard search strategy of the Cochrane Neonatal Group. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2016, Issue 1), PubMed (1966 to January 2016), CINAHL (1982 to January 2016) and EMBASE (1980 to January 2016) and conference proceedings. SELECTION CRITERIA All randomized or quasi-randomised controlled trials where oral immunoglobulins were used as prophylaxis against NEC in preterm (less than 37 weeks' gestation) or low birth weight (less than 2500 gram), or both, neonates. DATA COLLECTION AND ANALYSIS We performed data collection and analysis in accordance with the standard methods of the Cochrane Neonatal Review Group. MAIN RESULTS The search identified five studies on oral immunoglobulin for the prevention of NEC of which three met the inclusion criteria. In this review of the three eligible trials (including 2095 neonates), the oral administration of IgG or an IgG/IgA combination did not result in a significant reduction in the incidence of definite NEC (typical risk ratio (RR) 0.84, 95% confidence interval (CI) 0.57 to 1.25; typical risk difference (RD) -0.01, 95% CI -0.03 to 0.01; 3 studies, 1840 infants), suspected NEC (RR 0.84, 95% CI 0.49 to 1.46; RD -0.01, 95% CI -0.02 to 0.01; 1 study, 1529 infants), need for surgery (typical RR 0.21, 95% CI 0.02 to 1.75; typical RD -0.03, 95% CI -0.06 to 0.00; 2 studies, 311 infants) or death from NEC (typical RR 1.10, 95% CI 0.47 to 2.59; typical RD 0.00, 95% CI -0.01 to 0.01; 3 studies, 1840 infants). AUTHORS' CONCLUSIONS Based on the available trials, the evidence does not support the administration of oral immunoglobulin for the prevention of NEC. There are no randomized controlled trials of oral IgA alone for the prevention of NEC.

Abstract

OBJECTIVE The application of intravenous immune globulin (IVIG) has been recommended for treating hemolysis in neonates for several years. But in clinical work, more than one study reported that IVIG treatment maybe increased the risk of NEC in hemolytic patients. In light of this situation, we performed this meta-analysis. MATERIALS AND METHODS We searched in PubMed, Embase, Cochrane databases for English references, and in Wanfang, VIP, Cnki databases for Chinese references (all last launched on 2015/12/18). Ultimately, 5 studies (Including 4 Chinese articles) were incorporated into this meta-analysis. Odds ratio (OR) and weighted mean difference (WMD) were calculated using a random-effects or fixed-effects model, depending on the data type and heterogeneity of the included studies. RESULTS (1) Baseline data including gestational age, gender and TBil between IVIG and control groups were compared in hemolytic infants, and showed no significance. (2) With respect to possible inducement of NEC, SGA and formula feeding were found no significance between IVIG and control groups. In contrast, birth weight was found significantly different between the two groups (WMD = 33.35; 95% CI, 20.70-46.01; p < 0.00001). (3) Regarding the incidence of NEC and mortality, the result showed that there was a significant difference between the IVIG and the control groups in the risk of NEC (OR: 4.53; 95% CI, 2.34-8.79; p < 0.00001). CONCLUSIONS Our results indicate that IVIG treatment for hemolysis may increase the risk of NEC in infants. But it does not increase the risk of final mortality.

Abstract

BACKGROUND Neonates are at higher risk of infection due to immuno-incompetence. Maternal transport of immunoglobulins to the fetus mainly occurs after 32 weeks' gestation, and endogenous synthesis begins several months after birth. Administration of intravenous immunoglobulin (IVIG) provides immunoglobulin G (IgG) that can bind to cell surface receptors, provide opsonic activity, activate complement, promote antibody-dependent cytotoxicity and improve neutrophilic chemo-luminescence. Theoretically, infectious morbidity and mortality could be reduced by the administration of IVIG. OBJECTIVES To assess the effects of IVIG on mortality and morbidity caused by suspected or proven infection at study entry in neonates. To assess in a subgroup analysis the effects of IgM-enriched IVIG on mortality from suspected infection. SEARCH METHODS For this update, MEDLINE, EMBASE, The Cochrane Library, CINAHL, trial registries, Web of Science, reference lists of identified studies, meta-analyses and personal files were searched in 2013. No language restrictions were applied. SELECTION CRITERIA Randomised or quasi-randomised controlled trials involving newborn infants (< 28 days old); IVIG for treatment of suspected or proven bacterial or fungal infection compared with placebo or no intervention; and where one of the following outcomes was reported, mortality, length of hospital stay or psychomotor development at follow-up. DATA COLLECTION AND ANALYSIS Statistical analyses included typical risk ratio (RR), risk difference (RD), weighted mean difference (WMD), number needed to treat for an additional beneficial outcome (NNTB) or an additional harmful outcome (NNTH), all with 95% confidence intervals (CIs), and the I(2) statistic to examine for statistical heterogeneity. MAIN RESULTS The updated search identified one published study that was previously ongoing. A total of 9 studies evaluating 3973 infants were included in this review. Mortality during hospital stay in infants with clinically suspected infection was not significantly different after IVIG treatment (9 studies (n = 2527); typical RR 0.95, 95% CI 0.80 to 1.13; typical RD -0.01, 95% CI - 0.04 to 0.02; I(2) = 23% for RR and 29% for RD). Death or major disability at 2 years corrected age was not significantly different in infants with suspected infection after IVIG treatment (1 study (n = 1985); RR 0.98, 95% CI 0.88 to 1.09; RD -0.01, 95% CI -0.05 to 0.03). Mortality during hospital stay was not significantly different after IVIG treatment in infants with proven infection at trial entry (1 trial (n = 1446); RR 0.95, 95% CI 0.74 to 1.21; RD -0.01, 95% CI -0.04 to 0.03). Death or major disability at 2 years corrected age was not significantly different after IVIG treatment in infants with proven infection at trial entry (1 trial (n = 1393); RR 1.03, 95% CI 0.91 to 1.18; RD 0.01, 95% CI -0.04 to 0.06). Mortality during hospital stay in infants with clinically suspected or proven infection at trial entry was not significantly different after IVIG treatment (1 study (n = 3493); RR 1.00, 95% CI 0.86 to 1.16; RD 0.00, 95% CI - 0.02 to 0.03). Death or major disability at 2 years corrected age was not significantly different after IVIG treatment in infants with suspected or proven infection at trial entry (1 study (n = 3493); RR 1.00, 95% CI 0.92 to 1.09; RD -0.00, 95% CI -0.03 to 0.03). Length of hospital stay was not reduced for infants with suspected or proven infection at trial entry (1 study (n = 3493); mean difference (MD) 0.00 days, 95% CI -0.61 to 0.61). No significant difference in mortality during hospital stay after administration of IgM-enriched IVIG for suspected infection at trial entry was reported in 4 studies (n = 266) (typical RR 0.68, 95% CI 0.39 to 1.20; RD -0.06, 95% CI -0.14 to 0.02; I(2) = 17% for RR and 53% for RD). AUTHORS' CONCLUSIONS The undisputable results of the INIS trial, which enrolled 3493 infants, and our meta-analyses (n = 3973) showed no reduction in mortality during hospital stay, or death or major disability at two years of age in infants w

Abstract

BACKGROUND Nosocomial infections continue to be a significant cause of morbidity and mortality among preterm and/or low birth weight (LBW) infants. Preterm infants are deficient in immunoglobulin G (IgG); therefore, administration of intravenous immunoglobulin (IVIG) may have the potential of preventing or altering the course of nosocomial infections. OBJECTIVES To use systematic review/meta-analytical techniques to determine whether IVIG administration (compared with placebo or no intervention) to preterm (< 37 weeks' postmenstrual age (PMA) at birth) or LBW (< 2500 g birth weight) infants or both is effective/safe in preventing nosocomial infection. SEARCH METHODS For this update, MEDLINE, EMBASE, CINAHL, The Cochrane Library, Controlled Trials, ClinicalTrials.gov and PAS Abstracts2view were searched in May 2013. SELECTION CRITERIA We selected randomised controlled trials (RCTs) in which a group of participants to whom IVIG was given was compared with a control group that received a placebo or no intervention for preterm (< 37 weeks' gestational age) and/or LBW (< 2500 g) infants. Studies that were primarily designed to assess the effect of IVIG on humoral immune markers were excluded, as were studies in which the follow-up period was one week or less. DATA COLLECTION AND ANALYSIS Data collection and analysis was performed in accordance with the methods of the Cochrane Neonatal Review Group. MAIN RESULTS Nineteen studies enrolling approximately 5000 preterm and/or LBW infants met inclusion criteria. No new trials were identified in May 2013.When all studies were combined, a significant reduction in sepsis was noted (typical risk ratio (RR) 0.85, 95% confidence interval (CI) 0.74 to 0.98; typical risk difference (RD) -0.03, 95% CI 0.00 to -0.05; number needed to treat for an additional beneficial outcome (NNTB) 33, 95% CI 20 to infinity), and moderate between-study heterogeneity was reported (I(2) 54% for RR, 55% for RD). A significant reduction of one or more episodes was found for any serious infection when all studies were combined (typical RR 0.82, 95% CI 0.74 to 0.92; typical RD -0.04, 95% CI -0.02 to -0.06; NNTB 25, 95% CI 17 to 50), and moderate between-study heterogeneity was observed (I(2) 50% for RR, 62% for RD). No statistically significant differences in mortality from all causes were noted (typical RR 0.89, 95% CI 0.75 to 1.05; typical RD -0.01, 95% CI -0.03 to 0.01), and no heterogeneity for RR (I(2) = 21%) or low heterogeneity for RD was documented (I(2) = 28%). No statistically significant difference was seen in mortality from infection; in incidence of necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD) or intraventricular haemorrhage (IVH) or in length of hospital stay. No major adverse effects of IVIG were reported in any of these studies. AUTHORS' CONCLUSIONS IVIG administration results in a 3% reduction in sepsis and a 4% reduction in one or more episodes of any serious infection but is not associated with reductions in other clinically important outcomes, including mortality. Prophylactic use of IVIG is not associated with any short-term serious side effects.The decision to use prophylactic IVIG will depend on the costs and the values assigned to the clinical outcomes. There is no justification for conducting additional RCTs to test the efficacy of previously studied IVIG preparations in reducing nosocomial infections in preterm and/or LBW infants.