Intervention Protocol

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Adjuvant corticosteroids for reducing death in neonatal bacterial meningitis

  1. Tinuade A Ogunlesi1,*,
  2. Chibuzo C Odigwe2

Editorial Group: Cochrane Neonatal Group

Published Online: 28 MAR 2013

Assessed as up-to-date: 28 NOV 2012

DOI: 10.1002/14651858.CD010435


How to Cite

Ogunlesi TA, Odigwe CC. Adjuvant corticosteroids for reducing death in neonatal bacterial meningitis (Protocol). Cochrane Database of Systematic Reviews 2013, Issue 3. Art. No.: CD010435. DOI: 10.1002/14651858.CD010435.

Author Information

  1. 1

    Olabisi Onabanjo University, Olabisi Onabanjo University Teaching Hospital, Paediatrics (Neonatal Unit), Sagamu, Ogun State, Nigeria

  2. 2

    Institute of Tropical Disease Research & Prevention, Nigeria Effective Health Care Alliance Programme, Calabar, Cross River State, Nigeria

*Tinuade A Ogunlesi, Paediatrics (Neonatal Unit), Olabisi Onabanjo University, Olabisi Onabanjo University Teaching Hospital, Sagamu, Ogun State, 121001NG, Nigeria. tinuade_ogunlesi@yahoo.co.uk.

Publication History

  1. Publication Status: New
  2. Published Online: 28 MAR 2013

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Background

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Contributions of authors
  7. Declarations of interest
  8. Sources of support
 

Description of the condition

 

Epidemiology

Meningitis, an inflammatory condition of the leptomeninges, is a serious and potentially fatal infectious condition of the central nervous system. Meningitis occurs more commonly in the neonatal period than at any other time in life (Delouvois 1991), due to the increased susceptibility of newborn infants to infections by virtue of their immature cellular and humoral immunity.  

Due to improved antibiotic therapy and supportive care, there has been a remarkable decline in the mortality associated with neonatal meningitis since the 1990s. Mortality in the developed world has dropped from close to 50% to about 10%, while morbidity among survivors remains high (15% to 60%) (Harvey 1999). Although underreporting is a challenge in the developing world, mortality associated with neonatal meningitis remains as high as 40% to 60%, while morbidity figures vary greatly (Stoll 1997; Airede 2008). 

A high proportion of the survivors in neonatal meningitis develop chronic impairments with serious medical and psychosocial implications such as cerebral palsy, mental retardation, seizure disorder, hemiplegia, deafness and blindness (Airede 2008). 

 

Pathogenesis

The major pathogens associated with newborn meningitis include group B β-haemolytic streptococcus (GBS), Escherichia coli, Streptococcus pneumoniae, Listeria monocytogenes and other Gram-negative bacilli. The pattern of bacteriological aetiology in neonatal meningitis differs in some developing parts of the world; Escherichia coli still predominates in some settings (Laving 2003), Staphylococcus aureus predominates according to a Nigerian report (Airede 2008), while some reports of GBS predominance have also been made (Chang 2003).

The mortality and morbidity of neonatal meningitis is related to the inflammatory damage to neural tissues. Components of bacterial cell membrane in the meninges provoke the release of cytokines such as interleukins (IL-1β), tumour necrosis factor-γ (TNF) and platelet aggregation factor (PAF). These agents in turn offset an inflammatory cascade that ultimately results in cerebral oedema, elevated intracranial pressure, reduced cerebral perfusion, cerebritis, neuritis and vasculitis (Mustafa 1990). The end-result of all these pathological features include ischaemia, infarction and atrophy of neural tissues.

 

Clinical features

The clinical features of bacterial meningitis are usually subtle and non-specific in the early phase of the illness, including features such as abnormal temperature (hypothermia or fever), poor cry, poor skin colour, poor feeding, irritability, lethargy and respiratory distress, and can be easily overlooked. Late in the illness, classical features of raised intracranial pressure such as full and tense fontanelles, setting-sun eye appearance, retrocollis, opisthotonus and seizures can occur. If meningitis is not recognised and treated appropriately, complications such as the syndrome of inappropriate antidiuretic hormone secretion (SIADH), disseminated intravascular coagulation and hydrocephalus can develop.

 

Diagnosis

The diagnosis of bacterial meningitis is usually confirmed following bacteriological analysis (microscopy and culture) of cerebrospinal fluid (CSF). When bacteriological culture of CSF is difficult or impossible, the diagnosis can be made from specific microscopic and biochemical abnormalities of the CSF. Cell count greater than 32/mm3, protein level greater than 150 mg/dL, glucose level less than 1 mmol/L, or less than 50% of simultaneously determined random blood glucose are suggestive of bacterial meningitis. Serological methods such as polymerase chain reaction (PCR) may also detect the antigens of bacterial organism in the CSF.

 

Description of the intervention

Corticosteroids have metabolic and regulatory functions in humans. The regulatory functions include anti-inflammatory and immunosuppressive roles. Specifically, corticosteroids decrease influx and activity of leukocytes during acute inflammation, decrease the activities of cytokine-secreting T cells, decrease the production and activities of cytokines and decrease the production of immunoglobulin G (IgG) and the complement components in the blood.

In addition to endogenously produced corticosteroids such as hydrocortisone and corticosterone, there are many synthetic corticosteroids such as dexamethasone and betamethasone. In serious infections like meningitis, corticosteroids are commonly administered through the intravenous route. There are suggestions that the administration of dexamethasone before or with first doses of antibiotics may be beneficial compared to administration of dexamethasone after the institution of antibiotics therapy (Odio 1991).

Adverse effects of corticosteroid therapy include glucose intolerance, systemic hypertension, benign intracranial hypertension, poor response to infection and injury, easy bruising, cataracts and gastrointestinal bleeding (Rang 2003). Many of these adverse effects are uncommon following short duration corticosteroid use (McIntyre 1997).

 

How the intervention might work

Bacterial meningitis in the newborn infant is characterized by high risk of mortality and serious neurological sequelae among most survivors. It is believed that most of the sequelae occur as a result of the damage to neural tissues during the acute inflammatory process that characterise bacterial meningitis.

Corticosteroids when administered as adjunctive treatment in bacterial meningitis may help attenuate the acute inflammatory process while antibiotics clear the pathogenic microorganisms. This might improve clinical outcomes both in the short and long term.

 

Why it is important to do this review

Although the use of adjuvant corticosteroids has been traditionally employed in the treatment of meningitis among children of post-neonatal age and adults, randomised and non-randomised studies have given conflicting reports concerning the effectiveness of adjuvant dexamethasone in improving the survival and reducing neurological deficits including hearing loss in meningitis among children, particularly in low-income countries (Brouwer 2010).

Controlled trials among US children aged eight weeks to 12 years with meningitis demonstrated that the audiological and neurological outcome was similar among the dexamethasone-treated participants and saline-treated controls (Wald 1995). Similar findings were reported in a placebo-controlled study of children aged eight weeks to 13 years with bacterial meningitis in Blantyre, Malawi (Molyneux 2002).

In another placebo-controlled blinded trial of dexamethasone in childhood meningitis among infants and children aged between six weeks and 12 years conducted in Costa Rica, overall neurological and audiological sequelae were significantly lower among dexamethasone-treated children (Odio 1991).

Of note, subgroup analysis was not carried out for children aged six to 12 weeks in the cited studies, thus making extrapolation of the findings to the newborn period difficult. This analysis could have been useful since immune characteristics and range of pathogens causing sepsis at that age (four to 12 weeks) are usually similar to those of the newborn period.

Although, corticosteroids were reported to be effective in childhood bacterial meningitis in the developed world, the situation may be different in the developing world (Furyk 2011). This difference may be ascribed to the prevalent type of pathogen in the developing world, delay in the initiation of appropriate antibiotic treatment, partial treatment arising from indiscriminate antibiotic use outside hospitals as well as the lack of facilities for supportive care.

While mortality in neonatal meningitis has reduced globally, it is equally important to reduce the proportion of infants who survive with daunting neurological sequelae of meningitis. Therefore, in addition to antibiotics and other supportive therapeutic measures, corticosteroids are sometimes included in the management of childhood meningitis, in an effort to reduce inflammation and the attendant neural tissue damage.

Treatment guidelines for neonatal meningitis do not commonly include adjuvant corticosteroids due to possible lack of proof of benefits of corticosteroids on short- and long-term basis. 

Available systematic reviews of adjuvant corticosteroid treatment in bacterial meningitis focused only on children of post-neonatal age. This makes a systematic review of adjuvant corticosteroid treatment of bacterial meningitis in the newborn important in order to update the guidelines for the clinical management of neonatal bacterial meningitis.

 

Objectives

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Contributions of authors
  7. Declarations of interest
  8. Sources of support

To evaluate the efficacy of adjuvant corticosteroids in reducing death and neurodevelopmental sequelae in neonates with bacterial meningitis.

We will perform subgroup analyses to address:

  1. the efficacy of adjuvant corticosteroids in infants with gestational age < 37 weeks and those ≥ 37 weeks;
  2. the efficacy of corticosteroids as an adjuvant treatment in different antibiotic classes (comparison will be made for penicillins with or without aminoglycosides versus cephalosporins with or without aminoglycosides);
  3. the efficacy of adjuvant corticosteroids based on causative bacterial agent (comparison will be made for GBS and other Gram-positive bacteria versus Gram-negative bacteria);
  4. impact of the time of initiation of adjunctive corticosteroid treatment (comparison will be made for pre-antibiotic (up to one hour prior to the commencement of antibiotics) and post-antibiotic (simultaneously with antibiotics or after the commencement of antibiotics);
  5. impact of the duration of adjunctive corticosteroid treatment on the outcome of neonatal bacterial meningitis (comparison will be made for duration less than four days versus four days or more);
  6. impact of corticosteroids on the outcomes for studies conducted in developed countries versus developing countries;
  7. impact of corticosteroids on the outcomes among infants with confirmed meningitis (positive CSF culture or PCR) versus suspect meningitis (deranged cellular or chemical constituents of the CSF without positive CSF culture or PCR).

 

Methods

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Contributions of authors
  7. Declarations of interest
  8. Sources of support
 

Criteria for considering studies for this review

 

Types of studies

Randomised and quasi-randomised controlled trials (individually or cluster randomised). We will not include studies with a cross-over design.

 

Types of participants

Newborn infants aged from birth to 28 days with bacteriologically confirmed diagnosis of bacterial meningitis or suspect meningitis. We will include only bacterial meningitis (with the exception of tuberculous meningitis).

Bacteriologically confirmed diagnosis of bacterial meningitis will be defined using CSF microscopy, culture, PCR, or a combination.

Suspect meningitis will be defined as deranged CSF parameters such as leukocyte count greater than 32/mm3 or CSF protein greater than 150 mg/dL or CSF glucose less than 50% of simultaneously determined random blood glucose, in the absence of positive CSF culture.

 

Types of interventions

 

Intervention

Adjunctive parenteral corticosteroid (at any dose and for any duration of treatment). Corticosteroids of interest may include dexamethasone, hydrocortisone, betamethasone and methylprednisolone. Corticosteroids will be administered by the intravenous route.

 

Control

Appropriate antibiotic therapy alone or in combination with a placebo.

By adjunctive we mean that all the babies in the trial must have had parenteral antibiotics of a class and at a dose that would be considered sufficient for the treatment of neonatal meningitis. Classes of antibiotics allowed will include third-generation cephalosporins, penicillins, vancomycin and aminoglycosides. Penicillins alone or with aminoglycosides and cephalosporins alone or with aminoglycosides and at a dose that will be considered sufficient (doses vary with the drugs used but high doses are generally considered anti-meningitic).

 

Types of outcome measures

 

Primary outcomes

  1. All-cause death until hospital discharge.
  2. Presence of sensorineural deafness at one year of age (this will be assessed by clinical examination and audiometry at one year of age).
  3. Presence of severe neurological deficits or developmental delay between one and two years of age (a neurological deficit will be defined as a functional abnormality of a body area that is observed due to an abnormality in the function of the brain, spinal cord, muscles or nerves. Developmental delay will be defined as any significant lag in a child's physical or motor, cognitive, behavioural, emotional or social development, in comparison with other children of same age and sex within similar environments. Neurological deficits and developmental delay will be assessed using formal evaluation tools). Examples of neurological deficits include mental retardation, cerebral palsy, epilepsy, blindness and behavioural disorders. We will consider evaluation tools such as the Bayley's Infant Scale or the Griffith's Mental Development Scale (for neurodevelopmental deficits), the Gross Motor Functions Scale or the Movement Assessment Battery for Children (for cerebral palsy), Sonken-Silver visual acuity (for blindness), distraction test (for behavioural disorders) and electroencephalography (for epilepsy), all applied between one and two years of age.
  4. All-cause death during first year of life.

 

Secondary outcomes

  1. Number of patients with seizures at any time.
  2. Number of patients having seizures persisting beyond five days after initiation of treatment.
  3. Fever clearance time (the time between onset of treatment and sustained resolution of fever without recurrence during same illness).
  4. Duration of hospitalisation (in days).
  5. Serious adverse events (leading to death, disability or prolonged hospitalisation), for example, secondary fever and gastrointestinal bleeding. Adverse effects will be defined as unfavourable outcomes that occur during or after the use of an intervention but not necessarily caused by it. Serious adverse events are events that lead to death, disability or prolonged hospitalisation.
  6. Other adverse events.
  7. Incidence of ventriculitis (neuroimaging with evidence of intraventricular debris, pus and enhanced ventricular lining during hospitalisation).
  8. Incidence of hydrocephalus (clinically diagnosed with or without ultrasound confirmation of ventricular dilation occurring during hospitalisation or within one year of treatment).
  9. Incidence of SIADH at one month post treatment (rapid weight gain, decreased urine output, serum sodium less than 130 mmol/L, plasma osmolality less than 270 mOsm/kg, urinary osmolality greater than 100 mOsm/kg and urinary sodium greater than 40 mmol/L during hospitalisation).
  10. Incidence of bleeding diatheses at one month post treatment (external bleeding including oozing from puncture sites, purpura and petechiae, as well as evidence of internal bleeding such as haematuria and haematemesis occurring during hospitalisation).

 

Search methods for identification of studies

 

Electronic searches

We will contact the Neonatal Review Group Trials Search Co-ordinator to search the review group's trials registry. We will search the Cochrane Neonatal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (1966 to date); African Index Medicus (up to date), CINAHL (up to date), EMBASE (up to date), LILACS (up to date) and the Science Citation Index (up to date). We will also search the metaRegister of Controlled Trials (mRCT) to identify some completed/yet unpublished and ongoing trials. We will maintain no language restrictions. If we identify a study in abstract form only, we will evaluate it for possible inclusion in the review and will attempt to contact the authors for more information to either include or exclude the study. We will perform a handsearch of the reference lists of articles for which the full text is obtained.

We will use the search strategy provided in the guidelines of the Cochrane Neonatal Review Group. The key words will include [CORTICOSTEROIDS] OR [STEROIDS] OR [DEXAMETHASONE] OR [METHYLPREDNISOLONE] OR [BETAMETHASONE] OR [HYDROCORTISONE] AND [NEONATAL] OR [NEWBORN] OR [NEONATES] OR [INFANTS] AND [MENINGITIS] AND [BACTERIAL] OR [PYOGENIC] NOT [TUBERCULOUS] AND [CLINICAL TRIAL] OR [RANDOMIZED CONTROLLED TRIAL].

 

Searching other resources

We will contact researchers in the field to ask for knowledge of any ongoing studies and will handsearch the abstracts of neonatology conferences to identify further trials.

 

Data collection and analysis

 

Selection of studies

Two review authors (TAO and CCO) will independently screen the results (titles and abstracts) of the literature search for potentially relevant trials. We will retrieve full reports of the potentially relevant trials and independently determine if they meet the review inclusion criteria using a pre-tested eligibility form. For each step of the review, we will resolve contentious issues by discussion. We will consult an Editor within the Cochrane Neonatal Group, where necessary. We will also attempt to contact trial authors for further information if trial eligibility is unclear. We will list all excluded studies, along with the reason for excluding them. We will ensure that trials with multiple publications are included only once, but if we find that multiple publications include different but relevant outcomes, we will include all the publications in the review. All different references from the same study will be included under the main reference.

 

Data extraction and management

Two review authors (TAO and CCO) will independently extract data using a pre-tested data extraction form. One review author (CCO) will enter the data into Review Manager 5.1 (RevMan 2011 while a second review author (TAO) will cross-check the data for completeness and accuracy. Data will be extracted from the number of participants randomised and number analysed in each group for each reported outcome.

We will extract data for dichotomous outcomes by recording the total number of participants randomised, number of participants experiencing the events and number of participants in each treatment group.

For continuous outcomes, we will extract the number of participants for each treatment arm, arithmetic means and standard deviations (SDs). If we encounter data with skewed distribution, where the data have been reported as geometric means, we will extract geometric means and SDs on the log scale or as medians and ranges if medians have been used. For rate and count outcomes (such as participants with outcomes that occur more than once over the period of trial), we will extract the number of events or episodes experienced in each trial arm and person-time over which the events were experienced for each group. We will extract hazard ratios and SDs for time-to-event outcomes. We will extract data on reported adverse events.

We will attempt to contact the trial authors where the relevant details were not recorded or were unclear. If there are disagreements with regard to data extraction, we will resolve them by discussion and asking for the opinion of an Editor in the Neonatal Group.

 

Assessment of risk of bias in included studies

We will independently assess risk of bias for every eligible study using the guidelines provided in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

Disagreements will be resolved through discussions.  

We will independently assess the risk of bias within each included study in relation to the following five domains (allocation sequence generation, allocation concealment, blinding, handling of incomplete outcome data and selective outcome reporting) with ratings of 'Yes' (low risk of bias), 'No' (high risk of bias) and 'Unclear' (uncertain risk of bias).

Details of specific assessments are as outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

(1) Allocation sequence generation

We will describe, for each included study, the method used to generate the allocation sequence to allow an assessment of whether it should produce comparable groups.

The methods will be graded as follows:

  • low risk of bias (truly random processes such as the use of table of randomisation or computer-generated random numbers);
  • high risk of bias (non-random processes such as use of hospital record numbers or dates of birth);
  • unclear risk of bias.

(2) Allocation concealment

We will describe for each included study, the method used to conceal allocation to interventions prior to assignment and will assess whether intervention allocation could have been predicted before or changed after recruitment. The methods will be graded as follows:

  • low risk of bias;
  • high risk of bias;
  • unclear risk of bias.

(3) Blinding of participants and researchers

We will describe for each included study, the methods used to blind study participants and researchers from knowledge of which intervention a participant received. Blinded studies or studies in which non-blinding was not likely to affect results significantly will be classified as low risk of bias. Non-blinded studies will be classified as high risk of bias.

4) Incomplete outcome data

We will describe for each included study, the methods used to account for incomplete outcome data, with regard to the amount, nature and handling of incomplete outcome data. In instances where studies do not report complete outcome data, we will attempt to obtain missing data by contacting the study authors. We will extract and report on data on attrition and exclusions as well as the numbers involved (compared with total randomised), reasons for attrition/exclusion where reported or obtained from investigators, and any re-inclusions in analyses performed by review authors. Unbiased follow-up will be taken as when at least 80% of the participants can be continued to be followed up. Based upon this, we will judge whether the researchers dealt with incomplete data. We will rate as follows: 'yes' (low risk of bias); 'no' (high risk of bias) and 'unclear' (uncertain risk of bias). 

5. Selective outcome reporting

We will attempt to assess the possibility of selective outcome reporting by investigators in the included trials, where available we will also attempt to look at study protocols; based upon this, we will judge whether reports of the study were free from suggestion of selective outcome reporting.

We will rate as follows: 'yes' (low risk of bias), 'no' (high risk of bias) and 'unclear' (uncertain risk of bias).

We will explore other sources of bias, particularly the sources of funding of the included studies and other study peculiarities.

 

Measures of treatment effect

 

Continuous data 

If means and SDs are available, continuous data will be analysed. We will extract and utilise this for the analysis irrespective of provision of mean and SD if mean difference is provided. We will be interested in post intervention values. We will re-calculate the SD in instances where the standard error is reported. We will extract data from studies that reported adequately on skewed continuous data as medians rather than means. We will report these data separately where appropriate. We will calculate the weighted mean difference (WMD) and 95% confidence interval (CI) for continuous data.

 

Binary data 

We will analyse binary outcomes by calculating the risk ratio (RR), risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB) and number needed to treat for an additional harmful outcome (NNTH) with 95% CIs.

 

Unit of analysis issues

We will describe, for each included study, the observations on participants at selected time points. We will analyse follow-up data available at the point of discharge from the hospital as well as at the age of one month, three months, six months and one year as we will be assessing some of the outcomes at these different time points. We will adjust for clustering by applying the intracluster correlation coefficient if cluster trials are identified.

 

Dealing with missing data

When necessary, we will attempt to contact the study author(s) to supply any unreported data (e.g. group means and SDs, details of dropouts, and details of interventions received by the control group). If a study reports outcomes only for participants completing the trial or only for participants who followed the protocol, authors will be contacted and asked to provide additional information to facilitate an intention-to-treat analysis and in instances where this is not possible we will perform a complete case analysis.

 

Assessment of heterogeneity

Statistical heterogeneity will be assessed by examining the I2 statistic (Higgins 2002; Higgins 2003), a quantity that describes approximately the proportion of total variation that is due to variation between studies. In addition, a Chi2 test of homogeneity at 10% level of statistical significance will be employed to determine the strength of evidence against the hypothesis that all studies come from the same population. As a rough guide, an I2 statistic between 0% and 50% will represent mild heterogeneity, 51% to 75% will represent moderate heterogeneity and above 75% will indicates considerable heterogeneity. We will inspect forest plots, as poor overlap may be due to significant heterogeneity.

 

Assessment of reporting biases

We will prepare funnel plots (estimated treatment effects against their standard error) to explore publication bias if there are more than 10 trials in a comparison. Asymmetry could be due to publication bias, but can also be due to a relationship between trial size and effect size.

 

Data synthesis

We will conduct meta-analyses for trials with similar characteristics. We will carry out an intention-to-treat analysis or carry out a complete case analysis where there is loss to follow up. We will use the fixed-effect model and present all our results with 95% CI. We will calculate the NNTB, NNTH, WMD and 95% CIs for our continuous outcomes, and RR and RD with 95% CIs for our dichotomous outcomes.

 

Subgroup analysis and investigation of heterogeneity

We will conduct subgroup analyses to assess the benefit or otherwise of adjunctive corticosteroid treatment.

We will perform subgroup analyses to address:

  1. the efficacy of adjuvant corticosteroids in infants with gestational age < 37 weeks and those ≥ 37 weeks;
  2. the efficacy of corticosteroids as an adjuvant treatment in different antibiotic classes (comparison will be made for penicillins with or without aminoglycosides versus cephalosporins with or without aminoglycosides);
  3. the efficacy of adjuvant corticosteroids based on causative bacterial agent (comparison will be made for GBS and other Gram-positive bacteria versus Gram-negative bacteria);
  4. impact of the time of initiation of adjunctive corticosteroid treatment (comparison will be made for pre-antibiotic (up to one hour prior to the commencement of antibiotics) and post antibiotic (simultaneously with antibiotics or after the commencement of antibiotics));
  5. impact of the duration of adjunctive corticosteroid treatment on the outcome of neonatal bacterial meningitis (comparison will be made for duration less than four days and four days or more);
  6. impact of corticosteroids on the outcomes for studies conducted in developed countries versus developing countries;
  7. impact of corticosteroids on the outcomes among infants with confirmed meningitis (positive CSF culture or PCR) versus suspect meningitis (deranged cellular or chemical constituents of the CSF without positive CSF culture or PCR).

We will assess important clinical heterogeneity by comparing the distribution of important clinical heterogeneity factors (study participants, study setting, type of intervention and co-intervention, and baseline antibiotic treatment) and methodological heterogeneity factors (randomisation, allocation concealment, blinding of outcome assessment, losses to follow up).

 

Sensitivity analysis

We will conduct sensitivity analyses to explore the effect of the methodological quality of the trials, checking to ascertain if studies with a high risk of bias overestimate the effect of treatment. 

 

 

Acknowledgements

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Contributions of authors
  7. Declarations of interest
  8. Sources of support

Dr. Olufemi T Oladapo is acknowledged for his contributions to the design and content of the review protocol.

 

Contributions of authors

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Contributions of authors
  7. Declarations of interest
  8. Sources of support

TAO initiated and designed the future review.
CCO contributed to the design of the future review.
Both review authors made substantial intellectual contributions to the protocol.

 

Declarations of interest

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Contributions of authors
  7. Declarations of interest
  8. Sources of support

None.

 

Sources of support

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Contributions of authors
  7. Declarations of interest
  8. Sources of support
 

Internal sources

  • No sources of support supplied

 

External sources

  • Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Department of Health and Human Services, USA, under Contract No. HHSN267200603418C, USA.
    The Cochrane Neonatal Review Group has been funded in part with Federal funds from the Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Department of Health and Human Services, USA, under Contract No. HHSN267200603418C
  • Nigerian Branch of the South African Cochrane Centre, Nigeria.
    Reviews for Africa Programme (RAP) Fellowship 2012

References

Additional references

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Acknowledgements
  7. Contributions of authors
  8. Declarations of interest
  9. Sources of support
  10. Additional references
Airede 2008
  • Airede KI, Adeyemi O, Ibrahim T. Neonatal bacterial meningitis and dexamethasone adjunctive usage in Nigeria. Nigerian Journal of Clinical Practice 2008;11(3):235-45.
Brouwer 2010
Chang 2003
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Furyk 2011
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Higgins 2002
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