Abstract

Background: Placement of cerebrospinal fluid (CSF) shunt for diversion remains a primary treatment for patients with hydrocephalus despite its surgical complications, including shunt infection, that remain high and become a medical and social problem. The meta-analysis was conducted to investigate risk factors of shunt infection in pediatrics.

Methods: Literature was searched on PubMed, Scopus, and the Cochrane Library. The methodology used for this investigation was preferred reporting items for systematic reviews and meta-analysis.

Results: This meta-analysis included five publications. The only significant results were found in ages P

Conclusion: Younger age during the shunt placement procedure, Caucasian race, and African–American race have a significantly higher risk of CSF shunt infection. The previously reported higher risk of shunt infection in cohort studies, such as IVH of prematurity and the presence of gastrostomy, were not significant in this study. Primary studies regarding shunt infection are advocated to be performed in a more extensive population with further risk factors included in the analysis.

Keywords: Hydrocephalus, Pediatrics, Risk factors, Shunt infection

INTRODUCTION

Complications are frequent following cerebrospinal fluid (CSF) shunt placement. Infection is one of the most frequent and serious side effects, occurring in 5–25% of cases.[ 14 , 21 ] Shunt infection following shunt placement has been reported to have serious morbidity and mortality, including increased expenses for shunt revision, hospital readmission, prolonged antibiotic use, and related operations.[ 12 , 14 ]

Several studies with observational methods have previously been carried out to identify risk factors in the occurrence of shunt infections. Despite its various reports, there has been no systematic review and meta-analysis methods ever conducted as the basis for the strongest scientific evidence regarding shunt infection in pediatrics. The authors aim to collect studies that reported risk factors of shunt infection and analyze using a combined proportion system to assess the factors that provide the most impactful and significant role in shunt infection. The results of this research would be beneficial in predicting the incidence of shunt infections more accurately and developing prevention strategies.

MATERIALS AND METHODS

Literature search strategy

The journal search strategy was carried out according to the preferred reporting items for systematic review and meta-analysis protocol (PRISMA) guidelines [ Figure 1 ]. Journal data were collected through several databases, such as PubMed, Cochrane, and EMBASE.

Figure 1:

Literature search flow.

Study selection criteria

The authors reviewed published studies in the database. We excluded all unpublished studies or articles-in-press and used the keywords [ Table 1 ]. The articles searched had no limitations on the year published. To minimize bias, we manually searched the references mentioned in the appropriate articles to find further primary studies. Subjects were patients who underwent a primary CSF shunt procedure with age <16 years. Exclusion criteria were subjects with age >16 years, and the shunt procedure was not the first shunt procedure for the patient. Articles in indonesian or English were acceptable for this study and had no publication year restrictions. The data studied included age, hydrocephalus etiology, gastrostomy presence, race and ethnicity, comorbidity, and bias. Statistical averages and percentages for all populations and characteristics were examined and described descriptively.

Table 1:

Keywords search strategy

Analysis

RevMan version 5.4 from the Cochrane review was used. A forest plot was generated to show visual statistics between variables. Pooled effect sizes and matching 95% confidence intervals (CIs) were computed for relevant outcome measurements. Cochran’s Q test and the I² statistic were used to evaluate the heterogeneity among the studies. When necessary, subgroup and sensitivity analyses were carried out to investigate the causes of heterogeneity and evaluate the reliability of the results.

Quality assessment

A bias analysis (confounding, selection, information, and reporting bias) was conducted on five included studies. Authors assessed the bias based on the modified Cochrane collaboration tool: Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) [ Figure 2 ].[ 20 ]

Figure 2:

Bias analysis summary.

Protocol registration

The protocol for this systematic review and meta-analysis was filed with the relevant registry International prospective register of systematic reviews (PROSPERO) to guarantee transparency and adherence to standards. PROSPERO has already received the study’s registration (ID: 598408). In Figure 1 , the PRISMA flowchart is explained.

RESULTS

Characteristics of included studies

Five studies were included after conducting a literature search. The research flow diagram is shown in Figure 1 . The search was conducted in July 2024. After removing duplicates, 184 articles were excluded from the abstract review and a further 104 articles were in the full-text review. Of the remaining studies, we continued with a meta-analysis for five eligible. The five studies included retrospective cohort studies conducted in the United States and involved multicentres, with the average population size of these five studies being 2,568.2 pediatric patients. The average duration of observation carried out to identify the onset of shunt infection from the five studies was 291.2 days of observation, with the shortest observation duration carried out by Alvi et al.[ 1 ] in 2022 for 30 days. CSF shunt infections occurred at an incidence rate of 1162 incidents from 12,841 populations studied in the five literature in this meta-analysis, or 9.04%. These five studies did not report the duration of shunt infection calculated from when the shunt was placed. Research demographic data are shown in Table 2 .

Table 2:

Demographic summary of the studies.

Risk of bias assessment

As shown in Table 2 every study analyzed this way had a cohort design. The total risk of bias in the included studies was minimal, according to the evaluation of cohort studies using the (ROBINS-I).[ 20 ]

Meta-analysis of measured outcomes

A total of three studies in the <6 months group, two studies in the 6–12 months group, and two studies in the more than 12 months group were reported. The analysis showed a significant increase in the risk of infection in the age group <6 months with RR 33.06 (95% CI 9.27–117.99; P < 0.01) and at age more than 12 months at the time of CSF shunt installation with RR 3.58 (95% CI 1.37-9.36; P < 0.01 [ Figure 3 ].

Figure 3:

Forest plot of the RR on age groups (a) <6 months, (b) 6-12 months, and (c) more than 12 months. MH: Mantel-Haenszel analysis, CI: Confidence interval, RR: Relative risk.

Four of the five meta-analysis studies reported the incidence of infection after CSF shunt installation in the hydrocephalus group with intraventricular hemorrhage (IVH) of prematurity etiology, three studies in the congenital hydrocephalus etiology group, and four studies in the central nervous system (CNS) tumor etiology group. The relative risk meta-analysis test showed no significant results in all groups [ Figure 4 ]. Two studies in this meta-analysis were analyzed for the incidence of infection after CSF shunt installation in population groups using gastrostomy. The CSF shunt infection risk was not significant in the hydrocephalus group employing gastrostomy (RR = 3.8; 95% CI 0.91–15.88; P = 0.07) [ Figure 5 ].

Figure 4:

Forest plot of the RR on etiology of (a) intraventricular hemorrhage of prematurity, (b) congenital hydrocephalus, and (c) tumor. MH: Mantel-Haenszel analysis, CI: Confidence interval, RR: Relative risk.

Figure 5:

Forest plot of RR of gastrostomy status. MH: Mantel-Haenszel analysis, CI: Confidence interval, RR : Relative risk

Two studies in this meta-analysis were analyzed for the incidence of infection after CSF shunt installation in populations with comorbid malignancies. The result demonstrated a significant RR of CSF shunt infection with respiratory comorbidity (RR = 0.22; 95% CI 0.11–0.43; P < 0.01) [ Figure 6 ].

Figure 6:

Forest plot of RR of comorbid conditions, (a) malignancy and (b) respiratory. MH: Mantel-Haenszel analysis, CI : Confidence interval, RR: Relative risk.

Three studies in this meta-analysis analyzed the incidence of infection after cerebrospinal fluid (CSF) shunt installation in population groups of Caucasian race, three studies in population groups of African–American race, and two studies in population groups with Latin ethnicity. There were 500 incidents of infection from a total of 4775 hydrocephalus groups with Caucasians compared to 484 incidents of infection from a total of 3871 hydrocephalus populations other than Caucasians. The relative risk results demonstrated a significant risk in the probability of CSF shunt infection in the Caucasian hydrocephalus group with an RR of 15.24 (95% CI 6.77–34.34; P < 0.01) and African–American hydrocephalus group with an RR of 2.37 which was statistically significant (95% CI 2.07–2.7; P < 0.01) [ Figure 7 ].

Figure 7:

Forest plot of RR regarding the race of (a) Caucasian, (b) African-Americans, and (c) Latinos. MH: Mantel-Haenszel analysis, CI: Confidence interval, RR: Relative risk.

DISCUSSION

Age

This study obtained significant results in the age group of <6 months with an RR of 33.06 (95% CI 9.27–117.99; P < 0.01). This finding is consistent with earlier retrospective reports. There are several hypotheses to expound the relation of age and risk of CSF shunt infection. One of the established theories is an underdevelopment of the cellular and humoral immune systems in children under 12 months of age, where immunoglobulins in newborns are dominated by immunoglobulin G (IgG) obtained from maternal through the placenta. Maternal IgG concentration will decrease progressively due to physiological catabolism processes until 12 months of age. Maternal IgG has limited capacity because it relies on maternal history of antigen exposure. Antibody production begins in the 3^rd month of life, and at the age of 4–6 years, the IgG levels will be equivalent to adult IgG levels.[ 13 ] Newborns are susceptible to infection by Gram-negative pathogens; this finding is related to the absence of maternal immunoglobulin M (IgM) transport across the placenta, where IgM is the main antibody against Gram-negative pathogens.[ 3 , 13 ] Another established theory is the vulnerability and immaturity of the skin barrier with a higher density of skin bacterial flora colonies in younger age groups, causing a higher risk of longer wound healing than adults, longer hospital stays, and susceptibility to comorbidities.[ 9 , 22 ]

Etiology of hydrocephalus

IVH of prematurity as the cause of hydrocephalus showed a major significance in this study. Newborns with very low birth weight who survive the critical phase will have a high risk of IVH, including germinal matrix hemorrhage.[ 16 ] Very low birth weight is generally associated with prematurity, resulting in a vulnerable immune condition.[ 17 ] Infants born before 32 weeks of gestational age are prone to develop hypogammaglobulinemia due to the lack of transplacental maternal IgG transport, which generally occurs after 32 weeks of gestation. This hypogammaglobulinemia condition can result in susceptibility to infection.[ 8 ] These conditions concomitantly occurred with IVH in prematurity could increase the risk of infection from a CSF shunt.

CNS tumors, as the etiology of hydrocephalus, have been identified as a significant risk factor for CSF shunt infections. Hydrocephalus associated with malignancies is frequently observed in pediatric patients with primary brain tumors. Studies indicate that hydrocephalus is present in approximately 55–60% of cases, including 50% where it is diagnosed concurrently with the tumor itself.[ 23 ] This underscores the necessity of shunt placement in pediatric patients with CNS tumors complicated by hydrocephalus. While these associations have been well documented in previous cohort studies, the specific mechanisms linking individual risk factors to CSF shunt infections remain unelucidated.[ 5 ]

Presence of gastrostomy status

Placement of a CSF shunt is associated with a 2.49-fold increase in the risk of infection in patients undergoing gastrostomy. This increased risk is attributed to an incomplete skin barrier, which facilitates pathogen colonization around the CSF shunt.[ 4 ] In addition, the direct manipulation of the gastrointestinal tract during gastrostomy creates a connection between the peritoneal cavity and enteric microorganisms, potentially contributing to CSF shunt infections. A retrospective analysis of 208 gastrostomies performed using the image-guided retrograde percutaneous technique reported significant complications, including peritonitis, in 3% of cases.[ 7 ] Investigating whether the distance between the gastrostomy tube insertion site and the VP shunt tip influences the risk of shunt infections is a pertinent research question. Gassas et al. recommend delaying gastrostomy tube insertion in pediatric patients with brain tumors until after the VP shunt has fully healed, as early gastrostomy-related complications may increase the risk of ascending infections involving the VP shunt.[ 6 ]

Comorbid diseases

A meta-analysis of comorbid conditions associated with CSF shunt placement revealed heterogeneous findings. However, hydrocephalus with comorbid respiratory diseases significantly increases the risk of CSF shunt infection. Other comorbidities, including respiratory, cardiological, congenital, gastrointestinal, hematological, metabolic, and renal conditions, may elevate infection risk due to prolonged hospitalization, repeated surgeries, or immune deficiency.[ 11 ] At present, no studies have elucidated the mechanisms linking these comorbidities to CSF shunt infections, aside from the hypothesis that CNS tumors contribute to most pediatric hydrocephalus cases.[ 23 ] Severe comorbidities may also impair nutritional status, compromising immune function and increasing infection susceptibility. Malnutrition weakens the skin barrier through thinning of the dermis, reduces stratum corneum hydration, decreases epidermal cell proliferation, and lowers collagen levels, facilitating pathogen entry.[ 15 ]

Race and ethnicity

The meta-analysis included participants of Caucasian, African–American, and Latino ethnicities. Significant associations with CSF shunt infections were observed in Caucasians and African–Americans, while no significant link was found in Latinos. The reasons for the higher risk in Caucasians and lower risk in African–Americans remain unclear, and no literature currently explains this disparity. The predominance of Caucasian participants (55.2%) may have influenced the results.

Limitation

The authors did not review ongoing randomized trials because no literature or research reports analyzed risk factors for CSF shunt infection until this study was conducted. The amount of literature that meets the eligibility screening in this meta-analysis is limited, and the population of studies that meet the eligibility screening only comes from the United States, so it does not reflect the world’s global population.

CONCLUSION

Several risk factors, such as younger age during the shunt placement procedure, IVH of prematurity, presence of gastrostomy, African–American race, and respiratory comorbidities, have a significant tendency in the incidence of CSF shunt infection in pediatrics. This meta-analysis provides a foundation for future research with higher levels of evidence, as prior studies primarily relied on cohort designs. Future investigations involving larger, multicenter populations across diverse countries are recommended to achieve a more comprehensive global understanding of these risk factors.

Ethical approval:

Institutional Review Board approval is not required as it is a meta -analysis study.

Declaration of patient consent:

Patient’s consent is not required as there are no patients in this study.

Financial support and sponsorship:

Nil.

Conflicts of interest:

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation:

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.

Disclaimer

The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.

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