Intraligamentary Anesthesia in Pediatric Patients: Is It an Effective Technique? A Systematic Review and Meta-Analysis
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe manuscript presents a well-structured systematic review addressing a clinically relevant topic in pediatric dentistry. The authors adhered to PRISMA guidelines and registered the protocol in PROSPERO.
However, some minor issues should be addressed to improve interpretative balance, particularly concerning the meta-analysis and the strength of the conclusions.
Although the systematic review highlights several favorable outcomes of intraligamentary anesthesia, the meta-analysis demonstrated no statistically significant difference in pain perception between ILA and IANB, with very high heterogeneity.
Thus, the Conclusions section may slightly overstate the clinical superiority of ILA (a first-line anesthetic technique in pediatric dentistry?).
ILA is comparable rather than superior to IANB in terms of pain perception.
Most included studies involved cooperative children and focused primarily on primary mandibular molars. A short statement acknowledging that the findings may not be fully generalizable could be added.
Author Response
The manuscript presents a well-structured systematic review addressing a clinically relevant topic in pediatric dentistry. The authors adhered to PRISMA guidelines and registered the protocol in PROSPERO.
However, some minor issues should be addressed to improve interpretative balance, particularly concerning the meta-analysis and the strength of the conclusions.
Although the systematic review highlights several favorable outcomes of intraligamentary anesthesia, the meta-analysis demonstrated no statistically significant difference in pain perception between ILA and IANB, with very high heterogeneity.
Thus, the Conclusions section may slightly overstate the clinical superiority of ILA (a first-line anesthetic technique in pediatric dentistry?).
Reply: Following the reviewer suggestions, conclusions were modified, including the following sentence: «The present findings indicate that ILA is not associated with greater pain perception during injection when compared with the IANB. When considered alongside existing evidence demonstrating a lower incidence of undesirable soft-tissue anesthesia, such as lip biting, and overall efficacy comparable to other techniques, ILA appears to be a particularly suitable anesthetic option for young children».
ILA is comparable rather than superior to IANB in terms of pain perception.
Most included studies involved cooperative children and focused primarily on primary mandibular molars. A short statement acknowledging that the findings may not be fully generalizable could be added.
Reply: In accordance with the reviewer’s comment, we have modified the following statement to the Discussion section: Only a few studies included permanent teeth [23,27,34], suggesting the need for further investigation in this subgroup. Most participants were cooperative children (Frankl 3–4), indicating that findings may primarily reflect outcomes in children able to engage with dental procedures. Accordingly, caution should be exercised when extrapolating these findings to less cooperative children, permanent teeth, or more complex clinical situations”.
Reviewer 2 Report
Comments and Suggestions for AuthorsComments and suggestions for the manuscript “Intraligamentary Anesthesia in Pediatric Patients: Is It an Effective Technique? A Systematic Review and Meta-Analysis”.
The review is methodologically sound, generally well-written, and adheres to PRISMA and Cochrane guidance. The authors demonstrate strong domain knowledge, and the synthesis of behavioral, physiological, and patient-reported outcomes is a particular strength. However, several conceptual, methodological, and interpretative issues should be addressed to improve scientific rigor, transparency, and balance of conclusions.
Major Comments
Heterogeneity and Meta-Analysis Interpretation
The authors attribute heterogeneity mainly to clinical and subjective factors, but this remains speculative. They reported no sensitivity analysis or leave-one-out analysis.
The authors appropriately limited the meta-analysis due to heterogeneity, but the discussion does not sufficiently emphasize the implications of such high I² values.
Clearly acknowledge that high heterogeneity limits inferential certainty, and clarify that the meta-analysis supports equivalence, not superiority.
Consider adding a brief discussion of why subgroup or sensitivity analyses were not feasible.
Risk of Bias Assessment
The authors reported “overall low risk of bias,” although several studies have unclear randomization procedures, crossover designs without washout justification, or limited blinding.
Three studies were conducted on the same population, increasing the risk of population-level bias.
The authors need to temper the statement “overall low risk” by acknowledging design-related limitations inherent to pediatric dental trials, and clarify how repeated-population studies were handled to avoid overweighting similar samples.
External Validity and Generalizability
Most included studies involved cooperative children only (Frankl 3–4), focused primarily on primary mandibular molars, and were conducted in specific geographic regions (the Middle East, Turkey, Southern Europe).
Clearly state that findings may not generalize to uncooperative or highly anxious children, children with special healthcare needs, or complex multi-tooth or maxillary procedures.
This limitation is partially acknowledged, but it should be clearer.
Insufficient Long-Term Safety Evidence
The authors refer to long-term safety based on a single follow-up study evaluating DDEs.
Avoid framing long-term safety as “confirmed”, and rephrase to indicate that limited preliminary evidence suggests no major long-term harm, while emphasizing the need for longitudinal studies.
Scope of Conclusions vs. Strength of Evidence
While the authors conclude that ILA “may be considered a valid first-line anesthetic option”, this statement is stronger than the available evidence supports, particularly given that only three studies were eligible for meta-analysis. The meta-analysis showed no statistically significant difference in pain perception (VAS) between ILA and IANB, and there is a very high heterogeneity (I² = 93.24%) that undermines confidence in pooled estimates.
Reframe conclusions to reflect non-inferiority rather than superiority. Consider softening language such as “first-line anesthetic option” to “a viable alternative in selected clinical scenarios.”
Minor Comments
Tables
Table 2 is extremely dense and may be difficult for readers to interpret. Consider summarizing key outcomes in a condensed comparison table.
PICOs and Outcomes
The PICOs' question is well-structured, but the outcomes are broad and heterogeneous. In the Methods section, clarify which outcomes were considered primary vs. secondary, even retrospectively.
Language and readability
A careful language and style edit is advised for grammatical inconsistencies and typographical errors that appear throughout (e.g., repeated words, inconsistent hyphenation of “computer-controlled”).
Some outcomes (e.g., HR, SpOâ‚‚) are presented without clear clinical relevance thresholds. Briefly interpret physiological changes in clinical terms (e.g., what magnitude of HR change is meaningful).
Some abbreviations (e.g., CC-IANB) appear before a full contextual explanation.
Author Response
Comments and suggestions for the manuscript “Intraligamentary Anesthesia in Pediatric Patients: Is It an Effective Technique? A Systematic Review and Meta-Analysis”.
The review is methodologically sound, generally well-written, and adheres to PRISMA and Cochrane guidance. The authors demonstrate strong domain knowledge, and the synthesis of behavioral, physiological, and patient-reported outcomes is a particular strength. However, several conceptual, methodological, and interpretative issues should be addressed to improve scientific rigor, transparency, and balance of conclusions.
Major Comments
Heterogeneity and Meta-Analysis Interpretation
The authors attribute heterogeneity mainly to clinical and subjective factors, but this remains speculative. They reported no sensitivity analysis or leave-one-out analysis.
The authors appropriately limited the meta-analysis due to heterogeneity, but the discussion does not sufficiently emphasize the implications of such high I² values.
Clearly acknowledge that high heterogeneity limits inferential certainty, and clarify that the meta-analysis supports equivalence, not superiority.
Consider adding a brief discussion of why subgroup or sensitivity analyses were not feasible.
Reply: Sensitivity or subgroup analyses were not feasible due to the limited number of included studies and the small sample size. We agree that the source of heterogeneity remains speculative and we have updated the discussion section accordingly.
Risk of Bias Assessment
The authors reported “overall low risk of bias,” although several studies have unclear randomization procedures, crossover designs without washout justification, or limited blinding.
Three studies were conducted on the same population, increasing the risk of population-level bias.
The authors need to temper the statement “overall low risk” by acknowledging design-related limitations inherent to pediatric dental trials, and clarify how repeated-population studies were handled to avoid overweighting similar samples.
Reply :We thank te reviewer for the comment. The overall risk-of-bias judgment for each individual study was derived according to the RoB 2 algorithm, which generates the overall rating based on the highest level of risk identified across domains, following the Cochrane guidance. In our assessment, although some domains were judged as presenting “some concerns”, none of the studies reached a high-risk judgment in any domain. Consequently, the algorithm yielded an overall low-risk rating for each study.
Nevertheless, we agree that the original statement required further qualification. In the revised manuscript, we have tempered the expression “overall low risk of bias” by explicitly acknowledging domain-level limitations.
Regarding the three studies conducted on the same population, we did consider them as one in the qualitative analysis. This aspect is now clarified in both the results and discussion sections.
External Validity and Generalizability
Most included studies involved cooperative children only (Frankl 3–4), focused primarily on primary mandibular molars, and were conducted in specific geographic regions (the Middle East, Turkey, Southern Europe).
Clearly state that findings may not generalize to uncooperative or highly anxious children, children with special healthcare needs, or complex multi-tooth or maxillary procedures.
This limitation is partially acknowledged, but it should be clearer.
Reply: we thank the reviewer for the insightful observation. We have updated and further clarified those limitations in the discussion section.
Insufficient Long-Term Safety Evidence
The authors refer to long-term safety based on a single follow-up study evaluating DDEs.
Avoid framing long-term safety as “confirmed”, and rephrase to indicate that limited preliminary evidence suggests no major long-term harm, while emphasizing the need for longitudinal studies.
Reply: We appreciate the reviewer’s concern. The following sentence is now reported in the discussion section: Long-term safety was investigated in only one study, which reported no significant developmental defects of enamel in permanent teeth following previous ILA administration in primary molars. While these findings suggest the absence of major long-term adverse effects, the evidence remains limited and preliminary, underscoring the need for well-designed longitudinal studies to confirm long-term safety.
Scope of Conclusions vs. Strength of Evidence
While the authors conclude that ILA “may be considered a valid first-line anesthetic option”, this statement is stronger than the available evidence supports, particularly given that only three studies were eligible for meta-analysis. The meta-analysis showed no statistically significant difference in pain perception (VAS) between ILA and IANB, and there is a very high heterogeneity (I² = 93.24%) that undermines confidence in pooled estimates.
Reframe conclusions to reflect non-inferiority rather than superiority. Consider softening language such as “first-line anesthetic option” to “a viable alternative in selected clinical scenarios.”
Reply: we thank the reviewer for the comment, the conclusions section has been updated accordingly.
Minor Comments
Tables
Table 2 is extremely dense and may be difficult for readers to interpret. Consider summarizing key outcomes in a condensed comparison table.
Reply : We thank the reviewer for the comment. We have updated the table accordingly to a more concise and readable version.
PICOs and Outcomes
The PICOs' question is well-structured, but the outcomes are broad and heterogeneous. In the Methods section, clarify which outcomes were considered primary vs. secondary, even retrospectively.
Reply : We thank the reviewer for the observation, the PICOs section was modified accordingly
Language and readability
A careful language and style edit is advised for grammatical inconsistencies and typographical errors that appear throughout (e.g., repeated words, inconsistent hyphenation of “computer-controlled”).
Some outcomes (e.g., HR, SpOâ‚‚) are presented without clear clinical relevance thresholds. Briefly interpret physiological changes in clinical terms (e.g., what magnitude of HR change is meaningful).
Some abbreviations (e.g., CC-IANB) appear before a full contextual explanation.
Reply : We sincerely thank the reviewer for these valuable comments. The manuscript has undergone a careful language and stylistic revision to address grammatical inconsistencies, typographical errors, repeated words, and issues such as inconsistent hyphenation. We have also revised the outcomes section to better clarify the clinical relevance of the reported physiological parameters. Additionally, all abbreviations are now defined at first mention and properly contextualized within the text.
Round 2
Reviewer 2 Report
Comments and Suggestions for AuthorsThank you for addressing all comments and making the required corrections.
