Pediatrics · Medical Literature
A Systematic Review and Meta-Analysis of the Effectiveness of Physical Interventions Administered Orally for Infants for Reducing Distress During Vaccine Injections.
Abstract
Infants experience distress from repeated vaccine injections in the first year of life. This systematic review evaluated oral nutritive and non-nutritive interventions to reduce distress including: breastfeeding (pre-injection and during), bottle-feeding, sucrose solution, glucose/dextrose solutions, other sweet-tasting oral liquids, and non-nutritive sucking. Cochrane methodology and GRADE were used. Searches were conducted in MEDLINE, EMBASE, APA PsycINFO, CINAHL, and ProQuest Dissertations to identify relevant randomized and quasi-randomized controlled trials. Distress was the critical outcome. Placebo-controlled trials were prioritized when possible. Eligible studies were reviewed and data extracted by at least 2 reviewers. A random-effects model was used to pool the data; results are presented as standardized mean differences (SMDs) with 95% CIs. The certainty of evidence (graded from high, moderate, low, to very low) and the magnitude of effect were used to develop summary statements. Fifty-nine distinctive studies were included, with certainty of evidence ranging from moderate to very low. The magnitude of effect exceeded the minimum threshold (SMD ≥0.2) for all interventions. Breastfeeding during vaccinations likely results in a large reduction in distress (SMD=-2.38, moderate certainty). Breastfeeding pre-injection (SMD=-1.19, low certainty) and bottle-feeding (SMD=-1.65, low certainty) may both result in a large reduction in distress. Evidence from placebo-controlled trials shows that sucrose solution likely results in a large decrease in distress (SMD=-1.02, moderate certainty) and glucose/dextrose solutions likely reduce distress (SMD=-0.78, moderate certainty). Other sweet-tasting oral liquids likely result in a large decrease in distress (SMD=-1.47, moderate certainty). Non-nutritive sucking may reduce distress, but the evidence is very uncertain (SMD=-1.98, very low certainty). In infants, breastfeeding, sweet-tasting solutions, and other oral sweet-tasting liquids are preferred oral interventions to reduce vaccine injection-related distress.
Clinical relevance
Among infants in the first year of life receiving routine vaccine injections, do orally administered physical interventions—including breastfeeding, bottle-feeding, sucrose, glucose/dextrose solutions, other sweet-tasting liquids, and non-nutritive sucking—reduce procedural distress compared with control or placebo? __SNAPSHOT__ {"studyDesign":"Systematic review and meta-analysis of randomized and quasi-randomized controlled trials, conducted using Cochrane methodology and GRADE evidence certainty framework","setting":"Multi-database search (MEDLINE, EMBASE, APA PsycINFO, CINAHL, ProQuest Dissertations); conducted as part of the 2026 HELPinKids&Adults clinical practice guideline update","sampleSize":"59 distinctive studies included; aggregate participant numbers per intervention subgroup not reported in the abstract","population":"Infants in the first year of life undergoing routine vaccine injections; specific age range and inclusion/exclusion criteria beyond infancy not reported in the abstract","intervention":"Orally administered physical interventions: breastfeeding (pre-injection and during injection), bottle-feeding, sucrose solution, glucose/dextrose solutions, other sweet-tasting oral liquids, and non-nutritive sucking (pacifier use)","comparator":"Placebo (prioritized where available) or control (no intervention / standard care); placebo-controlled trials were preferentially analyzed for sweet-tasting solutions","primaryOutcome":"Infant distress during vaccine injection, assessed as the critical outcome (observer-rated; self-report not applicable in this population); measured as standardized mean difference (SMD) with 95% CI using a random-effects model","followUp":"Acute procedural period (during and immediately after vaccination); longer-term follow-up not reported","fundingSource":"Canadian Institutes of Health Research (FRN 159905), University of Toronto; A. Taddio holds the GSK Research Chair in Vaccine Education and Practice-Oriented Tools (endowment to university)"}
Key findings
Fifty-nine studies were included, with certainty of evidence (GRADE) ranging from moderate to very low. All interventions exceeded the pre-specified minimum clinically meaningful effect threshold (SMD ≥ 0.2). Breastfeeding administered during vaccination demonstrated the largest pooled effect at moderate certainty (SMD = −2.38), representing a large reduction in distress. Breastfeeding administered pre-injection (SMD = −1.19, low certainty) and bottle-feeding (SMD = −1.65, low certainty) may each produce large reductions in distress, but confidence in these estimates is lower. From placebo-controlled trials specifically: sucrose solution likely results in a large reduction in distress (SMD = −1.02, moderate certainty), and glucose/dextrose solutions likely reduce distress (SMD = −0.78, moderate certainty). Other sweet-tasting oral liquids (not further specified in the abstract) likely result in a large reduction in distress (SMD = −1.47, moderate certainty). Non-nutritive sucking may reduce distress, but the evidence is very uncertain (SMD = −1.98, very low certainty). Individual study-level confidence intervals, absolute risk differences, p-values, NNT, and adverse event data are not reported in the available abstract. No clinically important harms of these interventions were identified in the abstract, though a formal tolerability analysis is not described.
Practice implications
This meta-analysis, conducted as part of the 2026 HELPinKids&Adults guideline update, provides moderate-certainty evidence that breastfeeding during vaccination and sweet-tasting solutions (sucrose, glucose, other) produce large reductions in infant distress during vaccine injections — a finding consistent with, and updating, the prior 2015 evidence base. The results are most directly applicable to healthy infants in the first year of life receiving routine immunizations. The study did not establish superiority of one intervention over another (head-to-head comparisons were not the primary analytic focus reported in the abstract), did not assess long-term outcomes (e.g., needle fear, vaccine hesitancy, feeding behavior), and did not separately analyze effects by specific infant age subgroups, number of simultaneous injections, or vaccine type. The very low certainty for non-nutritive sucking means its effect estimate is highly uncertain and should not be weighted equally with the moderate-certainty findings. Bottle-feeding and pre-injection breastfeeding show large SMDs but carry only low certainty, limiting confidence in those estimates. Importantly, the GRADE framework used here reflects both the direction and certainty of evidence, not merely statistical significance — large SMDs at very low certainty should prompt caution. Because this review is part of a guideline update using established methodology, findings are unlikely to be overturned by single new trials, though the certainty for several interventions could improve with additional high-quality placebo-controlled studies. NOTE: This summary is based solely on the published abstract; the full paper should be consulted for subgroup analyses, individual study risk-of-bias assessments, heterogeneity statistics, and complete GRADE summaries. __LIMITATIONS__ Only the abstract was available for review; individual study risk-of-bias ratings, heterogeneity (I²) statistics, and complete GRADE summary-of-findings tables are not reported and cannot be evaluated.,Certainty of evidence ranges from moderate to very low across interventions, substantially limiting confidence for several comparisons (particularly non-nutritive sucking at very low certainty and bottle-feeding/pre-injection breastfeeding at low certainty).,Pooling across heterogeneous interventions, outcome measures, infant ages, vaccine types, and clinical settings may contribute to statistical heterogeneity not quantifiable from the abstract.,Breastfeeding analyses cannot be blinded by nature, introducing high risk of performance and detection bias; blinding limitations affect all behavioral/observational outcome measures.,Placebo-controlled comparisons were not available for all interventions; some analyses relied on active or no-treatment controls, which may inflate observed effect sizes.,Aggregate participant numbers per intervention arm are not reported in the abstract, precluding assessment of power and precision for individual subgroup analyses.,Inclusion of quasi-randomized controlled trials introduces risk of allocation bias.,The study population is restricted to infants in the first year of life; findings do not generalize to toddlers, older children, or populations with special needs (e.g., preterm infants, infants with chronic pain conditions).,Funding through a university endowment from a vaccine manufacturer (GSK Research Chair) and public government agencies introduces potential institutional conflicts of interest, though the lead author was appropriately recused from panel voting activities.,No formal assessment of publication bias is described in the abstract.,Long-term outcomes (needle fear, vaccine hesitancy, breastfeeding disruption) were not assessed. __BOTTOM_LINE_CATEGORY__ potentially_practice_informing __BOTTOM_LINE__ This well-conducted systematic review provides moderate-certainty evidence that breastfeeding during vaccination, sucrose solution, glucose/dextrose, and other sweet-tasting oral liquids produce large reductions in infant distress during routine immunizations, and all tested interventions exceeded the minimum clinically meaningful effect threshold. Breastfeeding during injection (SMD = −2.38) and sucrose (SMD = −1.02) should be considered standard-of-care comfort measures for vaccine-receiving infants, consistent with current guideline recommendations. Non-nutritive sucking shows a large point estimate but carries only very low certainty, warranting cautious interpretation pending higher-quality evidence.