This is an update of a Cochrane Review first published in 2015. The conclusions have not changed.
Hypodermic needles of different sizes (gauges and lengths) can be used for vaccination procedures. The gauge (G) refers to the outside diameter of the needle tubing. The higher the gauge number, the smaller the diameter of the needle (e.g. a 23 G needle is 0.6 mm in diameter, whereas a 25 G needle is 0.5 mm in diameter). Many vaccines are recommended for injection into muscle (intramuscularly), although some are delivered subcutaneously (under the skin) and intradermally (into skin). Choosing an appropriate length and gauge of a needle may be important to ensure that a vaccine is delivered to the appropriate site and produces the maximum immune response while causing the least possible harm. Guidelines conflict regarding the sizes of needles that should be used for vaccinating children and adolescents.Objectives
To assess the effects of using needles of different sizes for administering vaccines to children and adolescents on vaccine immunogenicity (the ability of the vaccine to elicit an immune response), procedural pain, and other reactogenicity events (adverse events following vaccine administration).Search methods
We updated our searches of CENTRAL, MEDLINE, Embase, and CINAHL to October 2017. We also searched proceedings of vaccine conferences and two trials registers.Selection criteria
Randomised controlled trials evaluating the effects of using hypodermic needles of any gauge or length to administer any type of vaccine to people aged from birth to 24 years.Data collection and analysis
Three review authors independently extracted trial data and assessed the risk of bias. We contacted trial authors for additional information. We rated the quality of evidence using the GRADE system.Main results
We included five trials involving 1350 participants in the original review. The updated review identified no new trials. The evidence from two small trials (one trial including infants and one including adolescents) was insufficient to allow any definitive statements to be made about the effects of the needles evaluated in the trials on vaccine immunogenicity and reactogenicity.
The remaining three trials (1135 participants) contributed data to comparisons between 25 G 25 mm, 23 G 25 mm, and 25 G 16 mm needles. These trials included infants predominantly aged from two to six months undergoing intramuscular vaccination in the anterolateral thigh using the World Health Organization (WHO) injection technique (skin stretched flat, needle inserted at a 90° angle and up to the needle hub in healthy infants). The vaccines administered were combination vaccines containing diphtheria, tetanus, and whole‐cell pertussis antigens (DTwP). In some trials, the vaccines also contained Haemophilus influenzae type b (DTwP‐Hib) and hepatitis B (DTwP‐Hib‐Hep B) antigen components.
Incidence of vaccine‐preventable diseases: No trials reported this outcome.
Procedural pain and crying: Using a wider gauge 23 G 25 mm needle may slightly reduce procedural pain (low‐quality evidence) and probably leads to a slight reduction in the duration of crying time immediately after vaccination (moderate‐quality evidence) compared with a narrower gauge 25 G 25 mm needle (one trial, 320 participants). The effects are probably not large enough to be clinically relevant.
Immune response: There is probably little or no difference in immune response, defined in terms of the proportion of seroprotected infants, between use of 25 G 25 mm, 23 G 25 mm, or 25 G 16 mm needles to administer a series of three doses of a DTwP‐Hib vaccine at ages two, three, and four months (moderate‐quality evidence, one trial, numbers of participants in analyses range from 309 to 402. The immune response to the pertussis antigen was not measured).
Severe and non‐severe local reactions: 25 mm needles (either 25 G or 23 G) probably lead to fewer severe and non‐severe local reactions after DTwP‐Hib vaccination compared with 25 G 16 mm needles (moderate‐quality evidence, one trial, 447 to 458 participants in analyses). We estimate that one fewer infant will experience a severe local reaction (extensive redness and swelling) after the first vaccine dose for every 25 infants vaccinated with the longer rather than the shorter needle (number needed to treat for an additional beneficial outcome (NNTB) with a 25 G 25 mm needle: 25 (95% confidence interval (CI) 15 to 100); NNTB with a 23 G 25 mm needle: 25 (95% CI 17 to 100)). We estimate that one fewer infant will experience a non‐severe local reaction (any redness, swelling, tenderness, or hardness (composite outcome)) at 24 hours after the first vaccine dose for every 5 or 6 infants vaccinated with a 25 mm rather than a 16 mm needle (NNTB with a 25 G 25 mm needle: 5 (95% CI 4 to 10); NNTB with a 23 G 25 mm needle: 6 (95% CI 4 to 13)). The results are similar after the second and third vaccine doses.
Using a narrow gauge 25 G 25 mm needle may produce a small reduction in the incidence of local reactions after each dose of a DTwP vaccine compared with a wider gauge 23 G 25 mm needle, but the effect estimates are imprecise (low‐quality evidence, two trials, 100 to 459 participants in analyses).
Systemic reactions: The comparative effects of 23 G 25 mm, 25 G 25 mm, and 25 G 16 mm needles on the incidence of postvaccination fever and other systemic events such as drowsiness, loss of appetite, and vomiting are uncertain due to the very low quality of the evidence.Authors' conclusions
Using 25 mm needles (either 23 G or 25 G) for intramuscular vaccination procedures in the anterolateral thigh of infants using the WHO injection technique probably reduces the occurrence of local reactions while achieving a comparable immune response to 25 G 16 mm needles. These findings are applicable to healthy infants aged two to six months receiving combination DTwP vaccines with a reactogenic whole‐cell pertussis antigen component. These vaccines are predominantly used in low‐ and middle‐income countries. The applicability of the findings to vaccines with acellular pertussis components and other vaccines with different reactogenicity profiles is uncertain.
Paul V Beirne, Sarah Hennessy, Sharon L Cadogan, Frances Shiely, Tony Fitzgerald, Fiona MacLeod
Plain language summary
Needle size for vaccination procedures in children and adolescents
Vaccines contain antigens that make the body's immune system produce antibodies that can protect against disease, which is known as an immune response. Antigens are modified or partial forms of the virus, bacteria, or toxin that cause the disease that the vaccine protects against. Because the antigen is altered from its original form, it cannot cause disease, but it can produce an immune response.
Vaccines can be injected using needles of different lengths and gauges. The needle gauge (G) refers to the width (diameter) of the needle. The higher the gauge number, the narrower the needle. For example, a 25 G needle is approximately 0.5 mm in diameter and is narrower than a 23 G needle, which has a diameter of 0.6 mm. Guidelines conflict regarding the lengths and gauges of needles that should be used for vaccinating children and adolescents.
We wanted to find out if the length and gauge of needles used to vaccinate children and adolescents has an influence on the:
1) immune response to the injected vaccine;
2) pain experienced during the vaccination procedure;
3) occurrence of reactions such as swelling, tenderness, and redness at the site where the vaccine is given; fever (high temperature); and other side effects that can occur after vaccination.
Quality of the evidence
We included five studies involving 1350 people. We rated the quality of the evidence from studies as very low, low, moderate, or high. Very low‐quality evidence means that we are very uncertain about the results. High‐quality evidence means that we are very confident in the results. There were problems with the design of some studies, and data were insufficient to answer some parts of our review question. The quality of the evidence from two studies was too low to allow us to draw any conclusions about the effects of the needles compared in the studies. However, there was sufficient evidence from the remaining three studies to allow us to reach conclusions.
The three studies that allowed us to reach conclusions involved 1135 healthy infants aged mostly between two and six months. The infants were vaccinated in the thigh with either 25 G 25 mm (narrow, long needles), 23 G 25 mm (wide, long needles), or 25 G 16 mm needles (narrow, short needles). The needles were inserted at right angles (90° angle) into the skin and pushed down into the muscle of the thigh. The vaccines injected were combination vaccines designed to protect against several diseases including diphtheria (D), tetanus (T), whooping cough (pertussis), and Haemophilus influenzae type b disease (Hib). The vaccines all contained whole‐cell pertussis (wP) vaccine antigens. These vaccines are commonly used in low‐ and middle‐income countries but not in high‐income countries. Our review findings are therefore most relevant to low‐ and middle‐income countries.
We found moderate‐quality evidence that infants vaccinated in the thigh with 25 mm needles probably have fewer severe reactions (extensive redness and swelling in the thigh) after DTwP‐Hib vaccination than infants vaccinated with 16 mm needles. We also found that the longer needles probably lead to fewer non‐severe reactions such as mild swelling, tenderness, and redness after vaccination. The immune response to the vaccine is probably similar with the long and the short needles.
We found low‐quality evidence that the wide, long needle may slightly reduce the pain of the vaccination procedure compared with the narrow, long needle. We found moderate‐quality evidence that the wide, long needle probably slightly reduces the duration of crying immediately following vaccination compared with the narrow, long needle. The differences in pain and crying between use of the wide and narrow needles are probably too small to be of any practical importance.
We found low‐quality evidence that infants vaccinated with the narrow, long needle may have slightly fewer non‐severe reactions than infants vaccinated with the wide, long needle.
We do not know if needle size has an effect on fever or other reactions that sometimes occur after vaccination including drowsiness, loss of appetite, and vomiting due to the very low quality of the evidence.
The evidence in our review is current to October 2017.
Paul V Beirne, Sarah Hennessy, Sharon L Cadogan, Frances Shiely, Tony Fitzgerald, Fiona MacLeod
Implications for practice
Our review findings are most applicable to healthy infants between the ages of approximately two and six months undergoing intramuscular vaccination in the anterolateral thigh with combined vaccines containing diphtheria, tetanus, and whole‐cell pertussis antigens (DTwP vaccines) using an injection technique (WHO technique) where the skin is stretched flat and the needle is inserted at a 90° angle through the skin and up to the needle hub:
The main findings of our review were derived from a small number of trials that evaluated the effects of using needles of different sizes to administer combination vaccines with a whole‐cell pertussis (wP) component. The review findings are therefore likely to be most relevant in low‐ and middle‐income countries, where wP vaccines are predominantly used. These vaccines have a different reactogenicity profile and cause more local and systemic reactions than vaccines with an acellular pertussis (aP) component that are used in most high‐income countries. It cannot be assumed that similar results to those reported in our review, particularly in relation to the effects of needle size on local reactions, would be observed in populations and settings where aP vaccines are predominantly or exclusively used.
Implications for research
Our review included only a small number of randomised controlled trials (RCTs) that evaluated the effects of a limited range of needle sizes for administering vaccines to a restricted number of populations (predominantly infants between the ages of two and six months). As such, our review has identified several areas where additional RCTs are required to inform healthcare decisions regarding the choice of appropriate needle sizes for vaccination procedures in children and adolescents. In formulating our research recommendations, we have considered the types of interventions and populations and the types of outcomes that should be considered in future trials. We have also included some recommendations regarding trial reporting.Types of populations and interventions
As highlighted in the Background section of this review, there are inconsistencies in the recommendations made by National Immunization Technical Advisory Groups (NITAGs) in different countries regarding the sizes of needles that should be used when administering vaccines to children and adolescents. These variations are indicative of uncertainty regarding the optimal needle sizes that should be used for vaccination procedures in people of specific ages or body masses. Randomised controlled trials are required to address these uncertainties, and we consider that the current recommendations made by NITAGs can act as a useful template to inform the interventions and populations that should be considered in future trials.
The aim of any vaccination procedure should be to attain the maximum immunity with the least possible harm. Trials evaluating the effects of needle size for vaccination procedures should therefore ideally measure both immunogenicity and reactogenicity outcomes.Immunogenicity outcomes
We identified no trials that reported on the incidence of vaccine‐preventable diseases. Although these endpoints could not reasonably be expected in trials conducted in countries with low disease incidence, in some settings and for some diseases (e.g. tetanus, Haemophilus influenzae type b (Hib)) clinical disease endpoints could potentially be used in trials. Where the use of clinical immunogenicity endpoints is neither practical nor feasible, two substitute immunogenicity outcomes should be used: 1) seroprotection (i.e. the proportion of vaccine recipients who responded in a prescribed manner by reaching predefined threshold levels of protection against disease); and 2) geometric mean antibody concentrations or geometric mean antibody titres. We have summarised generally accepted thresholds of vaccine‐induced correlates and surrogates of protection for selected vaccines in Appendix 3.Reactogenicity outcomes
We identified only one trial that evaluated the effect of needle size on vaccination‐related procedural pain and procedural crying (crying with immediate onset after vaccination). Future trials should use pain assessment tools with established validity and reliability to measure the pain response to vaccination procedures using needles of differing lengths and gauges. We have listed several of these tools in Appendix 2.
Some of the trials included in our review used different definitions of reactogenicity events, and some adverse events (e.g. fever, swelling, and tenderness) were measured in different ways in different trials. Future trials should use standardised case definitions for adverse events following immunisation (AEFI) to ensure comparability of results across clinical trials and to facilitate meta‐analysis of results from different trials. We suggest that researchers should adopt the case definitions for AEFIs developed by the Brighton Collaboration. Researchers should also consult the detailed guidelines accompanying each case definition, which are designed to facilitate the standardised collection, analysis, and presentation of information about adverse events following immunisation (Brighton Collaboration 2014; see also Beigel 2007; Gidudu 2008; Bonhoeffer 2009).Trial reporting
Some adverse events (e.g. needle contact with bone) were not reported in trial publications, and we were unable to determine definitively if such events did not occur, or if such events may have occurred but were simply not recorded and reported. We recommend that trial authors should explicitly mention in trial publications any adverse events that did not occur during the trial.
Our review identified several other deficiencies in trial reporting, most notably in relation to the details provided regarding the needles, vaccines, and the vaccination procedures used in trials. At a minimum, we would suggest that trial reports should provide details on:
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