Adverse reactions following upper arm vs. buttock DTaP vaccination in children: A retrospective observational study in Wuxi, China, 2020–2024

ABSTRACT

Adverse reactions are closely associated with vaccination sites, making site selection vital for clinical administration of the diphtheria, tetanus, and acellular pertussis (DTaP) vaccine. This retrospective observational study enrolled 636,169 DTaP inoculations in Wuxi from 2020 to 2024. Adverse reaction data were extracted from the National Adverse Events Following Immunization Surveillance System of China, and dose data were obtained from the Jiangsu Province Vaccination Integrated Service Management Information System. We compared adverse reaction reporting rates stratified by overall incidence, severity, vaccine dose, and clinical manifestations, as well as constituent proportions of adverse reactions according to onset time between upper arm and buttock injection groups. The upper arm group had slightly higher reporting rates of adverse reactions and common reactions than the buttock group, at 23.88 (95% CI: 22.54–25.22) vs. 17.89 (95% CI: 15.56–20.21) and 23.13 (95% CI: 21.81–24.45) vs. 16.94 (95% CI: 14.68–19.20) per 10,000 doses, both p < .001, while rare reaction rates were comparable, at 0.75 (95% CI: 0.51–0.98) vs. 0.95 (95% CI: 0.41–1.48) per 10,000 doses, p = .473. Slightly elevated adverse reaction rates were also found in upper arm administration for the first and second doses. Redness and swelling, induration, and fever were the predominant adverse symptoms, all showing modestly elevated rates after upper arm injection. The adverse reactions at both sites were predominantly common reactions within expected range. Despite a slightly elevated risk of common reactions, upper arm injection may be the preferred site for DTaP vaccination for overall safety.

Introduction

The diphtheria, tetanus, and acellular pertussis (DTaP) combined vaccine is indicated for the prevention of diphtheria, tetanus, and pertussis.^1–3 In China, the Expanded Program on Immunization (EPI) was launched in 1978 to provide free vaccination with the diphtheria, tetanus, and whole-cell pertussis (DTwP) combined vaccine for eligible children. Since 2007, the DTwP vaccine has been gradually replaced by the DTaP vaccine. Before 2025, children were administered the DTaP vaccine following a 4-dose immunization schedule at ages 3, 4, 5, and 18 months.⁴ In response to the epidemiological history of pertussis in China, the DTaP immunization schedule for children was revised in 2025 to a 5-dose regimen, with doses given at ages 2, 4, 6, 18 and 72 months.⁵ Studies have demonstrated that complete and timely vaccination in accordance with the DTaP immunization schedule is crucial for pertussis prevention and control.^6–9

However, historical surveillance data indicate that the reported incidences of adverse events following immunization (AEFI) associated with the DTaP vaccine have consistently ranked among the top 3 among all EPI vaccines, predominantly presenting as transient mild reactions.^10,11 The package insert of the DTaP vaccine specifies that intramuscular injection should be administered to either the buttock region or the lateral deltoid muscle of the upper arm.^12–15 In contrast, the National Immunization Program Vaccine Schedule and Guidelines for Children (2021 Edition) recommends the lateral deltoid muscle of the upper arm and the anterolateral mid-thigh as routine injection sites.⁴ In clinical practice, the upper arm is the most frequently selected injection site, whereas the buttock and thigh are relatively less common.¹⁶ Some clinicians tend to prefer the buttock site for vaccination, considering that its abundant muscle tissue and low immunogenicity may reduce the incidence of local reaction.¹⁶ However, buttock injection unavoidably carries a risk of sciatic nerve injury.¹⁷ Based on this, the present study proposes the following hypothesis: although the upper arm injection may be associated with a slightly higher overall incidence of reactions, these reactions are predominantly common reactions, and the incidence of rare reactions shows no significant difference compared with buttock injection. Therefore, in terms of overall safety, the upper arm site may be a more appropriate choice. Currently, there is a paucity of research focusing on adverse reactions associated with different DTaP injection sites. Current research on adverse reactions related to different DTaP injection sites has mainly compared buttock vs. thigh or the upper arm vs. thigh administration, with few studies directly comparing buttock and the upper arm sites.^18–20 Moreover, most studies have focused on DTaP-containing combination vaccines and have limited sample sizes.^21,22 Consequently, the evidence available to guide the selection of injection sites specifically for DTaP vaccination remains insufficient. To address this gap, we conducted a large retrospective observational study to compare the reporting rates of adverse reactions following DTaP vaccination between the upper arm and buttock injection sites among eligible children. We performed a comprehensive comparison across multiple dimensions, including the severity of reactions, number of vaccine doses administered, clinical manifestations, and time of onset, to characterize the profiles of adverse reactions associated with different injection sites. Based on surveillance data collected in Wuxi City from 2020 to 2024, this study systematically analyzes adverse reactions related to the two injection sites, aiming to provide scientific evidence for site selection in children’s DTaP vaccination.

Methods

Data source

We conducted a large retrospective observational study. The subjects of this study were eligible children who received DTaP vaccination in the upper arm or buttock from January 1, 2020 to December 31, 2024. The Jiangsu Province Vaccination Integrated Service Management Information System served as the main data collection tool. All vaccination clinics in Wuxi automatically upload children’s vaccination records to the system in real time via system terminals. All DTaP vaccination data were exported from the above system on September 24, 2025. The exported aggregated data were sorted by vaccine dose and injection site, without individual case details or personal privacy information. Records with erroneous documentation of vaccination dose counts (27 doses), incomplete injection site information (376 doses), doses administered in the thigh (4404 doses), and records of non-EPI vaccines containing DTaP components (i.e., DTaP-IPV/Hib and DTaP-Hib) were excluded prior to the final analytical procedures. Records lacking injection site information were scattered randomly across the full dataset, with no evidence of systematic missingness. AEFI surveillance data of the DTaP vaccine administered to eligible children in Wuxi City from 2020 to 2024 were retrieved from the National AEFI Surveillance System of China. The AEFI cases retrieved by vaccination date included those following either single DTaP vaccination or co-administration with other vaccines, provided that the DTaP vaccine was suspected to be the primary cause of the adverse event. All the AEFI data were exported on September 24, 2025.

Immunization schedule

The DTaP vaccines used in China’s EPI are manufactured by four companies: Beijing Institute of Biological Products Co., Ltd., Yuxi Walvax Biotechnology Co., Ltd., Chengdu Institute of Biological Products Co., Ltd., and Wuhan Institute of Biological Products Co., Ltd. The formulation of these vaccines consists of acellular pertussis vaccine bulk, diphtheria toxoid bulk, tetanus toxoid bulk, and aluminum hydroxide as an adjuvant.^12–15 From 2020 to 2024, the DTaP immunization schedule for eligible children in China consisted of a 4-dose regimen.⁴ The primary immunization series consists of one dose each at ages 3, 4, and 5 months, followed by a booster dose administered at 18 months.⁴ In accordance with the National Immunization Program Vaccine Schedule and Guidelines for Children and the package insert of the DTaP vaccine, this vaccine is intramuscularly injected at a single dose of 0.5 mL. The approved injection sites cover the lateral deltoid muscle of the upper arm, anterolateral mid-thigh and buttock region.^4,12–15

Adverse reaction surveillance

In accordance with the Vaccine Administration Law of the People’s Republic of China and the National AEFI Surveillance Protocol, passive monitoring was applied to collect adverse reaction data after DTaP vaccination from the national AEFI surveillance system.^23,24 AEFI is defined as any reaction or event occurring after vaccination that is suspected to be associated with immunization. AEFI reporting follows a localized management system. Once a responsible reporting unit or reporter identifies an AEFI, an online direct report must be submitted within 48 hours. If a death, serious disability, cluster AEFI, or an AEFI with major social impact suspected to be associated with vaccination is identified, the online direct report must be completed within 2 hours. AEFI reports are subject to a daily review system by disease control and prevention institutions at various levels and by adverse drug reaction monitoring agencies. After investigation and diagnosis by an expert panel, AEFI cases are classified into five categories based on the underlying cause: adverse reaction, vaccine quality-related incident, immunization error, coincidental event, and psychogenic reaction.

Adverse reaction refers to harmful and unintended effects that occur after the proper administration of a qualified vaccine during routine immunization, which are unrelated to the intended purpose of vaccination. Adverse reactions were classified into common and rare groups according to clinical severity. Common reactions were defined as transient physiological dysfunction, including local injection-site reactions (e.g., redness and swelling, induration) and systemic symptoms such as fever, malaise, somnolence, anorexia, and fatigue. In contrast, rare reactions were defined as events that cause damage to the recipient’s tissues, organs, and physiological functions.

In this study, manifestations of local adverse reactions included redness and swelling, induration, pruritus, and myalgia at the injection site. Systemic reactions included fever, persistent crying, anorexia, fatigue, cough, somnolence, vomiting, sweating, rhinorrhea, diarrhea, headache, pharyngeal congestion, dizziness, allergic rash, febrile convulsion, and angioedema. The severity of local redness and swelling or induration was defined based on maximum lesion diameter as mild (≤2.5 cm), moderate (2.6–5.0 cm), or severe (>5.0 cm). The severity of fever was graded based on axillary temperature as mild (37.1–37.5°C), moderate (37.6–38.5°C), or severe (≥38.6°C).

Statistical analysis

The data were collated and analyzed using Microsoft Excel 2016 (Microsoft Corporation, Redmond, OR, USA) and IBM SPSS Statistics for Windows (version 26.0; IBM Corporation, Armonk, NY, USA). The reporting rates and temporal distributions of adverse reactions following DTaP vaccination were compared between the upper arm and buttock injection groups. The reporting rates of adverse reactions (per 10,000 doses) were calculated as

$$\frac{\mathit{Number}\mathit{of}\mathit{reported}\mathit{adverse}\mathit{reaction}\mathit{cases}}{\mathit{Total}\mathit{number}\mathit{of}\mathit{DTaP}\mathit{vaccine}\mathit{doses}\mathit{administered}}\times 10,000.$$

We compared adverse reactions between the upper arm and buttock vaccination sites using reporting rates, including the overall situation, severity, vaccination doses, and clinical manifestations. In this study, the chi-square (χ²) test was used as the primary method for intergroup comparisons; the Cochran-Mantel-Haenszel (CMH) stratified chi-square test was further adopted to adjust for confounding bias derived from imbalanced distribution of vaccination doses between groups. Fisher’s exact test was applied when the expected frequency in any cell of the contingency table was less than 5, with a predefined significance level of a = 0.05. The time to onset of any adverse reaction was defined as the interval (in days) between the date of DTaP vaccination and the date of occurrence.

Ethical approval

In accordance with the Vaccine Administration Law of the People’s Republic of China and the National AEFI surveillance Protocol, adverse events following immunization must be reported to the national AEFI surveillance system as required, and analysis of such data constitutes legally stipulated regulatory activities. This study used anonymized data from the national AEFI surveillance system without extra data collection or interventions, and thus did not require additional ethical approval per public health surveillance regulations.

Results

General findings

In total, 636,169 doses of the DTaP vaccine administered to children in Wuxi City from 2020 to 2024 were included for analysis. During the surveillance period, 1,443 adverse reactions were reported to the National AEFI Surveillance System of China. Baseline characteristics of adverse reactions after DTaP vaccination among eligible children in Wuxi from 2020 to 2024 are provided in Supplementary Table 1. The proportions of DTaP vaccine-related adverse reactions occurring in the upper arm and buttock injection groups after vaccination were 84.27% and 15.73%, respectively. The reporting rate of adverse reactions was 23.88 (95% CI: 22.54–25.22) per 10,000 doses in the upper arm group and 17.89 (95% CI: 15.56–20.21) per 10,000 doses in the buttock group, with a statistically significant difference (χ² = 16.106, p < .001). For common reactions, the rate was 23.13 (95% CI: 21.81–24.45) per 10,000 doses and 16.94 (95% CI: 14.68–19.20) per 10,000 doses, respectively (χ² = 17.812, p < .001). For rare reactions, the corresponding rate was 0.75 (95% CI: 0.51–0.98) per 10,000 doses and 0.95 (95% CI: 0.41–1.48) per 10,000 doses, showing no statistical difference (χ² = 0.514, p = .473; Table 1).

Table 1.

Overall reporting rate of adverse reactions following DTaP vaccination in eligible children in Wuxi, 2020–2024.

Type of reaction	Injection site	Administered doses	Reported cases	Reporting rate (per 10,000 doses) (95% CI)	χ2	p
Adverse reaction	Upper arm	509,265	1,216	23.88 (22.54–25.22)	16.106	<.001
	Buttock	126,904	227	17.89 (15.56–20.21)
Common reaction	Upper arm	509,265	1,178	23.13 (21.81–24.45)	17.812	<.001
	Buttock	126,904	215	16.94 (14.68–19.20)
Rare reaction	Upper arm	509,265	38	0.75 (0.51–0.98)	0.514	.473
	Buttock	126,904	12	0.95 (0.41–1.48)

The χ² and p-values are from Pearson’s chi-square test for independence, with the null hypothesis of no difference in the reporting rates of adverse reaction, common reaction, and rare reaction between the upper arm and buttock groups.

Vaccination doses

For primary immunization, the reporting rate of adverse reactions was 11.40 (95%CI: 10.29–12.50) per 10,000 doses in the upper arm group and 6.77 (95%CI: 5.10–8.44) per 10,000 doses in the buttock group, with a statistically significant difference (χ² = 15.146, p < .001). For Dose 1, the rates were 8.78 (95% CI: 7.06–10.50) per 10,000 doses in the upper arm group and 4.65 (95% CI: 2.21–7.08) per 10,000 doses in the buttock group, respectively (χ² = 5.134, p = .023). For Dose 2, the rates were 8.74 (95% CI: 7.06–10.42) per 10,000 doses and 3.88 (95% CI:1.68–6.07) per 10,000 doses, respectively (χ² = 7.523, p = .006). For Dose 3 and Dose 4 (booster immunization), the reporting rates were 16.34 (95% CI: 14.09–18.58) per 10,000 doses and 11.57 (95% CI: 7.84–15.29) per 10,000 doses, and 53.18 (95% CI: 49.53–56.84) per 10,000 doses and 48.45 (95% CI: 41.05–55.85) per 10,000 doses, respectively (χ² = 3.771, p = .052; χ² = 1.191, p = .275; Table 2).

Table 2.

The reporting rate of adverse reactions by doses of DTaP vaccine among eligible children in Wuxi, 2020–2024.

Dose category	Upper arm group			Buttock group			χ2*	p
	Administered doses	Reported cases	Reporting rate (per 10,000 doses) (95% CI)	Administered doses	Reported cases	Reporting rate (per 10,000 doses) (95% CI)
Primary immunization	357,141	407	11.40 (10.29–12.50)	93,054	63	6.77 (5.10–8.44)	15.146	<.001
Dose 1	113,947	100	8.78 (7.06–10.50)	30,120	14	4.65 (2.21–7.08)	5.134	.023
Dose 2	118,939	104	8.74 (7.06–10.42)	30,952	12	3.88 (1.68–6.07)	7.523	.006
Dose 3	124,255	203	16.34 (14.09–18.58)	31,982	37	11.57 (7.84–15.29)	3.771	.052
Booster immunization	152,124	809	53.18 (49.53–56.84)	33,850	164	48.45 (41.05–55.85)	1.191	.275
CMH test	–	–	–	–	–	–	9.793	.002
χ2#	781.929			241.477
p	<.001			<.001

χ^2*: The χ² and p-values are from Pearson’s chi‑square test for independence, with the null hypothesis of no difference in adverse reaction reporting rates for primary immunization, doses 1, 2, 3, and booster immunization between the upper arm and buttock groups. Primary immunization is defined as the cumulative experience of doses 1, 2, and 3 of the DTaP vaccine, and booster immunization is defined as dose 4 of the DTaP vaccine.

χ^2#: The χ² and p-values are from Pearson’s chi‑square test for independence, with the null hypothesis of no difference in adverse reaction reporting rates between primary and booster immunizations within the upper arm group and within the buttock group.

The Cochran-Mantel-Haenszel (CMH) test was used to evaluate the overall inter-group difference after fully adjusting for confounding by vaccine dose strata.

In the upper arm group, the reporting rates for primary and booster immunization were 11.40 (95% CI: 10.29–12.50) per 10,000 doses and 53.18 (95% CI: 49.53–56.84) per 10,000 doses, respectively. In the buttock group, the corresponding rates were 6.77 (95% CI: 5.10–8.44) and 48.45 (95% CI: 41.05–55.85), respectively. Both differences were statistically significant (χ² = 781.929, p < .001; χ² = 241.477, p < .001; Table 2).

After CMH adjustment for dose strata, the overall group difference remained significant (χ²_MH = 9.793, p = .002; OR = 0.796, 95%CI: 0.691–0.917), reflecting lower odds of adverse reactions in buttock injection recipients. Mild inter-stratum heterogeneity was detected via Breslow–Day test (χ² = 8.755, df = 3, p = .033), with variable effect sizes across doses as shown in Table 2.

Clinical manifestations

In the upper arm and buttock injection groups, common reactions were dominated by redness and swelling, induration, and fever, with reporting rates of 17.50 (95%CI: 16.35–18.64) and 13.24 (95% CI:11.24–15.24), 10.88 (95%CI:9.97–11.78) and 6.07 (95%CI:4.71–7.42), and 6.87 (95% CI:6.15–7.59) and 5.04 (95%CI:3.81–6.28) per 10,000 doses, respectively. Rare reactions were mainly allergic rashes, with reporting rates of 0.73 (95%CI:0.49–0.96) and 0.87 (95%CI:0.35–1.38) per 10,000 doses, respectively. The upper arm injection group had higher reporting rates of redness and swelling, induration, fever, persistent crying, and anorexia, but lower reporting rates of pruritus, cough, and pharyngeal congestion than the buttock injection group. No statistically significant differences were observed in the reporting rates of other adverse reactions (Table 3).

Table 3.

Clinical manifestations of adverse reactions following DTaP vaccination by injection site in Wuxi, 2020–2024.

Clinical manifestations	Upper arm group		Buttock group		χ2	p
	Reported Cases	Reporting rate (per 10,000 doses) (95% CI)	Reported Cases	Reporting rate (per 10,000 doses) (95% CI)
Common reactions
Redness and swelling	891	17.50 (16.35–18.64)	168	13.24 (11.24–15.24)	11.080	.001
≤2.5 cm	101	1.98 (1.60–2.37)	10	0.79 (0.30–1.28)	8.319	.004
2.6–5.0 cm	460	9.03 (8.21–9.86)	75	5.91 (4.57–7.25)	11.789	.001
>5.0 cm	330	6.48 (5.78–7.18)	83	6.54 (5.13–7.95)	0.006	.940
Induration	554	10.88 (9.97–11.78)	77	6.07 (4.71–7.42)	23.728	<.001
≤2.5 cm	171	3.36 (2.85–3.86)	31	2.44 (1.58–3.30)	2.679	.102
2.6–5.0 cm	271	5.32 (4.69–5.95)	33	2.60 (1.71–3.49)	15.747	<.001
>5.0 cm	112	2.20 (1.79–2.61)	13	1.02 (0.47–1.58)	7.138	.008
Pruritus	92	1.81 (1.44–2.18)	51	4.02 (2.92–5.12)	22.123	<.001
Myalgia	13	0.26 (0.12–0.39)	7	0.55 (0.14–0.96)	–	.097
Fever	350	6.87 (6.15–7.59)	64	5.04 (3.81–6.28)	5.228	.022
37.1–37.5°C	41	0.81 (0.56–1.05)	2	0.16 (0.00–0.38)	6.301	.012
37.6–38.5°C	137	2.69 (2.24–3.14)	22	1.73 (1.01–2.46)	3.720	.054
≥38.6°C	172	3.38 (2.87–3.88)	40	3.15 (2.18–4.13)	0.155	.694
Persistent crying	257	5.05 (4.43–5.66)	33	2.60 (1.71–.349)	13.340	<.001
Anorexia	47	0.92 (0.66–1.19)	2	0.16 (0.00–0.38)	7.725	.005
Fatigue	34	0.67 (0.44–0.89)	5	0.39 (0.05–0.74)	1.241	.265
Cough	8	0.16 (0.05–0.27)	6	0.47 (0.09–0.85)	–	.043
Somnolence	5	0.10 (0.01–0.18)	3	0.24 (0.00–0.50)	–	.202
Vomiting	6	0.12 (0.02–0.21)	1	0.08 (0.00–0.23)	–	1.000
Sweating	5	0.10 (0.01–0.18)	2	0.16 (0.00–0.38)	–	.633
Rhinorrhea	5	0.10 (0.01–0.18)	1	0.08 (0.00–0.23)	–	1.000
Diarrhea	4	0.08 (0.00–0.16)	0	0.00	–	1.000
Headache	2	0.04 (0.00–0.09)	0	0.00	–	1.000
Pharyngeal congestion	0	0.00	2	0.16 (0.00–0.38)	–	.040
Dizziness	1	0.02 (0.00–0.06)	0	0.00	–	1.000
Rare reactions
Allergic rash	37	0.73 (0.49–0.96)	11	0.87 (0.35–1.38)	0.265	.607
Febrile convulsion	1	0.02 (0.00–0.06)	0	0.00	–	1.000
Angioedema	0	0.00	1	0.08 (0.00–0.23)	–	.199
Total	1216	23.88 (22.54–25.22)	227	17.89 (15.56–20.21)	16.106	<.001

The χ² and p-values are from Pearson’s chi‑square test for independence, testing the null hypothesis of no difference in reporting rates between the upper arm and buttock groups for each clinical manifestation, and for each severity category of redness and swelling, induration, and fever. The “-” in the table means Fisher’s exact test was used.

Redness and swelling were predominantly moderate to severe in both groups, with the upper arm group having significantly higher reporting rates of mild and moderate redness and swelling than the buttock group (both, p < .05). Induration was mainly mild to moderate in both groups, with significantly higher reporting rates of moderate and severe induration in the upper arm group than the buttock group (both, p < .05). Fever was predominantly moderate to severe in both groups, with a significantly higher reporting rates of mild fever in the upper arm group (p = .012; Table 3).

Time distribution

In the upper arm group, the proportions of DTaP vaccine-related adverse reactions occurring within 0–1, 2–3, 4–7, 8–14, and ≥15 d after vaccination were 91.12%, 5.84%, 1.97%, 0.74%, and 0.33%, respectively. At 0–1 d, the proportions of all adverse reactions exceeded 90% except for cough, vomiting, rhinorrhea, and allergic rash. In the buttock group, the proportions of DTaP vaccine-related adverse reactions occurring at 0–1 and 2–3 d after vaccination were 94.71% and 5.29%, respectively, and no adverse reactions were observed at 4 d or longer after vaccination. At 0–1 d, the proportions of all adverse reactions exceeded 90% except for anorexia, cough, and rhinorrhea (Table 4).

Table 4.

Time distribution of adverse reactions following DTaP vaccination by injection site in Wuxi, 2020–2024.

Clinical manifestations	Upper arm group						Buttock group
	Reported cases	Onset time in days, n (%)					Reported cases	Onset time in days, n (%)
		0–1	2–3	4–7	8–14	≥15		0–1	2–3
Common reactions
Redness and swelling	891	833 (93.49)	45 (5.05)	10 (1.12)	1 (0.11)	2 (0.22)	168	159 (94.64)	9 (5.36)
≤2.5 cm	101	93 (92.08)	5 (4.95)	3 (2.97)	0 (0.00)	0 (0.00)	10	9 (90.00)	1 (10.00)
2.6–5.0 cm	460	420 (91.30)	31 (6.74)	6 (1.30)	1 (0.22)	2 (0.43)	75	71 (94.67)	4 (5.33)
>5.0 cm	330	320 (96.97)	9 (2.73)	1 (0.30)	0 (0.00)	0 (0.00)	83	79 (95.18)	4 (4.82)
Induration	554	504 (90.97)	29 (5.23)	15 (2.71)	4 (0.72)	2 (0.36)	77	75 (97.40)	2 (2.60)
≤2.5 cm	171	154 (90.06)	6 (3.51)	8 (4.68)	1 (0.58)	2 (1.17)	31	30 (96.77)	1 (3.23)
2.6–5.0 cm	271	242 (89.30)	20 (7.38)	7 (2.58)	2 (0.74)	0 (0.00)	33	32 (96.97)	1 (3.03)
>5.0 cm	112	108 (96.43)	3 (2.68)	0 (0.00)	1 (0.89)	0 (0.00)	13	13 (100)	0 (0.00)
Pruritus	92	90 (97.83)	2 (2.17)	0 (0.00)	0 (0.00)	0 (0.00)	51	47 (92.16)	4 (7.84)
Myalgia	13	13 (100)	0 (0.00)	0 (0.00)	0 (0.00)	0 (0.00)	7	7 (100)	0 (0.00)
Fever	350	316 (90.29)	22 (6.29)	6 (1.71)	4 (1.14)	2 (0.57)	64	61 (95.31)	3 (4.69)
37.1–37.5°C	41	39 (95.12)	1 (2.44)	0 (0.00)	1 (2.44)	0 (0.00)	2	2 (100)	0 (0.00)
37.6–38.5°C	137	128 (93.43)	7 (5.11)	1 (0.73)	1 (0.73)	0 (0.00)	22	22 (100)	0 (0.00)
≥38.6°C	172	149 (86.63)	14 (8.14)	5 (2.91)	2 (1.16)	2 (1.16)	40	37 (92.50)	3 (7.50)
Persistent crying	257	245 (95.33)	8 (3.11)	2 (0.78)	2 (0.78)	0 (0.00)	33	30 (90.91)	3 (9.09)
Anorexia	47	47 (100)	0 (0.00)	0 (0.00)	0 (0.00)	0 (0.00)	2	1 (50.00)	1 (50.00)
Fatigue	34	34 (100)	0 (0.00)	0 (0.00)	0 (0.00)	0 (0.00)	5	5 (100)	0 (0.00)
Cough	8	6 (75.00)	2 (25.00)	0 (0.00)	0 (0.00)	0 (0.00)	6	4 (66.67)	2 (33.33)
Somnolence	5	5 (100)	0 (0.00)	0 (0.00)	0 (0.00)	0 (0.00)	3	3 (100)	0 (0.00)
Vomiting	6	4 (66.67)	1 (16.67)	0 (0.00)	1 (16.67)	0 (0.00)	1	1 (100)	0 (0.00)
Sweating	5	5 (100)	0 (0.00)	0 (0.00)	0 (0.00)	0 (0.00)	2	2 (100)	0 (0.00)
Rhinorrhea	5	3 (60.00)	2 (40.00)	0 (0.00)	0 (0.00)	0 (0.00)	1	0 (0.00)	1 (100)
Diarrhea	4	4 (100)	0 (0.00)	0 (0.00)	0 (0.00)	0 (0.00)	0	0 (0.00)	0 (0.00)
Headache	2	2 (100)	0 (0.00)	0 (0.00)	0 (0.00)	0 (0.00)	0	0 (0.00)	0 (0.00)
Pharyngeal congestion	0	0 (0.00)	0 (0.00)	0 (0.00)	0 (0.00)	0 (0.00)	2	2 (100)	0 (0.00)
Dizziness	1	1 (100)	0 (0.00)	0 (0.00)	0 (0.00)	0 (0.00)	0	0 (0.00)	0 (0.00)
Rare reactions
Allergic rash	37	33 (89.19)	0	1 (2.70)	2 (5.41)	1 (2.70)	11	11 (100.00)	0
Febrile convulsion	1	1 (100)	0 (0.00)	0 (0.00)	0 (0.00)	0 (0.00)	0	0 (0.00)	0 (0.00)
Angioedema	0	0 (0.00)	0 (0.00)	0 (0.00)	0 (0.00)	0 (0.00)	1	1 (100)	0 (0.00)
Total	1 216	1108 (91.12)	71 (5.84)	24 (1.97)	10 (0.74)	4 (0.33)	227	215 (94.71)	12 (5.29)

Discussion

Aluminum hydroxide is widely adopted as an adjuvant during the manufacturing of DTaP vaccines to potentiate host immune responses to vaccine antigens. However, aluminum-based adjuvants are capable of triggering local inflammatory reactions.^25,26 Accumulating evidence has revealed that the injection site is closely associated with the incidence of vaccine-related adverse events, and thus site selection constitutes a key issue requiring careful consideration in clinical vaccination practice.²⁷ To objectively assess the safety differences between different administration sites, the present study systematically analyzed the profiles of adverse reactions after DTaP vaccination via the upper arm and the buttock. This work intends to provide evidence-based guidance for the optimal selection of vaccination sites in clinical settings.

In this study, children vaccinated with DTaP vaccines in the upper arm had a slightly higher reporting rate of adverse reactions than those vaccinated in the buttock, consistent with other relevant study.²⁰ The elevated rate was mainly observed for common reactions, whereas no statistically significant difference was found in the rate of rare reactions. Redness and swelling, induration, and fever were the predominant common reactions in both groups, which aligns with the findings of prior studies.^28–31 Allergic rashes were the main rare reactions, and no other long-term or severe health impairments were reported in either group, consistent with previous literature.³² The upper arm group presented slightly higher reporting rates of common reactions including redness and swelling, induration, fever, persistent crying, and anorexia compared with the buttock group, particularly mild-to-moderate redness and swelling, moderate-to-severe induration, and mild fever. The overall distribution trends for the severity of redness and swelling, induration, and fever were consistent between groups, in agreement with other study.³³ This study suggests that the upper arm injection of DTaP vaccine may be associated with higher rates of certain local and systemic reactions than buttock injection, but the severity of these adverse reactions was not increased.

Stratified by vaccination dose, the relatively higher reporting rates of adverse reactions in the upper arm group were mainly observed after administration of the first and second doses. From the second dose onwards, the reporting rates of adverse reactions in both groups showed a gradual upward trend with increasing vaccination doses, which was consistent with the other regional studies.^33,34 With the increased doses of DTaP vaccine administered, the body’s cellular immune response to vaccine antigens may be progressively enhanced, which not only promotes an increase in specific antibody levels but also elevates sensitivity to vaccine antigens or adjuvants.³⁵ This study demonstrates that the difference in injection sites does not affect the overall trend of the increasing rates of adverse reactions with an increase in vaccination doses.

Furthermore, the results also reveal that adverse reactions following the DTaP vaccine in both groups occurred predominantly within 0–1 d post-vaccination, with a slightly higher proportion in the buttock group than in the upper arm group (94.71% vs. 91.12%). No adverse reactions were detected on day 4 post-vaccination or later in the buttock group. These findings suggest that adverse reactions following buttock vaccination occurred earlier and were more concentrated in time. Whether the DTaP vaccine is administered via the upper arm or buttock route, priority should be given to monitoring adverse reactions within 0–1 d post-vaccination. It is essential to inform the children’s parents/guardians in advance about the potential occurrence of common adverse reactions during this period, such as local redness and swelling, induration, and systemic fever. Additionally, enhanced support regarding medical consultation and management guidance should be provided to alleviate anxiety and vaccine hesitancy.³⁶

There were still several limitations. First, the study used passive AEFI surveillance data, which was inherently associated with underreporting and reporting bias. Nevertheless, the reporting rate of adverse reactions following DTaP vaccination in Wuxi was significantly higher than the national average (22.68 vs. 10.75 per 10,000 doses), suggesting that the data remain highly credible.³⁴ Second, as a limitation of the retrospective study design, inter-rater reliability and measurement uncertainty could not be formally assessed. However, the use of objective parameters and standardized reporting procedures minimized potential misclassification bias. Third, the vaccination data were aggregated without individual-level demographics (e.g., age, sex), precluding adjustment for these confounders. However, comparability between the two groups remains acceptable as injection site choice was not systematically associated with these factors. Future related studies should collect individual-level demographic data to achieve comprehensive adjustment for multiple confounders. Fourth, this analysis focused solely on AEFI cases where the DTaP vaccine was primarily suspected and did not consider the occurrence or potential impact of adverse reactions when the DTaP vaccine was co-administered with other vaccines, which may influence the interpretation of the findings.

Conclusion

Both injection sites were associated mainly with expected common reactions, with slightly higher reported common reaction rates in the upper arm group and no meaningful difference in rare reactions. Given the comparable safety profile between the two sites and the potential risk of sciatic nerve injury associated with buttock injections, healthcare providers should preferentially use the upper arm site for DTaP vaccination.

Biography

Shixin Xiu, the vice director of the department of immunization of Wuxi Center for Disease Control and Prevention, with extensive professional experience in immunization programming, encompasses AEFI surveillance, surveillance of vaccine-preventable diseases, clinical vaccine evaluation, and vaccine hesitancy research, etc.

Funding Statement

This work was supported by the Wuxi Municipal Health Commission Science and Technology Plan Project [Grant Number: T202528].

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets generated and analyzed during this study can be made available by the corresponding author, subject to reasonable terms.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/21645515.2026.2723634