Diphtheria Vaccine Administered in the Thigh Appears Safer

Barbara Boughton

January 14, 2013

A new study of 1.4 million US children aged from 1 to 6 years reveals that local reaction after diphtheria-tetanus–acellular pertussis (DTaP) vaccination is more common when the injection is given in the arm than in the thigh, particularly in younger children.

The study supports current recommendations to give vaccinations in the thigh to younger children (age, 12 months - 2 years), according to the authors of the study, which was published online January 14 in Pediatrics. However, whether or not to give vaccinations in the thigh to older children (age, 2 - 6 years) is a murkier question, according to experts.

In the study, children in the 12- to 35-month-old age group who received the DTaP vaccination in the arm rather than the thigh had an almost 2-fold increase in risk for a medically attended local reaction (relative risk [RR], 1.88; 95% CI, 1.34 - 2.65; P < .001), according to the authors of the study, led by Lisa A. Jackson MD, MPH, from the Group Health Research Institute in Seattle, Washington.

Current recommendations from the US Advisory Committee on Immunization Practices indicate that intravenous muscular vaccination given to children aged 12 months to 2 years should be given in the thigh. The same recommendations, however, indicate that the deltoid muscle in the arm is preferred for children starting at age 3 years.

In the new study, children aged 3 to 6 years who received the DTaP vaccine in the arm rather than the thigh were also more likely to have a medically attended local reaction, but the difference was not significant (RR, 1.41; 95% CI, 0 .84 - 2.34; P = .2).

The authors defined a medically attended local reaction as one in which the children received a diagnosis of cellulitis, limb swelling, pain in the limb, allergy, skin reaction, or lymphadenitis at an outpatient medical center 1 to 5 days after the administration of the vaccines.

Despite current guidelines, the choice of whether to give vaccines to children in the thigh or arm varies among medical providers, according to the authors of the new study. Their data indicate that some children in the study aged 12 to 36 months received the DTaP vaccine in the arm, and among 3- and 4-year-olds at least 20% received the vaccine in the thigh.

In addition, 2 earlier studies on administration of the DTaP vaccine to children from 4 to 6 years old showed that vaccinations in the arm were associated with a higher risk for local reaction.

The researchers in the new study used data from the Vaccine Safety Datalink, a database of the Centers for Disease Control and Prevention and 10 managed care organizations established to monitor vaccine safety. They analyzed the risk for local reaction among children aged 1 to 6 years who received the inactivated influenza, hepatitis A, and DTaP vaccine between 2002 and 2009.

There were no differences in local reactions to the inactivated influenza or hepatitis A vaccine among children who received the vaccines in the arm vs those who received the shots in the thigh, according to the authors.

Among the entire 1.4 million children the researchers studied, ranging in age from 1 to 6 years, the risk for a local reaction from the DTaP vaccine was significantly higher if the shot was given in the arm compared with shots given in the thigh (RR, 1.88; 95% CI, 1.42 - 2.49; P < .001).

Body mass index did not affect the risk for local reaction to the DTaP vaccine when administered in the arm vs the thigh.

"Our results support the current preference for thigh administration of [intravenous muscular] vaccinations to children 12 to 35 months of age, particularly for DTaP vaccine," the authors write.

Two previous studies using the Vaccine Safety Datalink for analysis also showed an increased risk for local reactions to arm injections of the fifth DTaP vaccine, the researchers note. When considered together with the results in the new study, the findings support giving the DTaP vaccine in the thigh to children up to age 6 years, they conclude.

At least one expert disagrees, however. The study does not provide enough evidence to warrant changing administration of the DTaP vaccine to the thigh in older children, commented James Cherry, MD, professor of pediatrics at the David Geffen School of Medicine and division of infectious diseases, Mattel Children's Hospital, University of California, Los Angeles.

"The problem is that in older children, the results did not reach statistical significance," Dr. Cherry said. The study merely supports the current guidelines for younger children, he added.

"Physicians in clinical practice might change administration of the DTaP vaccine to the thigh in older children after looking at this study," Dr. Cherry said. "But the study really doesn't contribute much to the scientific literature," he added.

The study was supported by the Centers for Disease Control and Prevention via America's Health Insurance Plans. Four of the 13 authors of the study, including Dr. Jackson, received research funding from Sanofi Pasteur, Pfizer, Novartis, GlaxoSmithKline, MedImmune, and/or Merck. Dr. Jackson also received travel support from Pfizer. Dr. Cherry has disclosed no relevant financial relationships.

Pediatrics. Published online January 14, 2013.