Vaccine injections not only provide crucial training for the immune system but also represent “the most common source of iatrogenic pain in childhood.”

Infants can’t say which vaccine schedule they prefer, but that has not stopped clinicians and researchers from trying to understand how to make the experience less painful and stressful for them.

One way doctors have sought to minimize distress for the child and optimize protection against disease is by using combination vaccine products and giving multiple injections per visit, when possible. Some biomarker data support this approach as reducing the overall number of stressful visits for the child.

Yet a recent executive order in the United States calls for moving the schedule in the other direction: more vaccine appointments, a single injection per visit, and possibly a net increase in injections.

The recommendation to give each vaccine at a separate visit is meant to give parents more options for the timing and frequency of the shots, the Trump Administration said.

How clinicians and parents navigate childhood vaccines could affect patients into adulthood.

“Vaccinations may seem routine, but these experiences can shape how children perceive needles and healthcare for many years,” said Evelyn Chan, MBBS, MSc, MPH, a pediatrician in Australia.

Chan is the founder of Smileyscope, a company that has developed a virtual reality headset to help children relax or reframe how they think about procedures involving needles.

Many children and a quarter of adults are afraid of needles, estimates showed. “Adults with needle phobia very often trace it back to a traumatizing healthcare experience in childhood, which is why how we manage these moments really matters,” Chan said.

Turning One Shot Into Three

In the case of the MMR vaccine, the new schedule recommends turning a single shot at one appointment into three shots over three appointments.

The executive order calls for breaking up the MMR vaccine into separate shots for each disease — measles, mumps, and rubella — with one injection per appointment.

“All childhood immunizations should be administered at separate medical visits” to the extent possible, the order states.

The executive order also seeks information about breaking other combination vaccine products into separate vaccines, as with the MMR vaccine.

Separate vaccines for measles, mumps, and rubella are not currently available — a fact infectious disease physician Demetre C. Daskalakis, MD, MPH, has noted leaves the new schedule “operationally impossible.”

The new schedule leaves it up to parents and clinicians to decide whether a child should receive vaccinations against COVID and influenza, rather than automatically recommending those vaccines for all children. Hepatitis B vaccination is recommended for certain high-risk groups or can be given based on shared clinical decision-making, rather than being automatically recommended for all. The American Academy of Pediatrics (AAP) continues to recommend those vaccines, however, and recommends “combination vaccines instead of separate injections when appropriate.”

The AAP has said that “there is no medical reason to delay or space out childhood immunizations.”

“Multiple vaccines in one shot don’t overwhelm a child’s immune system—they give it helpful practice,” the organization said on its website. “In childhood, the immune system develops by learning to ‘read’ germs like books. Vaccines are like beginner books that help the immune system get ready to read.”

‘Get It Over With’

When parents have asked Paul A. Offit, MD, over the years about the possibility of spacing out vaccines, the discomfort of vaccination procedures is not his top issue. First, he wants children to be protected for as long as possible.

Separating, spacing out, or delaying vaccines will do nothing to make vaccines safer, said Offit, the director of the Vaccine Education Center at the Children’s Hospital of Philadelphia in Philadelphia. “All it will do is increase the period during which children are susceptible to these infections with no benefit,” he said.

But the stressful nature of vaccination visits — gauged through biomarker clues — is a secondary consideration that Offit has mentioned, including in a 2022 YouTube video.

He sees biomarker data as supporting the case for vaccinating children as efficiently as possible.

The point is rooted in a 1994 paper in Child Development. A pair of researchers in New Jersey examined levels of cortisol, a marker of stress, in saliva samples from 80 infants before and after they received inoculations. Half received a single injection to protect against diphtheria, tetanus, and pertussis. The other half received that injection, plus a second, against Haemophilus influenzae type b.

The data “indicated that 2- and 6-month-old infants were no more likely stressed by two inoculations than by one,” the authors concluded. “From the point of view of clinical procedures, our results support the current practice of giving two injections on the same visit.”

“In other words, when the child is laid down and against their will being given a shot, that’s stressful,” Offit said in the video. “It’s no more stressful to get more shots at the same time, at least according to these studies. So better to get it over with then and not put your children at risk by delaying or spacing out or separating vaccines.”

Now, some children receive four and sometimes even five injections at a given appointment, Offit said.

An Opening Compromise

Nola Jean Ernest, MD, PhD, a pediatrician at Dothan Pediatric Healthcare Network in Enterprise, Alabama, has fielded parents’ questions about the safety of giving children multiple vaccines during the same visit. Minor adverse events such as fever or pain at the injection site may be slightly more common, she said.

“But when it comes to serious adverse events, studies have shown again and again that there is no increased risk of adverse events giving the vaccines together, and of course, it gets your child protected a lot faster,” Ernest said.

Vaccine research tends to focus on adverse events and immunogenicity, but anxiety in the child is not well studied. But they sometimes discuss that aspect as well.

“There is not great data on this, but in general, if your child is afraid of shots, having one stressful visit is much different than staggering injections over separate visits, which just increases the burden of stress and pain, rather than reducing it, for an individual child,” Ernest said.

Many parents appreciate that logic and opt to have vaccinations administered all at once.

In other cases, the clinic might turn to a compromise: They can administer some vaccines separately over the course of about a week. After parents see there is no major reaction to any one of them, Ernest suggests multiple vaccinations during subsequent visits so that the child does not experience the stress repeatedly.

There are other practical concerns. If parents need to take time off work for additional visits, that could be a barrier that leads to further delays and lapses in protection.

Customizing vaccine schedules can introduce opportunity for administrative error. Vaccine doses can be missed, Ernest said. Or children might end up needing an extra shot because a dosing interval was incorrect. For example, the hepatitis A vaccine is a two-shot series, and some schools require the injections be given 6 months apart. If the second shot is mistakenly given too soon, children could need a repeat dose.

Ernest does not foresee the executive order having a major effect on what pediatricians recommend for their patients, but it could shape parents’ perceptions, she said. Although government policy can influence access to vaccines, insurers might not limit their coverage.

“If you think about it logically, they wouldn’t,” she said. “Because insurance companies make their money by not having to pay for claims. If they have unvaccinated children, then there are more children that are going to wind up in a hospital.”

Lessons From the OUCH Lab

Rebecca Pillai Riddell, PhD, the director of the OUCH Lab at York University in Toronto, Ontario, Canada, has studied hundreds of children receiving thousands of vaccinations.

Her team recruited 760 parent-infant dyads who were videotaped during four immunization appointments in the first year of life. Researchers coded the videos to document pain-related distress behaviors in the infants, as well as pain management techniques used by the parents.

They found parents’ behaviors, including physical comfort, rocking, and verbal reassurance, accounted for up to 13% of the variance in infant pain-related distress scores.

Children in their cohort received about two shots per visit on average, with a range of one to three. Although the researchers were not focused on the number of injections, they controlled for that variable in some of their analyses and found it did not significantly alter the results.

To the extent increasing the number of medical visits that are painful to children and stressful to parents compromises a parent’s ability to soothe their child’s distress, the outcomes may not be optimal from a biopsychosocial perspective, she said.

Why Change?

The executive order intends to have approaches to vaccination in the United States align more closely with those in other countries, while supporting religious liberty and parental choice, it said. The executive order does not mention autism, but at the signing of the executive order, President Trump said he thinks the new schedule will have a huge impact on autism.

“While we do not know exactly what the cause is with respect to autism, it is essential to our research efforts that we have the very best vaccine recommendations in the entire world, so we’re reducing them,” he said.

ABCD’s, Three P’s, and Buzzy

Clinicians have devised various tips for helping children receive vaccines as successfully as possible. Riddell co-authored an evidence-based guideline on reducing the pain of childhood vaccination. Recommendations include injecting the most painful shot last when administering injections sequentially.

Based on observations from the OUCH cohort, Riddell has shared a mnemonic for parents that covers anxiety, breathing, cuddling, and distracting: ABCD.

Ernest noted that many pediatricians invest in distraction techniques such as Buzzy or ShotBlocker.

And Chan often discusses the three P’s with practices and parents:

• Physical: Reduce pain where possible, such as with topical anesthetic or cooling.
• Positioning: Keep children comfortable and upright, often with a parent providing a “comfort hug,” rather than pinning them down or lying them flat.
• Psychological: Prepare children and give them choices and a sense of control.

Offit co-invented a rotavirus vaccine. He has criticized Secretary of Health and Human Services Robert F. Kennedy, Jr, and last year was not renewed as a member of the FDA’s Vaccines and Related Biological Products Advisory Committee. Chan reported being the Australian CEO of Smileyscope. Ernest and Riddell had no disclosures.