INTRODUCTION — Routine immunization schedules vary from country to country. This topic will provide an overview of immunization for children and adolescents in the United States. Immunization schedules for other countries are available through the World Health Organization.
Detailed information about individual vaccines, vaccine refusal or hesitancy, and vaccination for adults is provided separately.
●(See "Hepatitis B virus immunization in infants, children, and adolescents".)
●(See "Rotavirus vaccines for infants".)
●(See "Diphtheria, tetanus, and pertussis immunization in children 6 weeks through 6 years of age".)
●(See "Prevention of Haemophilus influenzae type b infection".)
●(See "Pneumococcal vaccination in children".)
●(See "Poliovirus vaccination".)
●(See "Seasonal influenza in children: Prevention with vaccines".)
●(See "Measles, mumps, and rubella immunization in infants, children, and adolescents".)
●(See "Vaccination for the prevention of chickenpox (primary varicella infection)".)
●(See "Hepatitis A virus infection: Treatment and prevention".)
●(See "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age".)
●(See "Meningococcal vaccination in children and adults".)
●(See "Human papillomavirus vaccination".)
●(See "Standard childhood vaccines: Parental hesitancy or refusal".)
●(See "Standard immunizations for nonpregnant adults".)
BENEFITS OF VACCINES — Immunization is one of the most effective preventive health measures (figure 1) [1,2]. The number of cases of most vaccine-preventable illnesses in the United States declined by more than 90 percent after routine childhood immunizations were introduced.
Vaccination programs directly benefit the immunized child. They also indirectly benefit unimmunized persons through community ("herd") immunity. Community immunity occurs when the portion of the population that is immune to the infection is large enough to decrease the risk of transmission [3,4]. Community immunity protects children who are too young for immunization and persons with contraindications to vaccines. It relies on the majority of the population receiving routinely recommended immunizations. (See 'Vaccination coverage' below.)
COVID-19 VACCINE — During the coronavirus disease 2019 (COVID-19) pandemic, COVID-19 vaccination is recommended for children ≥6 months of age. The dose and schedule vary with age and vaccine formulation. (See "COVID-19: Vaccines", section on 'Children'.)
ROUTINE SCHEDULE — The routine immunization schedules for children (figure 2A) and adolescents (figure 2B) in the United States are updated annually. The schedule is recommended by the Advisory Committee on Immunization Practices and approved by the Centers for Disease Control and Prevention, American Academy of Pediatrics, American Academy of Family Physicians, American College of Obstetricians and Gynecologists, American College of Nurse-Midwives, American Academy of Physician Assistants, and National Association of Pediatric Nurse Practitioners [5].
Failure by health care providers, parents, and other caregivers to adhere to the recommended immunization schedules, including the timing of immunizations, leaves children susceptible to life-threatening vaccine-preventable diseases. (See "Standard childhood vaccines: Parental hesitancy or refusal", section on 'Consequences of vaccine refusal'.)
Infants and children — Immunizations that are routinely recommended for infants and children in the United States are usually administered at health supervision visits (figure 2A). However, every visit provides an opportunity to update vaccines. Multiple injections are required at most visits. The use of combination vaccines (eg, diphtheria, tetanus, acellular pertussis (DTaP)/hepatitis B (HepB)/inactivated poliovirus vaccine (IPV) [Pediarix]; DTaP/Haemophilus influenzae type b (Hib)/IPV [Pentacel]; measles, mumps, and rubella (MMR)/varicella [ProQuad]; and DTaP/IPV [Kinrix]) can help to reduce the number of injections at each visit and improve vaccination coverage [6-9].
Immunizations routinely recommended for infants and children in the United States include [5]:
●Hepatitis B vaccine – HepB vaccine is routinely recommended within 24 hours of birth, at age 1 through 2 months, and at age 6 through 12 months (table 1A-B). HepB vaccine is inactivated. It is administered intramuscularly (IM).
Immunization against hepatitis B virus for infants, children, and adolescents is discussed in detail separately. (See "Hepatitis B virus immunization in infants, children, and adolescents".)
●Rotavirus vaccine – The routine schedule for rotavirus vaccine depends upon the vaccine formulation (table 2).
•The pentavalent human-bovine rotavirus reassortant vaccine (RV5) is administered at 2, 4, and 6 months of age.
•The attenuated human rotavirus vaccine (RV1) is administered at 2 and 4 months of age.
Both rotavirus vaccines are live attenuated viral vaccines. They are administered orally.
Rotavirus immunization is discussed in detail separately. (See "Rotavirus vaccines for infants".)
●Diphtheria, tetanus, and/or pertussis vaccines – DTaP vaccine is routinely recommended for infants and children at ages 2 months, 4 months, 6 months, 15 through 18 months, and 4 through 6 years. Booster doses are required beginning at age 11 years. DTaP vaccine is an inactivated vaccine. It is administered IM.
Diphtheria, tetanus, and pertussis immunization for children is discussed in detail separately. (See "Diphtheria, tetanus, and pertussis immunization in children 6 weeks through 6 years of age".)
●H. influenzae type b conjugate vaccine – Hib conjugate vaccine is routinely recommended in a two- or three-dose primary series (at age 2 and 4 months or at age 2, 4, and 6 months, depending upon the vaccine formulation) with a booster dose at age 12 through 15 months (table 3). Hib vaccines are inactivated vaccines. They are administered IM.
Hib immunization is discussed in detail separately. (See "Prevention of Haemophilus influenzae type b infection", section on 'Routine childhood immunization in the United States'.)
●Pneumococcal conjugate vaccine – The 13-valent pneumococcal conjugate vaccine (PCV13) is routinely recommended at age 2, 4, 6, and 12 through 15 months. PCV13 is an inactivated vaccine. It is administered IM.
Pneumococcal immunization for children is discussed in detail separately. (See "Pneumococcal vaccination in children".)
●Inactivated poliovirus vaccine – IPV is routinely recommended at age 2 months, 4 months, 6 through 18 months, and 4 through 6 years (table 4). IPV is administered IM or subcutaneously.
Poliovirus immunization is discussed in detail separately. (See "Poliovirus vaccination".)
●Influenza vaccine – Influenza immunization is recommended annually for all children ≥6 months of age, particularly those at high risk for complications (table 5). Inactivated influenza vaccines (IIV) for children <18 years are administered IM (table 6). The live attenuated influenza vaccine (LAIV) is administered intranasally.
Influenza immunization in children is discussed in detail separately. (See "Seasonal influenza in children: Prevention with vaccines".)
●Measles, mumps, and rubella vaccine – MMR vaccine is routinely recommended at age 12 through 15 months and age 4 through 6 years. MMR is a live attenuated virus vaccine. It is administered subcutaneously.
Immunization against measles, mumps, and rubella is discussed in detail separately. (See "Measles, mumps, and rubella immunization in infants, children, and adolescents".)
●Varicella vaccine – Varicella-zoster virus (VZV; chickenpox) vaccine is routinely recommended at age 12 through 15 months and age 4 through 6 years. VZV vaccine is a live attenuated virus vaccine. It is administered subcutaneously.
Immunization against varicella-zoster virus is discussed in detail separately. (See "Vaccination for the prevention of chickenpox (primary varicella infection)".)
●Hepatitis A vaccine – Two doses of hepatitis A virus (HepA) vaccine are routinely recommended between 12 and 24 months; the doses should be separated by at least six months [10]. HepA vaccine is an inactivated vaccine. It is administered IM.
Immunization against hepatitis A virus is discussed in detail separately. (See "Hepatitis A virus infection: Treatment and prevention".)
Adolescents — Most of the immunizations that are routinely recommended for adolescents in the United States are administered at 11 through 12 years or 16 years of age (figure 2B) [5,11]. However, every visit provides an opportunity to update and/or complete an adolescent's immunizations [12]. (See 'Catch-up schedule' below.)
Immunizations that are routinely recommended for adolescents in the United States include [5]:
●Tetanus, diphtheria, and acellular pertussis vaccine – A dose of tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is routinely recommended at age 11 through 12 years. Tdap is an inactivated vaccine. It is administered IM.
Immunization against tetanus, diphtheria, and pertussis for older children and adolescents is discussed in detail separately. (See "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age".)
●Meningococcal vaccines – Quadrivalent meningococcal conjugate vaccine (MenACWY) is routinely recommended at age 11 through 12 years and at age 16 years. MenACWY is an inactivated vaccine. It is administered IM.
Meningococcal serogroup B vaccines are not routinely recommended for adolescents who are not at increased risk for meningococcal disease. However, they may be given to adolescents and young adults age 16 through 23 years (age 16 through 18 years is preferred) in the context of shared decision-making (eg, considering the severity of meningococcal disease, the epidemiology of serogroup B meningococcal disease, the duration of protection) [13].
Immunization against meningococcal disease is discussed in detail separately. (See "Meningococcal vaccination in children and adults", section on 'Routine immunization of adolescents and young adults'.)
●Human papillomavirus vaccine – Two doses of the 9-valent human papillomavirus (HPV) vaccine are routinely recommended for immune-competent adolescents 11 through 12 years of age; the doses should be separated by at least six months [5,14].
If the adolescent is immunocompromised or the HPV vaccine series is initiated at ≥15 years of age, three doses of HPV vaccine are recommended; the second dose should be given one to two months after the first dose; the third dose should be given six months after the first dose. (See "Human papillomavirus vaccination", section on 'Indications and age range'.)
●Influenza vaccine – Influenza immunization is recommended annually for all children ≥6 months of age, particularly those at high risk for complications (table 5). IIV for children are administered IM. LAIV is administered intranasally. (See "Seasonal influenza in children: Prevention with vaccines".)
CATCH-UP SCHEDULE — Children who are behind on vaccines should be caught up using the minimum intervals between doses (table 7A-B). It is not necessary to restart the series – even when the interval between doses is prolonged [15,16].
The Centers for Disease Control and Prevention has developed "job aids" to provide guidance for catch-up of individual vaccines:
●Pneumococcal conjugate vaccine
•Pneumococcal recommendations vaccine advisor tool
●H. influenzae type b (Hib)
•Previous immunization with PedVaxHIB or Comvax (discontinued in 2014)
●Diphtheria, tetanus, and pertussis-containing vaccines for children 4 months through 6 years of age
●Tetanus, diphtheria, and pertussis containing vaccines
•For children 7 through 9 years of age
•For children 10 through 18 years of age
SPECIAL CIRCUMSTANCES
Vaccine hesitancy or refusal — The approach to parents who are hesitant to have their child vaccinated or refuse childhood vaccines is discussed separately. (See "Standard childhood vaccines: Parental hesitancy or refusal", section on 'Approach to management'.)
Unknown or uncertain immunization record — For children with an unknown or uncertain immunization record, serologic testing for antibodies to vaccine-preventable illnesses (table 8), revaccinating (as if the child were unvaccinated), or a combination of the two approaches is reasonable [17,18]. The Centers for Disease Control and Prevention Advisory Committee on Immunization Practices generally recommends age-appropriate revaccination [19].
The approach to immunization of children in the United States who have unknown or uncertain immunization history generally is the same as that for children vaccinated outside the United States who have unknown or uncertain immunizations. It is discussed separately. (See "International adoption: Immunization considerations", section on 'Unknown or uncertain immunization'.)
Dengue endemic areas — Dengue endemic United States territories and sovereign states in free association with the United States include [5,20]:
●American Samoa
●Federated States of Micronesia
●Republic of Marshall Islands
●Republic of Palau
●Puerto Rico
●United States Virgin Islands
A three-dose series of dengue tetravalent live vaccine is recommended for children age 9 through 16 years who live in these dengue endemic areas and have laboratory confirmation of previous dengue infection [20]. Confirmation of previous dengue infection is necessary because this vaccine is associated with severe dengue disease in people who have their first dengue infection after dengue vaccination. Laboratory confirmation is based upon the 2015 Centers for Disease Control and Prevention case definition or a highly accurate serodiagnostic screening test [20,21]. The three 0.5 mL doses are administered subcutaneously and should be separated by six months. (See "Dengue virus infection: Prevention and treatment", section on 'CYD-TDV (Dengvaxia)'.)
Other special circumstances
●Preterm infants – The routine immunization schedule, dose, intervals, and contraindications/precautions are the same for preterm infants (born at <37 weeks' gestation) as for infants and children who were born at ≥37 weeks' gestation, with the exception of hepatitis B (HepB) vaccine [22]. For infants who weigh <2 kg (4.4 pounds) at birth and are born to women who are hepatitis B surface antigen negative, the first dose of HepB vaccine is postponed until hospital discharge or 30 days of age, whichever is earlier (table 1B). (See "Hepatitis B virus immunization in infants, children, and adolescents", section on 'Routine infant immunization'.)
●Immunocompromised children – Immunization of children with primary immunodeficiency, asplenia/hyposplenia, and human immunodeficiency virus (HIV) discussed separately. (See "Immunizations in patients with primary immunodeficiency" and "Immunizations in persons with HIV" and "Prevention of infection in patients with impaired splenic function", section on 'Vaccinations'.)
Specific caveats regarding immunization in children with secondary immunodeficiency (eg, high-dose glucocorticoids) or who are to initiate immunosuppressive therapies (including antitumor necrosis factor agents, such as infliximab or adalimumab) are discussed in topics related to individual vaccines. For example, (see "Measles, mumps, and rubella immunization in infants, children, and adolescents", section on 'Contraindications').
●Infants with in utero exposure to certain antitumor necrosis factor agents – Live vaccines should not be given to infants with in utero exposure to certain antitumor necrosis factor agents (eg, infliximab, adalimumab, golimumab) because newborns may have detectable serum levels of the drug for up to nine months [23-25]. The duration of avoidance varies with the agent, but it is generally at least six months. Refer to the Lexicomp drug information monographs included within UpToDate for details.
●Close contacts of immunocompromised persons – Close (eg, household) contacts of immunocompromised persons should receive all routinely recommended vaccines (figure 2A-B) [26]. Close contacts of immunocompromised persons should not receive smallpox vaccine, which is not routinely recommended for children or adolescents. (See "Vaccines to prevent smallpox, mpox (monkeypox), and other orthopoxviruses".)
●Children and adolescents with increased risk of bleeding – For children and adolescents at increased risk of bleeding following intramuscular (IM) injections, we suggest consultation with the child's hematologist. The Advisory Committee on Immunization Practices best practice guidelines indicate that IM injections can be administered to a child or adolescent with a bleeding disorder if a clinician familiar with the patient's bleeding risk determines that the vaccine can be administered with reasonable safety [19]. Additional suggestions include [19,27]:
•If possible, schedule IM injections shortly after administration of clotting factors or before administration of anticoagulant medications
•Use a 23-gauge or smaller caliber needle
•Apply firm pressure on the site, without rubbing, for at least two minutes after injection
●Pregnant adolescents – Live vaccines (eg, measles, mumps, and rubella [MMR] vaccine, varicella vaccine, MMR-varicella vaccine) and human papillomavirus vaccine should be avoided during pregnancy. The approach to immunizations during pregnancy is discussed separately. (See "Immunizations during pregnancy".)
●Children or close contacts of pregnant women – Children and close contacts of pregnant women should receive routinely recommended vaccines, including live virus vaccines (eg, MMR vaccine, varicella vaccine, rotavirus vaccine) [19].
●Recent or anticipated administration of immune globulin or blood products – MMR and varicella vaccines should not be administered on the same day as immune globulin or for several months after immune globulin or blood products (table 9). Immune globulin and blood products contain antibodies, which can interfere with the vaccine response.
If immune globulin or blood products must be given within 14 days after administration of MMR or varicella vaccine, another dose of the vaccine should be administered after the suggested interval (table 9).
●Immunizations for travel – Immunizations for travel are discussed separately. (See "Immunizations for travel".)
●Children vaccinated outside the United States – The approach to immunization of children who were vaccinated outside the United States is the same as that for internationally adopted children. It is discussed separately. (See "International adoption: Immunization considerations".)
VACCINE ADMINISTRATION — The Advisory Committee on Immunization Practices (ACIP) provides best practice recommendations for vaccine administration, including minimum ages and intervals between vaccine doses, as well as the recommended dose, route, and site of administration for individual vaccines (table 10) [28]. Variations from these recommendations may result in invalid doses. (See 'Invalid doses' below.)
Preadministration counseling — In the United States, the National Childhood Vaccine Injury Act requires clinicians to provide the relevant vaccine information statement(s) to the child's caregiver/legal guardian before vaccine administration. Vaccine information statements are available from the Centers for Disease Control and Prevention (CDC).
The CDC website provides a list of contraindications and precautions to vaccines commonly used for children and adolescents. The Immunize.org website provides screening checklists for contraindications or precautions. Contraindications and precautions for specific vaccines and combination vaccines are discussed in individual topics related to immunizations for children.
Educating parents/caregivers and patients about vaccine-related pain management may be helpful in reducing pain during and after injections [29]. Education tools that are freely available, including a pamphlet (available from the Canadian Medical Association Journal) and a video, have been developed for parents of newborn infants [30,31]. In a longitudinal randomized trial, provision of these tools to parents in the nursery was associated with increased use of pain reduction strategies for infant immunizations [32]. (See 'Reducing injection pain' below.)
Injectable vaccines — Most of the routinely recommended childhood vaccines are injected intramuscularly (IM) or subcutaneously (table 10). The preferred position of the child and site of injection vary with age and route of injection (table 11). The injection site should be as free as possible from risk of local neural, vascular, or tissue injury [28].
Patient position
●Infants <12 months – Infants <12 months usually are held by their caregiver during injections; skin-to-skin contact is preferred for infants younger than one month [33].
●12 months through 2 years – Children 12 months through 2 years usually are held by their caregiver during injections (figure 3).
●3 years and older – Children 3 years through 11 years usually are seated during injections; they may be held by their caregiver. Adolescents ≥12 years and young adults may be seated or lying down during injections.
Immunization technique — Injectable vaccines should be administered using sterile technique [28]. It is not necessary to change needles between drawing the vaccine into the syringe and injecting it. A new needle and a new syringe should be used for each injection.
●Intramuscular injection – The preferred site for IM injections varies with age:
•Infants <12 months – Anterolateral thigh (vastus lateralis) (figure 4) is preferred; if the anterolateral thigh cannot be used (eg, because it is covered by a cast), the ventrogluteal site (figure 5) can be used; the upper outer gluteal quadrant (the dorsogluteal site) of the buttock should be avoided because of the possibility of a suboptimal immune response [34,35].
•12 months through 2 years – Anterolateral thigh is preferred, but the deltoid area of upper arm may be used.
•≥3 years – Deltoid area of upper arm (figure 6).
For IM injections, a 22- to 25-gauge needle is recommended [28,36]. The suggested needle length varies with age, sex, and weight (table 12). The needles should be long enough to reach the muscle but not so long as to penetrate underlying nerves, blood vessels, or bone [28,37-42]. Penetration into the bone can cause pain, damage to the periosteum, and detachment of the needle from the syringe [43].
The angle between the needle and the skin should be 90°. It is not necessary to pull back on the syringe plunger after needle insertion before IM injection [28,44]. The recommended sites for IM injections do not contain large blood vessels, and aspiration before injection may increase injection pain [29,33,45,46].
For deltoid injections, in addition to using the appropriate size needle, the following steps should be taken to avoid inadvertent injection into the subdeltoid bursa or joint space, which may cause "shoulder injury related to vaccine administration" [47-50] (see 'Local and systemic reactions' below):
•Both the patient and the vaccinator should be seated.
•The arm should be completely exposed and lifted slightly out to the side (eg, with the hand placed on the ipsilateral hip), which causes the subdeltoid bursa to slide under the acromion for protection.
•The needle should be inserted into the center of the deltoid muscle, midway between the acromion and the deltoid tuberosity (the insertion of the deltoid at the middle of the humerus), a point that falls in the middle one-third of an inverted triangle between the acromion and the deltoid tuberosity (figure 6).
●Subcutaneous injection – The preferred site for subcutaneous injections varies with age:
•Infants <12 months – The fatty tissue over the anterolateral thigh is preferred (figure 4); the upper-outer triceps may be used if necessary.
•≥12 months – The fatty tissue over the upper-outer area of triceps is preferred.
For subcutaneous injections, a 23- or 25-gauge needle 5/8 inch (16 mm) long is recommended [42]. The angle between the needle and skin should be 45°.
Oral vaccines — Rotavirus is the only routine childhood vaccine that is administered orally. Administration of rotavirus vaccine is discussed separately. (See "Rotavirus vaccines for infants", section on 'Administration'.)
Intranasal vaccines — The live attenuated influenza vaccine (LAIV) is the only routine childhood vaccine that is administered intranasally; an inactivated influenza vaccine that is administered IM is an alternative to intranasal injection. Indications for and administration of LAIV are discussed separately. (See "Seasonal influenza in children: Prevention with vaccines", section on 'Route and dose'.)
Administration of multiple vaccines at one visit
Timing and spacing — There is no upper limit to the number of vaccines that may be administered at a single visit [15,16,51]. The vaccines should not be mixed in the same syringe unless the combination has been specifically approved by the US Food and Drug Administration.
Most routine vaccines for children and adolescents (figure 2A-B) can be administered on the same day (at different sites) without compromising effectiveness [16,52-56]:
●Inactivated vaccines – Two or more inactivated vaccines may be administered at the same visit as or at any interval before or after other inactivated vaccines with three exceptions:
•PCV13 and MenACWY-D – In persons with functional or anatomic asplenia, all necessary doses of 13-valent pneumococcal conjugate vaccine (PCV13) should be given at least 28 days before the Menactra quadrivalent meningococcal conjugate vaccine (MenACWY-D). (See "Prevention of infection in patients with impaired splenic function", section on 'Vaccinations'.)
•MenACWY-D and DTaP – For children <7 years with immunodeficiencies that increase the risk of meningococcal disease (eg, anatomic or functional asplenia, HIV infection, complement component deficiency), MenACWY-D should be given before or at the same visit as the diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine [13]. If MenACWY-D cannot be given before or at the same visit as DTaP, MenACWY-D should be administered ≥6 months later. However, if MenACWY-D is inadvertently administered within six months after DTaP, MenACWY-D need not be repeated. For children who are at increased risk for meningococcal disease because of an outbreak of serogroup A, C, W, or Y disease or planned travel to an area where serogroup A, C, W, or Y disease is hyperendemic or epidemic, MenACWY-D may be administered at any time in relation to DTaP. (See "Meningococcal vaccination in children and adults", section on 'Administration in relation to other vaccines'.)
In a phase 2 trial, there was interference in the immune response to meningococcal vaccine antigens when MenACWY-D was given to children age four through six years one month after one brand of DTaP (Daptacel) but not when the vaccines were given at the same visit or when MenACWY-D was administered before DTaP [57,58]. The trial did not evaluate meningococcal response to other brands of DTaP.
The Menveo quadrivalent meningococcal conjugate vaccine (MenACWY-CRM) and MenQuadfi quadrivalent meningococcal conjugate vaccine (MenACWY-TT) can be given any time before, at the same visit as, or any time after DTaP [13].
•PCV13 and PPSV23 – In persons who require both PCV13 and the 23-valent pneumococcal polysaccharide vaccine (PPSV23), PCV13 should be administered at least eight weeks before PPSV23.
●Inactivated and live vaccines – Inactivated and live vaccines (table 13) may be administered at the same visit or at any interval between doses.
●Live injectable or live intranasal vaccines – Two or more live injectable (table 13) vaccines (eg, measles, mumps, and rubella [MMR] vaccine, varicella vaccine, dengue vaccine) or live intranasal vaccines (eg, live attenuated influenza vaccine) may be administered on the same day or ≥28 days apart. Yellow fever vaccine is an exception; it should be administered on the same day as or ≥30 days apart from other live injectable or live intranasal vaccines [59].
Live oral rotavirus vaccine and live oral typhoid vaccine may be administered on the same day as or at any interval before inactivated or live injectable vaccines. (See "Immunizations for travel", section on 'Typhoid vaccine'.)
Site of injections — When multiple injectable vaccines are required at a single visit, separate limbs should be used if possible, particularly for injections more likely to cause a local reaction (eg, diphtheria, tetanus, acellular pertussis vaccine and PCV13) [28,42,51]. If necessary, two or more vaccines can be given in the same limb (usually the anterolateral thigh). If possible, the injections should be separated by at least 2.5 cm (1 inch) to avoid overlap of local reactions.
If a vaccine and immune globulin preparation are administered at the same visit (eg, hepatitis B vaccine and hepatitis B immune globulin; tetanus-containing vaccine and tetanus immune globulin, hepatitis A vaccine and immune globulin), different limbs should be used for each injection [28].
Order of administration — When multiple vaccines are required at one visit, administering the least painful vaccines first may lessen immunization-related pain and distress [29,33,60,61].
For infants who require rotavirus vaccine, we suggest administering rotavirus vaccine before injectable vaccines. The oral rotavirus vaccine is flavored with sucrose, which may reduce the pain associated with subsequent injections [29,62]. (See 'Reducing injection pain' below.)
We also suggest administering other injectable vaccines before MMR and PCV13. Administration of MMR and PCV13 is perceived to be more painful than administration of other injectable vaccines [29,33,60,61]. Information about the relative painfulness of other vaccines is lacking.
For infants <12 months of age, if possible, we suggest administration of two injections simultaneously (by two health care providers at two different sites) rather than one after the other. Simultaneous injection may reduce injection pain for infants but does not appear to reduce distress for older children [33,63].
Reducing injection pain — The pain associated with vaccine injections, particularly when multiple injections are required, is a source of anxiety for patients and caregivers [64]. Failure to adequately address pain at the time of vaccination may lead to subsequent delay or avoidance of vaccination [29,44,65-68].
Systematic reviews, meta-analyses of randomized controlled trials, and randomized controlled trials support several interventions to reduce the pain associated with injection of vaccines [33,69-72]. Although the evidence of benefit is of low or moderate quality, the interventions are unlikely to be harmful. Combinations of interventions (eg, topical anesthetic and distraction) may be more effective than using a single strategy [73].
Interventions with little support of benefit include warming the vaccine before administration and manual tactile stimulation (eg, pinching/pressing the skin near the injection site) during injection [33].
Our suggestions for reducing injection pain are generally in keeping with those of professional societies (table 11) [28,29,44]:
<12 months of age — For infants <12 months of age, interventions that may be helpful in reducing injection pain include [29,69,74]:
●Before injection
•Application of topical anesthetic agent (eg, cream, gel, patch) 30 to 60 minutes before injection if resources, availability, and time permit [75,76].
The risk of methemoglobinemia with topical anesthetic agents is discussed separately. (See "Methemoglobinemia", section on 'Topical anesthetics'.)
•Feeding (at breast or with bottle) or nonnutritive sucking [77,78].
•For infants who require rotavirus vaccine – Administration of rotavirus vaccine.
•For infants who do not require rotavirus vaccine – Administration of sucrose 2 mL of 24 percent or 50 percent strength solution one to two minutes before injection [74,79-82]. Glucose 2 mL of a 30 percent strength solution can be used if sucrose is not available.
●During injection
•Feeding (at breast or with bottle) or nonnutritive sucking [77,78,83].
•If multiple injections are required and another clinician is available, administering two injections simultaneously (at different sites) rather than one after the other [29].
•Administration of PCV13 after other injections.
•Administration of MMR (if needed for travel or outbreak) after other injections.
●After injection
•Feeding (at breast or with bottle) or nonnutritive sucking [77,78,84].
•Swaddling, holding, side/stomach position, shushing, and/or rocking [85].
•Therapeutic administration of acetaminophen or ibuprofen.
12 months through 2 years — For children 12 through 23 months years of age, interventions that may be helpful in reducing injection pain include [29,69]:
●Before injection
•Application of topical anesthetic agent (eg, cream, gel, patch) 30 to 60 minutes before injection if resources, availability, and time permit.
The risk of methemoglobinemia with topical anesthetic agents is discussed separately. (See "Methemoglobinemia", section on 'Topical anesthetics'.)
•Feeding (at breast or with bottle) or nonnutritive sucking (for children who continue to breastfeed or use a pacifier).
•For children <2 years – Administration of sucrose [86]; the typical dose is 2 mL of 24 percent or 50 percent strength solution administered one to two minutes before injection; glucose 2 mL of a 30 percent strength solution can be used if sucrose is not available [82].
●During injection
•Feeding (at breast or with bottle) or nonnutritive sucking (for children who continue to breastfeed or use a pacifier).
•Distraction (eg, with a video, toy) [70,87].
•Administration of PCV13 and MMR after other injections.
●After injection
•Feeding (at breast or with bottle) or nonnutritive sucking (for children who continue to breastfeed or use a pacifier).
•Stroking, rocking, or "blowing the pain away."
•Therapeutic administration of acetaminophen or ibuprofen.
3 years and older — For children ≥3 years, interventions that may be helpful in reducing injection pain include [29,69,72,88]:
●Before injection
•Application of topical anesthetic agent (eg, cream, gel, patch) 30 to 60 minutes before injection if resources, availability, and time permit.
●During injection
•For children <12 years – Video, music, verbal distraction, virtual reality distraction, or breathing distraction (eg, blowing bubbles or a pinwheel, deep breathing) [70,87,89-91].
•If PCV13 or MMR are necessary, administer after other injections.
●After injection
•Therapeutic administration of acetaminophen or ibuprofen.
Prophylactic medications
●Whether to administer – For infants and children who are receiving routine immunizations in the United States, we suggest not administering prophylactic antipyretic/analgesic agents. We suggest therapeutic antipyretic/analgesic agents (eg, acetaminophen, ibuprofen) for infants and children who develop fever or painful local or systemic reaction following immunizations. (See 'Reducing injection pain' above.)
A systematic review of randomized trials found that prophylactic acetaminophen reduced the risk of fever ≥38°C (100.4°F) 24 to 48 hours after primary immunization and booster immunization in children ≤6 years [92]. However, approximately one-half of children in the placebo groups remained afebrile. In addition, prophylactic administration of acetaminophen has been associated with decreased antibody concentrations for some vaccine antigens [93,94]. The clinical significance of this finding is uncertain, given that the antibody concentrations remained in the protective range.
Our suggestion not to routinely administer prophylactic antipyretic/analgesic agents at the time of or within four hours after immunization is consistent with recommendations of the ACIP [28], the World Health Organization [44], and an independent Canadian clinical practice guideline [29]. However, in the United Kingdom, where the meningococcal serogroup B vaccine (MenB-4C, Bexsero) is recommended during infancy, national guidelines advise administration of oral acetaminophen as soon as possible after MenB-4C immunization, four to six hours later, and four to six hours after that [95,96]. (See "Meningococcal vaccination in children and adults", section on 'Serogroup B vaccines'.)
●Choice of agent – For infants and children whose caregivers choose to administer prophylactic antipyretics/analgesics, we suggest acetaminophen rather than ibuprofen. We suggest that the first dose be administered within four hours after immunization.
In a systematic review of the effect of prophylactic antipyretic administration, acetaminophen reduced the risk of fever and local and systemic reactions in children ≤6 years [92]. Ibuprofen did not reduce the risk of fever and had inconsistent effects on the risk of local and systemic reactions. One of the included trials suggested that the acetaminophen dose given around the time of vaccination is more important than doses administered >4 hours after immunization [97].
NONSTANDARD VACCINE ADMINISTRATION
Invalid doses — Invalid doses need to be repeated because they may provide inadequate protection. Indications for repeating a vaccine dose include [28,51]:
●The full age-appropriate dose of an injectable vaccine was not administered (eg, the child moves before the injection is completed)
●Administration of expired vaccine
●Reconstitution with the wrong diluent
●Administration of any of the following vaccines by the subcutaneous rather than the intramuscular (IM) route: hepatitis B vaccine, human papillomavirus vaccine, or inactivated influenza vaccine that is labeled for IM administration
●Intradermal administration of any vaccine
●Administration of an injectable live virus vaccine (eg, measles, mumps, and rubella vaccine; varicella vaccine) <28 days after another injectable live virus vaccine
For inactivated vaccines, the invalid dose should be repeated as soon as possible. For live vaccines, the invalid dose should be repeated ≥28 days after the invalid dose.
Doses of vaccine that are administered ≥5 days before the recommended minimum age or interval are also invalid. Invalid doses of inactivated vaccines should be repeated when the child reaches the minimum age or the recommended minimum interval has elapsed. Invalid doses of live vaccines should be repeated ≥28 days after the invalid dose, provided that the child has reached the recommended minimum age or the recommended minimum interval as elapsed.
Additional information about how to avoid preventable vaccination errors, and how to respond if they occur, is available from the Immunize.org.
Doses that can be counted as valid — Nonstandard vaccine administration scenarios that do not require repeating the dose include [52]:
●Vaccine that is recommended to be given subcutaneously is administered IM
●Patient sneezes after nasal spray vaccine
●Infant regurgitates, spits, or vomits after oral rotavirus vaccine (see "Rotavirus vaccines for infants", section on 'Administration')
●The dose that was administered was greater than the age-appropriate dose (the parent/caregiver should be notified about the error)
●Doses administered <5 days before the minimum recommended age or interval, unless required by local or state mandates
VACCINE STORAGE AND HANDLING — Recommendations for storage and handling of vaccines, including a toolkit, are available from the Centers for Disease Control and Prevention.
ADVERSE EVENTS
Local and systemic reactions — Mild adverse local and systemic reactions occur with approximately 50 percent of vaccinations, depending upon the vaccine [98]. Localized tenderness, erythema, and swelling and/or mild fever are most common [99]. These reactions usually resolve in one to two days without intervention.
More serious local and systemic reactions may occur. Examples include:
●Shoulder injury related to vaccine administration/subdeltoid or subacromial bursitis – Clinical features of shoulder injury related to vaccine administration (SIRVA)/ subdeltoid or subacromial bursitis include shoulder pain and reduced range of motion at the shoulder within a few hours of vaccination without evidence of microbial infection [100-106]. Pain and reduced function can be prolonged. Management may include physiotherapy and intra-articular glucocorticoid injections. Proper intramuscular injection technique prevents SIRVA. (See 'Immunization technique' above.)
●Febrile seizures – The risk of febrile seizures is slightly increased following certain vaccines or combinations of vaccines. Genetic susceptibility may also play a role. (See "Clinical features and evaluation of febrile seizures", section on 'Immunization'.)
●Syncope – Postvaccination syncope occurs most frequently among adolescents and young adults, and can be associated with serious injury (eg, skull fracture, cerebral hemorrhage) [107]. Among cases of postvaccine syncope reported to the Vaccine Adverse Events Reporting System (VAERS), 80 percent occurred within 15 minutes of vaccination.
To prevent secondary injury associated with syncope, the Advisory Committee on Immunization Practices suggests observation of adolescent and young adult patients for 15 minutes after vaccination [108]. This suggestion is particularly important for patients with risk factors for presyncope, even though presyncope does not always progress to syncope. Risk factors for presyncope include a history of passing out or nearly passing out after an injection or venipuncture, prevaccine anxiety, receiving ≥2 shots, and more severe postvaccination pain [109]. Symptoms of presyncope include dizziness, faintness, weakness, lightheadedness, facial flushing, difficulty hearing, visual disturbance, rapid or pounding heartbeat, rapid or difficult breathing, sweating, and feeling cold and sweaty or "clammy." Drinking water 10 to 60 minutes before immunization does not appear to prevent presyncope in adolescents or young adults [109].
Risk of recurrence — Although the risk of recurrence of local and systemic reactions following revaccination is uncertain, observational studies suggest that most patients with mild or moderate adverse events can be safely immunized [110,111]. Published observational studies typically include small numbers of patients, and patients who had severe reactions (eg, anaphylaxis) often are not reimmunized. These limitations notwithstanding, a systematic review of 29 observational studies published between 1982 and 2016 provides estimates of the risk of recurrence of selected adverse effects [110]:
●Extensive limb swelling following diphtheria, tetanus, acellular pertussis (DTaP) vaccine – In a systematic review of three studies, extensive limb swelling occurred in 56 percent of 98 children after DTaP; all recovered completely
●Seizures – No recurrence in three studies
●Pain – Ranged from 9 to 36 percent following diphtheria, tetanus, and pertussis-containing vaccines, depending upon the type of vaccine (whole cell versus acellular) and the dose (eight studies)
●Redness and/or swelling ≥5 cm (2 inches) – Ranged from 23 to 67 percent following DTaP, depending upon the dose (three studies)
●Redness and/or swelling ≥10 cm (4 inches) – 40 percent (95% CI 12-74) following various vaccines (one study)
●Hypotonic hyporesponsive episodes – Pooled recurrence risk of 0 percent (95% CI 0-0.1) in nine studies
●Fever – Ranged from 0 to 84 percent depending upon the vaccine (10 studies)
●Persistent crying – 15 to 25 percent for DTaP (two studies)
Allergic reactions — Allergic reactions to vaccines, including the acute management of anaphylaxis and the approach to the patient with suspected vaccine allergy, are discussed separately. (See "Anaphylaxis: Emergency treatment" and "Allergic reactions to vaccines", section on 'Approach to the patient with suspected vaccine allergy'.)
Reporting adverse events — Adverse events associated with vaccines should be reported to the United States Department of Health and Human Services using VAERS (telephone number 1-800-822-7967).
The National Childhood Vaccine Injury Act requires health care providers in the United States to report:
●Adverse events listed in the VAERS table of reportable events following vaccination
●Adverse events that are listed by the vaccine manufacturer
The Centers for Disease Control and Prevention also encourages health care providers to report any clinically significant adverse event that occurs after vaccination, even if it is unclear whether the vaccine caused the event [112].
VACCINATION COVERAGE — National, regional, and state vaccination coverage estimates for children age 19 to 35 months, children enrolled in kindergarten, and teenagers are available from the Centers for Disease Control and Prevention (CDC). National age-appropriate vaccine coverage generally is >90 percent for most routinely recommended vaccines in preschool- and kindergarten-aged children. However, age-appropriate vaccination coverage is lower among preterm infants [113]. Age-appropriate vaccine coverage is also lower among adolescents, with rates of approximately 90 percent for ≥1 dose of Tdap, 89 percent for ≥1 dose of meningococcal conjugate vaccine, 77 percent for ≥1 dose of human papillomavirus (HPV) vaccine among female adolescents and 73 percent for ≥1 dose of HPV vaccine among male adolescents in 2020 [114]. Vaccination coverage estimates provided by the CDC do not reflect the timeliness of immunizations [115].
Provider-focused strategies to increase vaccination coverage include: use of combination vaccines [7,9]; reminder or recall systems, including text messaging [22,116-118]; electronic medical record alerts that the patient is due for specific vaccines; provision of educational brochures in the waiting area [119]; and use of standing orders for immunization to avoid missed opportunities for immunization [15,120]. Immunize.org provides resources for implementing standing orders for immunization. A systematic review of 55 randomized and observational studies concluded that reminder and recall messages probably are effective in increasing immunization rates in primary care (by an average of 8 percent) [22].
RESOURCES
●The Centers for Disease Control and Prevention provides a number of vaccine-related resources, including:
•Vaccine information statements
•A list of contraindications and precautions to commonly used vaccines
•Instant Childhood Immunization Schedule, a personal, customized immunization schedule based upon the child's birth date
•Information regarding vaccine administration
•Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book)
•An updated list of vaccine shortages and delays
•State specific vaccine requirements for daycare and school entry
•A resource library including videos on how to prepare and administer intramuscular, subcutaneous, intranasal, and oral vaccines
●Immunize.org provides numerous resources for health professionals and the public
●The Institute for Safe Medication Practices provides recommendations for practitioners to prevent vaccine errors
●National Foundation for Infectious Diseases and provides resources related to immunizations for adolescents
●The US Food and Drug Administration maintains a list of vaccines licensed in the United States
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Immunizations in children and adolescents".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)
●Basics topics (see "Patient education: Vaccines for babies and children age 0 to 6 years (The Basics)" and "Patient education: Vaccines for children age 7 to 18 years (The Basics)")
●Beyond the Basics topics (see "Patient education: Why does my child need vaccines? (Beyond the Basics)" and "Patient education: Vaccines for infants and children age 0 to 6 years (Beyond the Basics)" and "Patient education: Vaccines for children age 7 to 18 years (Beyond the Basics)")
SUMMARY
●COVID-19 vaccines – During the coronavirus disease 2019 (COVID-19) pandemic, COVID-19 vaccination is recommended for children ≥6 months of age in the United States. (See "COVID-19: Vaccines", section on 'Children'.)
●Routine schedule – Universally recommended vaccines for children and adolescents in the United States include: hepatitis B; rotavirus; diphtheria, tetanus, pertussis; Haemophilus influenzae type b; pneumococcal conjugate; inactivated polio; seasonal influenza; measles, mumps, rubella; varicella-zoster virus; hepatitis A; meningococcus; and human papillomavirus (figure 2A-B). Immunization schedules for other countries are available through the World Health Organization. (See 'Routine schedule' above.)
●Catch-up schedule – Children who are behind on vaccines should be caught up using the minimum intervals between doses (table 7A-B). It is not necessary to restart the series – even when the interval between doses is prolonged. (See 'Catch-up schedule' above.)
●Vaccine administration
•The Advisory Committee on Immunization Practices provides best practice recommendations for vaccine administration, including minimum ages and intervals between vaccine doses, as well as the recommended dose, route, and site of administration for individual vaccines (table 10). (See 'Vaccine administration' above.)
•Preadministration counseling includes provision of vaccine information statements, assessing for contraindications and precautions, and educating parents/caregivers and patients about management of vaccine-related pain. (See 'Preadministration counseling' above.)
•Most of the routinely recommended childhood vaccines are injected intramuscularly or subcutaneously (table 10). The preferred position of the child, site of injection, and strategies to reduce injection pain vary with age (table 11). (See 'Injectable vaccines' above and 'Reducing injection pain' above.)
●Reporting adverse events – Adverse events associated with vaccines should be reported to the United States Department of Health and Human Services using the Vaccine Adverse Events Reporting System (telephone number 1-800-822-7967). (See 'Reporting adverse events' above.)
