Pediatric fever of uncertain source: Difference between revisions
(219 intermediate revisions by 16 users not shown) | |||
Line 1: | Line 1: | ||
== | ==Background== | ||
*Fever accounts for 30% of pediatric visits | |||
*Children <3 months are immunocompromised (e.g. poor opsonization, poor IgG response to encapsulated bacteria, macrophage and neutrophil dysfunction, bone marrow insufficiency) | |||
''' | ===Epidemiology and Risk=== | ||
{| class="wikitable" | |||
| align="center" style="background:#f0f0f0;"|'''Age''' | |||
| align="center" style="background:#f0f0f0;"|'''0-14 days''' | |||
| align="center" style="background:#f0f0f0;"|'''14-28 days''' | |||
| align="center" style="background:#f0f0f0;"|'''28-60 days (pre vaccine)''' | |||
| align="center" style="background:#f0f0f0;"|'''28-60 days (post vaccine)''' | |||
| align="center" style="background:#f0f0f0;"|'''60-90 days''' | |||
| align="center" style="background:#f0f0f0;"|'''> 90 days''' | |||
|- | |- | ||
| | | [[Meningitis]]/SBI Prevalence ||1/10||1/20||1/100||1/1000||1/1000-10,000||> 1/10,000 | ||
| | |} | ||
*Serious bacterial illness (SBI) includes UTI, meningitis, pneumonia, bacteremia | |||
*7% of patients <2 years old with fever have [[pneumonia]], however the etiology (viral/bacterial) or even the presence of pneumonia has low inter-observer reliability even among pediatric radiologists<ref>ACEP's Clinical Policy on Pediatric Fever. Clinical Policy for Children Younger Than Three Years Presenting to the Emergency Department With Fever. Annuals of Emergency Medicine 2003 42. 530-545</ref> | |||
*4% Prevalence of [[UTI]] with common other sources of fever ([[OM]], viral [[URI]], etc)<ref>ACEP's Clinical Policy on Pediatric Fever. Clinical Policy for Children Younger Than Three Years Presenting to the Emergency Department With Fever. Annuals of Emergency Medicine 2003 42. 530-545</ref> | |||
0- | *0.3% of previously well children aged 3-36 months who have a fever without a source will develop significant sequelae, 0.03% will develop sepsis or meningitis<ref>ACEP's Clinical Policy on Pediatric Fever. Clinical Policy for Children Younger Than Three Years Presenting to the Emergency Department With Fever. Annuals of Emergency Medicine 2003 42. 530-545</ref> | ||
===Concomitant Respiratory Viral Infection=== | |||
*Relatively high coincidence of [[RSV]], [[enterovirus]], and [[paraflu]] with bacteremia (and UTIs), so positive lab test for these viruses should not change testing and management plan<ref>Greenes, D.S.M., & Harper, M. B.M. (1999). Low risk of bacteremia in febrile children with recognizable viral syndromes. Pediatric Infectious Disease Journal, 18(3), 258-261.</ref> | |||
**[[RSV]]+ neonates aged 0-28 days, 3.7% were bactremic (and 6.1% had [[UTI]]s) | |||
**RSV+ infants aged 29-60 days, (5.5% had [[UTI]]s) | |||
*There is a low coincidence of [[influenza]] with SBI, so postivie lab test for this virus may change testing and management plan (i.e. lower risk of concurrent bacterial illness)<ref>Greenes, D.S.M., & Harper, M. B.M. (1999). Low risk of bacteremia in febrile children with recognizable viral syndromes. Pediatric Infectious Disease Journal, 18(3), 258-261.</ref> | |||
==Clinical Features== | |||
*[[Acute fever|Febrile]] | |||
**Defined as [[Celsius Fahrenheit Temperature Conversion|temperature]] ≥38°C (100.4°F). | |||
**Peripheral temperature is not clinically accurate and central measurements are the preferred means of determining fever. | |||
**Parental report of confirmed fever at home (i.e. via thermometer), even with no fever in ED, has rates of SBIs high as 4.7% (0-28 day range)<ref>Serious bacterial infections in neonates presenting afebrile with history of fever Ramgopal S, Walker LW, Tavarez MM, et al. Pediatrics. 2019;144(2):e20183964.</ref> | |||
==Differential Diagnosis== | |||
{{Pediatric fever DDX}} | |||
==Evaluation & Management== | |||
*Preemies: Count age by estimated postconception date (not by actual delivery date) for 1st-90d | |||
===0-7 Days=== | |||
''For all infants (toxic and well-appearing)'' | |||
{| class="wikitable" | |||
|- | |- | ||
| | | '''Child Appearance''' | ||
| '''Work Up''' | |||
| '''Treatment''' | |||
| '''Disposition & Follow-up''' | |||
| '''Comments''' | |||
| | |||
| | |||
|- | |- | ||
| '''Temperature ≥38°''' | |||
'''Toxic or Well''' | |||
| | | | ||
*CBC | |||
*Blood cultures | |||
*[[Urinalysis]], Urine culture | |||
*[[LP]]-CSF | |||
*[[CXR]] | |||
*+/- Stool studies (if diarrhea) | |||
| | | | ||
{{Pediatric fever antibiotics 0-28)}} | |||
| Admit | |||
| SBI incidence | |||
*Ill appearing: 13%–21% | |||
*Not ill appearing: <5% | |||
| | |||
Admit | |||
| | |||
: | |||
|} | |} | ||
{{Pediatric fever acyclovir indications}} | |||
Note: | |||
*CXR is optional if no resp sx and another source identified | |||
*LP is necessary even if another source identified due to immature blood-brain barrier | |||
*Do not give ceftriaxone to children <28d as may cause hyperbilirubinemia | |||
=== | ===8-21 Days<ref>Evaluation and Management of Well-Appearing Febrile Infants 8 to 60 Days Old Robert H. Pantell, Kenneth B. Roberts, William G. Adams, Benard P. Dreyer, Nathan Kuppermann, Sean T. O'Leary, Kymika Okechukwu and Charles R. Woods; Subcommittee On Febrile Infants Pediatrics July 2021, e2021052228; DOI: https://doi.org/10.1542/peds.2021-052228 </ref>=== | ||
*For toxic infants, treat for sepsis and admit | |||
*For well-appearing infants, see below algorithm | |||
| | [[File:Peds fever 8-21 days (2.0).png|8-21 day algorithm]] | ||
===22-28 Days<ref>Evaluation and Management of Well-Appearing Febrile Infants 8 to 60 Days Old Robert H. Pantell, Kenneth B. Roberts, William G. Adams, Benard P. Dreyer, Nathan Kuppermann, Sean T. O'Leary, Kymika Okechukwu and Charles R. Woods; Subcommittee On Febrile Infants Pediatrics July 2021, e2021052228; DOI: https://doi.org/10.1542/peds.2021-052228 </ref>=== | |||
*For toxic infants, treat for sepsis and admit | |||
*For well-appearing infants, see below algorithm | |||
[[File:Peds fever 22-28 days (2.0).PNG]] | |||
=== | ===29-60 Days<ref>Evaluation and Management of Well-Appearing Febrile Infants 8 to 60 Days Old Robert H. Pantell, Kenneth B. Roberts, William G. Adams, Benard P. Dreyer, Nathan Kuppermann, Sean T. O'Leary, Kymika Okechukwu and Charles R. Woods; Subcommittee On Febrile Infants Pediatrics July 2021, e2021052228; DOI: https://doi.org/10.1542/peds.2021-052228 </ref>=== | ||
*For toxic infants, treat for sepsis and admit | |||
*For well-appearing infants, see below algorithm | |||
[[File:Peds fever 29-60 (2.0).PNG]] | |||
===60 Days - 36 Months<ref>Jaskiewicz, J.A., McCarthy, C.A., Richardson, A.C., White, K.C., Fisher, D.J., Powell, K. R., et al. (1994). Febrile infants at low risk for serious bacterial infection-an appraisal of the Rochester criteria and implications for management. Pediatrics 94(3), 390-396.</ref>=== | |||
{| class="wikitable" | |||
|- | |- | ||
| '''Appearance''' | | '''Appearance''' | ||
| '''Work Up''' | | '''Work Up''' | ||
| '''Treatment''' | | '''Treatment''' | ||
| '''Disposition | | '''Disposition & Follow-Up''' | ||
|- | |- | ||
| ''' | | '''T≥38° + Toxic''' | ||
| | | | ||
*CBC | |||
*Blood cultures | |||
*[[Urinalysis]], urine culture | |||
*[[LP]]-CSF | |||
*[[CXR]]^ | |||
| | | | ||
{{Pediatric fever antibiotics 90dy-36mo}} | |||
| Admit | | Admit | ||
|- | |- | ||
| '''T≥39°C + Well + Non-complete [[Prevnar]]''' | |||
(No [[Prevnar]] or <4 weeks post 1st [[Prevnar]] dose) | |||
| | | | ||
*[[Urinalysis]], Urine culture | |||
*CBC | |||
*+/- CXR | |||
| If WBC(+): | |||
*[[Ceftriaxone]] 50mg-100mg/kg (also then consider [[blood culture]] and [[LP]], especially in <6mo old) | |||
| Outpatient (24 hour follow-up) | |||
| Outpatient | |||
|- | |- | ||
| '''T≥39°C + Well + [[Prevnar]]''' | |||
(2 [[Prevnar]] or ≥4 weeks post 1st [[Prevnar]] dose) | |||
| | | | ||
*Urine workup (UA, urine culture) for: | |||
**Circumcised males <6 months | |||
**Uncircumcised males <12 months | |||
**All females | |||
*+/- CXR | |||
| Treat [[cystitis]] or [[pneumonia]] if postitive | |||
| Outpatient (48hour follow up) | |||
| | |||
| | |||
|- | |- | ||
| | | '''T≥38-38.9°C + Well''' | ||
| | | Consider UA, CXR based on symptoms, etc | ||
| | | Treat [[cystitis]] or [[pneumonia]] if positive | ||
| Outpatient (48-72 hour follow-up)<ref>Baker, M.D., Bello, L.M., & Avner, J.R. (1993). Outpatient management without antibiotics of fever in selected infants. New England Jouranl of Medicine, 329(20), 1437-1441.</ref> | |||
|- | |- | ||
| | |} | ||
{{Pediatric fever CXR indications}} | |||
*Non-UTI SBI incidence of <.4% in children >6 mo | |||
==Low Risk Lab Criteria== | |||
''If low-risk criteria below not met, then perform the LP (if not done) and admit for inpatient antibiotics''<ref> Smitherman, H.F. & Macias, C.G. (2014). Evaluation and management of fever in the neonate and young infant (less than three months of age) [Electronic Version]. UpToDate,Teach, S.J., Kaplan, SL, Wiley, JF.</ref><ref>Dagan, R. Sofer, S., Phillip, M., & Shachak, E. (1988). Ambulatory care of febrile infants younger than 2 months of age classified as being at low risk for having serous bacterial infections. Journal of Pediatrics, 112(3), 355-360.</ref> | |||
===CBC=== | |||
*WBC 5-15 /mm<sup>3</sup> | |||
*Absolute Band count <1500 /mm<sup>3</sup> | |||
*Procalcitonin ≤0.5 ng/mL | |||
*ANC ≤4000/mm<sup>3</sup> | |||
===Urinalysis=== | |||
*Clear | |||
*Neg Nitrate and Leukocyte esterase | |||
*WBC <10/high powered field | |||
===CSF=== | |||
*Studies should include WBC, protein, glucose, Gram stain, and culture for bacteria. Consider viral studies (HSV). | |||
====0-28 days==== | |||
*WBC: 0-22/mm<sup>3</sup> | |||
*Protein: <100mg/dL | |||
====>29 days==== | |||
*WBC 0-7/mm<sup>3</sup> | |||
*Protein: 15-25mg/dL | |||
==Additional Management== | |||
===Initial Empiric Antibiotics for Well-Appearing Infants<ref>Evaluation and Management of Well-Appearing Febrile Infants 8 to 60 Days Old Robert H. Pantell, Kenneth B. Roberts, William G. Adams, Benard P. Dreyer, Nathan Kuppermann, Sean T. O'Leary, Kymika Okechukwu and Charles R. Woods; Subcommittee On Febrile Infants Pediatrics July 2021, e2021052228; DOI: https://doi.org/10.1542/peds.2021-052228 </ref>=== | |||
{| {{table}} | |||
| align="center" style="background:#f0f0f0;"|'''Suspected Infection Source''' | |||
| align="center" style="background:#f0f0f0;"|'''8-21 Days Old''' | |||
| align="center" style="background:#f0f0f0;"|'''22-28 Days Old''' | |||
| align="center" style="background:#f0f0f0;"|'''29-60 Days Old''' | |||
|- | |- | ||
| | | [[UTI]]|| | ||
*[[Ampicillin]] IV or IM (150 mg/kg per day divided q8) AND either: | |||
**[[Ceftazidime]] IV or IM (150 mg/kg per day divided q8) or | |||
| | **[[Gentamicin]] IV or IM (4 mg/kg per dose q24) | ||
|| | |||
*[[Ceftriaxone]] IV or IM (50 mg/kg per dose q24) | |||
|| | |||
*[[Ceftriaxone]] IV or IM (50 mg/kg per dose q24) | |||
*Oral options: | |||
**[[Cephalexin]] 50-100 mg/kg per day QID or | |||
| | **[[Cefixime]] 8 mg/kg QD | ||
|- | |- | ||
| | | No source identified | ||
|| | |||
*[[Ampicillin]] IV or IM (150 mg/kg per day divided q8) AND either: | |||
**[[Ceftazidime]] IV or IM (150 mg/kg per day divided q8) or | |||
**[[Gentamicin]] IV or IM (4 mg/kg per dose q24) | |||
| | || | ||
*[[Ceftriaxone]] IV or IM (50 mg/kg per dose q24) | |||
|| | |||
*[[Ceftriaxone]] IV or IM (50 mg/kg per dose q24) | |||
| | |||
|- | |- | ||
| | | Bacterial [[meningitis]] | ||
|| | |||
*[[Ampicillin]] IV or IM (300 mg/kg per day divided q6) AND | |||
*[[Ceftazidime]] IV or IM (150 mg/kg per day divided q8) | |||
|| | |||
*[[Ampicillin]] IV or IM (300 mg/kg per day divided q6) AND | |||
*[[Ceftazidime]] IV or IM (150 mg/kg per day divided q8) | |||
|| | |||
*Cephalosporin | |||
| | **[[Ceftriaxone]] IV (100 mg/kg QD) or | ||
**[[Ceftazidime]] IV (150 mg/kg QD) | |||
*AND [[Vancomycin]] IV (60 mg/kg QD) | |||
| | |||
| | |||
| | |||
| | |||
( | |||
( | |||
( | |||
|} | |} | ||
{{Acetaminophen pediatric dosing chart}} | |||
*[[ | ==See Also== | ||
*[[Sepsis ( | *[[Acute fever]] | ||
*[[Meningitis ( | *[[Fever of unknown origin (peds)]] | ||
*[[Febrile | *[[Urinary tract infection (peds)]] | ||
*[[Sepsis (peds)]] | |||
*[[Meningitis (peds)]] | |||
*[[Febrile seizure]] | |||
*[[PECARN Febrile Infant]] | |||
== | ==External Links== | ||
*[http://www.pemed.org/blog/2011/10/9/fever-of-unknown-source-part-1.html PEM ED Algorithm for Pediatric Fever] | |||
*[http://ddxof.com/pediatric-fever/ DDxOf: Pediatric Fever] | |||
==References== | |||
<references/> | |||
[[Category: | [[Category:Pediatrics]] | ||
[[Category:ID]] |
Latest revision as of 16:46, 15 March 2023
Background
- Fever accounts for 30% of pediatric visits
- Children <3 months are immunocompromised (e.g. poor opsonization, poor IgG response to encapsulated bacteria, macrophage and neutrophil dysfunction, bone marrow insufficiency)
Epidemiology and Risk
Age | 0-14 days | 14-28 days | 28-60 days (pre vaccine) | 28-60 days (post vaccine) | 60-90 days | > 90 days |
Meningitis/SBI Prevalence | 1/10 | 1/20 | 1/100 | 1/1000 | 1/1000-10,000 | > 1/10,000 |
- Serious bacterial illness (SBI) includes UTI, meningitis, pneumonia, bacteremia
- 7% of patients <2 years old with fever have pneumonia, however the etiology (viral/bacterial) or even the presence of pneumonia has low inter-observer reliability even among pediatric radiologists[1]
- 4% Prevalence of UTI with common other sources of fever (OM, viral URI, etc)[2]
- 0.3% of previously well children aged 3-36 months who have a fever without a source will develop significant sequelae, 0.03% will develop sepsis or meningitis[3]
Concomitant Respiratory Viral Infection
- Relatively high coincidence of RSV, enterovirus, and paraflu with bacteremia (and UTIs), so positive lab test for these viruses should not change testing and management plan[4]
- There is a low coincidence of influenza with SBI, so postivie lab test for this virus may change testing and management plan (i.e. lower risk of concurrent bacterial illness)[5]
Clinical Features
- Febrile
- Defined as temperature ≥38°C (100.4°F).
- Peripheral temperature is not clinically accurate and central measurements are the preferred means of determining fever.
- Parental report of confirmed fever at home (i.e. via thermometer), even with no fever in ED, has rates of SBIs high as 4.7% (0-28 day range)[6]
Differential Diagnosis
Pediatric fever
- Upper respiratory infection (URI)
- UTI
- Sepsis
- Meningitis
- Febrile seizure
- Juvenile rheumatoid arthritis
- Pneumonia
- Acute otitis media
- Whooping cough
- Unclear source
- Kawasaki disease
- Neonatal HSV
- Specific virus
Evaluation & Management
- Preemies: Count age by estimated postconception date (not by actual delivery date) for 1st-90d
0-7 Days
For all infants (toxic and well-appearing)
Child Appearance | Work Up | Treatment | Disposition & Follow-up | Comments |
Temperature ≥38°
Toxic or Well |
|
|
Admit | SBI incidence
|
^Acyclovir if:
Note:
- CXR is optional if no resp sx and another source identified
- LP is necessary even if another source identified due to immature blood-brain barrier
- Do not give ceftriaxone to children <28d as may cause hyperbilirubinemia
8-21 Days[7]
- For toxic infants, treat for sepsis and admit
- For well-appearing infants, see below algorithm
22-28 Days[8]
- For toxic infants, treat for sepsis and admit
- For well-appearing infants, see below algorithm
29-60 Days[9]
- For toxic infants, treat for sepsis and admit
- For well-appearing infants, see below algorithm
60 Days - 36 Months[10]
Appearance | Work Up | Treatment | Disposition & Follow-Up |
T≥38° + Toxic |
|
|
Admit |
T≥39°C + Well + Non-complete Prevnar |
|
If WBC(+):
|
Outpatient (24 hour follow-up) |
T≥39°C + Well + Prevnar |
|
Treat cystitis or pneumonia if postitive | Outpatient (48hour follow up) |
T≥38-38.9°C + Well | Consider UA, CXR based on symptoms, etc | Treat cystitis or pneumonia if positive | Outpatient (48-72 hour follow-up)[11] |
- Consider CXR for:
- Respiratory symptoms
- Fever >48 hrs
- Tachypnea
- Hypoxia
- Non-UTI SBI incidence of <.4% in children >6 mo
Low Risk Lab Criteria
If low-risk criteria below not met, then perform the LP (if not done) and admit for inpatient antibiotics[12][13]
CBC
- WBC 5-15 /mm3
- Absolute Band count <1500 /mm3
- Procalcitonin ≤0.5 ng/mL
- ANC ≤4000/mm3
Urinalysis
- Clear
- Neg Nitrate and Leukocyte esterase
- WBC <10/high powered field
CSF
- Studies should include WBC, protein, glucose, Gram stain, and culture for bacteria. Consider viral studies (HSV).
0-28 days
- WBC: 0-22/mm3
- Protein: <100mg/dL
>29 days
- WBC 0-7/mm3
- Protein: 15-25mg/dL
Additional Management
Initial Empiric Antibiotics for Well-Appearing Infants[14]
Suspected Infection Source | 8-21 Days Old | 22-28 Days Old | 29-60 Days Old |
UTI |
|
|
|
No source identified |
|
|
|
Bacterial meningitis |
|
|
|
Acetaminophen Pediatric Dosing Chart
Weight (kg) | Weight (lbs) | Age | Dosage (mg) |
3-4 | 6-11 | 0-3 mo | 40 |
5-7 | 12-17 | 4-11 mo | 80 |
8-10 | 18-23 | 1-2 y | 120 |
11-15 | 24-35 | 2-3 y | 160 |
16-21 | 36-47 | 4-5 y | 240 |
22-26 | 48-59 | 6-8 y | 320 |
27-32 | 60-71 | 9-10 y | 400 |
33-43 | 72-95 | 11 y | 480 |
- Dosage can be given q6 hours
See Also
- Acute fever
- Fever of unknown origin (peds)
- Urinary tract infection (peds)
- Sepsis (peds)
- Meningitis (peds)
- Febrile seizure
- PECARN Febrile Infant
External Links
References
- ↑ ACEP's Clinical Policy on Pediatric Fever. Clinical Policy for Children Younger Than Three Years Presenting to the Emergency Department With Fever. Annuals of Emergency Medicine 2003 42. 530-545
- ↑ ACEP's Clinical Policy on Pediatric Fever. Clinical Policy for Children Younger Than Three Years Presenting to the Emergency Department With Fever. Annuals of Emergency Medicine 2003 42. 530-545
- ↑ ACEP's Clinical Policy on Pediatric Fever. Clinical Policy for Children Younger Than Three Years Presenting to the Emergency Department With Fever. Annuals of Emergency Medicine 2003 42. 530-545
- ↑ Greenes, D.S.M., & Harper, M. B.M. (1999). Low risk of bacteremia in febrile children with recognizable viral syndromes. Pediatric Infectious Disease Journal, 18(3), 258-261.
- ↑ Greenes, D.S.M., & Harper, M. B.M. (1999). Low risk of bacteremia in febrile children with recognizable viral syndromes. Pediatric Infectious Disease Journal, 18(3), 258-261.
- ↑ Serious bacterial infections in neonates presenting afebrile with history of fever Ramgopal S, Walker LW, Tavarez MM, et al. Pediatrics. 2019;144(2):e20183964.
- ↑ Evaluation and Management of Well-Appearing Febrile Infants 8 to 60 Days Old Robert H. Pantell, Kenneth B. Roberts, William G. Adams, Benard P. Dreyer, Nathan Kuppermann, Sean T. O'Leary, Kymika Okechukwu and Charles R. Woods; Subcommittee On Febrile Infants Pediatrics July 2021, e2021052228; DOI: https://doi.org/10.1542/peds.2021-052228
- ↑ Evaluation and Management of Well-Appearing Febrile Infants 8 to 60 Days Old Robert H. Pantell, Kenneth B. Roberts, William G. Adams, Benard P. Dreyer, Nathan Kuppermann, Sean T. O'Leary, Kymika Okechukwu and Charles R. Woods; Subcommittee On Febrile Infants Pediatrics July 2021, e2021052228; DOI: https://doi.org/10.1542/peds.2021-052228
- ↑ Evaluation and Management of Well-Appearing Febrile Infants 8 to 60 Days Old Robert H. Pantell, Kenneth B. Roberts, William G. Adams, Benard P. Dreyer, Nathan Kuppermann, Sean T. O'Leary, Kymika Okechukwu and Charles R. Woods; Subcommittee On Febrile Infants Pediatrics July 2021, e2021052228; DOI: https://doi.org/10.1542/peds.2021-052228
- ↑ Jaskiewicz, J.A., McCarthy, C.A., Richardson, A.C., White, K.C., Fisher, D.J., Powell, K. R., et al. (1994). Febrile infants at low risk for serious bacterial infection-an appraisal of the Rochester criteria and implications for management. Pediatrics 94(3), 390-396.
- ↑ Baker, M.D., Bello, L.M., & Avner, J.R. (1993). Outpatient management without antibiotics of fever in selected infants. New England Jouranl of Medicine, 329(20), 1437-1441.
- ↑ Smitherman, H.F. & Macias, C.G. (2014). Evaluation and management of fever in the neonate and young infant (less than three months of age) [Electronic Version]. UpToDate,Teach, S.J., Kaplan, SL, Wiley, JF.
- ↑ Dagan, R. Sofer, S., Phillip, M., & Shachak, E. (1988). Ambulatory care of febrile infants younger than 2 months of age classified as being at low risk for having serous bacterial infections. Journal of Pediatrics, 112(3), 355-360.
- ↑ Evaluation and Management of Well-Appearing Febrile Infants 8 to 60 Days Old Robert H. Pantell, Kenneth B. Roberts, William G. Adams, Benard P. Dreyer, Nathan Kuppermann, Sean T. O'Leary, Kymika Okechukwu and Charles R. Woods; Subcommittee On Febrile Infants Pediatrics July 2021, e2021052228; DOI: https://doi.org/10.1542/peds.2021-052228