2023

Manejo de la hiperbilirrubinemia en recién nacidos de 35 semanas y más

de edad gestacional
CLINICAL PRACTICE GUIDELINE

Recomendaciones
Guidance for the Clinician in Rendering Pediatric Care

Clinical Practice Guideline Revision:

Management of Hyperbilirubinemia in
the Newborn Infant 35 or More
Weeks of Gestation
- 80% de los RN tendrán algún grado de Alex R. Kemper, MD, MPH, MS, FAAP,a Thomas B. Newman, MD, MPH, FAAP,b Jonathan L. Slaughter, MD, MPH, FAAP,c
M. Jeffrey Maisels, MB BCh, DSc, FAAP,d Jon F. Watchko, MD, FAAP,e Stephen M. Downs, MD, MS,f
Randall W. Grout, MD, MS, FAAP,g David G. Bundy, MD, MPH, FAAP,h Ann R. Stark, MD, FAAP,i Debra L. Bogen, MD, FAAP,j
Alison Volpe Holmes, MD, MPH, FAAP,k Lori B. Feldman-Winter, MD, MPH, FAAP,l Vinod K. Bhutani, MD,m

ictericia
Steven R. Brown, MD, FAAFP,n Gabriela M. Maradiaga Panayotti, MD, FAAP,o Kymika Okechukwu, MPA,p
Peter D. Rappo, MD, FAAP,q Terri L. Russell, DNP, APN, NNP-BCr

- El control cuidadoso y la aplicación de
More than 80% of newborn infants will have some degree of
jaundice.1,2 Careful monitoring of all newborn infants and the
a
Division of Primary Care Pediatrics, Nationwide Children’s Hospital,
Columbus, Ohio; bDepartments of Epidemiology & Biostatistics and

tratamientos de forma oportuna evita llegar a altos niveles de bilirrubina

application of appropriate treatments are essential, because high
bilirubin concentrations can cause acute bilirubin encephalopathy and
kernicterus.3 Kernicterus is a permanent disabling neurologic condition
characterized by some or all of the following: choreoathetoid cerebral
Pediatrics, School of Medicine, University of California, San Francisco, San
Francisco, California; cCenter for Perinatal Research, Nationwide Children’s
Hospital, Columbus, Ohio; dDepartment of Pediatrics, Oakland University
William Beaumont School of Medicine, Rochester, Michigan; eDepartment
of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh,
Pennsylvania; fDepartment of Pediatrics, Wake Forest University, Winston-

que puedan causar kernicterus.

palsy, upward gaze paresis, enamel dysplasia of deciduous teeth,
sensorineural hearing loss or auditory neuropathy or dyssynchrony
spectrum disorder, and characteristic findings on brain MRI.4 A
description of kernicterus nomenclature is provided in Appendix A.
Salem, North Carolina; gChildren’s Health Services Research, Indiana
University School of Medicine, Indianapolis, Indiana; hMedical University of
South Carolina, Charleston, South Carolina; iDepartment of Neonatology,
Beth Israel Deaconess Medical Center, Boston, Massachusetts; jAllegheny
County Health Department, Pittsburgh, Pennsylvania; kGeisel School of

- En el 2004 la AAP realiza recomendaciones para el manejo y

Central to this guideline is having systems in place including policies in
hospitals and other types of birthing locations to provide the care
necessary to minimize the risk of kernicterus.
Medicine at Dartmouth, Children's Hospital at Dartmouth-Hitchcock,
Lebanon, New Hampshire; lDepartment of Pediatrics, Division of
Adolescent Medicine, Cooper Medical School of Rowan University, Camden,
New Jersey; mDepartment of Pediatrics, Neonatal and Developmental
Medicine Stanford University School of Medicine, Stanford, California;

prevención de la hiperbilirrubinemia en RN de 35 semanas o más

This article updates and replaces the 2004 American Academy of
Pediatrics (AAP) clinical practice guideline for the management and
prevention of hyperbilirubinemia in the newborn infant $35 weeks’
gestation.3 This clinical practice guideline, like the previous one, addresses
n
University of Arizona College of Medicine – Phoenix Family Medicine
Residency, Phoenix, Arizona;oDivision of Primary Care, Duke Children’s
Hospital and Health Center, Duke University Medical Center, Durham, North
Carolina; pDepartment of Quality, American Academy of Pediatrics,
Itasca, Illinois; qSouth Shore Hospital, South Weymouth, Massachusetts;
and rNational Association of Neonatal Nurses, Chicago, Illinois

- En el 2022 se actualizan las recomendaciones en base a nueva

issues of prevention, risk assessment, monitoring, and treatment.
This document is copyrighted and is property of the American
Academy of Pediatrics and its Board of Directors. All authors have
GUIDELINE DEVELOPMENT PROCESS
The AAP convened a clinical practice guideline committee with To cite: Kemper AR, Newman TB, Slaughter JL, et al. Clinical

evidencia y experiencia clínica

membership that included neonatologists, hospitalists, primary care Practice Guideline Revision: Management of
Hyperbilirubinemia in the Newborn Infant 35 or More Weeks
pediatricians, a nurse, and breastfeeding experts. Some members also of Gestation. Pediatrics. 2022;150(3):e2022058859
had special expertise in neonatal hyperbilirubinemia. This committee

Se elevan los umbrales de tratamiento especí cos manteniendo la

PEDIATRICS Volume 150, number 3, September 2022:e2022058859
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FROM THE AMERICAN ACADEMY OF PEDIATRICS

seguridad
on 05 August 2022

1-Prevención de la hiperbilirrubinemia
1. Prevención de la hiperbilirrubinemia asociada a la enfermedad
hemolítica isoinmune en el embarazo

2. Proporcionar apoyo para la alimentación a todos los RN evitando

descensos de pesos fuera de lo normal

2- Evaluación y seguimiento de la hiperbilirrubinemia

1. Identi cación de factores de riesgo (FR) de hiperbilirrubinemia para
control más estricto (Tabla 1)

2. Identi cación de necesidad de tratamiento. Iniciar fototerapia (FT)

en base a los valores de bilirrubina sérica total (BST) y presencia de
FR para neurotoxicidad (Tabla 2)

3. Usar en la evaluación de todos los RN Estimación visual de la

concentraciones de Bb total es usada para guiar la decisión de
obtención de muestras

4. Niveles de bilirrubina transcutánea, recordar que existe buena

correlación generalmente de 3 mg/dl si la BST es menor de 15. Se
fi
fi
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aconseja su medición de rutina a las 24 y 48 h

3- Tratamiento
1. Fototerapia (FT): se ha determinado que la neurotoxicidad no
ocurre hasta que las concentraciones están muy por encima de los
umbrales de ET de 2004 lo que lleva a aumentar el umbral de las
curvas actuales. Los umbrales de FT tienen en cuenta EG y FR de
neurotoxicidad. Figuras 2 y 3

2. Ictericia indirecta prolongada: aquellos RN con 7 días o más que

la BST total es mayor a 2 mg/dl siendo en la mayoría asociada a
lactancia debiendo estar atentos a otras causas

3. Monitoreo de RN en FT: medir la BST a las 12 h de iniciada la FT y

luego guiar controles posteriores por edad y FR

4. Suspensión de la FT: evaluar en base a las diferentes variables

teniendo en cuenta el riesgo de ictericia de rebote. Se de ne
como aquella que alcanza nuevamente el umbral de FT a las 72-96
h luego de la interrupción de la FT. Son FR: edad menor a 48 h de
edad al inicio de la FT, enfermedad hemolítica, menor a 38
semanas, valor altos al momento de suspender. Se sugiere
suspender la FT tener un valor de 2 mg/dl por debajo del
umbral de FT

5. Seguimiento: el control de valores al suspender la FT se basará en

el riesgo de rebote debiendo al menos pasar 12 h desde la
suspensión de la FT y de preferencia 24h
Umbral de intensi cación del tratamiento y exanguinotransfusión
(ET). El umbral de intensi cación se considera cuando está 2 mg/
dl por debajo del umbral de ET en estos casos se recomienda
hidratación i/v y FT intensiva así como ingresó a unidad neonatal.
Se debe medir nuevamente la BST a las 2 h de intensi car el
tratamiento
fi
fi
fi
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 24

22

2023 20

Total Serum Bilirubin (mg/dL)

18

Phototherapy Thresholds: No Hyperbilirubinemia Neurotoxicity Risk Factors

16

14 Gestational Age
≥ 40 Weeks
12 39 Weeks
38 Weeks
37 Weeks
10
36 Weeks
35 Weeks
8

6
0 12 24 36 48 60 72 84 96 108 120 132 144 156 168 180 192 204 216 228 240 252 264 276 288 300 312 324 336
(1d) (2d) (3d) (4d) (5d) (6d) (7d) (8d) (9d) (10d) (11d) (12d) (13d) (14d)
Age – hours
(days)

FIGURE 2
Phototherapy thresholds by gestational age and age in hours for infants with no recognized hyperbilirubinemia neurotoxicity risk factors other than gesta-
tional age. These thresholds are based on expert opinion rather than strong evidence on when the potential benefits of phototherapy exceed its potential
harms. Use total serum bilirubin concentrations; do not subtract direct-reacting or conjugated bilirubin from the total serum bilirubin. In rare cases of
severe hyperbilirubinemia in which the direct-reacting or conjugated bilirubin exceeds 50% of the TSB, consult an expert. Note that infants <24 hours old
with a TSB at or above the phototherapy threshold are likely to have a hemolytic process and should be evaluated for hemolytic disease as described in rec-
ommendation 14. Hyperbilirubinemia neurotoxicity risk factors include gestational age <38 weeks; albumin <3.0 g/dL; isoimmune hemolytic disease,
glucose-6-phosphate dehydrogenase (G6PD) deficiency, or other hemolytic conditions; sepsis; or any significant clinical instability in the previous 24 hours.
See Supplemental Fig 1.

8 FROM THE AMERICAN ACADEMY OF PEDIATRICS

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on 05 August 2022

20

18

16
Total Serum Bilirubin (mg/dL)

Phototherapy Thresholds: One or More Hyperbilirubinemia Neurotoxicity Risk Factors

14

12

Gestational Age
10
≥ 38 Weeks
37 Weeks
8 36 Weeks
35 Weeks
6

4
0 12 24 36 48 60 72 84 96 108 120 132 144 156 168 180 192 204 216 228 240 252 264 276 288 300 312 324 336
(1d) (2d) (3d) (4d) (5d) (6d) (7d) (8d) (9d) (10d) (11d) (12d) (13d) (14d)
Age – hours
(days)

FIGURE 3
Phototherapy thresholds by gestational age and age in hours for infants with any recognized hyperbilirubinemia neurotoxicity risk factors other than gesta-
tional age. These thresholds are based on expert opinion rather than strong evidence on when the potential benefits of phototherapy exceed its potential
harms. Use total serum bilirubin concentrations; do not subtract the direct-reacting or conjugated bilirubin from the total serum bilirubin. In rare cases of
severe hyperbilirubinemia in which the direct-reacting or conjugated bilirubin exceeds 50% of the TSB, consult an expert. Hyperbilirubinemia neurotoxicity
risk factors include gestational age <38 weeks; albumin <3.0 g/dL; isoimmune hemolytic disease, glucose-6-phosphate dehydrogenase (G6PD) deficiency,
or other hemolytic conditions; sepsis; or any significant clinical instability in the previous 24 hours. See Supplemental Fig 2.

the treatment threshold should also important to recognize that the ! TSB concentration no more than
consider the risk of overtreatment on amount of irradiance received by 1 mg/dL above the phototherapy
the infant and family. Whenever infants is higher directly below the treatment threshold (Fig 2;
possible, phototherapy should be light source than at the periphery.104 Supplemental Table 1 and
provided in the mother’s room or in a The irradiance levels recommended Supplemental Fig 1)
room in which the mother can remain in these guidelines refer to those ! An LED-based phototherapy de-
with the infant. measured below the center of the vice will be available in the home
light source. without delay
To optimize the effectiveness of ! TSB can be measured daily
inpatient phototherapy, hospitals KAS 11: For newborn infants who
should verify that phototherapy have already been discharged and Home phototherapy can be less costly
systems provide the intended then develop a TSB above the and disruptive to family routines and
irradiance, following the phototherapy threshold, breastfeeding and may help improve
recommendations of the treatment with a home LED-based bonding and reduce stress compared
manufacturer. Although the routine phototherapy device rather than with readmission for phototherapy.106
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28

26

Total Serum Bilirubin (mg/dL) 24

Exchange Transfusion Thresholds: No Hyperbilirubinemia Neurotoxicity Risk Factors

22

20
Gestational Age
≥ 38 Weeks
18 37 Weeks
36 Weeks
35 Weeks
16

14
0 12 24 36 48 60 72 84 96 108 120 132 144 156 168 180 192 204 216 228 240 252 264 276 288 300 312 324 336
(1d) (2d) (3d) (4d) (5d) (6d) (7d) (8d) (9d) (10d) (11d) (12d) (13d) (14d)
Age − hours
(days)

FIGURE 5
Exchange transfusion thresholds by gestational age for infants with no recognized hyperbilirubinemia neurotoxicity risk factors other than gestational age.
See Fig 4, which describes escalation of care. These thresholds are based on expert opinion rather than strong evidence on when the potential benefits of
escalation of care exceed its potential harms. The stippled lines for the first 24 hours indicate uncertainty because of the wide range of clinical circumstan-
ces and responses to intensive phototherapy. Use total serum bilirubin concentrations; do not subtract direct bilirubin from the total serum bilirubin. In
rare cases of severe hyperbilirubinemia in which the direct-reacting or conjugated bilirubin exceeds 50% of the TSB, consult an expert. Hyperbilirubinemia
neurotoxicity risk factors include albumin <3.0 g/dL; isoimmune hemolytic disease, glucose-6-phosphate dehydrogenase (G6PD) deficiency, or other hemo-
lytic conditions; sepsis; or any significant clinical instability in the previous 24 hours. See Supplemental Fig 4.

proceed according to the section escalation-of-care guidelines should deferred while continuing
“C. Monitoring Infants Receiving continue to be followed if IVIG is used. intensive phototherapy and
Phototherapy.” (Aggregate following the TSB every 2 hours
Evidence Quality Grade X, KAS 22: An urgent exchange until the TSB is below the
Recommendation) transfusion should be performed escalation of care threshold.
for infants with signs of (Aggregate Evidence Quality
KAS 21: Intravenous immune intermediate or advanced stages Grade C, Recommendation)
globulin (IVIG;240.5 to 1 g/kg) over of acute bilirubin encephalopathy
2 hours may be provided to (eg, hypertonia, arching,
Cross-matched washed packed red
infants with isoimmune hemolytic retrocollis, opisthotonos, high-
blood cells mixed with thawed adult
disease (ie, positive
22 DAT) whose pitched cry, or recurrent apnea).
fresh-frozen plasma to a hematocrit
TSB reaches or exceeds escalation (Aggregate Evidence Quality
approximating 40% is preferred for
of care threshold. The dose can be exchange transfusions.127–129 The
Grade C, Recommendation)
Total Serum Bilirubin (mg/dL)

repeated in 12 20 hours. (Aggregate additional albumin-containing fresh-

Evidence Quality Grade C, Option) Exchange KASTransfusion Thresholds:
23: An urgent 1 or More Hyperbilirubinemia Neurotoxicity Risk Factors
exchange frozen plasma that infants receive by
transfusion should be performed keeping the hematocrit close to 40%
18
The effectiveness of IVIG to prevent the for infants if the TSB is at or will augment bilirubin removal.127–129
need for an exchange transfusion is above the exchange transfusion Gestational Age
unclear. Observational studies suggest threshold. If, while preparing for The bilirubin≥ 38to Weeks
albumin ratio can
16
an association between IVIG and the exchange transfusion but be used in conjunction
37 Weeks with the TSB
necrotizing enterocolitis. A detailed before starting the exchange level in determining
36 Weeksthe need for
review of the potential benefits and transfusion, a TSB concentration 35 Weeks The bilirubin
exchange transfusion.
14
harms is provided in the technical is below the exchange transfusion to albumin ratio treatment
report. Factors that should be threshold and the infant does not threshold for exchange transfusion,
considered include
12 response to show signs of intermediate or measured as TSB (measured in mg/
0 12 24 36 48 60 72 84 96 108 120 132 144 156 168 180 192 204 216 228 240 252 264 276 288 300 312 324 336
phototherapy, TSB rate of (1d)increase,
(2d) and(3d) advanced
(4d) (5d)stages
(6d)of acute
(7d) bilirubin
(8d) (9d) dL)
(10d)divided
(11d) by(12d)
serum(13d)
albumin
(14d)
Age – hours
the challenge of providing a timely encephalopathy, then the
(days) (measured in g/dL), varies by gestational
exchange transfusion. All aspects of the exchange transfusion may be age and risk. In addition to the criteria
FIGURE 6
Exchange transfusion thresholds by gestational age for infants with any recognized hyperbilirubinemia neurotoxicity risk factors other than gestational
age. See Fig 4, which describes escalation of care. These thresholds are based on expert opinion rather than strong evidence on when the potential benefits
of escalation
PEDIATRICS of care150,
Volume exceed
numberits potential harms.2022
3, September The stippled lines for the first 24 hours indicate uncertainty because of the wide range of clinical13
circum-
stances and responses to intensive phototherapy. Use total serum bilirubin concentrations; do not subtract direct bilirubin from the total serum bilirubin.
Downloaded from http://publications.aap.org/pediatrics/article-pdf/doi/10.1542/peds.2022-058859/1346778/peds_2022058859.pdf
by guest In rare cases of severe hyperbilirubinemia in which the direct-reacting or conjugated bilirubin exceeds 50% of the TSB, consult an expert. Hyperbilirubine-
on 05 August 2022
mia neurotoxicity risk factors include albumin <3.0 g/dL; isoimmune hemolytic disease, glucose-6-phosphate dehydrogenase (G6PD) deficiency, or other he-
molytic conditions; sepsis; or any significant clinical instability in the previous 24 hours. See Supplemental Fig 5.

described above, an exchange
transfusion may be considered if the clinically significant
bilirubin to albumin ratio is:
! $8.0 if the gestational ageProf.
is
$38 weeks’ gestation and there
are no hyperbilirubinemia neuro-
toxicity risk factors, or
! $7.2 if the gestational age is
$38 weeks’ gestation and there
assessing the risk of developing measurements (Fig 7). This
approach incorporates both gestational
Febrero 2023
hyperbilirubinemia based on a age and other hyperbilirubinemia
nomogram using postnatal age in neurotoxicity risk factors into the
Adjunta de the
hours and Neonatologia H. Sobrero
bilirubin concentration decision-making process. This
coupled with the presence or approach has been studied in newborn
absence of hyperbilirubinemia risk infants in the Kaiser Permanente
factors to determine the need for Northern California hospitals.72 The
monitoring. Those follow-up timing of postdischarge follow-up
recommendations used a previous (Fig 7) should also take into
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