Practitioners in North America are advised to follow the 2004 AAP guidelines.

Although the 2004 AAP guidelines do not provide guidance for treatment of jaundice
in the smaller and more premature/immature infants, a group of US experts recently
published their suggestions for management of jaundice in preterm infants younger
than 35 weeks' gestation.[36]

Clinicians in different ethnic or geographic regions should consider tailoring these

guidelines as pertinent to their own populations and must consider factors that are
unique to their medical practice settings. Such factors may include racial
characteristics, prevalence of congenital hemolytic disorders, prevalence of genetic
variants, and environmental concerns. Such adaptation of guidelines should also
take into consideration how healthcare delivery systems are organized, as this is
likely affect both in-hospital delivery of care as well as follow-up. At present, the
wisest course of action may be to apply local guidelines, assuming that these have
been successful in the prevention of kernicterus..

With this background and the clear understanding that this is meant only as an
example, the image below shows the chart currently in use in all pediatric
departments in Norway. These guidelines are the result of a 2006 consensus in the
Neonatal Subgroup of the Norwegian Pediatric Society. The similarities between the
Norwegian chart and the 2004 AAP guidelines are apparent.
 Guidelines for management of
neonatal jaundice currently in use in all pediatric departments in Norway. The
guidelines were based on previously used charts and were created through a
consensus process in the Neonatal Subgroup of the Norwegian Pediatric Society.
These guidelines were adopted as national at the fall meeting of the Norwegian
Pediatric Society. The reverse side of the chart contains explanatory notes to help
the user implement the guidelines. A separate information leaflet for parents was
also created.

The Norwegian chart suggests intervention limits for premature/immature infants. For
infants of less than 1000 gram birthweight, these guidelines propose starting
phototherapy at 100 µmol/L (6 mg/dL) at age 24 hours, increasing gradually to 150
µmol/L (8.8 mg/dL) at age 4 days, and remaining steady thereafter at that level. This
compares with a range of 85 µmol/L (5 mg/dL) to 171 µmol/L (10 mg/dL) used in a
Neonatal Research Network (NRN) phototherapy trial in infants of less than 1000
gram birthweight. The intervention level depended on postnatal age and whether the
infant was allocated to conservative or aggressive phototherapy. [37]

In a post hoc analysis of the NRN data, which compared infants who had not
received any phototherapy with those who had received such treatment, the
subgroup of infants with birthweights of 501-750 grams who had not received any
phototherapy had a significantly higher rate of mental developmental index of less
than 50.[38] However, it should be noted that in the original trial analysis, mortality in
the aggressive phototherapy group at 501- to 750-g birthweight was 5 percentage
points higher than in the conservative group, which, although not significant with the
statistical approach chosen for analysis, appeared to offset the possible
developmental gain in survivors.[37] Recently these data were reanalyzed using
Bayesian statistics[39] and showed that aggressive phototherapy significantly
increased the risk of death in the sickest (being on mechanical ventilation at 24 h)
and smallest infants (≤750 g birthweight), while at the same time reducing
impairment/severe impairment.

Key points in the practical execution of phototherapy include maximizing energy

delivery and the available surface area. Also consider the following:

 The infant should be naked except for diapers (use these only if deemed
absolutely necessary and cut them to minimum workable size), and the eyes
should be covered to reduce risk of retinal damage.
 Check the distance between the infant's skin and the light source. With
fluorescent lamps, the distance should be no greater than 50 cm (20 in). This
distance may be reduced down to 10-20 cm (4-8 in) if temperature
homeostasis is monitored to reduce the risk of overheating. Note that this
does not apply to quartz lamps.
 Cover the inside of the bassinet with reflecting material; white linen works
well. Hang a white curtain around the phototherapy unit and bassinet. These
simple expedients can multiply energy delivery by several fold.
 When using spotlights, ensure that the infant is placed at the center of the
circle of light, since photoenergy drops off towards the circle's perimeter.
Observe the infant closely to ensure that the infant doesn't move away from
the high-energy area. Spotlights are probably more appropriate for small
premature infants than for larger near-term infants.
 Older data suggested that phototherapy was associated with increased
insensible water loss; therefore, many clinicians have routinely added a
certain percentage to the infant's estimated basic fluid requirements. Newer
data suggest that if temperature homeostasis is maintained, fluid loss is not
 significantly increased by phototherapy. At the author's institution, routine fluid
supplementation for infants under phototherapy has not been used for more
than a decade and is not recommended in national guidelines. Rather, the
infant is monitored for weight loss, urine output, and urine specific gravity.
Fluid intake is adjusted accordingly. In infants who are orally fed, the preferred
fluid is milk because it serves as a vehicle to transport bilirubin out of the gut.
 Timing of follow-up serum bilirubin testing must be individualized. In infants
admitted with extreme serum bilirubin values (>500 µmol/L or 30 mg/dL),
monitoring should occur every hour or every other hour. Reductions in serum
bilirubin values of 85 µmol/L/h (5 mg/dL/h) have been documented under such
circumstances. In infants with more moderate elevations of serum bilirubin,
monitoring every 6-12 hours is probably adequate.
 Expectations regarding efficacy of phototherapy must be tailored to the
circumstances. In infants in whom serum bilirubin concentrations are still
rising, a significant reduction of the rate of increase may be satisfactory. In
infants in whom serum bilirubin concentrations are close to their peak,
phototherapy should result in measurable reductions in serum bilirubin levels
within a few hours. In general, the higher the starting serum bilirubin
concentration, the more dramatic the initial rate of decline.
 Discontinuation of phototherapy is a matter of judgment, and individual
circumstances must be taken into consideration. In practice, phototherapy is
discontinued when serum bilirubin levels fall 25-50 µmol/L (1.5-3 mg/dL)
below the level that triggered the initiation of phototherapy. Serum bilirubin
levels may rebound after treatment has been discontinued, and follow-up
tests should be obtained within 6-12 hours after discontinuation.
 Indications for prophylactic phototherapy are debatable. Phototherapy
probably serves no purpose in an infant who is not clinically jaundiced. In
general, the lower the serum bilirubin level, the less efficient the phototherapy.
It seems more rational to apply truly effective phototherapy once serum (and
skin) bilirubin has reached levels at which photons may do some good.
 Wherever phototherapy is offered as a therapeutic modality, a device for
measuring the irradiance delivered by the equipment used should be readily
at hand. This assists in configuring the phototherapy set-up to deliver optimal
efficiency. Some recommend this routinely, every time phototherapy is
 initiated, and use this as a tool to focus staff attention on maximizing energy
delivery.

Generally, phototherapy is very safe and may have no serious long-term effects in
neonates; however, the following adverse effects and complications have been
noted:

 Insensible water loss may occur, but data suggest that this issue is not as
important as previously believed. Rather than instituting blanket increases of
fluid supplements to all infants receiving phototherapy, the author
recommends fluid supplementation tailored to the infant's individual needs, as
measured through evaluation of weight curves, urine output, urine specific
gravity, and fecal water loss.
 As noted above, a reanalysis of the NRN trial of ”aggressive” versus
”conservative” phototherapy in premature infants of less than 1000 g
birthweight showed that mortality was increased in the subgroup of sick 501-
to 750-g birthweight infants receiving aggressive' phototherapy. [39] In a recent
recommendation for treatment of hyperbilirubinemia in premature infants
younger than 35 weeks’ gestation, the authors propose that initial irradiance
should be reduced in the most vulnerable infants. [36] However, as pointed out
in an editorial to this paper, extant data seem to be more compatible with the
interpretation that duration of phototherapy is more dangerous than irradiance
levels. [40] Thus, it may be argued that phototherapy should be short and
efficient rather than less efficient and of longer duration. This question is still
open to interpretation and discussion.
 Phototherapy may be associated with loose stools. Increased fecal water loss
may create a need for fluid supplementation.
 Retinal damage has been observed in some animal models during intense
phototherapy. In an NICU environment, infants exposed to higher levels of
ambient light were found to have an increased risk of retinopathy. Therefore,
covering the eyes of infants undergoing phototherapy with eye patches is
routine. Care must be taken lest the patches slip and leave the eyes
uncovered or occlude one or both nares.
  The combination of hyperbilirubinemia and phototherapy can produce DNA-
strand breakage and other effects on cellular genetic material. In vitro and
animal data have not demonstrated any implication for treatment of human
neonates. However, because most hospitals use (cut-down) diapers during
phototherapy, the issue of gonad shielding may be moot.
 Skin blood flow is increased during phototherapy, but this effect is less
pronounced in modern servocontrolled incubators. However, redistribution of
blood flow may occur in small premature infants. An increased incidence of
patent ductus arteriosus (PDA) has been reported in these circumstances.
The appropriate treatment of PDA has been reviewed. [41]

 Hypocalcemia appears to be more common in premature infants under

phototherapy lights. This has been suggested to be mediated by altered
melatonin metabolism. Concentrations of certain amino acids in total
parenteral nutrition solutions subjected to phototherapy may deteriorate.
Shield total parenteral nutrition solutions from light as much as possible.
 Regular maintenance of the equipment is required because accidents have
been reported, including burns resulting from a failure to replace UV filters.

Intravenous immune globulin

In recent years, IVIG has been used for numerous immunologically mediated
conditions. In the presence of Rh, ABO, or other blood group incompatibilities that
cause significant neonatal jaundice, IVIG has been shown to significantly reduce the
need for exchange transfusions. However, it must be recognized that some studies
have failed to show efficacy. The reasons for this discrepancy have not been
explained. One can speculate that differences in the origin and characteristics of the
IVIG preparation could play a role. If one particular IVIG preparation appears not to
work, it may be worthwhile to try IVIG from a different source/manufacturer.

The 2004 AAP guidelines suggest a dose range for IVIG of 500-1000 mg/kg.[35]

The author routinely uses 500 mg/kg infused intravenously over a period of 2 hours
for Rh or ABO incompatibility when the total serum bilirubin levels approach or
surpass the exchange transfusions limits. The author has, on occasion, repeated the
dose 2-3 times. In most cases, when this is combined with intensive phototherapy,
avoiding exchange transfusion is possible. In the authors' institution, with about 750
NICU admissions per year, the use of exchange transfusions has decreased to 0-2
per year following the implementation of IVIG therapy for Rh and ABO
isoimmunization.[33] The author does not use IVIG in the presence of hydrops.
Anecdotally, IVIG appears less likely to be successful when the infant is anemic (Hb
< 10 g/dL).

Exchange transfusion

Exchange transfusion is indicated for avoiding bilirubin neurotoxicity when other

therapeutic modalities have failed or are not sufficient. In addition, the procedure
may be indicated in infants with erythroblastosis who present with severe anemia,
hydrops, or both, even in the absence of high serum bilirubin levels.

Exchange transfusion was once a common procedure. A significant proportion was

performed in infants with Rh isoimmunization. Immunotherapy in Rh-negative
women at risk for sensitization has significantly reduced the incidence of severe Rh
erythroblastosis. Therefore, the number of infants requiring exchange transfusion is
now much smaller, and even large NICUs may perform only a few procedures per
year. ABO incompatibility has become the most frequent cause of hemolytic disease
in industrialized countries.

Early exchange transfusion has usually been performed because of anemia (cord
hemoglobin < 11 g/dL), elevated cord bilirubin level (>70 µmol/L or 4.5 mg/dL), or
both. A rapid rate of increase in the serum bilirubin level (>15-20 µmol/L /h or 1
mg/dL/h) was an indication for exchange transfusion, as was a more moderate rate
of increase (>8-10 µmol/L/h or 0.5 mg/dL/h) in the presence of moderate anemia
(11-13 g/dL).

The serum bilirubin level that triggered an exchange transfusion in infants with
hemolytic jaundice was 350 µmol/L (20 mg/dL) or a rate of increase that predicted
this level or higher. Strict adherence to the level of 20 mg/dL has been jocularly
referred to as vigintiphobia (fear of 20).
Currently, most experts encourage an individualized approach, recognizing that
exchange transfusion is not a risk-free procedure, that effective phototherapy
converts 15-25% of bilirubin to nontoxic isomers, and that transfusion of a small
volume of packed red cells may correct anemia. Administration of IVIG (500 mg/kg)
has been shown to reduce red cell destruction and to limit the rate of increase of
serum bilirubin levels in infants with Rh and ABO isoimmunization (see above).

Current AAP guidelines distinguish between 3 risk categories: low, intermediate, and
high.[35] These correspond to 3 levels of suggested intervention, which increase from
birth and plateau at age 4 days. Naturally, intervention levels associated with
exchange transfusion are higher than those for phototherapy. Intensive phototherapy
is strongly recommended in preparation for an exchange transfusion. In fact,
intensive phototherapy should be performed on an emergency basis in any infant
admitted for pronounced jaundice; do not await laboratory test results in these cases.
Phototherapy has minimal side effects in this scenario, whereas the waiting period
for laboratory test results and blood for exchange can take hours and could
constitute the difference between intact survival and survival with kernicterus. If
phototherapy does not significantly lower serum bilirubin levels, exchange
transfusion should be performed.