Predict, Prevent and Manage Severe Hyperbilirubinemia in Term and Late Preterm Newborns

Detailed Recommendations

A. Prevention of severe hyperbilirubinemia:

Before Delivery:

Q1: How can SNH be prevented among newborns with gestational age ≥35 weeks with possible isoimmune hemolytic disease?

·       All pregnant women should be tested for ABO and Rh (D) blood types. An antibody titer should be performed for mothers with suspected incompatibility.

·       If the mother was not screened for anti-erythrocyte antibodies during pregnancy, evaluation and treatment should occur shortly after delivery.

·       The American College of Obstetricians and Gynecologists recommends that pregnant women be tested to determine their ABO blood group and Rh (D) type and receive an antibody screen to determine the need for Rh (D) immunoglobulin (RhIG) and to assess the potential for isoimmune hemolytic disease of the fetus or newborn. ⁽²⁹⁾

·       If the maternal antibody screen is positive or unknown because the mother did not have prenatal antibody screening, the infant should have a direct antiglobulin test (DAT) and the infant’s blood type should be determined as soon as possible using either cord or peripheral blood. (Aggregate Evidence Quality Grade B, Recommendation). ^(29,30)

·       The DAT helps to identify infants at risk for hyperbilirubinemia attributable to hemolysis. DAT negative infants may be managed with usual care.

·       Mothers who received RhIG can have a positive antibody screen for anti-Rh (D), and RhIG can cause a positive DAT (anti Rh [D]) in the infant but generally no hemolysis. ⁽³⁶⁾

·       If the maternal blood type is Rh (D) negative, the Rh type of the infant should be determined to assess the need for administration of RhIG to the mother.

·       If the maternal blood is O positive and the maternal antibody screen is negative, it is an option to test the cord blood for the infant’s blood type and/or DAT. ⁽³⁰⁾

Following delivery:

Q2: What is the feeding counselling required for mothers to decrease risk of severe neonatal hyperbilirubinemia among newborns with gestational age ≥ 35 weeks?

·       Breast milk is the best means of nutrition for the newborn.

·       It is contraindicated to supplement infants with anything other than mother’s own milk in the absence of a specific clinical indication.

·       Jaundice in breastfed infants falls into 2 main categories, depending on its timing of onset:

_-   Suboptimal intake can lead to hyperbilirubinemia, the so called “breastfeeding jaundice,” which typically peaks on days 3 to 5 after birth and is frequently associated with excess weight loss. it is more correctly described as “suboptimal intake hyperbilirubinemia”⁽³⁷⁾ Breastfeeding fewer than 8 times per day has been associated with higher TSB concentrations. ⁽³³⁾ Low milk and low caloric intake contribute to decreased stool frequency and increased enterohepatic circulation of bilirubin.⁽³⁷⁾

_-   Hyperbilirubinemia that persists with adequate human milk intake and weight gain is referred to as “breast milk jaundice” or the “breast milk jaundice syndrome.” This cause of prolonged unconjugated hyperbilirubinemia, which can last up to 3 months, is almost always non-pathologic and not associated with direct or conjugated hyperbilirubinemia. which can last up to 3 months. ⁽³⁸⁾

·       Clinicians should promote breastfeeding support for all mothers and breast milk feeding within the first hour after birth with frequent feeding on demand (i.e., at least 8 times in 24 hours ⁽³³⁾. Evidence of adequate breastfeeding includes the following:

_-   Normal weight loss by hour of age and delivery method. Maximum weight loss by day 3 is on average 5% - 10% of the birth weight then they begin to gain 15 to 30 g daily, regaining birthweight by 10 to 14 days of age.

_-  Appropriate urine output and transitional stooling (Four to six thoroughly wet diapers in 24 hours and the passage of 3 to 4 stools per day by the fourth day).

_-   Absence of maternal discomfort, and audible swallowing as the mother’s milk volumes increase. ⁽⁴⁰⁾

·       Loss of >10% of the birth weight by day 3, suggests inadequacy of intake. ⁽⁴⁰⁾

·       Breastfed infants who are adequately hydrated should not routinely receive supplementation with commercially available infant formula. ⁽³⁹⁾

Q3: How to screen for neonatal jaundice among healthy neonates with gestational age ≥ 35 weeks in the maternity unit?

·       All infants should be visually assessed for jaundice at least every 12 hours following delivery until discharge. TSB or TcB should be measured as soon as possible for infants noted to be jaundiced.

·       Although jaundice before 24 hours of age may not have an identifiable cause, ⁽⁴¹⁾ when a cause is identified, it is most likely to be a hemolytic process. The consequences of missing early jaundice attributable to significant hemolysis justify TSB or TcB measurement. This recommendation for visual assessment DOES NOT replace the need to obtain at least 1 screening TSB or TcB.

·       The TcB or TSB should be measured between 24 and 48 hours after birth or before discharge if that occurs earlier. (Aggregate Evidence Quality Grade C, Recommendation).

·       TcB measurements are valid and reliable when used as a screening test to identify infants who require a TSB measurement.⁽⁴²⁾ This may result in a reduction in blood draws and easier follow up of neonatal jaundice ⁽⁴³⁾ There is a good correlation between TcB measures and TSB concentrations, with the TSB generally within 3 mg/dL of the TcB among newborn infants with TSB concentrations<15 mg /dl. ⁽⁴⁴⁾

·       TSB should be measured if the TcB exceeds or is within 3 mg/dL of the phototherapy treatment threshold or if the TcB is ≥15 mg/dL. (Aggregate Evidence Quality Grade C, Recommendation)

·       If more than 1 TcB or TSB measure is available, the rate of increase may be used to identify infants at higher risk of subsequent hyperbilirubinemia.⁽⁴⁵⁾ A rapid rate of increase (≥0.3 mg/dL per hour in the first 24 hours or ≥0.2 mg/dL per hour thereafter) is exceptional ⁽⁴⁶⁾ and suggests hemolysis. In this case, perform a DAT if not previously done. (Aggregate Evidence Quality Grade D, Option)

·       If available, measurement of end tidal carbon monoxide production, corrected for ambient carbon monoxide (ETCOc), is a potentially useful method for quantifying hemolysis.⁽⁴⁷⁾ Carbon monoxide is produced in equimolar amounts with bilirubin when heme is catabolized to bilirubin.

·       If appropriate follow up cannot be arranged for an infant recommended to have an outpatient follow up bilirubin measure, discharge may be delayed. (Aggregate evidence Quality Grade D)

·       Once a spontaneous decline in TcB or TSB over at least 6 hours is noted, the risk of subsequent hyperbilirubinemia is low and it is not necessary to obtain additional bilirubin measurements unless there are worrying signs.

Monitoring for hyperbilirubinemia:

Q4:  What message should parents of newborns with GA ≥ 35 weeks, receive before discharge from maternity hospital? What is the time of primary care follow up?

·       In the antenatal clinic, expecting mothers should be offered information about neonatal jaundice especially those with risk of incompatibility. Information should be provided through verbal discussion backed by a handout. Care should be taken to avoid causing unnecessary anxiety to parents or caregivers. ⁽⁴⁸⁾

·       Before discharge, all families should receive written and verbal education about neonatal jaundice. Parents should be provided written information to facilitate post-discharge care, including the date, time, and place of the follow-up appointment and, when necessary, a prescription and appointment for a follow-up TcB or TSB. Birth hospitalization information, including the last TcB or TSB and the age at which it was measured, and DAT results (if any) should be transmitted to the primary care provider who will see the infant at follow-up.  (Aggregate Evidence Quality Grade X, Strong Recommendation)

·       The timing of pediatric primary care follow-up be based on the difference between the bilirubin concentration and the phototherapy threshold at the time of bilirubin measurement to determine the interval between discharge and follow-up and the need for additional TSB or TcB measurements. This approach incorporates both gestational age and other hyperbilirubinemia neurotoxicity risk factors. ⁽⁴⁵⁾

·       If appropriate follow-up cannot be arranged for an infant recommended to have an outpatient follow-up bilirubin measure, discharge may be delayed. (Aggregate Evidence Quality Grade D, Option).

·       For infants who required phototherapy before nursery discharge, the timing of follow-up bilirubin testing after discontinuing phototherapy should be based on the risk of rebound hyperbilirubinemia. In most instances, a follow-up bilirubin concentration should be obtained at least 12 hours, and preferably 24 hours, after phototherapy is discontinued to allow for sufficient time for rebound hyperbilirubinemia. ⁽³⁵⁾

Q5: What are the risk factors for SNH and how to identify them in every newborn with gestational age ≥ 35 weeks?

·       Infants with risk factors for hyperbilirubinemia (Table-8) require closer monitoring than infants without risk factors. Determining the presence of these risk factors requires examining the infant, assessing laboratory data, and obtaining a family history of blood disorders or neonatal jaundice.

Laboratory assessment:

- Complete blood count and reticulocyte count.

-  Maternal and child blood group and Rh.

-  DAT test.

-  Further investigation as required Identification of predisposing factors.

·       Before discharge, every newborn should be assessed for the risk of developing significant hyperbilirubinemia (Table-8), and all nurseries should establish protocols for assessing this risk. This is particularly important in infants who are discharged before the age of 72 hours.

·       These risk factors should be explained to the mother before discharge so she can attend timely follow-up and understand the need for additional clinical and laboratory evaluation.

Q6:  How to identify need for treatment for babies with gestational age ≥ 35 weeks presenting with indirect neonatal hyperbilirubinemia?

·       Visual estimation of bilirubin levels:

Ø  Visual estimation is routinely used to guide decisions about obtaining TCB or TSB measures a term-born outpatients 3 or more days old, for whom treatment thresholds are high enough that distinguishing between milder degrees of jaundice is not important. However, all infants should have at least 1 TCB or TSB measured. ⁽⁶⁾

·       Estimation of bilirubin level either by skin (TcB) or TSB measured in the laboratory:

- TcB (Bili-Check) devices measure the yellowness of reflected light transmitted from the skin and use an algorithm to predict the TSB level from the objective measurement of skin color. Although TcB measurements do not directly assess bilirubin levels, they are valid and reliable when used as a screening test to identify infants who require a TSB measurement ⁽⁴²⁾ Using TcB measures in this way may result in a reduction in blood draws. ⁽⁴³⁾ Implementing universal TcB screening during the nursery stay and at subsequent public health nurse visits has been associated with a reduction in both blood draws and the likelihood of having a TSB level ≥20 mg/dL. ⁽⁴⁶⁾

Ø  There is a good correlation between TcB measures and TSB concentrations, with the TSB generally within 3 mg/dL of the TcB among newborn infants with TSB concentrations <15 mg/dL. ^(43-46)

- The magnitude and direction of the average difference between TcB measures and TSB concentrations may depend on skin melanin concentration and the instrument used to measure TcB. For example, Bili-Chek instruments may underestimate TSB at higher levels (e.g., above about 15 mg/dL) in infants with greater skin melanin concentration by an average of about 1 to 2 mg/dL. In contrast, JM instruments may overestimate the TSB infants with greater skin melanin concentration by an average of about 0.7 to 2.5 mg/dL. ⁽⁴⁹⁾ The recommendations for the use of TcB measures takes into account the degree of uncertainty related to skin melanin concentration. ^(46,49)

-  TcB is NOT recommended in case of: ⁽⁵⁰⁾

-Making a treatment decision.

-Prolonged jaundice.

-   Conjugated hyperbilirubinemia.

-   During or after phototherapy.

-Following an exchange transfusion.

·       Plot total serum bilirubin on Hour-Specific Phototherapy Nomogram and Exchange Nomogram: (www.bilitool.org or www.peditools.org/bili2022) ⁽⁶⁾

- TcB is resorted to if TSB is not available.

- The early onset of jaundice (detectable < 24 hours of age) is a risk factor for severe hyperbilirubinemia requiring early treatment. ⁽⁶⁾

- Babies who develop jaundice in the first 24 hours of life, usually due to hemolysis, are at risk of developing SNH and acute and chronic bilirubin encephalopathy. ⁽⁴¹⁾

-  The risk of jaundice in the first 24 hours of life is higher in babies 35 to 36 weeks' gestation. ⁽⁴¹⁾

·       In Egypt where babies are discharged early (before 12 hours from delivery), assessment of jaundice should be performed by nurses or health workers during postpartum home visits at Days 2,4,7 of life or in the Maternal Child health center (MCHC) during the administration of first dose of Hepatitis B vaccine on day 1 of life.

B- Assessment:

Q7:  What should be included in the formal assessment of babies with gestational age ≥35 weeks presenting with indirect neonatal hyperbilirubinemia?

·       History and family history (risk factors for significant hyperbilirubinemia and neurotoxicity risk factors (Table-9).

·       Clinical examination (Modified BIND SCORE). ⁽⁵¹⁾

·       Laboratory assessment:

-Complete blood count and reticulocyte count.

-Maternal and child blood group and Rh.

-DAT test.

·       Further investigation as required.

Q8: When and how to assess for ABE among newborns with gestational age ≥ 35 weeks presenting with indirect neonatal hyperbilirubinemia?

·       ABE may occur in the first days of life and causes a temporary alteration in neurologic state. ^(52-55)

·       The risk and severity of ABE increase with rising bilirubin level.

·       Neurotoxicity risk factors include: ⁽⁶⁾ (Table-9)

- Isoimmune hemolytic disease, G6PD Deficiency, or other hemolytic conditions.

- Sepsis.

-  Significant clinical instability in the past 24h.

- Preterm < 38 wks.

- Sepsis.

- Clinical instability and Albumin Level <3.0 Mg/dl.

·       Clinical presentation of ABE is subtle and non-specific initially and manifests with poor feeding. This progresses to high pitched cry, high temperature and lethargy. Subsequently disturbance in neurobehavioral state, hypertonia, retrocollis and opisthotonus may occur. ⁽⁵³⁾

·       The modified bilirubin-induced neurologic dysfunction scale (M-BIND) ⁽⁵¹⁾ is a 12-point score, incorporating eye abnormalities with the original BIND score ⁽⁵³⁾ to assess bilirubin induced neurological damage in an objective manner (Table-10). It facilitates diagnosis of ABE as well as monitors the neurological progress in neonates with severe hyperbilirubinemia.

·       Any infant with evidence of acute bilirubin encephalopathy should have an immediate exchange transfusion. ⁽⁵⁶⁾

·       Severe neonatal hyperbilirubinemia is a medical emergency that should be handled promptly to prevent ABE.  Severely jaundiced babies should NOT be allowed to wait.

Q9: How to suspect and evaluate elevated conjugated bilirubin concentration, for newborns with gestational age ≥ 35 weeks presenting with neonatal hyperbilirubinemia?

·       For breastfed infants who are still jaundiced at 3-4 weeks of age and 2 weeks for formula -fed infants, the total and conjugated bilirubin concentration should be measured to identify possible pathologic cholestasis. ⁽⁵⁷⁾

·       Infants who have an elevation of direct reacting or conjugated bilirubin should have a urine analysis and culture. Additional laboratory evaluation for sepsis and other possible causes should be performed if indicated by history and physical examination. ⁽⁵⁸⁾

·       Infection:

-C-reactive protein (may be false negative near onset of infection).

-Blood culture–unwell baby of any age.

-Urine–microscopy and culture.

-Investigate for congenital infections if there are other indications, e.g. clinical signs of suggestive history, severe jaundice, elevated conjugated bilirubin, thrombocytopenia (Toxoplasmosis, Rubella, Cytomegalovirus (CMV) Herpes simplex virus, Syphilis).

·       Inborn errors of metabolism: if baby looks unwell and the jaundice is severe, e.g. galactosemia, tyrosinemia.

·       Liver disease:

-Albumin (decreased levels result in poor bilirubin binding capacity and risk of bilirubin toxicity).

-Liver function tests (LFT) as liver enzymes may be increased, e.g. in congenital infections, inborn errors of metabolism.

- If the direct reacting or conjugated bilirubin is elevated, additional evaluation for the causes of cholestasis is recommended.

C- Treatment of neonatal hyperbilirubinemia:

Phototherapy:

Q10: In babies ≥ 35 weeks  gestation with neonatal hyperbilirubinemia receiving phototherapy:

Q10-A: When should phototherapy be prescribed? ^{(4, 5, 59)}

·       In using the guidelines for phototherapy and exchange transfusion (Figures-4, 5, 9 & 10), the direct reacting (or conjugated) bilirubin level should not be subtracted from the total bilirubin.

·       Measurement of direct bilirubin is not accurate and there is a large variability between labs. There is no harm to treat according to total bilirubin if the direct portion is < 50% of total. In unusual situations in which the direct bilirubin level is 50% or more of the total bilirubin, there are no good data to provide guidance for therapy, and consultation with an expert in the field is recommended. ⁽⁶⁾

·       All nurseries and services treating infants should have the necessary equipment to provide intensive phototherapy (appendix).

·       Intensive phototherapy means an irradiance >30 µW/cm² per nm at a wavelength around 475 nm.

·       Recommendations for phototherapy treatment are given in Table-14 & Figures-4 & 5.

·       Do not use phototherapy in babies unless indicated.

·       The amount of irradiance received by infants is higher directly below the light source than at the periphery.

·       If the TSB does not fall or continues to rise despite intensive phototherapy, it is likely that hemolysis is occurring. Examine baby daily for signs of ABE.

Q10-B: What is the breast-feeding recommendation for babies under phototherapy?

·       Factors affecting phototherapy, side effects, precautions, dose and equipment (phototherapy appendix-).

·       In breastfed infants who require phototherapy, it is recommended that, breastfeeding should be continued unless there is a clear contraindication.

·       Feeding should be maintained during phototherapy to promote bilirubin clearance and avoid dehydration. Interrupting phototherapy for breastfeeding does not impact the overall effectiveness of phototherapy if it is otherwise appropriately used. ⁽⁶⁰⁾ These interruptions should be minimized if the bilirubin concentration is approaching the need to escalate care.

·       If a breastfed infant’s intake is inadequate as proven by weight loss > 10% of the birth weight or the infant is dehydrated while on phototherapy, supplementation with expressed breast milk or formula is appropriate.

·       Poor feeding leads to reduced caloric intake and dehydration resulting in elevated TSB.

·       Intravenous fluids are NOT necessary for term or near-term infants receiving phototherapy unless there is evidence of dehydration not corrected by adequate oral intake. ⁽⁶⁾

Q10-C: How should babies under phototherapy be monitored ?

·       For infants receiving intensive phototherapy: ⁽⁴⁾

- If TSB ≥ 25 mg/dL, repeat TSB within 2–3 h.

-  If TSB 20–25 mg/dL, repeat within 3–4 h.

- If TSB <20 mg/dL repeat in 4–6 h. If TSB continues to fall, repeat in 8–12 h.

·       For infant requiring phototherapy measure the hemoglobin concentration, hematocrit, or complete blood count to assess the presence of anemia and to provide a baseline in case subsequent anemia develops. ⁽⁶⁾

·       Evaluate the underlying cause or causes of hyperbilirubinemia in infants who require phototherapy by obtaining a DAT:

-  In infants whose mother had a positive antibody screen.

-Or whose mother is blood group O, regardless of Rh status.

-Or whose mother is Rh (D) negative.

·       G6PD activity should be measured in: ⁽⁶⁾

-Any infant with jaundice of unknown cause whose TSB increases despite intensive phototherapy.

-Whose TSB increases suddenly.

-Or increases after an initial decline or who requires escalation of care.

Q10-D: When should phototherapy be discontinued?

·       The decision to discontinue phototherapy is based on balancing the desire to minimize exposure to phototherapy and separation of mothers and infants against the desire to avoid a rebound in TSB following phototherapy.

·       Discontinuing phototherapy is an option when the TSB has decreased by at least 2 mg/dL below the hour-specific threshold at the initiation of phototherapy. A longer period of phototherapy is an option if there are risk factors for rebound hyperbilirubinemia.

·       Rebound hyperbilirubinemia is defined as a TSB concentration that reaches the phototherapy threshold for the infant’s age within 72 to 96 hours of discontinuing phototherapy. Risk factors for rebound hyperbilirubinemia include ⁽³⁵⁾

- Gestational age < 38 weeks.

- Age <48 hours at the start of phototherapy.

-  Infants who had a positive DAT.

- Hemolytic disease.

-  Higher TSB at the time of phototherapy discontinuation in relationship to the phototherapy threshold.

Q 10-E: When to monitor for rebound hyperbilirubinemia following discontinuation of phototherapy?

·       Repeat bilirubin measurement after phototherapy is based on the risk of rebound hyperbilirubinemia.

·       Risk factors are:

-  Infants who received phototherapy before 48 hours.

-  Infants who had a positive DAT.

-  Infants who had known or suspected hemolytic disease.

- Infants with risk for hyperbilirubinemia and hyperbilirubinemia neurotoxicity risk factors. (Tables-9)

·       In the presence of one of the above risk factors TSB should be measured for rebound at: 6-12 hours after phototherapy discontinuation and the day after

·       All other infants should be followed up for TSB after 24 hours.

·       It is an option to measure TcB instead of TSB if it has been at least 24 hours since phototherapy was stopped. ⁽⁶¹⁾

Q11: Escalation of care: In babies ≥ 35 weeks gestation with neonatal hyperbilirubinemia  requiring escalation of care,

Escalation of care refers to the intensive care that some infants with elevated or rapidly increasing bilirubin concentrations need to prevent the need for an exchange transfusion and possibly prevent kernicterus. ⁽⁶⁾

Q11-A: What is the threshold for escalation of care?

·       The escalation-of-care threshold is 2 mg/dL below the exchange transfusion threshold.

·       The direct-reacting or conjugated bilirubin value should not be subtracted from the total bilirubin value when determining management.

Q11-B: What is the approach for escalation of care?  (Figure-6) ⁽⁶⁾

·       Initiating escalation of care is a medical emergency. The escalation-of care period starts from the time the infant’s TSB result first mandates starting escalation of care and ends when the TSB is below the escalation of care threshold.

·       These infants are optimally managed in a neonatal intensive care unit (NICU). If the infant is in an institution that lacks facilities for an emergent exchange transfusion, a neonatologist should be consulted about urgent transfer to a NICU that can perform an exchange transfusion.

·       The infant should be admitted directly to the NICU rather than through the emergency department to avoid delaying care.

·       For infants requiring escalation of care, blood should be sent STAT .for total and direct reacting serum bilirubin, a complete blood count, serum albumin, serum chemistries and type and cross match.

·       Intensive phototherapy and intravenous hydration should be initiated immediately.

·       TSB should be measured at least every 2 hours during the escalation period. Once the TSB is lower than the escalation of care threshold, continue phototherapy according the bilirubin level.

·       Intravenous immune globulin (IVIG: 0.5 to 1 g/kg) over 2 hours may be provided to infants with isoimmune hemolytic disease (i.e., positive DAT) whose TSB reaches or exceeds escalation of care threshold. The dose can be repeated in 12 hours.

Exchange Transfusion:

Q12: In babies ≥ 35 weeks’ gestation with neonatal hyperbilirubinemia, when is exchange transfusion indicated?

·       Recommendations for exchange transfusion are given in Figures-7 & 8.

·       The aim of an exchange transfusion is to rapidly reduce the TSB by removing small aliquots of blood from the baby and replacing it with donor blood components. ⁽⁶²⁾

·       Recommendations for exchange transfusion are given in Figures-7 & 8.

·       Indications:

-Infants with signs of intermediate or advanced stages of acute bilirubin encephalopathy.

-If the TSB is at or above the exchange transfusion threshold.

-TSB continues to rise despite intense phototherapy.

-If the bilirubin albumin ratio exceeds the threshold for GA and risk factors.

·       Post exchange transfusion:

-Continue intensive phototherapy.

-Measure TSB within 2 hours of exchange transfusion.

·       What the indications of IVIG: ⁽⁶⁾

-Intravenous immune globulin (IVIG; 0.5 to 1 g/kg) over 2 hours may be provided to infants with isoimmune hemolytic disease (i.e., positive DAT) whose TSB reaches or exceeds escalation of care threshold. The dose can be repeated in 12 hour.

-It acts by blocking Fc receptors on macrophages thereby reducing the breakdown of antibody-coated RBCs and also enhancing the clearance of maternal antibodies. ⁽⁶³⁾

Drugs (adjuvant therapy):

Q13: Which drugs can increase the risk of bilirubin neurotoxicity, in newborns with gestational age ≥ 35 weeks suffering from significant hyperbilirubinemia?

·       Use the following medications with caution in a baby with hyper-bilirubinemia as they may cause bilirubin to be displaced from albumin binding sites and increase the risk of ABE:

-Synthetic Vitamin K (medadione). ⁽⁶⁴⁾

-Digoxin. ⁽⁶⁵⁾

-Diazepam. ⁽⁶⁵⁾

-Salicylates. ⁽⁶⁶⁾

-Diuretics e.g. furosemide and hydrochlorothiazide. ⁽⁶⁷⁾

-Sulfamethoxazole such as in trimethoprim/sulfamethoxazole (cotrimoxazole). ⁽⁶⁷⁾

-Ceftriaxone. ⁽⁶⁸⁾

-Ibuprofen. ⁽⁶⁹⁾

Q14: Which drugs are NOT recommended for the treatment of neonatal hyperbilirubinemia in newborns with gestational age ≥35 weeks?

·       There is NO role for the use of the following medications to treat neonatal hyperbilirubinemia (Phenobarbitone, Agar, Clofibrate, albumin, charcoal, and metalloporphyrins). ⁽²³⁾

D- Follow up after discharge:

Q15: How to follow up the baby≥ 35 weeks gestation with severe hyperbilirubinemia after discharge from the NICU?

·       Infants requiring exchange transfusion or those who exhibit neurological abnormalities should be referred to a neurological follow-up programs and must have a hearing screen. Their hearing screen should include brainstem auditory evoked potentials. ⁽⁷⁰⁾

·       Acute bilirubin encephalopathy may progress to athetoid cerebral palsy, deafness and blindness due to paralysis of ocular muscles so neurodevelopmental follow up programs are essential.

·       Hearing assessment:

-Babies should have a hearing screen according to local protocols usually after completion of phototherapy.

-Elevated ABR thresholds may indicate SNHL due to hyperbilirubinemia and require further investigations and treatment.

·       Infants with isoimmunization are at risk for severe anemia after several weeks; it is suggested that a repeat hemoglobin measurement be performed at two weeks of age if it was low at discharge and at four weeks if it was normal. ⁽⁷¹⁾

·       Antibodies persist for weeks, with continued hemolysis and can cause anemia as late as age 6 months (especially in infants who had received intrauterine transfusions).