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CLIPP 8 - neonatal jaundice
#ir #peds

8. 6-day-old with jaundice - Meghan

February 1, 2017 1:39:29 PM EST



Jaundice is the physical finding associated with hyperbilirubinemia and may result from both unconjugated and conjugated forms of bilirubin.

Unconjugated hyperbilirubinemia can have serious consequences.



Kernicterus is the pathological term used to describe staining of the basal ganglia and cranial nerve nuclei by bilirubin. Kernicterus also describes the clinical condition that results from the toxic effects of high levels of unconjugated bilirubin.


Severely affected newborn infants may:

lose the suck reflex become lethargic develop hyperirritability and seizures, and ultimately die

Infants who survive may develop:

opisthotonus (abnormal posturing that involves rigidity and severe arching of the back, with the head thrown backward) rigidity oculomotor paralysis tremors

Cho Sooyoung - 1/22

hearing loss, and ataxia

Screening and Treatment

In the past, kernicterus among full-term newborn infants primarily resulted from the hemolysis and subsequent unconjugated hyperbilirubinemia that was caused by Rh incompatibility (erythroblastosis fetalis). These infants typically were severely anemic, in shock and acidotic, and had total bilirubin levels well above 25 mg/dL (428 μmol/L). Screening for Rh incompatibility and the use of anti-Rh immunoglobulin (RhoGAM®) have markedly reduced Rh-induced hemolysis and the incidence of kernicterus. In addition, treatment of unconjugated hyperbilirubinemia with phototherapy has had an important impact on management of hyperbilirubinemia.

See the associated reference ranges in conventional and SI units. (

Newborn Bilirubin Physiology

Most (~75%) of the bilirubin produced in the healthy newborn comes from physiological breakdown of red blood cells.


The hemoglobin released from the red cells is converted to unconjugated bilirubin that is insoluble in aqueous solutions and binds to albumin in the blood stream. In the liver the bilirubin is extracted by the hepatocytes where it binds to cytosolic proteins and is then conjugated with glucuronide by uridine diphosphate glucuronyl transferase (UDPGT, also known as glucuronosyl transferase). The conjugated bilirubin is water-soluble and is excreted into the bile and then into the intestine.

In adults, most of the bile is metabolized by the intestinal flora to urobilin and excreted in the stool. The newborn infant, however, lacks the gastrointestinal flora to metabolize bile, which allows the β-glucuronidase present in the meconium to hydrolyze the conjugated bilirubin back to its unconjugated form.

The unconjugated bilirubin is then reabsorbed into the blood stream where it binds to albumin. Newborns absorb significant quantities of bilirubin through this process, known as enterohepatic circulation.

Etiologies of Jaundice


Physiologic Jaundice

This is defined as a total bilirubin level ≤ 15 mg/dL (≤ 257 μmol/L) in full-term infants who are otherwise healthy and have no other demonstrable cause for elevated bilirubin.

Almost all newborn infants have hyperbilirubinemia, but it is benign and self- limited.

Physiologic jaundice in a full-term baby is usually first noticed on the second or third day of life, with the bilirubin level reaching its peak at day three or four of life.

Numerous factors promote the increased enterohepatic circulation that results in physiologic jaundice:

Increased bilirubin production (from the breakdown of the short-lived fetal red cells) Relative deficiency of hepatocyte proteins and UDPGT Lack of intestinal flora to metabolize bile High levels of β-glucuronidase in meconium Minimal oral (enteral) intake in the first 2-4 days of life, resulting in slow excretion of meconium (especially common with breastfed infants).


Jaundice Associated with Breastfeeding

Some clinicians divide this into two separate entities--breastfeeding jaundice and breast-milk jaundice. There is probably overlap, where a combination of both of these problems occurs simultaneously.

1. Breastfeeding jaundice

Happens early in the first week of life and occurs when the milk supply is relatively or absolutely low, resulting in limited enteral intake. This may be referred to as a "lack-of-breast milk jaundice" or "breastfeeding- associated jaundice." The low intake results in decreased gastrointestinal motility that in turn promotes retention of meconium. The β-glucuronidase in meconium deconjugates bilirubin and the unconjugated bilirubin is reabsorbed via the enterohepatic circulation, causing an elevation of serum levels. Breast milk production typically increases greatly once "let-down" occurs. Occasionally, persistently low volume of breast milk can cause the neonate to become dehydrated and malnourished. Breastfeeding jaundice is often difficult to distinguish from physiologic jaundice.

2. Breast-milk jaundice

Begins in the first 4 to 7 days of life but may not peak until about 10 to 14 days. Not the result of low breast milk volume. While the cause is not completely understood, one explanation is that β- glucuronidase present in breast milk deconjugates bilirubin in the intestinal tract; the unconjugated bilirubin is then reabsorbed via enterohepatic circulation. Breast-milk jaundice can persist for up to 12 weeks, but total bilirubin concentration rarely, if ever, reaches concerning levels. The time course of breast-milk jaundice is quite different from that of physiologic jaundice.


In pathological processes hemolysis causes breakdown of red blood cells (RBCs). The hemoglobin released is metabolized to unconjugated bilirubin, which results in jaundice.

Antibody-positive hemolysis is labeled "direct Coombs" or "direct antibody test (DAT)" positive. The most common forms of antibody-positive hemolysis include:


Rh incompatibility (mother is Rh-negative and baby is Rh-positive) ABO incompatibility (mother is type O and baby is type A or B) Incompatibilities with minor blood group antigens (much less common)

Antibody-negative hemolysis occurs in infants who have red blood cell membrane defects (e.g., spherocytosis) or red blood cell enzyme defects (glucose-6- phosphate dehydrogenase or pyruvate kinase deficiency).

Other Causes

Non-hemolytic red cell breakdown causes increased bilirubin production and development of jaundice and occurs in a variety of conditions, including:

Extensive bruising from birth trauma Large cephalohematoma or other hemorrhage (e.g., intracranial) Polycythemia Swallowed blood (large amounts) during delivery.

Metabolic errors

Crigler-Najjar syndrome: hyperbilirubinemia results from decreased bilirubin clearance caused by deficient or completely absent UDPGT. Galactosemia and hypothyroidism also have jaundice as prominent clinical findings.

These congenital disorders are detected by neonatal screening.


Hyperbilirubinemia is more common in Asian newborn infants than in Caucasian infants and is less common in black infants.

These additional factors can also contribute to hyperbilirubinemia:

Prematurity Bowel obstruction Birth at high altitude

See the associated reference ranges in conventional and SI units. (


Typical Breastfeeding Pattern

A successfully breastfed baby typically nurses 8-12 times in 24 hours.

Feedings may initially last up to 60 minutes but gradually become shorter in duration, ~10-15 minutes at each breast. (Increasingly frequent or consistently lengthy feeding sessions may indicate a problem, especially if the infant is not gaining weight.)

Benefits of Breastfeeding

For Infants

Maternal-infant bonding Protection against some infections (e.g. otitis media, respiratory infections, diarrhea) Reduced rates of Sudden Infant Death Syndrome Reduced rates of some allergic reactions

For Mothers

Decreased postpartum bleeding and more rapid uterine involution Lactational amenorrhea and delayed resumption of ovulation with increased child spacing Earlier return to pre-pregnant weight (compared with women who formula-feed) Improved bone remineralization postpartum with reduction in hip fractures in the postmenopausal period Decreased cost, relative to formula Ready availability without preparation time

Common Breastfeeding Problems

Enlarged, tender breasts-commonly caused by engorgement, mastitis, or plugged ducts (galactocele) Improper latch, suckle Prolonged feedings Infants fall asleep before they finish feeding Maternal inexperience/anxiety: This often represents an expectation that breastfeeding is "natural" and should therefore be intuitive. Many obstetrical services in the U.S. routinely provide lactation counseling and education by highly trained certified lactation consultants and lactation educators. They provide practical instruction on topics such as proper latch and suckling, holding infant(s) during feeding, proper use of breast pumps, and breast care. Breast pumps are often available for rental from hospitals.


Breast Milk Nutrients

Breast milk has the perfect balance of carbohydrates, fats (lipids), and proteins for human infants.

In addition, it provides antibodies, oligosaccharides, lactoferrin, lysozyme, growth factors, bifidobacteria, and other non-nutritive substances that protect against infection and promote growth.

These non-nutritive substances are especially concentrated in colostrum, the yellowish fluid produced in first few days postpartum. Mature human milk gradually replaces colostrum as nursing progresses.

If a mother cannot breastfeed, or chooses to not do so, she may feed her infant with a formula made from cow's milk or soy protein isolate, with assurance that the major nutrients will be provided by either.

Infants younger than 12 months should not be fed unmodified cow's milk.


Both human milk and standard infant formulas contain lactose as the major carbohydrate. Lactose intolerance is uncommon in the first year of life.


Approximately 50% of calories in human milk come from lipids. The lipid concentration in breast milk increases as the nursing episode proceeds; therefore, it is important that an infant empty the breast before going to the next breast.


Human milk contains a combination of whey proteins (70%) and casein (30%). Formulas provide nutrition comparable for all major nutrients to human milk, although they contain slightly more protein than human milk. The casein:whey ratio of cow-milk-based formulas varies. Unmodified cow milk contains approximately three times the protein content of human milk and has ~80% casein and 20% whey proteins. As mentioned above, it is not suitable for young infants.

Hereditary Forms of Hemolysis

Because many causes of hemolysis are hereditary, a family history of anemia or jaundice can provide important information.


Hemolysis leading to elevated circulating bilirubin and possible jaundice can be caused by a variety of disorders in the red blood cell, including:

Intrinsic cell membrane defects (such as spherocytosis and elliptocytosis) Enzyme disorders (such as G6PD deficiency and pyruvate kinase deficiency) Hemoglobinopathies (such as the thalassemias and sickle cell anemia)

These disorders have varied modes of inheritance (X-linked, autosomal dominant, autosomal recessive) and may be found with greater prevalence among certain ethnicities, or in certain parts of the world. For example, glucose-6-phosphate dehydrogenase (G6PD) deficiency, an X-linked disorder, is more common in families of Mediterranean or West African origin than in other ethnic groups.

Biliary Atresia

A healthy-appearing infant who develops jaundice, dark urine, and acholic (pale) stools between 3 and 6 weeks of age may have biliary atresia.

Any infant who develops jaundice after two weeks of age must be evaluated with fractionated bilirubin (i.e., total and direct bilirubin levels).

A patient suspected of having biliary atresia generally will be referred to a pediatric gastroenterologist or pediatric surgeon.

Treatment When diagnosed early, biliary atresia can be treated surgically with the Kasai procedure (anastomosis of the i ntrahepatic bile ducts to a loop of intestine to allow bile to drain directly into the intestine).

If done early, the Kasai procedure will restore bile flow and prevent liver damage.

Voiding and Stooling Patterns in the Newborn


Urination changes in the first days after birth:

Day 3: The baby should be voiding 3-4 times a day.

Day 6: Baby should be voiding at least 6-8 times a day.

Urine should be pale yellow.



The stooling pattern also changes:

Day 3: Meconium should no longer appear in the stool and bowel movements should begin to appear yellow.

Day 6 or 7: Most newborns have 3-4 stools per day, although many infants pass stool with every feeding.

Stool passed by breastfed infants has little odor. You should be concerned if an infant's stool gradually loses color and becomes "acholic," as this may be a sign of biliary atresia.

Prognosis of Hyperbilirubinemia in the Newborn

Kernicterus is the most serious outcome of unconjugated hyperbilirubinemia, but it is rare in healthy, term babies who do not have hemolysis.

Most jaundiced newborns do not have major risks for adverse outcomes.

The American Academy of Pediatrics Clinical Practice Guideline Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation ( includes a nomogram that delineates risk associated with hyperbilirubinemia as "Low," "Intermediate," or "High" based on age and bilirubin level. It also lists clinical risk factors for severe hyperbilirubinemia in infants of 35 or more weeks' gestation:

Major Risk Factors

Pre-discharge total serum bilirubin (TSB) or total conjugated bilirubin (TcB) level in the high- risk zone Jaundice observed in the first 24 hours of life Blood group incompatibility, with positive direct antiglobulin test Gestational age 35-36 week Previous sibling received phototherapy Cephalohematoma or significant bruising Exclusive breastfeeding, particularly if nursing is not going well and weight loss is excessive East Asian race

Minor Risk Factors

Pre-discharge TSB or TcB level in the high intermediate-risk zone Gestational age 37-38 week Jaundice observed before discharge Previous sibling with jaundice Macrosomic infant of a diabetic mother Maternal age >25 y


Male gender

Decreased Risk

TSB or TcB level in the low-risk zone Gestational age 41 week Exclusive bottle feeding Black race Discharge from hospital after 72 hours

Key Physical Findings

A cephalohematoma (see photo) is a subperiosteal hemorrhage that is localized to the cranial bone that was traumatized during delivery.

The swelling does not extend across a suture line. As the blood is reabsorbed from the cephalohematoma it will contribute to hyperbilirubinemia.

Bruising on the head-or elsewhere on the body-from birth trauma or any other bleeding can also lead to increased bilirubin production because blood extravasated into tissues will be broken down and converted to bilirubin.

Hyperlink "(see photo) "

This Multimedia material is not included in this Summary, please open Case to review.

Developmental Dysplasia of the Hip (DDH)

It is important to assess every newborn for DDH (previously known as congenital dislocation of the hip).

Clinical features include:

Partial or complete dislocation Instability of the femoral head.

Risk factors include:

Breech position (30-50% of DDH cases occur in infants born in the breech position) Gender (9:1 female predominance) Family history


Screening recommendations

There are varied recommendations regarding screening for DDH:

American Academy of Pediatrics (AAP): 2000 ( sid=9d9a4077-451c-4684-ada8-b93441cccca8)

Serial clinical examinations of all infants' hips to the age of 12 months Hip imaging for female infants born in the breech position Optional hip imaging for boys born in the breech position Optional hip imaging for girls with a positive family history

American Academy of Orthopaedic Surgeons: 2014 (endorsed by AAP)

Limited recommendation for clinical examination of an infant's hips following a normal hip examination on subsequent visits prior to 6 months of age Moderate recommendation for an imaging study before 6 months of age in infants with one or more of the following risk factors: breech presentation, family history, or history of clinical instability

Canadian Task Force on Preventive Health Care: 2001

Serial clinical examinations of all infants' hips until they are walking independently No radiographic screening

US Preventive Services Task Force (USPSTF): 2006

Insufficient evidence to recommend routine screening for DDH in infants as a means to prevent adverse outcomes

Data from the Physician Insurers Association of America documents that medical malpractice lawsuits related to DDH have decreased significantly over the years, presumably because of better awareness of the condition with earlier and better diagnosis.


Pediatric care providers may need to make clinical decisions in the presence of differing guidelines. Although practice variation exists, most pediatricians in the US follow the AAP guidelines and routinely screen all infants by physical examination and by ultrasonography in the circumstances indicated above.

View hip exam. (

Signs and Symptoms of Untreated Congenital Hypothyroidism

Hypothyroidism that is not detected early in life can cause the following:

Prolonged jaundice Lethargy Large fontanelles Macroglossia (enlargement of the tongue) Umbilical hernia Constipation Abdominal distention Severe developmental delay

Timing of Neonatal Screen

The optimal time for testing is ≥ 24 hours after birth. A specimen obtained before 24 hours of age may miss PKU and other disorders with metabolite accumulation. If the first specimen is obtained prior to 24 hours, a second specimen should be obtained in the next one to two weeks.

Clinical Skills

Interviewing New Parents

When seeing a newborn or young infant, there are a variety of ways to help bring up issues or concerns the family might have:

Offering congratulations and commenting on the baby's current weight and rate of weight gain may be an easy place to start. Inviting the family to ask questions might be helpful; for example, you could ask, "W hat are some of your questions?" If there are other children in the family, you might ask how they have reacted to the new baby.


Also, be aware of the mood of the parents, especially the new mother:

Screening for maternal depression is important, as major depression can occur before, during, or after delivery of a baby in an estimated 10-20% of women. Ask about sources of support for the family, including transportation and finances.

For a resource that provides helpful advice on age-appropriate interview questions, child development, and guidance for families, see the American Academy of Pediatrics' Bright Futures: Guidelines for Health Supervision of Infants, Children and Adolescents. (

Clinical Observation

A skilled clinician observes a great deal during any clinical encounter.

Observing breastfeeding is an excellent way to assess mother-infant interaction as well as many of the factors that contribute to the success of breastfeeding.

It is essential to observe feedings if there are nutritional or growth concerns.

Weight Gain in Newborns

It is very important to monitor weight gain for all infants. Breastfed infants may lose up to 7%-10% of their birth weight during the first 4 to 5 days of life, and typically regain birth weight by at least 2 weeks of age. A more rapid weight loss in the first days after birth or delayed weight gain would mandate further assessment and intervention.


When monitoring a newborn infant, it is helpful to compare the birth weight and the discharge weight with the current office weight. Remember, some differences between an infant's weight in the nursery and in the office could be caused by differences in scales. It is also important to be consistent in the method of weighing: It is best to always weigh an infant fully undressed.

Physical Examination of the Newborn

View an instructional video on physical examination of the newborn ( (This video is 15 minutes long and recommended only for users with fast internet access.)


Jaundice Evaluation Methods


Jaundice typically is first noticed on a newborn's face at a bilirubin level of approximately 4-5 mg/dL (68-86 μmol/L). It then progresses down the trunk to the extremities (cephalocaudal progression) as the bilirubin level rises.

In most infants, experienced pediatricians would estimate the bilirubin level to be in the 10-15 mg/dL (171-257 μmol/L) range when jaundice is visible below the knees, but the experienced pediatrician also knows that this is only an estimate of serum bilirubin levels.

Serum Bilirubin Measurement

A visual estimate of bilirubin level is not a substitute for serum bilirubin levels as it can easily understimate the true level of hyperbilirubinemia.

Whenever there is concern about hyperbilirubinemia, a serum total bilirubin level should be obtained.

Transcutaneous Bilirubin Measurement

Devices that measure transcutaneous bilirubin are effective tools for monitoring jaundice, although they cannot substitute for serum bilirubin levels.

See the associated reference ranges in conventional and SI units (

Clinical Reasoning

Evaluation of the Etiology of Hyperbilirubinemia in a Newborn

The following information is all necessary in determining the cause of hyperbilirubinemia:

Age at which jaundice begins

Can help determine the risk for severe hyperbilirubinemia and can direct you to specific causes of jaundice, especially hemolysis.


Breastfed infants may lose up to 7-10% of their birth weight during the first 4 to 5 days of life and typically regain birth weight by at least 2 weeks of age.

Weight history

A more rapid weight loss in the first days after birth or delayed weight gain mandates further assessment and intervention. Inadequate weight gain indicates a potential insufficient fluid and calorie intake making a diagnosis of breastfeeding jaundice more likely.

Feeding history

Aids in distinguishing among possible causes of jaundice.

Pregnancy history

Maternal infections may affect the fetus in utero, resulting in congenital infection and intrauterine growth restriction (IUGR). The consequence may be a newborn who is born small for gestational age (SGA) with risk of direct hyperbilirubinemia.

Signs of illness in the newborn

It is important to inquire about fever or other signs of illness in jaundiced newborns because septic infants can have jaundice (with elevated total and direct bilirubin) as one sign of serious infection, along with other clinical manifestations, such as:

Temperature instability Respiratory distress Apnea Irritability Lethargy Poor tone Vomiting Poor feeding

When jaundice is the only clinical finding, sepsis is highly unlikely as the cause of the increased bilirubin levels.

Differential Diagnosis for Jaundice in the Newborn

Diagnosis Comment

Breast milk jaundice

Begins in the middle of the first week of life (usually day 4 through 7) but may not reach its peak until the second week.


Physiologic Physiologic jaundice

jaundice typically appears earlier than on day 4. The level of hyperbilirubinemia and the time course helps to distinguish physiologic from breast milk jaundice.


Possible reasons for hemolysis include:

ABO incompatibility Rh incompatibility G6PD deficiency

To completely investigate the possiblity of a hemolytic process you need a laboratory test (a peripheral smear).

Hypothyroidism Typically detected by the neonatal screen.

Metabolic disease

Often children with inborn errors of metabolism-such as galactosemia or urea cycle defects-present with liver dysfunction, including jaundice, in addition to other features (like seizures, sepsis, ascites) depending on the defect. The newborn screen can help rule out these diagnoses.

Biliary atresia

Typically presents after 2 weeks of age with progressive jaundice and acholic stools. Causes a direct hyperbilirubinemia.

Intrinsic liver disease

Very rare cause of neonatal jaundice

Birth trauma (cephalohematoma or other bruising)

Reabsorption of blood and metabolism of red blood cells can cause jaundice.


While sepsis can lead to jaundice, jaundice as the only sign of sepsis is rare. Breastfeeding offers some protection against infection, particularly early on when colostrum provides preformed antibodies, cells, and other anti-infective substances.


In utero exposure to one of the TORCH infections can lead to jaundice. TORCH infection

Physical findings may include hepatosplenomegaly, microcephaly, and/or rash.

Gilbert syndrome

Gilbert's syndrome (reduced activity of the enzyme glucuronyltransferase) is a relatively common cause of harmless jaundice (~5% of the population). Final diagnosis usually does not occur until later in life, when it is found that hyperbilirubinemia persists, with no other abnormalities.

Crigler-Najjar syndrome

Due to the absence or low levels of UDP glucuronosyltransferase 1 family, polypeptide A1. Can cause severe (type I) or mild/moderate (type II) jaundice. Also very rare.


Evaluation of Neonatal Hyperbilirubinemia

Test Indication

Maternal ABO and Rh typing and screen for unusual isoimmune antibodies

During prenatal testing, this test identifies an Rh-sensitized mother who could put the fetus at risk for Rh-isoimmune disease.

Infant (cord blood) ABO and Rh typing, and direct Coombs' test

When mother is Rh-negative (or prenatal testing has not been done). Saving a sample of cord blood is encouraged for future testing of blood type and Coombs' (particularly when the mother's blood type is Group O).

Note: A family might ask you about cord blood banking. Learn more in the AAP Policy Statement: Cord Blood Banking for Potential Future Transplantation ( 4804-9e2e-b2a23c276d76) .


When the family history, the ethnic or geographic origin, or the time of the onset of jaundice suggests the possibility of G6PD deficiency G6PD screen

(particularly if late-onset jaundice). Similar criteria can be used to justify testing of an infant whose jaundice is caused by other specific hemolytic disorders.

Total serum bilirubin (TSB)

If jaundice is noted in the first 24 hours of life or with significant jaundice.

Direct bilirubin level and/or urine dipstick for bilirubin

Infant has dark urine or light stools. Persistent jaundice (> 3 weeks). Infant is ill (there will be an increased direct bilirubin with sepsis/congenital infection).

Note: Most pediatricians would order a direct bilirubin level at least once during the evaluation of an exaggerated/high level of total bilirubin.

CBC or hemoglobin level

If there is a suspicion of hemolytic disease or anemia (e.g., jaundice in the first day of life or TSB >14 mg/dL in the first 48 hours). If anemia is found, an elevated reticulocyte count would be further evidence of hemolysis (some might obtain a reticulocyte count with the CBC).

Reticulocyte count and blood smear

Consider if infant is anemic or there is a strong clinical suspicion of hemolytic disease other than isoimmunization.

Neonatal screening

All infants need to have a neonatal screen. There is no uniform screening program throughout the U.S.; s pecific disorders tested by the screen vary from state to state. There is a movement to try to establish standards that specify the number and types of disorders that are screened.


Tests for newborn sepsis:

CBC and d ifferential cell count C-reactive protein Blood cultures Lumbar puncture with chemistry and cultures

If the jaundiced infant is ill or has other clinical signs suggesting possible infection. Jaundice as the only sign of sepsis would be rare.

Tests for congenital infections (TORCHS titres)


titres test for congenital infections: TOxoplasmosis; Rubella; Cytomegalovirus; Herpes; and

Syphilis. Obtain if the maternal history or infant's physical exam and clinical course suggested a congenital infection.


Management of Jaundice in the Breasfed Infant

Infants who are breastfed have a higher incidence of elevated bilirubin levels than formula-fed babies. However, stopping breastfeeding is NOT necessary in almost all cases, although some pediatricians will recommend temporary cessation of breastfeeding (for 24-48 hours) if breast milk jaundice causes extremely high bilirubin levels.

In their policy statement on breastfeeding, Breastfeeding and the Use of Human Milk (, the American Academy of Pediatrics (AAP) discourages the interruption of breastfeeding by healthy term newborns with jaundice and encourages continued and frequent breastfeeding (at least 8 to 10 times every 24 hours).

Transfer of Chemicals into Breast Milk

To learn more about drugs and other chemicals that pass into breast milk, see the AAP's policy


statement, The Transfer of Drugs and Other Chemicals into Human Milk. (

As an example, Tylenol #3 (a combination of acetaminophen and codeine, a narcotic analgesic) would not be recommended as a first choice. Codeine, which metabolizes to morphine, is passed into breast milk. Although the amount is probably insignificant, some women who are rapid metabolizers of codeine may excrete high levels of morphine in breast milk. There is a case report of a breastfed infant who died from a morphine overdose when the mother was taking codeine; the mother was found to be a rapid metabolizer (see Koren, et al, Lancet, vol 368 p. 704, Aug 2006).


Vitamin D

To avoid the development of rickets, exclusively breastfed infants need vitamin D supplementation in the first 6 months of life. Supplementation with 400 IU of vitamin D should be initiated within days of birth for all breastfed infants. Infants who are not breastfed should also receive supplementation with 400 IU of vitamin D if they do not ingest at least 1 L of vitamin D-fortified formula daily. (The Canadian Paediatric Society recommends 800 IU intake per day-from all sources-between October and April depending upon where the family lives.) Remember, sunlight is required to hydroxylate vitamin D. Vitamin D deficiency rickets generally appears between 6 and 24 months and responds to treatment with vitamin D.


Although a 2010 AAP clinical report recommended iron supplementation for all exclusively breastfed infants beginning at 4 months of age, this recommendation has been debated. Most pediatricians do recommend the addition of iron-containing foods to the infant's diet, starting at age 6 months. Most standard formulas are iron-fortified.


Breast- and bottle-fed infants both should receive fluoride supplements after the age of 6 months if the water supply lacks fluoride (< 0.3 ppm).

Note that most bottled and filtered water has low fluoride levels.

Tools to Evaluate Risk of Neonatal Jaundice

This nomogram, ( which is now widely


used, was originally published in:

Bhutani VK, Johnson L, and Sivieri EM. Predictive ability of a predischarge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns. Pediatrics, 1999;103:6-14.

Many pediatricians also use the BiliTool ( to determine risk.

Management of Persistent Jaundice

If jaundice is barely noticeable at the 2-week check, you might not order any further testing, choosing continued breastfeeding and observation

However, almost a third of healthy breastfed infants can have persistent jaundice at 2 weeks of age. Remember that with breast milk jaundice, jaundice may persist for up to 12 weeks.

When jaundice persists, however, it is important to check for either dark urine or acholic- appearing stools that might signify the development of cholestasis. It is also reasonable to obtain total and direct bilirubin levels (also known as "fractionated bilirubin") to be sure that the direct bilirubin is not beginning to climb. An increasing direct bilirubin at this age would lead to a new differential diagnosis that includes conditions such as biliary atresia and alpha-1 antitrypsin deficiency.


1. Luzzatto L, Mehta A. Glucose-6-phosphate dehydrogenase deficiency. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic Basis of Inherited Disease-II, 6th ed. London: McGraw- Hill, 1989: 2237.

2. Corchia C, Balata A., Meloni GF, Meloni T. Favism in a female newborn infant whose mother ingested fava beans before delivery; Journal of Pediatrics, 1995, 127: 807-8.

3. Kaplan M, et al. Bilirubin Conjugation, Reflected by Conjugated Bilirubin Fractions. In: Glucose- 6-Phosphate Dehydrogenase-deficient Neonates: A Determining Factor in the Pathogenesis of Hyperbilirubinemia. Pediatrics. 1998; 102: e37.

Subcommittee on Hyperbilirubinemia, American Academy of Pediatrics: Practice guidelines on management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2004; 114: 297-316.

Hsia DY-Y, Allen FH, Gellis SS, Diamond LK. Erythroblastosis fetalis, VIII: studies of serum


Hsia DY-Y, Allen FH, Gellis SS, Diamond LK. Erythroblastosis fetalis, VIII: studies of serum bilirubin in relation to kernicterus. N Engl J Med. 1952; 247: 668-671

Watchko JF. Oski FA. Bilirubin 20 mg/dL = vigintiphobia. Pediatrics. 71:660-3, 1983

Newman TB, Maisels MJ, Evaluation and treatment of jaundice in the term newborn; a kinder, gentler approach; Pediatrics 89:809-18, 1992

Subcommittee on Hyperbilirubinemia, American Academy of Pediatrics: Practice guidelines on management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation, Pediatrics, 2004; 114: 297-316. (;114/1/297

Misra M, Pacaud D, et al. Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Pediatrics. 2008; 122: 398-417.

Godel JC. Vitamin D supplementation: recommendations for Canadian mothers and infants. Access at

Baker RD, Greer FR; Committee on Nutrition American Academy of Pediatrics. Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0-3 years of age). Pediatrics. 2010;126(5):1040-50. doi: 10.1542/peds.2010-2576. Epub 2010 Oct 5.

Martinez JC. Maisels MJ. Otheguy L. Garcia H. Savorani M. Mogni B. Martinez JC Jr. Hyperbilirubinemia in the breast-fed newborn: a controlled trial of four interventions. Pediatrics. 91(2):470-3, 1993.

Neonatal Jaundice and Kernicterus (, Pediatrics. 2001; 108(3): 763-765


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