Neonatal Jaundice

Neonatal jaundice is a condition in newborns where the skin and eyes appear yellow due to high levels of bilirubin in the blood.

Physiology of Bilirubin Metabolism in the newborn

Bilirubin Production:

Bilirubin is a byproduct of haemoglobin breakdown from red blood cells. In newborns, particularly premature infants this process is more active due to increased red blood cell turnover. Since the lifespan of neonatal red blood cells is shorter (approximately 70–90 days) compared to adults (about 120 days), the bilirubin load on the infant’s metabolic system is significantly higher. Newborn infants produce bilirubin at more than twice the adult rate, largely due to relative polycythaemia and accelerated red blood cell breakdown. This elevated bilirubin production, combined with immature liver enzymes responsible for bilirubin conjugation, contributes to the risk of accumulation. Bilirubin levels usually decrease to adult levels within 10 to 14 days after birth. The breakdown of red blood cells occurs in the reticuloendothelial system, primarily the liver and spleen, where aged or damaged red blood cells are removed from circulation.

(Moncrieff., 2018, Ifeanyi Obeagu & Katya, 2022., Ullah et al., 2016, Ansong-Assoku et al, 2024, Kain & Mannix 2024, Gardner et al 2021).

Unconjugated (Indirect) Bilirubin: In the bloodstream, bilirubin initially exists in an unconjugated (indirect) form, which is not water-soluble. This fat-soluble form has an affinity for subcutaneous tissues and the brain, making it potentially harmful and difficult to excrete. To be safely eliminated from the body, it must first be transported to the liver, where it undergoes conjugation. Unconjugated bilirubin is carried through the bloodstream bound to albumin, as it is poorly soluble on its own. Albumin acts as a carrier protein, with one high-affinity binding site and additional lower-affinity sites for bilirubin. When bilirubin is not tightly bound—referred to as “free” bilirubin, it can cross the blood-brain barrier and pose a risk of neurotoxicity. The binding capacity of albumin can be influenced by various factors, including plasma pH, levels of free fatty acids, and certain medications, all of which may reduce its ability to effectively bind bilirubin. (Ifeanyi Obeagu & Katya, 2022., Ansong-Assoku et al, 2024, Kain & Mannix 2024, Gardner et al 2021).

Liver Processing: The liver converts unconjugated (indirect) bilirubin into a water-soluble form known as conjugated (direct) bilirubin by attaching it to glucuronic acid, a process called conjugation. This transformation is catalysed by the enzyme UDP-glucuronosyltransferase (UDPGT), and it requires glucuronic acid, which is synthesized from glucose. In newborn infants, especially during the first few days of life, this conjugation process is less efficient due to immature liver enzyme activity. After unconjugated bilirubin is released into the bloodstream, it quickly binds to albumin and is transported to the liver. Although albumin-bound bilirubin is still considered “free,” it is no longer toxic. Within liver cells (hepatocytes), bilirubin is conjugated with glucuronic acid by the enzyme UDPGT, forming bilirubin glucuronide. This conjugated form is water-soluble, allowing it to be excreted into the bile and eventually reach the intestines for elimination. (Moncrieff., 2018, Ullah et al., 2016, Kain & Mannix 2024, Gardner et al 2021).

Excretion: Once conjugated, bilirubin is excreted into the bile and transported to the intestines. There, it is further broken down into stercobilin and urobilin, which are eventually eliminated in the faeces and urine. However, certain characteristics of the newborn digestive system can interfere with this elimination process. In newborn infants, the gut is initially sterile, and intestinal motility may be slow. These conditions can promote a process known as enterohepatic circulation. Within the intestinal lumen, the enzyme beta-glucuronidase can deconjugate bilirubin—converting it back into its unconjugated form. This unconjugated bilirubin can then be reabsorbed into the bloodstream, increasing the overall bilirubin load in the infant. (Chen & Yuan, 2020; Sisay et al., 2023, Kain & Mannix 2024, Gardner et al 2021).

Hyperbilirubinemia

Neonatal hyperbilirubinemia is one of the most common clinical disorders in the neonatal period, with 85% of preterm infants and 75% of full-term having visible jaundice (Ansong-Assoku et al, 2024;). Midwives require clinical skills to recognise physiological jaundice, understand the clinical significance and provide the appropriate midwifery management.

Hyperbilirubinemia occurs when serum bilirubin levels have exceeded the normal range for the infant’s gestation, age, and weight. It can be physiological or pathological in nature and can be classified as either increased bilirubin production or decreased bilirubin excretion.

Physiological: As bilirubin clearance transitions from placental to liver-based processing after birth, the newborn liver can easily become overwhelmed. This is especially true in preterm infants, who have insufficient levels of the enzyme UDPGT, typically taking 6 to 7 days to produce adequate amounts. Additional contributing factors include the shorter lifespan of neonatal red blood cells (70–90 days compared to 120 days in adults), increased red blood cell volume, and enhanced enterohepatic circulation, all of which elevate bilirubin production and recycling. Physiological jaundice typically appears between days 2 and 3 of life, peaks around day 6, and resolves by day 10 (Safer Care., 2017, Moncrieff, 2018., Ullah et al., 2016, Hansen & Aslam, 2017, Perrone et al., 2023, Ansong-Assoku et al, 2024, Kain & Mannix 2024, Gardner et al 2021).

However, jaundice is never considered physiological if it:

• Appears within the first 24 hours of life,

• Persists beyond 14 days, or

• Is associated with signs of illness in the infant.

Causes of Physiological Jaundice

Common causes of physiological jaundice include:

• Prematurity: Preterm infant’s red blood cells can last as little as 40 days and this combined with the preterm infant’s slow gut motility, decreased gut bacteria, decreased albumin binding sites and the delayed maturation of glycuronyl transferase significantly increases the preterm infant’s risk of becoming jaundice (
• Medications: Some medications compete with the bilirubin for albumin binding sites, thus making the albumin unavailable for the bilirubin
• Bruising: Bruising, cephalhematoma and swallowed blood can increase the amount of bilirubin due to the rapid breakdown of the red blood cells
• Gastrointestinal system: Inadequate oral intake can cause delayed bacterial colonisation of the gut and increase the entero-hepatic circulation. And or delayed stooling due to the vast amount of bilirubin in meconium, the longer it takes to clear the intestine the greater the amount of bilirubin is absorbed.
• Breastfeeding: Breast milk inhibits glycuronyl transferase and due to the minimal amounts of milk available in the first few days of breastfeeding the entero-hepatic circulation is increased.

(Safer Care., 2017, Moncrieff, 2018., Hansen et al., 2020; Itoh et al., 2022; Sisay et al.,2023, Kain & Mannix 2024, Gardner et al 2021).

Pathological Jaundice

Pathological jaundice is best discussed in relation to time it arises after birth:

• Early: less than 24 hrs Always pathological, usually haemolytic (excess production of bilirubin); ABO incompatibility, RH immunisation, G6PD or sepsis
• Normal: Days two to ten, usually uncomplicated, mild dehydration/insufficient milk supply, haemolysis (breakdown of bruising), polycythaemia (too many RBC, infants of diabetic mother’s, twin to twin transfusion) or infection
• Late: Day fourteen onwards, mostly persistent unconjugated, such as Breast milk jaundice– related to ingredients in breast milk (>fat effects conjugation), haemolysis, hypothyroidism – need thyroxine for removal or late onset sepsis

 Causes of Pathological jaundice 

Pathological jaundice may appear within the first 24 hours of life, rises rapidly, or persists longer than expected. Causes are grouped by mechanism, Haemolysis (Increased RBC breakdown), Infections, Liver dysfunction (Impaired conjugation), Biliary obstruction (Impaired excretion) or other (bruising, or polycythaemia).

(Safer Care, 2017, Moncrieff, 2018., Ifeanyi Obeagu & Katya, 2022., Ansong-Assoku et al, 2024, Kain & Mannix 2024, Gardner et al 2021).

Common causes of pathological jaundice include (click on the > to expand each disorder):

Bilirubin toxicity

Unconjugated bilirubin is neurotoxic, and its accumulation can lead to acute brain dysfunction known as bilirubin encephalopathy. This condition can progress to kernicterus, a chronic and potentially fatal outcome. Bilirubin encephalopathy refers to the early, acute signs of bilirubin toxicity typically seen in the first few weeks of life, while kernicterus describes the long-term, irreversible neurological damage resulting from such toxicity. There is no clearly defined serum bilirubin level considered entirely safe, as toxicity can occur at varying thresholds. Preterm infants are particularly vulnerable to the harmful effects of bilirubin. Several clinical factors may increase the risk of bilirubin toxicity, including prematurity, the infant’s postnatal age, the rate of bilirubin increase, and medications that reduce bilirubin’s binding to albumin (Ansong-Assoku et al, 2024, Hansen et al., 2020, Kain & Mannix 2024, Gardner et al 2021).

Jaundiced Newborn Receiving Treatment under a Bili Light from Maternal-Newborn Nursing by Amy Giles, Regina Prusinski, Laura Wallace OpenStax  is licenced under CC BY 4.0

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