In a study published recently in the Future Journal of Pharmaceutical Sciences, the researchers sought to summarize the cause of neonatal hyperbilirubinemiaHyperbilirubinemia A common cause of jaundice, this refers to higher than normal bilirubin levels in the blood. by conducting a comprehensive review of clinical studies on the subject, including the effects of various treatment modalities and the impact of adjuvant therapies used together with phototherapyPhototherapy A treatment that uses special blue light to help newborns break down bilirubin and prevent kernicterus..
Neonatal unconjugated hyperbilirubinemia can be caused by many factors, including hemolytic disease of the fetus and newborn (HDFN), physiologic jaundiceJaundice A common symptom of HDFN, jaundice is caused by excess bilirubin and is characterized by a yellow tint to the skin or eyes., breast milk jaundice, congenital hyperbilirubinemia and sepsis and a variety of approaches are used to manage and treat the disorder.
The primary endpoints of the analysis were total serum bilirubinBilirubin A yellow substance produced when red blood cells break down. High bilirubin levels in newborns with HDFN can cause jaundice or, in severe cases, brain damage., length of hospital stay and duration of phototherapy.
Based on the type of elevated bilirubin involved, neonatal hyperbilirubinemia can be classified into the following two categories: unconjugated (indirect) hyperbilirubinemia and conjugated (direct) hyperbilirubinemia.
Unconjugated hyperbilirubinemia is the most common form of the disorder. It can be either pathologic or physiologic in nature. There are four main categories of unconjugated hyperbilirubinemia, which are based on the pathophysiology involved:
- Enhanced enterohepatic circulation
- Heightened production
- Reduced clearance
- Compromised conjugation
Read more about HDFN testing and diagnosis
Hemolytic jaundice associated with Rhesus (RhRh factor A protein or antigen found on red blood cells. When an Rh-negative mother carries an Rh-positive fetus, her immune system may make antibodies that attack the fetus' red blood cells.) or ABO blood groupBlood group A classification of blood based on inherited markers found on red blood cells. The ABO and Rh blood groups are most common in HDFN. incompatibility is one of the most common types of jaundice. It usually occurs because of the mixing of mother and fetal blood during delivery. When this happens, the mixing of even a small number of fetal red blood cells (RBCs) in the mother’s circulation can lead to the mother developing antibodiesAntibody A protein made by the immune system that recognizes and attacks foreign substances, such as bacteria, or in HDFN, fetal red blood cells carrying incompatible antigens. against the fetal RBCs.
This rapid breakdown and destruction of fetal or neonatal RBCs results in increased production of bilirubin, thus overwhelming the immature hepatic conjugation and excretion mechanisms of the neonate. This type of jaundice often is evident in the first day of life and escalates rapidly.
Physiologic jaundice typically develops after 24 hours of life and is due to the metabolism of neonatal bilirubin. This type of jaundice, which is reported in about 80% of preterm and 65% of term neonates, typically resolves when the neonate is 2 to 3 weeks of age.
Approximately 65% of hospital readmissions among neonates are due to severe unconjugated hyperbilirubinemia in the first week of life. Breast milk jaundice is considered a benign type of unconjugated hyperbilirubinemia.
Treatment options for unconjugated hyperbilirubinemia
Phototherapy is the initial treatment option for neonates with hyperbilirubinemia. Other treatment strategies involve the utilization of intravenous immunoglobulinIntravenous immunoglobulin A therapy made from donated antibodies that may help reduce the mother’s immune response and protect the fetus. and exchange transfusion.
Notwithstanding the short-term and long-term effects of phototherapy, it is still considered a core treatment for patients with neonatal hyperbilirubinemia. In those patients in whom phototherapy proves unsuccessful, exchange transfusion often is considered.
A number of studies have evaluated the use of various agents either to replace phototherapy or to be used as an adjunctive treatment, with the latter intended to decrease the amount of time needed for phototherapy and thus reduce any adverse effects.
Although positive outcomes have been reported in some studies, which are indicative of their effectiveness, others have not succeeded in yielding any reductions in phototherapy treatment duration.
Phototherapy-generated side effects include disruptions in circadian rhythm, dehydration, diarrhea, hypocalcemia (low calcium levels), inhibition of the pineal gland (which can lower the release of melatonin and secretion of cortisol), weakening of the skin’s protective barrier, skin rashes and petechiae, phototherapy-induced oxidative stress, bronze baby syndrome and exacerbation of hemolysis (breakdown of RBCs)
“Studies introducing adjuvants such as zinc sulfate and ursodeoxycholic acid have demonstrated promising results in reducing the duration of phototherapy and minimizing the side effects,” the authors highlighted. “However, these results are inconclusive, and further research is required to validate the safety and efficacy of these adjuvants,” they concluded.
