Prolongation of Jaundice in Infants at the University Clinical Center of Kosovo During 2020

Neonatal jaundice is the yellowing of the skin and whites of the eyes in a newborn baby due to high levels of bilirubin. Other symptoms may include excessive sleepiness or refusal to eat. Complications may include seizures, cerebral palsy, or kernicterus [1]. Approximately 60% of newborn babies and 80% of premature babies may have jaundice [1]. In most cases there is no specific underlying (physiological) disorder. In other casesthis disease results from the destruction of red blood cells, liver disease, infection, hypothyroidism or metabolic (pathological) disorders. A bilirubin level greater than 34 μmol/l (2 mg/dL) may be evident. Concerns in healthy infants occur when levels are greater than 308 μmol/L (18 mg/dL). The main features of pathological hyperbilirubinemia are as follows: jaundice appears in the first hours after birth (icterus praecox), progresses quickly, is more intense than physiological (icterus gravis) and lasts a long time (icterus prolongatus). Considering these worrisome findings, further investigationsare recommended to determine the underlying cause [2]. Globally, more than 100,000 premature and late-term infants die each year as a result of jaundice [3].

Epidemiology: Many factors influence the epidemiology of jaundice, although their clinical significance is often controversial. According to some studies, the highest levels of bilirubin in the blood are found in infants in East Asia, and in some Hispanic babies of Mexican origin. However, black infants in America and Great Britain have lower bilirubin levels than white infants [4]. The nature of familial inheritance of jaundice in Chinese and Danish infants has also been confirmed. When a sibling has high blood bilirubin concentrations, the risk for subsequent children increases up to 12.5 times [4]. In the developed world, the most common causes of jaundice are Rh incompatibility, ABO incompatibility, infections, sepsis, etc. [4].

Genetics: Several epidemiological studies support the assertion that genetic contributors are important moderators of neonatal jaundice. These include: disorders of heme bilirubin production, bilirubin metabolism, and damage to genes that regulate red blood cell lifespan [5].

Pathogenesis: Bilirubin is the end product of heme catabolism, and is produced mainly by the breakdown of hemoglobin by erythrocytes. Under normal circumstances, bilirubin undergoes conjugation within the liver, making it soluble in water. It is then excreted through the bile into the GI tract, and eliminated through the feces. Approximately10% of urobilinogen is returned to the bloodstream and excreted through the kidneys. As a consequence ofdysfunction of this pathway, the level of bilirubin in the blood increases, and jaundice appears [6].Hyperbilirubinemia was classified as: Unconjugated Hyperbilirubinemia (indirect) or Conjugated Hyperbilirubinemia (direct) [6]. Unconjugated hyperbilirubinenia is the most common form of NAFLD in the newborn period and manifestsas jaundice [7].

Clinical manifestations: The main symptom is yellowing of the skin and whites of the eyes in a newborn baby. It is first noticed on the face, especially on the nose, while it then spreads to other parts of the body. Other symptoms may include excessive sleepiness or refusal to eat [8]. A bilirubin level greater than 34 μmol/l (2 mg/dL) can be detected, while jaundice is observed when the concentration of bilirubin in the serum is 85.5-119.7 μmol/l [8].

Complications: Unconjugated hyperbilirubinemia (severe jaundice) may result in bilirubin encephalopathy (kernicterus). Prompt and accurate treatment of neonatal jaundice helps reduce the risk of newborn patients developing kernicterus. Prevention of hyperbilirubinemic encephalopathy is performed by early feeding of breast milk and prevention of premature birth[9].

Infants with kernicterus may have lethargy, loud crying, hypertonia or hypotonia, fever, neurological disorders and even death [9].

Causes of the disease: In newborns, jaundice develops as a result of an increase in the concentration of bilirubin in the blood.Hyperbilirubinemia is the main cause of jaundice. Internal bleeding, blood infections (sepsis), Rh and ABO incompatibility, liver dysfunction, blockage of the baby's bile ducts, enzyme deficiencies, and red blood cell abnormalities that cause them to breakdown quickly can also cause jaundice. Prolonged neonatal jaundice is severe and should be managed as soon as possible [10].Hyperbilirubinemia can be:

Unconjugated andconjugated [11].

Diagnosis: Diagnosis was made by performing hematological and biochemical analyses. In those born after 35 weeks, a transcutaneous bilirubinometer can also be used for more than one day. It is also recommended to use an icterometer, a device that measures the degree of yellowness in the skin [12].

The gold standard for assessing bilirubin in the blood is the van Den Bergh reaction, which is a chemical reaction used to determine conjugated bilirubin levels. The principle of this reaction is the reaction of bilirubin with diazotized sulfonyl acid, and purple-colored bilirubin is produced. This reaction is performed to determine the type of jaundice. The patient's serum was mixed with diazo reagent; if a red color immediately appeared, then conjugated bilirubin was present.This type of test is called direct positive.In the indirect positive test, the patient's serum is first treated with alcohol and later mixed with diazo reagent.If the color appears red, we are dealing with unconjugated bilirubin; if conjugated and unconjugated bilirubin are present, then the reaction is biphasic [13].

Treatment: Bilirubin levels vary with the age and health status of the newborn. However, any newborn with a total serum bilirubin level greater than 359 μmol/l (21 mg/dL) should receive phototherapy [14]. Babies with neonatal jaundice can be treated with a colored light called phototherapy, which works by changing trans-bilirubin to the water-soluble isomer cis-bilirubin. Phototherapy is not ultraviolet light therapy, but rather a specific frequency of blue light. Light can be applied with air lamps, which means that the baby's eyes must be covered, or with a device called a biliblanket, which sits under the baby's clothing close to his skin. The use of phototherapy was first discovered at Rochford Hospital in Essex, England, when a nurse, Nurse Jean Ward, noticed that babies exposed to sunlight had reduced jaundice, and a pathologist Dr. Perryman, who noticed that a drop of blood left in the sun turned green. Dr. Cremer, Richards, and Dobbs combined these observations, leading to a randomized clinical trial that was published in Pediatrics in 1968 and took another ten years to run. There is currently no reliable evidence as to whether phototherapy applied at home or in hospitals is more effective for jaundiced infants [15].