A case of indirect hyperbilirubinemia in a child with diabetic fetopathy

Introduction

Jaundice is a visual manifestation of hyperbilirubinemia. Initially, yellowing of the skin in newborns appears on the forehead and face, then, as it progresses, on the trunk and extremities; later on, it disappears in the opposite direction. This is the so-called “cephalocaudal progression”. This sequence of jaundice appearance has been known for a long time, but there is still no clear explanation for this pattern. It is assumed that such a sequence may be related either to the relationship of bilirubin with albumin, depending on pH values, or to different blood flow intensity and body temperature discrepancies in different areas [1–3].

Jaundice in young children is a common clinical symptom in practical medicine. According to various sources, in the early neonatal period, hyperbilirubinemia syndrome occurs in 25–65% of full-term and 70–90% of premature infants. In severe cases, jaundice may be accompanied by the neurotoxicity manifestation of indirect bilirubin; it can also be associated with some delay in diagnosis and prolonged course (biliary atresia) or be a harbinger of a serious underlying disease leading to death. Therefore, jaundice in young children should not be perceived as a routine condition, and the appearance of jaundice in the lower extremities requires mandatory monitoring of the dynamics of the bilirubin level in the blood serum. Regardless of the level of hyperbilirubinemia, the appearance of jaundice in the first 24 hours of life, a high rate of hourly increase in the bilirubin level in the blood serum in combination with the severity of hemolysis require urgent examination and treatment of the newborn [4][2].

During the first week of life, the total bilirubin level in the serum of most full-term infants usually amounts to more than 34 μmol/L, but it can increase up to 103–137 μmol/L by the 3rd–5th days with subsequent decline. Often, an increase in bilirubin up to 221 μmol/L can be considered as the “physiological range”, not being neurotoxic, i.e. it is regarded as benign. In “late preterm infants” with a gestational age of 35–37 weeks, the total bilirubin can be at the level of 171–205 μmol/L on the 5th day after birth and then continues to increase. However, this increase in the bilirubin level in premature infants should not be considered benign, especially in infants with low birth weight [2].

Total bilirubin levels above 340 μmol/L in full-term and late preterm infants are rare. “Clinically significant” hyperbilirubinemia in such infants is defined when total bilirubin concentration in the blood serum is above 256 μmol/L, and in infants born before the 35th week of gestation, above 171 μmol/L. The main diagnostic and prognostic significance is the rapid increase in jaundice, as well as the detection of coloration of the palms and feet in a child at any age. The latter sign almost always indicates an excess of bilirubin levels (256 μmol/L) and serves as an indication for urgent determination of the bilirubin concentration in the blood serum [4].

It is well known that the investigation of the bilirubin level with a transcutaneous bilirubinometer is an accurate non-invasive method for diagnosing and predicting hyperbilirubinemia, which is used to screen for jaundice in newborns from 24 weeks of gestation and has a high correlation with the results of laboratory tests [2][3][5–7]. It is worth noting that this method ensures a linear relationship with the level of serum bilirubin up to a concentration of 250–260 μmol/l [7][8]. Moreover, “the diagnostic and prognostic significance is not so much the absolute value of this indicator but its correspondence or discrepancy with the physiological rates of increase in bilirubin concentration in a child in the first days of life” [2].

However, it should be noted that transcutaneous determination of bilirubin does not replace standard laboratory testing but it allows one to avoid unnecessary sampling of capillary or venous blood in full-term and premature infants and not to miss potentially dangerous hyperbilirubinemia, especially during early discharge from hospital [2][3][6][7].

Taking into account the limitations of the transcutaneous method, the determination of bilirubin concentration in the blood serum using standard laboratory methods is recommended for the following cases [2][4]:

• all premature infants with gestational age less than 35 weeks with jaundice;
• all newborns who develop jaundice in the first 24 hours of life;
• newborns with signs of hemolytic disease or other known risk factors for the development of pathological hyperbilirubinemia, such as the presence of severe hyperbilirubinemia in previous children in the family, significant weight loss, etc.;
• full-term newborns, if bilirubin is determined by the transcutaneous method at the level of >140 μmol/l at the age of 24–48 hours; >200 μmol/l at the age of 48–72 hours; or >250 μmol/l at the age of over 72 hours;
• all children receiving phototherapy.

Early discharge from the maternity hospital and inadequate monitoring of children after discharge increase the probability of developing bilirubin encephalopathy, especially in premature infants who are susceptible to brain damage associated with elevated bilirubin levels and may suffer from pathologically confirmed nuclear jaundice even without typical clinical manifestations. Visual single assessment and the practical significance of detecting the jaundice degree according to Cramer's rule during early discharge of children from the maternity hospital seem to be relatively low [2, 4].

The causes of neonatal jaundice are numerous, extremely diverse, and accompanied by indirect or direct hyperbilirubinemia or a combination of both. In each group of jaundice, hereditary and acquired causes can be distinguished.

Conjugation jaundice. This type of jaundice is manifested in hereditary diseases due to a defect in bilirubin uptake by hepatocytes (Gilbert’s disease), a defect in bilirubin conjugation (Crigler-Najjar syndromes type I, II), and features of the composition of breast milk (Lucey-Driscoll syndrome). The conjugation nature is intrinsic to physiological jaundice of newborns, jaundice caused by mother’s milk, jaundice of premature and immature newborns, as well as to jaundice in newborns with polycythemia, extensive cephalhematomas and intracranial hemorrhages; it is also characteristic of children born to mothers with diabetes mellitus, children with congenital hypothyroidism, pyloric stenosis, high intestinal obstruction, meconium ileus, intestinal paresis, and massive drug therapy [1][3][9].

Hemolytic jaundice. It is associated with the following reasons: hereditary pathologies such as erythrocyte membranopathy, enzymopathies, and hemoglobinopathies; cases of incompatibility of the mother’s and child’s blood by erythrocyte antigens; using a number of medications that destroy erythrocytes; hemolysis stipulated by infectious diseases (intrauterine infections, sepsis) if their pathogens and toxins have hemolytic properties; the presence of polycythemia or large hematomas in premature and injured children [1][4][9].

Parenchymatous jaundice. The causes of its occurrence are very diverse. In particular, it can be caused by hereditary metabolic disorders, including galactosemia, tyrosinosis, and fructose intolerance. In addition, it can be caused by exogenous factors, which include viruses (hepatitis B, C, rarely A, cytomegalovirus, rubella, herpes, Coxsackie), bacteria (listeria, treponema, mycobacterium tuberculosis, and mycoplasma); and parasites (toxoplasma); as well as antibacterial drugs (tetracycline, erythromycin, lincomycin, novobiocin) and total parenteral nutrition [1][3].

Mechanical jaundice. It is associated with atresia or hypoplasia of the extrahepatic bile ducts of the fetal type (syndromic anomalies of the bile ducts), familial non-syndromic cholestasis, symptomatic cholestasis in hereditary diseases (cystic fibrosis, adrenogenital syndrome, Dubin-Jones and Rotor syndromes), and cholestasis with dilation of the intrahepatic bile ducts (Caroli disease, congenital liver fibrosis, polycystic disease). Its occurrence can be caused by atresia/hypoplasia of the extrahepatic bile ducts due to perinatal hepatitis, intrahepatic atresia in primary biliary cirrhosis, primary sclerosing cholangitis, choledocholithiasis, tumors or bile thickening syndrome, as well as transient cholestasis in toxic hepatitis, multiple organ failure, blood transfusion, long-term parenteral nutrition, and massive antibacterial therapy [1][3].

It should be noted that some jaundices have a mixed genesis. Such an example is a case of a combination of hyperproduction of bilirubin caused by hemolysis and the impairment of bilirubin conjugation mechanisms (intrauterine infections, sepsis), resulting in a sharp increase in the bilirubin level in combination with anemia manifestation [4]. In other jaundices, an increase in the concentration of the direct fraction of bilirubin in the blood serum is noted.

It is also important to remember that the main causes of frequent indirect, non-hemolytic hyperbilirubinemia in young children are associated with the impaired conjugation of bilirubin in hepatocytes due to an insufficiently rapid increase in the activity of the liver glucuronyl transferase system after birth, retardation of passage through the intestine with increased reabsorption of bilirubin against the background of gastrointestinal tract obstruction, enterostasis or endocrine pathology, as well as hereditary pathology [4].

Up to a third of breastfed infants have been found to remain jaundiced after two weeks of life, and they account for the vast majority of visits with regard to prolonged jaundice. Exclusive breastfeeding and hyperbilirubinemia are closely related. For instance, a number of studies have shown that breastfed infants have higher bilirubin levels compared to formula-fed infants [1–4].

Physiological, transient jaundice appears 24–36 hours after birth. It increases during the first 3–4 days and begins to decline from the end of the first week of life, disappearing by the 2nd–3rd week. The general condition of the child is usually satisfactory; the liver and spleen are not enlarged, the color of feces and urine is normal. The concentration of bilirubin in the umbilical cord blood is less than 51 μmol/l; the concentration of hemoglobin is normal. Total bilirubin increases due to the indirect fraction, while the relative proportion of conjugated bilirubin is less than 15–`20%.

According to leading neonatologists [1], a number of indicators should be considered as signs of pathology, detecting deviations from the “normal” course of physiological jaundice. They include such manifestations as the appearance of jaundice before 24 hours of life, its late appearance or an increase in the second week of life, prolonged persistence for more than 3 weeks, “wave-like” course and the presence of signs of hemolysis associated with anemia and high reticulocytosis, as well as aggravation in the general condition of the child against the background of progressive jaundice and hepatosplenomegaly, dark urine and discolored stool, the level of indirect bilirubin (IB) in the cord blood serum of more than 60–85 μmol/l in the first 12 hours of life, the rate of IB increase of more than 3.4 μmol/l/hour, exceeding IB values on any day of life of more than 289 μmol/l, and the level of direct bilirubin of more than 25 μmol/l.

Additional examination is required for jaundice if previous children in the family had hyperbilirubinemia, which required treatment; if other family members had jaundice, anemia, liver disease, and splenectomy; if the mother took drugs or any medications during pregnancy and while breastfeeding; if the mother was sick during pregnancy with viral or other infections; if the child lost a lot of weight; if there were symptoms of hypothyroidism and metabolic diseases [1][2].

Breastfeeding jaundice (“hyperbilirubinemia of insufficient breast milk intake”) is usually associated with insufficient lactation during the first week after birth, which leads to increased reabsorption of bilirubin from the intestine and a transient deficiency of intestinal microbiota. In young children, this condition is characterized by insufficient milk intake, weight loss of more than 8–10% of the initial weight, decreased stool frequency, slower bilirubin excretion, and increased enterohepatic circulation. As the volume of feeding increases, metabolic processes are normalized, intestinal passage is restored, and jaundice is stopped [2].

Breast milk jaundice (long-term indirect hyperbilirubinemia with adequate milk consumption) is related to a genetic predisposition stipulated by a polymorphism of the gene, which determines the structure of the uridine diphosphate glucuronyl transferase isoenzyme, responsible for bilirubin conjugation [3][4]. This impairment results in the inhibition of bilirubin conjugation in the child’s liver by glucuronidation inhibitors found in breast milk, such as pregnanediol and non-esterified long-chain fatty acids. This process occurs in 2.4% of all children and begins at 3–5 days, reaching a maximum at 2 weeks of age (indirect bilirubin is more than 184 μmol/l). If breastfeeding continues, bilirubin gradually returns to normal levels over 3–12 weeks. However, if breastfeeding is interrupted, bilirubin levels may fall rapidly within 48 hours. When breastfeeding resumes, bilirubin may rise modestly (35–70 μmol/L). These infants with breast milk jaundice have good weight gain, normal liver transaminase levels, and no signs of hemolysis.

The above-mentioned breastfeeding jaundices can be the cause of prolonged, up to 3 months, unconjugated hyperbilirubinemia, which is always physiological. Yellowness of the skin appears in approximately 60% of full-term and late premature infants, for whom mother’s milk is the best nutrition from a clinical and biological point of view.

The prognosis of this polyetiological disease depends on the rapidity and adequacy of the examination of the newborn and the efficacy of the complex therapy.

The purpose of the study is to highlight the problems, which primary care pediatricians and hospital neonatologists face when attempting to make early diagnostics of the cause of jaundice or its protracted course in children in the neonatal period. Unfortunately, prenatal and early natal diagnostics of neonatal hyperbilirubinemia are sometimes difficult.

A study was devoted to the investigation of the etiostructure of neonatal jaundice and the features of its clinical course in the Department of Pathology of Newborns and Premature Infants of the Research Institute of Obstetrics and Pediatrics (DPN and PI RIOP), which made it possible to identify the main risk factors for its development and the correlation/correction of the severity of the course depending on the etiology.

Materials and methods

The work was carried out at the clinical base of the Federal State Budgetary Educational Institution of Higher Education Rostov State Medical University of the Ministry of Health of the Russian Federation in the Research Institute of Obstetrics and Pediatrics in the Department of Pathology of Newborns and Premature Infants. An analysis of the structure of morbidity of young children with jaundice was carried out for 2021. A description of a clinical case of indirect hyperbilirubinemia is given.

The total number of newborns hospitalized in 2021 in the DPN and PI of the RIOP amounted to 700 cases. Of these, 157 children were hospitalized with hyperbilirubinemia syndrome (22.4%). The following clinical and laboratory characteristics of the disease were studied: complete blood count (CBC), general urine analysis, blood biochemistry (total protein and its fractions in blood serum, bilirubin level and its fractions, AST and ALT), PCR diagnostics and ELISA on herpes viruses types 1, 2 and 6, Epstein-Barr virus and Cytomegalovirus, as well as the severity of clinical manifestations in the child according to the level of bilirubin in the blood serum, and the results of additional examination methods including neurosonography (NSG), ultrasound of the abdominal organs, ultrasound of the heart, and electrocardiography.

Results

The analysis of 157 medical records of patients showed that neonatal jaundice was the main disease. All children with jaundice syndrome were admitted to the department with a preliminary diagnosis of “Neonatal jaundice, unspecified” (P59.9 according to ICD-10). The average maternal age was 31 years. An adverse obstetric and gynecological history was found in the overwhelming majority of mothers (91.1%): previous medical abortions, miscarriage, frozen pregnancy, and stillbirth. Almost all women (98.7%) had a complicated course of the pregnancy associated with anemia, toxicosis, and the threat of termination of pregnancy at various stages.

The average age of children with hyperbilirubinemia admitted from the maternity hospital to the DPN and PI was 6 days; of which 61.1% were boys; the average birth weight was 3300 g. In most cases (70.7%), icteric discoloration of the skin and sclera was detected on the 3rd–4th day of life. The overwhelming majority of children were full-term (65.0%).

In hospitalized young children, the conjugation jaundice took the leading place (47.8%), the causes of which were prematurity and immaturity of newborns, jaundice of maternal milk, polycythemia, diabetic fetopathy, cephalohematomas, and intracranial hemorrhages.

Hemolytic jaundice was observed in 5.7% of young children, the main cause of which was hemolytic disease stipulated by Rh and group antigenic factors. Parenchymatous jaundice accounted for 7% of the total number and was a consequence of infectious liver lesions due to intrauterine infections on its etiological structure.

Mechanical jaundice caused by extrahepatic cholestasis (in particular, compression of the common bile duct) was observed in 4.5% of young children.

It should be noted that the concomitant pathology in 26% of children was intrauterine and intranatal hypoxia, while 9.0% of patients had cephalhematomas, subdural hematomas, and intracranial hemorrhages, as well as hemorrhages into the skin, which were accompanied by hyperproduction of bilirubin, hemolysis of erythrocytes, and a protracted course of the disease.

Description of a clinical case

The girl was born on March 31, 2023, in the maternity ward of the Research Institute of Obstetrics and Pediatrics of the Federal State Budgetary Educational Institution of Higher Education Rostov State Medical University from a young primiparous mother with blood group O (I) (anti-A antibody titer 1:4), who had an aggravated somatic and infectious history: type 1 diabetes mellitus, grade 2 diabetic encephalopathy, grade 2–3 diabetic sensorimotor polyneuropathy, chronic pyelonephritis, myopic astigmatism of both eyes, and chronic gastritis. Pregnancy I was proceeding extremely unfavorably since the first half was associated with manifestations of type 1 diabetes mellitus, irregular glycemic control; threat of miscarriage and hospital treatment at 15–16 weeks. The second half of pregnancy was complicated by hyperglycemia 17.0 mmol/l and nagging pain in the lower abdomen (hospital treatment at 27.5 weeks; prophylaxis of fetal RDS was performed); grade 1 anemia; swelling of the shins and feet; hypothyroidism, asymptomatic bacteriuria, and an increase in blood pressure to 135/90 mm Hg.

The delivery was operative and performed at a gestational age of 38.2 weeks. A female child was born with a weight of 3500 g, a length of 50 cm, a head circumference of 34 cm, a chest circumference of 35 cm, and an Apgar score of 8–9. Signs of diabetic fetopathy were revealed at birth. The child cried immediately, the cry was loud, and she turned pink on her own. The umbilical cord was in a clamp. The head was round; the large fontanelle was 1.0×1.0 cm at the level of the skull bones. Breathing was rhythmic and did not involve the accessory respiratory muscles. During auscultation, the breathing was puerile, evenly distributed throughout the body, and no wheezing was heard. Heart sounds were loud and rhythmic. The abdomen was soft; the liver and spleen were not enlarged; the anus was “+”. The external genitalia were of the female type and developed correctly. Muscle tone was slightly reduced, and reflexes were elicited.

In the children’s department of the maternity hospital, the child’s condition was assessed as satisfactory. The CBC was monitored on the 2nd day of life and was as follows: Er 5.3 × 10¹²/l, Hb 198 g/l, Leuk 12.2 × 10⁹/l, Tr 245 x 10⁹/l; leukocyte formula without pathology; the hematocrit level was 56.6. Umbilical cord bilirubin included the detection of total bilirubin (34.5 μmol/l) and direct one (9.4 μmol/l); glycemia was at the levels of 2.8–3.5–3.7–4.2–4.6 mmol/l. The signs of a non-critical amount of dysembryogenesis stigmas were noted. The umbilical cord was in a staple. The baby was in joint stay and on breastfeeding from the first day; she sucked well and did not regurgitate.

From the 4th day of life, an increase in the yellowness of the skin was revealed; the skin was “marbled”, subicteric against the background of erythema of the newborn; transcutaneous bilirubin amounted to 280 μmol/l, venous bilirubin was 292.4 μmol/l, direct one was 7.5 μmol/l; the glucose level was 5.1 mmol/l. The assessment of the neurological status revealed muscle dystonia, a positive Babinski reflex on both sides, and a decrease in spinal automatisms. According to the neurosonography data from April 3, 2023, two small periventricular cysts were located on both sides, and on the right in the caudo-thalamic region, there was a subependymal pseudocyst and diffuse hypoxic-ischemic changes in the parenchyma of the brain. Venous outflow was not difficult.

Phototherapy with eye protection was started. Considering the presence of signs of diabetic fetopathy, yellowness of the skin with an increase in the level of indirect bilirubin, and the presence of neurological symptoms, the child was transferred for further examination and treatment to the DPN and PI with the diagnosis of “Neonatal jaundice (unspecified). Stage 1 cerebral ischemia, acute period, autonomic dysfunction syndrome. Syndrome of the newborn from a mother with diabetes mellitus: diabetic fetopathy. Intrauterine infections?”

In the department, the child was placed in a crib. Phototherapy was started in continuous mode. The general condition of the child was moderate; skin and mucous membranes were erythematous, icteric; “marbling”; perioral acrocyanosis, increasing with anxiety and exertion, was pronounced. Transcutaneous bilirubin amounted to 268 μmol/l. Body weight was 3328 g, body length was 50 cm, head circumference was 34 cm, chest circumference was 35 cm, body temperature was 36.7° C, HR was 138 beats per min, RR was 40 per min, SO₂ was 97%. Nutritional status was satisfactory.

During the examination, the following additional features were revealed: dry skin and its purple-blue tint, swelling of the legs and lower back, subicteric sclera, and satisfactory turgor. The lymph nodes were not enlarged and were painless on palpation. Signs of diabetic fetopathy included pastosity of soft tissues, friability of subcutaneous fat, puffiness of the face (moon-shaped) and erythema with a cyanotic tint of the skin, edematous eye slits, short neck, and wide shoulder girdle. The large fontanelle was 2.0 × 2.0 cm, the small fontanelle was closed, and sutures were clamped. Skull bones were dense, the chest was cylindrical, extremities were not deformed.

The respiratory system was characterized by the following features: the RR was 40/min, breathing was rhythmic without the participation of accessory muscles, and SO₂ was 96%. On percussion, the pulmonary sound was present throughout; on auscultation, breathing was weakened and was carried out in all areas; no wheezing was detected. No runny nose or cough was revealed. The apical impulse of the heart was in the IV intercostal space; on auscultation, the heart tones were rhythmic, somewhat muffled, with a gentle systolic murmur at the apex. The mucous membranes of the cheeks and tongue were clean; appetite was preserved. The pharynx was calm. The abdomen was soft and painless; peristalsis was audible. No regurgitation or vomiting was noted at the time of examination. The condition of the umbilical wound had the following features: the umbilical cord remnant was in a staple, in the stage of mummification. The liver was + 2.0 cm from the edge of the costal arch; the edge was elastic. The spleen was at the edge of the costal arch. Stool was yellow-green, mushy. The genitourinary system was developed according to the female type and formed correctly.

The child was conscious; the examination was accompanied by motor activity and painful crying. Cranial nerves did not show any visible pathology. The motor sphere was characterized by the range of active movements, which was slightly reduced; passive movements were in full range. Tendon reflexes were evoked, quickly faded, D=S. There were no meningeal signs. Physiological reflexes of oral-spinal automatisms quickly depleted, the sucking reflex was active. During verticalization, the support reflex was “-” with knee bending; the stepping reflex was “-”, the grasping reflex was “-”, and the crawling reflex was “-”. The eye slits were clear; the pupil diameter was normal, D=S; the reaction to light was lively; inconstant convergent strabismus was noted. Muscle tone was dystonic with a tendency to hypotension. Tremor of the chin during anxiety; twitching, convulsions, and convulsive readiness were not noted. Positive Babinsky reflex on both sides was revealed.

As can be seen from the indicators given in Tables 1–4, the child’s blood manifested the presence of monocytosis (15%), polycythemia (hemoglobin 201 g/l, hematocrit 61.4%), a tendency to hypoglycemia (2.9 mmol/l), a high level of indirect bilirubin fraction indicated by transcutaneous and biochemical methods, and low oxygen content in the blood. Blood glucose levels were monitored twice daily; no episodes of hypoglycemia were observed.

Observation of the child in dynamics against the background of phototherapy (Tables 1, 4, 5, 6) revealed the absence of inflammatory changes in the hemogram and a moderate decrease in total bilirubin. The repeated NSG study established the presence of bilateral intraventricular hemorrhages of the 1st degree, signs of immaturity of the brain, diffuse hypoxic-ischemic changes in the parenchyma of the brain, edema of the periventricular zones, and moderate dilation of the 3rd ventricle and interhemispheric fissure. The immunological study (Tables 5, 6) showed the absence of antibodies to the herpes virus, cytomegalovirus, and Epstein-Barr virus.

Infectious diseases were not detected in the child, and the indicators of a hormonal study of thyroid function were normal (Table 7) despite the presence of initial monocytosis according to the CBC in the absence of inflammatory changes and a number of other unfavorable factors including a significant burden of maternal history on endocrine (type 1 diabetes mellitus and hypothyroidism) and infectious pathology (asymptomatic bacteriuria and multiple threats of miscarriage during pregnancy); as well as the bacterial contamination of the umbilical wound, pharynx, and nose of the child (Table 8); and the presence of a congenital isolated malformation of the right eye (coloboma of the iris, optic nerve, and retina).

Further consultations with medical specialists and instrumental examinations were carried out to clarify the diagnosis:

1. NSG and Doppler ultrasonography of the cerebral vessels on April 7, 2023 indicated the following: S:D=1.1:1.1 mm, the 3rd ventricle was 4.1–4.4 mm, V. Gall was 9.4 cm/s. Besides, it revealed IVH grade 1 on both sides, signs of brain immaturity, diffuse hypoxic-ischemic changes in the brain parenchyma, edema of the periventricular zones, moderate dilation of the 3rd ventricle, and interhemispheric fissure; Doppler ultrasonography showed cerebral venous dysgemia of the intracranial liquorodynamic type.
2. Ultrasound of the abdominal organs and urinary system on April 6, 2023 revealed no pathology at the time of examination. A slight increase in liver size was detected.
3. Heart ultrasound on April 7, 2023 showed that myocardial contractility was preserved.
4. Ophthalmologist consultations on April 7, 2023 and April 11, 2023 established congenital coloboma of the iris of the right eye; congenital coloboma of the optic nerve disc and retina of the right eye. A planned consultation with a pediatric ophthalmologist of the Regional Children’s Clinical Hospital was recommended after discharge from the department.

Complex treatment carried out in the DPN and PI of RIOP included vitamin therapy by alternating pyridoxine (vitamin B6) and thiamine chloride (vitamin B1) according to the scheme; probiotic bifidumbacterin; orthopedic collar Shantz; and phototherapy.

Based on the anamnesis, clinical symptoms, and the results of laboratory and instrumental studies, the child was given a clinical diagnosis.

Main clinical diagnosis (2 competing):

• 8 Neonatal jaundice stipulated by other specified causes (intraventricular hemorrhages).
• P 52.0 Intraventricular (non-traumatic) hemorrhage of the 1st degree on both sides. Moderate cerebral ischemia, acute period, muscular dystonia syndrome, vegetative-visceral syndrome.

Associated clinical diagnoses:

• 1 Functioning fetal communications: patent foramen ovale.
• 2 Congenital isolated malformation of the right eye: coloboma of the iris, optic disc and retina of the right eye.
• 1 Syndrome of newborn born to a mother with diabetes: diabetic fetopathy.

The dynamics of the disease was positive: the child began to gain weight; neurological symptoms and jaundice of the skin decreased; the level of total bilirubin in the serum reduced to 126 μmol/l; motor activity was at full capacity, and there were no episodes of hypoglycemia during the stay in the department.

The cause of prolonged jaundice in a newborn with diabetic fetopathy was due to polycythemia and immaturity of the enzyme systems of hepatocytes.

The child was discharged on the 12th day of life in satisfactory condition under the supervision of a local pediatrician, neurologist, and ophthalmologist. The recommendations were given.