A case of severe combined pathology in a late premature infant with hypoxic-ischemic damage to the central nervous system

Introduction

The physiological course of pregnancy is the most important factor for adequate growth and development of the child not only in utero but also postnatally; it largely determines the formation of health in the future [1].

According to data from 2018, the prevalence of premature birth in the Russian Federation was 6% of the total number of births¹. At the present time, the problem of premature birth remains highly relevant, which is associated with a high level of perinatal and infant morbidity and mortality [2]. The category of late prematurity includes children born as a result of premature birth, born between the gestational ages of 34 + 0 and 36 + 6 weeks, or between 239 and 259 days from the first day of the last menstruation. In foreign literature for several decades, late premature babies have been defined by several terms: late preterm, marginally preterm, moderately preterm, minimally preterm, and mildly preterm. The increase in the prevalence of late preterm birth in the world is associated with several reasons: an increase in the frequency of medical interventions and surgical delivery, multiple pregnancies, the number of women with an unfavorable obstetric and gynecological history and complications of pregnancy, as well as improved obstetric care and improved monitoring of pregnant women [3]. Nursing premature newborns is a priority area of national health. In Russia, premature newborns are 4–16% of all newborns. On average, early neonatal mortality accounts for up to 28%. It should be noted that premature birth often increases the risk of various complications. They are characterized by a higher incidence of respiratory system diseases, hyperbilirubinemia, neurological and metabolic disorders, and nutritional and feeding problems [4]. In this regard, interest in studying the features of adaptation, the course of the neonatal period, as well as the long-term outcomes of newborns of late premature age does not diminish.

The purpose of the study is to diagnose and treat severe combined pathology in a late premature infant with hypoxic-ischemic central nervous system (CNS) injury.

Case report

The child Muhammad M. was admitted from the maternity hospital to the Department of Pathology of Newborns and Premature Infants of Rostov Medical University Obstetrics and Pediatrics Research Institute for examination and treatment.

The child was born to a mother with type 1 diabetes, chronic cystitis, pyelonephritis in remission, class III obesity, arterial hypertension, ventral hernia, varicose veins of the lower extremities, with a burdened obstetric and gynecological history (miscarriage, frozen pregnancy). The child was from the 6th pregnancy. This pregnancy proceeded with an increase in blood pressure. During an ultrasound examination, hepatomegaly and signs of diabetic fetopathy in the fetus were revealed in the 34th week of the gestation period. In urinalysis, leukocyturia was revealed; microbiological examination of urine revealed fungi of the genus Candida albicans 103 CFU\ml, in those separated from the cervix – Candida albicans 107 CFU\ml. At the 31–32 weeks of gestation, threatening premature birth was noted, which required hospitalization of the mother. Delivery was at 34 weeks and 4 days of gestation. Birth weight was 3600 g, length was 50 cm, head circumference was 37 cm, and chest circumference was 36 cm. Apgar score was 4–5–6 points. The child was born in a serious condition due to prematurity, morpho-functional immaturity, diabetic fetopathy, and respiratory failure (8 points of Silverman score). Skin cyanosis, decreased response to examination, muscle atony, hyporeflexia, dysrhythmic respiratory movements of the gasping type with intercostal retraction, and inflation of the nose wings were noted immediately after birth. With auscultation, breathing in the lungs was sharply weakened, which required artificial lung ventilation. Due to the continuing serious condition and the need to continue respiratory therapy, the child was transported to the intensive care unit for further treatment in a heated transport cuvez on an intensive care vehicle on transport artificial lung ventilation.

The child was admitted to the intensive care unit on the 1st day of life. The condition was extremely serious, due to respiratory failure, which required respiratory therapy in the form of artificial lung ventilation, neurological symptoms, and signs of diabetic fetopathy.

The skin was pale pink. Perioral and acrocyanosis were observed, decreasing with oxygen therapy. There were hematomas in the right hand, forearm, and feet. Visible mucous membranes were moist and pink. There were pasty facial tissues. Heart tones were muffled and rhythmic. The patient was on artificial lung ventilation. Auscultation breathing was carried out in all parts of the lungs and was weakened in the posterior-lower parts. In the posterior regions of both lungs, crepitus was heard. The abdomen was soft, moderately swollen, and painless on palpation. A catheter was located in the umbilical vein. The liver was located +2 cm from the edge of the costal arch, Spleen was not enlarged. Urination was independent, urine was straw-yellow. Stool was meconial. The genitourinary system was formed according to the male type.

Neurological status: the child was lethargic. For examination, the reaction was reduced. Spontaneous locomotor activity was decreased. The large fontanelle was 2.0 × 2.0 cm, not stressed. Muscle tone was increased. Reflexes of oral-spinal automatism were reduced. No seizures were noted. There were no meningeal symptoms. The pupil diameter was normal, D = S. There was horizontal spontaneous nystagmus. Tendon reflexes were alive S = D.

The child was in the intensive care unit for 16 days and then was transferred to the Department of Pathology of Newborns and Premature Babies, where he stayed for 18 days. During hospitalization, all the necessary laboratory and instrumental diagnostics were carried out, which made it possible to make the main and concomitant diagnoses and to determine the tactics for managing and treating this child.

At the time of hospitalization on the 1st day, neutropenia (34%) and eosinophilia (12%) attracted attention in the complete blood count; no pathology was detected in the urinalysis. Monitoring of the acid-base state of the blood showed respiratory alkalosis and hyperlactatemia (5.77 mmol/L). A biochemical study revealed hyperbilirubinemia (141.6 μmol/L) and a direct fraction (45.4 μmol/L – 32% of the total).

During the course of the disease, anemia increased in the complete blood count (erythrocytes – 3.13 × 1012/L; hemoglobin – 98 g/L), in the biochemical blood test, an increased level of direct bilirubin (21.7 μmol/L – 25.1% of the total) remained against the background of a decrease in the level of total bilirubin (86.3 μmol/L),. At the same time, there was an increased level of aspartate aminotransferase up to 39.0 μmol/L. On the 10th day of life, there was a decrease in the level of total protein (40.1 g/L) and albumin (28.4 g/L), followed by normalization over time. The levels of urea and glucose were kept within the standard values. A coagulogram examination did not reveal a decrease in the synthesis of coagulation factors.

Audio screening was performed: L (+), R (+).

Instrumental examinations

The neurosonogram showed the level of the ventricular index (29%). Lateral ventricles – S:D 2.7:2.4 mm, III ventricle – 3.0 mm. Increased echogenicity of the periventricular region, subcortical nuclei, and thalamus was shown. Heterogeneity of vascular plexuses was shown. Some dilatation of the interhemispheric fissure and subarachnoid space was shown.

Diffuse hypoxic-ischemic brain parenchymal changes were revealed.

Signs of brain immaturity were found. On the left, in the projection of the posterior horn, platelet concentrate was determined in the lysis stage (intraventricular hemorrhage of the 2nd degree); on the right in the area of the anterior horn of the lateral ventricle – subependymal hematoma at the stage of lysis 2.0 × 4.5 mm. Signs of intraventricular hemorrhage of the 2nd degree on the left were found.

Signs of grade I intraventricular hemorrhage on the right was found. Moderate dilatation of the interhemispheric fissure, subarachnoidal space, lateral ventricles in the area of the bodies, and the posterior horn of the lateral ventricle on the left were observed.

Transcranial Doppler imaging showed marked cerebral venous dysgemia by intracranial liquorodynamic type.

Ultrasound examination of the abdominal cavity and kidneys revealed non-coarse changes in the liver parenchyma and inflection of the gallbladder.

According to echocardioscopy, the fetal duct (open oval window) was functioning, myocardial contractility was preserved. Botall's duct was buried.

According to electrocardiography, tachyarrhythmia was recorded; the heart rate was 170–180 beats per minute. Moderate changes in the ventricular myocardium were observed.

Consultations with narrow specialists were also held. An ophthalmologist: organs of vision were without visible pathology, grade I retinal angiopathy of both eyes was found. An endocrinologist: diabetic fetopathy was found. A pediatric neurologist: chronic intrauterine hypoxia was observed. Grade II cerebral ischemia was found. Grade 2 intraventricular hemorrhages in the posterior horn of the lateral ventricle, grade 1 hydrocephalus syndrome, and muscular dystonia syndrome were found.

Based on clinical, laboratory, and instrumental data, the child was given the main clinical diagnosis "Other cases of prematurity: prematurity at a gestational age of 34.5 weeks with a weight of 3600.0, a large fetus for gestational age". The combined main clinical diagnosis was "Сongenital early bilateral pneumonia" (Candida parapsilosis etiology), DN II.

Concomitant clinical diagnoses were "Candidiasis of the newborn. Grade 2 intraventricular hemorrhage in the region of the posterior horn of the lateral ventricle on the left, grade 1 in the region of the anterior horn of the lateral ventricle on the right. Newborn syndrome from a mother with diabetes: diabetic fetopathy, macrosomal form. Neonatal jaundice associated with preterm delivery. Functioning fetal communications – an open oval window; open ductus arteriosus (closed). Respiratory disorder syndrome".

A complication of the underlying disease was mild anemia of prematurity.

The child underwent the following treatment:

• antibiotic therapy: ampicillin + sulbactam, amikacin, zivox, cefepime, netilmicin;
• infusion therapy: glucose 10% with components, 10% aminovene, 20% SMOF – lipid;
• antifungal therapy: fluconazole, voriconazole;
• antihemorrhagic therapy: 1% Vicasol, 12.5% Dicynone; freshly frozen quarantined plasma A (II) Rh negative;
• respiratory analeptic –20% caffeine;
• respiratory therapy: artificial lung ventilation, non-invasive lung ventilation in the SNIPPV mode, spontaneous breathing with positive airway pressure;
• enteral feeding: pre-NA – 40.0 mL every 3 hours through an orogastric tube;
• antianemic therapy – ferrum-lack;
• metabolic therapy – cytoflavin;
• biologics – bifidum bacterin;
• nootropic therapy – cortexin;
• symptomatic therapy – sabsimplex, aquamaris.

During the therapy, stabilization of the condition was noted, the general condition was satisfactory. The child was calm. The reaction to the inspection was a loud cry.

Motor activity was in full value. Positive weight gain: the child added 460 g in weight and increased the length by 6 cm in 1 month and 3 days. Tendon reflexes: S = D, live. The muscle tone was satisfactory. Physiological reflexes were evoked. There was an increase in the volume of spontaneous motor activity. Symptoms of respiratory failure and icteric skin disappeared. Puerile breathing was in the lungs. There was no shortness of breath. Percutaneous pulmonary sound and auscultatory puerile respiration were observed. Heart tones were muffled and rhythmic; the abdomen was soft and painless. The liver was at the edge of the costal margin, the spleen was not enlarged. Urination was not impaired, adequate. The child was discharged in satisfactory condition at the place of residence.

Discussion

The peculiarity of this case was the combined nature of the pathology in a late premature infant. There was demonstrated an extremely unfavorable effect of maternal pathology, in particular diabetes mellitus, on the intrauterine state of the fetus, which led to the birth of a premature baby, followed by the development of hypoxic-ischemic damage to the CNS, intraventricular non-traumatic hemorrhages and diabetic fetopathy, hyperbilirubinemia, and the implementation of the infectious process in the form of congenital bilateral pneumonia and neonatal candidiasis. The detected structure of morbidity in a late preterm patient treated in the neonatal pathology department did not differ from the existing literature [5].

In newborns from mothers with diabetes mellitus, the risk factors for the formation of hypoxic-ischemic damage to the CNS are not only intrauterine hypoxia as a damaging factor, but also hyperglycemia, leading to intrauterine and postnatal hyperproduction of insulin, which leads to metabolic disorders in the developing brain of the fetus and newborn and the formation of cerebral disorders.

This clinical case confirms the available literature data that 30% of late premature newborns need intensive therapy in the early neonatal period. Taking into account the combination of pathologies, a multidisciplinary approach should be used in their management [6].

Conclusion

Despite the fact that late premature newborns have anthropometric data at the time of birth comparable to full-term ones, their incidence rates in the early neonatal period are higher. Neonatologists should be wary of this population of children in order to timely determine the scope of the complex of therapeutic measures.