RU2314526C1 - Method for predicting the development of ventriculomagaly in neonatals after perinatal hypoxia - Google Patents

Abstract

FIELD: clinical medicine, pediatrics.

SUBSTANCE: the present innovation deals with predicting ventriculomegaly in neonatals after hypoxia under in-patient conditions. It is necessary to sample venous blood in neonatals on the 4^th - 7^th d of life to detect the quantity of HCO₃ ions and its value being under 21 mM/l one should predict the risk in the development of ventriculomegaly. The innovation enables to predict the development of ventriculomegaly during the 1^st wk of life by the end of the 1^st mo of life in neonatals after perinatal hypoxia that favors earlier diagnostics and therapy of the disease in question.

EFFECT: higher efficiency and accuracy of prediction.

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Description

The present invention relates to clinical medicine, pediatrics and can be used to predict the development of ventriculomegaly in newborns undergoing hypoxia in a hospital.

Posthypoxic brain damage is a problem that has long been in the focus of attention of researchers both in our country and abroad. This is due to the prevalence of the disease and the severity of the consequences. So, in the structure of childhood disability, damage to the nervous system is about 50%, while in 70-80% of cases they are due to perinatal factors [1].

One of the leading syndromes of perinatal damage to the central nervous system of hypoxic origin is hydrocephalic [2, 3, 4]. The frequency of development of hydrocephalic syndrome according to different authors ranges from 0.28 to 3 per thousand born alive. By the year, the number of children with identified hydrocephalic syndrome increases to 1% [5].

Ventriculomegaly is one of the manifestations of hydrocephalic syndrome according to the classification of Yakunin and Yampolskaya or hydrocephalus according to the ICD X. According to the data of Zubareva EA and others. Light ventriculomegaly is considered to be an increase in the size of the ventricular system to 5-8 mm, moderate - with the size of the lateral ventricles of 8-9 mm, III ventricle of 5-6 mm, severe - with the size of the lateral ventricles of more than 9, III of the ventricle - more than 6 mm.

Moreover, studies by foreign authors have shown that ventriculomegaly at an early age leads to impaired formation of cognitive and motor functions in preschoolers and schoolchildren [6]. In addition, normotensive hydrocephalus, which does not require surgical treatment, with progression can transform into a hypertensive variant, in which the patient needs a shunt [7]. Moderate ventriculomegaly may be the first manifestation of this disease.

Therefore, issues of early diagnosis of ventriculomegaly to address the issue of subsequent therapy are especially important.

Currently, predicting the development of ventriculomegaly in newborns who have undergone hypoxia is practically not carried out due to the lack of a clearly developed technique. An analysis of the relationship between the development of ventriculomegaly by the end of the first month of life and the presence of changes in biochemical parameters in the early neonatal period was not carried out.

Closest to the proposed method can be considered a method for assessing the degree of hypoxia and predicting the expected outcome in premature infants with peri-, intraventricular hemorrhages [8].

For all children during the diagnostic collection of cerebrospinal fluid, part of the material was taken in glass heparinized capillaries with anaerobic plugs to determine the indicators of acid-base balance (pH, НСО ₃ ^- , BE) and gas composition (pCO ₂ , pO ₂ ). In parallel, within half an hour, the same parameters of capillary blood obtained by the same anaerobic method were determined. The material was studied on a Radiometer ABL 500 apparatus (Denmark). The parameters from previously published sources were taken outside the normal range. The first blood and cerebrospinal fluid samples were taken 1-3 days after the transfer of the newborn from the maternity hospital. Age at admission ranged from 2 to 12 days. It was concluded that mixed cerebrospinal fluid acidosis, including both metabolic and gas components, lasting longer than the 20th day of life, is an unfavorable prognostic sign of the outcome of peri-, intraventricular hemorrhages in premature infants. The worst prognostic criterion for a long-term outcome is a decrease in the base deficit below 10 mmol / l by the 20th day of a child’s life, which in all children determines a gross neurological defect with deep disability in the future. With BE - 4 mmol / l and higher, a favorable outcome of the disease with social habitation of the child was observed in 84% of cases.

However, to assess the risk of ventriculomegaly in all children who have experienced, along with severe, moderate hypoxia, this method is not applicable.

Firstly, in the prototype, the acid-base state is determined in the cerebrospinal fluid, a biological environment that is not always available for research. Lumbar puncture with a cerebrospinal fluid intake is performed according to strict indications and cannot be recommended to all children who have undergone hypoxia.

Secondly, the age at which the study was conducted was not strictly defined. As you know, in the first three days of life in newborns, especially premature infants who underwent hypoxia, hemodynamic instability is noted, which cannot but affect the acid-base state of the blood and cerebrospinal fluid. At this time, changes in the acid-base balance and gas composition to a greater extent reflect transient changes. At the age of 20 days, therapy may be somewhat late.

Thirdly, there was no analysis of the dependence of acid-base disorders on the leading neurological syndrome.

And, finally, the study included the determination of the full range of indicators characterizing the gas composition and the acid-base composition of the cerebrospinal fluid, which requires observing the strictest sampling rules (it is practically impossible to avoid contact of the cerebrospinal fluid with air at this moment) and complicates the interpretation of the results.

The objective of the invention is the development of an affordable and reliable method for early prediction of the risk of ventriculomegaly in newborns admitted for treatment to a hospital with a diagnosis of perinatal CNS damage of hypoxic origin.

This object is achieved by a method of forecasting the development ventriculomegaly in newborns with perinatal hypoxia, by examining the ion HCO ₃ ^- in biological fluid and is achieved by the fact that for the study of a newborn taking venous blood for 4-7 days of life, it is determined in the amount of ions HCO ₃ ^- and with a value below 21 mmol / L, the risk of ventriculomegaly is predicted.

We believe that the level of venous blood bicarbonates most fully reflects the possibility of developing ventriculomegaly due to increased formation of cerebrospinal fluid, since cerebrospinal fluid and blood have similar mechanisms for compensating metabolic acidosis due to the activation of the carbonic anhydrase enzyme contained in the epithelium of the vascular plexuses and erythrocytes and catalyzing the formation of carbonic acid. The term "bicarbonates" refers to HCO ₃ ^- ions that are part of the bicarbonate buffer system, as is customary in domestic literature. Of all the buffer systems of the body, bicarbonate is the most labile. And the level of bicarbonates in venous blood most accurately reflects the contribution of tissue metabolism to the acid-base state of the blood. Bicarbonate ion is the predominant form of CO ₂ in the blood. The bicarbonate anion is the product of the reaction of CO ₂ with water to form carbonic acid and its dissociation. The blood-brain barrier is relatively impenetrable for H ⁺ and HCO ₃ ^- ions. But if the pH shift of the cerebrospinal fluid persists for a long time, then bicarbonates cross the blood-brain barrier. [9]

In the available literature, the authors did not find a similar method for predicting the development of ventriculomegaly in newborns undergoing hypoxia. Therefore, they believe that the solution is new and meets the criterion of "inventive step".

We examined 43 children admitted to the neonatal pathology department of Children's Clinical Hospital No. 1 of Nizhny Novgorod with a diagnosis of perinatal central nervous system damage of hypoxic genesis of moderate severity. 34 babies were full-term, 9 were born with gestational age of 35-37 weeks. Periventricular hemorrhages of the I degree at neurosonographic (NSG) examination were detected in 32 children. All children had echographic signs of hypoxia. All children were observed in dynamics. The examination included a clinical examination, conducting standard laboratory tests, NSG and determination of venous blood bicarbonates in dynamics on days 4-7, 10-14 and at the end of the neonatal period.

Blood for the study was taken from the peripheral vein by venipuncture into a plastic heparinized syringe with a plug and delivered to the laboratory within 10 minutes after collection. The study was conducted on a Radiometer ABL 555 analyzer (Denmark). Statistical processing was performed using the program Stadia 6.0. Data are presented as M ± σ. The data obtained were compared with age standards [4].

Of the 43 children, ventriculomegaly by the end of the first month of life developed in 8 newborns. At the same time, 4 children from this group had clinical signs of intracranial hypertension. In the group of children who did not develop ventriculomegaly, signs of intracranial hypertension were observed in 16 newborns. Thus, the clinical manifestations of perinatal CNS damage in both groups were similar and could not help in deciding on the appointment of dehydration therapy. (Differences are not significant: chi-square = 0.03; p = 0.862).

When determining the level of venous blood bicarbonates, the following patterns were identified.

1. Decompensated metabolic acidosis was not detected in any child (pH remained within the age norm).

2. 7 out of 8 children in the group with ventriculomegaly had a level of bicarbonates below 21 mmol / L on the 4-7th day of life. In a group of children with normal ventricular sizes, 7 out of 35 children had this level of bicarbonates. The differences between the groups according to this criterion are significant: chi-square = 10.612; p = 0.001.

3. 5 children with ventriculomegaly had a level of bicarbonates - below 19 mmol / l. In the second group of such children there were 4. The differences between the groups according to this criterion are also significant: chi-square = 7.409; p = 0.006.

4. In children with later developed ventriculomegaly, the level of venous blood bicarbonates on days 4-7 was significantly lower (19.46 ± 2.832 mmol / L) than in newborns who had normal ventricular sizes (23.14 ± 2.882 mmol / L) ( t = 3.301; p = 0.0023).

5. All children from the second group (with normal ventricular sizes) who had low bicarbonate values received diacarb for the first month of life according to clinical indications. Perhaps the absence of ventricular dilatation indicates the effectiveness of the therapy.

Thus, the level of venous blood bicarbonates is an indicator reflecting the probable risk of developing ventriculomegaly. Their determination is recommended to be carried out on 4-7 days of life and if their level is reduced to 21 mmol / l, the risk of ventriculomegaly by the end of the neonatal period is considered significant, and if it is reduced to 19 mmol / l or less, it is high.

The question of the appointment of treatment in each case should be decided individually, since it is possible that ventriculomegaly in some cases is compensatory in nature.

The following are extracts from case histories illustrating the development of the pathological process in newborns undergoing hypoxia.

Example 1 illustrates the course of a disease in an only child with developed ventriculomegaly without lowering the level of bicarbonates in venous blood.

Boy S. was admitted for treatment to the Department of Pathology of Newborns at the age of 4 days with a diagnosis of perinatal CNS damage of hypoxic genesis, prematurity of the 1st st. The boy from the first pregnancy, proceeding against the background of anemia of the first degree, the mother has a diffuse increase in the thyroid gland of the 1st degree Childbirth at 36 weeks of gestation. Early discharge of amniotic fluid was noted, amniotic fluid turbid. Body weight at birth 2000 g, body length 45 cm, head circumference 29 cm, chest circumference 26 cm. Apgar score 6/7 points.

Condition upon admission to the moderate department. Spontaneous motor activity and muscle tone are moderately reduced, newborn reflexes from the arms are caused, from the legs - are weakened. The large fontanel is 2.5 × 2.5 cm, the edges are supple, the discrepancy of the sagittal suture is up to 0.5 cm, the small fontanel is 1 × 1 cm. The skin is clean, pale. Heart sounds are muffled, rhythmic. Heart rate - 154 per minute. Pueryl breathing, fine bubbling rales on both sides. BH - 54 per minute. Hypospadias.

In the general analysis of blood at the age of 6 days - hemoglobin 130 g / l; erythrocytes 4.3 t / l, the number of leukocytes and the leukocyte formula within the age norm. Biochemical blood test and general urine analysis without features. In dynamics, a decrease in hemoglobin to 110 g / l.

Chest x-ray without features.

On the neurosonogram at the age of 6 days - periventricular hemorrhage of the II degree on the left. Cysts of the subependymal zones. The dimensions of the anterior horns of the lateral ventricles are 5 mm, the posterior horns of the lateral ventricles are 13 mm, and the third ventricle is 3 mm.

Acid-base state: pH 7, 42; BE = 1.5 mmol / L; NSO ₃ ^- - 25.5 mmol / L.

The treatment prescribed piracetam, Actovegin, triampur, antibiotic therapy (pefotaxime).

Clinical diagnosis: perinatal damage to the central nervous system, moderate severity, hypoxic-hemorrhagic, PVK-II on the left, acute period, hydrocephalic syndrome. Prematurity I degree. Intrauterine growth retardation by hypotrophic type. Hypospadias. Risk group for intrauterine infection.

Screening for intrauterine infections by ELISA (mycoplasma, chlamydia) - neg. Screening for other infections has not been conducted.

During therapy, the dynamics are positive. Motor activity increased, newborn reflexes are caused, head circumference for a month increased by 3 cm, fontanel size and ventricular size according to the neurosonogram remained the same.

In this case, a child with ventriculomegaly did not experience a decrease in bicarbonate levels. However, the pathological process in this child began in utero (subependymal cysts and ventriculomegaly during the first ultrasound examination). In addition, in the neonatal period, an increase in ventricular size did not occur.

Since boy S. was the only child with ventriculomegaly who did not have a decrease in the level of venous blood bicarbonates, this exception only confirms the rule.

Example 2 illustrates the course of the disease in a child who has undergone perinatal hypoxia, whose ventriculomegaly has not developed in dynamics.

Girl M. was admitted for treatment to the Department of Pathology of Newborns at the age of 4 days with a diagnosis of perinatal CNS damage of hypoxic origin, moderate severity, acute period, muscle dystonia syndrome.

A girl from II pregnancy (the first ended with a medical abortion a year ago), the mother has candidal colpitis during pregnancy. Delivery is urgent, quick. Body weight at birth 2880 g, body length 48 cm. Apgar score - 7/8 points.

Condition upon admission to the department of moderate severity. The scream is loud. The muscle tone is variable. Hands are fin. Reflexes of newborns from the arms are caused, from the legs are reduced, the cross of the lower legs in the lower third when walking. He throws back his head. Large fontanel 2 × 2 cm. The skin is clean, pink. Heart sounds are muffled, rhythmic. Heart rate - 134 per minute. Pueril breathing, no wheezing. BH - 52 per minute.

General analysis of blood and urine at admission, biochemical analysis of blood without features.

On the neurosonogram at the age of 6 days, periventricular hemorrhage of I degree on the right. The size of the ventricular system is not increased. (III ventricle 3 mm, anterior horns of the lateral ventricles - 4 mm, posterior horns - 9 mm).

Acid-base state upon admission: pH 7.4; BE = 0.8 mmol / L; NSO ₃ ^- - 24.8 mmol / l, which indicated a lack of risk of ventriculomegaly.

Clinical diagnosis: perinatal CNS damage of moderate severity, hypoxic-hemorrhagic, PVC I on the right, acute period, muscular dystonia syndrome.

In treatment received triampur, actovegin, piracetam.

In dynamics, an improvement in the condition: gradual normalization of muscle tone, expansion of the ventricular system according to ultrasound data was not observed (the dimensions are the same). However, a low increase in body weight and subfebrile temperature remained. In the general analysis of urine, two weeks from the moment of admission to the hospital, leukocytes are up to 20 in the field of view. Urine culture on the flora - E. coli in the titer of 500,000 CFU. Antibacterial therapy has been prescribed for urinary tract infections. In the dynamics, normalization of urinalysis, improvement was noted.

This example illustrates the course of the pathological process in a child with normal indicators of the acid-base state upon admission and the absence of ventricular expansion in dynamics.

Example 3 illustrates the course of a disease in a child who had a level of venous blood bicarbonates below 21 mmol / L in the first week of life with ventriculomegaly that developed towards the end of the neonatal period.

Girl U. Received treatment in the Department of Pathology of Newborns at the age of 1 day with a diagnosis of perinatal CNS damage of moderate severity, closed fracture of the left humerus in the middle third with a shift.

A girl from III pregnancy (the first is a medical abortion, the second is fetal death at a period of 31 weeks). Pregnancy against the background of anemia of the I degree, SARS for a period of 26-27 weeks, polyhydramnios. Childbirth by cesarean section. Body weight at birth is 3245 g, body length is 49 cm, head circumference is 35 cm, chest circumference is 34 cm. Apgar score is 7/8 points.

Upon receipt, a moderate condition. Is active. The scream is pretty loud. The muscle tone is variable. Reflexes of newborns from arms and legs are weakened. Large fontanel 2 × 2 cm. Skin with a light marble pattern. Heart sounds are clear, clean, rhythmic. Heart rate - 144 per minute. Pueril breathing, no wheezing. BH - 44 per minute.

Complete blood count, general urine analysis without features. In a biochemical analysis of blood at the age of 6 days, an increase in indirect bilirubin to 164 μmol / L.

On the neurosonogram at the age of 6 days - periventricular hemorrhage of I degree on the left. Dimensions of the ventricles: III - 3 mm, the front horns of the lateral ventricles - 5 mm, the back horns - 10 mm.

Acid-base state: pH 7.34; BE = -8.6 mmol / L; NSO ₃ ^- - 17.6 mmol / l, which indicates a high risk of ventriculomegaly.

Clinical diagnosis: perinatal damage to the central nervous system of moderate severity, hypoxic-hemorrhagic, PVC I on the left, acute period, muscle dystonia syndrome. Closed fracture of the left shoulder in the middle third with displacement. Conjugation jaundice.

The treatment was carried out: limb immobilization, piracetam, actovegin, cerebrolysin.

Against the background of treatment, clinically improvement, normalization of acid-base status at the age of 14 days (BE = -2 mmol / L; NSO ₃ ^- - 23.2 mmol / L),

however, according to the results of a nerosonographic study at the age of 26 days, there was an increase in the size of the posterior horns of the lateral ventricles to 14 mm, in connection with which the child was prescribed diacarb. An increase in head circumference over a month by 2 cm, no seam divergence was observed. Discharged home in satisfactory condition.

In this case, a decrease in the level of venous blood bicarbonates of a child with perinatal damage to the central nervous system of moderate severity preceded an increase in the size of the lateral ventricles.

Literature

1. Palchik A.B., Shabalov N.P. Hypoxic-ischemic encephalopathy of the newborn: a guide for doctors. - St. Petersburg: Publishing House "Peter", 2000. - 224 p.

2. Hydrocefalus - what's new? Leading article // Arch Dis Child Fetal Neonatal Ed. - 2001; 85; F.149-154.

3. Wyldes M., Watkinson M. Isolated mild fetal ventriculomegaly // Arch Dis Child Fetal Neonatal Ed. - 2004; 89; 9-13.

4. Shabalov N.P. Neonatology in 2 vols. - St. Petersburg: Peter, 2005.

5. Stepakina E.I., Kuzenkova L.M., Maslova O.I., Studenikin V.M. Methods of instrumental diagnosis of hydrocephalus in children // Questions of modern pediatrics. - 2004, vol. 3, No. 5. - p. 82-85.

6. Ment L. R., Vohr B., Allan W. et cet. The etiology and outcome of cerebral ventriculomegaly at term in very low birth weight preterm infants // Pediatrics. - 1999, vol. 104, N2. - p. 243-248.

7. Mirsadykov D.A. Diagnosis and treatment of normotensive hydrocephalus. Abstract ... doctors honey. sciences. - St. Petersburg, 2004 .-- 41 p.

8. Aksenov D. B., Keshishyan E. S., Rudnitskaya S. Ya. Prognostic value of changes in acid-base balance and gas composition of cerebrospinal fluid in premature infants with peri-, intraventricular hemorrhages // Russian Bulletin of Perinatology and Pediatrics. - 2005, No. 3. - p. 25-29.

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Claims (1)

A method of predicting ventriculomegaly neonates with perinatal hypoxia, by investigating ion HCO ₃ ^-, characterized in that for studying neonatal taking venous blood for 4-7 days of life, it is determined the number of ions HCO ₃ ^- and its magnitude below 21 mmol / L predict the risk of ventriculomegaly.