RU2758757C1 - Method for predicting cerebral palsy in premature infants - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to the field of medicine, namely pediatrics, neonatology and child neurology. In order to predict cerebral palsy in premature infants with a birth weight of less than 1,500 g and a gestation period of 32 weeks or less, such risk factors as: birth weight; gestation age of 27 weeks or less; birth body length less than 36 cm; severe asphyxia at birth; Apgar score; disseminated intravascular blood coagulation syndrome; congenital sepsis; blood circulation insufficiency of the 2nd degree; posthemorrhagic hydrocephalus; cerebral ischemia; motor skills disorder, spastic hemiparesis; neonatal convulsions; CNS suppression syndrome; antenatal and postnatal intraventricular hemorrhage; subarachnoid hemorrhage of any localisation and/or hemorrhage into the posterior cranial fossa; parenchymal hemorrhage; periventricular leukomalacia; epileptiform activity according to the EEG data; seizure pattern according to the cerebral function monitoring data. The sum of the prognostic points is then calculated, wherein said points are used to estimate the risk of developing cerebral palsy.

EFFECT: method provides a possibility of predicting the risk of developing cerebral palsy in premature infants with a gestation period of 32 weeks or less and a birth weight of less than 1,500 g with a high degree of accuracy, sensitivity and specificity.

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Description

The invention relates to medicine, namely to pediatrics, neonatology and neurology of childhood, and can be used in the neonatal period to predict the development of cerebral palsy in children with a birth weight of less than 1500 grams and a gestation period of 32 weeks or less.

According to the World Health Organization (WHO), about fifteen million premature babies are born annually, representing more than 10% of all babies born worldwide (World Health Organization. Born Too Early: Global Action Report on Preterm Birth 2014). Perinatal brain injuries play a leading role in pediatric neurology, demonstrating colossal difficulties in carrying out postnatal adaptation of premature babies and, as a result, their high disability. Deeply premature babies are at high risk for the formation of adverse neurological outcomes, including cerebral palsy (cerebral palsy).

Some scientific publications have shown that cognitive and behavioral disorders at school age are diagnosed in 50% of premature babies (Allin MPG, Kontis D., Walshe M., Wyatt J., Barker GJ, Kanaan RAA, et al., White matter and cognition in adults who were born preterm.PLoS One. 2011; 6 (10): e24525), and cerebral palsy - in 10% of cases (Volpe JJ. Neonatal neurology - my personal journey and some lessons learned.Pediatr Neurol. 2014; 51 (6 ): 753-7). According to other authors, the risk of developing cerebral palsy exceeds the risks of developing cognitive impairments and mental retardation (Hielkema T., Hadders-Algra M. Motor and cognitive outcome after specific early lesions of the brain - a systematic review.Dev Med Child Neurol. 2016; 58 Suppl 4: 46-52).

Particular attention should be paid to children born with a body weight of less than 1500 g, whose risk of developing cerebral palsy is 20-30 times higher than that in the general population of newborns (The role of periventricular leukomalacia in the development of cerebral palsy / E.D. Belousova, M. Yu Nikanorova, V.S.Keshishyan, O.N. Malinovskaya // Russian Bulletin of Perinatology and Pediatrics. - 2001. - No. 5. - P. 26-32 / K.S.K. Kuban, A. Levition Cerebral Palsy // New England Journal of Medicine. - 1994. - Vol. 330, No. 3. - P. 188-195).

The need to identify among children born with a body weight of less than 1500 grams, a risk group for the formation of cerebral palsy is due to the possibility of a differentiated approach to their treatment and early rehabilitation, which can help reduce the likelihood of this disabling pathology.

The leading risk factors for adverse neurological outcomes in very premature infants include: complicated pregnancy, opportunistic infections of the mother, congenital and neonatal infections, severe asphyxia, functioning ductus arteriosus, respiratory disorders, a combination of iatrogenic factors: transfusion of blood group drugs, painful therapeutic manipulations, duration and invasiveness of mechanical ventilation, etc. (Palchik AB Basic principles of developmental neurology. Pediatrician. 2011; 2 (3): 90-7).

A known method for predicting infantile cerebral palsy in term infants (Pat. 2357655 Russian Federation. A method for predicting infantile cerebral palsy in term infants / Aronskind E.V., Shershnev V.N.; applicant and patentee State educational institution of higher professional education "Ural State Medical Academy of the Federal Agency for Healthcare and Social Development ". - No. 2007148115; filed. December 26, 2007; published. June 10, 2009, Bulletin No. 16), which allows predicting the formation of cerebral palsy on the 30th day of life based on perinatal risk factors.

Disadvantages of the method.

1. The method is not designed to predict cerebral palsy in premature infants.

2. The method does not take into account the birth weight of the child.

3. The method is not applicable during the entire neonatal period.

4. Factors of social and obstetric-gynecological history, contributing to the formation of cerebral palsy, are not taken into account.

5. The accuracy of the method is unknown.

A known method for predicting spastic forms of infantile cerebral palsy in premature infants, which takes into account gestational age, the duration of the anhydrous period, artificial ventilation of the lungs and partial parenteral nutrition, as well as the presence of peri-intraventricular hemorrhage of III-IV degree, periventricular leukomalacia, cerebral edema and the size of the posterior horns of the lateral ventricles. The method allows to predict the formation of spastic forms of cerebral palsy in premature infants on the 21st day of life (Pat. educational institution of higher professional education "Ural State Medical Academy of the Federal Agency for Healthcare and Social Development." - No. 2006146598; application. 27.12.06; published 10.06.2008 ,. Bul. No. 16).

Disadvantages of the method.

1. The data of obstetric-gynecological and socio-biological anamnesis are not taken into account.

2. The method is designed to predict only spastic forms of cerebral palsy.

3. The accuracy of the method is unknown.

There is also a known method for predicting infantile cerebral palsy in very premature infants weighing less than 1500 grams at birth on 10-14 days of life, based on the determination of prognostically significant socio-biological risk factors for the development of cerebral palsy, expressed by prognostic coefficients in points: cerebral ischemia of the III degree, syndrome movement disorders, extremely serious condition of the child at birth, Apgar score at the first minute of 4 points or less, periventricular leukomalacia, prematurity 28 weeks or less, congenital malformations, chronic inflammatory diseases of the genital area in the mother, medical abortion in the mother in history, history of miscarriages in the mother (authors O.M. Filkina, O.G. Andreyuk, N.V. Dolotova, L.A. Pykhtina, E.A. Vorobieva, T.G. Shanina, E.A. Matveeva Patentee: Federal state institution "Ivanovo Research Institute of Maternity and Childhood named after V. N. Gorodkov of the Federal Agency for you juice technology medical care ", application No. 2010120331/14, 05/21/2010, publ. 27.10.2011. Bul. No. 30). This method was chosen by us as the closest analogue.

Disadvantages of the method

1. Does not take into account somatic diseases of the neonatal period.

The novelty of the proposed method lies in the fact that a prognostic algorithm is proposed, taking into account the scoring of ante-, intra- and postnatal factors to predict the formation of cerebral palsy in very premature infants born at a gestational age of 32 weeks or less, with a birth weight of less than 1500 grams ...

Statistical processing of the clinical material was carried out to identify reliable signs that distinguish premature babies born at a gestational age of 32 weeks or less, with a birth weight of less than 1500 grams, who developed or did not have cerebral palsy at the age of 24 corrected months of life.

To determine the significance of the identified factors and develop a forecast, the ratio of the risks of developing cerebral palsy was calculated by constructing conjugation tables. The determination of the sensitivity and specificity of the scale was carried out using the ROC analysis: with a cut-off threshold of 29.5 points, the sensitivity of the scale was 90.2%, specificity was 88.2%, the predictive value of a positive result was 56.1%, and the predictive value of a negative result was 98 , 2%.

Prediction is carried out according to a specially developed scale (table 1), where each feature corresponds to the number of prognostic points.

Predictive scores are calculated for significant signs of a socio-biological history, which can be widely used in practice.

Parameters such as weight, gestational age, body length at birth, antenatal intraventricular hemorrhage refer to antenatal factors due to the fact that these parameters are known by the end of the antenatal period and do not change during childbirth, in contrast, for example, from the assessment by Apgar scale or severe asphyxia at birth, which are intranatal factors due to the fact that they are formed during childbirth and can change depending on the process of childbirth (Shabalov N.P., Neonatology in 2 volumes, 6th edition, supplemented and revised. Moscow, "GEOTAR-Media", 2016).

In paragraph 2 of the table, it is indicated that severe asphyxia at birth and an Apgar score are classified as intranatal factors that are assessed in children and are significant for prognosis.

The described invention is based on the assessment of ante-, intra- and postnatal risk factors for the formation of infantile cerebral palsy in very premature infants. The ante-, intra- and postnatal periods in modern neonatology are combined into the perinatal period, which includes the period from 28 weeks of gestation to 7 days of a child's life. The neonatal period in full-term babies includes the period from birth to 28 days of life; in very premature infants, the neonatal period includes the entire period from birth to the post-conceptual age of 44 weeks. Considering that at present, deeply premature babies born at a gestational age of 22 weeks or more are being nursed, the time frame of the perinatal period has been extended to include the period from 22 weeks of gestation to 7 days of life. Taking into account the fact that timely delivery occurs at 37-42 weeks and that the standard gestational age when calculating the adjusted age is 39-40 weeks of gestation, in the method described by us, the standard time point for assessing postnatal factors is the post-conceptual age of 40 weeks.

The syndrome of movement disorders (hemiparesis) and the syndrome of movement disorders (changes in muscle tone + anisoreflexia) are presented in separate items due to the fact that the degree of significance of each of these factors differs in premature infants, the combination of these factors increases the risk of cerebral palsy.

List of abbreviations

CNS - central nervous system,

IVH - intraventricular hemorrhage,

EEG - electroencephalography,

aEEG - amplitude-integrated electroencephalography.

The most significant factors for the formation of cerebral palsy are: birth weight 970 grams or less, gestational age of 27 weeks or less, disseminated intravascular coagulation syndrome, congenital sepsis, post-hemorrhagic hydrocephalus, cerebral ischemia of the 3rd degree, syndrome of motor disorders in the neonatal period, neonatal convulsions, antenatal IVH of the 2nd and 3rd degree, postnatal IVH of the 3rd degree, subarachnoid and parenchymal hemorrhages, periventricular leukomalacia.

The method is carried out as follows

1. According to the proposed table at the postconceptual age of 40 weeks in a premature baby born at a gestational age of less than 32 weeks with a birth weight of less than 1500 grams, the presence or absence of factors influencing the formation of cerebral palsy is determined.

2. Summarize the prognostic scores of the risk factors identified in the patient.

3. If the sum of the predictive coefficients is equal to or exceeds 29.5 points, a high risk of developing cerebral palsy is predicted.

4. If the sum of the predictive coefficients is equal to or less than 29 points, then a low risk of developing cerebral palsy is predicted.

The use of the proposed method allows, with a high accuracy of 98.2%, a sensitivity of 90.2% and a specificity of 88.2%, to predict at the postconceptual age of 40 weeks the risk of cerebral palsy in premature infants with a gestational age of 32 weeks or less and a birth weight of less than 1500 grams.

The essence of the proposed method is illustrated by the following examples.

Example 1.

Boy S.M. from multiple pregnancies, operative delivery at 27 weeks of gestation (8.8), 2nd of twins, birth weight 970 g (10.0), body length 33 cm (6.1), Apgar score 6 / 7 points (0). The condition after birth is severe, the course of congenital sepsis (8.1), disseminated intravascular coagulation (13.2), circulatory failure of the 2nd degree (5.8), neonatal convulsions (6.3), syndrome of movement disorders (8.8 ), depression syndrome (3.2), IVH degree 2 (4.9), epileptiform activity according to EEG data (5.8), seizure pattern according to monitoring of cerebral functions (4.9).

Points total: 8.8 + 10 + 6.1 + 8.1 + 5.8 + 6.3 + 8.8 + 3.2 + 4.9 + 5.8 + 4.9 + 13.2 = 85 , 7 points.

Conclusion: the child is predicted to have a high risk of developing infantile cerebral palsy.

The prognosis for this method was confirmed: at the age of 12 corrected months of life, the diagnosis was made: Cerebral palsy, atonic-astatic form.

Example 2.

Boy S.D., from multiple pregnancy, operative delivery at 27 weeks of gestation (8.8), 1st of twins, birth weight 980 g and body length 34 cm (6.1), Apgar score 5/7 points (3.9). The state after birth is severe, the course of congenital pneumonia (0), the syndrome of CNS depression (3,2), according to the NSG data - signs of structural immaturity (0), according to the EEG data, typical epileptiform activity is not registered (0).

Points total: 8.8 + 6.1 + 3.9 + 3.2 = 22 points.

Conclusion: the child is predicted to have a low risk of developing infantile cerebral palsy.

The prognosis was confirmed: at the age of 6, 12, 18 and 24 corrected months of life, the neurological status, motor and psycho-speech development of the child corresponded to the age norm.

This method examined 290 premature babies born at a gestational age of 32 weeks or less, with a body weight of less than 1500 grams.

The calculation of accuracy, sensitivity and specificity was carried out in accordance with the guidelines (Assessment of the diagnostic information content of laboratory tests: guidelines // Clinical laboratory diagnostics. - 1992. - No. 1-2. - P. 49-58).

The advantages of the method:

- allows in the neonatal period, taking into account the analysis of ante-, intra- and postnatal factors, to predict the risk of infantile cerebral palsy in premature infants with a birth weight of less than 1500 grams and a gestation period of 32 weeks or less;

- high accuracy 98.2%, sensitivity 90.2% and specificity 88.2%;

- simplicity and availability of the technique, does not require much time;

- the method allows you to develop the correct algorithm for patient management;

- the method allows you to start habilitation activities in a timely manner.

Claims (1)

A method for predicting cerebral palsy in premature infants with a birth weight of less than 1500 grams and a gestation period of 32 weeks or less by identifying ante-, intra- and postnatal risk factors, characterized in that during the neonatal period, prognostically significant socio-biological risk factors for the formation of infantile cerebral palsy, expressed by prognostic points: weight at birth 970 grams or less - +10; gestational age 27 weeks or less - +8.8; birth weight 971-999 grams and / or body length at birth less than 36 cm - +6.1; severe asphyxia at birth - +4.5; Apgar score in the 1st minute less than 6 points - +3.9; Apgar score at the 5th minute less than 7 points - +4.2; disseminated intravascular coagulation syndrome - +13.2; congenital sepsis - +8.1; circulatory failure of the 2nd degree - +5.8; post-hemorrhagic hydrocephalus - +8.3; cerebral ischemia of the III degree - +7.6; cerebral ischemia II degree - +4.5; syndrome of movement disorders, spastic hemiparesis - +8.8; neonatal convulsions - +6.3; movement disorders syndrome - +4.4; central nervous system depression syndrome - +3.2; antenatal IVH of the 3rd degree - +8.3; antenatal IVH of the 2nd degree - +7.8; postnatal IVH of the 3rd degree - 7.4; postnatal IVH of the 2nd degree - +4.9; subarachnoid hemorrhage of any localization and / or hemorrhage in the posterior cranial fossa - +8.3; parenchymal hemorrhage - +7.8; periventricular leukomalacia - +8.7; epileptiform activity according to EEG data - +5.8; paroxysmal pattern according to monitoring of cerebral functions - +4.9; then the sum of the prognostic points is calculated, and if the value of the sum is equal to 29.5 or more points, the result is regarded as a high risk of developing infantile cerebral palsy, and with a value of 29 or less points - as a low risk of developing infantile cerebral palsy.