Screening for cystic fibrosis: identification of a dangerous monogenic pathology that is asymptomatic. Analysis for cystic fibrosis

Date: 10.04.2019

What is newborn screening, how and when is it done?

Screening of newborns, or "heel test" is massively carried out in Russia, Europe, the United States. Usually the analysis is done in the hospital on the 4th or 5th day of the baby's life. Results come in three weeks on average. Most often, during this examination, a disease called cystic fibrosis is found in children.

Screening of newborns (from English screening - sorting) is one of the most effective methods for diagnosing genetic diseases of the neonatal period. Genetic research is being carried out at the initiative of the World Health Organization (WHO). In Russia, screening is included in the list of mandatory diagnostic activities over the past fifteen years. From a large list of genetic diseases, it is recommended to diagnose five pathologies, taking into account such factors: prevalence, severity of diseases, as well as the ability to obtain reliable test results and apply effective treatment.

Screening terms and conditions

How is newborn screening done?

📍 In full-term babies, the analysis is done on day 4 at the hospital.
📍Premature babies are screened on the 7th day of life and later. If the child was discharged from the hospital earlier, the baby is analyzed at home or at the local polyclinic.
📍For screening, peripheral blood (from the heel) is taken, hence the "heel test".
📍The blood is applied to 5 separate blanks (circles) of filtered paper.
📍The test is taken on an empty stomach, you cannot feed the newborn 3 hours before screening.

When to do the screening? If you do the analysis earlier - on the 2nd or 3rd day of life - the results can be both false positive and false negative. It is advisable to pass the test within the first 10 days of life. Early detection of genetic metabolic disorders is important for a favorable prognosis.

Diagnostics of pathologies of the gene level

What congenital diseases are diagnosed by screening in Russia? The list includes those diseases that can be cured or reduced in severity at an early stage of detection. These are pathologies associated with various metabolic disorders. This, for example, does not include the diagnosis of a chromosomal disease such as Down syndrome.

📍 Hypothyroidism. This disease is associated with a violation of the production of thyroid hormones. The consequences of this disease are severe: general physical and mental retardation. On average, one case of hereditary hypothyroidism is recorded per 5 thousand newborns, and girls are more likely to get sick. The chances of completely curing the disease detected after positive screening results are quite high, hypothyroidism can be defeated. Hormone therapy is required. Read more about hypothyroidism, about TSH rates in children in our other article.

📍 Cystic fibrosis. With this disease, the production of secretions in the lungs and the digestive tract is disrupted. The fluid secreted by the cells becomes thick, this leads to serious dysfunctions of the lungs, liver, and pancreas. Cystic fibrosis is one of the most frequent illnesses, which is detected during screening, one case is registered in 2-3 thousand newborns. The prognosis is favorable if timely treatment begins.

📍Adrenogenital syndrome. It is rare, about one case in 15 thousand newborns. This includes a group of genetic diseases that are triggered by a violation of the production of cortisol (in the adrenal cortex). What are the consequences of this disease? The development of the genitals is delayed, the kidneys, heart, blood vessels are affected. Death is likely if medical attention is not provided. Treatment consists of lifelong hormonal therapy.

📍 Galactosemia. The cause of this disease is a deficiency of an enzyme that breaks down galactase. This substance enters the body with glucose and is contained in lactose. The symptoms of galactosemia appear gradually, and the newborn seems to be quite healthy child... But after a few weeks, vomiting, loss of appetite, swelling, protein in the urine, jaundice may appear. Galactosemia is dangerous in its consequences: serious violations of liver function, decreased visual acuity, slow physical, intellectual development... This is the rarest disease diagnosed at screening, occurs once in 30 thousand newborns. Treatment for galactosemia is a strict dairy-free diet.

📍Phenylketonuria. A rare hereditary disease that occurs once in 15 thousand newborns. Phenylketonuria occurs as a result of a disruption in the production of an enzyme that is supposed to destroy the acid of phenylalanine. The breakdown products of phenylalanine negatively affect the entire body and accumulate in the blood. First of all, the central nervous system, the brain suffers, convulsions appear. To avoid complications of the disease, a strict diet is required, which excludes the intake of phenylalanine into the body.

In medicine, there are about five hundred diseases associated with metabolic disorders, or metabolism. For example, in Germany, 14 genetic diseases are diagnosed through newborn screening, in the USA - over 40 diseases. In Russia, neonatal screening is carried out to diagnose the five most dangerous pathologies that begin to develop at an early age. At the request of the parents, if the baby is at risk, screening can be expanded to 16 diseases.

There is a lot of controversy around the topic of newborn screening. Parents who have experienced stress after a false positive result in a baby are not advised to undergo the procedure. Other mothers and fathers, whose babies had serious diagnoses, are grateful to this diagnosis, because they managed to save the child from serious consequences, to suspend or cure the disease.

5 questions parents are worried about

Screening is anxiety for many mums and dads, and the waiting period is filled with anxiety and fear. Especially anxious moms may even have lactation problems. Perhaps that is why in some maternity hospitals they do not notify mothers at all, for what purposes the analysis is taken.

📍When can you get the result? The analysis is carried out within three weeks. If the results are negative (and this is the case in most cases), no one reports it. But the data is recorded in the baby's medical card. If there is a positive result, then they will definitely call back from the clinic and ask to take the test again. Most often, false positive tests are for cystic fibrosis.
📍If the re-screening confirmed the previous test? Parents are invited to a conversation with a geneticist. He gives referrals to narrow specialists where additional examination: coprogram, DNA diagnostics, dry blood spot analysis, if cystic fibrosis is suspected - sweat test.
If after additional analyzes the diagnosis is still confirmed, the question of the tactics of treating the baby is being decided.
📍Can newborn screening be done at home? If for some reason the screening was not carried out in the hospital or the discharge was on the 3rd day, the analysis is done at the polyclinic at the place of residence. Some mothers, commenting on the situation, share their experience: someone called the nurse at home, someone went to the clinic, and to someone the nurse came home and took blood samples for screening. If you have any difficulties, and the time for taking blood for screening is running out, you can do an analysis in a paid laboratory. You can also contact the higher health authorities, which are subordinate to the district maternity hospital and polyclinic, and ask how to act in this situation.
📍How high is the screening confidence? If the analysis is carried out on time, if the baby has not eaten 3 hours before blood sampling, the reliability of the tests is high. But the diagnosis is never made after the first positive result. There are rare cases when screening shows false negative results. In this case, the disease is detected late, when symptoms already appear.
📍Can I opt out of screening? Yes, you can. Parents take responsibility and sign a document refusing to screen their newborn. This paper is glued into the baby's card. The nurse or the doctor of the district clinic will call, come home, leave notes with a request to undergo screening until a parental refusal is written.

It is important to know that pathological disorders metabolism can be not only hereditary diseases. Children with cystic fibrosis, hypothyroidism, galactosemia, phenylketonuria, adrenogenital syndrome can be born to perfectly healthy parents. It is also important to know that when confirming the diagnosis, one should not delay treatment and neglect the recommended diet for phenylketonuria or galactosemia.

Newborn screening at the maternity hospital is quick, free and painless for babies. Medical professionals recommend that parents consciously approach this diagnosis, which is carried out according to the state program and the WHO initiative. Unfortunately, late detection of genetic metabolic diseases leads to irreversible consequences, disability and mortality of children.

E.I. Kondratyeva, Doctor of Medical Sciences, Professor, V.D. Sherman, Ph.D., N.I. Kapranov, Doctor of Medical Sciences, Professor, N.Yu. Kashirskaya, doctor of medical sciences, professor, non-profit organization of cystic fibrosis, FSBSI "MGNTs", GBUZ "DGKB No. 13 named after N.F. Filatov DZM ", Moscow

Cystic fibrosis (CF), or cystic fibrosis, is one of the most common monogenic hereditary diseases with multiple organ pathology, which sharply reduces the duration and quality of life of patients without adequate complex treatment throughout life. CF is common among the world's population, but most often affects Caucasians: on average, with an incidence of 1 in 2500-4500 newborns. More recently, patients with cystic fibrosis died in an early childhood or even in the first year of life from pneumonia and malabsorption malabsorption wasting.
Keywords: diagnostics, genetics, mutations, neonatal screening, sweat test, fecal elastase.
Key words: cystic fibrosis, diagnosis, genetics, mutation, newborn screening, sweat test, fecal elastase.

The disease is primarily characterized by increased production of viscous bronchial secretions, frequent lung infections and airway obstruction. As pulmonary disease progresses, areas of atelectasis are formed, emphysema develops, the parenchyma of the lungs is gradually destroyed with the development of bronchiectasis and areas of pneumosclerosis, and the patient has a high risk of dying from pulmonary heart disease. In the final stage of the disease, transplantation of the heart-lung complex remains the only hope for the patient. In addition to the bronchopulmonary system, the pancreas is affected in most patients with cystic fibrosis, while this occurs intrauterinely. Lack of pancreatic enzymes leads to impaired absorption of fats and proteins, the development of nutritional deficiency. As a result, patients are stunted and suffer from hypotrophy. Insulin production can also be impaired, leading to the development of diabetes. TO frequent complications the course of cystic fibrosis includes osteoporosis, as well as fatty hepatosis with a transition to cirrhosis. In the presence of a "soft" mutation, clinical manifestations develop gradually, monosymptoms prevail, the diagnosis of "cystic fibrosis" is established late or accidentally.

Timely diagnosis of cystic fibrosis, which in most cases provides an early start of therapy, including at the preclinical stage, improves the prognosis of the disease, increases the effectiveness of treatment, prevents the development of severe complications, a significant delay in physical development, and in some cases irreversible changes in the lungs. Early diagnosis allows the family to timely resolve the necessary issues related to the birth of a healthy child (genetic counseling, prenatal CF diagnosis in subsequent pregnancies).

Diagnostics are divided into:

1) prenatal diagnosis;
2) diagnostics by neonatal screening (before clinical manifestations or at their debut);
3) diagnostics in case of clinical manifestations:

patients who were not included in the neonatal CF screening program, which has been conducted since 2006-2007. Risk groups: patients with gastrointestinal tract pathology, bronchopulmonary disorders, pathology of other organs;

false negative results from neonatal screening and sweat test;

patients with neonatal hypertrypsinogenemia who have not received a sweat test;

4) diagnostics among relatives of patients.

Currently, prenatal diagnosis of cystic fibrosis is being established in promising and informative families (Moscow, St. Petersburg, Ufa, Tomsk, Krasnoyarsk, Rostov-on-Don, Vladivostok and some other cities), which is certainly important for the prevention of this severe pathology. Prenatal diagnostics is possible in the form of DNA diagnostics during amniocentesis (obtaining amniotic fluid in the early period -13-14 weeks and late - usually 16-20 weeks of pregnancy) in a family of carriers of one CFTR gene mutation and having a sick child. The diagnosis can be suspected by intrauterine ultrasound of the fetus in the presence of a characteristic ultrasound characteristic in the form of a hyperechoic intestine. Ultrasound during pregnancy is recommended at screening times: 11-14, 18-21 and 30-34 weeks of pregnancy. Re-examination is mandatory. In 50-78% of cases, this condition will be associated with CF and manifest as meconium ileus. In this case, the diagnosis can be made even before the baby is born. At the same time, this symptom is not highly specific for CF, it can be a transient phenomenon, as well as associated with other pathological conditions... At the same time, DNA diagnostics of parents provides the necessary information about the presence of mutations in each of the parents and allows one to assume that the child has a disease at birth.

Clinical signs

1. Diagnosis of the classic form of CF is usually not difficult. The classic patient phenotype is the result of the presence of two mutant copies of the cystic fibrosis transmembrane regulator (CFTR) gene and is characterized by chronic bacterial infection of the respiratory tract and paranasal sinuses, steatorrhea due to exocrine pancreatic insufficiency, male infertility due to obstructive azoospermia, and increased concentration chlorides of sweat.
2. Problems in the diagnosis of CF, as a rule, are associated with the phenotypic diversity of its forms, caused by genetic polymorphism.

In some cases of atypical course of CF, it can be diagnosed in adulthood. As a rule, in this group of patients, a milder course of the disease is noted due to the preservation of the function of the pancreas and mild damage to the respiratory system.

In the vast majority of cases, CF can be diagnosed in early childhood (in 90% of cases, in the first year of life). Unfortunately, CF is often diagnosed in adults with a classic phenotype.

Diagnosis of CF in carriers of "soft" genotypes (relevant for children born before 2006-2007 and adults):

late debut;

monodebut, mono-defeat, monosymptomatic from the respiratory system;

clinical symptoms of lung damage are erased, or not expressed, or masked (bronchial asthma, pneumonia);

a relatively high proportion of negative, doubtful or not sharply elevated sweat chlorides;

mutations are often not among the mutations most often identified in genetic counseling and require sequencing;

consultation of an ENT doctor, andrologist is necessary.

Currently, there are several CF risk groups.

The main risk group for the disease in the Russian Federation is currently newborns with neonatal hypertrypsinogenemia. Considering the possibility of obtaining false-negative results of neonatal screening, as well as the fact that neonatal screening for CF has been carried out in the Russian Federation since 2006-2007, the analysis of risk groups, including patients with pathology of the gastrointestinal tract, bronchopulmonary disorders, pathology of other organs and relatives of CF patients (Table 1).

Table 1.

Risk groups for the differential diagnosis of cystic fibrosis

I. Bronchopulmonary disorders

1. Repeated and recurrent pneumonia with a protracted course, especially bilateral
2. Bronchial asthma, refractory to traditional therapy
3. Recurrent bronchitis, bronchiolitis, especially with seeding Ps. aeruginosa
4. Bilateral bronchiectasis

II. Changes in the gastrointestinal tract

1. Syndrome of impaired intestinal absorption unclear genesis
2. Meconium ileus and its equivalents
3. Hyperechogenicity of the intestine of the fetus
4. Jaundice of obstructive type in newborns with a protracted course
5. Liver cirrhosis
6. Diabetes
7. Gastroesophageal reflux
8. Rectal prolapse

III. Pathology from other organs

1. Disorders of growth and development
2. Delayed sexual development
3. Male infertility
4. Chronic sinusitis
5. Nasal polyps
6. Electrolyte disturbances

IV. Family members of patients with cystic fibrosis

Among the clinical manifestations characteristic of CF, highly and less specific ones can be distinguished (Table 2). The conditions presented in the left column of the table are found in the vast majority of cases in CF patients. The conditions in the right column can be caused by other diseases, for example, primary ciliary dyskinesia, humoral immunodeficiency, etc.

Table 2.

Clinical manifestations specific to CF

Highly specific for CF	Less specific for CF
Gastrointestinal: Meconium ileus Exocrine pancreatic insufficiency in children	Gastrointestinal: Lagging physical development Hypoproteinemia Fat-soluble vitamin deficiency Rectal prolapse Biliary cirrhosis Portal hypertension GSD in children without hemolytic syndrome Primary sclerosing cholangitis Exocrine pancreatic insufficiency in adults Recurrent pancreatitis
Chronic mucoid infection Ps. aeruginosa Bronchiectasis in the upper lobes of both lungs Persistent B. cepacia infection Nasal polyps in children	From the respiratory tract: Chronic or recurrent St. aureus, Ps. aeruginosa, Ach. xilosoxidans, H. Influenzae X-ray signs of bronchiectasis, atelectasis, hyperinflation, or chronic infiltration on chest x-ray Hemoptysis associated with diffuse lung disease other than tuberculosis or vasculitis Chronic and / or productive cough Nasal polyps in adults X-ray signs of chronic pansinusitis
Other: Hypochloremic alkalosis in the absence of vomiting Congenital bilateral absence of the vas deferens	Other: Thickening of the terminal phalanges Osteopenia / Osteoporosis in Age<40 лет Atypical diabetes

Table 3 presents the features of the manifestations of CF in different age periods. Knowledge of these features helps professionals who follow a patient with certain symptoms to include CF in the list of diseases for differential diagnosis. This is especially true for young children, when the clinical picture may still be incomplete, but some manifestations will pay attention to themselves, for example, meconium ileus at birth or salt loss syndrome, which has no connection with kidney pathology. In this case, the diagnosis can be made even before the baby is born. At the same time, this symptom is not highly specific for CF, it can be a transient phenomenon, as well as associated with other pathological conditions.

Table 3.

Clinical features of CF manifestations in different age periods

0-2 years
Poor weight gain Steatorrhea Recurrent bronchitis / bronchiolitis Meconium ileus Rectal prolapse Hypoproteinemic edema	Pneumonia / empyema Salt loss syndrome Prolonged jaundice of newborns Increased bleeding associated with vitamin K deficiency
3-16 years old
Recurrent respiratory infection or asthma Idiopathic bronchiectasis Steatorrhea Acute or chronic pancreatitis	Sinusitis and nasal polyposis Chronic intestinal obstruction, intussusception Heatstroke with hyponatremia Family CF diagnosis

Diagnostic criteria for CF
To solve the problems of diagnosis of CF, including its atypical forms, criteria were developed according to which the presence of a characteristic clinical syndrome plus proof of any dysfunction of the chlorine channel is mandatory for CF.

Taking into account all the scientific advances in understanding the nature of cystic fibrosis and CF-dependent diseases over the past 10 years, in 2013 a group of experts from the European Cystic Fibrosis Society, led by Carlo Castellani, prepared new diagnostic standards edited by Alan R. Smyth and Scott Bell ( scheme).

Scheme.

Diagnostic Criteria for Cystic Fibrosis ECFS 2013

Neonatal screening
It is carried out on the basis of the Guidelines for neonatal screening in the Russian Federation using the European recommendations for neonatal screening. 90% of newborns without clinical manifestations of cystic fibrosis can be diagnosed by screening before 6 weeks of age. In 5-10% of cases, there are difficulties with the diagnosis of cystic fibrosis (Cystic Fibrosis Foundation Patient Registry, 2005 Annual Data Report to the Center Directors. Bethesda, MD: CFF).

Neonatal screening problems:

5-10 newborns out of 1000 have neonatal hypertrypsinogenemia.

Failure to comply with the timing of blood sampling leads to diagnostic errors. The test is on the 4-5th day, the retest is carried out no later than 8 weeks (optimally the 21-28th day of life).

IRT is not stable in blood samples during storage (max. 14 days).

Meconial ileus, hyperechoic intestine of the fetus in the second trimester requires examination for CF regardless of the screening program.

RTI increases in newborns not only in CF (trisomy 13 and 18, renal failure, intrauterine infection, intestinal atresia, renal diabetes insipidus, newborns of North African and African American descent, heterozygous carriers of CFTR mutations?).

False negative result for meconial ileus, prematurity, blood transfusions, viral infection.

There is a need to discuss the definition of a lower threshold for the diagnosis of neonatal hypertrypsinogenemia for each laboratory.

Sweat sample
Indications:

1. With a positive result of neonatal screening (a twofold increase in the level of immunoreactive trypsinogen in the blood during the first month of a child's life).
2. If the patient has any characteristic clinical manifestations of CF.
3. Family history of CF.

The sweat test is a reliable diagnostic tool for CF in 98% of patients. The test can be performed on all babies 48 hours after birth, although newborns may have trouble gaining sweat. Despite the fact that the "gold standard" for CF diagnostics is the quantitative determination of chlorides in sweat (the classical Gibson - Cook method), the method for determining conductivity on the Macrodact and Nanodact devices (Vescor, USA) showed a good correlation with it. in numerous studies.

Result evaluation
If the result of a sweat test is positive (chlorides> 60 mmol / L with the classical Gibson-Cook method and / or conductivity> 80 mmol / L NaCl), the diagnosis is confirmed.

Genetic research
Genetic testing is done after a sweat test. However, due to the limited possibilities of DNA diagnostics in Russia, this method is not mandatory, but it is used for research purposes and for the final confirmation of the diagnosis.

At the first stage of DNA examination, a panel is most often used, which includes 28 mutations, both the most frequent in the world and specific for Russia: F508del, CFTRdele2,3 (21kb), 3849 + 10kbC> T, W1282X, 2143delT, 2184insA, 1677delTA, N1303K, G542X, R334W, E92K, L138ins, 394delTT, 3821delT, S1196X, 2789 + 5G> A, G85E, 2183AA> G, 604insA, 621 + 1G> T, R117H, R347P, R553X, 36671insTCA17- G55 1G> A, 2184delA. According to the laboratory of genetic epidemiology of the Federal State Budgetary Institution "Medical Genetic Research Center" (MGSC) of the Russian Academy of Medical Sciences, when using this panel, it is possible to detect only about 82.5% of mutant alleles in CF patients. In the case when a positive sweat test does not find a single gene mutation (which in itself is unlikely), sequencing of the CF gene may be required to identify approximately 98% of mutations in the CFTR gene.

1. Based on the data of the national register of CF patients on DNA diagnostics of the CFTR gene, the characteristics of the nature and frequency of mutations in the regions of the country were established. On the basis of the register data, it is recommended to create regional recommendations for the identification of mutations with reference to the register ( latest version).
2. Absence of mutations without sequencing is not enough to exclude CF.
3. Several CFTR mutations (3849 + 10 kb C> T) are associated with normal or marginal sweat test results.
4. "Soft" mutations are characterized by a late onset of the disease, the borderline value of sweat samples, and are more often detected during sequencing.
5. Patients with borderline sweat test results (chlorides 30-60 mmol / l and / or conductivity 50-80 mmol / l), a single gene mutation present real difficulties for diagnosis.

To diagnose CF or exclude it with borderline test results, it is necessary:

the use of several methods for the determination of sweat chlorides;

advanced DNA analysis (gene sequencing);

clinical, laboratory and instrumental examination: scatology and fecal elastase 1, sputum culture / smear from the posterior pharyngeal wall, consultation with an ENT doctor and andrologist, chest x-ray, sinuses;

observation in the center of cystic fibrosis until the final decision is made.

In European countries, to confirm a defect in ion transport, a method is used to determine the difference in nasal potentials or to measure electric current in a biopsy specimen of the intestine, reflecting a dysfunction of the chlorine channel. Both methods are based on the electrical nature of ion transport and are highly informative for CF diagnostics.

Diagnosis of pancreatic insufficiency includes:

scatology (neutral fat);

fecal elastase 1 feces, followed by dynamic control once a year, regardless of the result;

fecal lipid profile;

Ultrasound of the pancreas;

DNA diagnostics of CFTR mutations.

In CF patients, the elastase index may decrease during the first years of life, therefore, it is determined over time. A low level of pancreatic elastase is one of the hallmarks of CF. Approximately 1% of CF patients have a borderline sweat test result in combination with intact pancreatic function and chronic bronchitis.

Diagnostics of the chronic bronchopulmonary process:

CT diagnostics (age in European consensus - 7 years and earlier according to indications, in some countries - from 3-4 years);

early X-ray examination (at birth and then once a year);

lung function - spirography (FEV1) (once every 3 months);

the regularity of sputum microflora testing (once every 3 months) and antibiotic sensitivity;

genotyping of microorganisms, PCR diagnostics;

indications for examination and the use of special media and methods for certain types of microorganisms (B. cepacia, NTMB, tuberculosis, aspergillosis, pulmonary candidiasis with reference to Russian and foreign consensus and recommendations).

Azoospermia in post-pubertal age, identification of CF-associated pathogens from the respiratory tract, and radiographic signs of sinusitis can be used as additional diagnostic markers.

Knowledge of the main symptoms of CF and the characteristics of its course at different age periods allows one to promptly suspect the presence of the disease and refer the patient for further examination. Frequent cases of late diagnosis of CF are associated both with the lack of sufficient knowledge of the disease among doctors and with the phenotypic diversity of its forms. Limited opportunities DNA diagnostics of CF in Russia and its low availability complicate and delay the final verification of the disease.

LITERATURE

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2. Welsh M.J., Ramsey B.W., Accurso F.J., Cutting G.R. Cystic fibrosis. In: Scriver C.R., Beaudet A.L., Sly W.S., Valle D., eds. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill, 2001: 5121-88.
3. European cystic fibrosis society standards of care working group. Best practice guidelines. Edited by Alan R. Smith and Scott Bell, 2014.
4. Farell P.M., Rosenstein B.J., White T.B. et al. Cystic fibrosis foundation. Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic Fibrosis Foundation consensus report // J. Pediatr., 2008; 153 (2): S4-S14.
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6. de Boeck K., Wilschanski M., Castellani C. et al. Cystic fibrosis: terminology and diagnostic algorithms. Thorax, 2006; 61: 627-635.
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Home> Abstract

Organization of neonatal screening for cystic fibrosis, adrenogenital syndrome and galactosemia

Cystic fibrosis(cystic fibrosis; CF) is a frequent monogenic autosomal recessive disease characterized by damage to the exocrine glands and vital organs and systems and usually heavy course and forecast. The prevalence of CF varies in different European populations from 1: 600 to 1: 12000 (average 1: 5000) newborns. Adrenogenital syndrome(AGS, congenital adrenal hyperplasia) is a group of diseases with an autosomal recessive mode of inheritance, the development of which is associated with impaired secretion of corticosteroids due to a congenital defect in enzymes responsible for the biosynthesis of these hormones. Screening of newborns is carried out for 21 hydroxylase deficiency, the frequency of which ranges from 90% to 95% of all variants of AHS. The frequency of ASH in Europe is practically the same and varies in the range from 1: 10,000 to 1: 14,000 live births. Galactosemia- a group of hereditary diseases caused by a deficiency of enzymes involved in the metabolism of galactose. Mass screening of newborns is aimed at identifying classic galactosemia (type I), which is the most severe pathology that requires urgent correction of the pathology. The frequency of galactosemia in Europe ranges from 1: 18000 to 1: 180,000, with an average of 1: 47000. The frequency of galactosemia in Japan is 1: 667000. In order to implement the national project "Health" in the Krasnodar Territory in 2006. in addition to PKU and VH, screening for cystic fibrosis, adrenogenital syndrome and galactosemia began.

Table 8 The results of newborn screening for hereditary metabolic diseases in the Krasnodar Territory for the period from 1.07.06. until 30.06.08.
Disease	Examination of newborns	Number of primary deviations in analyzes	Number of re-examined children	Number of repeated deviations in analyzes	Number of identified patients
cystic fibrosis
AGS
galactosemia

For 24 months (July 2006-June 2008) 114,253 (99.7%) newborns were examined for AGS and cystic fibrosis, 10 children with cystic fibrosis, 15 patients with adrenogenital syndrome were identified. For galactosemia for 24 months (October 2006-September 2008), 116,041 (99.2%) newborns were examined, 6 patients were identified (Table 8). Primary elevated levels of IRT and 17-OHP were detected in 1.1%, total galactose in 1.9% of the examined children. In order to identify possible causes affecting the increase in the studied metabolites in the blood of newborns, we carried out an analysis unfavorable factors affecting the development of the child during pregnancy and after birth. The following factors were analyzed: placental insufficiency, anemia of pregnant women, preterm labor, delivery stimulation, operative delivery, newborn body weight less than 2 kg and more than 4 kg, hypoxia, jaundice, congenital infections and infusion therapy. The effect of these factors on the level of 17-OHP and galactose was not revealed. Revealed the dependence of the level of IRT in the blood of newborns on anemia of pregnant women, jaundice and hypoxia of newborns, infusion therapy (Table 9).

Table 9 Factors influencing the increase in neonatal RTI
	Number of newborns with increased RTI (n = 305)		Control group n = 20,000
		infusion therapy was not performed	Control group n = 20,000

infusion therapy
anemia of pregnancy
hypoxia

Of 1201 newborns with a high level of RTI, a second study of RTI in the informative period (at the age of 21-28 days of life) was carried out in 717 (59.7%) children, in 132 (18.4%) a second increased level of RTI was determined. Children with elevated RTI were born on average by 39 + 2 weeks pregnant with body weight 3329 + 620 grams with an average body length of 52.0 + 3.0 cm.When examined in the maternity hospital, the IRT level ranged from 70.0 to 556.0 ng / ml, averaging 110.0 + 56.0 ng / ml. During retest, the IRT level ranged from 6.0 to 448.0 nmol / l, averaging 67.0 + 41.0 ng / ml. The dependence of the level of IRT on the weight of newborns was not revealed. For a more reliable assessment of the dependence of the level of RTI on the physical development of children, we determined the mass-growth index (MRI). In children with MRI less than 90, indicating a deficiency in body weight, the average RTI level was 107 + 44 ng / ml. With normal MRI values (from 90 to 99), the average level of IRT is 107 + 43 ng / ml. With MRI of 100 or more, indicating overweight, the average level of IRT is 113 + 71 ng / ml. Thus, no correlation was found between the level of neonatal RTI and the height and weight indices of newborns. As noted above, when examining 114,253 newborns, 10 children with cystic fibrosis were identified, which made it possible to determine the preliminary frequency of cystic fibrosis 1: 11425. We analyzed the detection of CF depending on the level of IRT during retest. In MGK, 83 children with a positive retest were examined. In the largest group of newborns with an IRT level of less than 100 ng / ml, consisting of 71 people, 3 children with CF were identified (4.2%). Among 8 children with RTIs from 100 to 200 ng / ml, cystic fibrosis was detected in 3 (37.5%). Out of 4 infants with RTIs more than 200 ng / ml, 2 patients (50%) were identified. Thus, there is a direct relationship between the degree of increase in the biochemical marker and the proportion of identified patients. In children with cystic fibrosis, the primary level of IRT ranged from 88 to 346 ng / ml (average 162 + 85 ng / ml), with retest - from 70 to 448 ng / ml (average 162 + 129 ng / ml). The identified patients by physical indicators did not differ from newborns in the control group. Children were born on average at 39 + 1 week of pregnancy. Their average body length was 51 + 2 cm (48 to 55), average weight 3094 + 432 grams (from 2700 to 4100), MRI 92 + 10. The sweat test was carried out at the age of 37-157 days of life, the level of chlorides in the sweat fluid ranged from 54 to 144 mmol / l (average 92 + 38 mmol / L). Average age diagnosis of cystic fibrosis was 92 + 40 days of life. As part of neonatal screening, we carried out a molecular genetic study of mutations in the CFTR gene using the CF-9 and CF-5 kits, developed by the State Institution MGSC RAMS. 4 types of mutations were found out of 14 studied (del21kb, delF508, delI507, 1677delTA, 2143delT, 2184insA, 394delTT, 3821delT, G542X, W1282X, N1303K, L138ins, R334W, 3849 + 10kbc-> T): in 3 children delF508 homozygous, in 6 delF508 in a compound state (2 with 2184insA mutation, 1 with del21kb mutation, 1 with 3849 + 10kbC → T mutation, 2 with unknown mutation). The studied mutations were not identified in 1 child. Thus, the total information content of chromosomes for the studied spectrum of mutations was 80.0%. The frequency of the delF508 major mutation was 60.0%. Out of 1212 newborns with a high 17-OHP level, 878 (72.4%) children were re-examined, 92 (10.5%) children were under dynamic observation due to a secondary elevated 17-OHP level. 15 children with adrenogenital syndrome were identified. The preliminary frequency of the AGS is 1: 7617. The main part of the established diagnoses (10 patients - 66.7%) was observed in the group of children with a level of 17-0HP during the initial examination of more than 100.0 nmol / L (mean value 602.2 + 384.4 nmol / L). In 8 children, the salt-wasting form of AHS was diagnosed, in 2 - the viril form. In the group of children with primary 17-OHP less than 100.0 nmol / L, 5 patients were identified, of them with the viril form - 3, with the salt-wasting form - 2. The average level of neonatal 17-OHP was 41.1 + 31.6 nmol / l. The results of the first 2 years of screening for AGS showed that the primary blood sampling for 17-OHP in identified patients was carried out on average for 4 + 1 day of life, repeated blood sampling - from 10th to 34th day of life, on average 18 + Day 8. Patients were started at the age of 20 + 12 days of life.

Table 10 Indicators of the level of 17-OHP in newborns depending on the timing of gestation
Gestational age	Number of examined	Percentiles 17-OHP nmol / L
Gestational age	Number of examined

The implementation of the Neoscrin software package made it possible to carry out a statistical analysis of the 17-ОНР level in healthy newborns and to determine its values for the 99th percentile depending on weight and gestational age (Table 10). The results of our studies showed a decrease in the level of 17-ОНР from 150.0 nmol / L with a gestation period of 30 weeks to 28.5 nmol / L with a gestation period of 40 weeks. ОНР "test systems were modified, which led to a change in the results obtained. In order to determine new cut-off levels of 17-OHP concentration in dry blood spots, we carried out a comparative analysis of the 17-OHP level in 1740 newborns, depending on the "Neonatal 17-OHP" kits used: kit A024-110 (modified version ) or kit A015-110 (previous version) (table 11).

Table 11 Indicators of the level of 17-OHP in newborns using the Neonatal 17α-OH-progesterone kit A024-110 and kit A015-110
Gestational age (weeks)	Birth weight (grams)	Percentiles 17-OHP (nmol / L)
		Neonatal set 17α-OHP kit A024-110	Neonatal set 17α-OHP kit A015-110

As our studies have shown, when working with the kits of the modified version of A024-110, the cut-off value of 17-OHP concentration in term infants was 2.5 times lower than when working with the kits of the old version A015-110 (12.2 nmol / L and 30.6 nmol / l, respectively). A similar trend was noted in premature infants, however, the small number of subjects in these groups does not allow to reliably evaluate the statistical data obtained. Thus, the systematic monitoring of screening results using the Neoscrin software package allows calculating the threshold level of the determined metabolites depending on the gestational age and weight of the newborn, evaluating the data obtained and avoiding errors associated with misinterpretation of the results. Of 2205 newborns with high galactose levels, 51 (2.3%) were born before 37 weeks, 2154 (97.7%) - at 37 to 42 weeks of gestation. The average gestational age was 39 + 3 weeks. Average weight newborn 3362 + 526 grams, average body length 51 + 4 cm, MRI 93 + 15. At the threshold level of galactose in dry blood spots of 7.1 mg / dl, the range of its increased values according to the results of stage I of screening ranged from 7.1 to 85.0 mg / dl, the average level was 8.7 mg / dl. In 86.8% of initially positive cases, the galactose level did not exceed 10.0 mg / dL. No dependence of the Gal level on the weight of newborns was revealed. A repeated study was carried out in 1849 (83.9%) children, an average of 18 + 8 day of life. 174 (9.4%) children were under dynamic observation due to a secondary increased level of Gal. Six children with galactosemia were identified: 2 with classical galactosemia, 4 with Duarte's variant. The preliminary frequency of galactosemia is 1: 19340 (classic 1: 58021, Duarte 1: 29010). In children with classical galactosemia, the primary levels of Gal were 20.4 and 85.0 mg / dl, with retest 17.5 and 22 mg / dl, respectively. Average weight 3390 + 205 grams, average body length 51 + 1 cm, MRI 101 + 3. At the initial examination, both children showed regurgitation, icterus of the skin and sclera, the second child - vomiting, loose stools, hepatomegaly. A molecular genetic study revealed the Q188R and K285N mutations in the compound state in one child, the K285N mutation in the heterozygous state in the second; the second mutation was not identified. In children with Duarte's galactosemia, the primary level of Gal ranged from 7.2 to 33.4 mg / dL, with retesting - from 11.5 to 18.4 mg / dL. Average weight 3483 + 505 grams, average body length 53 + 3 cm, MRI 100 + 9. During the initial examination, three children had subicteric sclera, two had regurgitation, one had loose stools, and one had a weeping navel. A molecular genetic study revealed the Q188R and N314D mutations in the compound state in two children, and the N314D mutation in the homozygous state in two children.

Computerization and Neonatal Screening Software

Neonatal screening is a multifaceted complex of measures that requires the constant participation and attention of a number of medical services. Screening involves examining every newborn in the population. At the first stages, the coverage of newborns by screening was monitored by comparing the number of examined children and children born alive. In the first year (1987) of screening, 61.7% of newborns were examined; - 88.0%. More than 10% of newborns remained not examined due to the lack of information about their surname and place of residence, which made it impossible to call children to the Moscow City Hall for examination. In 1990. we developed and implemented a system of personal registration of newborns, which provided for the monthly receipt of lists of children born from all maternity hospitals in the region to KMMGK, comparison of lists and received samples, identification of unexamined ones. Emergency notifications about the need to urgently send unexamined children to the KMMGC were sent to the name of the chief doctors of the healthcare facility. Through the regional health department, service letters were regularly sent to the heads of the territorial health authorities "The results of the neonatal screening program in obstetric institutions of the Krasnodar Region." This system of organizing screening made it possible to increase the level of those examined at PKU up to 99.0% in 1997. Thanks to the established relationship with obstetric institutions of the region during neonatal screening for PKU, in 1994. screening for congenital hypothyroidism has been introduced without much difficulty. Usage manual labor, associated with the registration and registration of the examined newborns, required significant labor costs of the KMMGK employees. The statistical processing of the large volume of information recorded in the work logs was complex and often inaccurate, which necessitated re-calculation. Dynamic changes in screening data made it difficult to keep statistics on paper. All this required an improvement in the methods of organizing screening. To optimize the screening, mutual coordination of actions of obstetric institutions and KMMGK, we in 1997. a computer program was developed "Neonatal screening", which made it possible to automate the registration of test forms received by KMMGK, to take into account the quality and delivery time of samples, to register data on born and examined children. Every month, from each maternity hospital, KMMGK received information on the number of newborns and examined newborns with an attached handwritten list of children. The data on the number of newborns examined in each territory were entered into the form of the computer program "Control by lists", taking into account the date of birth and the date of the analysis. Based on the results of the registered information, the program created a monthly automated report containing information about the quality and timing of delivery of blood samples to the Moscow City Center, the level of screening coverage. Reconciliation of information from maternity hospitals about newborns with received blood samples made it possible to identify children who were not covered by screening. In order to control their examination, the information was registered in the form "Uninvestigated" of the computer program "Neonatal screening". The introduction of this program made it possible to move to a higher level of assessing the quality of neonatal screening, analyze the work of each territory and take measures to improve the organization of screening. Screening coverage for PKU and VH increased from 99.0% in 1997 to 99.6% in 2007. In 2006. 3 new diseases were added to the existing screening for PKU and GV - adrenogenital syndrome, cystic fibrosis and galactosemia. Since it is extremely important in the diagnosis of AHS and galactosemia to establish a diagnosis in the first 2 weeks of life, allowing timely initiation of treatment and prevention of early death of newborns, we have improved the previously existing algorithm for examining newborns. For this purpose, in 2007. we have developed a software package "Neoscreen", consisting of two separate programs: "Registration of newborns in the maternity hospital" and "Screening of newborns". The programs are created using Microsoft Office Access 2003, which is included in the professional edition of Microsoft Office 2003. The program "Registration of newborns in the maternity hospital" is designed to enter information about births, transfer data about them to the Moscow City Center on electronic media, form a territorial register of newborns, daily quality assessment screening, reporting. This program was integrated into all maternity hospitals of the region after conducting training seminars for those responsible for neonatal screening. In order to unify information flows coming from all maternity hospitals, the KMMGK has established the Newborn Screening program. Figure 2 shows a diagram of the information interaction of the Neoscreen software package.

Rice. 2 Scheme of information flows of the Neoscreen software package.

Program "Registration of newborns in the maternity hospital" is the main source of data on births. The main file of the program "screen.mde" can be placed on the computer of the maternity hospital in any convenient place. In addition to this file, the delivery includes an additional file "List of newborns .mbd". This is an intermediary file required for transferring data to and from KMMGK. The main form that appears when the program "Registration of newborns in the maternity hospital" is launched is shown in Fig. 3. Information about the birth is entered in the newborn's card, which opens after clicking the "Cards" button in the main form. The features of the course of pregnancy, childbirth, taking medications, diagnosis in the maternity hospital, Apgar scale, etc. are noted. The data entered in the maternity hospital in the newborn cards are sent to the file "List of newborns.mbd", which is transferred to the KMMGK. In the "Main form" of the program, the time interval corresponding to the date of birth of children, whose analyzes will be sent to KMMGK, is marked. When you click the "Preview information for MGC" button, a table will appear with a list of newborns born in a given period of time. The table shows the date the blood was taken for the test form, or the reason the blood was not drawn.

Fig.3 The main form of the program "Registration of newborns in the maternity hospital".

The list formed in the maternity hospital is preliminarily verified with blood samples from newborns intended for sending to KMMGK. If the information is the same, the table is exported to the file "List of newborns .mbd", which is delivered to the registry of the neonatal screening laboratory KMMGK on an electronic carrier along with test forms by courier. The receptionists check the quality of the delivered test forms, check them against the list and transfer the information about the newborns to the register of the medical genetic consultation. Each child is assigned a personal number, the day and hour of receipt of blood samples in the laboratory are indicated. After that, the MGK data are already recorded on an electronic carrier and sent by courier to the territory. The feedback received from the KMMGK allows the doctor responsible for neonatal screening in the territory to independently and timely analyze the quality of the first stage of neonatal screening (maternity hospital - MHC). The Newborn Screening Program, established at the Moscow City Conservatory, brings together all information about newborns coming from the territories of the region. By analogy with the program "Registration of newborns in a maternity hospital", there is a newborn card (Figure 4), which automatically includes information about the newborn received from the maternity hospital and the results of screening.

Rice. 4 Card of the newborn of the computer program "Screening of newborns".

In case of deviations in the analyzes, the program automatically generates a call and sends it by e-mail to the name of the head physician of the healthcare facility (Figure 5). At the end of the month, the program generates and sends by e-mail reports on the results of screening to each territory. The program "Registration of newborns in a maternity hospital" generates a similar report. Employees of the maternity hospital check the generated report with the report received from the Moscow City Clinical Center, which makes it possible to quickly control the quality of the screening. The Newborn Screening program also optimizes the performance of the neonatal screening laboratory. After entering the information received by the MGK from the territories, the program automatically generates a list of samples for research with the Victor-2 laboratory complex, which can significantly reduce personnel labor costs and the likelihood of errors in preparing samples for research. The accumulation of statistical information during the operation of the Neoscrin software package allows for a personalized analysis of research results and determination of the threshold concentration levels for each screened disease for a specific population.

Fig. 5 Automated form of calling children with high screening results, sent by e-mail

CONCLUSIONS

guidelines

First stage

WORKS PUBLISHED ON THE THEME OF THE DISSERTATION

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Endocrinological problems.

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Medical genetics

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S.A. Matulevich,

	17-hydroxyhydroprogesterone
	adrenogenital syndrome
	congenital hypothyroidism
	total galactose
	immunoreactive trypsin
	iodine deficiency
	Krasnodar region
	Kuban interregional medical and genetic consultation
	medical institutions
	cystic fibrosis
	medical genetic consultation
	mass growth index
	hereditary metabolic diseases
	general intelligence
	polymerase chain reaction
	thyroid-stimulating hormone
	phenylalanine
	phenylalanine hydroxylase
	phenylketonuria
	central nervous system

Cystic fibrosis in newborns is a dangerous pathology that can seriously harm the body. The disease affects organs that are necessary for the production of certain enzymes. Quite often, with such a diagnosis, the glands in the baby suffer, which should produce sweat and mucus. In this case, the resulting enzymes have too high a viscosity, therefore they quickly thicken. Against this background, the elimination of some components from the body becomes difficult. Diagnosis of cystic fibrosis in newborns is based on screening. Additionally, the doctor takes a sweat sample. Only after that, a course of treatment is prescribed, which will minimize the likelihood of anxiety symptoms.

Symptoms of the disease

According to statistics, about 20% of all babies, after being born, suffer from intestinal obstruction. In this case, the meconial ileus is diagnosed. The disease develops in case of insufficient entry into the organs. digestive system sodium, chlorine and water. In the process of its progression, the stomach and intestines are affected. At the next stage, meconium is blocked in them. This feces begins to form immediately after the baby is born. However, only in rare cases does this disease signal the presence of cystic fibrosis. It can only be confirmed by specially conducted screening.

For example, jaundice is characteristic of only half of children whose intestines suffer from obstruction. but this symptom can also indicate the development of a more serious illness in the body. Pathology is formed against the background of excessive thickening of bile. It cannot be cleared from the gallbladder for a long time.

Additionally, the following symptoms of cystic fibrosis may also appear:

Immediately after giving birth, the baby begins to suffer from a severe cough, which greatly debilitates him.
With a detailed study of the glands on the surface, you can find the appearance of a large amount of mucus. Its excessive accumulation appears in the bronchi. It should be removed in time. Otherwise, the risk of blockage increases.
The screening reveals a clinical picture that confirms the presence of serious obstacles to the optimal respiratory regime.

When mucus stagnates in the body, harmful microorganisms begin to actively grow and multiply in infants. Against this background, the risk of developing inflammation of a purulent nature increases. The child also suffers from bronchi from lung infection. A detailed examination can reveal a large number of irregularities in the work of all respiratory organs. The bronchial type of the disease is formed with a genetic predisposition to it. However, there are other reasons that significantly aggravate the situation.

With cystic fibrosis, therapy lasts a lifetime.

Additional signs of the disease

Signs of cystic fibrosis can be noticed when analyzing the physical development of the child. For example, he does not gain weight well. Violations lead to a regression of the fiber, which is located under the skin.

Symptoms are easy to notice with the naked eye - the child is very stunted when compared with peers. When the disease turns into a chronic form, an unpleasant odor begins to emanate from the child.

The stool becomes oily. In it, you can see the remnants of food that has not yet had time to be digested. It contains a large amount of oil impurities. That is why it is very difficult to wash feces from the diaper. This manifestation develops due to a malfunction of the pancreas. Clots of enzymes clog some of its parts. They are necessary for the proper breakdown of food that has entered the intestines. At the last stage of the development of the disease, the digestion process becomes completely disrupted. The organs cannot exchange fats or proteins. To make a diagnosis, a special analysis and screening is carried out general condition health of the little patient. Additionally, a sweat sample is also required.

In the presence of this diagnosis, one should understand the main points that characterize this type of pathology:

If the child does not undergo corrective treatment, then in the future he will lag far behind in development from his peers.
Enzymes cannot enter the intestines. They begin to actively accumulate, which leads to disruptions in the work of this organ.
Within a month, the tissue of the pancreas is completely replaced by the connective tissue. In this case, the child is diagnosed with cystofibrosis.

With the active development of pathology, the normal functioning of the gastrointestinal tract is impossible. Mycoviscidosis most often develops in the intestines. However, against the background of pathology, the work of the lungs is aggravated. Screening helps to diagnose the disease.

Features of the diagnosis

The disease must be identified as soon as possible. Most often, neonatologists diagnose it immediately after birth. It is also important to analyze the general health of the child. Pathology can negatively affect blood vessels or other internal organs.

Diagnostic measures must be carried out without fail during the first month of a child's life. Additionally, it should be noted that a large amount of hormones accumulates in the blood of such children. They can be ten times the normal level. This enables accurate screening results to be obtained. To obtain a complete clinical picture, it is important to carry out the following diagnostic measures:

If the child suspects the presence of this pathology, then sweat samples are taken first. On their basis, it is possible to confirm or deny the diagnosis with confidence. A study is carried out in the ratio of chlorides to the total mass of the liquid. For the analysis, a special marker is used - pilocarpine. It is introduced into the composition skin by means of electrophoresis. Thanks to this, it is possible to activate the work of the sweat gland. After receiving sweat, it will need to be weighed and split into sodium and chlorine ions. For accurate analysis in addition, you will need to hold several such fences. Only after this is it advisable to proceed to screening.
It is important to identify problems in the work of the pancreas. It will be possible to choose the right course of treatment only on the basis of coprological screening. In this case, the amount of fat masses in the general stool is revealed. Today, identification of elastase-1 is most commonly used. This enzyme is produced only by the pancreas.

If cystic fibrosis has been diagnosed, then it will be necessary to establish the degree of its severity. For this, all the results obtained are summarized and generalized in prenatal diagnostics.

Features of restoring the functioning of the body

Only combined treatment can help get rid of cystic fibrosis. You will have to go through it until the end of your life. The action is aimed at thinning sputum with subsequent excretion from the bronchi. Medications also counteract the active growth and development of bacteria harmful to the body in the area of the lungs. Missing pancreatic enzymes are also completely replaced by drugs. Regular intake of vitamins and minerals is also important. With their help, it is possible to liquefy bile.

Diagnostic examination

V medical practice situations arise when it is required to prescribe a dose of the drug that is several times higher than the standard one. Such a need arises in the event of a violation of absorption. Additionally, it is also required to take medications to replace the lack of iron in the body. Thanks to this, it is possible to minimize the negative impact of pathologies.

In the presence of active growth and development of viruses in the lungs, it is required to take antibacterial drugs... Pre-culture of sputum helps to choose the right medicine. Thanks to this, it is possible to identify the microorganism that causes most of the negative manifestations.

To correct the course, sowing will have to be done every three months. It is best to conduct research when the disease is not in an exacerbation stage. If you adhere to this cycle, it will be possible to identify potentially dangerous microorganisms even before the stage of exacerbation. The course of treatment lasts at least three weeks.

To dilute sputum, it is advisable to use various mucolytics.

However, when assigning them, a number of nuances should be taken into account:

If the pathology was diagnosed earlier, then it is advisable to carry out further treatment with the help of Pulmosia. Its positive effect is several times higher than that which is expected from the use of the usual means.
It is allowed to use mucolytics not only as inhalation. They can be given to children in pill form. However, before the appointment, the patient undergoes screening without fail.

The disease is diagnosed in the first days of a child's life.

For quick and effective recovery of the child's body, kinesitherapy is also prescribed. She suggests regular holding specially selected exercises that are performed in a mask. To get a positive result, they should be repeated every day throughout life. The duration of the lesson directly depends on the general condition of the little patient. On average, you will need to allocate about an hour for training.

It is necessary to choose the right remedial measure. This is possible only after confirming the diagnosis. Today, special centers are popular where children undergo rehabilitation for cystic fibrosis.

Key points in feeding your baby

If the baby was previously diagnosed with this diagnosis, then it is best for the woman to breastfeed him. Mixtures can only make the problem worse. However, if there is no other option, then only a specialist in this field can choose it correctly. The process is carried out on the basis of screening.

When diagnosed with cystic fibrosis, a child should receive at least 120% of the nutritional norm for a child at a given age. Of these, only 30% is allocated to fatty foods.

If the baby has been prescribed classical enzymes for the pancreas, then his diet will continue as usual. It is important to consider age characteristics.

Immediately after birth, the baby still does not know how to swallow capsules. It is allowed to pour their contents into a spoon, and then stir with milk. You can also replace it with a mixture or natural juice. The baby should receive pills immediately before the meal. After the teeth appear, parents should make sure that the child does not chew on individual granules.

Cystic fibrosis is a serious diagnosis. It is important to deliver it on time and direct all efforts to eliminate it. Parents should regularly visit the specialist's office and follow all his recommendations. To prolong the life of the baby and his health, he is constantly under close scrutiny.

Today, many maternity hospitals carry out the so-called screening of newborns - an analysis for congenital genetic diseases (phenylketonuria, congenital hypothyroidism, adrenogenital syndrome, galactosemia and cystic fibrosis). The initiative, of course, is very necessary, but it would be nice if the parents were also warned about the observance of some necessary conditions before taking the tests. For example, that it is advisable not to feed the child for half an hour before donating blood. Conversely, the test results may be inaccurate due to the child not getting enough nutrition. This is exactly what happened in our case.
The babies were in their second month. We just managed to get used to a new life, more or less to establish a regime and nutrition. It was a wonderful March day, we were returning from a walk. And then, like a bolt from the blue, a pediatrician called: "According to the screening results, your children have cystic fibrosis, you need to see a genetics specialist, but don't go tomorrow, they take tests from Monday." It was Thursday evening. Out of fright, I confused cystic fibrosis with mononucleosis and managed to ask, "Well, is it being treated?" The pediatrician replied that, they say, I do not know anything, ask the geneticist everything on Monday. At home, of course, the first thing I did was go to consult with Dr. Google. And she died. I learned what cystic fibrosis is and what it is average duration life in patients in our country - 16 years with constant medication. I had a hysteria, it's good that my husband is a more reserved person and poked me at the cystic fibrosis forum, where it was said that the results of the first studies are often false. On this I somehow survived until the morning. In the morning we visited a geneticist. A stern woman doctor greeted us very disapprovingly, they say, why have we got it, we can still take tests on Monday. But when I asked: "Would you be able to wait three days if this was your child?" she softened a little and began to ask about childbirth, nutrition in other conditions. I comforted that with genetic diseases, pregnancy is often difficult, and at that time we already had two older healthy children, and even that pregnancy proceeded without complications. But the analysis was still scheduled for Monday. The next days I either cried, then hoped, then filled out a form for receiving a "Green Card", because I read that in the United States the life expectancy of patients with cystic fibrosis reaches 60 years. I also read that patients with this disease have very salty sweat and it is felt even when kissing. and all three days I didn’t just kiss my daughters, I just licked them, trying to understand whether they were salty or not. And then came Monday. At 8.00 we stood under the geneticist's office. Then an hour for the collection of sweat-salt samples (a cotton swab moistened with saline solution and an electrode are placed on the child's handle, then skin discharge is taken for analysis). And another day of waiting for the results of the analysis. And the long-awaited "The result is negative." My husband shook me and yelled, "Well, I told you so !!!" And I was crying and could not come to my senses.
And only later, from other doctors, I learned about the necessary conditions for screening. And that the result of the first screening is not a verdict or even a diagnosis. For example, for the same cystic fibrosis, after the first screening, a second screening is performed (just in our case, the results came quite late and the geneticist decided not to carry it out), then a sweat-salt test, twice, and if all the results are positive, a genetic analysis for cystic fibrosis. The results of the first analysis were also very surprised - there are two girls, they are identical twins, respectively, if the disease is genetic, most likely both would be sick. Or there should have been some kind of mark, which of the twins had an indicator above normal. Our name and indicator were simply on the map.
In general, dear mothers, any diagnosis requires careful rechecking and you should not panic ahead of time. I know that it is very difficult, almost impossible, I myself am. Still, all children need healthy mothers with strong nerves. What I wish everyone)