One of the most important periods in a woman's life is the period of bearing a child. And in these few months, the expectant mother must do everything in her power to give birth to a healthy baby.

Of course, a pregnant woman should lead healthy lifestyle life: eat right, pay the necessary attention to physical activity and try to avoid any health disorders. But pregnancy lasts nine calendar months - it is very difficult during this time to never feel any ailments or health problems.

How can a pregnant woman cope with possible ailments, and even diseases, if the number of drugs that are allowed for pregnant women is very limited?

Possible effects on the fetus of drugs

It has been repeatedly proven that different drugs can affect the developing fetus at any stage of pregnancy.

The most dangerous influence is in the first trimester of pregnancy, when in a rapidly growing organism, and then in the fetus, all organs and systems of the future organism are laid. The fact is that during this period the placenta is still in the process of formation and cannot become an obstacle to a variety of chemicals, including those that can have an extremely negative effect on the fetus.

Attention! Even drugs that are officially approved for use during pregnancy can sometimes cause various complications in the body of the fetus, and then in the newborn.

If it is necessary to use any drug during pregnancy, the expectant mother should remember:

• Any drug during pregnancy (at any time) can be used only in accordance with the indications and only as prescribed by the attending physician;
• When choosing a medicinal product, it is necessary to give preference only to those medicinal products that have proven tolerability;
• During the period of bearing a child, monotherapy should be preferred, that is, treatment should, if possible, be carried out with only one drug; combined treatment during this period is undesirable;
• A pregnant woman should remember that completely safe and absolutely harmless drugs do not exist.

Careless and / or excessive use of drugs during pregnancy can cause many complications of pregnancy, especially since it is almost impossible to predict the reaction of a pregnant woman's body to a particular drug, even if it is officially approved for use in pregnant women, since sensitivity to certain substances and, accordingly, to medicines can be genetically predetermined, and a substance that is safe in one case can be very dangerous in another.

Careless, thoughtless and improper use of medications during the period of bearing a child can cause such undesirable, and sometimes extremely dangerous consequences:

• Spontaneous abortion, or miscarriage, which can happen at any gestational age;
• Premature onset of the birth process (premature birth), which can result in death and / or the birth of a non-viable baby;
• Cases of stillbirth are possible;
• The result of the use of drugs in different periods of pregnancy may be congenital deformities and anomalies of various organs of the fetus;
• It is believed that one of the consequences of using pregnant medications can be cerebral palsy (cerebral palsy);
• The result of exposure to the fetus of various drugs can be behavioral disorders that appear over time, or mental retardation of the child.

Attention! Even if taking drugs during pregnancy does not cause organic lesions in the fetus, it is very likely that the child will develop allergic reactions.

Scientists and clinicians point out that the effects of taking medications during pregnancy can manifest themselves after the birth of the baby, including even after a few months or even after a few years.

Unfortunately, pregnant women also sometimes get sick, and diseases can be both acute and chronic. And almost any disease of the expectant mother can have an undesirable, that is, harmful, effect on the fetus, which can lead to serious consequences. In such cases, it is necessary to use different medicines to protect the unborn child.

In addition, sometimes pregnant women are prescribed drugs that have a specific effect on the fetus for therapeutic purposes, when it is necessary to correct the condition of the fetus during the prenatal period. And sometimes the fetus has to be treated, for which it is necessary to provide a very specific therapeutic effect.

Of course, these are very responsible appointments, therefore, when prescribing any medication to a pregnant woman, first of all, the doctor evaluates how the potential benefits and possible harm from taking any drug correlate.

Attention! Any medicines for pregnant women are prescribed only if the possible therapeutic effect for the mother's body will undoubtedly exceed the risk of undesirable or even harmful effects on the developing and growing fetus.

In medical practice, it is customary to prescribe to pregnant women only those medications that have been tested and have proven themselves well when used during childbearing.

Is there a list of medications that are safe for pregnant women? Unfortunately, such a list is impossible in principle, since the body of each woman is unique, as is the development of each pregnancy. In addition, as is known, some reactions to various substances in the body can be genetically determined.

Attention! To date, doctors can only assume that some drugs are safer for pregnant women than others, but they cannot be considered completely harmless to the body of the expectant mother, since the possibility of potential harm to a greater or lesser extent is never excluded.

The danger of using drugs during pregnancy

The most dangerous period for the use of any drugs, both of chemical and natural origin, is considered (the first 12 gestational weeks), when all organs and systems are laid in the fetus, which will only develop in the future. It is at this time that the fetus is considered the most vulnerable to any influences, including chemical (medicinal) substances. Among other things, the danger also increases because in the first weeks of pregnancy, the placenta, which will later filter the substances entering the fetal body, has not yet been formed and does not work at full strength.

It should also be taken into account that some medications can have a negative and even damaging effect on male (spermatozoa) and female (ovum) germ cells even before conception. That is, conception can occur with the participation of damaged cells, while it is completely unknown how the embryo will develop and what disorders will appear in the fetus, and then in the newborn.

Attention! Immunosuppressive drugs, certain antibacterial drugs (antibiotics), antitumor drugs, as well as psychotropic drugs and hormonal drugs that have a steroid structure can damage male and / or female germ cells even before pregnancy.

If a man and / or a woman took such drugs, then it makes sense for them to postpone pregnancy planning for about six months after taking such drugs. The fact is that taking certain drugs even at the stage of pregnancy planning can cause undesirable consequences:

• Some drugs are capable of exhibiting an embryotoxic effect, that is, an extremely negative effect on the developing embryo, and this is especially pronounced in the first, second and third gestational weeks - the development of the fetal egg in such cases simply stops.
• There are drugs that have a teratogenic effect on the embryo and fetus, which causes the appearance of a variety of developmental anomalies in the fetus. It is important to understand that the nature of the abnormal development of the fetus is highly dependent on the gestational age, since the fetus at any stage of its development reacts differently to the effects of the drug, although such a reaction is almost always negative.

The teratogenic properties of drugs, that is, their ability to provoke the formation of fetal mutilations, depends on several characteristics of the drug, including:

• The chemical structure of the drug is very important, that is, the structure of the molecules that make up the drug;
• Equally important is how easily the drug (drug molecules) is able to cross the placental barrier;
• Of course, the dosage of the drug and the duration of its administration are of great importance;
• Metabolic features are also important, that is, with what speed the half-life products of this drug can be excreted from the body of a pregnant woman.

Attention! Simultaneous intake of certain drugs enhances their teratogenic effects: if two or more drugs with a teratogenic effect are used simultaneously, this significantly (several times) increases the risk of possible development of various congenital malformations and defects in the fetus.

Drugs that have a fetotoxic effect can have a negative effect on the developing and growing embryo, and then on the fetus, that is, these drugs can have a toxic effect on the fetus after 12 weeks of gestation and until the very birth. The fetotoxic effect manifests itself in different ways: a delay in the general indicators of the fetus, low indicators of physical development (weight and length), dysfunction of various organs and systems of the fetus. It is very important that the fetotoxic effect of some drugs can manifest itself in an already born baby.

It must be remembered that any complications during the development of pregnancy, including such as and / or kidney problems, lead to the fact that drugs accumulate in the mother's body, creating higher concentrations in the blood than the fetotoxic effect increases.

Attention! To protect the fetus from the fetotoxic effects of various drugs, the placenta and its functional state are very important, on which the possibility of manifestation of protective functions depends. It is the placenta that is the barrier that protects the body of the developing fetus from the harmful effects of any factors that can pose a danger to it.

Metabolic processes associated with the excretion of harmful chemicals from the body include not only the placenta, but also the kidneys, liver, adrenal glands and pancreas, as well as other organs.

Five groups of drugs that affect the body of a pregnant woman and the fetus in different ways

• The first group includes those drugs that have successfully passed controlled trials, even on pregnant women. As a result of the tests, it was proved that taking these drugs does not carry any risk to the fetus and its development during the first trimester of pregnancy. Also, no data and / or evidence of possible harm to the fetus of these drugs in late pregnancy has been identified.
• The first group of drugs includes potassium chloride, triiodothyronine, iron preparations, many multivitamin complexes and some other drugs.
• The second group includes medicinal substances that have been tested. But no teratogenic effect on the fetus was found if the mothers took these drugs while carrying the child. However, when tested on animals, some deviations from the norm were observed in the offspring.
• The second group of drugs includes aspirin, insulin, heparin, penicillin antibiotics, metronidazole and other medications.
• The third group includes drugs that have shown teratogenic and / or embryotoxic effects during animal testing. No controlled clinical trials have been conducted in humans or possible results the use of this drug has not been studied. Such drugs are prescribed to pregnant women only when the expected potential benefit outweighs the potential risk.
• The third group of drugs includes fluoroquinolones, isoniazid, gentamicin, antidepressants, antiparkinsonian drugs, and other drugs.
• The fourth group includes drugs, the use of which during pregnancy carries some risk for the growing and developing fetus, but it has been proven that the benefits of using these drugs outweigh the possible harm from side effects.
• The fourth group of drugs includes diclofenac, doxycycline, kanamycin, anticonvulsants and other drugs.
• The fifth group includes drugs whose teratogenic effect has been proven, so their use during pregnancy and even during pregnancy planning is contraindicated. If the use of such drugs is absolutely necessary, for example, to save the life of the mother, then the pregnancy cannot be maintained and must be terminated.

Attention! At any gestational age, the decision on the need for a pregnant woman to take any drug can only be made by the attending gynecologist or a narrow specialist, and only after a detailed study of the pregnant woman's history, the results of all studies and clinical analyzes.During the first trimester of pregnancy, taking any medication is highly undesirable. Only drugs that belong to the first group can be safe during this period..

Attention! If conception occurred spontaneously while taking oral contraceptives, and if oral contraceptives are not stopped until the pregnancy is known for certain, then this almost three times increases the likelihood of chromosomal abnormalities in the fetus, and the risk of having a child with Down syndrome increases by 2 .8 times. In addition, the risk of developing neuroblastoma in newborns, especially in boys, increases (at least 1.2 times).

For reference: Neuroblastoma is a malignant tumor that affects the sympathetic nervous system.

conclusions

It is very important that every pregnant woman remember that any drug during pregnancy can bring not only benefits, but also considerable harm, therefore, any self-administration during this period is unacceptable, since their consequences are unpredictable and in many cases can cause irreparable harm to the developing fetus.

In the early 60s of the XX century, when almost 10,000 children with phocomelia were born in Europe, the relationship of this developmental deformity with the intake of the tranquilizer thalidomide during pregnancy was proved, that is, the fact of drug teratogenesis was established. It is characteristic that preclinical studies of this drug, performed on several types of rodents, did not reveal a teratogenic effect in it. In this regard, at present, most developers of new drugs in the absence of embryotoxic, embryonic and teratogenic effects of the substance in the experiment still prefer not to recommend using during pregnancy until the full safety of such a drug is confirmed after statistical analysis of its use by pregnant women,

At the end of the 60s, the fact of drug teratogenesis was established, which was of a different nature. It was determined that many cases of squamous cell carcinoma of the vagina at puberty and young age are recorded in girls whose mothers during pregnancy took diethylstilbestrol, a synthetic drug of a nonsteroidal structure with a pronounced estrogen-like effect. Later it was found that, in addition to tumors, such girls more often had various anomalies in the development of the genital organs (saddle-shaped or T-shaped uterus, uterine hypoplasia, cervical stenosis), and in male fetuses, the drug caused the development of cysts of the epididymis, their hypoplasia and cryptorchidism in postnatal period. In other words, it has been proven that the side effects of using drugs during pregnancy can be recorded not only in the fetus and newborn, but also develop after a fairly long period of time.

In the late 80s - early 90s, during an experimental study of the effects on the fetus of a number of hormonal drugs (initially, synthetic progestins, and then some glucocorticoids) prescribed to pregnant women, the fact of the so-called behavioral teratogenesis was established. Its essence lies in the fact that until the 13-14th week of pregnancy there are no gender differences in the structure, metabolic and physiological parameters of the fetal brain. Only after this period, the features characteristic of male or female individuals begin to appear, which later determine the differences between them in behavior, aggressiveness, cyclicity (for women) or acyclicity (for men) in the production of sex hormones, which is obviously associated with the sequential inclusion of hereditarily deterministic mechanisms that determine sexual, including psychological differentiation of the male or female organism that is formed in the future.

Thus, if at first drug teratogenesis was understood literally (teratos - freak, genesis - development) and associated with the ability of drugs used during pregnancy to cause gross anatomical developmental anomalies, then in recent years, with the accumulation of factual material, the meaning of the term significantly expanded and currently teratogens are substances whose use before or during pregnancy causes the development of structural disorders, metabolic or physiological dysfunction, changes in psychological or behavioral reactions in a newborn at the time of his birth or in the postnatal period.

The cause of teratogenesis in some cases may be mutations in the germ cells of the parents. In other words, the teratogenic effect in this case is indirect (through mutations) and delayed (the effect on the body of the parents is carried out long before the onset of pregnancy). In such cases, the fertilized egg may be defective, which automatically leads either to the impossibility of its fertilization, or to its improper development after fertilization, which, in turn, can result in either spontaneous cessation of embryo development, or the formation of certain anomalies in the fetus. An example is the use of methotrexate in women for the purpose of conservative treatment. ectopic pregnancy. Like other cytostatics, the drug inhibits mitosis and inhibits the growth of actively proliferating cells, including germ cells. Pregnancy in such women is at high risk of fetal abnormalities. Due to the peculiarities of the pharmacodynamics of anticancer drugs, after their use in women of reproductive age, the risk of having a child with developmental anomalies will remain, which should be taken into account when planning pregnancy in such patients. After antineoplastic therapy, women of childbearing age should be referred to the risk group for developing fetal anomalies, which further requires prenatal diagnosis, starting from early pregnancy.

A certain danger is also presented by drugs with prolonged action, which, when administered to a non-pregnant woman, are in the blood for a long time and can have a negative effect on the fetus if pregnancy occurs during this period. For example, etretinate, one of the metabolites of acitretin, a synthetic analogue of retinoic acid, widely used in recent years for the treatment of psoriasis and congenital ichthyosis, has a half-life of 120 days and has a teratogenic effect in the experiment. Like other synthetic retinoids, it belongs to the class of substances that are absolutely contraindicated for use during pregnancy, as it causes abnormalities in the development of the limbs, bones of the face and skull, heart, central nervous, urinary and reproductive systems, underdevelopment of the auricles.

The synthetic progestin medroxyprogesterone in depot form is used for contraception. A single injection provides a contraceptive effect for 3 months, but later, when the drug no longer has such an effect, its traces are found in the blood for 9-12 months. Synthetic progestins also belong to the group of drugs that are absolutely contraindicated during pregnancy. In case of refusal to use the drug before the onset of a safe pregnancy, patients should use other methods of contraception for 2 years.

How do drugs affect the fetus?

Most often, fetal developmental anomalies are the result of improper development of a fertilized egg due to the action of adverse factors, in particular drugs, on it. At the same time, the period of influence of this factor is important. Applicable to a person, there are three such periods:

1. up to 3 weeks pregnancy (the period of blastogenesis). It is characterized by rapid segmentation of the zygote, the formation of blastomeres and blastocysts. Due to the fact that during this period there is still no differentiation of individual organs and systems of the embryo, for a long time it was believed that in this period the embryo is insensitive to drugs. Later it was proved that the action of drugs in the earliest stages of pregnancy, although not accompanied by the development of gross anomalies in the development of the embryo, but, as a rule, leads to its death (embryo-lethal effect) and spontaneous abortion. Since the medicinal effect in such cases is carried out even before the fact of pregnancy is established, the fact of termination of pregnancy often goes unnoticed by the woman or is regarded as a delay in the onset of the next menstruation. A detailed histological and embryological analysis of the abortion material showed that the effect of drugs during this period is characterized mainly by a general toxic effect. It has also been proven that a number of substances are active teratogens during this period (cyclophosphamide, estrogens);
2. The 4th-9th weeks of pregnancy (the period of organogenesis) are considered the most critical period for inducing birth defects in humans. During this period, there is an intensive crushing of germ cells, their migration and differentiation into various organs. By the 56th day (10 weeks) of pregnancy, the main organs and systems are formed, except for the nervous, genital and sensory organs, the histogenesis of which lasts up to 150 days. During this period, almost all drugs are transferred from the mother's blood to the embryo and their concentration in the blood of the mother and fetus is almost the same. At the same time, the cellular structures of the fetus are more sensitive to the action of drugs than the cells of the mother's body, as a result of which normal morphogenesis may be disturbed and congenital malformations may form;
3. the fetal period, by the beginning of which differentiation of the main organs has already occurred, is characterized by histogenesis and fetal growth. During this period, the biotransformation of drugs in the mother-placenta-fetus system is already underway. The formed placenta begins to perform a barrier function, and therefore the concentration of the drug in the fetus, as a rule, is lower than in the mother's body. The negative effect of drugs during this period usually does not cause gross structural or specific developmental anomalies and is characterized by a slowdown in fetal growth. At the same time, their possible influence on the development of the nervous system, organs of hearing, vision, the reproductive system, especially the female one, as well as the metabolic and functional systems that are forming in the fetus, remains. So, atrophy of the optic nerves, deafness, hydrocephalus and mental retardation are observed in newborns whose mothers used the coumarin derivative warfarin in the II and even III trimesters of pregnancy. During the same period, the phenomenon of “behavioral” teratogenesis described above is formed, which is obviously associated with a violation of the processes of fine differentiation of metabolic processes in brain tissues and functional connections of neurons under the influence of sex steroid hormones.

In addition to the duration of exposure, the dose of the drug, the species sensitivity of the organism to the action of the drug, and the hereditarily determined sensitivity of an individual to the action of a particular drug are important for drug teratogenesis. Thus, the thalidomide tragedy largely occurred because the effect of this drug in the experiment was studied in rats, hamsters and dogs, which, as it turned out later, unlike humans, are not sensitive to the action of thalidomide. At the same time, mouse fetuses were sensitive to the action of acetylsalicylic acid and highly sensitive to glucocorticosteroids. The latter, when used in early pregnancy in humans, lead to cleft palate in no more than 1% of cases. It is important to assess the degree of risk of using certain classes of drugs during pregnancy. As recommended by the Quality Assurance Department food products and medicines, US drugs (FDA), all drugs, depending on the degree of risk and the level of adverse, primarily teratogenic effects on the fetus, are divided into five groups.

1. Category X - drugs, the teratogenic effect of which has been proven in the experiment and clinic. The risk of their use during pregnancy exceeds the possible benefits, and therefore they are categorically contraindicated in pregnant women.
2. Category D - drugs, the teratogenic or other adverse effect of which on the fetus is established. Their use during pregnancy is associated with a risk, but it is lower than the expected benefit.
3. Category C - drugs, the teratogenic or embryotoxic effect of which has been established in the experiment, but clinical trials have not been conducted. The benefits outweigh the risks.
4. Category B - drugs, the teratogenic effect of which was not detected in the experiment, and the embryotoxic effect was not detected in children whose mothers used this drug.
5. Category A: in the experiment and in controlled clinical trials, no negative effect of the drug on the fetus was revealed.

Medicines absolutely contraindicated during pregnancy (category X)

Medications	Consequences for the fetus
Aminopterin	Multiple anomalies, postnatal fetal growth retardation, facial anomalies, fetal death
Androgens	Masculinization of the female fetus, shortening of the limbs, anomalies of the trachea, esophagus, defects in the cardiovascular system
Diethylstilbestrol	Adenocarcinoma of the vagina, pathology of the cervix, pathology of the penis and testicles
Streptomycin
Dieulfiram	Spontaneous abortions, split limbs, clubfoot
Ergotamine	Spontaneous abortions, symptoms of CNS irritation
Estrogens	Congenital heart defects, feminization of the male fetus, vascular anomalies
Inhalation anesthetics	Spontaneous abortions, malformations
Iodides, iodine 131	goiter, hypothyroidism, cretinism
	Mental retardation, ototoxicity, congenital glaucoma, anomalies of the urinary and reproductive systems, fetal death
Thalidomide	Limb defects, anomalies of the heart, kidneys and digestive tract
Trimethadione	Characteristic face (Y-shaped eyebrows, epicanthus, underdevelopment and low position of the auricles, sparse teeth, cleft palate, low-set eyes), anomalies of the heart, esophagus, trachea, mental retardation
Synthetic retinoids (isotretinoin, etretinate)	Anomalies of the limbs, the facial part of the skull, heart defects, central nervous system (hydrocephalus, deafness), urinary and reproductive systems, underdevelopment of the auricles. Mental retardation (>50%)
Raloxifene	Developmental disorders of the reproductive system
Progestins (19-norsteroids)	Masculinization of the female fetus, clitoral enlargement, lumbosacral fusion

Medicines associated with high risk during pregnancy (category B)

Medications	Consequences for the fetus and newborn
Antibiotics Tetracyclines (doxycycline, demeclopicline, minocycline) Aminoglycosides (amikacin, kanamycin, neomycin, netilmicin, tobramycin) Fluoroquinolones Chloramphenicol (levomycetin)	Safe during the first 18 weeks of pregnancy. In more late dates cause discoloration of teeth (brown color), hypoplasia of tooth enamel, impaired bone growth Congenital deafness, nephrotoxic effect Act on cartilage tissue (chondrotoxicity) Agranulocytosis, aplastic anemia, gray syndrome in the neonatal period
Nitrofurintoin	Hemolysis, yellow discoloration of teeth, neonatal hyperbilirubinemia
Antivirals Ganciclovir Ribavirin Zalcitabine	In the experiment, it has a teratogenic and embryotoxic effect. It has a teratogenic and/or embryo-lethal effect in almost all animal species. Described teratogenic effect in two animal species
Antifungals Griseofulvin Fluconazole	Arthropathy A single dose of 150 mg does not lead to a negative effect on the course of pregnancy. Regular intake of 400-800 mg / day causes fetal malformations
	In an experiment on some animal species, a teratogenic effect was registered.
Antidepressants lithium carbonate Tricyclic MAO inhibitors	Congenital heart defects (1:150), especially Ebstein's anomaly, cardiac arrhythmias, goiter, CNS depression, arterial hypotension, neonatal cyanosis Respiratory disorders, tachycardia, urinary retention, neonatal distress Slowdown in the development of the fetus and newborn, impaired behavioral responses
Coumarin derivatives	Warfarin (coumarin) embryopathy in the form of nasal hypoplasia, choanal atresia, chondrodysplasia, blindness, deafness, hydrocephalus, macrocephaly, mental retardation
Indomethacin	Premature closure of the ductus arteriosus, pulmonary hypertension, with prolonged use - growth retardation, impaired cardiopulmonary adaptation (more dangerous in the third trimester of pregnancy)
Anticonvulsants Phenytoin (difenin) Valproic acid Phenobarbital	Hydantoin fetal syndrome (expanded flat and low-lying nail, short nose, ptosis, hypertelorism, maxillary hypoplasia, large mouth, protruding lips, upper lip cleft, etc.) Spina bifida, palate, often additional small anomalies - hemangiomas, inguinal hernia, divergence of the rectus abdominis muscles, telangiectasia, hypertelorism, deformity of the auricles, delayed development. CNS depression, hearing loss, anemia, tremor, withdrawal syndrome, arterial hypertension
ACE inhibitors	Oligohydramnios, malnutrition, contractures of the extremities, deformity of the facial part of the skull, lung hypoplasia, sometimes antenatal death (more dangerous in the second half of pregnancy)
Reserpine	Nasal mucosal hyperemia, hypothermia, bradycardia, CNS depression, lethargy
Chloroquine	Nervous disorders, hearing, balance, vision disorders
Anticancer drugs	Multiple malformations, miscarriage, intrauterine growth retardation
Antithyroid drugs (thiamazole)	Goiter, ulceration of the middle part of the scalp
Pituitary hormone inhibitors Danazol Gesterinone	When taken after 8 weeks, from the moment of conception, it can cause virilization of the female fetus. May cause masculinization of a female fetus
Benzodiazepine derivatives (diazepam, chlozepid)	Depression, drowsiness in the neonatal period (due to very slow elimination), Rare - malformations resembling fetal alcohol syndrome, congenital heart and vascular defects (not proven)
Vitamin D in high dose	Organ calcification
Penicillamine	Possible defects in the development of connective tissue - developmental delay, skin pathology, varicose veins, fragility of venous vessels, hernias

In conclusion, I would like to note that despite the 40 years that have passed since the first description of cases of drug-induced teratogenesis, the study of this problem is still largely at the stage of accumulation and primary comprehension of the material, which is due to a number of reasons. Only a relatively small list of drugs is systematically used and cannot always be canceled in a patient due to pregnancy (anti-epileptic, anti-tuberculosis, tranquilizers for mental illness, oral hypoglycemic drugs for diabetes mellitus, anticoagulants after prosthetic heart valves, etc.). It is the side effects on the fetus of such drugs that have been studied most fully. Every year, a number of new drugs are introduced into medical practice, often with a fundamentally new chemical structure, and although their possible teratogenic effect is being investigated in accordance with international rules, there are species differences that do not allow at the stage of preclinical studies or clinical trials to fully assess the safety of the drug in in terms of its teratogenic effect. These data can only be obtained by conducting expensive multicenter pharmaco-epidemiological studies with an analysis of the use of a particular drug by a large array of patients. It is difficult to assess the long-term effects of the use of drugs during pregnancy, especially when it comes to their possible impact on the mental status or behavioral responses of a person, since their features can be not only a consequence of the use of drugs, but also be determined by hereditarily determined factors, social living conditions. and upbringing of a person, as well as the action of other adverse (including chemical) factors. When registering certain deviations in the development of the fetus or child after using the drug by a pregnant woman, it is difficult to differentiate whether this is the result of the action of the drug or a consequence of the influence of a pathogenic factor on the fetus, necessitating the use of the drug.

Taking into account by doctors of various specialties in their daily activities the facts already accumulated to date will optimize the pharmacotherapy of diseases both before and during pregnancy and avoid the risk of side effects of drugs on the fetus.

Many medicinal substances prescribed during pregnancy pass through the placental barrier and reach the fetus.

There are several options for the passage of chemicals through the placenta: ultrafiltration, simple and facilitated diffusion, active transport, and others. Ultrafiltration processes that depend on the molecular weight of the chemical take place when the molecular weight of the substance does not exceed 100 D. Most drugs used in obstetrics have a large mass, and such a mechanism is irrelevant for them. But many drugs have a molecular weight of 250-500 D and cross the placenta quite easily. Diffusion means the transition of a substance from an area of ​​higher concentration to an area of ​​lower concentration. With the help of this mechanism, the transplacental transition of most lipotropic drugs is carried out. Facilitated diffusion differs from simple diffusion in that the transfer of chemical compounds across the placental membrane along the concentration gradient is carried out by special carriers (enzyme proteins) at a higher rate than is possible with simple diffusion. In this way, for example, the transfer of amino acids is carried out. With the active transport of medicinal substances through the placenta, they are carried by special molecule carriers. These processes are associated with the enzymatic activity of the placenta and are carried out with the expenditure of energy.

The placenta, including the early one, is a metabolically active organ with enzyme systems. It contains enzymes that can play a role in the rate of transfer of certain groups of drugs through the placenta and catalyze the biotransformation of drugs. Therefore, the placenta serves as a kind of final biochemical defense site against exogenous substances before they enter the fetal circulation. For the transfer of chemicals, the thickness of the placental membrane is important: at the beginning of pregnancy, it has a relatively large thickness (25 microns), and in the last trimester of pregnancy, the thickness of the epithelial layer of the trophoblast sharply decreases to 2 microns by the time of delivery, which greatly facilitates the passage of drugs. Various diseases, including diabetes mellitus, preeclampsia, significantly affect the permeability of the placental membrane.

The ability of the drug to bind to blood proteins has a significant effect on the transplacental transition. The higher its ability to bind like this, the slower it crosses the placenta.

Until the end of the 1970s, there was a misconception that a drug that does not cross the placenta to the fetus is harmless and can be widely used for ante and intranatal therapy. In 1969, the results of experimental studies by I.P. Romanyugin, who found that the administration of oxytocin and viadril to pregnant female rats worsens a number of fetal vital signs, while the intake of these drugs directly to intrauterine fetuses does not cause changes in their condition. The author believed that this circumstance can be explained by the negative effect of these drugs on the placenta. The conducted studies of placental bioenergy confirmed the inhibition of respiratory processes and oxidative phosphorylation in placental mitochondria under the influence of intravenous administration of oxytocin. Less harmful was its subcutaneous injection. Practically did not cause changes in bioenergetics stimulation labor activity intravenous administration of oxytocin against the background of serotonin, which can be explained by the electron-donor properties of the latter and its stimulation of adaptive reactions through cyclase systems.

Significantly worsens the bioenergetics of the fetus predion (viadryl), used to relieve childbirth. At the same time, the use of sodium oxybate (sodium hydroxybutyrate) for labor pain relief not only does not lead to disturbances in redox processes in placental mitochondria, but even somewhat stimulates their respiratory activity.

It should be borne in mind that, in addition to the transplacental exchange of drugs, their paraplacental transition is also possible.

The organs of the fetus, especially the gastrointestinal tract, are directly connected with the amniotic cavity and the fluid that fills it, so the drugs present in it are easily absorbed by the fetus.

The intestines and kidneys are involved in excretion. These modes of transport of substances include not only maternal and fetal blood, but also amniotic fluid and fetal urine.

According to the effect on the fetus, drugs are divided into three main groups:

• do not cross the placenta and, therefore, do not have a direct effect on the fetus;
• carrying out the transplacental transition and affecting the fetus;
• passing through the placenta and accumulating in the body of the fetus.

It should be noted that for substances capable of penetrating the placenta, there is no proportional dependence of toxicity on the degree of their penetration.

Substances with toxic effects can be classified according to their ability to cause non-specific and specific toxic effects in the fetus.

Non-specific reactions can be induced by most drugs if their dosage is exceeded.

Substances that exhibit a specific effect affect the development of the fetus, regardless of whether they have a toxic effect on the mother's body or not.

The specific toxic effect of drugs can be embryotoxic, fetotoxic and teratogenic.

The embryotoxic effect is especially evident in the first three weeks of pregnancy due to the effect of the drug on the zygote and blastocyst. Some antibiotics have a similar effect, as well as hormones (for example, estrogens), cytostatics, barbiturates, sulfa drugs.

The fetotoxic effect of pharmacological preparations is manifested in a general strong toxic effect on the fetus or the occurrence of one or another specific side effect. The fetotoxic effect of drugs can be expressed in the form of both structural and functional abnormalities. So, for example, indomethacin, like most NSAIDs received by pregnant women in the first trimester, leads to IGR.

Teratogenic effect is a property of a physical, chemical or biological factor, in particular a drug, to cause disturbances in the processes of embryogenesis, leading to developmental anomalies.

The nature of the defect is determined by the gestational age. Chemical substances can significantly affect the development of organs during their intensive formation. Some authors distinguish the "classic teratogenic period", during which the greatest teratogenic effect of substances is noted. This is due to the fact that a certain violation of morphogenesis corresponds to the action of a particular substance on target organs during their intensive formation. The duration of the "classic teratogenic period" is 31-71 days from the last menstruation (5-10 weeks of gestation), which corresponds to the beginning of the formation of the main organs and tissues (from the heart and central nervous system to the palate and auricles).

The action of some chemicals may be slow, delayed, there may be a latent period lasting years: from the effect of the substance on the fetus to the discovery of its effect. Diethylstilbestrol is a classic example of a delayed-acting teratogen. From 1940 to 1971, 6,000,000 mothers and their children were exposed to this estrogen, which was prescribed to treat miscarriage and premature birth. In women whose mothers received diethylstilbestrol, the risk of developing adenocarcinoma of the cervix and vagina (a very rare form of cancer in women under the age of 50 years) is increased, and in men - reproductive diseases.

It must be borne in mind that not only drugs that a woman receives during pregnancy can have a teratogenic effect. Some of them, used before conception, cause fetal malformations. For example, retinoids, teratogens with a long latency period, can affect the development of the fetus even if the course of their use is completed before conception.

Taking medications by the father affects gametogenesis and can cause fetal malformations. These drugs include drugs for anesthesia, antiepileptic drugs, diazepam, spironolactone, cimetidine.

For example, the use of diazepam by the father increases the likelihood of a non-closure of the upper lip and / or hard palate in the unborn child. In the semen of men receiving antiepileptic drugs, especially phenytoin, morphologically altered and inactive spermatozoa were found.

The term "teratogenicity" is used quite widely by some authors. They bring into this concept all deviations from the norm in the process of development from the moment of fertilization to childbirth: death, deformities, developmental delay, functional insufficiency.

Some authors distinguish "behavioral teratogenicity". It consists in a violation of behavior, intelligence, memory in postnatal life in a person exposed to perinatal (or neonatal) exposure to xenobiotics, including drugs. In humans, a negative effect on the behavior of offspring of ethanol, a number of narcotic analgesics, phenytoin, and sex hormones has been reliably established. In animal experiments, a significant number of pharmacological agents have been identified, the impact of which disrupts behavior in postnatal life. These substances include: chlorpromazine, haloperidol, phenytoin, corticosteroids, sex hormones, retinol, cytostatics. These substances disrupt the production of conditioned reflexes, lead to explosive bursts of hyperactivity, and social behavior disorders.

The most reliable information about the risk of using a particular drug is provided by direct clinical observations. However, these data are scarce. Clinical observations should be preceded by an experimental study of the properties of a pharmacological preparation in experiments on laboratory animals.

The primary basis for the use of animals in biological experimental systems is the fact that known base chemicals that are teratogenic in humans are most often teratogenic in animals. But the inverse relationship is not always noted, and a substance that is harmless to animals is not always safe for humans. This is due to interspecific differences, which are due to the difference in the internal sensitivity of embryonic and fetal processes to the penetration of chemicals, the rate of embryogenesis, and the characteristics of pharmacokinetic factors.

Although almost 1,000 chemicals are known to be teratogenic in animals, only a few chemicals have been proven to be teratogenic in humans. These include: alcohol, chemotherapy drugs (antimetabolites, alkylating agents), anticonvulsants (trimethadione, valproic acid, phenytoin, carbamazepine), androgens, warfarin, danazol, diethylstilbestrol, lithium, retinoids, thalidomide.

In 1991, the WHO International Commission for the control of the use of drugs during pregnancy began to work. According to her, 86% of the women observed were taking medications, while receiving an average of 2.9 drugs (from 1 to 15) prescribed by a doctor.

According to V.V. Abramchenko (1994), 80–90% of women take medications during pregnancy, 40–60% use them in the first trimester of pregnancy, and 25% take them for a long time.

Most doctors around the world have decided to stop the uncontrolled use of drugs during pregnancy. Government programs are being implemented to control the use of medicines.

One of the steps to organize safe treatment during pregnancy was the mandatory introduction of special labeling of medicines. Labels contain information about the degree of risk of using the drug during pregnancy and the level of studies proving its safety. For example, the classifications introduced by the Australian government (An Australian cate- orisation of risk of dru-use in pre-nancy) and The US Food and Drug Administration (FDA) are very similar and contain 5 main categories:

Category A - the drug that was used big amount pregnant women (including in controlled studies) and women of childbearing age, while there is no reasonable evidence that this led to an increase in the incidence of fetal malformations, no direct or indirect side effects on the fetus were detected (example: folic acid, levothyroxine sodium) .

Category B - Animal studies have shown the safety of the drug, but there are no data from clinical trials, or side effects have been identified in animal studies that have not been confirmed by clinical trials (example: amoxicillin).

Category C - a drug that, due to the pharmacological effect, causes (or may cause) adverse side effects, but does not cause malformations (side effects may be reversible), or animal studies have proven the danger of the drug, but clinical trials have not been conducted. A drug in this category should only be used if the benefit outweighs the potential risk to the fetus (example: nifedipine, omeprazole).

Category D - a drug that, due to the pharmacological effect, causes (or may cause) irreversible adverse side effects, malformations. Or studies have proven the danger of the drug for people, but despite this, it is possible to use the drug for health reasons when safer drugs are ineffective (example: phenytoin, propylthiouracil).

The drug is contraindicated in pregnant women and women in whom pregnancy may occur (example: warfarin, thalidomide).

The appendix presents data on the safety of using various groups of drugs and their effect on the fetus.

Impact on the fetus of certain groups of drugs taken during pregnancy

The most commonly used drugs include the central neurotropic antihypertensive drugs methyldopa and clonidine (category B). The mechanism of their action is not quite usual: they have a partial central agonistic effect and at the same time inhibit sympathetic activity at the level of preganglionic sympathetic endings. Due to the fact that against the background of these drugs, the excretion of sodium and water decreases, it is advisable to combine their administration with diuretics. It should be borne in mind that at high dosages, the fetus is able to accumulate drugs, which can reduce the excitability of its central nervous system and cause a depressive state.

A dangerous complication may be the development of autoimmune hemolytic anemia, liver damage with prolonged use of drugs.

Ganglioblockers. Hexamethonium benzosulfonate (benzohexonium), azamethonium bromide (pentamine) and other drugs are increasingly used in obstetrics. Caution is required in their use due to the possible deterioration of uteroplacental circulation. Cases of fetal death due to hypoxia have been described.

Sympatholytics. Reserpine and other similar drugs disrupt the transmission of excitation at the level of the presynaptic membrane of adrenergic fibers. With prolonged use, depletion of catecholamines in the brain is possible, which leads to depression of the fetal central nervous system, drowsiness, and depression in the newborn. May cause fetal growth retardation. During pregnancy, it must be used with great caution.

b Adrenoblockers. Propranolol, atenolol, metoprolol (category C), having a structural similarity to endogenous catecholamines, bind to postsynaptic membrane receptors. Their use should be avoided in the first trimester and a few days before delivery due to possible side effects. The drugs of this group cause a decrease in renal blood flow and a drop in glomerular filtration. Removing the inhibitory effect of adrenomimetics, drugs can lead to premature birth, worsen uteroplacental circulation, which is fraught with a delay in fetal development. The effect on the fetus is manifested in the development of bradycardia, hypoglycemia, jaundice, respiratory depression of the newborn.

Vasodilators. There are venous, arteriolar and mixed vasodilators. Typical venous vasodilators include nitroglycerin. It reduces blood pressure in the mother, improves fetoplacental circulation.

It is not believed to lower fetal blood pressure. However, the drug is classified as category C, and its use is recommended only during childbirth. Hydralazine (category C) is an arteriolar vasodilator. In women, it can cause tachycardia, angina pectoris, gastrointestinal dysfunction, accompanied by vomiting.

Diazoxide is a thiazidine derivative with a vasodilating effect. The drug, passing through the placenta, inhibits the secretion of insulin by the fetus, which can lead to prolonged hyperglycemia.

Calcium channel blockers prevent the entry of calcium ions into the cell through voltage-gated channels of the cytoplasmic membrane. As a result of this, the substances of this group have a relaxing effect on blood vessels, the gastrointestinal tract, urinary tract, uterus. There are the following chemical groups of calcium channel blockers:

phenylalkylamines: verapamil;

benzodiazepines: diltiazem;

Dihydropyridines: nifedipine, nicardipine, nimodipine, isradipine;

diphenylpiperazines: cinnarizine, lidoflazin;

tetralin derivatives: mibefradin.

There is experience in the use of these drugs during pregnancy in hypertensive conditions, premature birth, with an asymmetric form of fetal growth retardation. However, the use of these drugs must be treated with extreme caution. Their effect on the fetus is not well understood. Most of the drugs in this group are classified as category C. There is a known negative effect on the fetus associated with the use of large dosages, which is expressed in the deterioration of uterine blood flow.

Angiotensin-converting enzyme inhibitors prevent the conversion of angiotensin I to angiotensin II, which causes vasospasm and promotes the release of aldosterone. Preparations of this group (captopril, saralazine) are contraindicated during the entire pregnancy, since their administration leads to a delay in fetal development, oligohydramnios, and damage to the kidneys of the fetus.

Medicinal plants have antihypertensive activity: hawthorn flowers, motherwort grass, cudweed grass, chamomile flowers, cumin seeds, valerian root, white mistletoe grass. They must be applied in the form of fees. There are biologically active additives (BAA) that normalize blood pressure. These include: circulin, hawthorn, hypotensin plus.

Diuretics. Diuretics are substances that cause an increase in the excretion of urine from the body and a decrease in the fluid content in the tissues and serous cavities.

The appointment of diuretics is necessary according to strict indications, especially with preeclampsia. It is necessary to be guided by the severity of violations of the concentration and excretory function of the kidneys, the presence of symptoms of overload of the right heart. All three groups of drugs are used, however, it should be remembered that spironolactone derivatives (category C) are contraindicated in initial renal failure, their use is not recommended before 12 weeks of pregnancy. Triamterene (category C) should be prescribed only for strict indications.

Long-term therapy with thiazide diuretics can lead to significant electrolyte imbalance in the mother and fetus. Hydrochlorothiazide (category D) is contraindicated in pregnancy. The use of saluretics before childbirth can cause hyperbilirubinemia in the newborn. Some authors recommend avoiding furosemide (category C) during pregnancy. The shorter the gestational age, the more pronounced the delay of furosemide in the fetus. Long-term effects of the use of furosemide, which acts as a behavioral teratogen, causing increased irritability and excitability of children, were also found.

It should be borne in mind that, according to several controlled studies, the use of diuretics during preeclampsia not only does not improve long-term results, but may also worsen the prognosis of childbirth.

Attention should be paid to a wide range of herbal diuretics, the toxic effect of which is much less pronounced. Cowberry leaves, staminate orthosiphon, bearberry, blue cornflower flowers have diuretic properties. For edema of pregnant women, it is recommended to use preparations that also contain birch leaves and buds, licorice root, lingonberry berries, horsetail grass, three-leaf watch leaves, crushed rose hips. It is possible to use dietary supplements.

Anti-inflammatory drugs. The most common group in this area is non-steroidal anti-inflammatory drugs (NSAIDs). This group of drugs has analgesic and antipyretic properties along with a particularly pronounced anti-inflammatory activity. The drugs of this group include a number of derivatives of phenylpropionic, phenylacetic acids [ibuprofen, diclofenac (category B)], compounds containing an indole group (indomethacin (category C)), drugs of the pyrazolone series [phenylbutazone (category C)]. Pregnant women often use these medicines for self-medication at various stages of pregnancy, without realizing what consequences this will entail. The drugs of this group, with rare exceptions, are contraindicated in the III trimester of pregnancy (pass into category D) due to the risk of premature closure of the ductus arteriosus. In the next few hours after administration, the drugs of this group lead to a decrease in the pulsation parameters of the fetal vessels. In the early stages of pregnancy, it is also necessary to avoid taking NSAIDs, since they have an embryotoxic effect, can lead to left ventricular hypoplasia, ventricular septal defects. The safest agent of this group can be considered acetylsalicylic acid. There are results of controlled studies that allow us to consider aspirin (in small doses - up to 100 mg / day) safe in the II and III trimesters of pregnancy. It was previously believed that taking aspirin leads to internal hemorrhages of the fetus, but at present this fact is not confirmed in scientific studies.

Conducted multicenter randomized placebo-controlled study (CLASP) on the prophylactic use of low doses of aspirin (60 mg) in pregnant women at high risk of developing obstetric and perinatal pathology with a burdened obstetric and somatic history showed that long-term administration of low doses of aspirin, starting from the second half of pregnancy, had no effect on the incidence of preeclampsia and gestational hypertension, but contributed to a decrease in the incidence of severe forms of these complications, there was a clear tendency to prolong pregnancy, reduce rates of preterm birth and low birth weight babies. Experience has been gained in the use of microdoses of acetylsalicylic acid in patients with the threat of early spontaneous miscarriage, as well as with extragenital diseases, starting from early gestation. The inclusion of microdoses of aspirin in the complex of preventive and therapeutic measures of primary PI improved blood flow in microvessels, corrected tissue hypoxia, and suppressed apoptosis. Despite the absence of a decrease in the incidence of preeclampsia in women with aggravated current pregnancy, there was a significant decrease in their severity against the background of taking microdoses of aspirin from early gestation. In small doses, acetylsalicylic acid affects the ratio of prostacyclin / thromboxane, selectively inhibits the synthesis of thromboxane, thus affecting the aggregation properties of blood and microcirculation. Acetylsalicylic acid blocks the cyclooxygenase of endothelial cells, in which prostacyclin is synthesized, the membrane-stabilizing effects of aspirin are also described.

In recent years, more and more attention of specialists has been directed to a new group of NSAIDs - selective cyclooxygenase2 inhibitors. These include: celecoxib, valdecoxib, refecoxib. Their advantages, in comparison with classical NSAIDs, are significantly lower toxicity, less effect on the fetus, and high efficiency. For example, in 2002, a controlled study was conducted comparing the safety of the selective cyclooxygenase 2 inhibitor celecoxib with indomethacin (a non-selective NSAID). The scientists concluded that celecoxib is significantly safer than indomethacin. There is an assumption that selective NSAIDs can be used to treat preterm labor, in vitro studies confirm their pronounced tocolytic activity.

It should be borne in mind that there are medicinal plants and dietary supplements with anti-inflammatory properties. For example, evening primrose oil relieves pain and inflammation, and has a calming effect on the nervous system. Its preparations are recommended for acute and especially chronic, long-term inflammatory processes that worsen during pregnancy, including sexually transmitted diseases, diseases of the respiratory and urinary organs. In the perinatal aspect, their long-term use in combination with antioxidants (vitamin E in the form of a sum of tocopherols) is promising for placental insufficiency caused or combined with chronic infection, as well as prolonged intoxication.

Glucocorticoids. Systemic use of glucocorticoids is safe only in case of adrenal insufficiency in the mother, when dosages close to physiological are used. Glucocorticoids are classified as category C, that is, they must be prescribed for good reasons (systemic diseases of the connective tissue, hormone-dependent bronchial asthma). Sometimes the therapeutic effect of these drugs in the mother is taken into account more than the risk of fetal dysmorphogenesis. But it should be remembered that long-term use of prednisolone and other glucocorticoids, in addition to an anomaly in the development of connective tissue, can lead to a delay in fetal development. With prolonged use of prednisolone (category B) in the last trimester of pregnancy, a newborn can experience hypoglycemia, adrenal crises. Cases of stillbirth are described when a woman takes cortisol throughout her pregnancy (at autopsy, atrophy of the adrenal cortex). For the prevention of hyaline membrane disease, glucocorticoids are prescribed shortly before childbirth. The maximum effect is achieved in children born more than 24 hours and less than 7 days after the start of treatment. Glucocorticoids reduce not only the risk of developing respiratory diseases, but also some other forms of neonatal pathology. Thus, the risk of intraventricular hematomas is halved after the use of corticosteroids.

A positive effect is also noted in the case of necrotizing enterocolitis. Phytohormones, in particular licorice root, have a corticosteroid-like, immunomodulatory, anti-inflammatory effect, they can be used for preconception preparation during pregnancy, allowing you to reduce the dose of prescribed corticosteroids.

Antihistamines. Histamine plays an important role in the development of the fetus. It easily passes the placental barrier, provides normal conditions for implantation and development of the embryo, as it promotes the transformation of endometrial stroma cells into decidual tissue. Influencing the permeability of membranes, it regulates the exchange processes between mother and fetus, organogenesis. Therefore, the appointment of antihistamines during pregnancy should be treated with extreme caution. There are data in the literature on the teratogenicity of antihistamines. Meclizine and cyclizine can cause pyloric stenosis, syndactyly, anal atresia, hypoplasia of the lungs, bladder, kidneys, and hydrocephalus in the fetus. Their use in early pregnancy caused fetal resorption. It has been proven that the frequency of anomalies is 5% (against 1.5% in the population). Taking diphenhydramine by the mother shortly before childbirth can lead to a generalized tremor in the child, diarrhea a few hours after birth (a manifestation of diphenhydramine intoxication).

If the mother has been taking diphenhydramine for a long time, the newborn may experience withdrawal symptoms, manifested by anxiety, increased excitability, and convulsions.

Antidiabetic agents. It is difficult to establish the harmful effect of antidiabetic drugs on the fetus, since diabetes mellitus itself can lead to fetal abnormalities.

Insulin (category B) has a large molecular weight and almost does not penetrate the placental barrier, therefore it has a minimal effect on the fetus. During pregnancy, women with diabetes should use insulin. Recently, information has emerged about the possible ability of insulin to increase the likelihood of heart defects in children. Information requires deep research.

When using sulfanilamide hypoglycemic agents, a high level of perinatal mortality is noted, when using chlorpropamide (category D) - 63%, tolbutamide (category D) - 23%. They note a violation of the implantation process, fetal resorption, growth arrest, in 6–13% of cases developmental anomalies (microphthalmos, anophthalmia, cataracts, anencephaly) are detected. The use of these drugs during pregnancy is contraindicated. You should also abandon glibenclamide, glipizide, metformin, repaglinide.

To achieve the main goal in solving the urgent problem of "diabetes and pregnancy" - normoglycemia - with a decrease in the intake of insulin and sulfonamide derivatives, you can use herbal preparations (bean leaves, blueberry leaves, chopped burdock root, chopped oat straw, flax seeds, dioecious nettle leaves, leaves birch, dandelion root, St.

cardiac glycosides. They easily cross the placental barrier. When they are used, the same concentration of the substance in the plasma of the mother and fetus is established. However, there is an opinion that the fetus has an increased resistance to cardiac glycosides. Some authors argue that in the first trimester of pregnancy, the fetus is subject to a pronounced effect of digitoxin and digoxin (category B), which leads to bradycardia.

Data on the teratogenic effect of cardiac glycosides have not been received.

Anticoagulants. Due to the fact that during pregnancy conditions for the occurrence of thrombosis are often created, the question of the use of anticoagulants is relevant. For a long time, sodium heparin (category B) was the drug of choice during pregnancy. Due to its high molecular weight, it almost does not pass the placental barrier and, therefore, has no direct effect on the fetus. The drug can be used at any stage of pregnancy. However, there are certain inconveniences of its use: the need to control the time of blood clotting with prolonged administration, the possibility of thrombocytopenia. Therefore, some authors suggest the use of low-dose heparin, which is devoid of the disadvantages inherent in heparin.

As a prophylactic agent in the II and III trimester of pregnancy, it is possible to use small doses of acetylsalicylic acid.

Blueberry extract is recommended for the prevention of thrombotic complications. It contains more than 15 different anthocyanosides, which improve the functioning of cell membranes, prevent the aggregation of blood cells, preventing the formation of blood clots, the destruction of collagen, which strengthens the walls of blood vessels.

Bilberry extract also has antioxidant properties, which allows you to use both of these effects in violation of vascular tone and hypoxia.

Anti-infective agents. Most anti-infective agents adversely affect the fetus, so only a limited number of them are used during pregnancy. In the case of this group of drugs, it is necessary to carefully consider the ratio of benefit to the mother and risk to the fetus.

Antibiotics. The most safe for the fetus are antibiotics of the penicillin group (benzylpenicillin, ampicillin, oxacillin, dicloxacillin, amoxicillin) and the cephalosporin group (cephalexin, cephalothin, cephaloridine).

Benzylpenicillin (category B) easily crosses the placenta (25-75%). From the blood of the fetus, the substance quickly enters the tissues. According to experimental studies and clinical observations, penicillin is safe for the fetus. However, there are experimental studies on animals that have shown an embryotoxic effect with the combined use of penicillin and sulfonamides (deformity of the limbs, rupture of the anterior abdominal wall, microphthalmia, hydronephrosis have been noted).

A feature of ampicillin (category B) is its ability to accumulate in the amniotic fluid (against the background of a decrease in its concentration in the fetal blood). Therefore, the therapeutic use of ampicillin in chorioamnionitis is advisable. The drug has neither teratogenic nor embryotoxic effects.

Cephalosporins (category B) differ in their pharmacological properties. Cefalotin and cephaloridine quickly pass through the placenta (up to 100%), cephalexin to a lesser extent (40%). The drugs can be used in the treatment of fetal infections. Cephalosporins can lead to hypoprothrombinemia due to a decrease in vitamin K metabolism, which poses a risk of bleeding.

Imipenem is a blactam antibiotic. Widely used, does not have fetotoxic and teratogenic effects.

Erythromycin (category B) is a macrolide. It is considered a relatively harmless antibiotic. Has a low degree of penetration through the placenta (10-12%). However, it should be borne in mind that erythromycin is able to accumulate in the fetal liver and has hepatotoxicity. The exception is erythromycin estolate (category X), which, due to hepatotoxicity, is contraindicated in pregnancy.

Levomycetins are slowly excreted from the body of the fetus, have a teratogenic, embryotoxic effect. In experiments on animals under the influence of chloramphenicol (levomycetin), anophthalmia, hydronephrosis, and weight loss were noted. The use of chloramphenicol during pregnancy is dangerous because of the possibility of developing a "gray" syndrome in the fetus associated with a violation of the glucuronization process in the liver.

The placental permeability index for tetracyclines is 25–70%. These include tetracycline (category D), doxycycline (category D) and others. In experiments on animals, the accumulation of these drugs in bone tissue and teeth is noted. Observe the deformation of the limbs, weight loss, fetal death, hydronephrosis.

Tetracyclines can cause fatty liver, a violation of protein synthesis. Therefore, the use of tetracyclines during pregnancy is contraindicated.

Aminoglycosides are able to pass the placental barrier to varying degrees. Amikacin (category C), streptomycin (category D) - 100%, kanamycin (category D) - 20-50%. Aminoglycosides have ototoxicity, nephrotoxicity. Streptomycin is the most toxic. Toxicity is most pronounced when taking drugs from 12 to 20 weeks of pregnancy. Similar properties are possessed by gentamicin (category C), tobramycin (category C), sisomycin. Aminoglycosides are contraindicated during pregnancy.

Antifungal drugs (nystatin, miconazole) used topically in pregnant women do not have an embryofetotoxic effect. However, the systemic use of drugs is not recommended, since the consequences have been little studied.

Sulfanilamide drugs cross the placental barrier and reach the fetus. They are able to displace bilirubin from protein binding, increasing jaundice, increasing the risk of bilirubin encephalopathy. Long-acting sulfonamides are the most dangerous for pregnant women. The use during pregnancy of combined preparations containing trimethoprim (category C), which disrupts the synthesis of folic and nucleic acids in fetal tissues, is contraindicated.

Fluoroquinolones (category C) are also contraindicated during pregnancy: ofloxacin, ciprofloxacin.

Nitrofurans (category B) cross the placenta and accumulate in the amniotic fluid in a limited amount, but they can cause hemolysis of the blood in the fetus due to the effect on glucose-6-phosphate dehydrogenase. It is not recommended to prescribe nitrofurans in the first trimester, at the end of pregnancy and during childbirth.

Metronidazole is an antiprotozoal agent. Easily overcomes the placental barrier and penetrates the fetus. In animal experiments and in clinical observations, no fetotoxic effect of the drug was noted, therefore, it is believed that metronidazole is safe. However, there is evidence of the ability of metronidazole to inhibit a number of fetal hepatic enzymes, and there is also evidence of its teratogenic activity. The drug is contraindicated in the first trimester of pregnancy.

Anti-tuberculosis drugs cause significant damage to the fetus. In the case of the use of isonicotinic acid hydrazides (isoniazid) in the first trimester of pregnancy, gross anomalies in the development of the fetus occur (anencephaly, heart defects, hydrocephalus, ectopia of the bladder, hypospadias, closure of the anus, and others). These drugs are neurotoxic and cause neuroplegia.

Antiviral drugs. Among antiviral drugs, acyclovir (category C) is considered the most acceptable, but its administration requires strict indications. The closer to the date of birth it is prescribed, the less consequences can be expected. In HIV infection, zidovudine (category C) is used from the 14th week of pregnancy.

Antiemetics. Treatment should begin with vitamin B6 preparations (category A) (pyridoxine, pyridoxal phosphate). In case of ineffectiveness, metoclopramide is used, which is relatively safe.

Doxylamine and chlorpromazine are contraindicated in the last weeks of pregnancy. These drugs can cause fetal malformations.

Anticonvulsants. Among anticonvulsants, the safest drug is magnesium sulfate. It has no embryofetotoxic effect and is the drug of choice in the treatment of eclampsia. With epileptic convulsions, the use of carbamazepine, clonazepam, ethosuximide (category C) is possible. These drugs have a proven teratogenic effect associated with damage to the neural tube of the fetus, increase the risk of bleeding in the fetus. Contraindicated: valproic acid, phenytoin, phenobarbital, as they have pronounced teratogenic properties.

Sedatives and hypnotics. The most acceptable of this group are buspirone and zolpidem. The use of benzodiazepines (diazepam, oxazepam, chlordiazepoxide) is undesirable, as it increases the risk of fetal malformations (cleavage of the hard palate, upper lip, impaired nervous development). The use of benzodiazepines can lead to drug depression in the fetus and newborn. Long-term use of high doses of these drugs during full-term pregnancy may lead to drug dependence in the fetus. Barbiturates are contraindicated (see "Anticonvulsants").

Many medicinal plants that can be used, including for the purpose of labor pain relief, have a sedative and hypnotic effect. The collections include: peppermint leaves, three-leaf watch leaves, valerian root, hop seedlings, chamomile flowers, cumin seeds, fennel fruits, motherwort herb. The appointment of dietary supplements (kawakava, evening primrose oil, gingko biloba extract, gotu kola) is recommended.

Antidepressants. Many antidepressants are considered teratogens, including amitriptyline (category D), clomipramine (category C), imipramine (category D), nortriptyline (category D). Monoamine oxidase inhibitors (MAOIs) are contraindicated in pregnancy. Fluoxetine, a serotonin reuptake inhibitor, can be considered relatively safe. It can be used in the first trimester of pregnancy. New antidepressants are used: setralin (category B), paroxetine (category B). So far, there is no evidence that they increase the risk of congenital malformations of the fetus.

Almost any drug, directly or indirectly through the maternal organism, affects the development of the fetus. The pharmacological and teratogenic effects of most drugs on the fetus are not well understood. Therefore, they must be treated as potentially dangerous.

In the context of increasing polypharmacy (unreasonable prescribing of combinations of drugs), it must be remembered that even outside of pregnancy, the appointment of 1-5 drugs leads to the development unwanted effects in 5% of patients, with the simultaneous use of 15 medications, complications are observed in 54% of patients.

The situation worsens during pregnancy.

Clinicians prescribing drugs to pregnant women should follow these guidelines:

· try to avoid any medications during the first trimester of pregnancy;

Give preference to monotherapy, using short-acting drugs;

give preference to local treatment, if possible;

use the lowest dose of the safest drug;

use the drug if the benefit outweighs the possible risk to the fetus;

The doctor, prescribing medication to a pregnant woman, takes on a great responsibility for the life and health of the mother and her child.

The effect of drugs on the fetus and newborn

(abstract).

1. Mechanisms of action of drugs on the fetus

and newborn 3

2. Medications and fetus 6

3. Medicines and breastfeeding 12

4. List of sources used 17

1. Mechanisms of action of drugs on the fetus and newborn

To date, considerable experience has been accumulated indicating that many drugs can have an adverse effect on the developing fetus and newborn. The ratio of risk to potential benefit from prescribing drugs is the main problem of pharmacotherapy during pregnancy.

Most drugs penetrate the fetus quickly enough. At the end of the gestational period, the main biological systems begin to function in the fetus, and the drug can cause its pharmacological effect. There are three pathological variants of the action of drugs on the fetus:

1. embryotoxic;

2.teratogenic;

3.fetotoxic.

The embryotoxic effect consists in the negative effect of the substance on the zygote and blastocyst located in the lumen of the fallopian tubes or in the uterine cavity. Most often, the result is the formation of gross malformations, which leads to termination of pregnancy. I.I. Ivanov and O.S. Sevostyanova note that the teratogenic (teratos - freak) effect of drugs pose the greatest danger, as they lead to the development of congenital anomalies in the fetus. The fetotoxic effect is manifested in the closure of the natural openings of the fetus, the development of hydrogenesis, hydrocephalus and specific organ damage.

It has been established that during pregnancy there are a number of metabolic features that affect both the mother and the fetus and can affect the pharmacokinetics of drugs. Pregnant women are characterized by “physiological hypervolemia”, which reaches a maximum at 29-32 weeks. The concentration of drugs per unit volume decreases, and the beneficial effect decreases, and an increase in the dose of drugs taken increases the risk of fetal pathologies. G.F. Sultanov, as well as O.I. Karpov and A.A. Zaitsev indicate that during pregnancy there is a slowdown in the absorption of drugs. Due to the decrease in intestinal motility, there is a decrease in the bioavailability of substances inactivated in the gastrointestinal tract. At the same time, the adsorption of medicinal substances administered by inhalation increases due to changes in the volume of inhaled air and pulmonary blood flow in pregnant women. An increase in the formation of hepatic microsomal enzymes (hydrolases) leads to an acceleration of the metabolism of xenobiotics. The excretion of medicinal substances during pregnancy increases due to an increase in renal blood flow and glomerular filtration, and at the beginning of childbirth, all indicators of the activity of the mother's kidneys decrease, the reverse transplacental flow of substances decreases, which leads to their accumulation in the child's body.

1.simple diffusion;

2. facilitated diffusion;

3. active transport;

4. entry through the pores of the membrane;

5. pinocytosis.

Simple diffusion is the most common way of transferring drugs, proceeding without energy consumption. It depends on the concentration gradient of the substance in the blood of the pregnant woman and the fetus, the transfer surface area, the membrane thickness, as well as the physicochemical characteristics of the drugs (molecular weight, lipid solubility, degree of ionization). Active transport is carried out with the expenditure of energy, does not depend on the concentration gradient, and obeys the laws of competitive inhibition. S.I. Ignatov established that fluorouracil penetrates the placenta in this way. The diaplacental passage of drugs is carried out through the pores in the chorionic membrane. Their diameter is 1 nm, which corresponds to the diameter of the pores in the intestinal tract and the blood-brain barrier. Pinocetosis is one of the possible ways of transferring drugs with a predominantly protein structure, the absorption of maternal plasma droplets by syncytium microvilli along with the substances they contain.

2. Medications and fetus

There are many drugs that are potentially dangerous in terms of teratogenesis, and their effect may be manifested in the presence of certain favorable factors. Drugs can affect the fetus at all stages of pregnancy, but most reliable data have been obtained when studying their action during the period of organogenesis (18-55 days) and the period of growth and development of the fetus (over 56 days). In this regard, when prescribing a drug to women of the childbearing period, it is important to take very seriously the assessment of the benefit-risk ratio of the prescribed device during pregnancy. No less important is the exclusion of pregnancy when prescribing devices with teratogenic properties.

Based on human or animal data, drugs are currently classified according to the degree of risk to the fetus in a number of countries (USA, Australia) into categories from A (safe) to D (contraindicated during pregnancy), as indicated by O.C. . Sevostyanov. There is also category X, which includes drugs that are absolutely contraindicated for pregnant women. V.A. Tabolin and A.D. Tsaregorodtseva argue that category X drugs do not have a sufficient therapeutic effect, and the risk of their use outweighs the benefits.

A - drugs that have been taken by a large number of pregnant women and women of childbearing age without any evidence of their effect on the incidence of congenital anomalies or damaging effects on the fetus.

B-drugs that were taken by a limited number of pregnant women and women of childbearing age without any evidence of their effect on the frequency of congenital anomalies or damaging effects on the fetus.

C-drugs that have shown teratogenic or embryotoxic effects in animal studies. It is suspected that they may cause reversible damaging effects on the fetus or newborn, but not causing congenital anomalies. No controlled studies have been conducted in humans.

D - drugs that cause or are suspected of causing congenital anomalies or irreversible damage to the fetus.

X - drugs with a high risk of congenital anomalies or permanent damage to the fetus, since there is evidence of their teratogenic or embryotoxic effects in animals and humans. Br. Bratanov and I.V. Markov, this group includes the following drugs:

- androgens represent a great danger due to the occurrence of hermaphroditism in female fetuses, the possibility of congenital anomalies (shortening of the limbs, anomalies of the trachea, esophagus, defects of the cardiovascular system) is also possible;

- diethylstilbestrol causes major changes. In girls whose mothers took this drug during pregnancy, there are modifications of the uterus and vagina. Most often, these changes occurred when the mother took the drug from the eighth to the sixteenth week of pregnancy. The action of this substance is manifested in a negative effect on the male fetus, namely, in the expansion of the ducts, wall hypotrophy and metaplasia of the prostate epithelium. Epididymal cysts were also found.

-ergotamine ( belongs to the group of ergot drugs) increases the risk of spontaneous abortion and symptoms of CNS irritation, as indicated by N.P. Shabalov.

- progestins can cause pseudohermaphroditism in girls, precocious puberty in boys, and lumbosacral fusion in fetuses of both sexes.

- quinine leads to pronounced changes in the central nervous system (underdevelopment of the cerebral hemispheres, cerebellum, quadrigemina, etc.), the formation of congenital glaucoma, anomalies of the genitourinary system, fetal death.

If taking the medicine during pregnancy cannot be avoided, then the consequences of treatment with various drugs should be clearly understood.

O.S. Sevostyanova notes that the most common manifestations of early toxicosis of pregnant women - nausea and vomiting, which occur in 80% of pregnant women in the first trimester and sometimes persist in the second and third - do not always require medical intervention. She also recommends primarily dietary measures. If necessary, appoint pyridoxine (10 mg) and dicyclomine (10 mg) 2-3 times a day inside. If there is no effect, drugs of the phenothiazine series (aminazine, promethazine, meclozine) are used, but they can cause the formation of fetal malformations.

According to V.A. Tabolin myotropic antihypertensive drugs (diabazol, magnesium sulfate) usually do not have a negative effect on the fetus, with the exception of magnesium sulfate, which can accumulate in the fetus, causing CNS depression.

Reserpine, raunatin cause fetal growth retardation. Once in the fetus, reserpine uses MAO for its metabolism, which leads to a delay in the inactivation of histamine (also oxidized by MAO) and the appearance of rhinorrhea, bronchorrhea.

The a-adrenoreceptor antagonist methyldopa (dopegyt, aldomet) acts on CNS receptors. The fetus is also able to accumulate the drug, which may be accompanied by a decrease in the excitability of the central nervous system. I.V. Markova considers autoimmune hemolytic anemia, liver damage (with prolonged use) to be dangerous complications.

b-Adrenergic blockers cause a decrease in renal blood flow and glomerular filtration. Removing the inhibitory effect of adrenomimetics on the muscles of the uterus, they can lead to premature birth and miscarriage. The use of these drugs is fraught with a delay in the development of the fetus, as noted by A.P. Kiryushchenkov and M.L. Tarakhovsky.

It is unlikely that anyone will be surprised that pregnant women use drugs very widely. Statistics show that at least 97% of women take certain medications during pregnancy. As a rule, these are iron compounds recommended by a doctor for anemia, vitamins, sedatives and painkillers, drugs that normalize the excretory system, as well as hormones, antibiotics and antihistamines. Indeed, these drugs are often necessary for the normal course and completion of pregnancy.

However, very often women self-medicate and take medications during the first three months of pregnancy, that is, during the period of the most active organogenesis in the fetus. It is during these periods that the teratogenic and (or) embryotoxic effects of altering factors are most clearly manifested. In addition, from 15 to 20% of women (for different countries these figures are not the same) during the gestation period use four or more types of drugs, and cases of their simultaneous administration are not uncommon. Many modern medicines are potent, multicomponent, chemically active, often with a very wide spectrum of action and side effects and, more importantly, with a completely unexplored and unpredictable effect when several drugs are combined at once, which can have the most adverse effect on the normal course of pregnancy. : starting from early termination of pregnancy due to miscarriage or intrauterine death of the fetus, various deformities and to long-term consequences in the form of biochemical and functional abnormalities in the child.

Of course, you should not overdramatize the situation - most drugs do not have teratogenic properties, but nevertheless, with unauthorized "prescription" of drugs, when their number reaches 5-8 or more at the same time (how drugs are chosen in this case is a special topic) , then the effect of the combined action of several drugs is unpredictable.

We must also not forget that medicinal substances that cause severe defects in small doses still exist. The best known of these is, of course, thalidomide.

The effect on the fetus and newborn of certain groups of drugs administered during pregnancy, childbirth and in the postpartum period is the subject of close attention of obstetricians and gynecologists. In a number of countries, special studies are being carried out to identify the teratogenic properties of drugs. [show]

All drugs are tested for teratogenicity before being used in clinical practice.

The effect on the fetus of medicinal substances is determined by:

• features of the pharmacokinetics and metabolism of the drug in the mother's body;
• the rate and degree of transplacental transfer of the drug and metabolism in the placenta;
• route of entry into the mother's body and dose;
• embryotoxic, teratogenic properties of the pharmacological agent.

Absolute teratogens are: antimetabolites (6-mercaptopurine, aminopterin...), alkylating compounds (cyclophosphamide, dopan, thiophosfamide...), anti-cancer antibiotics (actinomycin, sarcolysin...).

This is due, first of all, to the basic principle of action of such drugs. The main task of tumor chemotherapy is to kill malignant cells or suppress their activity to a large extent. This is achieved in different ways - depending on the chemical structure and pharmacological properties of the selected drugs, which can deprive the cell of the ability to divide, interfere with protein synthesis processes, disrupt individual stages of nucleic acid synthesis or energy metabolism.

However, almost all antitumor substances have a slight selectivity of action: not only malignantly altered cells, but also many others are affected. In this case, of course, cells that are in a state of active reproduction suffer the most. It is clear that in the developing embryo, all developing tissues and organs are covered by mitotic processes, so it is very easily exposed to antitumor drugs. What this leads to is not difficult to guess. And if, for medical reasons, you still have to resort to such therapy, then there is nothing left but to sacrifice the life of the unborn child and terminate the pregnancy.

Anticancer drugs have a history that is very similar to, and even precedes, thalidomide, but, fortunately, its consequences were much smaller in scale. [show]

In the treatment of acute leukemia in children, back in the late 40s, the substance aminopterin was used, the mechanism of action of which is to inhibit the biosynthesis of nucleic acids. In the early 50s, it was noticed that aminopterin, in addition to the antitumor effect, has another feature: when taken in the early stages of pregnancy (third to eighth weeks), it causes an abortion.

In the US, attempts have been made to use this drug to interrupt unwanted pregnancy. Indeed, some women achieved the necessary goal. In some cases, the drug did not have the expected effect, and the development of the embryo continued. However, even a short-term effect of aminopterin on embryogenesis was enough for the children who were born to develop a whole complex of congenital malformations and deformities.

The synthesis of nucleic acids is the most important stage in the life cycle of any dividing cell, so aminopterin caused deformities in a variety of tissues and organs of the child. But those rudiments, on which the drug acted during periods of their active formation, turned out to be more disturbed, of course, than others. In any case, in children whose mothers took aminopterin during pregnancy, various anomalies of the nervous system, anencephaly, defects in the skeleton, ears, mouth, cleft palate, underdevelopment of the endocrine glands, weight loss, horse foot, violations of the blood formula were found ...

By the way, the teratogenic properties of aminopterin were revealed in animal experiments even before the use of this drug in gynecology, but in those years, experimental studies in the field of developmental anomalies existed almost on their own, without affecting the clinic. One can only regret that the appearance of "aminopterin" newborns, apparently, did not teach medicine anything. It took another ten years for the birth of thousands of "thalidomide" children to change the attitude towards the experiment.

Over the past three decades, the direction of non-infectious immunology has been intensively developing, associated with the suppression of the immunological reactivity of the body. Doctors in many countries around the world use immunosuppressive substances to treat various allergies and autoimmune disorders. Immunosuppressive agents are most widely used in connection with organ and tissue transplants: the body rejects foreign transplanted organs, and in order for the transplant to be successful, it is necessary to suppress its immunity.

There are probably millions of women around the globe who suffer from allergies or autoimmune diseases (in which immune cells lose their ability to distinguish "self" from "foreign" and attack their own tissues). Thousands of transplants are successfully carried out - kidney, heart and other organs. In all these cases, immunosuppressive therapy is used, of course, of varying intensity: it is clear that the rejection of a transplanted kidney should be prevented by other means than, say, an allergy to flower pollen. But one way or another, many women are forced to take drugs that affect the immune system, so the relationship between immunosuppression and the development of the fetus is of considerable interest to practical medicine.

The principles and mechanisms of action of most modern immunosuppressants are the same as those of anticancer drugs: inhibition of the viability of immunocompetent cells by interfering with the processes of metabolism or division. No wonder some immunosuppressants are simultaneously used as antitumor substances, for example, in malignant neoplasms of the hematopoietic tissue.

The side effects caused by drugs of both groups are also similar: strict selectivity, that is, the ability of the drug to act only on certain cells, is still an unattainable ideal. Therefore, we have the right to assume that immunosuppressants can have an adverse effect on the organism that is formed in the womb.

This assumption is supported by medical observations. In particular, one of the most widely used immunosuppressants in clinical practice, cyclophosphamide, is certainly a factor that has a teratogenic effect on the human fetus.

However, even immunosuppressive therapy for a transplanted organ (for example, a kidney) does not become an absolutely insurmountable obstacle to motherhood. If the choice of a particular drug is thought out with skill, the optimal doses and terms of its administration are selected, then the teratogenic risk can be significantly reduced, although, of course, it is unlikely that adverse effects can be completely avoided (as well as completely eliminate the risk of deformities).

Judging by the published data, newborns of such mothers have a weight significantly lower than normal - 1.5 kilograms instead of 3.5. The size of the central organ of immunity - the thymus gland, or thymus, is also, as a rule, smaller than expected. Various disorders in peripheral blood cells are not uncommon, which, fortunately, usually disappear by the age of two or three, unless, of course, bone marrow has been damaged as a result of immunosuppression. Nevertheless, anatomical damage, deformities, are usually not detected in these newborns.

Over the past few years, new immunosuppressive agents with high specificity of action have become increasingly widespread in clinical immunology. These include, for example, cyclosporine, a substance that has a very good selectivity in relation to the hematopoietic tissue - side effects when using it are minimal. Almost unknown are the facts of the birth of children in mothers who would take cyclosporine during pregnancy, but it can be assumed that the teratogenic or embryotoxic risk from its use is much lower than from the "old" immunosuppressants used.

Of course, antitumor and immunosuppressive drugs are not among the most used and even more recommended during pregnancy. In addition, it is difficult to imagine that someone would take them on their own initiative, without a doctor's prescription. With this, apparently, the circumstance is connected that the occurrence of specific deformities is relatively rare, at least, they are much less than one would expect, knowing the high activity of these drugs, aimed at biological structures and processes.

Constant medical supervision of a pregnant woman who is forced to take such drugs, and the existing methods of prenatal diagnosis, make it possible to monitor the development of the fetus and, if necessary, terminate the pregnancy without bringing the matter to the birth of an abnormal child.

However, among huge amount There are a lot of drugs that are often taken not only without a doctor's prescription, but also without a clear idea of ​​the direction of action and side effects of the drug. Self-medication is generally fraught with serious and dangerous consequences; Judging by the publications of recent years, the scale of this phenomenon is enormous. But the consequences are even more dangerous if a pregnant woman is self-medicating.

Obviously, you should not intimidate readers (more precisely, readers) by convincing them of the harmfulness of taking medications during pregnancy. Most of the 350 drugs for which teratogenic activity is shown show it only in sufficiently high doses and, as a rule, only under unfavorable circumstances, for example, with increased sensitivity of the maternal and (or) fetal organism to a certain drug. But still, we emphasize once again: only a doctor should prescribe a medicine and determine its dose, even if it concerns the most harmless, at first glance, drugs, say, salicylates.

What do we do when we get the flu? Often, instead of going to the doctor, we choose medications ourselves, among which there will almost certainly be acetylsalicylic acid - aspirin. No doubt, the medicine is good, its analgesic and antipyretic properties have been known since the last century. No wonder its annual world production reaches 40 thousand tons!

Side effects when taking aspirin, of course, exist (mainly digestive disorders and allergies), but they are mild, and often completely absent. You just need to exercise reasonable caution when using aspirin (however, like any other medicine). And if a pregnant woman uses salicylates (in addition to aspirin, this group of substances also includes another widely used drug - sodium salicylate)?

By the way, not only the flu can be the reason for this: salicylates help with acute and chronic rheumatic diseases, they relieve joint pain, and are useful for neuralgia and myalgia. However, the use of salicylates in early pregnancy significantly increases the risk of combined ear and eye anomalies. A study conducted in Finland back in the early 70s showed a clear relationship between taking salicylates during the flu and the appearance of a cleft palate in the offspring - "cleft palate", they provoke the occurrence of heart disease.

Moreover, prolonged use of aspirin during pregnancy increases the incidence of anemia, complicates the prenatal and birth periods, and often stimulates bleeding. But that's not all. Aspirin increases the number of stillbirths, increases early childhood mortality.

Of course, all these disorders are associated with taking very large doses of salicylates, but, as many doctors rightly believe, it is better not to prescribe this group of drugs during pregnancy unless absolutely necessary.

Sex hormones are strong teratogens. It can be assumed that self-medication with this group of substances, if it occurs, is very rare; usually therapy is associated with tumor or endocrine diseases, but the use of hormones for contraceptive purposes is quite common.

In the 30s of our century, it was found that injections of the sex hormone progesterone into female rabbits cause suppression of ovulation, that is, the process of final maturation and release of the egg from the ovary. Based on this, tablet preparations with a similar effect for humans were subsequently developed.

Progesterone was then obtained from the roots of Mexican grapes, later synthetic analogues were created - progestins, the activity of which is several times higher than that of natural ones. Since then, various types of hormonal contraceptives have gained immense popularity around the world as an alternative to abortion.

However, although rare, conception still occurs while taking hormonal contraceptives. In this case, the initial, yet undiagnosed terms of pregnancy will proceed against the background of the continued use of these drugs. And until the situation is clarified, one or two months may pass, that is, the sex hormones will act on the embryo precisely in the most dangerous period in the teratological sense.

Medicinal contraceptives are usually used by women. However, traditional medicine in this respect has not bypassed the attention of men. IN different countries to prevent conception, men drank, for example, juice of unripe pineapples, milk of unripe coconuts, oil from hydrangea roots, a solution of mature dry spores of club moss, castor oil. It is believed that the active components of these drugs have the ability to suppress spermatogenesis and sperm maturation.

Traditional pharmacology has also begun to test extracts of various plants for contraception. From cottonseed oil, for example, an effective drug called gossypol was obtained, which is also sold in our country. Such contraceptives are called spermicides (Latin caedere - to kill). It would seem that the risk of adverse effects on the embryo from spermicides is completely excluded. Nevertheless, they can also pose a certain danger to the fetus.

The fact is that these contraceptives sometimes suppress spermatogenesis incompletely, the remaining spermatozoa in this case will carry chromosomal damage; and if such damage does not affect the fertilizing ability of the male germ cell, then the probability of the formation of a zygote with genetic abnormalities will be very high.

In particular, for the drug "Nonoxynol 9", it was found that a pregnancy that occurred despite its use is twice as likely to end in the birth of an ugly baby than happens on average.

The list of drugs that are teratogenic to humans continues with warfarin, a substance that inhibits blood clotting. Anticoagulant drugs are often used in medical practice, for example, for the treatment of thrombophlebitis. However, some of them have adverse effects on embryogenesis, and warfarin can even cause deformities described by the warfarin syndrome, when eyes, brain, limbs are affected by anomalies, i.e. develop multiple congenital malformations.

Vitamins are most often taken without consulting a doctor. And although the possibility of hypervitaminosis - poisoning with vitamin preparations (especially fat-soluble ones - A, D, E, K) - really exists, teratogenic properties of these substances have not been found. More precisely, they were not found at doses that can be imagined at all: in order to cause a teratogenic effect, for example, with vitamin A, a pregnant woman would have to eat up to 200 thousand vitamin balls at once (these figures were obtained by recalculating experimental data).

And even those doses that are prescribed in the hospital for medicinal purposes are thousands of times less than teratogenic. This does not mean that vitamins can be safely taken in any amount. Deformity is only an extreme manifestation of adverse effects on the fetus. Moreover, for the synthetic analogue of vitamin A - the drug isotretinoin - the ability to cause congenital anomalies has been proven quite definitely. [show]

Isotretinoin, marketed in the United States in 1982, was intended for the treatment of certain skin diseases. Despite the fact that the annotation accompanying the drug contained a warning against its use during pregnancy, already in 1983 the first reports of the embryotoxic and teratogenic properties of isotretinoin appeared. Pregnancies of women who used it by accident usually ended either in spontaneous abortion or in the birth of a malformed child; especially often this substance disrupted the development of the nervous system and sensory organs.

Isotretinoin turned out to be a strong teratogen, even stopping its use a few days before conception by no means guaranteed a successful completion of the pregnancy.

Thus, deformities, functional pathologies of newborns, long-term consequences can cause quite a few drugs. Diuretics, sedatives, antibacterials should also be used with very great care during pregnancy.

Some antibiotics adversely affect the fetus due to their permeability through the placenta. These include:

• tetracycline - causes fetal growth retardation, splitting of the upper palate, fusion of fingers and toes, damage to the rudiments of milk teeth, has a hepatotoxic effect;
• levomycetin - causes a change in the liver of the fetus and affects its hematopoietic system (hypoplastic anemia);
• streptocide - can lead to irreversible degeneration of the auditory nerve in the fetus and cause deafness.

Long-acting sulfonamides, antidiabetic hypoglycemic sulfonamides, a number of hormonal drugs (adrenocorticotropic hormone, diethylstilbestrol, androgenic drugs, thyreostatic drugs), indirect anticoagulants (dicumarin, pelentan), inhibitors of platelet function, anticonvulsants (carbamazepine, phenyton, trimetine, ethosuxemide), antidepressants (amitriptyline, imizin, etc.), tranquilizers (meprotan, sibazon), antihypertensive drugs of the rauwolfia group, antimalarials, antifungal drugs (levorin, griseofulvin), antihistamines (meclizine, cyclizine).

Many chemicals and drugs pass not only to the fetus through the placenta, but also into the milk of a nursing mother. In this regard, the prescription of the drug to women of childbearing age, pregnant and lactating women is made taking into account the assessment of the benefit-risk ratio of the prescribed drug and the possibility of its teratogenic effect.

Currently, drugs are classified according to the degree of risk to the fetus, as safe, relatively contraindicated during pregnancy, and absolutely contraindicated during pregnancy and breastfeeding.

And at the end of the "drug" topic, there are a few rules that can significantly reduce the risk of a child being born with deviations - be it deformities, functional or biochemical defects. These rules are very simple and obvious, they have been known for a long time and it is not difficult to follow them. Difficulty elsewhere:

everyone who wants to see their future children healthy must convince themselves that
that these rules are for him.

So, if during pregnancy you can not take drugs, then it is better not to take them. However, often the need for this still arises, and then the choice of medication, dose, method and frequency of administration should be determined only by the doctor.

Self-medication is completely unacceptable. You can’t be deceived by the means of traditional medicine: herbs, infusions, decoctions often contain very active principles, and even if their properties in relation to a specific disease are known, then in relation to the embryo or fetus, the consequences of use are usually unpredictable.

Many drugs are very slowly excreted from the body, so they have their effect for a long time after they stop taking them. This means that it is necessary to plan the future addition of the family only after two or three months (in some cases even longer) after the end of the course of drug therapy, and this applies to both women and men.

In general, it is better to make such plans in advance, with the appropriate supervision of a specialist, including preparation for the planned conception.

Compiled based on: Balakhonov A.V. Development mistakes.
Ed. 2nd, revised. and additional - SPb., "ELBI-SPb." 2001. 288 p.

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