The first slide of the presentation: The influence of harmful factors on the fetus. Presentation on the topic "the influence of harmful factors on the fetus" Prepare a presentation on the influence of external factors on the embryo

Kazan State Medical University
Department of Obstetrics and Gynecology №2
Influence of harmful
factors on the fetus
Doctor of Medical Sciences, Professor Gabidullina R.I.

INFLUENCE OF HARMFUL FACTORS ON THE FETUS

Prevalence of spontaneous abortions
makes up 15-20% of the total number of pregnancies;
50% of miscarriages in the first trimester are gross
violations
3-5% of newborns have malformations;
in 15% of children, malformations are detected at the age
5-10 years

REPRODUCTIVE HEALTH
DYNAMICS OF SPONTANEOUS ABORTIONS IN RUSSIA
(% of the total number of abortions)
12
10,2
9,8
10
8,9
9,0
2000
2001
8,3
8
7,2
7,3
1995
1996
7,5
7,8
6
1997
1998
1999
2002
2003
Radzinsky V.E.

Teratogenesis

The occurrence of malformations under
the influence of environmental factors
(teratogenic factors) or in
as a result of hereditary diseases

Teratogenic factors

Distributed widely. During pregnancy
each woman takes an average of 3.8
drug names. In the USA 10-20%
pregnant women take drugs.
In addition, harmful substances are found in everyday life.
(microwave oven, electronic clock) and on
work

Teratogenic factors

Chemical
Physical
Biological

Criteria for teratogenic factors

The connection between the action of the factor and
the formation of a malformation
Epidemiological studies confirm
this connection
The action of the harmful factor coincides with
critical periods of intrauterine
development
With rare exposure to a damaging factor
characteristic malformations are rare

The main groups of teratogenic factors

(tetracyclines, trichopolum, androgens, mercury, lead,
phosphorus)
Ionizing radiation (radioactive fallout,
radioisotope diagnostics, radiation therapy)
Viral and bacterial infections (herpes, rubella,
syphilis, toxoplasmosis)
Metabolic disorders and bad habits (sugar
diabetes, endemic goiter, phenylketonuria; smoking,
alcoholism, drug addiction)
In the United States, a special register of teratogenic factors is published

Features of the influence of teratogenic factors (TF)

Dose dependent.
For each TF there is a dose of teratogenic
actions. Usually it is 1-3 orders of magnitude lower
lethal.
Sensitivity to various TFs during
intrauterine development may vary.
Infectious agents as teratogenic factors are not
have a threshold dose and dose-dependent character

Periods of intrauterine development of a person

Initial - from the moment of fertilization to
blastocyst implantation (up to 11 days).
Ebrionic (18-60 days after
fertilization)
Fetal (from 9 weeks of pregnancy to
birth)

Initial period

Differs in large compensatory-adaptive
embryonic possibilities. The all-or-nothing law
damage to a large number of cells, the embryo dies, with
damage to individual blastomeres, further development is not
violated
30-36 h
3-4 day
2 cells
4 cells
fertilization
rhenium
Ovary
Ovum
Ovulation
8 cells
morula
Blasto
cyst
5-6day

Embryonic period

SPONTANEOUS RECU
Embryonic period
Explaina
The embryo is most sensitive to the action of TF. gene
infection
Gross malformations are formed
Causes:
endo
autoi
S
Unexpla
allog
to

fruiting period

Malformations are not typical. Under the influence of external
environment, growth inhibition and / or death occurs
cells, which is further manifested by underdevelopment or
functional immaturity of organs

Major malformations

Malformations of the central nervous system - anencephaly, cleft
spine, hydrocephalus. Formed as a result
neural tube rupture due to folate deficiency
acids, infections, diabetes.
Congenital heart defects - ASD, tetralogy of Fallot, stenosis
aorta, etc. (phenylketonuria, SLE, rubella virus,
genetic factors, alcohol, NSAIDs, diabetes mellitus)
Cleft lip, hard palate
congenital clubfoot
Congenital dislocation of the hip
Malformations of the gastrointestinal tract - pyloric stenosis, disease
Hirschsprung, atresia of the esophagus, anus, etc.

General approaches to prenatal prevention

1.
2.
3.
4.
5.
6.
environmental protection
Family planning (consanguineous marriages,
childbearing after age 35)
Prenatal diagnosis - elimination
embryos with pathology
Identification of heterozygous carriers
Periconception preparation
Invasive and non-invasive methods
intrauterine diagnosis

Periconception preparation

medical genetic counseling,
carrier diagnosis and treatment
viral and bacterial infection,
exception prof. harmfulness,
rejection of bad habits,
taking folic acid and tocopherols)

Methods of intrauterine diagnosis

1.
2.
Non-invasive methods:
Ultrasound (10-14, 22-24, 32-34 weeks),
Biochemical markers:
9-14 weeks b-hCG, PAPP-A
17-19 weeks AFP, 17-OPK, b-hCG,
estradiol
Invasive methods:
Chorionic biopsy (9-11 weeks)
Cordocentesis (22-24 weeks)

Medicines and chemicals

for the placental transition
meaning:
The molecular weight of the drug (up to 600 easily pass,
600 - 1000 is limited, more than 1000 almost do not penetrate).
Most drugs are less than 600 and easily
penetrate the fetus.
Fat-soluble substances easily diffuse through
placenta (ether, nitrous oxide).
Binding to blood proteins. The more connection, the
slower penetration through the placenta and accumulation in
fetus.
Route of administration to the mother
Stage of intrauterine development

Categories of drug safety

Categories of risk of using drugs during
pregnancy FDA (Food and Drug Administration)
A - no risk to the fetus;
B - no risk to the fetus has been established in animals or in
person;
C - the risk to the fetus has not been established in humans;
controlled studies in humans have not been conducted;
D - there is a risk to the fetus, but can only be used when
life risk; it is necessary to assess the degree of risk and
benefits;
X - proven risk to the fetus. During pregnancy
contraindicated.

Absolute teratogens

Medicines used in
oncology:
1. Antimetabolites (6 - mercaptopurine)
2. Alkylating compounds
(cyclophosphamide)
3. Antitumor antibiotics
(actinomycin, sarcolysin)

Antibacterial drugs during pregnancy (Gurtova B.L. et al. 2004)

Group I - contraindicated in pregnancy:
tetracyclines, chloramphenicol, trimetaprim.
Group II - apply only for vital
indications: aminoglycosides, nitrofurans,
sulfonamides.
Group III - antibiotics without
embryotoxic action: penicillins,
cephalosporins, macrolides.

Impact of antibiotics

Tetracycline and its derivatives in the early
timing leads to malformations, in
late - slowing down the growth of the fetus,
damage to the rudiments of the teeth,
hepatotoxic effect
Levomycetin - hypoplastic anemia
Aminoglycosides - ototoxic
action

Hormonal drugs

Estrogens lead to the development of adenosis and
clear cell adenocarcinoma of the vagina
and cervix in girls

ionizing radiation

The effect of radiation on the female body occurs through
general laws of radiation damage
a-radiation practically does not penetrate the skin, but very
dangerous if swallowed
b-radiation penetrates to a depth of 1-2 cm
g-radiation has the highest penetrating
ability to form free radicals,
leads to gene mutations
Transplacental transfer is the main
penetration of isotopes

Mechanisms of transplacental transfer of radionuclides

Hematogenous pathway - free transition of isotopes
from mother's blood to fetal blood
transplacental membrane (131I, 32P, etc.)
Accumulation in the tissues of the placenta, followed by
effects on the fetus (transuranium elements)
Paraplacental passage through the fetal
membranes and amniotic fluid (radioactive
plutonium)

1.
2.
Viruses (cytomegalvirus, herpes, rubella),
penetrating to the embryo and fetus, can have
directly teratogenic
Infection leads to changes in metabolism and
functions of the endometrium, which causes
implantation failure or
placental development

Infection (mechanisms of action)

3. Viral and bacterial infection can
influence the development of the placenta and
lead to HFPN and IUGR
fetus
4. Toxic effect on the fetus can
render bacterial toxins

Bad habits

Smoking
Alcohol consumption
Addiction

REPRODUCTIVE HEALTH
TOBACCO SMOKING DURING PREGNANCY
Moscow, 2002
23%
active smoking
No
77%
of which 20-30 years - 70%
Radzinsky V.E.

Smoking

Tobacco contains more than 600 harmful factors:
organic and inorganic acids, proteins,
esters, aldehydes, phenols, etc.
Currently found in tobacco smoke
radioactive polonium
Nicotine has the greatest effect

Nicotine

Early exposure to nicotine
pregnancy can lead to
implantation of the ovum and spontaneous
abortion.
Abortion and preterm birth can be
caused by an increase in contractile
uterine activity during smoking
Nicotine causes uterine blood vessels to contract and
placenta with development of placental
fetal insufficiency and hypoxia

Nicotine

Fetal hypoxia is also associated with an increase in
carboxyhemoglobin level
Placental developmental disorder contributes to
occurrence of HFPN and fetal IUGR
Nicotine penetrates intensively through the placenta and
accumulating in it, penetrating through the amnion,
accumulating in the internal organs of the fetus, causes
prolonged intoxication

REPRODUCTIVE HEALTH
ALCOHOL USE DURING PREGNANCY
Moscow, 2002
use moderately
42%
46%
abused
do not use
12%
of which 20-25 years - 43%
26-30 years old - 26%
Radzinsky V.E.

Alcohol

The systematic use of alcohol in
pregnancy can lead to
development of fetal alcohol syndrome
(ASP)

ASP

Violation of the structure and function of the central nervous system
(microcephaly, intellectual disability,
movement coordination)
Growth retardation, especially noticeable after
child birth
Characteristic anomalies in the development of the facial skull
(microphthalmia, facial lengthening, low forehead,
underdevelopment of the chin, small saddle
nose, large wide open mouth, strabismus,
neck flattening)

ASP pathogenesis

Not studied enough. It is known that
Ethanol readily crosses the placenta and
fetal blood-brain barrier, accumulates in the CNS,
having a toxic effect
The liver of the fetus lacks the enzyme alcohol dehydrogenase,
destroying ethanol, so the fetus is exposed
prolonged exposure
Embryotoxic and teratogenic effects
ethanol metabolite - acetaldehyde

REPRODUCTIVE HEALTH
THE SHARE OF TEENAGE GIRLS,
DRUG USERS
Moscow, 2002
CAUSES:
- just like that - 70%
- for the company - 20%
- other - 10%
10%
Average age
first
use
drugs
15.8 ± 0.2 years
Radzinsky V.E.

REPRODUCTIVE HEALTH
COMPLICATIONS OF PREGNANCY IN DRUG addicts
Fetal growth retardation
Preeclampsia
Threat of interruption
pregnancy
Toxicosis
67 %
16 %
4% 4%
Radzinsky V.E.

REPRODUCTIVE HEALTH
CONDITION OF NEWBORN IN DRUG addicts
(Apgar score)
25%
30%
8 points and
more
6-7 points
4-5 points
45%
Radzinsky V.E.

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Due to nutritional deficiencies and circulatory disorders in the uterus (after the use of amphetamines), there is a delay in the mental and physical development of the fetus. A child under the influence of amphetamines seems half-asleep, sucks badly at the breast, and loses weight quickly. There is an opinion that LSD causes mutations, premature births, miscarriages, placental abruption, etc. Often LSD is used together with marijuana, cocaine, amphetamines or other psychoactive substances, which negates all its relative "safety". Almost all drugs cause a delay in the physical and mental development of the fetus, and some threaten his life, provoke miscarriage, all kinds of malformations. Children born after substance abuse suffer from flattening of the bridge of the nose, a narrow upper lip, fusion of the eyelids at the corners of the eyes, and so on. The physical and mental development of such children is delayed, they have mental disorders. Often, these babies are born with very small heads or very tiny eyes, and they often have hydrocephalus (a disorder in the structure of the brain).

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How does the fetus feel during the mother's drug intoxication or during the "withdrawal" that she experiences? Most likely the same as the mother. Narcotic substances cross the placenta into the blood of the fetus and cause changes in his psyche. A mother who uses drugs risks getting not only a physically weak child with a "programmed" mental retardation, but also a mentally disabled child. Unfortunately, the constant "bombardment" of a child's body with toxic substances is not limited to drugs. Their use is usually accompanied by smoking and drinking alcohol. As a result, the effect of malignant effects on the fetus is multiplied many times over.

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Smoking can put a baby's health at significant risk even before birth. But even if the mother stops smoking in the last month of pregnancy, the benefits for her and for the child will be palpable. Babies born to smoking mothers are often underweight, more difficult to adapt to life "outside the mother", have problems with the central nervous system, and generally have poor health.

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RUSSIAN STATE MEDICAL UNIVERSITY Department of Obstetrics and Gynecology of the Medical Faculty (Head of the Department Professor, Doctor of Medical Sciences O.V. Makarov) LECTURE INFLUENCE OF HARMFUL FACTORS ON THE FETUS Teratology is the science of impaired development or the formation of defects in the fetus (Greek: Teras - “ monster") HARMFUL FACTORS Hypoxia Hyperthermia Hypothermia Ionizing radiation Organic teratogens Inorganic teratogens Infections Medicinal substances Stages of intrauterine development Preimplantation period 7 days after fertilization Implantation 7th day after fertilization Organogenesis and placentation Until the end of 3-4 months of intrauterine development Fetal period 12 - 40 weeks Pregnancy Embryonic period Stage of development Organogenesis Time from conception 4-8 weeks Formation of the brain and spinal cord 4 weeks heart, kidneys and limbs Rapid development of the brain, eyes, heart and limbs Early development of the intestines and ileus Mild Appearance of fingers Development of ears, kidneys, liver and muscles Closing of palate, formation of joints at 6 weeks 10 weeks Half day differentiation 12 weeks 8 weeks Congenital anomaly - structural, metabolic and functional disorders of an organ, part of an organ or a large area of ​​the body that occur in utero. Congenital malformation is a term that includes various structural defects. The overall incidence of congenital malformations is 600 per 10,000 of all live and stillborn children (6%). Unknown cause 20% Monogenic - 6% Chromosomal - 5% Environmental - 6% Multifactorial 63% Classification of CM Common CM > 1 per 1000 newborns By frequency Moderately common CM 0.1 - 0.99 per 1000 newborns Rare CM< 0,01 на 1000 новорожденных По распространенности в организме - изолированные -системные -множественные -гаметопатии, бластопатии По сроку действия вредного фактора -эмбриопатии -фетопатии Классификация ВПР по степени тяжести и прогнозу для жизнеспособности Летальные пороки развития - 8% Малые аномалии развития - 60% ВПР средней степени тяжести - 32% Взаимосвязь сроков беременности и повреждающих факторов при возникновении пороков развития плода Порок развития Анэнцефалия Расщелина губы Расщелина неба Атрезия пищевода Атрезия прямой кишки Синдактилия Диафрагмальная грыжа Гипоспадия Крипторхизм Неправильное положение крупных сосудов Дефект межжелудочковой перегородки Открытый аортальный проток Терминационный срок беременности 26 дней 36 дней 10 недель 30 дней 6 недель 6 недель 6 недель 12 недель 7- 9 месяцев 34 дня 6 недель 9 месяцев Факторы риска развития ВПР непланируемые беременности поздний материнский возраст недостаточный пренатальный контроль вирусные инфекции прием лекарств с тератогенным действием алкоголь курение наркотики недостаточное питание профессиональные вредности бедное здравоохранение многих стран Ионизирующие излучения Ионизирующие излучения высоких энергий - рентгеновские лучи -гамма-лучи - естественная радиоактивность Электромагнитные излучения низких энергий - микроволны - радиоволны - ультразвук - радиолокационные волны -шум - вибрации TORCH - инфекции Т - toxoplasmosis - токсоплазмоз О - others - другие инфекции (сифилис, хламидиоз, энтеровирусные инфекции, гепатиты А и В, листериоз, корь, эпидемический паротит, папилломавирусная инфекция, грипп и др.) R - rubeola - краснуха С - сytomegalia - цитомегаловирусная инфекция H - herpes - герпесвирусная инфекция Инфекции Эмбриотоксические или фетолитические дефекты вирусов вызываются непосредственно трансплацентарной инфекцией (заражение вирусом плода), или опосредованно - через лихорадочное состояние матери Вирус краснухи, особенно в первые 90 дней беременности, вызывает врожденные пороки сердца, глухоту и катаракту Цитомегаловирусная инфекция может привести к микроцефалии и СЗРП Вирус Коксаки (энтеровирус) связан со значительным увеличением частоты возникновения расщелин губы и лица, стеноза привратника и других аномалий пищеварительного тракта и врожденных пороков сердца Вирус герпеса II типа (урогенитальный) может приводить к микроцефалии Онкогены и неорганические тератогены К онкогенам относятся вещества, способные реагировать с ДНК и видоизменять ее Доказана трансплацентарная токсичность полициклических ароматических углеводородов, бензо-а-пирена, метилхолантрена, различных триацинов, нитрозомочевины и вторичных аминов Повышение концентрации неорганических тератогенов происходит при горнорудных работах, металлургических и металлообрабатывающих процессах Свинец приводит к нарушению функции ЦНС, развитию умственной отсталости, церебральных параличей, микроцефалии Воздействие ртути приводит к нарушению двигательной активности и умственного развития у детей Кадмий, мышьяк, хроматы являются тератогенами, приводящими к снижению умственной активности Другие факторы окружающей среды недостаточность питания прием недоброкачественных продуктов (проросший картофель) загрязнение питьевой воды физические агенты, используемые в медицине и др. Алкоголь и курение при беременности Алкоголь менее 30 мл этилового спирта в день не оказывает вредного влияния на плод При употреблении 30-60 мл этилового спирта в день у 10% детей происходит задержка внутриутробного роста и наблюдается небольшое число врожденных аномалий При ежедневном употреблении > 60 ml of ethyl alcohol, the pregnant woman is classified as an alcoholic, anomalies in the fetus are expressed mainly in a decrease in body weight at birth and postnatal delay in physical and mental development. Smoking during pregnancy may be accompanied by an increase in the frequency of spontaneous abortions and neural tube defects, placental abruption, premature birth, preeclampsia General recommendations for prescribing drugs during pregnancy Assess potential benefits and potential harms. Avoid drug use in the first trimester Do not prescribe drug combinations. Use the lowest effective dose for the shortest amount of time. Give preference to local dosage forms. Advise the pregnant woman about taking any medications, including analgesics, vitamins, dietary supplements, herbal preparations, and other self-medication. Monitor the intake of all medications by the pregnant woman Monitor the condition of the mother and fetus during the period of drug therapy. Determination of risk categories for teratogenicity of drugs in the Food and Drug Administration (FDA) classification - no risk - 0.7% of drugs B (“best” - the best) - no evidence of risk - 19% C (“coution” - caution) - no risk excluded - 66% D ("dangerous" - dangerous) - proven risk - 7% X - contraindicated in pregnancy - 7% A Drugs that have an undesirable effect on the growth and development of the fetus Drugs a n d s A c n i n b i t o r s A n ti ti r e o i d drugs Benzodiazepines Beta blockers B NSAID arbitrages Tetracyclines Warfarin P o b tible effect Renal failure o f f etition or newborn s r o v ke) n e m e r a n i n g y o n d o u t h o u t h o u t n o l o l a) D u c t u c tu s a rte rio s u s (beginning and o f the sec ond t ri m e s t r e f on e) s t r o m e n g r e s (short application at the beginning of the 1st trimester of the coun try fetal brain hemorrhage Antimicrobial agents Penicillins, cephalosporins, macrolides are not dangerous for the fetus Aminoglycosides - best avoided, they have an otonephrotoxic effect Streptomycin - only for tuberculosis in pregnant women, in this case the risk of its use is lower than for tuberculosis irreversible change in brain function). Nalidixic acid derivatives - do not prescribe during pregnancy, cause hydrocephalus. Levomycetin - use before childbirth leads to the development of a "gray syndrome" of the fetus, it is less dangerous for the fetus during pregnancy. Metronidazole - it is possible to use from the II trimester, in I it is better not to prescribe Antifungal drugs - they are not absorbed in the digestive tract, therefore they are safe. Antihypertensive drugs The best drug is hydralazine (peripheral vasodilator) Dopegyt can lead to hemolytic anemia, cause intestinal meconial obstruction Beta-blockers in large doses increase the tone of the uterus, contribute to intrauterine growth retardation of the fetus Ganglioblockers - paralytic ileus in the newborn Rauwolfia drugs - nasal congestion, oppression respiratory function Nitrates are metabolized into cyanides, which poison the newborn (with prolonged use) Recommendations for prescribing drugs during + -pregnancy drug of choice and in (+) -may be prescribed postpartum (-) -best not to prescribe - -contraindicated analgesics, antipyretics, anti-inflammatory drugs phenacetin _ paracetamol + antipyrine, amidopyrine - cause agranulocytosis in the fetus (+) be careful! agranulocytosis rarely quinine butadione - nephritis; neonatal liver necrosis in the postpartum period as a teratogen, embryonic death indomethacin (-) with prolonged use in high doses. No more than 1 week, up to 28 weeks. pregnancy, in small doses of prostaglandins + quickly excreted drugs, opiates + once without consequences. Do not administer less than 2-3 hours before the birth of the fetus, depression of the respiratory center. Nursing is not allowed. Contraindicated for the treatment and analgesia of preterm labor. atropine + in therapeutic doses harmless anesthesia + local anesthesia + Recommendations for prescribing drugs during pregnancy and in the postpartum period Drugs of choice are penicillins, cephalosporins, macrolides Antibiotics and chemotherapy drugs penicillins + cephalosporins + aminoglycosides - serious otonephrotoxic effect tetracyclines - deposition in bone growth zones and inhibition of skeletal growth, yellow teeth, nuclear jaundice in the postpartum period due to blocking of bilirubin transport systems levomycetin - agranulocytosis in the prenatal period. Teratogen? The newborn has a “gray syndrome” - collapse, asphyxia, cyanosis, vomiting, flatulence clindamycin + erythromycin + sulfonamides (+) anemia. Do not use during lactation. Inhibition of bilirubin elimination, nuclear jaundice possible furadonin (-) hemolysis, yellow teeth, in the newborn hyperbilirubinemia (during feeding) antifungal + antitrichomonas + from the second trimester doses - slowing down the development of the brain (+) swelling of the nasal mucosa, shortness of breath; in rare cases, drowsiness, lethargy, anorexia and atony of the intestine Antihypertensive drugs reserpine peripheral vasodilators + the newborn may have hypoxia and hypotension autonomic nervous system (hypersecretion, decreased activity, hypoglycemia and bradycardia) Are used for health reasons (+) malformations? It is good to use when introducing into anesthesia (do not increase blood pressure). Inhibition of the respiratory center in the newborn + delayed decay in the fetal liver: drowsiness in the postpartum period Recommendations for prescribing drugs during pregnancy and in the postpartum period +) tachycardia, hypoglycemia in the fetus corticosteroids (+) long-term use leads to intrauterine adrenal insufficiency indirect anticoagulants (-) penetrate the placenta, hemorrhages in the fetus. Due to poverty, you can use heparin + the drug of choice for heart defects, it does not cross the placenta. Diuretics (-) very carefully! When gestosis is contraindicated. Only with pulmonary edema, cerebral edema, nephrotic syndrome Cardiac glycosides + toxic effects of overdose Antithrombotic agents are possible only with Recommendations for prescribing drugs during pregnancy and in the postpartum period Hormones natural estrogens + harmless stilbenes - can induce adenocarcinoma of the vagina in the fetus sigetin + prevention of hypoxia fetus, improvement of uteroplacental circulation gestagens (progesterone, duphaston) + with 19-norsteroids (norcolut, norethisterone, primolyut - norms) (-) virilization of female fetuses is possible hormonal contraceptives (accidental intake) synthetic estrogens + 19norsteroids (-) are acceptable for a few weeks in early pregnancy. Virilization of female fetuses of luteal phase insufficiency is possible, it can be used from the beginning of pregnancy up to 20 weeks. androgens - virilization of female fetuses anabolics - virilization of female fetuses thyroxine (+) in hypothyroidism, euthyroid goiter. Known cases of fetal hyperthyroidism iodine preparations (-) goiter and hyperthyroidism in the newborn antithyroid drugs (-) congenital goiter, hypothyroidism, cretinism Recommendations for prescribing drugs during pregnancy and in the postpartum period Vaccines tetanus + rabies + cholera, diphtheria, paratyphoid whooping cough , typhoid, (+) (+) can cause abortion, premature birth vitamin A (+) very carefully - malformations of the central nervous system, eyes, upper palate vitamin B + vitamin C (+) in large doses - death of the embryo, abortion in the first trimester ; aortic stenosis vitamin D (-) in case of overdose - calcification of organs vitamin K (vikasol) + vitamin B12 + Laxatives Vitamins no side effects when feeding may be jaundice in the newborn Indications for periconceptual prevention of congenital malformations Diabetes mellitus and other endocrine and metabolic diseases. Repeated spontaneous abortions and the birth of dead fetuses. Genetic risk of multifactorial malformations. The birth of fetuses with intrauterine growth retardation and a history of premature birth. Chronic diseases (hypertension, epilepsy, bronchial asthma, etc.). Obesity. Prolonged use of drugs. Some infectious diseases (rubella, toxoplasmosis, etc.) Decalogue of commandments for the prevention of congenital malformations (geneticist Eduardo Castillo, Brazil) Any fertile woman can be pregnant. Try to complete your family while you are young. Carry out prenatal control in the prescribed manner. Get vaccinated against rubella before pregnancy. Avoid medications unless strictly necessary. Avoid alcoholic drinks. Avoid smoking and smoking areas. Eat well and varied, preferring fruits and vegetables. Ask for advice about pregnancy risks at your job. If in doubt, consult your doctor or specialist doctor. Thank you for your attention!

RUSSIAN NATIONAL RESEARCH FACILITY
MEDICAL UNIVERSITY them. N.I. PIROGOV
MINISTRY OF HEALTH AND DEVELOPMENT OF THE RUSSIAN FEDERATION
Department of Obstetrics and Gynecology, Faculty of Medicine
(Head of the Department Professor, Doctor of Medical Sciences Yu.E. Dobrokhotova)
LECTURE
IMPACT OF HARMFUL FACTORS
ON THE FRUIT

Teratology is the science of developmental disorders or
the formation of defects in the fetus
(Greek Teras - "monster")
HARMFUL FACTORS
hypoxia
hyperthermia
Hypothermia
ionizing radiation
Organic teratogens
Inorganic teratogens
infections
medicinal substances

Stages of intrauterine development
Preimplantation
period
7 days after
fertilization
Implantation
7th day after
fertilization
Organogenesis and
placentation
Until the end of 3-4 months of intrauterine development
fetal period
12 - 40 weeks
pregnancy

Congenital anomaly - structural, metabolic and
functional disorders of an organ, part of an organ or large
parts of the body that occur in utero.
Congenital malformation is a term that includes various
structural defects. The overall frequency of congenital malformations is 600 per 10,000 of all
live and stillborn children (6%).
Unidentified cause 20% Monogenic - 6%
Chromosomal - 5%
External - 6%
Multifactorial 63%

Classification of VLOOKUP

By frequency
Common CM > 1 in 1000
newborns
Moderately frequent congenital malformations 0.1 - 0.99 per
1000 newborns
Rare congenital malformations< 0,01 на 1000
newborns
Prevalence in the body
- isolated
-systemic
-multiple
- gametopathies, blastopathies
By expiration date
harmful factor
-embryopathy
- fetopathy

Classification of congenital malformations by severity and prognosis for viability

Lethal vices
development - 8%
Minor anomalies
development - 60%
CD of an average degree
severity - 32%

Preembryonic period

Stage of development
First crush division
Movement into the uterine cavity
Time from
conception
30 hours
4 days
Implantation
5-6 days
Dual layer disc
12 days
Lionization (female fetuses)
16 days
Three-layer disc and primary strip
19 days

Embryonic period
Stage of development
Organogenesis
Time from
conception
4-8 weeks
Formation of the brain and spinal cord
4 weeks
Bookmark of the heart, kidneys and limbs
The rapid development of the brain, eyes, heart and
limbs
Beginning of intestinal and lung development
Appearance of fingers
Development of ears, kidneys, liver and muscles
Closing of the sky, formation of joints
6 weeks
10 weeks
Sexual differentiation
12 weeks
8 weeks

Relationship between gestational age and damaging factors in the event of fetal malformations

malformation
Anencephaly
cleft lip
cleft palate
Esophageal atresia
rectal atresia
syndactyly
Diaphragmatic hernia
hypospadias
cryptorchidism
Incorrect position of large vessels
Ventricular septal defect
Open aortic duct
Termination
gestational age
26 days
36 days
10 weeks
30 days
6 weeks
6 weeks
6 weeks
12 weeks
7- 9 ​​months
34 days
6 weeks
9 months

ionizing radiation

ionizing
radiation
high energy
- X-rays
-gamma rays
- natural
radioactivity
electromagnetic
radiation
low energy
- microwaves
- radio waves
- ultrasound
- radar
waves
-noise
- vibrations

infections

Embryotoxic or fetolytic defects
viruses are caused directly
transplacental infection (infection with a virus
fetus), or indirectly - through febrile
mother's condition
Rubella virus, especially in the first 90 days
pregnancy, causes congenital heart defects,
deafness and cataracts
Cytomegalovirus infection can lead to
microcephaly and sdfd
Coxsackievirus (enterovirus) is associated with significant
increased incidence of cleft lip and
face, pyloric stenosis and other anomalies
digestive tract and birth defects
hearts
Herpesvirus type II (urogenital) can
lead to microcephaly

TORCH - infections

T - toxoplasmosis - toxoplasmosis
O - others - other infections (syphilis, chlamydia,
enterovirus infections, hepatitis A and B, listeriosis,
measles, mumps, papillomavirus
infection, influenza, etc.)
R - rubeola - rubella
C - cytomegalia - cytomegalovirus infection
H - herpes - herpes virus infection

Oncogenes and inorganic teratogens

Oncogenes are substances that can react with
DNA and modify it
Proved transplacental toxicity of polycyclic
aromatic
hydrocarbons,
benzo-a-pyrene,
methylcholanthrene, various triacines, nitrosoureas and
secondary amines
Increasing the concentration of inorganic teratogens
occurs during mining, metallurgical and
metalworking processes
Lead leads to dysfunction of the central nervous system, the development
mental
backwardness,
cerebral
paralysis,
microcephaly
Mercury exposure leads to impaired motor
activity and mental development in children
Cadmium,
arsenic,
chromates are teratogens,
leading to a decrease in mental activity

Other environmental factors

malnutrition
reception of substandard
products (sprouted
potato)
drinking water pollution
physical agents,
used in medicine, etc.

Drugs that have an undesirable effect on the growth and development of the fetus

Medicinal
facilities
ACE inhibitors
Antithyroid
drugs
Benzodiazepines
Beta blockers
Barbiturates
NSAIDs
Tetracyclines
warfarin
Possible effect
fetal kidney failure or
newborn
Hypothyroidism in the fetus (with overdose)

When used during pregnancy
possible growth retardation (indicated for
atenolol)
Drug dependence in the fetus
Narrowing of the ductus arteriosus (starting from the second
trimester and beyond)
Disturbance of pigmentation of teeth, can slow down
bone growth (short application at the beginning of I
trimester did not lead to teratogenic
effect)
Hemorrhage in the fetal brain

Alcohol and smoking during pregnancy

Alcohol less than 30 ml of ethyl alcohol per day
has a harmful effect on the fetus
When using 30-60 ml of ethyl alcohol per day
10% of children develop IUGR and are observed
congenital anomalies
With daily use of >60 ml of ethyl
alcohol, the fetus develops FGR, congenital
anomalies, postnatal delay in physical and
mental development
Smoking
in
time
pregnancy
maybe
be accompanied
increase
frequencies
spontaneous abortions and defects of the nervous
tubes, placental abruption, premature
childbirth, gestosis.

Antimicrobials

Penicillins, cephalosporins, macrolides
dangerous to the fetus
Aminoglycosides - best avoided, they have
otonephrotoxic action
Streptomycin - only for tuberculosis in
pregnant women, in which case the risk of its use
lower than tuberculosis
Tetracyclines - absolutely contraindicated -
lead to impaired development of bones, teeth
Sulfonamides - should not be used, they
interfere with bilirubin binding
newborn and lead to the development of nuclear
jaundice (an irreversible change in the function
brain).

Antimicrobials

Derivatives of nalidixic acid - not
prescribe during pregnancy, cause
hydrocephalus.
Levomycetin - use before childbirth
leads to the development of "gray syndrome"
fetus, less dangerous to the fetus during
pregnancy.
Metronidazole - possible use with II
trimester, in I it is better not to prescribe
Antifungal drugs are not
absorbed in the digestive tract
therefore safe.

Antihypertensive drugs

The best drug is hydralazine (peripheral
vasodilator)
Dopegyt can lead to hemolytic anemia,
cause meconium ileus
Beta-blockers in high doses increase
uterine tone, promote intrauterine
fetal growth retardation
Ganglioblockers - paralytic intestinal
obstruction in a newborn
Rauwolfia preparations - nasal congestion,
respiratory depression
Nitrates are metabolized to cyanides,
poisoning the newborn (with prolonged
application).

General recommendations for prescribing
medicines during pregnancy
Assess potential benefits and potential harms.
Avoid medications in the first trimester
Do not prescribe drug combinations.
Use the lowest effective dose for
minimum time.
Give preference to local dosage forms.
Advise pregnant women about taking any
drugs, including analgesics, vitamins, dietary supplements,
herbal preparations and other drugs used for
self-treatment.
Monitor the intake of all medications during pregnancy
Monitor the condition during drug therapy
mother and fetus.

Definition of risk categories
teratogenicity of drugs in
food and drug classification
Administration (FDA)
A - no risk - 0.7% of drugs
B (“best” - the best) - no evidence of risk 19%
С (“сaution” - caution) - the risk is not excluded
- 66%
D (“dangerous” - dangerous) - proven risk - 7%
X - contraindicated during pregnancy - 7%

Risk factors for the development of congenital malformations

unplanned pregnancies
late maternal age
insufficient prenatal control
viral infections
taking teratogenic drugs
alcohol
smoking
drugs
malnutrition
occupational hazards
poor healthcare in many countries

Indications for periconceptual prophylaxis
congenital malformations
Diabetes mellitus and other endocrine and metabolic
diseases.
Repeated spontaneous abortions and stillbirths
fruits.
Genetic risk of multifactorial defects
development.
The birth of fetuses with intrauterine growth retardation and
history of premature birth.
Chronic diseases (hypertension, epilepsy,
bronchial asthma, etc.).
Obesity.
Prolonged use of drugs.
Some infectious diseases (rubella,
toxoplasmosis, etc.)

Scheme of measures for periconceptual prevention of congenital malformations

Geneticist
– 1st meeting before the onset
pregnancy, 2nd and 3rd meeting in period I and II
trimester of pregnancy.
Anamnesis
Pedigree
Inspection
Cytogenetic and other genetic
research according to indications
Offspring prognosis
Recommendations for planning pregnancy
and prevention of congenital malformations in the fetus.

Periconceptual treatment for women:
High Content Multivitamins
folic acid
Diet for 2-3 months. before conception and 2-3 months.
after pregnancy
Prenatal diagnosis of congenital malformations and
chromosomal abnormality in the fetus
ultrasound examination
Screening of maternal serum
markers
Invasive diagnostic methods (according to
testimony)

Geneticist - 4th meeting

Medical genetic
counseling
Examination of a newborn
testimony)
(on

Decalogue of commandments for the prevention of congenital malformations (geneticist Eduardo Castillo, Brazil)

Any fertile woman can be pregnant.
Try to complete your family while you are young.
Carry out prenatal control in the prescribed manner.
Get vaccinated against rubella before pregnancy.
Avoid medications unless strictly necessary.
Avoid alcoholic drinks.
Avoid smoking and smoking areas.
Eat well and varied, preferring fruits and vegetables.
Ask for advice on the risks to pregnancy in your
work.
If in doubt, consult your doctor or doctor
specialized service.

INFLUENCE OF HARMFUL FACTORS ON THE FETUS INFLUENCE OF HARMFUL FACTORS ON THE FETUS The prevalence of spontaneous abortions is 15-20% of the total number of pregnancies; 50% of miscarriages in the first trimester have gross violations. The prevalence of spontaneous abortions is 15-20% of the total number of pregnancies; 50% of miscarriages in the first trimester have gross violations; 3-5% of newborns have malformations; 3-5% of newborns have malformations; in 15% of children, malformations are detected at the age of 5-10 years; 15% of children, malformations are detected at the age of 5-10 years

Teratogenic factors Widely distributed. During pregnancy, each woman takes an average of 3.8 drugs. In the US, 10-20% of pregnant women take drugs. In addition, harmful substances are found in everyday life (microwave oven, electronic clock) and at work.

Criteria of teratogenic factors The relationship between the action of the factor and the formation of malformation has been proven The relationship between the action of the factor and the formation of malformation Epidemiological studies confirm this relationship Epidemiological studies confirm this relationship The action of the harmful factor coincides with the critical periods of intrauterine development rare exposure to a damaging factor, characteristic malformations are rarely formed; rare exposure to a damaging factor, characteristic malformations are rarely formed

The main groups of teratogenic factors Drugs and chemicals (tetracyclines, trichopolum, androgens, mercury, lead, phosphorus) Drugs and chemicals (tetracyclines, trichopolum, androgens, mercury, lead, phosphorus) therapy) Ionizing radiation (radiation fallout, radioisotope diagnostics, radiation therapy) Viral and bacterial infections (herpes, rubella, syphilis, toxoplasmosis) Viral and bacterial infections (herpes, rubella, syphilis, toxoplasmosis) Metabolic disorders and bad habits (diabetes mellitus, endemic goiter, phenylketonuria; smoking, alcoholism, drug addiction) Metabolic disorders and bad habits (diabetes mellitus, endemic goiter, phenylketonuria; smoking, alcoholism, drug addiction) A special registry of teratogenic factors is published in the United States

Features of the influence of teratogenic factors (TF) Dose-dependent character. Dose-dependent character. For each TF there is a teratogenic dose. Usually it is 1-3 orders of magnitude lower than the lethal one. There is a dose of teratogenic effect for each TF. Usually it is 1-3 orders of magnitude lower than the lethal one. Sensitivity to different TFs during fetal development may vary. Sensitivity to different TFs during fetal development may vary. Infectious agents as teratogenic factors do not have a threshold dose and are dose-dependent.

Periods of intrauterine development of a person Initial - from the moment of fertilization to implantation of the blastocyst (up to 11 days). Initial - from the moment of fertilization to implantation of the blastocyst (up to 11 days). Embryonic (18-60 days after fertilization) Embryonic (18-60 days after fertilization) Fetal (from 9 weeks of pregnancy to birth) Fetal (from 9 weeks of pregnancy to birth)

Initial period Differs in large compensatory-adaptive capabilities of the embryo. The law of "all or nothing" - if a large number of cells are damaged, the embryo dies, if individual blastomeres are damaged, further development is not disturbed Ovary Ovum Fertilization Ovulation h 3-4 days 5-6 days 2 cells 4 cells 8 cells Morula Blasto cyst

Major malformations CNS malformations - anencephaly, spina bifida, hydrocephalus. They are formed as a result of non-closure of the neural tube with a deficiency of folic acid, infection, diabetes mellitus. Malformations of the central nervous system - anencephaly, spina bifida, hydrocephalus. Formed as a result of non-closure of the neural tube with folic acid deficiency, infection, diabetes mellitus. Congenital heart defects - ASD, tetralogy of Fallot, aortic stenosis, etc. (phenylketonuria, SLE, rubella virus, genetic factors, alcohol, NSAIDs, diabetes mellitus) Congenital heart defects - ASD, tetralogy of Fallot, aortic stenosis, etc. (phenylketonuria, SLE, rubella virus, genetic factors, alcohol, NSAIDs, diabetes mellitus) Cleft lip, hard palate Cleft lip, hard palate Congenital clubfoot Congenital clubfoot Congenital hip dislocation Congenital hip dislocation Malformations of the gastrointestinal tract - pyloric stenosis, Hirschsprung disease, esophageal atresia , anus, etc. Malformations of the gastrointestinal tract - pyloric stenosis, Hirschsprung's disease, atresia of the esophagus, anus, etc.

General approaches to prenatal prevention 1. Environmental protection 2. Family planning (consanguineous marriages, childbearing after 35 years) 3. Prenatal diagnosis - elimination of embryos with pathology 4. Identification of heterozygous carriers 5. Periconceptual preparation 6. Invasive and non-invasive methods of intrauterine diagnosis

Periconceptual preparation, medical genetic counseling, medical genetic counseling, diagnosis of carriage and treatment of viral and bacterial infections, diagnosis of carriage and treatment of viral and bacterial infections, exclusion of prof. harmfulness, exclusion prof. harmfulness, giving up bad habits, giving up bad habits, taking folic acid and tocopherols) taking folic acid and tocopherols)

Methods of intrauterine diagnosis 1. Non-invasive methods: Ultrasound (10-14, 22-24, weeks), Ultrasound (10-14, 22-24, weeks), Biochemical markers: Biochemical markers: 9-14 weeks - HCG, PAPP-A 9-14 weeks - hCG, PAPP-A weeks AFP, 17-OPK, -hCG, estradiol weeks AFP, 17-OPK, -hCG, estradiol 2. Invasive methods: Chorionic biopsy (9-11 weeks) Chorionic biopsy (9-11 weeks ) Cordocentesis (22-24 weeks) Cordocentesis (22-24 weeks)

Medicines and chemicals For the transplacental transition, the following matters: The molecular weight of the drug (up to 600 easily pass, 600 - 1000 limited, more than 1000 almost do not penetrate). Most drugs are less than 600 and easily penetrate to the fetus. The molecular weight of the drug (up to 600 is easily transferred, 600 - 1000 is limited, more than 1000 almost do not penetrate). Most drugs are less than 600 and easily penetrate the fetus. Fat-soluble substances easily diffuse through the placenta (ether, nitrous oxide). Fat-soluble substances easily diffuse through the placenta (ether, nitrous oxide). Binding to blood proteins. The greater the connection, the slower the penetration through the placenta and accumulation in the fetus. Binding to blood proteins. The greater the connection, the slower the penetration through the placenta and accumulation in the fetus. Method of mother administration Method of mother administration Stage of intrauterine development Stage of intrauterine development

Categories of drug safety Risk categories for the use of drugs during pregnancy FDA (Food and Drug Administration) A - no risk to the fetus; B - the risk to the fetus has not been established either in animals or in humans; C - the risk to the fetus has not been established in humans; controlled studies in humans have not been conducted; D - there is a risk to the fetus, but can only be used if there is a risk to life; it is necessary to assess the degree of risk and benefit; X - proven risk to the fetus. During pregnancy are contraindicated.

Antibacterial drugs during pregnancy (Gurtovoy B.L. et al.) Group I - contraindicated in pregnancy: tetracyclines, chloramphenicol, trimetaprim. Group I - contraindicated in pregnancy: tetracyclines, chloramphenicol, trimetaprim. Group II - use only for health reasons: aminoglycosides, nitrofurans, sulfonamides. Group II - use only for health reasons: aminoglycosides, nitrofurans, sulfonamides. Group III - antibiotics without embryotoxic action: penicillins, cephalosporins, macrolides. Group III - antibiotics without embryotoxic action: penicillins, cephalosporins, macrolides.

The impact of antibiotics Tetracycline and its derivatives in the early stages lead to malformations, in the later stages - a slowdown in fetal growth, damage to the rudiments of teeth, hepatotoxic effect hepatotoxic effect Levomycetin - hypoplastic anemia Levomycetin - hypoplastic anemia Aminoglycosides - ototoxic effect Aminoglycosides - ototoxic effect

Ionizing radiation The effect of radiation on the female body occurs according to the general laws of radiation damage radiation practically does not penetrate the skin, but it is very dangerous when it gets inside radiation practically does not penetrate the skin, but it is very dangerous when it gets inside radiation penetrates to a depth of 1-2 cm radiation penetrates to depth of 1-2 cm radiation has the greatest penetrating power with the formation of free radicals, leads to gene mutations radiation has the greatest penetrating power with the formation of free radicals, leads to gene mutations Transplacental transfer is the main in the penetration of isotopes

Mechanisms of transplacental transfer of radionuclides Hematogenous pathway - free transfer of isotopes from mother's blood to fetal blood through the transplacental membrane (131 I, 32 P, etc.) Hematogenous path - free transfer of isotopes from mother's blood to fetal blood through the transplacental membrane (131 I, 32 P, etc.) Accumulation in placental tissues with subsequent exposure to the fetus (transuranium elements) Accumulation in placental tissues with subsequent exposure to the fetus (transuranic elements) Paraplacental passage through the membranes and amniotic fluid (radioactive plutonium) membranes and amniotic fluid (radioactive plutonium)

Infection (mechanisms of action) 1. Viruses (cytomegalvirus, herpes, rubella), penetrating to the embryo and fetus, can have a direct teratogenic effect 2. Infection leads to a change in the metabolism and function of the endometrium, which causes a violation of implantation or a violation of the development of the placenta

TOBACCO SMOKING DURING PREGNANCY of them years - 70% REPRODUCTIVE HEALTH Radzinsky V.Ye. Moscow, 2002

Smoking Tobacco contains more than 600 harmful factors: organic and inorganic acids, proteins, esters, aldehydes, phenols, etc. Tobacco contains more than 600 harmful factors: organic and inorganic acids, proteins, esters, aldehydes, phenols, etc. radioactive polonium currently found in tobacco smokeradioactive polonium currently found in tobacco smoke nicotine has the greatest impact nicotine has the greatest impact

Nicotine Exposure to nicotine in early pregnancy can lead to impaired implantation of the ovum and spontaneous abortion. Exposure to nicotine in early pregnancy can lead to impaired implantation of the ovum and spontaneous abortion. Abortion and premature birth may be due to an increase in uterine contractility when smoking Abortion and premature birth may be due to an increase in uterine contractility when smoking Nicotine leads to contraction of the vessels of the uterus and placenta with the development of placental insufficiency and fetal hypoxia development of placental insufficiency and fetal hypoxia

Nicotine Fetal hypoxia is also associated with an increase in the level of carboxyhemoglobin in it Fetal hypoxia is also associated with an increase in the level of carboxyhemoglobin in it Disturbance of placental development contributes to the occurrence of HFPN and IUGR of the fetus through the amnion, accumulating in the internal organs of the fetus, causes long-term intoxication Nicotine, intensively penetrating through the placenta and accumulating in it, penetrating through the amnion, accumulating in the internal organs of the fetus, causes prolonged intoxication ) Violation of the structure and function of the central nervous system (microcephaly, impaired intelligence, coordination of movements) Growth retardation, especially noticeable after the birth of a child Growth retardation, especially noticeable after the birth of a child Characteristic anomalies in the development of the facial skull (microft almia, facial lengthening, low forehead, chin underdevelopment, small saddle nose, large wide open mouth, strabismus, flattening of the occiput) Characteristic anomalies in the development of the facial skull (microphthalmia, face lengthening, low forehead, chin underdevelopment, small saddle nose, large wide open mouth , strabismus, flattening of the occiput)

The pathogenesis of ASP is not well understood. It is known that ethanol easily crosses the placenta and the blood-brain barrier of the fetus, accumulates in the central nervous system, causing toxic effects. Ethanol easily penetrates the placenta and the blood-brain barrier of the fetus, accumulates in the central nervous system, causing a toxic effect. long-term effects In the liver of the fetus there is no alcohol dehydrogenase enzyme that destroys ethanol, so the fetus is exposed to prolonged exposure Embryotoxic and teratogenic effects are caused by the metabolite of ethanol - acetaldehyde Embryotoxic and teratogenic effects are exerted by the metabolite of ethanol - acetaldehyde