Ethics in OB/GYN�Influence of unfavorable factors on embrio and fetus��� Medvediev M.V., MD, PhD� Department of Ob/Gyn

• Respect for patient autonomy
• Beneficence and nonmaleficence
• Justice

Principle-Based Ethics

Ethical foundations

• Patient-Physician Relationship
• Physician Conduct and Practice
• Avoiding Conflicts of Interest
• Professional Relations
• Societal Responsibilities
• Informed Consent
• Rights of the mother take precedence over those of the fetus

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Steps of ethical disicion-making

• Identify the decision makers
• Collect data, establish facts
• Identify all medically appropriate options
• Evaluate options according to the values and principles involved
• Identify ethical conflicts and set priorities
• Select the option that can be best justified
• Reevaluate the decision after it is acted on

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POSSIBLE HARMFUL EXOGENOUS ACTIONS ON FETUS

Radiation

exposure

Infections

Influence of different enviromental factors (climate, nourishment, smoking,

use of alcohol, working conditions, social and economic circumstances)

Chemical substances

(drugs, chemical substances)

REASONS FOR FETAL PATHOLOGY DURING INTRAUTERINE PERIOD

• Threatened abortion
• heavy vomiting of pregnant
• prolonged severe preeclampsia
• Placental insufficiency
• Breech presentation
• etc.

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Obstetric complications

Somatic diseases of mother

• Cardiovascular system
• Respiratory system
• Kidney diseases
• Endocrinopathy
• Immunopathologic diseases (antiphospholipid syndrome)
• etc.

REASONS FOR FETAL PATHOLOGY DURING INTRAUTERINE PERIOD

• hereditary pathology is found in 4-6% of newborns
• in opinion of pediatricians, in 20-25% of schoolboys slight stigmas of disembriogenesis can be found

Hereditary factors

• about 50-70% of fertilized eggs are not developed, moreover chromosomal and genetic mutations are in 90% of cases the reason for their loss
• with the spontaneous abortions chromosomal anomalies found in 20-65% of cases

REASONS FOR FETAL PATHOLOGY DURING INTRAUTERINE PERIOD

• cleft palate
• cleft lip
• chondrodystrophy
• anomalies of sex chromosomes

Predisposing factors

• defects of respiratory system

Maternal age

is older than 30 years

Maternal age

is more than 35 years

• defects of CNS
• trisomia of the 13th, 18th or 21^st pairs of chromosomes

Young age of mother is

less than 16 years

The influence of the age of parents is caused by the accumulation of sex cells with the damaged genetic apparatus

PATHOGENESIS OF ANTENATAL PATHOLOGY

• radiation
• lethal mutations
• infectious agents

Direct damage

• intrauterine hypoxia (pathologic acidosis)
• retardation of fetal development (hypotrophy)
• disorder of morphogenesis
• stigmas of disembriogenesis

Disturbance of uteroplacental

blood circulation and function of the placenta

FORMS OF ANTENATAL PATHOLOGY CAUSED BY HARMFUL EXOGENOUS ACTIONS ON FETUS

1. Innate defects of development - gross anatomical changes in the organs and tissues (or the system of organs), which lead to the disorders of the function:

• in 0,27-7,5% among live born
• in 15-25% of perinatal deaths
• in 70-80% of the spontaneous abortuses

2. Intrauterine growth retardation - in 6,5-30% of all newborns

FORMS OF ANTENATAL PATHOLOGY

• GAMETOPATHY - pathologic changes in the sex cells, which occurred before or during fertilization and which lead to the spontaneous termination of pregnancy or innate developmental defects and hereditary diseases

• ovum

• spermatozoid

FORMS OF ANTENATAL PATHOLOGY

• BLASTOPATHY - damage of zygote during first week after fertilization, which cause loss of embryo, severe developmental defects

• zygote

FORMS OF ANTENATAL PATHOLOGY

• EMBRYOPATHY - defeat of embryo from the moment of its implantation (15th day after fertilization) up to formation of the placenta (75^th day of intrauterine life), which are manifested by the defects of development of individual organs, systems, terathomas or termination of pregnancy

FORMS OF ANTENATAL PATHOLOGY

• FETOPATHY – diseases which appear since 76^th day (12th week) of intrauterine life up to the beginning of labor

CLINICAL MANIFESTATIONS OF FETOPATHY

• Intrauterine grow retardation

• Retention of the initial arrangement of organs (cryptorchism)

• Innate developmental defects as a result of persistence of embryonic structures (for example, urachus, opened arterial duct or oval window) or embryonic slots (cleft palate, cleft lip)

CLINICAL MANIFESTATIONS OF FETOPATHY

• Hypoplasia and dysplasia of individual organs and tissues (dysplasia of kidneys, microcephaly, hydrocephaly)

• Innate diseases (hemolytic disease of newborn, hepatitis, cirrhosis, pneumonia, myocarditss, vasculitis, encephalitis)

• Excess growth of connecting and other tissues due to infections (fibroelastosis, cataract )

CAUSES OF FETOPATHY

• prematurity
• asphyxia
• other disturbances of newborn’s adaptation to the extrauterine life
• fetopathy is the most frequent reason for neonatal morbidity and mortality

Classification of innate developmental defects

• Malformation - morphological defect as a result of internal disturbances of fetal development due to genetic factors

• Disruption – morphological defect as a result of external action or any action on the originally normal process of development teratogenic factors

Classification of innate �developmental defects

• Deformation – disturbance of form or position of the part of the body, caused by the mechanical actions

• Dysplasia – disturbance of cells organization in tissues as a result of dishistogenesis

RISK OF APPLICATION OF MEDICINES DURING PREGNANCY

• 80% of pregnant women use episodically or regularly from 4 to 10 different medicines

• 3-5% of defects in fetus and newborn are caused by the action of the medicines

• frequently woman can take medicines either before woman knows about her pregnancy or without consultation with doctor

RISK OF APPLICATION OF MEDICINES DURING PREGNANCY

Medicines can be divided into three groups:

• not penetrating through the placenta, and therefore not causing direct harm to the fetus

• penetrating through the placenta but not rendering harmful effect on fetus

• penetrating through the placenta and accumulating in fetal tissues with possible danger to fetus

(Food and Drug Administration)

• A – medicines, which were accepted by a large quantity of pregnant females without any proofs of their influence on the frequency of development of innate anomalies or damaging action on fetus (SAFE)

FDA CATEGORIES OF SAFETY

А

• В – medicines, which were received on limited quantity of pregnant females without any proofs of their influence on the frequency of development of innate anomalies or damaging action on fetus (CONDITIONALLY SAFE)

В

(Food and Drug Administration)

• C – medicines which in studies on animals demonstrated teratogenic or embryotoxic action. There are suspicions they can cause irreversible damaging action on fetus but not causing development of the innate anomalies (POTENTIALLY UNSAFE)

• А – (safe)

• В – (conditionally safe)

FDA CATEGORIES OF SAFETY

С

(Food and Drug Administration)

• D – medicines which cause or suspected of the fact they can cause the innate anomalies or the irreversible injuries of fetus (UNSAFE). The risk for the fetus should be correlated with the potential benefit from the application of a medicine.

• А – (safe)
• В – (conditionally safe)
• C – (potentially unsafe)

FDA CATEGORIES OF SAFETY

D

• X – medicine with high risk of innate development anomalies with proofs of their teratogenic or embryotoxic action both on animals and human (DANGEROUS) Prohibited to use during the pregnancy!!!

А – (safe)

В – (conditionally safe)

C – (potentially unsafe)

D - (unsafe)

X

(Food and Drug Administration)

FDA CATEGORIES OF SAFETY

EFFECTIVENESS OF DRUG PENETRATION THROUGH PLACENTA DEPENDS ON:

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• size of molecules
• solubility in the lipids
• degree of ionisation and binding to the protein
• thickness of placental membrane and speed of blood flow through placenta

Passage of medicines through the placenta increases with an increase in gestational age

SPECIAL FEATURES OF MEDICINAL SUBSTANCES METABOLISM IN FETUS

• Incomplete destruction of medicines in fetal organism since the system of conjugation of medicines with the glucuronic acid begins to function only in 50 days from the moment of fertilization

• High permeability of medicines through blood-brain barrier as a result of its incomplete development

SPECIAL FEATURES OF MEDICINAL SUBSTANCES METABOLISM IN FETUS

• High vulnerability of the rapidly growing organs

• Accumulation of medicines in the amniotic liquid and entry into gastrointestinal tract with the active ingestion by fetus

SPECIAL FEATURES OF MEDICINAL SUBSTANCES METABOLISM IN FETUS

• In the placenta medicinal substances can be metabolized into the intermediate products, which possess specific toxic properties

• As a result of metabolism in placenta components of drug become more hydrophylic than initial product, which makes transfer back to maternal circulation more difficult and leads to drug metabolites accumulation

INFLUENCE OF MEDICINES

ON FETUS

• TERATOGENIC
• EMBRYOTOXIC
• FETOTOXIC

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PRINCIPLES OF MEDICINES APPLICATION DURING PREGNANCY

• use medicines only with the established safety

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• application of medicines during first 5 months of pregnancy must be limited

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• during process of treatment it’s necessary to perform thorough control of maternal and fetal state

MEDICINES WITH THE TERATOGENIC PROPERTIES

• aminoglucosides (ototoksc action - deafness in newborn)
• alkylating substances
• antimetabolia (cytostatics)
• radioactive diagnostic substances (cretinism in newborn)
• tetracycline (disturbance of the mineralization of the bones and hepatotoxic action)
• talidomid (generation of children with the underdevelopment of extremities)
• estrogens (adenosis of sheath or the development of adenocarcinoma in fetus feminine sex)
• immunnodepresants

SMOKING AND PREGNANCY

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• At the 56th session WHO (World Health Organization), which took place in Geneva on May 19 to 22, 2003 ; tobacco smoking, together with atypical pneumonia and HIV, was related to the greatest threats to health of people in the entire world
• Tobacco smoking has serious consequences for health, first of all, of children and women

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• in Ukraine there is a negative tendency of the propagation of tobacco smoking precisely among the female population, the problem of tobacco smoking in the pregnant females in consequence of which acquires ever greater urgency

INFLUENCE OF SMOKING ON FETUS

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• Nicotine and its metabolites by simple diffusion penetrate through the placental barrier to fetal circulation where their concentration composes 90% of the maternal level

MECHANISMS OF THE NICOTINE DAMAGING ACTIONS ON FETUS

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• Vasoconstriction
• Teratogenic action

INFLUENCE OF SMOKING ON FETUS

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• Fetal distress during pregnancy and labor
• low birth weight
• delay in mental development
• children more frequently suffer from respiratory infections
• ENT problems�

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ALCOHOL AND PREGNANCY

FETAL ALCOHOL SYNDROME (alcoholic embriofetopathy)

• innate anomalies of the fetal development is a result of alcohol teratogenic influence
• it is encountered with frequency 2 per 1000 newborns whose mothers used alcohol during pregnancy

Symptoms of alcoholic embriofetopathy

Symptoms of alcoholic embriofetopathy

• asphyxia
• syndrome of hyperirritability
• delay of psychomotor development
• oligophrenia
• aggressiveness
• epilepsy
• abnomalities of vision

Complete failure of taking alcohol during pregnancy is necessary for delivery of healthy child

data about safe

dose of alcohol is absent

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Thank you!