congenital anomalies.ppt FOR EASY READING
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Feb 27, 2025
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About This Presentation
HELLO
Slide Content
1
CONGENITAL FETAL ANOMALIES
CONGENITAL FETAL ANOMALIES
2
Terminology
Congenital means exist since birth, whether
clinical evidences are obvious or not obvious.
Anomaly means a deviation from the normal.
CA: defects present at birth
Malformation means faulty development of a
structure
Terminology
Congenital means exist since birth, whether
clinical evidences are obvious or not obvious.
Anomaly means a deviation from the normal.
CA: defects present at birth
Malformation means faulty development of a
structure
Congenital anomalies: defects present at
birth
Can be physical, behavioral, psychological
Can be obvious at birth or develop later
3
birth
Can be physical, behavioral, psychological
Can be obvious at birth or develop later
3
Classification of anomalies
Minor anomalies:
Account for 21%. Include birth marks, small
ears, short palpebral fissures.
Non detrimental to life but may be associated
with major defects.
Infants with one minor anomaly have a 3%
chance of having a major anomaly. For 2
minor, chance of major is 10%, and 20% for
three minor anomalies
Minor anomalies:
Account for 21%. Include birth marks, small
ears, short palpebral fissures.
Non detrimental to life but may be associated
with major defects.
Infants with one minor anomaly have a 3%
chance of having a major anomaly. For 2
minor, chance of major is 10%, and 20% for
three minor anomalies
Minor anomaly: birth mark
5
5
Minor anomaly: microtia
6
6
Major anomalies: affects social,
psychological, behavioural, economic well
being of an individual.
Can affect appearance, function and some
may be fatal
Examples include spina bifida,
hydrocephalus, polydactyly, club feet
psychological, behavioural, economic well
being of an individual.
Can affect appearance, function and some
may be fatal
Examples include spina bifida,
hydrocephalus, polydactyly, club feet
Limb defects due to thalidomide
8
8
Types of Anomalies
Malformations
Occur during formation of structures
Complete or partial absence
Alterations of its normal configuration
Disruptions
Morphological alterations of structures after
formation
Due to destructive processes
–Vascular accidents bowel atresias
Malformations
Occur during formation of structures
Complete or partial absence
Alterations of its normal configuration
Disruptions
Morphological alterations of structures after
formation
Due to destructive processes
–Vascular accidents bowel atresias
Types of Anomalies (cont.)
Deformations
Due to mechanical forces that mold a part of
fetus over a prolonged period of time
Clubfeet due to compression in the amniotic cavity
Often involve the musculoskeletal system & may
be reversible postnatally
Syndromes
Group of anomalies occuring together with a
specific common etiology
Diagnosis made & risk of recurrence is known
Deformations
Due to mechanical forces that mold a part of
fetus over a prolonged period of time
Clubfeet due to compression in the amniotic cavity
Often involve the musculoskeletal system & may
be reversible postnatally
Syndromes
Group of anomalies occuring together with a
specific common etiology
Diagnosis made & risk of recurrence is known
Syndrome examples
CHARGE
Colobomas
Heart defects
Atresia of the choanae
Retarded growth
Genital anomolies
Ear anomalies
VACTERL
Verterbral anomalies
Anal
Cardiac
Tracheoesophageal
Renal
Limb
CHARGE
Colobomas
Heart defects
Atresia of the choanae
Retarded growth
Genital anomolies
Ear anomalies
VACTERL
Verterbral anomalies
Anal
Cardiac
Tracheoesophageal
Renal
Limb
12
Types of congenital
anomalies:
Physical structural
defects:
Single structure is
affected.
Multiple structures are
affected.
Non-structural defects
Inherited metabolic
defects
Functional and
behavioral deficits e.g.
congenital mental
retardation.
Incidence:
Major congenital anomalies:
affects about 2 to 5% of all
newborns.
Minor anomalies occur in higher
percentage of newborn (about 10%).
The risk of recurrence of
congenital malformations with the
same patient is very important in
genetic counseling.
Most of congenital anomalies are
single primary developmental
anomaly
general empirical average figure of 2
to 5%, to the apparently known
healthy parents with one affected
child.
More accurate figures could be
calculated only when the etiology is
due to a defect in a single gene and
according to the laws of inheritance
e.g. hemophilia
Types of congenital
anomalies:
Physical structural
defects:
Single structure is
affected.
Multiple structures are
affected.
Non-structural defects
Inherited metabolic
defects
Functional and
behavioral deficits e.g.
congenital mental
retardation.
Incidence:
Major congenital anomalies:
affects about 2 to 5% of all
newborns.
Minor anomalies occur in higher
percentage of newborn (about 10%).
The risk of recurrence of
congenital malformations with the
same patient is very important in
genetic counseling.
Most of congenital anomalies are
single primary developmental
anomaly
general empirical average figure of 2
to 5%, to the apparently known
healthy parents with one affected
child.
More accurate figures could be
calculated only when the etiology is
due to a defect in a single gene and
according to the laws of inheritance
e.g. hemophilia
13
Etiology of Congenital Anomalies
Unknown cause (60%):
The causes of malformations are not
identifiable in the majority of cases.
Multifactorial factors (20%):
Multifactorial etiology denotes the presence
of an interaction between genetic
predisposition and non-genetic intrauterine
factors.
Common examples include neural tube
defects, certain forms of hydrocephaly,
facial clefts, cardiac anomalies, and
imperforate anus.
Etiology of Congenital Anomalies
Unknown cause (60%):
The causes of malformations are not
identifiable in the majority of cases.
Multifactorial factors (20%):
Multifactorial etiology denotes the presence
of an interaction between genetic
predisposition and non-genetic intrauterine
factors.
Common examples include neural tube
defects, certain forms of hydrocephaly,
facial clefts, cardiac anomalies, and
imperforate anus.
14
Genetic basis:
Thousands of known genetic diseases that may affect
humans as all inherited disorders
Are passed from one generation to another.
Genetic diseases may be secondary to either of the following:
Secondary to a single mutant genes (7.5%): ‘Mendelian
single gene disorders’ that carries a risk of causing
congenital malformations.
– Autosomal dominant and recessive disorders:
» About 3000 disorders are inherited in humans due to
single gene disorder. e.g Hemoglobinopathies. sickle
cell disease, thalassemia&Renal disorders: polycystic
kidney disease.
– Sex chromosomal traits (X-linked diseases): There is no male
to male transmission e.g. hemophilia, muscular dystrophy.
Genetic basis:
Thousands of known genetic diseases that may affect
humans as all inherited disorders
Are passed from one generation to another.
Genetic diseases may be secondary to either of the following:
Secondary to a single mutant genes (7.5%): ‘Mendelian
single gene disorders’ that carries a risk of causing
congenital malformations.
– Autosomal dominant and recessive disorders:
» About 3000 disorders are inherited in humans due to
single gene disorder. e.g Hemoglobinopathies. sickle
cell disease, thalassemia&Renal disorders: polycystic
kidney disease.
– Sex chromosomal traits (X-linked diseases): There is no male
to male transmission e.g. hemophilia, muscular dystrophy.
15
Secondary to chromosomal anomalies (6%).
Abnormality of chromosome number (numerical
abnormalities):
»Triplicate number of portion or an entire
chromosome: clinically
- Autosomal abnormalities: e.g. Trisomies e.g.
trisomy 21, 18 and 13. Trisomy 13 and 18 are
fatal.
- Sex chromosome anomalies: The most common are
Turner’s syndrome (45,X), Kleinfelter’s syndrome
(47,XXY).
»Monosomies: Single number of chromosome:
monosomy X. e.g. X-linked mental retardation
(fragile X syndrome).
Abnormality of chromosome structure: Deletions,
translocations, inversions.
Secondary to chromosomal anomalies (6%).
Abnormality of chromosome number (numerical
abnormalities):
»Triplicate number of portion or an entire
chromosome: clinically
- Autosomal abnormalities: e.g. Trisomies e.g.
trisomy 21, 18 and 13. Trisomy 13 and 18 are
fatal.
- Sex chromosome anomalies: The most common are
Turner’s syndrome (45,X), Kleinfelter’s syndrome
(47,XXY).
»Monosomies: Single number of chromosome:
monosomy X. e.g. X-linked mental retardation
(fragile X syndrome).
Abnormality of chromosome structure: Deletions,
translocations, inversions.
16
Exogenous influences
Teratogen exposures :Teratogenesis mostly occurs before the
tenth week of intrauterine life (the period of embryogenesis).
Intrinsic insults:
–Maternal infections:
rubella virus,
cytomegalovirus,
toxoplasmosa gondi,
human parovirus B19
infection, and syphilis.
–Noninfectious systemic
e.g. diabetes mellitus,
phenylketonuria, and
seizure disorders.
–Functional virilizing
lesions of the ovary and
adrenal glands.
Extrinsic insults:
Environmental agents:
–organic solvents, pesticides, anesthetic
gases and heavy metals like lead,
lithium, and organic mercury.
Drug exposure and medications:
–Examples of known human teratogenic
medications:
»Hormonal agents: Progesterone ,
androgenic hormones causing
masculinization of the female fetus
and thyroid and antithyroid drugs.
»Thalidomide causing phocomelia
and other limb congenital
malformations.
Physical injury: Exposure to high doses
of ionizing radiation produces gene
mutation, chromosomal aberrations and
abnormalities.
Exogenous influences
Teratogen exposures :Teratogenesis mostly occurs before the
tenth week of intrauterine life (the period of embryogenesis).
Intrinsic insults:
–Maternal infections:
rubella virus,
cytomegalovirus,
toxoplasmosa gondi,
human parovirus B19
infection, and syphilis.
–Noninfectious systemic
e.g. diabetes mellitus,
phenylketonuria, and
seizure disorders.
–Functional virilizing
lesions of the ovary and
adrenal glands.
Extrinsic insults:
Environmental agents:
–organic solvents, pesticides, anesthetic
gases and heavy metals like lead,
lithium, and organic mercury.
Drug exposure and medications:
–Examples of known human teratogenic
medications:
»Hormonal agents: Progesterone ,
androgenic hormones causing
masculinization of the female fetus
and thyroid and antithyroid drugs.
»Thalidomide causing phocomelia
and other limb congenital
malformations.
Physical injury: Exposure to high doses
of ionizing radiation produces gene
mutation, chromosomal aberrations and
abnormalities.
17
The Food and Drug Administration
“FDA” lists five categories of
tabling for drug use in pregnancy
A.Controlled studies in women failed to demonstrate a risk to
the fetus in the first trimester, and the possibility of fetal
harm appears remote.
B.Animal studies do not indicate a risk to the fetus, there are
no controlled human studies, or animal studies do show an
adverse effect on the fetus, but well –controlled studies in
pregnant women have failed to demonstrate a risk to the
fetus.
C.Studies have shown the drug to have animal teratogenecity
or embryocidal affects, but no controlled studies are
available in either animals or women.
D.Positive evidence of human fetal risk exists, but benefits in
certain situations (e.g., serious diseases for which safer
drugs are ineffective) may make use of the drug acceptable
despite its risks.
X.Studies in animals or humans have demonstrated fetal
anomalies and the risk clearly outweighs any possible
benefit.
The Food and Drug Administration
“FDA” lists five categories of
tabling for drug use in pregnancy
A.Controlled studies in women failed to demonstrate a risk to
the fetus in the first trimester, and the possibility of fetal
harm appears remote.
B.Animal studies do not indicate a risk to the fetus, there are
no controlled human studies, or animal studies do show an
adverse effect on the fetus, but well –controlled studies in
pregnant women have failed to demonstrate a risk to the
fetus.
C.Studies have shown the drug to have animal teratogenecity
or embryocidal affects, but no controlled studies are
available in either animals or women.
D.Positive evidence of human fetal risk exists, but benefits in
certain situations (e.g., serious diseases for which safer
drugs are ineffective) may make use of the drug acceptable
despite its risks.
X.Studies in animals or humans have demonstrated fetal
anomalies and the risk clearly outweighs any possible
benefit.
Environmental factors
Infectious agents
Radiation
Chemical Agents
Hormones
Maternal Disease
Nutritional Deficiencies
Hypoxia
Infectious agents
Radiation
Chemical Agents
Hormones
Maternal Disease
Nutritional Deficiencies
Hypoxia
Infectious Agents
Rubella (German Measles), Greggs 1940
Malformations of the eye
Cataract (6
th
week)
Microphthalmia
Malformations of the ear (9
th
week)
Congenital deafness
–Due to destruction of cochlea
Malformations of the heart (5
th
-10
th
week)
Patent ductus arteriosus
Atrial septal defects
Ventricular septal defects
Rubella (German Measles), Greggs 1940
Malformations of the eye
Cataract (6
th
week)
Microphthalmia
Malformations of the ear (9
th
week)
Congenital deafness
–Due to destruction of cochlea
Malformations of the heart (5
th
-10
th
week)
Patent ductus arteriosus
Atrial septal defects
Ventricular septal defects
Infectious Agents (cont.)
Rubella (German measles)
May be responsible for some brain
abnormalities
Mental retardation
Intrauterine growth retardation
Myocardial damage
Vascular abnormalites
Incidence
47%- during 1
st
four weeks
22% - 5
th
– 8
th
weeks
13% - 9
th
– 16
th
week
Rubella (German measles)
May be responsible for some brain
abnormalities
Mental retardation
Intrauterine growth retardation
Myocardial damage
Vascular abnormalites
Incidence
47%- during 1
st
four weeks
22% - 5
th
– 8
th
weeks
13% - 9
th
– 16
th
week
Infectious Agents (cont.)
Rubella (cont.)
Lab tests permit detection of virus
Antibody levels can be determined
In one study 85 % of women tested were
immune (n = 600)
Virus infects fetus via the placenta
Infection of the child may persist after birth for a
number of years
–Infection can be transmitted to hospital personnel
Vaccines are considered safe & effective
Rubella (cont.)
Lab tests permit detection of virus
Antibody levels can be determined
In one study 85 % of women tested were
immune (n = 600)
Virus infects fetus via the placenta
Infection of the child may persist after birth for a
number of years
–Infection can be transmitted to hospital personnel
Vaccines are considered safe & effective
Rubella measles
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22
Infectious Agents (cont.)
Herpes Simplex Virus
Intrauterine infection of fetus occasionally occurs
Usually infection is transmitted close to time of
delivery
Abnormalities (rare)
Microcephaly
Microphthalmos
Retinal dysplasia
Hepatosplenomegaly
Mental retardation
Usually child infected by mother at birth
Inflammatory reactions during first few weeks
Herpes Simplex Virus
Intrauterine infection of fetus occasionally occurs
Usually infection is transmitted close to time of
delivery
Abnormalities (rare)
Microcephaly
Microphthalmos
Retinal dysplasia
Hepatosplenomegaly
Mental retardation
Usually child infected by mother at birth
Inflammatory reactions during first few weeks
Infectious Agents (cont.)
Herpes Simplex Virus
Intrauterine infection of fetus occasionally occurs
Usually infection is transmitted close to time of
delivery
Abnormalities (rare)
Microcephaly
Microphthalmos
Retinal dysplasia
Hepatosplenomegaly
Mental retardation
Usually child infected by mother at birth
Inflammatory reactions during first few weeks
Herpes Simplex Virus
Intrauterine infection of fetus occasionally occurs
Usually infection is transmitted close to time of
delivery
Abnormalities (rare)
Microcephaly
Microphthalmos
Retinal dysplasia
Hepatosplenomegaly
Mental retardation
Usually child infected by mother at birth
Inflammatory reactions during first few weeks
Herpes simplex infections
25
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26
Infectious Agents (cont.)
Toxoplamosis
Protozoa parasite (Toxoplama gondii)
Sources
–Poorly cooked meat
–Domestic animals (cats)
–Contaminated soil with feces
Syphilis
Congenital deafness
Mental retardation
Diffuse fibrosis of organs (eg. liver & lungs)
In general most infections are pyrogenic
Hyperthemia can be teratogenic
Fever
Hot tubs & Saunas
Toxoplamosis
Protozoa parasite (Toxoplama gondii)
Sources
–Poorly cooked meat
–Domestic animals (cats)
–Contaminated soil with feces
Syphilis
Congenital deafness
Mental retardation
Diffuse fibrosis of organs (eg. liver & lungs)
In general most infections are pyrogenic
Hyperthemia can be teratogenic
Fever
Hot tubs & Saunas
Radiation
Teratogenic effect of ionizing radiation well
established
Microcephaly
Skull defects
Spina bifida
Blindness cleft palate
Extremity defects
Direct effects on fetus or indirect effects on
germ cells
May effect succeeding generations
Avoid X-raying pregnant women
Teratogenic effect of ionizing radiation well
established
Microcephaly
Skull defects
Spina bifida
Blindness cleft palate
Extremity defects
Direct effects on fetus or indirect effects on
germ cells
May effect succeeding generations
Avoid X-raying pregnant women
Radiation
Studies of offspring of Japanese women
who were pregnant at the time of the
atomic bomb explosions over Hiroshima &
Nagasaki who survived the blast
28% aborted
25% gave birth to children who did not survive
their first year
25% of the surviving children had
abnormalities of CNS
e.g. Microcephaly & mental retardation
Studies of offspring of Japanese women
who were pregnant at the time of the
atomic bomb explosions over Hiroshima &
Nagasaki who survived the blast
28% aborted
25% gave birth to children who did not survive
their first year
25% of the surviving children had
abnormalities of CNS
e.g. Microcephaly & mental retardation
Chemical agents/Drugs
Role of chemical agents & drugs in
production of anomalies is difficult to assess
Most studies are retrospective
Relying on mother’s memory
Large # of pharmaceutical drugs used by
pregnant women
NIH study – 900 drugs taken by pregnant women
–Average of 4/woman during pregnancy
–Only 20% of women use no drugs during pregnancy
Very few drugs have been positively identified
as being teratogenic
Role of chemical agents & drugs in
production of anomalies is difficult to assess
Most studies are retrospective
Relying on mother’s memory
Large # of pharmaceutical drugs used by
pregnant women
NIH study – 900 drugs taken by pregnant women
–Average of 4/woman during pregnancy
–Only 20% of women use no drugs during pregnancy
Very few drugs have been positively identified
as being teratogenic
Drugs
Thalidomide
Antinauseant & sleeping pill
Found to cause amelia & meromelia
Total or partial absence of the extremities
Intestinal atresia
Cardiac abnormalities
Many women had taken thalidomide early in
pregnancy (in Germany in 1961)
Thalidomide
Antinauseant & sleeping pill
Found to cause amelia & meromelia
Total or partial absence of the extremities
Intestinal atresia
Cardiac abnormalities
Many women had taken thalidomide early in
pregnancy (in Germany in 1961)
Limb defects due to thalidomide
32
32
Drugs (cont.)
Aminopterin
Antagonist of Folic Acid
Antineoplastic agent which inhibits mitosis
Defects
Anencephaly
Meningocele
Hydrocephalus
Cleft lip & palate
Aminopterin
Antagonist of Folic Acid
Antineoplastic agent which inhibits mitosis
Defects
Anencephaly
Meningocele
Hydrocephalus
Cleft lip & palate
Drugs (cont.)
Anticonvulsants (to treat epilepsy)
Diphenylhydantoin (phenytoin)
Craniofacial defects
Nail & digital hypoplasia
Growth abnormalities
Mental deficiency
The above pattern is know as “fetal hydantoin
syndrome”
Valproic acid
Neural tube defects
Heart defects
Craniofacial & limb anomalies
Anticonvulsants (to treat epilepsy)
Diphenylhydantoin (phenytoin)
Craniofacial defects
Nail & digital hypoplasia
Growth abnormalities
Mental deficiency
The above pattern is know as “fetal hydantoin
syndrome”
Valproic acid
Neural tube defects
Heart defects
Craniofacial & limb anomalies
Drugs (cont.)
Trimethadione (syndrome)
Malformed ears
Cleft palate
Cardiac defects
Urogenital anomalies
Skeletal anomalies
Trimethadione (syndrome)
Malformed ears
Cleft palate
Cardiac defects
Urogenital anomalies
Skeletal anomalies
Drugs (cont.)
Antipsychotic drugs (major tranquilizers)
Phenothiazine & lithium
Suspected teratogenic agents
Antianxiety drugs (minor tranquilizers)
Meprobamate, chlordiazepoxide,
Severe anomalies in 11-12% of offspring where
mothers were treated with the above compared to
2.6% of controls
diazepam (valium)
Fourfold in cleft lip with or without cleft palate
Antipsychotic drugs (major tranquilizers)
Phenothiazine & lithium
Suspected teratogenic agents
Antianxiety drugs (minor tranquilizers)
Meprobamate, chlordiazepoxide,
Severe anomalies in 11-12% of offspring where
mothers were treated with the above compared to
2.6% of controls
diazepam (valium)
Fourfold in cleft lip with or without cleft palate
Drugs (cont.)
Anticoagulants
Warfarin (A.K.A cumadin or cumarol)
Teratogenic
Hypoplasia of nasal cartilage
Chondrodysplasia
Central nervous system defects
–Mental retardation
–Atrophy of the optic nerves
Antihypertensive agents
angiotensin converting enzyme (ACE) inhibitor
Growth dysfunction, renal dysfunction,
oliogohydramnios, fetal death
Anticoagulants
Warfarin (A.K.A cumadin or cumarol)
Teratogenic
Hypoplasia of nasal cartilage
Chondrodysplasia
Central nervous system defects
–Mental retardation
–Atrophy of the optic nerves
Antihypertensive agents
angiotensin converting enzyme (ACE) inhibitor
Growth dysfunction, renal dysfunction,
oliogohydramnios, fetal death
Drugs (cont)
Propylthiouracil
Goiter
Mental retardation
Potassium iodide
Goiter
Mental retardation
Streptomycin
deafness
Sulfonamides
kernicterus
Imipramine (antidepr.)
Limb deformaties
Tetracyclines
Bone & tooth anomalies
Amphetamines
Oral clefts
CV abnormalities
Quinine
Deafness
Aspirin
Potentially harmful in
large doses
Propylthiouracil
Goiter
Mental retardation
Potassium iodide
Goiter
Mental retardation
Streptomycin
deafness
Sulfonamides
kernicterus
Imipramine (antidepr.)
Limb deformaties
Tetracyclines
Bone & tooth anomalies
Amphetamines
Oral clefts
CV abnormalities
Quinine
Deafness
Aspirin
Potentially harmful in
large doses
Drugs (cont.)
Isotretinoin (13-cis-retinoic acid)
Analogue of vitamin A
Drug is prescribed for treatment of cystic acne
& other chronic dermatoses
Highly tertogenic
Reduced & abnormal ear development
Flat nasal bridge
Cleft palate
Hydrocephaly
Neural tube defects
Heart anomalies
Isotretinoin (13-cis-retinoic acid)
Analogue of vitamin A
Drug is prescribed for treatment of cystic acne
& other chronic dermatoses
Highly tertogenic
Reduced & abnormal ear development
Flat nasal bridge
Cleft palate
Hydrocephaly
Neural tube defects
Heart anomalies
Recreational drugs
PCP angel dust
Possible malformations & behavioral
disturbances
Cocaine-vasoconstrictor hypoxia
Spontaneous abortion
Growth retardation
Microcephaly
Behavioral problems
Urogenital anomalies
gastroschisis
PCP angel dust
Possible malformations & behavioral
disturbances
Cocaine-vasoconstrictor hypoxia
Spontaneous abortion
Growth retardation
Microcephaly
Behavioral problems
Urogenital anomalies
gastroschisis
Alcohol
Relationship between alcohol consumption
& congenital abnormalities
Fetal alcohol syndrome
Craniofacial abnormalities
Short palpebral fissures
Hypoplasia of the maxilla
Limb deformities
Altered joint mobility & position
Cardiovascular defects
Ventricular septal abnormalites
Mental retardation
Growth deficiency
Relationship between alcohol consumption
& congenital abnormalities
Fetal alcohol syndrome
Craniofacial abnormalities
Short palpebral fissures
Hypoplasia of the maxilla
Limb deformities
Altered joint mobility & position
Cardiovascular defects
Ventricular septal abnormalites
Mental retardation
Growth deficiency
42
Cigarette Smoking
Has not been linked to major birth defects
Smoking does contribute to intrauterine
growth retardation & premature delivery
Some evidence that is causes behavioral
disturbances
Has not been linked to major birth defects
Smoking does contribute to intrauterine
growth retardation & premature delivery
Some evidence that is causes behavioral
disturbances
Hormones
Androgenic Agents
Synthetic progestins were used frequently to prevent
abortion
Ethisterone & norethisterone
–Have considerable androgenic activity
»Masculinization of female genitalia
Diethylstilbesterol
Commonly used in the 1940’s & 1950’s to prevent
abortion; in 1971 determined that DES caused
increased incidence of vaginal & cervical cancer in
women who had been exposed to DES in utero
In addition high % suffered from reproductive
dysfunction
Oral Contraceptives
Low teratogenic potential, discontinue if pregnancy
suspected
Cortisone-cleft palate in mice (not humans)
Androgenic Agents
Synthetic progestins were used frequently to prevent
abortion
Ethisterone & norethisterone
–Have considerable androgenic activity
»Masculinization of female genitalia
Diethylstilbesterol
Commonly used in the 1940’s & 1950’s to prevent
abortion; in 1971 determined that DES caused
increased incidence of vaginal & cervical cancer in
women who had been exposed to DES in utero
In addition high % suffered from reproductive
dysfunction
Oral Contraceptives
Low teratogenic potential, discontinue if pregnancy
suspected
Cortisone-cleft palate in mice (not humans)
Maternal Disease
Disturbances in CHO metabolism (diabetic
mothers)
High incidence of stillbirth, neonatal deaths
Abnormally large infants
Congenital malformations
risk 3-4X
Cardiac, Skeletal, CNS Anomalies
Caudal dysgensis
–Partial or complete agenesis of sacral vertebrae in
conjuction with hindlimb hypoplasia
Hypoglycemic episodes teratogenic (why?)
Oral hypoglycemic agents maybe
teratogenic
Disturbances in CHO metabolism (diabetic
mothers)
High incidence of stillbirth, neonatal deaths
Abnormally large infants
Congenital malformations
risk 3-4X
Cardiac, Skeletal, CNS Anomalies
Caudal dysgensis
–Partial or complete agenesis of sacral vertebrae in
conjuction with hindlimb hypoplasia
Hypoglycemic episodes teratogenic (why?)
Oral hypoglycemic agents maybe
teratogenic
Maternal Disease (cont.)
Phenylketonuria (PKU)
Enzyme phenylalanine hydroxylase is
deficient phenylalanine (PA) concentrations
Mental retardation
Microcephaly
Risk can be with low PA diet
Phenylketonuria (PKU)
Enzyme phenylalanine hydroxylase is
deficient phenylalanine (PA) concentrations
Mental retardation
Microcephaly
Risk can be with low PA diet
Hypoxia
Associated with congenital malformations
in a great variety of experimental animals
In humans ???
Maybe smaller babies e.g. offspring at high altitude
Associated with congenital malformations
in a great variety of experimental animals
In humans ???
Maybe smaller babies e.g. offspring at high altitude
Environmental Chemicals
Mercury
Fish, seed corn sprayed with mercury
containing fungicide
Multiple neurological symptoms
Lead
abortions
Growth retardation
Neurological disorders
Mercury
Fish, seed corn sprayed with mercury
containing fungicide
Multiple neurological symptoms
Lead
abortions
Growth retardation
Neurological disorders
Chromosomal & Genetic Factors
Numerical Abnormalities
Trisomy 21 (Down syndrome)
Trisomy 18
Trisomy 13
Klinefelter Syndrome
Turner Syndrome
Triple X Syndrome
Structural Abnormalities
Mutant Genes
Numerical Abnormalities
Trisomy 21 (Down syndrome)
Trisomy 18
Trisomy 13
Klinefelter Syndrome
Turner Syndrome
Triple X Syndrome
Structural Abnormalities
Mutant Genes
Chromosomal Abnormalities
May be numerical or structural
Important causes of congenital
malformations & spontaneous abortions
Estimated that 50% of all conceptions end
in spontaneous abortion & 50% of these
have major chromosome abnormalities
Most common chromosome abnormalities
in aborted fetuses is:
Turner syndrome (45,X)
triploidy
trisomy 16
May be numerical or structural
Important causes of congenital
malformations & spontaneous abortions
Estimated that 50% of all conceptions end
in spontaneous abortion & 50% of these
have major chromosome abnormalities
Most common chromosome abnormalities
in aborted fetuses is:
Turner syndrome (45,X)
triploidy
trisomy 16
Numerical Abnormalities
Normal gametes are haploid (n =23)
Normal human somatic cell contains 46
chromosomes; Diploid (2n = 46)
Euploid-Exact multiple of n
Aneuploid-Any chromosome # that is noneuploid
Additional chromosome
Missing chromosome
Most common cause is nondisjunction during
either meiosis to mitosis
Risk of meiotic nondisjunction with maternal age
Normal gametes are haploid (n =23)
Normal human somatic cell contains 46
chromosomes; Diploid (2n = 46)
Euploid-Exact multiple of n
Aneuploid-Any chromosome # that is noneuploid
Additional chromosome
Missing chromosome
Most common cause is nondisjunction during
either meiosis to mitosis
Risk of meiotic nondisjunction with maternal age
Down syndrome (trisomy 21)
Extra copy of Chromosome 21 (95%)
Growth retardation
Varying degrees of mental retardation
Craniofacial abnormalities
Upward slanting eyes
Epicanthal folds
Flattened facies
Small ears
Cardiac defects
Hypotonia
Most of the time due to meiotic nondisjunction
risk in women > 35 (1 in 1000 1 in 400)
Extra copy of Chromosome 21 (95%)
Growth retardation
Varying degrees of mental retardation
Craniofacial abnormalities
Upward slanting eyes
Epicanthal folds
Flattened facies
Small ears
Cardiac defects
Hypotonia
Most of the time due to meiotic nondisjunction
risk in women > 35 (1 in 1000 1 in 400)
53
Trisomy 18
Mental retardation
Congenital heart defects
Low set ears
Flexion of fingers & hands
Micrognathia
Renal anomalies
Syndactyly
Malformations of the skeletal system
Infants usually die by age 2 months
Incidence is 1 in 5000
Mental retardation
Congenital heart defects
Low set ears
Flexion of fingers & hands
Micrognathia
Renal anomalies
Syndactyly
Malformations of the skeletal system
Infants usually die by age 2 months
Incidence is 1 in 5000
Trisomy 18
55
55
56
Trisomy 13
Mental retardation
Holoprosencephaly
Congenital heart defects
Deafness
Cleft lip & palate
Eye defects
Microphthalmia
Anophthalmia
Coloboma
Most infants die by age 3 months
Incidence 1 in 15,000
Mental retardation
Holoprosencephaly
Congenital heart defects
Deafness
Cleft lip & palate
Eye defects
Microphthalmia
Anophthalmia
Coloboma
Most infants die by age 3 months
Incidence 1 in 15,000
58
59
Klinefelter Syndrome: XXY,
XXXY
Found only in males (47, XXY most common)
Usually detected at puberty
I in 500 males
Nondisjunction of XX homologues
Sterility
Testicular atrophy
Hyalinization of seminiferous tubules
Gynecomastia
Maybe some mental impairment
with # of X chromosomes (e.g. 48, XXXY)
XXXY
Found only in males (47, XXY most common)
Usually detected at puberty
I in 500 males
Nondisjunction of XX homologues
Sterility
Testicular atrophy
Hyalinization of seminiferous tubules
Gynecomastia
Maybe some mental impairment
with # of X chromosomes (e.g. 48, XXXY)
Copyright 2009, John Wiley &
Sons, Inc.
Sons, Inc.
Turner Syndrome: XO
Found in women with unmistakably female
appearance
Absence of ovaries (gonadal dysgenesis)
Short stature
Webbed neck (frequently)
Lymphedema of the extremities
Skeletal deformities
Broad chest with widely spaced nipples
Usually (45, X) missing one X chromosome
Found in women with unmistakably female
appearance
Absence of ovaries (gonadal dysgenesis)
Short stature
Webbed neck (frequently)
Lymphedema of the extremities
Skeletal deformities
Broad chest with widely spaced nipples
Usually (45, X) missing one X chromosome
Turners syndrome
Copyright 2009, John Wiley &
Sons, Inc.
Copyright 2009, John Wiley &
Sons, Inc.
Triple X
Patients with triple X are infantile
Scanty menses
Some degree of mental retardation
Patients with triple X are infantile
Scanty menses
Some degree of mental retardation
Structural Abnormalities
May involve one or more chromosomes
Usually result from chromosome breakage
Broken piece may be lost
Partial deletion of chromosome 5
Cri-du-chat (cry of the cat)
Microcephaly
Mental retardation
Congenital heart disease
Many other relatively rare syndromes
result from a partial chromosome loss
May involve one or more chromosomes
Usually result from chromosome breakage
Broken piece may be lost
Partial deletion of chromosome 5
Cri-du-chat (cry of the cat)
Microcephaly
Mental retardation
Congenital heart disease
Many other relatively rare syndromes
result from a partial chromosome loss
Microdeletions
Deletion on long arm of C 15
Angelman syndrome (maternal chromosome)
Mental retardation
Cannot speak
Exhibit poor motor development
Prone to unprovoked & prolonged periods of
laughter
Prader-Willi syndrome (paternal chromosome)
Hypotonia
Obesity
Mental retardation
Hypogonadism
cryptorchidism
Deletion on long arm of C 15
Angelman syndrome (maternal chromosome)
Mental retardation
Cannot speak
Exhibit poor motor development
Prone to unprovoked & prolonged periods of
laughter
Prader-Willi syndrome (paternal chromosome)
Hypotonia
Obesity
Mental retardation
Hypogonadism
cryptorchidism
Structural Abnormalities
Fragile sites
Regions of chromosomes that demonstrate a
propensity to separate or break under certain
conditions
Fragile X syndrome
–Mental retardation
–Large ears
–Prominent jaw
–Pale blue irides
–Male (4/2000) vs. females (1/4000)
–2
ND
to Down syndrome as a cause of chromosomally
derived mental retardation
Fragile sites
Regions of chromosomes that demonstrate a
propensity to separate or break under certain
conditions
Fragile X syndrome
–Mental retardation
–Large ears
–Prominent jaw
–Pale blue irides
–Male (4/2000) vs. females (1/4000)
–2
ND
to Down syndrome as a cause of chromosomally
derived mental retardation
68
Mutant Genes
Many congenital malformations are
inherited
Some show a clear mendelian pattern of
inheritance
In many cases abnormality is attributed to a
change in the structure or function of a single
gene. “single gene mutation”
Estimated that this type of defect makes up
about 8% of all human malformations
Dominant vs. recessive vs. X-linked (also
recessive)
Many congenital malformations are
inherited
Some show a clear mendelian pattern of
inheritance
In many cases abnormality is attributed to a
change in the structure or function of a single
gene. “single gene mutation”
Estimated that this type of defect makes up
about 8% of all human malformations
Dominant vs. recessive vs. X-linked (also
recessive)
Principles of teratology
Were first formulated by Wilson (1959)
Susceptibility to teratogens depend on genotype
and its environmental interaction
Susceptibility varies with developmental stage at
time of exposure
Most sensitive period for inducing birth defect is weeks 3-
8 of gestation
Manifestations of abnormal development depend
on dose & duration of exposure
Teratogens act in specific ways on developing cells
& tissues to initiate abnormal embryogenesis
manifestations of abnormal development death,
malformation, growth retardation, functional
disorders
Were first formulated by Wilson (1959)
Susceptibility to teratogens depend on genotype
and its environmental interaction
Susceptibility varies with developmental stage at
time of exposure
Most sensitive period for inducing birth defect is weeks 3-
8 of gestation
Manifestations of abnormal development depend
on dose & duration of exposure
Teratogens act in specific ways on developing cells
& tissues to initiate abnormal embryogenesis
manifestations of abnormal development death,
malformation, growth retardation, functional
disorders
71
Prevention of birth defects
Good prenatal care
Iodine supplementation eliminates mental
retardation & bone deformities
Prevent cretinism
Folate/Folic Acid supplementation
incidence of neural tube defects
Avoidance of alcohol & other drugs during
all stages of pregnancy
incidence of birth defects
Good prenatal care
Iodine supplementation eliminates mental
retardation & bone deformities
Prevent cretinism
Folate/Folic Acid supplementation
incidence of neural tube defects
Avoidance of alcohol & other drugs during
all stages of pregnancy
incidence of birth defects
73
Prevention Of Having An Offspring
With Congenital Anomalies
Pre-Pregnancy assessment
Antenatal Diagnosis
Postnatal
Assessment
General Guidelines
Prevention Of Having An Offspring
With Congenital Anomalies
Pre-Pregnancy assessment
Antenatal Diagnosis
Postnatal
Assessment
General Guidelines
74
I. General guidelines:
Control of medications during pregnancy:
Minimize drug exposure.
Detection and control of relevant maternal
diseases.
Genetic counseling.
Prenatal diagnosis of genetic conditions and
selective termination of the affected pregnancy or
in-utero treatment if possible.
Discourage consanguineous marriages when
appropriate e.g. closed family, previous
inheritable malformation in the family.
I. General guidelines:
Control of medications during pregnancy:
Minimize drug exposure.
Detection and control of relevant maternal
diseases.
Genetic counseling.
Prenatal diagnosis of genetic conditions and
selective termination of the affected pregnancy or
in-utero treatment if possible.
Discourage consanguineous marriages when
appropriate e.g. closed family, previous
inheritable malformation in the family.
75
Pre-Pregnancy Assessment
Genetic counseling:
A pre-pregnancy information given to couples with family
history of congenital and inherited disorders, helping them to
make a decision regarding future childbearing.
The correct advice provides accurate information concerning the
recurrence risks.
General screening programs:
The aim is to identify some of the common genetic disorders in
a community.
–Adult screening programs in selected high-risk groups:
»Common examples of autosomal recessive disorders: sickle
cell anemia, thalassemia major.
»Gravidas over 35 years: Cytogenic studies on fetal cells
obtained by amniocentesis or chorionic villus sampling.
»Neonatal screening programs: Some of the disorders that are
in needs for immediate identification after delivery and to be
screened soon after delivery are phenylketonuria, congenital
hypothyroidism, sickle cell disease and galactosemia.
Pre-Pregnancy Assessment
Genetic counseling:
A pre-pregnancy information given to couples with family
history of congenital and inherited disorders, helping them to
make a decision regarding future childbearing.
The correct advice provides accurate information concerning the
recurrence risks.
General screening programs:
The aim is to identify some of the common genetic disorders in
a community.
–Adult screening programs in selected high-risk groups:
»Common examples of autosomal recessive disorders: sickle
cell anemia, thalassemia major.
»Gravidas over 35 years: Cytogenic studies on fetal cells
obtained by amniocentesis or chorionic villus sampling.
»Neonatal screening programs: Some of the disorders that are
in needs for immediate identification after delivery and to be
screened soon after delivery are phenylketonuria, congenital
hypothyroidism, sickle cell disease and galactosemia.
76
Pre-natal Diagnostic Procedures
History Taking
Abnormal findings during routine examination
Abnormal findings during routine investigations
Specific Antenatal diagnostic procedures
Pre-natal Diagnostic Procedures
History Taking
Abnormal findings during routine examination
Abnormal findings during routine investigations
Specific Antenatal diagnostic procedures
77
History Taking
leading questions of special significance:
Maternal age.
Personal or family history of congenital anomalies e.g.
familial disorders in the blood relatives.
The ethnic origin.
Significant maternal diseases: diabetes mellitus,
infections, and acute maternal illness.
History Taking
leading questions of special significance:
Maternal age.
Personal or family history of congenital anomalies e.g.
familial disorders in the blood relatives.
The ethnic origin.
Significant maternal diseases: diabetes mellitus,
infections, and acute maternal illness.
78
Suspicious Findings On Clinical Examination
A higher incidence of congenital anomalies
are detected in association with :
Oligohydramnious:
–renal dysplasia, renal agenesis,
– bladder outlet obstruction and
–intrauterine growth retardation.
Polyhydramnios:
–Central nervous system anomalies: anencephaly,
hydrocephaly.
–Gastrointestinal malformations: Tracheoesophageal fistula,
duodenal atresia.
Threatened abortion.
Unexplained IUGR.
Suspicious Findings On Clinical Examination
A higher incidence of congenital anomalies
are detected in association with :
Oligohydramnious:
–renal dysplasia, renal agenesis,
– bladder outlet obstruction and
–intrauterine growth retardation.
Polyhydramnios:
–Central nervous system anomalies: anencephaly,
hydrocephaly.
–Gastrointestinal malformations: Tracheoesophageal fistula,
duodenal atresia.
Threatened abortion.
Unexplained IUGR.
79
Suspicious Findings On Routine
Investigations
Suspicious findings on ultrasound screening:
Early IUGR
IUGR
Oligohydramnios
Hydramnios
Restricted fetal movements
Suspicious Findings On Routine
Investigations
Suspicious findings on ultrasound screening:
Early IUGR
IUGR
Oligohydramnios
Hydramnios
Restricted fetal movements
80
Abnormal maternal serum alpha-fetoprotein
(MSAFP)
MSAFP is elevated (2.5 MOM)
–Fetal anomalies such as neural tube defects, abdominal wall
defects e.g. omphalocele, esophageal or intestinal obstruction,
cystic hygroma, urinary obstruction, renal anomalies: polycystic
kidneys, osteogenesis imperfecta, Turner’s syndrome, and Rh
disease.
–Obstetrical complications such as low birth weight,
oligohydramnios, multifetal gestation.
MSAFP is abnormally low (<0.2 MOM)
–Chromosomal trisomies of the fetus. The values are low in only
one third of Down’s syndrome,
–Gestational trophoblastic disease, and fetal death.
The triple test:
–Specified combinations of maternal serum assay of AFP,
unconjugated oestriol (uE3) and hCG. Special tables are used
to interpret the results.
Abnormal maternal serum alpha-fetoprotein
(MSAFP)
MSAFP is elevated (2.5 MOM)
–Fetal anomalies such as neural tube defects, abdominal wall
defects e.g. omphalocele, esophageal or intestinal obstruction,
cystic hygroma, urinary obstruction, renal anomalies: polycystic
kidneys, osteogenesis imperfecta, Turner’s syndrome, and Rh
disease.
–Obstetrical complications such as low birth weight,
oligohydramnios, multifetal gestation.
MSAFP is abnormally low (<0.2 MOM)
–Chromosomal trisomies of the fetus. The values are low in only
one third of Down’s syndrome,
–Gestational trophoblastic disease, and fetal death.
The triple test:
–Specified combinations of maternal serum assay of AFP,
unconjugated oestriol (uE3) and hCG. Special tables are used
to interpret the results.
81
82
Specific Prenatal Techniques
Non-invasive techniques:
Malformation ultrasound scan
2D Vs3D and 4D scans
MRI.
Invasive techniques:
Amniocentesis
Chorionic villous sampling (CVS),
Cordocentesis,
Fetoscopy
Tapping of fluid filled fetal structure e.g. collection of
fetal urine for assessment of the renal function.
Specific Prenatal Techniques
Non-invasive techniques:
Malformation ultrasound scan
2D Vs3D and 4D scans
MRI.
Invasive techniques:
Amniocentesis
Chorionic villous sampling (CVS),
Cordocentesis,
Fetoscopy
Tapping of fluid filled fetal structure e.g. collection of
fetal urine for assessment of the renal function.
83
Anomaly Scans
Structural Assessment:
Systematic documentation of the essential fetal
anatomy: head, neck, chest, abdomen, limbs, external
genitalia,
Assessment of amniotic fluid volume.
The umbilical cord and its vessels.
Measurements are calculated (Biometry): The
most significant measurements are BPD
(biparietal diameter), OFD (occipto-frontal
diameter), HC (head circumference), and femur
length.
Serial measurements are used to evaluate the growth
pattern of organs.
Anomaly Scans
Structural Assessment:
Systematic documentation of the essential fetal
anatomy: head, neck, chest, abdomen, limbs, external
genitalia,
Assessment of amniotic fluid volume.
The umbilical cord and its vessels.
Measurements are calculated (Biometry): The
most significant measurements are BPD
(biparietal diameter), OFD (occipto-frontal
diameter), HC (head circumference), and femur
length.
Serial measurements are used to evaluate the growth
pattern of organs.
84
85
86
Amniocentesis
It is the most frequently and the established
invasive procedure to be performed.
The samples contain:
Fetal somatic cells that can identify the cytogenetic
constitution of the fetus.
Fluid that can be used to assess variety of biochemical
processes.
Indications of amniocentesis
Chromosomal abnormality,
open neural tube defect,
inborn error of metabolism.
Amniocentesis
It is the most frequently and the established
invasive procedure to be performed.
The samples contain:
Fetal somatic cells that can identify the cytogenetic
constitution of the fetus.
Fluid that can be used to assess variety of biochemical
processes.
Indications of amniocentesis
Chromosomal abnormality,
open neural tube defect,
inborn error of metabolism.
87
12 weeks 14 weeks 16 weeks
40 ml 100 ml 185 ml
12 weeks 14 weeks 16 weeks
40 ml 100 ml 185 ml
88
89
90
•Fetal Loss 0.5%
•Failed Amino. 1.0%
•Culture Failure 0.5%
Problems
•Fetal Loss 0.5%
•Failed Amino. 1.0%
•Culture Failure 0.5%
Problems
91
Chorionic Villous Sampling (CVS)
The aim is to obtain chorionic cells (fetal in
origin) for laboratory study.
Advantages of (CVS) over amniocentesis:
Fetal cells could be obtained at an earlier gestational
age.
Lengthy culture procedures are unnecessary, as
chorion cells divide very rapidly.
–A decision for termination, if necessary, could be taken at an
earlier stage of pregnancy with greater safety and less legal
and religious concerns.
Chorionic Villous Sampling (CVS)
The aim is to obtain chorionic cells (fetal in
origin) for laboratory study.
Advantages of (CVS) over amniocentesis:
Fetal cells could be obtained at an earlier gestational
age.
Lengthy culture procedures are unnecessary, as
chorion cells divide very rapidly.
–A decision for termination, if necessary, could be taken at an
earlier stage of pregnancy with greater safety and less legal
and religious concerns.
92
93
Needle
Chorionic
Tissue
Needle
Chorionic
Tissue
94
CVS - Complications
Fetal loss ~1%
Unsuccessful CVS 1 – 5% (Depends on
operator experience and accessibility
of placenta)
Ambiguous results/maternal cell
contamination ~1-2%
Culture failure 1-2%
CVS - Complications
Fetal loss ~1%
Unsuccessful CVS 1 – 5% (Depends on
operator experience and accessibility
of placenta)
Ambiguous results/maternal cell
contamination ~1-2%
Culture failure 1-2%
95
Factors Affecting Rate of
Fetal Loss Following CVS
Experience of operator
Number of attempts
Time of sampling
Manipulation required
Route of CVS
Who Report 1991
Factors Affecting Rate of
Fetal Loss Following CVS
Experience of operator
Number of attempts
Time of sampling
Manipulation required
Route of CVS
Who Report 1991
96
Percutaneous
Umbilical Cord Blood Sampling
‘Cordocentesis’
The aim is to obtain fetal blood,
using ultrasound directed
needling of the umbilical cord.
The needle is directed to enter
an umbilical vessel at the cord
root.
Possible indications of
cordocentesis:
Diagnostic:
Fetal karyotype.
Other blood tests: Coagulation
factors, hemoglobin
composition, blood cells and
platelets, Respiratory gases.
Cases with isoimmunization:
Fetal blood type and Rh status,
coombs antibody testing,
complete blood cell count
Therapeutic: Transfusion of
compatible donor blood.
Fetal Loss in ~1% of the cases.
Percutaneous
Umbilical Cord Blood Sampling
‘Cordocentesis’
The aim is to obtain fetal blood,
using ultrasound directed
needling of the umbilical cord.
The needle is directed to enter
an umbilical vessel at the cord
root.
Possible indications of
cordocentesis:
Diagnostic:
Fetal karyotype.
Other blood tests: Coagulation
factors, hemoglobin
composition, blood cells and
platelets, Respiratory gases.
Cases with isoimmunization:
Fetal blood type and Rh status,
coombs antibody testing,
complete blood cell count
Therapeutic: Transfusion of
compatible donor blood.
Fetal Loss in ~1% of the cases.
97
Laboratory Investigative Procedures
Chromosome analysis:
simple cytogenic techniques
special culture and examination for minor
chromosome aberrations
Biochemical analysis:
Bilirubin in rhesus isoimmunization: normally it
is excreted in fetal urine.
Microvillar enzymes from the fetal gut for cystic
fibrosis.
Alpha-fetoprotein: nearly all of AFP is fetal in
origin.
Laboratory Investigative Procedures
Chromosome analysis:
simple cytogenic techniques
special culture and examination for minor
chromosome aberrations
Biochemical analysis:
Bilirubin in rhesus isoimmunization: normally it
is excreted in fetal urine.
Microvillar enzymes from the fetal gut for cystic
fibrosis.
Alpha-fetoprotein: nearly all of AFP is fetal in
origin.
98
Laboratory Investigative Procedures
DNA analysis:
Polymerase chain reaction (PCR)
–Chorionic villi.
–Amniotic fluid or fetal blood.
Molecular genetics is the study of the structure of the genes. Its value in the
obstetric practice is related to the study of inherited disease.
Fetal Gender Determination
risk of a serious X-linked hereditary disorders, for which no specific prenatal
diagnostic test is readily available.
The aim is termination of pregnancy if the fetus is of the exposed type of the X-
linked disorder.
Fetal infection
Testing either the amniotic fluid or the chorionic villi or fetal blood.
Testing for possible fetal viral infection is indicated in cases of maternal virus
infection.
Hematological analysis:
haemoglobinopathies, coagulation disorders, and fetal blood grouping
Laboratory Investigative Procedures
DNA analysis:
Polymerase chain reaction (PCR)
–Chorionic villi.
–Amniotic fluid or fetal blood.
Molecular genetics is the study of the structure of the genes. Its value in the
obstetric practice is related to the study of inherited disease.
Fetal Gender Determination
risk of a serious X-linked hereditary disorders, for which no specific prenatal
diagnostic test is readily available.
The aim is termination of pregnancy if the fetus is of the exposed type of the X-
linked disorder.
Fetal infection
Testing either the amniotic fluid or the chorionic villi or fetal blood.
Testing for possible fetal viral infection is indicated in cases of maternal virus
infection.
Hematological analysis:
haemoglobinopathies, coagulation disorders, and fetal blood grouping
99
What to Do when a CFA is Discovered?
Termination of pregnancy:
Cultural background and religious beliefs play
a role in the decision,
Indicated with malformations incompatible
with life to e.g. anencephaly, and multiple
malformations with poor prognosis.
Counseling
What to Do when a CFA is Discovered?
Termination of pregnancy:
Cultural background and religious beliefs play
a role in the decision,
Indicated with malformations incompatible
with life to e.g. anencephaly, and multiple
malformations with poor prognosis.
Counseling
100
What to Do when a CFA is Discovered?
Prenatal therapy or surgery, available for few
conditions only:
Medical treatment:
Intrauterine heart failure and supraventricular arrhythmia’s:
–maternal medication of digoxin and propranolol.
Congenital adrenal hyperplasia:
– dexamethasone to the mother to reduces accumulation of
androgenic steroids and to lessens virilization of female fetus.
Surgical treatment:
Isoimmune anemias: (e.g. due to Rhesus disease) In utero
treatment by intravascular or intraperitoneal transfusion.
Obstructive hydrocephalus: attempts at intrauterine
ventriculo-amniotic shunts are being tested.
Urinary tract obstruction: implanting a catheter from the fetal
bladder to the amniotic cavity.
Gene therapy: still experimental.
Counseling
What to Do when a CFA is Discovered?
Prenatal therapy or surgery, available for few
conditions only:
Medical treatment:
Intrauterine heart failure and supraventricular arrhythmia’s:
–maternal medication of digoxin and propranolol.
Congenital adrenal hyperplasia:
– dexamethasone to the mother to reduces accumulation of
androgenic steroids and to lessens virilization of female fetus.
Surgical treatment:
Isoimmune anemias: (e.g. due to Rhesus disease) In utero
treatment by intravascular or intraperitoneal transfusion.
Obstructive hydrocephalus: attempts at intrauterine
ventriculo-amniotic shunts are being tested.
Urinary tract obstruction: implanting a catheter from the fetal
bladder to the amniotic cavity.
Gene therapy: still experimental.
Counseling
101
What to Do when a CFA is Discovered?
Planning the best circumstances for delivery.
Congenital anomalies requiring urgent surgical
procedures and special care after delivery:
Gastrointestinal tract obstruction: pyloric stenosis,
esophageal atresia, intestinal atresia, duodenal atresia,
jejuno-ileal atresia, colonic atresia, ano-rectal malformations.
Urinary tract obstruction.
Congenital diaphragmatic hernia.
Exomphalos and extrophy (bladder cloaca).
Open neural tube defects.
Congenital adrenal hyperplasia.
Counseling
What to Do when a CFA is Discovered?
Planning the best circumstances for delivery.
Congenital anomalies requiring urgent surgical
procedures and special care after delivery:
Gastrointestinal tract obstruction: pyloric stenosis,
esophageal atresia, intestinal atresia, duodenal atresia,
jejuno-ileal atresia, colonic atresia, ano-rectal malformations.
Urinary tract obstruction.
Congenital diaphragmatic hernia.
Exomphalos and extrophy (bladder cloaca).
Open neural tube defects.
Congenital adrenal hyperplasia.
Counseling
102
Postnatal Diagnosis Of
Congenital Fetal Malformations
Many cases of congenital malformation,
even in the current obstetric practice are
detected only after delivery.
Routine examination of all newborns
immediately after birth and few days later is
essential component in the routine practice.
Postnatal Diagnosis Of
Congenital Fetal Malformations
Many cases of congenital malformation,
even in the current obstetric practice are
detected only after delivery.
Routine examination of all newborns
immediately after birth and few days later is
essential component in the routine practice.
103
Some Congenital Fetal Anomalies
Anomalies of the Nervous System
Anomalies of the GIT
Anomalies of the Genito-urinary Tract
Cardiovascular Anomalies
Anterior Abdominal wall defects
Diaphragmatic hernia
Down’s Syndrome
Non Immune Hydrops Fetalis
Some Congenital Fetal Anomalies
Anomalies of the Nervous System
Anomalies of the GIT
Anomalies of the Genito-urinary Tract
Cardiovascular Anomalies
Anterior Abdominal wall defects
Diaphragmatic hernia
Down’s Syndrome
Non Immune Hydrops Fetalis
104
Prevention of CNS Anomalies
Correction of dietary habits: Certain
dietary patterns are deficient in folic acid,
and need to be modified.
Peri-conceptional folate administration.
Peri-conceptional control of DM
Special tests during pregnancy in high-
risk individuals for early detection of such
anomalies.
Prevention of CNS Anomalies
Correction of dietary habits: Certain
dietary patterns are deficient in folic acid,
and need to be modified.
Peri-conceptional folate administration.
Peri-conceptional control of DM
Special tests during pregnancy in high-
risk individuals for early detection of such
anomalies.
105
Anencephaly
Anencephaly is a lethal anomaly due to the absence of
The membrane-ossifying bones of the cranial vault and
consequently the skull and scalp.
The cerebral hemispheres, underlying the above structures
It is more common in girls.
Antenatal diagnosis:
Clinical features: Polyhydramnios and abdominal palpation (absence
of head).
Investigations:
–Raised plasma and amniotic fluid -fetoprotein levels and
–ultrasound features.
Management of anencephalic pregnancy:
Elective abortion.
Vaginal delivery :there is an increased incidence of face
presentation and shoulder dystocia
Anencephaly
Anencephaly is a lethal anomaly due to the absence of
The membrane-ossifying bones of the cranial vault and
consequently the skull and scalp.
The cerebral hemispheres, underlying the above structures
It is more common in girls.
Antenatal diagnosis:
Clinical features: Polyhydramnios and abdominal palpation (absence
of head).
Investigations:
–Raised plasma and amniotic fluid -fetoprotein levels and
–ultrasound features.
Management of anencephalic pregnancy:
Elective abortion.
Vaginal delivery :there is an increased incidence of face
presentation and shoulder dystocia
106
107
Hydrocephalus
Hydrocephalus is an excess of
cerebrospinal fluid within the
ventricles, and the subarachnoid
space.
Congenital cerebral malformations: e.g.
Arnold-Chiari malformation.
Congenital fetal infections e.g.
toxoplasmosis, cytomegalovirus.
Intrauterine intracranial hemorrhage.
Certain forms are multifactorial origin.
Obstruction of the aqueduct of Sylvius
which may be due to genetic disorders
as trisomy 21, infection as toxoplasmosis
and cytomegalovirus, intracranial tumors,
and intracerebral hemorrhage.
Chromosomal abnormalities: triploidy,
trisomy 18, and X-linked trait.
Hydrocephalus
Hydrocephalus is an excess of
cerebrospinal fluid within the
ventricles, and the subarachnoid
space.
Congenital cerebral malformations: e.g.
Arnold-Chiari malformation.
Congenital fetal infections e.g.
toxoplasmosis, cytomegalovirus.
Intrauterine intracranial hemorrhage.
Certain forms are multifactorial origin.
Obstruction of the aqueduct of Sylvius
which may be due to genetic disorders
as trisomy 21, infection as toxoplasmosis
and cytomegalovirus, intracranial tumors,
and intracerebral hemorrhage.
Chromosomal abnormalities: triploidy,
trisomy 18, and X-linked trait.
108
Antenatal diagnosis of hydrocephalus:
Clinical:
– Polyhydramnios.
–Large size head.
– Breech presentation is common
– During labor, vaginal examination: Wide sutures, large fontanelles and
thin, soft identable cranial bones.
Ultrasound:
–Diagnostic value: serial ultrasound studies are important to avoid false
positive diagnosis.
–Prognostic value:
» the type of hydrocephalus
»the site and extent of the brain injury
»The cerebral cortex compression is followed regularly.
Congenital hydrocephalus is commonly associated
with other neurological or general congenital
malformations e.g. spina bifida, harelip, clubfoot, or
imperforate anus.
Antenatal diagnosis of hydrocephalus:
Clinical:
– Polyhydramnios.
–Large size head.
– Breech presentation is common
– During labor, vaginal examination: Wide sutures, large fontanelles and
thin, soft identable cranial bones.
Ultrasound:
–Diagnostic value: serial ultrasound studies are important to avoid false
positive diagnosis.
–Prognostic value:
» the type of hydrocephalus
»the site and extent of the brain injury
»The cerebral cortex compression is followed regularly.
Congenital hydrocephalus is commonly associated
with other neurological or general congenital
malformations e.g. spina bifida, harelip, clubfoot, or
imperforate anus.
109
Management Options
Termination of pregnancy could be offered, if
diagnosis is definite in the early second
trimester.
Search for associated anomalies.
Establishment of the etiology if possible.
Amniocentesis to determine fetal karyotype.
Intrauterine therapy (under ultrasound guide):
Attempts at intrauterine ventriculo-amniotic
shunts (with a one way valve may be done to
drain CSF from cerebral ventricles into the
amniotic sac to prevent compression and
atrophy of brain tissues) are being tested.
Management Options
Termination of pregnancy could be offered, if
diagnosis is definite in the early second
trimester.
Search for associated anomalies.
Establishment of the etiology if possible.
Amniocentesis to determine fetal karyotype.
Intrauterine therapy (under ultrasound guide):
Attempts at intrauterine ventriculo-amniotic
shunts (with a one way valve may be done to
drain CSF from cerebral ventricles into the
amniotic sac to prevent compression and
atrophy of brain tissues) are being tested.
110
Management Options
Effects of hydrocephaly on vaginal delivery:
Breech presentation is common.
Feto-pelvic disproportion: Non-engagement of the presenting large head
and obstructed labor. Some infants cannot be delivered without
destructive procedure or cesarean section.
Conduct of delivery:
Destructive procedures to facilitate vaginal delivery.
The head is perforated and cerebrospinal fluid is drawn off.
In breech presentation, the aftercoming head is either perforated or spinal
tapping is carried out. A metal canula is introduced through the spinal canal (or
through spina bifida is present).
Delivery of a live newborn, with possible cesarean section, when
there are favorable signs.
Absence of associated anomalies.
Stable hydrocephalus.
Cerebral mantel remains more than 10 mm (thickness of cerebral cortex)
and the newborn will have surgical procedures after delivery i.e. shunting
operations (ventriculo-peritoneal shunt).
Management Options
Effects of hydrocephaly on vaginal delivery:
Breech presentation is common.
Feto-pelvic disproportion: Non-engagement of the presenting large head
and obstructed labor. Some infants cannot be delivered without
destructive procedure or cesarean section.
Conduct of delivery:
Destructive procedures to facilitate vaginal delivery.
The head is perforated and cerebrospinal fluid is drawn off.
In breech presentation, the aftercoming head is either perforated or spinal
tapping is carried out. A metal canula is introduced through the spinal canal (or
through spina bifida is present).
Delivery of a live newborn, with possible cesarean section, when
there are favorable signs.
Absence of associated anomalies.
Stable hydrocephalus.
Cerebral mantel remains more than 10 mm (thickness of cerebral cortex)
and the newborn will have surgical procedures after delivery i.e. shunting
operations (ventriculo-peritoneal shunt).
111
Microcephaly
Microcephaly is an abnormally
small head.
Diagnosis depends on biometry:
Occipto-frontal diameter (OFD)
and BPD are reduced.
Complications of microcephalus:
Mental retardation: the smaller the
head the worse the prognosis.
The presence of associated
anomalies
Microcephaly
Microcephaly is an abnormally
small head.
Diagnosis depends on biometry:
Occipto-frontal diameter (OFD)
and BPD are reduced.
Complications of microcephalus:
Mental retardation: the smaller the
head the worse the prognosis.
The presence of associated
anomalies
112
Spina bifida and Meningomyelocele
Spina bifida is a defect in the spine
resulting from failure of the two halves of
the vertebral arch to fuse.
Ultrasound features of spina bifida:
–The features appear by 18-20 weeks gestation in about 90
per cent of cases.
–The posterior ossification centers of the spine, at the level
of the defect are widely spaced. The vertebral segment
appears in U-shape. The defect may be visualized on
longitudinal scanning.
–There is restricted motility of the lower limbs
Spina bifida and Meningomyelocele
Spina bifida is a defect in the spine
resulting from failure of the two halves of
the vertebral arch to fuse.
Ultrasound features of spina bifida:
–The features appear by 18-20 weeks gestation in about 90
per cent of cases.
–The posterior ossification centers of the spine, at the level
of the defect are widely spaced. The vertebral segment
appears in U-shape. The defect may be visualized on
longitudinal scanning.
–There is restricted motility of the lower limbs
113
114
The prognosis is related to the following:
–Presence and severity of neurological involvement
–The presence of associated abnormalities: e.g.
» Arnold-Chiari malformation (coexisting
hydrocephalus due to prolapse of the cerebellar
hemispheres (obstructing the flow of CSF). It is
to be noted that 90 per cent of cases of spina
bifida have or develops hydrocephalus later on.
»Orthopedic malformations: congenital
dislocation of hips, foot deformity e.g. talipes,
and kyphoscoliosis.
»Chromosomal defects: e.g. trisomy 18.
The prognosis is related to the following:
–Presence and severity of neurological involvement
–The presence of associated abnormalities: e.g.
» Arnold-Chiari malformation (coexisting
hydrocephalus due to prolapse of the cerebellar
hemispheres (obstructing the flow of CSF). It is
to be noted that 90 per cent of cases of spina
bifida have or develops hydrocephalus later on.
»Orthopedic malformations: congenital
dislocation of hips, foot deformity e.g. talipes,
and kyphoscoliosis.
»Chromosomal defects: e.g. trisomy 18.
115
Types:
Spina bifida occulta: The bone only is affected, while the
spinal cord and the membranes are intact. There may be
a patch of hairy skin or a dimple over the affected area. It
has a good prognosis. No treatment is required.
Spina bifida cystica ‘ overta’which includes:
»Meningocele. It is protrusion and herniation of the meninges,
through a bony deficit to the skin.
»Meningomyelocele: It is a protrusion of heterotopic neural tissue
with the meninges. The defect is in the midline and affects the
skin of the back, muscles, bones of the vertebral arches and
neural tube. The membrane is easily ruptured
»Myelocele: No skin or meninges to cover the lesion. It is usually
incompatible with life.
Immediate care after delivery:
Cover the lesion with a sterile non-adhesive dressing to
minimize trauma and infection.
Search for associated malformations
Consult a neurosurgeon.
Types:
Spina bifida occulta: The bone only is affected, while the
spinal cord and the membranes are intact. There may be
a patch of hairy skin or a dimple over the affected area. It
has a good prognosis. No treatment is required.
Spina bifida cystica ‘ overta’which includes:
»Meningocele. It is protrusion and herniation of the meninges,
through a bony deficit to the skin.
»Meningomyelocele: It is a protrusion of heterotopic neural tissue
with the meninges. The defect is in the midline and affects the
skin of the back, muscles, bones of the vertebral arches and
neural tube. The membrane is easily ruptured
»Myelocele: No skin or meninges to cover the lesion. It is usually
incompatible with life.
Immediate care after delivery:
Cover the lesion with a sterile non-adhesive dressing to
minimize trauma and infection.
Search for associated malformations
Consult a neurosurgeon.
116
Anterior Abdominal Wall Defects
The defect in closure may involve the lower
part of abdominal wall only, or bladder,
urethra and penis, and/or clitoris and labia.
These are associated with increased MSAFP.
Unfortunately high percentage of cases have
an associated cardiac and chromosome
abnormalities.
Anterior Abdominal Wall Defects
The defect in closure may involve the lower
part of abdominal wall only, or bladder,
urethra and penis, and/or clitoris and labia.
These are associated with increased MSAFP.
Unfortunately high percentage of cases have
an associated cardiac and chromosome
abnormalities.
117
Types:
Omphalocele (exomphalos):
Congenital herniation of some of the intra-
abdominal contents through the umbilical
ring.
DD. Gastroschisis – Hernia of the
umbilical cord
Ectopia vesicae:
the defect involves the bladder.
[Exstrophy of bladder: The trigone and
urethral orifices are exposed]
Management of defects of
the anterior abdominal wall:
Immediate care:
Do not clamp protruding mass.
Clamp the umbilical cord few
centimeters distal to the
swelling.
Keep the hernial sac moist and
warm, using pads soaked in a
normal saline solution.
Protect from irritation,
traumatic injury of covering
membrane or organs and from
infection.
Empty the stomach of air with
a nasogastric tube.
Surgical corrective repair.
Types:
Omphalocele (exomphalos):
Congenital herniation of some of the intra-
abdominal contents through the umbilical
ring.
DD. Gastroschisis – Hernia of the
umbilical cord
Ectopia vesicae:
the defect involves the bladder.
[Exstrophy of bladder: The trigone and
urethral orifices are exposed]
Management of defects of
the anterior abdominal wall:
Immediate care:
Do not clamp protruding mass.
Clamp the umbilical cord few
centimeters distal to the
swelling.
Keep the hernial sac moist and
warm, using pads soaked in a
normal saline solution.
Protect from irritation,
traumatic injury of covering
membrane or organs and from
infection.
Empty the stomach of air with
a nasogastric tube.
Surgical corrective repair.
118
119
Gastrointestinal Tract Anomalies
The prognosis is generally good after surgical correction
[provided NO other anomalies co-exist]
Malformations presenting with intestinal obstruction:
Bowel obstruction above the ileum.
All usually results in polyhydramnios due to failure of
absorption of swallowed amniotic fluid.
After delivery there is vomiting and abdominal distension.
Surgery at early neonatal life is successful in duodenal
atresia, esophageal atresia, pyloric stenosis, jejeunal and
ileal atresia.
Bowel obstruction below the ileum.
Generalized distention of bowel loops on ultrasound
The causes are:
– Dysfunctional: the distention may be transient and
resolve spontaneously.
– Meconium ileus.
– Anal atresia and imperforate anus.
– Hirschsprung’s disease
Gastrointestinal Tract Anomalies
The prognosis is generally good after surgical correction
[provided NO other anomalies co-exist]
Malformations presenting with intestinal obstruction:
Bowel obstruction above the ileum.
All usually results in polyhydramnios due to failure of
absorption of swallowed amniotic fluid.
After delivery there is vomiting and abdominal distension.
Surgery at early neonatal life is successful in duodenal
atresia, esophageal atresia, pyloric stenosis, jejeunal and
ileal atresia.
Bowel obstruction below the ileum.
Generalized distention of bowel loops on ultrasound
The causes are:
– Dysfunctional: the distention may be transient and
resolve spontaneously.
– Meconium ileus.
– Anal atresia and imperforate anus.
– Hirschsprung’s disease
120
121
Cleft Lip and Cleft Palate
Several teratogens may cause either of the two conditions. Generally
both are not associated with other gastrointestinal malformations.
Cleft Lip: It is cleft in the upper lip.
It may be unilateral or bilateral.
a small notch in the vermilion to a complete separation extending into the of
the nose.
There may be feeding problems.
It is often associated with floor cleft palate.
Surgical repair can be done in the first few days of life.
Cleft Palate:
Bifid uvula. A cleft on midline uvula.
Cleft soft palate.
Cleft bony palate.
Gap in the alveolar arch.
Feeding problems may develop e.g. aspiration and infection.
Corrective surgery: best results if performed around one year of age.
Postoperative complications: are not rare.
– Recurrent otitis media.
–Speech and hearing problems.
Cleft Lip and Cleft Palate
Several teratogens may cause either of the two conditions. Generally
both are not associated with other gastrointestinal malformations.
Cleft Lip: It is cleft in the upper lip.
It may be unilateral or bilateral.
a small notch in the vermilion to a complete separation extending into the of
the nose.
There may be feeding problems.
It is often associated with floor cleft palate.
Surgical repair can be done in the first few days of life.
Cleft Palate:
Bifid uvula. A cleft on midline uvula.
Cleft soft palate.
Cleft bony palate.
Gap in the alveolar arch.
Feeding problems may develop e.g. aspiration and infection.
Corrective surgery: best results if performed around one year of age.
Postoperative complications: are not rare.
– Recurrent otitis media.
–Speech and hearing problems.
122
Urogenital System Abnormalities
Renal Agenesis:
It is a rare abnormality. It is fatal when bilateral.
Potter’s syndrome:
–Renal agenesis,
–pulmonary hypoplasia,
–oligohydramnios,
–IUGR, characteristic compressed facial features, flattened nose, small chin, prominent
epicanthal folds and with a low-set ears.
–At birth there is severe respiratory problems. Ultrasonic confirmation is difficult because it
is based on the documentation of the absence of the renal echoes, in severe
oligohydramnios. Also perirenal fat or adrenal glands may mimic the renal shadow.
Obstructive uropathy:
Various causes of obstruction to urinary flow. Ultrasound diagnosis: Enlarged
bladder and/or hydronephrosis. The condition may be unilateral or bilateral.
Features after delivery: abdominal mass because of enlarged bladder and/or
hydronephrosis.
Types:
–Pelviureteric junction obstruction is considered as acute rather than chronic obstruction.
The prognosis is favorable.
Posterior urethral valves: occur in male. They are responsible to varying degrees of
dilatation of the renal tract.
Complete urethral stenosis: complete absence of amniotic fluid and gross dilatation
of the renal tract. Kidneys may be subjected to severe dysplasia, and appears small
with increased echogenicity
Urogenital System Abnormalities
Renal Agenesis:
It is a rare abnormality. It is fatal when bilateral.
Potter’s syndrome:
–Renal agenesis,
–pulmonary hypoplasia,
–oligohydramnios,
–IUGR, characteristic compressed facial features, flattened nose, small chin, prominent
epicanthal folds and with a low-set ears.
–At birth there is severe respiratory problems. Ultrasonic confirmation is difficult because it
is based on the documentation of the absence of the renal echoes, in severe
oligohydramnios. Also perirenal fat or adrenal glands may mimic the renal shadow.
Obstructive uropathy:
Various causes of obstruction to urinary flow. Ultrasound diagnosis: Enlarged
bladder and/or hydronephrosis. The condition may be unilateral or bilateral.
Features after delivery: abdominal mass because of enlarged bladder and/or
hydronephrosis.
Types:
–Pelviureteric junction obstruction is considered as acute rather than chronic obstruction.
The prognosis is favorable.
Posterior urethral valves: occur in male. They are responsible to varying degrees of
dilatation of the renal tract.
Complete urethral stenosis: complete absence of amniotic fluid and gross dilatation
of the renal tract. Kidneys may be subjected to severe dysplasia, and appears small
with increased echogenicity
123
Anomalies of the external genitalia
Chromosomal anomalies.
Adrenal cortical hyperplasia.
Maternal intake of adrenogenic substances.
Undescended Testicles
Preterm
When to correct
Epispadius/Hypospadius
Associated with XXY, Trisomy 18
Anomalies of the external genitalia
Chromosomal anomalies.
Adrenal cortical hyperplasia.
Maternal intake of adrenogenic substances.
Undescended Testicles
Preterm
When to correct
Epispadius/Hypospadius
Associated with XXY, Trisomy 18
124
Cardiac Anomalies
Some are minor self-limiting or easily correctable
defects, while some are serious and can be lethal.
The common lesions are ventricular septal defects,
patent ductus arteriosus, atrial septal defect,
pulmonary stenosis, fallot’s tetralogy.
Associated extra-cardiac lesions are present in 30 %
of cases.
Ultrasound examination of the fetal chest:
Four-chamber view of the heart: View at right angles to the
longitudinal aspect of the fetal spine. That view demonstrates
arrhythmias.
M-mode tracings of different cardiac chambers or structures.
Doppler color-flow mapping. To define the pattern of the blood flow.
Fetal Echocardiography
Cardiac Anomalies
Some are minor self-limiting or easily correctable
defects, while some are serious and can be lethal.
The common lesions are ventricular septal defects,
patent ductus arteriosus, atrial septal defect,
pulmonary stenosis, fallot’s tetralogy.
Associated extra-cardiac lesions are present in 30 %
of cases.
Ultrasound examination of the fetal chest:
Four-chamber view of the heart: View at right angles to the
longitudinal aspect of the fetal spine. That view demonstrates
arrhythmias.
M-mode tracings of different cardiac chambers or structures.
Doppler color-flow mapping. To define the pattern of the blood flow.
Fetal Echocardiography
125
Single umbilical artery
May be a single anomaly
Possible associated malformations
Esophageal atresia,
Imperforate anus,
Trisomy 18 syndrome.
Single umbilical artery
May be a single anomaly
Possible associated malformations
Esophageal atresia,
Imperforate anus,
Trisomy 18 syndrome.
126
Diaphragmatic Hernia
Pulmonary hypoplasia is a
common serious associated
anomaly.
Chromosomal anomalies are
commonly encountered
Antenatal diagnosis by
ultrasound (cystic spaces
within the chest).
Presentation at birth:
Respiratory distress,
scaphoid abdomen, displaced
apex beat.
Radiological examination:
intrathoracic bowel shadows
Diaphragmatic Hernia
Pulmonary hypoplasia is a
common serious associated
anomaly.
Chromosomal anomalies are
commonly encountered
Antenatal diagnosis by
ultrasound (cystic spaces
within the chest).
Presentation at birth:
Respiratory distress,
scaphoid abdomen, displaced
apex beat.
Radiological examination:
intrathoracic bowel shadows
127
Hydrops Fetalis
Hydrops fetalis is excessive fluid accumulation within the fetal
soft tissues (tissue edema) and body cavities (effusions).
Ultrasound features of full blown hydrops:
Increased skin thickening: > 5 mm.
Placental thickening: > 4 cm.
Body cavities: Significant pleural and pericardial effusions and ascites.
Hydrops Fetalis
Hydrops fetalis is excessive fluid accumulation within the fetal
soft tissues (tissue edema) and body cavities (effusions).
Ultrasound features of full blown hydrops:
Increased skin thickening: > 5 mm.
Placental thickening: > 4 cm.
Body cavities: Significant pleural and pericardial effusions and ascites.
128
Hydrops Fetalis
Causes of fetal hydrops:
Immune hydrops fetalis.
Due to chronic intrauterine anemia. The well-known example is Rh
isoimmunization.
Non-immune hydrops fetalis: Generally it has a high incidence of
mortality.
Fetal cardiac arrhythmias e.g. supraventricular tachycardia. Due to heart
failure.
Fetal structural cardiac anomalies e.g. hypoplastic left heart, due to heart
failure.
Pulmonary hypoplasia
Renal dysplasia.
Hypoproteinaemia
Congenital nephrosis.
Intrauterine infections: due to chronic intrauterine anemia e.g.
toxoplasmosis, rubella, cytomegalovirus infections, congenital hepatitis,
parvovirus infection.
Chromosomal abnormalities: e.g. Turner’s syndrome, trisomy 18 or 21.
Congenital hematological disorders: e.g. thalaaemia.
Twin-to-twin transfusion.
Hydrops Fetalis
Causes of fetal hydrops:
Immune hydrops fetalis.
Due to chronic intrauterine anemia. The well-known example is Rh
isoimmunization.
Non-immune hydrops fetalis: Generally it has a high incidence of
mortality.
Fetal cardiac arrhythmias e.g. supraventricular tachycardia. Due to heart
failure.
Fetal structural cardiac anomalies e.g. hypoplastic left heart, due to heart
failure.
Pulmonary hypoplasia
Renal dysplasia.
Hypoproteinaemia
Congenital nephrosis.
Intrauterine infections: due to chronic intrauterine anemia e.g.
toxoplasmosis, rubella, cytomegalovirus infections, congenital hepatitis,
parvovirus infection.
Chromosomal abnormalities: e.g. Turner’s syndrome, trisomy 18 or 21.
Congenital hematological disorders: e.g. thalaaemia.
Twin-to-twin transfusion.
129
Down’s syndrome
It is Trisomy 21 syndrome.
Incidence: general incidence is 1:600. The incidence rises with
increase of maternal age.
–1:365 at 36 years and 1:40 at the age of 40 years
Neonatal features:
Head: Flat face and flat occiput, third fontanelle, upward slanted
palpebral fissure, inner epicanthal folds and simply formed ears,
nose: small, flat nasal bridge, mouth: small and the tongue
protrudes.
Neck: short, broad. Loose folds in posterior neck.
Hands: simian single palmar crease, short metacarpals and
phalanges. Hypotonia.
Short humerus and femur
Heart: High incidence of cardiac defects e.g. artrioventricular
canal defect.
Increased incidence of leukemias
Gastrointestinal: Duodenal atresia, Hirschsprung’s disease.
Down’s syndrome
It is Trisomy 21 syndrome.
Incidence: general incidence is 1:600. The incidence rises with
increase of maternal age.
–1:365 at 36 years and 1:40 at the age of 40 years
Neonatal features:
Head: Flat face and flat occiput, third fontanelle, upward slanted
palpebral fissure, inner epicanthal folds and simply formed ears,
nose: small, flat nasal bridge, mouth: small and the tongue
protrudes.
Neck: short, broad. Loose folds in posterior neck.
Hands: simian single palmar crease, short metacarpals and
phalanges. Hypotonia.
Short humerus and femur
Heart: High incidence of cardiac defects e.g. artrioventricular
canal defect.
Increased incidence of leukemias
Gastrointestinal: Duodenal atresia, Hirschsprung’s disease.
130
Antenatal Diagnosis
First trimester
Increased Nuchal Thickness
PAPP-A
Failure to detect the nasal bone
Antenatal Diagnosis
First trimester
Increased Nuchal Thickness
PAPP-A
Failure to detect the nasal bone
131
When the nasal bone line appears as a thin line, less
echogenic than the overlying skin, it suggests that the nasal
bone is not yet ossified, and it is therefore classified as
being absent [ 11-13
+6
weeks]
When the nasal bone line appears as a thin line, less
echogenic than the overlying skin, it suggests that the nasal
bone is not yet ossified, and it is therefore classified as
being absent [ 11-13
+6
weeks]
132
Second Trimester Screening
The Triple Test
The Quad Test
Triple Test + Dimeric Inhibin A (DIA)
Integrated first and Second Trimester
Screening
Diagnostic procedures MUST involve
genetic testing of samples obtained from
the baby
Second Trimester Screening
The Triple Test
The Quad Test
Triple Test + Dimeric Inhibin A (DIA)
Integrated first and Second Trimester
Screening
Diagnostic procedures MUST involve
genetic testing of samples obtained from
the baby
133
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