[EMBRYO] Chapter 9 Birth Defects and Prenatal Diagnosis

teratology and dysmorphology

Terms used to describe the study of the Birth defect, congenital malformation, and congenital anomaly

those that are caused by environmental factors (15%)

those caused by genetic factors (30%)

those caused by an interaction of the environment with a person's genetic susceptibility

The causes of birth defects fall into three categories:

third to the end of the eighth week of gestation

Many malformations occur during formation of structures, for example, during the period of organogenesis that extends from the be ginning of the

malformations

Disruptions

Deformations

syndrome

What are the four types of abnormalities

malformations

type of abnormalities that occur during formation of structures

fertilization through the eighth week of gestation

the critical period for causing most structural birth defects extends from

Disruptions

result in morphological alterations of already formed structures and are caused by destructive processes.

vascular accidents leading to transverse limb defects and defects produced by amniotic bands

Example of an abnormality caused by Disruption

Deformations

result from mechanical forces that mold a part of the fetus over a prolonged period; often involve the musculoskeletal system and may be reversible postnatally

syndrome

is a group of anomalies occurring together that have a specific common cause

association

is the nonrandom appearance of two or more anomalies that occur together more frequently than by chance alone, but the cause has not been determined.

An example is the VACTERL association (ver tebral anomalies, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb defects)

Give an example of an Association

thalidomide

In 1961, observations by W. Lenz linked limb defects to the sedative ---and made it clear that drugs could also cross the placenta and produce birth defects

teratogens

factors that cause birth defects

principles of teratology

Factors determining the capacity of an agent to produce birth defects have been defined and set forth as the

1. Genotype of the conceptus and manner of how these genome interact with t he environment

2. Varies on the development stage at the time of exposure

3. Depends on the dose and duration

4. Teratogens have different mechanism on how they act on the developing tissue

5. Manifestations of abnormal development are death, malformation, growth retardation, and functional disorders

5 principles of teratology

rubella

Birth defects due to --- (German measles) during pregnancy (congenital rubella syndrome) used to be a major problem, but development and widespread use of a vaccine have nearly elimi nated congenital malformations from this cause

delivery

Herpes-induced ab normalities are rare, and usually, infection is transmitted to the child during

Cytomegalovirus

It is a serious threat and often the mother has no symptoms, but the effects on the fetus could be devastating. Some infants were asymptomatic at birth but developed abnormalities later (i.e. hearing loss, visual impairment, intellectual disability)

Congenital Zika syndrome (CZS)

Zika Virus causes --- following transmission of the virus from an infected mother to her unborn child.

Neural progenitor cells

What is the target of the Zika Virus

1. Severe microcephaly with overlapping cranial sutures, redundant scalp skin, and prominent occipital bone.

2. Thinning of the cerebral cortex with abnormal gyri and subcortical calcifications.

3. Microphthalmia and coloboma.

4. Joint contractures (arthrogryposis)

5. Neurological sequelae (motor and cognitive deficits)

Zika infection causes a unique pattern of birth de fects in affected children including (5)

Coxsackie B virus

virus that may cause an increase in spontaneous abortion

Measles and mumps

may cause an increase in early and late fetal death

echoviruses

seem to have no adverse effect on the fetus

Toxoplasmosis

caused by undercooked meat, feces of domestic animals especially cats and soil contaminated with feces that can carry the protozoan parasite

Ionizing radiation

kills rapidly proliferating cells, so it is a potent teratogen, producing any type of birth defect.

Thalidomide

an antinauseant and sleeping pills. It results in heart malformations, autism, orofacial clefts, intellectual disability, and defects on urogenital and gastrointestinal systems

Isotretinoin (Accutane)

an analogue of vitamin A. It is prescribed for the treatment of cystic acne and chronic dermatoses. Malformation known as isotretinoin embryopathy

Anticonvulsants, diphenylhydantoin (phenytoin), valproic acid, trimethadione and Topamax

used by women who have seizure disorders

Topamax (topi ramate)

Even newer anticonvulsant drugs like --- increase the risk for cleft lip and/or cleft palate.

Carbamazepine

Pharmaceutical Drugs and Chemical Agents that cause neural tube defects

Opioid (codeine, hydrocodone and oxycodone)

used to treat severe pain. It results in neural tube defects, heart defects and gastroschisis

Mycophenolate mofetil (MMF)

immunosuppressant drug used to prevent rejection in organ transplant patients. Result to cleft palate, microtia (small ears), microcephaly and heart defects.

Anticoagulant warfarin

Pharmaceutical Drugs and Chemical Agents that cause Skeletal abnormalities

Antihypertensive agents that inhibits Angiotensin-converting enzyme (ACE inhibitor)

Pharmaceutical Drugs and Chemical Agents that cause growth retardation, renal dysfunction, fetal death and oligohydramnios

Lysergic Acid Diethylamide

Illicit Drugs, Alcohol, and Cigarettes

limb abnormalities and malformation of the CNS. But moderate doses are not teratogenic.

Cocaine

Illicit Drugs, Alcohol, and Cigarettes

premature labor, uterine groeth retardation and spontaneous abortion malformation of the heart, genitourinary system and brain

Alcohol

Illicit Drugs, Alcohol, and Cigarettes

congenital abnormalities. Leading cause of intellectual disability.

Fetal Alcohol Syndrome (FAS)

represents the severe end of the spectrum and includes structural defects, growth deficiency and intellectual disability

Diethylstilbestrol (DES)

synthetic estrogen which was used to prevent abortion, raised the incidence of carcinomas of the vagina and cervix in wom

Intracytoplasmic sperm injection (ICSI)

this procedure has a higher rate of increased birth defects

Diabetes

Maternal Disease

causes a high incidence of stillbirths, neonatal deaths, abnormally large infants, and congenital malformations. It includes neural tube defects and congenital heart defects. There is also a higher risk for caudal dysgenesis

Phenylketonuria (PKU)

the enzyme phenylalanine hydroxylase is deficient or reduced, resulting in increased serum concentrations of phenylalanine, are at risk for having infants with intellectual disability, microcephaly, and cardiac defects.

Endemic cretinism

Nutritional Deficiencies

◆ Iodine deficiency ◆ Stunted mental and physical growth

Methyl-deficient diets

◆ Altered expression of imprinted genes ◆ Birth defects ◆ Diseases, such as cancer

Ultrasonography

It is a relatively noninvasive technique that uses high-frequency sound waves reflected from tissues to create images.

Nuchal translucency

test involves measurement of the translucent space at the posterior of the baby's neck, where fluid accumulates when Down syndrome and some other abnormalities, especially heart defects are present. The test is performed at 11 to 14 weeks of pregnancy

Maternal Serum Screening

searching for biochemical markers of fetal status.

Alpha-fetoprotein (AFP)

is produced normally by the fetal liver, peaks at approximately 14 weeks, and "leaks" into the maternal circulation via the placenta.

Amniocentesis

A needle is inserted transabdominally into the amniotic cavity (identified by ultrasound), and approximately 20 to 30 mL of fluid is withdrawn.

Chorionic Villus Sampling

involves inserting a needle transabdominally or transvaginally into the placental mass and aspirating approximately 5 to 30 mg of villus tissue

Fetal Transfusion

FETAL THERAPY

- In cases of fetal anemia produced by maternal antibodies or other causes, blood transfusions for the fetus can be performed.

- Ultrasound is used to guide insertion of a needle into the umbilical cord vein, and blood is transfused directly into the fetus.