Embryo: Birth Defects & Prenatal Diagnosis (Ch.9)

minor anomalies are present in what percent of newborns?

~15%

major anomalies are present in what percent of newborns?

~3%

what percent of anomalies account for ~25% of infant deaths

~25%

birth defects are caused by:

1. 55% multifactorial

2. 30% genetic

3. 15% environmental

minor anomalies

structural abnormalities

- ex. microtia (small ears), pigmented spots, short palpebral fissures are not themselves detrimental to health but, in some cases, are associated with major defects

the more minor anomalies an infant has, what increases?

chance of major malformation

- serve as clues for more serious underlying defects

what particular minor anomaly is easily recognizable for an indicator of other defects?

ear anomalies

- observed in virtually all children with syndromic malformations

malformations

occur during formation of structures

- ex: period of organogenesis that extends from the beginning of the 3rd-8th week of gestation (embryonic period)

disruptions

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

- vascular accidents leading to transverse limb defects or amniotic bands = examples of destructive factors that produce disruptions

deformations

result from mechanical forces that mold a part of the fetus over a prolonged period

- ex: clubfeet are caused by compression in amniotic cavity

- often involve MSK system and may be reversible postnatally

the highest incidence of birth defects happens when?

during the embryonic period

- risk decreases from there until brith

syndrome

group of anomalies occurring together that have a specific common cause

- indicates that a diagnosis has been made and that the risk of recurrence is known

association

nonrandom appearance of 2 or more anomalies that occur together more frequently than by chance alone, but the cause has not been determined

- ex: VACTERL

teratogen: rubella virus = what congenital malformations?

1. cataracts

2. glaucoma

3. heart defects

4. hearing loss

5. tooth abnormalities

teratogen: cytomegalovirus = what congenital malformations?

1. microcephaly

2. visual impairment

3. intellectual disability

4. fetal death

5. hearing loss

- often, the mother has no symptoms, but can seriously effect fetus

- can be fatal

- some are asymptomatic at birth but develop abnormalities later

teratogen: herpes simplex virus = what congenital malformations?

1. microphthalmia

2. microcephaly

3. retinal dysplasia

- rare

- usually transmitted to child during delivery causing severe illness and sometimes death

teratogen: toxoplasmosis = what congenital malformations?

1. hydrocephalus

2. cerebral calcifications

3. microphthalmia

4. microcephaly/macrocephaly

- poorly cooked meat, domestic cat feces, soil contaminated with feces = Toxoplasmosis gondii

- can appear normal at birth and develop symptoms later

teratogen: isotrentinoin (Accutane) = what congenital malformations?

analog of vitamin A

- isotretinoin embyropathy

1. small abnormally shaped ears, mandibular hypoplasia, cleft palate, heart defects

- prescribed for cystic acne and chronic dermatoses

teratogen: valproic acid = what congenital malformations?

- treats seizure disorders

1. neural tube defect

- spina bifida

2. heart

- ASDs

3. craniofacial + limb

anomalies

- cleft palate

- hypospadias

- polydactyly

- craniocynostosis

teratogen: SSRIs = what congenital malformations?

1. heart malformations

2. neural tube defects

3. anal atresia

4. facial cleft

- serotonin has a role in establishing the L/R ais (laterality)

teratogen: opioid (codeine, hydrocodone, oxycodone) = what congenital malformations?

1. neural tube defects

2. heart defects

3. gastroschisis

- prematurity

- low birth weight

- stillbirths

teratogen: alcohol = what congenital malformations?

1. fetal alcohol syndrome (FAS)

2. fetal alcohol spectrum disorder (FASD)

3. intellectual disability

4. structural brain abnormalities

5. alcohol-related neurodevelopmental disorder (ARND) = cases with evidence of involvement of CNS that do not meet diagnostic criteria for FAS

6. short palpebral fissures

7. maxillary hypoplasia

8. heart defects

9. intelectual disability

- death of neural crest cells = essential for normal craniofacial development

what is the leading cause of intellectual disability?

alcohol

teratogen: marijuana = what congenital malformations?

1. increase in neural tube defect anencephaly

2. increase in neurodevelopmental deficiencies, like ADHD, learning disabilities, learning disabilities, memory impairment

3. premature birth and low birth weight

teratogen: cigarette smoking = what congenital malformations?

1. increased risk for orofacial clefts

2. heart defects

- transposition of great vessels

- ASD

- pulmonary stenosis

- common truncus arteriosus

3. intrauterine growth restriction

4. premature delivery

5. spontaneous abortions

6. stillbriths

7. low birth weight

8. SIDS

9. asthma

10. upper respiratory infections

teratogen: diethylstilbestrol (DES) = what congenital malformations?

synthetic estrogen

1. raised incidence of carcinomas of the vagina and cervix in women exposed in utero

2. reproductive dysfunction

- congenital malformations of uterus, uterine tubes, upper vagina

3. male embryos = increased malformations of testes and abnormal sperm analysis

teratogen: amphetamines = what congenital malformations?

1. cleft lip and palate

2. heart defects

teratogen: maternal diabetes = what congenital malformations?

1. various malformations

2. heart and neural tube defects most common

3. stillbirths

4. neonatal deaths

5. abnormally large infants

6. caudal dysgenesis

- sirenomelia

teratogen: maternal obesity = what congenital malformations?

1. neural tube defects (2x increase)

2. heart defects

3. omphalocele

teratogen: organic mercury = what congenital malformations?

1. neurologic symptoms similar to those of cerebral palsy

2. prematurity

3. intrauterine growth retardation (IUGR)

4. stillbirths

teratogen: advanced paternal age = what congenital malformations?

1. structural birth defects

2. Down syndrome

3. new autosomal dominant mutations

- higher number of mutations to their children than women and the age of the father is the dominant factor in determining how many de novo mutations appear in the child

prenatal diagnosis

1. ultrasound

2. maternal serum screening

3. amniocentesis

4. chorionic villus sampling (CVS)

- detect malformations, genetic abnormalities, overal fetal growth, complications of pregnancy, such as placental or uterine abnormalities

ultrasonography

high-frequency sound waves reflected from tissues to create images

- transabdominal or transvaginal (higher resolution in the latter)

- detects fetal age, growth, congenital anomalies, status of uterine environment, amniotic fluid amount, placental position, umbilical blood flow, multiple gestations

amniocentesis

needle is inserted transabdominally into amniotic cavity

- not performed before 13 weeks of gestation

- fluid analyzed for biochemical factors = AFP and ACh

- fetal cells can be used for metaphase karyotyping and other genetic analyses

chorionic villus sampling (CVS)

A technique associated with prenatal diagnosis in which a small sample of the fetal portion of the placenta is removed for analysis to detect certain genetic and congenital defects in the fetus

- information on neural tube, ventral body wall, cannot be obtained

Cordocentesis (Percutaneous Umbilical Blood Sampling (PUBS))

sampling of fetal blood drawn from the umbilical vein and performed under ultrasound guidance

invasive prenatal diagnostic tests are reserve for what?

high risk pregnancies:

- advanced maternal age

- family history

- maternal disease

- abnormal ultrasound or serum screening test

maternal serum screening

assesses AFP concentrations

- produced by fetal liver

- neural tube defects, gastroschisis, bladder exstrophy, amniotic band syndrome, sacrococcygeal teratoma, intestinal atresia

non-invasive prenatal screening

SCREENING TEST

screens fetus for possible chromosomal abnormalities

relies on ratios found for DNA from each chromosome

preimplantation genetic diagnosis

is a technique used to identify genetic defects in embryos created through in vitro fertilization (IVF) before transferring them into the uterus

fetal transfusion

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

fetal medical treatment

Treatment for infections, fetal cardiac arrhythmias, compromised thyroid function, and other medical problems is usually provided to the mother and reaches the fetal compartment after crossing the placenta. In some cases, however, agents may be administered to the fetus directly by intramuscular injection into the gluteal region or via the umbilical vein.

fetal surgery

a surgical operation on the fetus while it is still in the uterus

stem cell transplantation and gene therapy

Because the fetus does not develop any immunocompetence before 18 weeks' gestation, it may be possible to transplant tissues or cells before this time without rejection.