Topic 5 Part 1 Preconception and prenatal genetic health issues

Question 1

Preconception period

Answer 1

1. Refers to health status and risks before first pregnancy, or health status shortly before any pregnancy.
2. Applies to the father as well as the mother.

Question 2

Periconception period

Answer 2

1. The period immediately before conception through organogenesis (6 weeks).
2. Applies primarily to the mother - critical time period for the development of the embryo.

Question 3

Interconception period

Answer 3

1. The period between pregnancies.
2. Focus is on the mother regaining normal functions after the pregnancy as well as addressing any health issues that occurred during the pregnancy (e.g., hypertension).

Question 4

Goals of preconception genetic health promotion

Answer 4

(Umbrella goal: To refer the woman/couple for genetic counseling if red flags are identified.)

1. To improve women’s wellness.
2. To increase intendedness of pregnancy (better outcomes are associated with intended pregnancies).
3. To educate women/partners about risks.
4. To decrease or modify amenable risks.
5. To offer reproductive options and reduce transmission of potential problems.

Question 5

_ is a health care specialty that provides patient care throughout life.

Answer 5

Genetic counseling.

Question 6

Red flags for further assessment and genetic counseling

Answer 6

Focus is on identifying modifiable risks:

1. History of birth defects.
2. History of infertility.
3. Stillbirths, neonatal death, miscarriages.
4. Maternal illness (diabetes, infections).
5. Family history of genetic disorders (single gene, chromosomal, multi-factorial, carrier status) - cleft palate, heart defects, cancers, etc.
6. Also: Advanced maternal age (35 years or older), maternal exposures (environment, chemicals), abnormal ultrasounds, etc.

Question 7

Consanguinity within a family tree increases the risk for _

Answer 7

Recessive disorders.

Question 8

Ethnicity-based genetic screening - Ashkenazi Jewish ancestry

Answer 8

Cystic fibrosis, Tay-Sachs, Canavan disease, Bloom syndrome, Gaucher’s disease, familial dysautonomia, Fanconi anemia.

Question 9

Ethnicity-based genetic screening - northern European/caucasian ancestry

Answer 9

Cystic fibrosis.

Question 10

Ethnicity-based genetic screening - African ancestry

Answer 10

Sickle cell anemia, beta thalassemia.

Question 11

Ethnicity-based genetic screening - Mediterranean ancestry

Answer 11

Beta thalassemia.

Question 12

Ethnicity-based genetic screening - Asian/south Pacific ancestry

Answer 12

Alpha thalassemia.

Question 13

Advanced maternal age

Answer 13

1. A maternal age 35 years or older at the time of delivery.
2. As a woman’s age increases, her chance of giving birth to a child with a chromosomal abnormality called trisomy increases.
3. Trisomy refers to the presence of three chromosomes instead of the usual two; example: Down syndrome (trisomy 21).

Question 14

Pre-gestational diabetes mellitus

Answer 14

1. Women with pre-gestational DM are at an increased risk for birth defects (NTDs; cardiac, skeletal, and renal anomalies) as well as early spontaneous abortions.
2. This is believed to be related to hyperglycemic states in the very early stages of pregnancy. Early, consistent, and tight control of diabetes in the periconception period can decrease the incidence of congenital anomalies.

Question 15

Routine prenatal screenings are performed _

Answer 15

Before conception through 20 weeks of pregnancy.

Question 16

Multiple marker prenatal screening (biochemical)

Answer 16

1. Performed at 16-18 weeks of pregnancy.
2. Indicates increased genetic risks for NTDs and chromosomal anomalies.
3. Methods: Analysis of four substances produced by fetus and/or placenta - alpha-fetoprotein (AFP); unconjugated estriol (UE3); human chorionic gonadotropin (hCG); and dimeric inhibin (DIA).
4. Disadvantage: Significant incidence of false positive screens - may be caused by presence of twins, insulin dependent diabetes, etc. The majority of women with abnormal multiple marker screenings have healthy babies.

Question 17

For multiple marker prenatal screening, it is important that _

Answer 17

The pregnancy be aged correctly (by last menstrual period or ultrasound).

Question 18

Elevated alpha-fetoprotein (AFP) level

Answer 18

1. Suggests the presence of neural tube defects.

2. Next steps: Confirm gestational age, repeat AFP, high-resolution ultrasound, amniocentesis, offer genetic counseling.

Question 19

Low alpha-fetoprotein (AFP) level

Answer 19

1. Suggests the presence of Down syndrome.

2. Next steps: High-resolution ultrasound, amniocentesis, offer genetic counseling.

Question 20

Low levels of alpha-fetoprotein (AFP), unconjugated estriol (UE3), and human chorionic gonadotropin (hCG)

Answer 20

1. Suggests the presence of trisomy 18 (Edwards syndrome).

2. Next steps: High-resolution ultrasound, amniocentesis, offer genetic counseling.

Question 21

Prenatal diagnostic tests

Answer 21

1. Usually performed through 20 weeks of pregnancy, but may be performed later.
2. Goal is to determine the genotype of the fetus, or to study fetal chromosomes (FISH).
3. Methods: Collection of fetal DNA samples through CVS (chorionic villus sampling), amniocentesis, or other sampling techniques; high-level ultrasound in a perinatal center; FISH (visualization of chromosomes); direct DNA (for suspected mutation).

Question 22

Ultrasound

Answer 22

1. Noninvasive - transducer placed on the abdomen.
2. Uses reflected sound waves converted to an image - can see physical features of the fetus (NTDs, heart defects), not chromosomes (but some chromosomal abnormalities can be identified through physical features).

Question 23

Amniocentesis

Answer 23

1. Performed at 14-18 weeks if deciding whether to maintain a pregnancy; can be performed until term for other reasons.
2. Cells from the amniotic fluid are used to diagnose over 100 chromosomal and biochemical disorders.
3. Carries a risk of infection and spontaneous abortion, so is usually reserved for cases involving: Advanced maternal age; family/parent history of chromosomal abnormalities; mother carrier of recessive or X-linked disorder; need for more accurate fetal AFP level.

Question 24

Chorionic villus sampling (CVS)

Answer 24

1. Performed at 10-13 weeks (earlier than amniocentesis).
2. Karyotypes available within a few hours or days; increased risk of spontaneous abortion (0.5-2% or about 1:100) and infection.

Question 25

Non-invasive prenatal testing (NIPT)

Answer 25

1. Performed after 10 weeks.
2. Analyzes cell-free fetal DNA circulating in the maternal blood.
3. New option for prenatal screening for trisomy 18 and 21 - 99% detection rate; continued research on use for other conditions.

Question 26

Pre-implantation genetic diagnosis (IVF)

Answer 26

1. Identifies embryo genotype before an embryo is implanted and the pregnancy proceeds. Could be used to diagnose aneuploidy, sex-linked disorders, or autosomal single gene disorders (e.g., cystic fibrosis).
2. Avoids pregnancy termination, but not embryo selection/discard.
3. Possible ethical issues due to selectivity and the specter of human engineering.
4. Steps: Access to embryo, blastomere biopsy - around 3 days after fertilization, genetic analysis (karyotyping, biochemical testing, etc.), and embryo transfer.

Question 27

For pre-implantation genetic diagnosis, one cell, a _, is removed.

Answer 27

Blastomere.

Question 28

_ is the most specific and sensitive test for autosomal disorders.

Answer 28

DNA direct analysis.

Question 29

“Major” congenital anomalies

Answer 29

1. Anomalies that produce structural and functional changes.
2. Examples: Neural tube defects, anencephaly, spina bifida, heart defects, orofacial clefts.

Question 30

“Minor” congenital anomalies

Answer 30

1. Anomalies that produce structural changes only.

2. Examples: Epicanthal folds, extra finger, extra nipple, umbilical hernia.

Question 31

The first _ weeks during the embryonic period are considered highly critical for organ development.

Answer 31

Eight.

Question 32

The neural tube closes at the _ week of pregnancy.

Answer 32

Fourth.

Question 33

The _ of the fetus spends the longest time developing during pregnancy.

Answer 33

Central nervous system (essentially takes the entire pregnancy to fully develop).

Question 34

Teratogen

Answer 34

An agent that produces or increases the incidence of congenital malformations.

Question 35

Examples of teratogenic medications

Answer 35

Cocaine, diethylstilbestrol, lithium, anti-seizure medications (e.g., Dilantin, valproic acid), tetracycline, anticoagulants, Accutane.

Question 36

Organization of Teratology Information Specialists (OTIS)

Answer 36

National organization that counsels and educates patients and health professionals about risks related to teratogenic agents and risks of exposure. Also provides education regarding risks associated with lactation.

Question 37

Fetal hydantoin effects

Answer 37

Congenital malformations associated with phenytoin (Dilantin) - cleft lip/palate, characteristic unusual faces (eyes more widely spaced, “cupid’s bow”-shaped upper lip), limb defects (hypoplasia of the distal phalanges, small nails).

Question 38

Fetal valproate syndrome

Answer 38

Congenital malformations associated with valproic acid (Depakote) - epicanthal folds that connect with an infraorbital crease, short nose, long philtrum, small mouth; cardiovascular abnormalities (aortic coarctation, hypoplastic left heart, aortic valve stenosis); long, thin fingers and toes; increased risk for midline defects (NTD, cleft lip/palate).

Question 39

Folic acid for the prevention of neural tube defects

Answer 39

1. The best plan is to take a multivitamin daily that includes 0.4 mg or 400 mcg of folic acid, even when not trying to get pregnant.
2. For women who have had previous pregnancies with NTDs, 10 times (4.0 mg) the normal dose of folic acid is recommended, beginning at least one month prior to attempting conception and continuing throughout the first trimester.
3. Folic acid prevents up to 60-70% of NTD cases, but there are other pathways for the development of NTDs. Other risks include smoking and secondhand smoke.

Question 40

Genetics and adoption

Answer 40

1. Both the adoptee and his or her biological parents (as related to themselves or future children) can lose access to genetic information as a consequence of adoption.
2. The adoption process should include construction of a genetic history and maintenance of genetic information in the adoptee’s files - most states now require this at the outset of the adoption process.
3. The American Society of Human Genetics recommends providing for the updating of genetic information after adoption, even in the cases of closed adoptions, through a non-identifying mutual registry.

Question 41

Cord blood banking

Answer 41

1. Service being marketed to new parents - cord blood contains stem cells that can be extracted, frozen, and used to treat a child or his or her siblings.
2. Used for: Aplastic anemia, leukemia, cerebral palsy, type 1 diabetes, sickle cell, beta thalassemia, hydrocephalus.

Question 42

The advantage of chorionic villus sampling (CVS) over amniocentesis is that _

Answer 42

It can be performed earlier (as early as 10 weeks vs. 14 weeks).

Question 43

CVS can be performed in the first or second trimester, ideally between _ of gestation.

Answer 43

10 and 13 weeks.

Question 44

A pregnant client is at 18 weeks gestation. Which screening test should the nurse recommend be ordered for this client?

Answer 44

Maternal serum alpha fetoprotein (MSAFP). [The biochemical assessment MSAFP test is performed from week 15 to week 20 of gestation (weeks 16 to 18 are ideal).]

Question 45

Which analysis of maternal serum may predict chromosomal abnormalities in the fetus?

Answer 45

Multiple marker screening. [Maternal serum can be analyzed for abnormal levels of alpha-fetoprotein, human chorionic gonadotropin, and estriol. The multiple-marker screening may predict chromosomal defects in the fetus.]

Question 46

An MSAFP screening indicates an elevated level of alpha-fetoprotein. The test is repeated, and again the level is reported as higher than normal. What is the next step in the assessment sequence to determine the well-being of the fetus?

Answer 46

Ultrasound for fetal anomalies. [If MSAFP findings are abnormal, then follow-up procedures include genetic counseling for families with a history of NTD, repeated MSAFP screenings, an ultrasound examination, and possibly amniocentesis.]