Preconception Counseling, Genetics, and Prenatal Dx

Question 1

Pt’s first pregnancy –> spontaneous loss in first trimester… pt is concerned about possibility of recurrent miscarriages.

What is the appropriate response re: risk of recurrence after one miscarriage?

Answer 1

It is no different than it was prior to the miscarriage.

Question 2

A 29 yo G3P0 presents to your office for preconception counseling. All of her pregnancies were lost in the first trimester. She has no significant PMH or surgical hx. She should be counseled that without evaluation and tx, her chance of having a live birth is which of the following?

a. <20%
b. 20% to 35%
c. 40% to 50%
d. 70% to 85%
e. >85%

Answer 2

c. 40% to 50%

Miscarriage risk rises with the number of prior spontaneous abortions. Without tx, the live birth rate approaches 50%. With tx, successful pregnancy rates of 70% to 85% are possible in a pt with a dx of habitual abortion, depending on the underlying cause.

When cervical incompetence is present and a cerclage is placed, success rates can approach 90%.

Question 3

A 26 yo G3P0030 has had three consecutive spontaneous abortions in first trimester. As part of an evaluation for this problem, which of the following tests is most appropriate in the evaluation of this patient?

a. Hysterosalpingogram
b. Chromosomal analysis of the couple
c. Endometrial biopsy in the luteal phase
d. Postcoital test
e. Cervical length by U/S

Answer 3

b. Chromosomal analysis of the couple

A major cause of spontaneous abortions in the first trimester is chromosomal abnormalities. Parental chromosome anomalies account for 2% to 4% of recurrent losses; therefore, karyotype evaluation of the parents is an important part of the evaluation.

Question 4

A 30 yo G1P0 at 8 weeks’ gestation presents for her first prenatal visit. She has no significant past medical or surgical history. A 29 yo friend of hers just had a baby with Down syndrome and she is concerned about her risk of having a baby with the same problem. The patient reports no family hx of genetic disorders or birth defects.

You should tell her that she has an increased risk of having a baby with Down syndrome in which of the following circumstances?

a. The age of the father of the baby is 40 years or older.
b. Her pregnancy was achieved by induction of ovulation and artificial insemination.
c. She has an incompetent cervix.
d. She has a luteal phase defect.
e. She has had three first-trimester spontaneous abortions.

Answer 4

e. She has had three first-trimester spontaneous abortions.

The risk of aneuploidy is increased with multiple miscarriages not attributable to other causes such as endocrine abnormalities or cervical incompetence.

Question 5

Which of the following ultrasound markers is most closely associated with Down syndrome?

a. Choroid plexus cyst
b. Ventriculomegaly
c. Increased nuchal translucency (NT)
d. Intracardiac echogenic focus
e. Echogenic bowel

Answer 5

c. Increased nuchal translucency (NT)

The optimal time to schedule NT measurement is between 12 and 13 weeks, but results are considered valid between 10 4/7 and 13 6/7 weeks. This results in DS detection rates of 72% at a screen positive rate of 5%.

Question 6

Mother is a 27 yo pt presenting to office for prenatal visit. This is her first pregnancy. She is an achondroplastic dwarf. Her husband is of normal stature. In regards to delivery instructions, what should you tell her?

Answer 6

She likely has some degree of spinal stenosis which could present a difficulty with spinal or epidural anesthesia. Recommendation: C-section

Question 7

A 24 yo white woman has a maternal serum a-fetoprotein (MSAFP) level at 17 weeks’ gestation of 6.0 multiples of the median (MOM). She had an ultrasound the same day that appeared normal.

What is the most appropriate next step in mgmt?

The fetus is confirmed to have an open NTD with a dx of spina bifida.

What is the most appropriate counseling for this woman regarding future pregnancies?

Answer 7

1. Recommend an amniocentesis. Evaluate for elevated AFP in the amniotic fluid, as well as elevated acetylcholinesterase. In the setting where both of these amniotic fluid levels are elevated, this test has been shown to ID 100% of cases of anencephaly and open NTDs, as well as 20% of ventral wall defects. The other benefit of amniocentesis is that amniotic fluid may be used for karyotype assessment, as several studies have shown that elevated MSAFP independently increases the risk of fetal aneuploidy.

Regarding future pregnancies, she should take 4 mg of folic acid daily before conception and through first trimester.

Note: Women with no prior hx of NTD who are of childbearing age should be encouraged to take 400micrograms of folic acid daily.

Question 8

A 41 yo woman had a baby with DS 10 years ago. She is anxious to know the chromosome status of fetus in her current pregnancy. She is currently at 8 weeks of gestation. Which of the following will provide the most rapid and reliable dx of Down Syndrome?

a. Amniocentesis
b. Multiple maternal serum marker analysis (Quad screen)
c. Chorionic villi sampling (CVS)
d. First trimester screening using nuchal fold measurements and maternal serum markers
e. Cell free fetal DNA testing

Answer 8

c. CVS

Amniocentesis and CVS are techniques of obtaining fetal cells for cytogenetic analysis. Amniotic fluid cells (obtained by amniocentesis at 15-20 weeks) require tissue culture to obtain adequate cell numbers for analysis. CVS at 10 to 13 weeks, either by transcervical or transabdominal access to the placenta, will provide the earliest results in order to dx Down syndrome.

Multiple maternal serum marker analysis (Quad screen) may be done between 15 and 21 weeks, but it is primarily used for screening otherwise low-risk women for DS.

Question 9

Fetal effects of the following:

TMP/SMX

Tetracyclines

Chloramphenicol

Answer 9

• TMP/SMX: kernicterus (3rd trimester)
• Tetracyclines: dental anomalies and inhibition of bone growth (2nd and 3rd trimester)
• Chloramphenicol: gray baby syndrome (vomiting, impaired respiration, hypothermia, cardiovascular collapse)

Question 10

Children born to mothers who smoke are at increased risk of (3):

Answer 10

Asthma, obesity, colic

Question 11

MMR vaccine recommendation for nonpregnant/pregnant woman

Answer 11

• Nonpregnant: check for immunity against rubella virus prior to conception and vaccinated at least 28 days prior to conception b/c rubella vaccine contains live virus and should not be given during pregnancy
• Pregnant: immediately postpartum

Question 12

Tdap vaccine recommendation during pregnancy

Answer 12

Tdap should be offered to all pregnant women during each pregnancy between 27 and 36 weeks, regardless of the pt’s prior hx of receiving Tdap –> helps prevent mother from acquiring the disease and passing it to her newborn, and also provides passive immunity to the infant

The level of pertussis antibodies decreases over time, hence the recommendation to administer during every pregnancy

In addition, all family members and caregivers of infants should be vaccinated with Tdap

Question 13

Eastern European Jewish ancestry carrier screening (4)

Answer 13

• Tay-Sachs (CF 1/30)
• Canavan disease (CF 1/40)
• Familial dysautonomia (CF 1/32)
• CF (CF 1/29)

Question 14

Inheritance of the following disorders:

• Sickle cell disease
• G6PD
• NF
• CF
• Huntington disease

Answer 14

• Sickle cell disease: AR
• G6PD: XLR
• NF: AD
• CF: AR
• Huntington disease: AD

Question 15

Is pregnancy a contraindication to Hepatitis B vaccination?

Answer 15

No

Question 16

A 24 yo woman presents with a hx of one first-trimester spontaneous abortion.

What is the single most common specific chromosome abnormality associated with first trimester miscarriage?

Answer 16

Trisomy 21

Autosomal trisomy = most common group of chromosomal anomalies leading to first trimester miscarriage. However, 45 X (Turner Syndrome) is the most common single abnormality found.