A 29-year-old woman, gravida 2 para 0, comes to the physician for a routine prenatal visit. She previously had regular menses every 28 days and is at 18 weeks gestation based on her last menstrual period and physical examination. The patient had a first-trimester miscarriage during her prior pregnancy. She takes prenatal vitamins but otherwise has no medical problems and takes no medications. Her pre-pregnancy weight was 54 kg (119 lb) and she has gained 1 kg (2.2 lb) during this pregnancy. Vital signs and physical examination are normal. The uterus is soft and palpable just below the umbilicus. The maternal serum α-fetoprotein protein level obtained last week is significantly elevated. Which of the following is the most likely abnormality associated with this finding?
Maternal serum α-fetoprotein screening | |
↑ MSAFP | ↓ MSAFP |
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MSAFP = maternal serum α-fetoprotein. | |
Alpha-fetoprotein (AFP) is a major protein produced by the fetal yolk sac, liver, and gastrointestinal tract. Maternal serum AFP (MSAFP) is measured at 15-20 weeks gestation (optimally at 16-18 weeks) to screen for fetal anomalies. MSAFP is used primarily to screen for open neural tube defects. Increased levels are also associated with fetal abdominal wall defects (eg, gastroschisis, omphalocele) and multiple gestation. Less commonly, an increased MSAFP can be seen in fetal congenital nephrosis and benign obstructive uropathy.
An elevated MSAFP warrants careful ultrasound evaluation of the fetal anatomy. In addition, the number of fetuses should be clarified as multiple gestations produce more AFP. Gestational age is also confirmed as interpretation of AFP level depends on an accurate gestational age.
(Choice A) Cystic fibrosis results most commonly from ΔF508 mutation. If both parents are carriers of the genetic mutation, fetal diagnosis can be made by chorionic villus sampling, amniocentesis, or fetal blood sampling. Cystic fibrosis does not affect AFP levels.
(Choice C) Most major fetal cardiac anomalies can be diagnosed by a screening second-trimester ultrasound. Congenital heart disease does not affect AFP levels.
(Choice D) Elevated levels of AFP can be seen in patients with hepatocellular carcinoma, tumors of gonadal origin, and liver disease (eg, acute or chronic viral hepatitis). It is very unlikely that this patient has any of these as she has no symptoms.
(Choices E and G) Down syndrome can be caused by meiotic nondisjunction or Robertsonian translocation. Trisomy 18 is usually caused by meiotic nondisjunction. Down syndrome has a profile of low MSAFP, low estriol, elevated β-HCG, and an increased inhibin A level. Trisomy 18 has low MSAFP, very low estriol, very low β-HCG, and normal inhibin A level. This patient had an elevated, not low, AFP, so trisomy is unlikely.
(Choice F) Multiple gestation is an unlikely cause of increased MSAFP in this patient because the uterine size is consistent with her reliable dates and an early pelvic examination. This patient is also relatively slender so the evaluation of fundal height is more accurate than in an obese patient.
Educational objective:
Elevated maternal serum α-fetoprotein is seen in fetal abnormalities such as open neural tube defects, gastroschisis, and omphalocele. It is also elevated in a multiple-gestation pregnancy. An ultrasound should be performed to evaluate the fetal anatomy.