Review Question - QID 216544

This patient without previous prenatal care presents with elevated serum levels of alpha-fetoprotein and elevated amniotic fluid levels of AChE, most suggestive of a neural tube defect. Neural tube defects can be prevented with maternal supplementation of folic acid, which is necessary for neural tube closure.

Neural tube defects are congenital abnormalities that occur due to failure of neural tube closure between the third and fourth weeks of development. Folic acid (folate) is necessary for this process, and thus folic acid supplementation is necessary prior to conception. The recommended dose of folic acid supplementation in low-risk pregnancies is 0.4-0.8 mg daily. Drugs that inhibit folate metabolism or action, such as trimethoprim or methotrexate, can increase risk of neural tube defects and are thus contraindicated during pregnancy. Genetic mutations in folate metabolism enzymes such as methylenetetrahydrofolate reductase (MTHFR) can also predispose patients to neural tube defects. In utero surgical repair of these defects is an important novel treatment to reduce the morbidity from these disorders.

Copp et al. review the molecular and developmental mechanisms underpinning neural tube defects. They discuss how primary prevention through folate supplementation has dramatically reduced the prevalence of these disorders. They recommend using in-utero corrective measures to decrease the neurological deficits seen in these children.

Incorrect Answers:
Answer 1: Blood glucose level optimization can prevent the effects of maternal hyperglycemia, which include macrosomia, fetal hyperinsulinemia, and organomegaly. Severe hyperglycemia during early fetal development (e.g., in maternal diabetes) can increase the risk of neural tube defects, but this is not the most likely cause of a neural tube defect in this woman with no history of diabetes.

Answer 2: Cessation of alcohol use can prevent fetal alcohol syndrome, which is characterized by intellectual disability, microcephaly, facial abnormalities (e.g., smooth philtrum, small palpebral fissures), and heart defects. Alcohol is not associated with neural tube defects.

Answer 3: Cessation of amphetamine use could prevent many obstetric complications, including growth restriction, spontaneous abortion, preeclampsia, and preterm birth. However, this patient presents with elevated serum alpha-fetoprotein and amniotic fluid AChE, indicative of a neural tube defect. Amphetamine use is not associated with neural tube defects.

Answer 4: Combined antiretroviral therapy, particularly zidovudine, can prevent the transplacental transmission of HIV. Fetal HIV does not cause neural tube defects but instead leads to early onset and frequent childhood infections. Treatment is with antiretroviral therapy in the neonatal period.

Bullet Summary:
Elevated serum alpha-fetoprotein and amniotic fluid AChE are indicative of a neural tube defect, which can be prevented with maternal folic acid supplementation.