A 35-year-old woman, gravida 2 para 1, comes to the office for prenatal evaluation. The patient says she had been using condoms for birth control and unintentionally became pregnant. Her last menstrual period was 2 months ago, and home pregnancy tests are positive. She has not been taking prenatal vitamins. The patient has a healthy, 5-year-old daughter who was born after an uneventful pregnancy. She has a history of rheumatoid arthritis, and her joint symptoms are controlled with methotrexate therapy. The patient has no other medical conditions and takes no other medications. She does not use tobacco, alcohol, or illicit drugs. Vital signs are within normal limits, and physical examination shows no abnormalities. Serum β-hCG is elevated, and transvaginal ultrasonography shows a normal gestational sac and embryo. This patient's unborn child is at the greatest risk for which of the following congenital defects?

Question

A 35-year-old woman, gravida 2 para 1, comes to the office for prenatal evaluation.  The patient says she had been using condoms for birth control and unintentionally became pregnant.  Her last menstrual period was 2 months ago, and home pregnancy tests are positive.  She has not been taking prenatal vitamins.  The patient has a healthy, 5-year-old daughter who was born after an uneventful pregnancy.  She has a history of rheumatoid arthritis, and her joint symptoms are controlled with methotrexate therapy.  The patient has no other medical conditions and takes no other medications.  She does not use tobacco, alcohol, or illicit drugs.  Vital signs are within normal limits, and physical examination shows no abnormalities.  Serum β-hCG is elevated, and transvaginal ultrasonography shows a normal gestational sac and embryo.  This patient's unborn child is at the greatest risk for which of the following congenital defects?

Quizplus · Accepted Answer

11ec160b_374b_0fb4_9249_5bda70b2beb6_MD0001_00 This patient with an unintended pregnancy has been taking methotrexate, a disease-modifying antirheumatic drug, to control symptoms of rheumatoid arthritis. Methotrexate is a folic acid analog that competitively inhibits dihydrofolate reductase, which produces nucleic acid precursors that are essential to DNA synthesis and repair. Rapidly dividing cells (eg, neural tube cells, stem cells, hepatic cells, epithelial cells) are particularly susceptible to folate antagonism. All patients taking methotrexate should also take a daily folic acid supplement to ameliorate the potential adverse effects (eg, oral ulcers, hepatotoxicity). Methotrexate and other folate antagonists have abortifacient and/or teratogenic effects when used during the first trimester. They are contraindicated in pregnant women except under specific circumstances (eg, cancer therapy with no better alternative, treatment of ectopic pregnancy). Adverse effects of methotrexate use to the fetus include cardiovascular, urinary tract, and neural tube defects (eg, anencephaly, spina bifida). (Choice A) Under the influence of Hox (homeobox) genes, the branchial arches develop into many head and neck tissues (eg, muscles, bones, and cartilage of the face, neck, and pharynx). Retinoids (eg, topical tretinoin) are vitamin A derivatives used in the treatment of acne that interfere with the Hox signaling pathways. If used during pregnancy, they can cause branchial arch abnormalities (eg, CNS, thymic, and craniofacial defects). (Choice C) Renal dysplasia can be a complication of second or third trimester fetal exposure to ACE inhibitors in hypertensive mothers. Because fetal renal function is essential to maintain amniotic fluid volume, impaired renal function can lead to pulmonary hypoplasia, limb contractions, growth restriction, or cord compression with poor fetal outcomes. (Choice D) Sacral agenesis (ie, caudal regression syndrome) is a rare malformation that occurs almost exclusively in infants of diabetic mothers. Defects can include incomplete development of the sacrum, lumbar vertebrae, and lower extremities. (Choice E) Skeletal lesions can occur in congenital syphilis infection due to an inflammatory response (eg, periostitis, osteochondritis) to Treponema pallidum spirochetes in highly vascular areas of bones (eg, Hutchinson teeth). Although methotrexate exposure can cause skeletal development abnormalities, discrete inflammatory lesions would not be expected. (Choice F) Thyroid hypoplasia is a complication of inadvertent fetal exposure to radioactive iodine (I131) in patients receiving treatment for hyperthyroidism or thyroid cancer who unintentionally become pregnant. Educational objective: Methotrexate and other folic acid antagonists adversely affect rapidly dividing cells (eg, epithelial cells, stem cells, neural tube cells) by limiting the production of precursors essential to DNA synthesis and repair. If used in the first trimester of pregnancy, these drugs can cause major congenital abnormalities (eg, cardiovascular abnormalities, neural tube defects). __________ References: Folic acid antagonists during pregnancy and the risk of birth defects. (http://www.ncbi.nlm.nih.gov/pubmed/11096168)

A 35-Year-Old Woman, Gravida 2 Para 1, Comes to the Office