Perinatal/Neonatal Case Presentation

Journal of Perinatology (2005) 25, 555–556. doi:10.1038/sj.jp.7211343; published online 9 June 2005

Myelomeningocele in an Infant with Intrauterine Exposure to Efavirenz

Akihiko Saitoh MD1, Andrew D Hull MD2, Patricia Franklin NP1 and Stephen A Spector MD1

  1. 1Division of Infectious Diseases (A.S., P.F., S.A.S.), Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA
  2. 2Department of Reproductive Medicine (A.D.H.), University of California, San Diego, La Jolla, CA, USA

Correspondence: Akihiko Saitoh, University of California, San Diego 9500 Gilman Dr. MC 0672, La Jolla, CA 92093-0672, USA

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Abstract

We report a case of myelomeningocele in an infant whose mother was exposed to efavirenz during the first 16 weeks of pregnancy. Although the true risk for myelomeningocele with the use of efavirenz early in pregnancy is still unknown, the findings in humans are consistent with those observed in primates and suggest that efavirenz is a potent teratogen. Thus, we suggest that efavirenz only be prescribed for women of childbearing potential when no other comparable antiretroviral options are available.

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INTRODUCTION

Efavirenz is a highly effective non-nucleoside reverse transcriptase inhibitor (NNRTI) that is widely recommended in combination with other antiretrovirals for initial antiretroviral therapy.1, 2 However, the use of efavirenz is not recommended for pregnant women because of the potential risk for neural tube defects in neonates.3 We report a case of myelomeningocele in an infant whose mother was exposed to efavirenz during pregnancy.

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CASE REPORT

A 36-week gestation newborn was born to a 27-year-old HIV-infected mother by Cesarean section. The mother was diagnosed with AIDS 16 months prior to delivery with a CD4+ T lymphocyte count of 175/mul (8%) and a plasma HIV-1 RNA of 203 copies/ml. Efavirenz, lamivudine and tenofovir were initiated.

At 9 months after starting antiretroviral therapy, the mother was found to be 16 weeks pregnant. Efavirenz was immediately discontinued and switched to nevirapine. Maternal serum-alpha-fetoprotein screening was negative for open neural tube defect, but an ultrasound at 20-weeks-gestation showed a lumbosacral mass consistent with myelomeningocele. No fetal hydrocephalus was observed on ultrasound examination. No risk factors for myelomeningocele other than efavirenz were identified. Her pregnancy course was uncomplicated except for gestational diabetes during late in pregnancy.

At birth, the male infant weighed 4150 g (>95th percentile), with a length of 54 cm (>95th percentile) and a head circumference of 31.5 cm (10th percentile). A 3 times 3 cm open, lumbosacral mass at L3 consistent with a myelomeningocele was observed. There was associated muscle weakness in the lower extremities and weak anal tone. Cranial ultrasound did not show the cisterna magna and fourth ventricle, consistent with an Arnold-Chiari malformation with myelomeningocele. The infant's ventricles were normal in size. Closure of the myelomeningocele was performed without complications. His ventricle size had enlarged from 7 to 12 mm bilaterally by cranial ultrasound, but became stabilized 7 days after surgical repair without the need for a ventriculo-peritoneal shunt. The infant was discharged from the hospital on the 11th day of life. PCR for HIV-1 DNA was negative at birth and 6 weeks of age. Chromosome studies were normal.

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DISCUSSION

Efavirenz use during pregnancy is not recommended because of the potential risk for neural tube defects in neonates.3 In animal studies, among 20 pregnant primates exposed to plasma efavirenz concentrations comparable to systemic human therapeutic levels during the early pregnancy, three cases developed significant central nervous system malformations including anencephaly, micropthalmia and cleft palate.4 The first human case was reported in an infant whose mother was exposed to efavirenz during the first 24 weeks of pregnancy.5, 6 The baby was born at 38 weeks gestation and was appropriate for gestational age. The infant had a lumbo-sacral mass compatible with a 13 cm diameter myelomeningocele.

To our knowledge, this is the second reported case of myelomeningocele in a live born infant whose mother was exposed to efavirenz during pregnancy. Reviewing the retrospective data from the Antiretroviral Pregnancy Registry,7 two additional fetuses with neural tube defects (myelomeningocele) have been described following elective termination of pregnancies for serious abnormalities diagnosed in utero. Of note, no cases of neural tube defects were documented among 71 reported cases to the Registry who were exposed to other antiretroviral combinations including nucleoside reverse transcriptase inhibitors (NRTIs) alone (n=39), NRTIs and protease inhibitors (PIs) (n=30) or PIs alone (n=2) during the first trimester.

Despite counseling with regard to the use of barrier protection in addition to birth control for prevention of pregnancy and HIV transmission, many women still become pregnant while receiving antiretrovirals. Unfortunately, the neural tube closes within the first 28 days of gestation,8 usually before women realize that they are pregnant. Thus, by the time pregnancy is diagnosed, the risk for efavirenz toxicity has already occurred.

Although the true risk for neural tube defects with the use of efavirenz early in pregnancy is still unknown, the findings in humans are consistent with those observed in primates and suggest that efavirenz is a potent teratogen. Recently, efavirenz was classified as Pregnancy Category D, indicating that there is evidence of human fetal risk. Thus, we suggest that efavirenz only be prescribed for women of childbearing potential when no other comparable antiretroviral options are available.

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References

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  2. Staszewski S, Morales-Ramirez J & Tashima KT et al. Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. Study 006 Team. N Engl J Med 1999; 341: 1865−1873. | Article | PubMed | ISI | ChemPort |
  3. Perinatal HIV Guidelines Working Group. Public Health Service Task Force. Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States. Available on at: http://www.aidsinfo.nih.gov/guidelines updated June 23, 2004; Accessed January 6, 2005.
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  6. De Santis M, Carducci B, De Santis L, Cavaliere AF & Straface G. Periconceptional exposure to efavirenz and neural tube defects. Arch Intern Med 2002; 162: 355. | Article | PubMed |
  7. Antiretroviral Pregnancy Registry Steering Committee. Antiretroviral Pregnancy Registry International Interim Report for January 1989 through 31 January 2004 Wilmington, NC: Registry Coordinating Center 2004; Available from URL: http://www.apregistry.com.
  8. Botto LD, Moore CA, Khoury MJ & Erickson JD. Neural-tube defects. N Engl J Med 1999; 341: 1509−1519. | Article | PubMed | ISI | ChemPort |
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