PERINATAL/NEONATAL CASE PRESENTATION Encephalocele following a periconceptional exposure to efavirenz: a case report W Gudu 1 and D Bekele 2 The use of Efaverinz in reproductive age women needs caution as its use in the first trimster of pregnancy is reportedly associated with an increased risk of neural tube defect (NTD) in the newborn. This concern is based on evidence from animal studies and two human case reports. We report here yet another case of encephalocele born from a mother who was taking efaverenze during conception and the first 8 weeks of gestation, the critical time in the pathogenesis of NTDs. Journal of Perinatology (2013) 33, 987–988; doi:10.1038/jp.2013.121 Keywords: efaverinz; neural tube defect; encephalocele INTRODUCTION Efavirenz (EFV) is a first-line anteretroviral drug used in the managment of HIV infection in many developing countries. Its use in reproductive age women, particularly in the first trimester, has been a concern as it potentially is associated with the develop- ment of neural tube defects (NTDs) in the exposed fetuses. CASE A 35-year-old Para III known HIV-positive woman on HAART presented to the antiretroviral treatment clinic of Karamara Hospital for her scheduled visit. She complained of nausea and occasional vomiting of 2 weeks and amenorrhea of 2 months. A urine pregnancy test was positive. Gestational age calculated from last menstrual period was 8 weeks and 5 days. The woman was diagnosed to be HIV positive 2 years prior to this pregnancy and with the assessment of WHO clinical stage 3, and CD4 count of 216 mm À 3 was initiated on HAART at that time. The HIV treatment regimen included Zidovudine, Lamivudine and EFV. She was not in any form of contraceptives throughout the course of antiretroviral therapy. EFV was switched to Neverapine the day pregnancy was con- firmed and she was linked to an antenatal clinic. A comprehensive prenatal evaluation was done. She had no significant complaints except those mentioned above. All her previous pregnancies and deliveries were uneventful. On physical examination she had stable vital signs and the findings in all systems were unremarkable. Initial prenatal laboratory tests were within normal limits and CD 4 count was 321 mm À 3 . Ultrasound scanning was performed in the second trimester and revealed a 21-week gestation singleton viable intrauterine pregnancy with a heterogeneous occipital mass measuring 4.5 cm  4.0 cm with a defect in the occipital bone, which was consistent with encephalocele. The mother was counseled on the anomaly detected, the available postnatal management options, the prognosis and the possibility of termination of pregnancy. She decided to carry on with the pregnancy and continued follow-up. At 34 weeks of gestation, the woman presented with decreased fetal movement of 1 week duration, and upon examination fetal heart beat was absent and fetal death was confirmed with ultrasound examination. The encephalocele had increased to 6.5 cm  6.0 cm. The mother was informed and was counseled on the options of management and opted for immediate termination of pregnancy. After ripening of the cervix with misoprostol and induction of labor with oxytocin, she delivered a 2100 g female fresh stillborn with an occipital encephalocele measuring 7.0 cm  6.0 cm (Figure 1). There were no other associated gross congenital malformations. The mother refused autopsy. She had an uncomplicated postpartum course and was discharged with an advice on contraception and preconception care before any planned future pregnancy. DISCUSSION The association between the use of EFV during pregnancy and NTDs has not been established by human studies, as pregnant women are always excluded from any clinical trials during drug development. 1 But teratogenic effects of EFV during pregnancy involving the NTDs have been suggested in animal studies, birth registries and retrospective case reports. The first evidence came from a developmental toxicity study in primates, which reported anomalies in 3 out of 20 fetuses of cynomologus monkeys exposed to EFV from the 20th to the 150th days of gestation at therapeutic doses comparable to those used in humans. The anomalies observed were one case of anencephaly and unilateral anophthalmia, one case of micro- ophthalmia and one case of cleft palate. 2 Subsequently two human cases of NTDs (meningomyeloceles) were reported in neonates exposed accidentally to EFV in the first trimester, which were consistent with those reported in animal studies. 3,4 Following these case reports, EFV was reclassified by the United States Food and Drug Administration (FDA) from a category C (‘risk cannot be ruled out’) to a category D (‘evidence of human fetal risk’). 5 1 Department of Gynecology and Obstetrics, Karamara Referral Hospital, Jigjiga, Ethiopia and 2 Department of Gynecology and Obstetrics, Saint Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia. Correspondence: Dr D Bekele, Assistant Professor of Obstetrics and Gynecology, Saint Paul’s Hospital Millennium Medical College, PO Box 143079, Addis Ababa 143970, Ethiopia. E-mail: dilayehu@yahoo.com Received 3 March 2013; revised 20 August 2013; accepted 21 August 2013 Journal of Perinatology (2013) 33, 987–988 & 2013 Nature America, Inc. All rights reserved 0743-8346/13 www.nature.com/jp