Letters to the Editor
Lithium-Associated Anencephaly
Dear Editor:
The most common congenital malformation (CMF) associated with lithium is Ebstein’s anomaly. Other reported effects on the fetus are poor respiratory effort, cyanosis, rhythm disturbances, nephrogenic diabetes insipidus, thyroid dysfunction, hypoglycemia, hyperbilirubinemia, floppy baby syndrome, and large-for-gestational-age infants (1). Neural tube defects have not been reported in humans.
Case Report
A woman, aged 21 years, with no medical or psychiatric history developed acute-onset manic illness that was initially treated with haloperidol (dosage unknown) and lasted for 3 weeks. She presented to our services with neuroleptic malignant syndrome and was treated with bromocriptine up to 15 mg daily, lorazepam up to 6 mg daily, and supportive management. She improved without any neurologic sequel and was started on lithium.
She remained euthymic on lithium 900 mg daily for 2 years (her serum levels were monitored regularly). She married during this period and had genetic counselling (wherein she was advised to practise contraception and to stop taking lithium if she planned a pregnancy). However, owing to contraceptive failure, she conceived. The patient and her husband decided to continue the pregnancy, despite repeat counselling. She stopped taking lithium before 8 completed weeks of pregnancy.
An investigation profile (specifically, HIV, Venereal Disease Research Laboratory slide test, TORCH Screen, hepatitis B antigen, hemogram, renal and liver function tests, and blood sugar level) was normal. She started taking folic acid, calcium, and iron supplements at approximately 8 weeks. Ultrasonography at 12 weeks showed a live fetus, aged 9 weeks. Ultrasonography at 20 weeks showed a live fetus, aged 16 weeks, with evidence of a supraorbital cranial bony defect (suggesting anencephaly) along with a retroplacental hypoechoic lesion, 4 cm × 3 cm in size (suggesting a retroplacental hematoma). Repeat ultrasonography at 23 weeks showed additional evidence of widening of the lower part of the spine. Because anencephaly was present in the fetus, the patient was advised to terminate the pregnancy medically. The patient refused and dropped out of treatment.
Discussion
Animal, but not human, studies have found lithium to be associated with increased neural tube defects manifesting as exencephaly (2). Anencephaly has been seen in only one animal study (3), whereas evidence for association with exencephaly is more robust (2). However, sonographic and pathologic evidence points to a close link between exencephaly and anencephaly, with exencephaly being seen as a stage in the development of anencephaly (4).
Our patient became pregnant while taking lithium, and the fetus developed anencephaly. The possible association of anencephaly with lithium in this patient cannot be ruled out, owing to the temporal relation of lithium use in the first 6 to 8 weeks of pregnancy (the period of embryogenesis and most vulnerable period for developing CMF), the absence of a family history of CMF, and exencephaly–anencephaly being recognized as occuring in animal studies involving lithium.
References
1. Llewellyn A, Stowe ZN, Strader JR Jr. The use of lithium and management of women with bipolar disorder during pregnancy and lactation. J Clin Psychiatry 1998;59(Suppl 6):57–64.
2. Smithberg M, Dixit PK. Teratogenic effects of lithium in mice. Teratology 1982;26:239–45.
3. Blaas H-GK, Eriksson AG, Salvesen KC, Isaksen CV, Christensen B, Mrllerlrkken G, and others. Brains and faces in holoprosencephaly: pre- and postnatal description of 30 cases. Ultrasound Obstet Gynecol 2002;19:24–38.
4. Necas M, DuBose T, Taylor V. Exencephaly– anencephaly sequence and its sonographic features. Approved by Peer Review June 2000. Available: http://www.obgyn.net/us/cotm/0006/exencephaly-
anencephaly.htm. Accessed 2005 January 19.
Sandeep Grover, MD
Chandigarh, India
Nitin Gupta, MD,
Burton upon Trent, UK
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