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Women who take valproate (Depacon) during pregnancy may increase the risk of childhood autism and its spectrum disorders in their children, a population-based study showed.
In utero exposure to the drug was associated with a five-fold elevated risk of autism and three-fold elevated risk for autism spectrum disorder, Jakob Christensen, PhD, of Denmark’s Aarhus University Hospital, and colleagues found.
The absolute risks were 2.5% and 4.4%, respectively, and remained significantly elevated after adjustment for parents’ epilepsy and psychiatric disease, the group reported in the April 24 issue of the Journal of the American Medical Association.
“For women of childbearing potential who use anti-epileptic medications, these findings must be balanced against the treatment benefits for women who require valproate for epilepsy control,” they concluded.  But “because autism spectrum disorders are serious conditions with lifelong implications for affected children and their families, even a moderate increase in risk may have major health importance,” they added.
The American Academy of Neurology recommends avoiding valproate in pregnancy whenever possible due to cognitive and physical birth defect problems for children exposed in utero.
The additional risk of autism and spectrum disorders needs to be included in counseling for women now too, Kimford Meador, MD, and David Loring, PhD, both of Emory University in Atlanta, recommended in an accompanying editorial.
“Because approximately half of the pregnancies in the U.S. are unplanned, delaying discussions of treatment risks until a pregnancy is considered will leave a substantial number of children at unnecessary risk,” they warned. “Women of childbearing potential should be informed of the potential risks of fetal valproate exposure before valproate is prescribed.”
The drug has an indication for manic and mixed episodes in bipolar disorder and for migraine prevention in addition to seizure control.
Primary source: Journal of the American Medical Association

Source reference:
Christensen J, et al “Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism” JAMA 2013; 309: 1696-1703.
Additional source: Journal of the American Medical Association
Source reference:
Meador KJ, Loring DW “Risks of in utero exposure to valproate” JAMA 2013; 309: 1730-1731.

May is National Skin Cancer Awareness Month and this time of year brings skin, our body’s largest organ, into focus as the  weather warms up and people spend more time outside in the sun. Skin cancer is sometimes referred to as a “lifestyle disease” because its occurrence can be dramatically reduced through behavior modification, education, and early detection. Learning more about the disease and how it can be easily prevented and/or treated if found early, will hopefully inspire our readers to make some positive lifestyle changes and reduce their risk of skin cancer.

What is skin cancer exactly? Skin cancer is defined as the uncontrolled growth of abnormal skin cells. It occurs when unrepaired DNA damage to skin cells, most often caused by ultraviolet radiation from sunshine or tanning beds, triggers mutations, or genetic defects, that lead the skin cells to multiply rapidly and form malignant tumors. Cancer of the skin is often divided into two categories: non-melanoma and melanoma. The American Cancer Society estimates there are well over 1 million unreported cases of non-melanoma (basal cell or squamous cell) cancers annually in the United States. Melanoma, the more-serious form of skin cancer, is the most common form of cancer for young adults 25-29 years old and the second most common form of cancer for young people 15-29 years old. Furthermore, women aged 39 and under have a higher probability of developing melanoma than any other cancer except breast cancer, and up until age 40, significantly more women than men develop melanoma.

Current statistics show that skin cancer is the most common type of cancer in the United States, as well as some other countries, and unfortunately the incident rate continues to rise.  Although the frequency of melanoma and non-melanoma skin cancer diagnoses indicate that this disease remains a significant health concern, it’s important to note that, research and public awareness campaigns are promoting prevention and early detection of skin cancer. Staying informed with the latest news on prevention and screening are important steps in reducing your risk of developing skin cancer. Here are a few tips from the Skin Cancer Foundation for reducing your skin cancer risk:

• Seek the shade, especially between 10 AM and 4 PM.
• Do not burn.
• Avoid tanning and UV tanning booths.
• Cover up with clothing, including a broad-brimmed hat and UV-blocking sunglasses.
• Use a broad spectrum (UVA/UVB) sunscreen with an SPF of 15 or higher every day. For extended outdoor activity, use a water-resistant, broad spectrum (UVA/UVB) sunscreen with an SPF of 30 or higher.
• Apply 1 ounce (2 tablespoons) of sunscreen to your entire body 30 minutes before going outside.
• Reapply every two hours or immediately after swimming or excessive sweating.
• Keep newborns out of the sun. Sunscreens should be used on babies over the age of six months.
• Examine your skin head-to-toe every month.
• See your physician every year for a professional skin exam.

In April, the Oncofertility Consortium hosted a Virtual Grand Rounds with Clarisa Gracia, MD, MSCE, entitled, “Case Studies in Oncofertility,” in which she discussed five theoretical young cancer patients and how oncofertility could be incorporated into their medical care. These patients included pediatric girls, adolescents, and young adult women with a variety of diseases including lymphoma, leukemia, ovarian, breast, and bone cancer. Dr. Gracia’s talk not only included the clinical recommendations for each of these patients, but also the scientific evidence that supported such suggestions. If you didn’t watch the live Rounds you can view a recording of the talk, with an option to obtain CMEs from the recording.  Following are some of the questions and answers posed to Dr. Gracia that she was able to answer after the Rounds ended.

Question: Are there differences in the impact of chemotherapeutics on primordial vs. growing follicles?

Answer: There is destruction of both growing follicles and primordial follicles. The article, “How do chemotherapeutic agents damage the ovary?” by Morgan, Anderson, Gourley, Wallace, and Spears provides a good review of some of the evidence. Briefly, chemotherapeutics may affect a variety of cell types within the ovary. A reduction in primordial follicles may be caused by direct damage by chemotherapeutics. However, chemotherapy also damages growing follicles, which increases recruitment of the primordial pool of follicles to begin growing. This increased recruitment also means that chemotherapy may indirectly decrease primordial follicle numbers.

Question: How do you build relationships with oncologist to ensure they are willing to start the fertility preservation discussion with patients?

Answer: It is important to reach out to oncologists and oncology nurses and let them know that you provide fertility preservation services for their patients. Provide flyers, letters, and make an effort to give presentations to oncology groups in your area. Please refer to the oncofertility website for more information.

Question: Are there functional analyses after uterine or whole body irradiation to determine if the uterus will be able to carry a healthy growing fetus to term?

Answer: The studies have focused only on uterine size and blood flow post radiation exposure, not functional in vitro studies.

Question: What do you/your patients consider a good number of oocytes? If a patient doesn’t get enough after one stimulation protocol, will you allow them to delay treatment in order to do another?

Answer: That is a difficult question and depends on a patient’s age and egg quality. We generally think getting more eggs is better than few eggs, but there is no guarantee of pregnancy even with many eggs. Ideally, a patient gets at least 10 oocytes in an egg retrieval. It is reasonable to pursue another stimulation cycle only if the oncologist feels comfortable delaying therapy.

Join the next Oncofertility Virtual Grand Rounds in June on the topics, “Sexuality After Cancer” with Dr. Kamaljeet Murthy and “Hormonal impact of cancer treatment and management of hormonal symptoms in female cancer survivors” with Dr. Catherine Stika.

Did you know that this week is National Infertility Awareness Week (NIAW)? NIAW is a movement that began in 1989 to raise awareness about the disease of infertility and encourage the public to understand their reproductive health. RESOLVE: The National Infertility Association founded this movement to:

• Ensure that people trying to conceive know the guidelines for seeing a specialist when they are trying to conceive.
• Enhance public understanding that infertility is a disease that needs and deserves attention.
• Educate legislators about the disease of infertility and how it impacts people in their state.

Infertility is a disease of the reproductive system that impairs the body’s ability to perform this basic function.  Pediatric and young adult cancer patients undergoing treatment are at high risk of having impaired fertility as a result of their disease or its treatment. Reproductive medicine provides a number of sophisticated options for assisted reproductive technologies (ART) such as egg, embryo, and sperm banking, ovarian tissue cryopreservation, and third party reproduction options (egg, sperm, and embryo donation, and gestational carrier/surrogacy) which help many people achieve parenthood.

Studies show that fertility preservation can bring hope to a patient undergoing cancer treatment, that there will be options and renewed life beyond their cancer diagnosis. Studies also indicate that individuals who do not receive fertility preservation information or treatment options following a cancer diagnosis are more likely to experience profound emotional consequences once they began to navigate family planning. While adoption and third party options make parenting possible, it does not always eradicate the feeling of loss one can suffer as a result of impaired fertility.

In support of NIAW, we ask you to help us and join the movement to increase and protect access to all family building options, and to help make fertility preservation counseling part of comprehensive cancer care in pediatric and young adult patients. For more information about your fertility options, please visit www.SaveMyFertility.org.