Case A: A male veteran returning from Afghanistan is concerned about an exposure to Tritium

From the desk of M. Roth- Teratogen Information Specialist/ Pregnancy Risk Network

Response that was prepared and discussed with caller.

Background Risk - All pregnancies carry a background risk of 3 to 5% for major or minor birth defects.

Paternal Exposures – To date there are no confirmed paternal exposures that increase risks for adverse pregnancy outcomes. There are ongoing studies that look into men with certain occupations and these often include exposure to metals. However, no conclusions can be drawn and there is often a bias in the case reports. Agents that cause birth defects do not reach the developing fetus from the father as they do from the mother.

Tritium - Although we did not locate published studies on tritium ingestion, it is likely that the effects noted for ionizing radiation would apply to tritium exposure. The effect of radiation on the male reproductive system affects the production of sperm and not the quality of the sperm produced. Infertility is the main complication of radiation exposure.

Citing a recommendation by the Health Physics Society for men who have received high doses of radiation to the testes, theoretical concerns encourage men to wait two spermatogenesis cycles or about four months before conceiving, even though theoretical concerns have not been demonstrated in studies. Studies of atomic bomb survivors indicate even in the high exposure group that there is not an increased incidence of chromosome abnormalities or genetic diseases in the next generation.

Bio-Chemicals, unknown - Without knowledge of the possible chemical or biologic agents you may have been exposed to or the extent of these exposures it is not possible to make an assessment. Though, it is likely that even with that information, the assessment would remain the same. We are only able to cite what's available in the medical literature.

In the event that there was a potentially harmful exposure, waiting to conceive is the precaution available to you.

Our recommendation would be to wait approximately ninety days but in the event of a higher radiation exposure about 120 days from the time of exposure is a way to minimize risks of conceiving with sperm formed during period of exposure. This period of time helps to ensure that sperm used at conception are unlikely to be affected by the exposure(s).

Case B: Consumer who is presently taking Keppra wants to start a family and was seeking pre-conception information .

From the desk of M. Roth- Teratogen Information Specialist/ Pregnancy Risk Network

Levetiracetam (Keppra): This information was relayed to patient.

Background Risk - All pregnancies carry a background risk of 3 to 5% for major or minor birth defects.

Levetiracetam – Animal studies have suggested a potential for an increased risk in minor skeletal abnormalities and growth retardation. However, findings from animal studies have not been borne out in human experience. Studies and reports of Keppra use in pregnancy are limited. In a report from the Epilepsy and Pregnancy Registry of the UK , of 22 women taking levetiracetam there were no major congenital malformations reported. However, the number involved in the registry report is too low to make an assessment. In this study, when antiepileptic drugs were part of a polytherapy regimen, risks were increased significantly. Information from the US Keppra Pregnancy Registry is also too incomplete to draw conclusions. Here again, polytherapy suggests greater increased risks than monotherapy with Keppra. Of those pregnancies exposed to monotherapy, no birth defects were reported. This should be re-assuring to you in the event it is deemed necessary you maintain keppra use in pregnancy.

In a Dutch study three of eleven babies exposed to Keppra had reduced birth weight, but in reviewing the literature, two of these pregnancies involved polytherapy and one involved exposure to cigarettes throughout pregnancy.

To summarize, that a consistent adverse response is not seen in the reports is assuring. But information is too limited to be able to assess risks from Keppra use in pregnancy. It is necessary to weigh the risks and benefits with your physician in managing potential for seizure.

If used in pregnancy, the lowest possible dose is recommended.

A pregnancy registry by the manufacturer is maintained. The registry can be reached at 888-537-7734. In the event of pregnancy while exposed to Keppra, we strongly encourage you to contact the registry.

Case C. Pregnant Poultry Farmer

From the desk of M. Roth- Teratogen Information Specialist/ Pregnancy Risk Network

I got a call from a pregnant women concerned about what she might be exposing her baby to at work. She was a chicken farmer at a relatively small farm. There aren't a lot of studies in the literature documenting exposures in pregnancy for chicken farmers, or even poultry farmers in general. In fact, there is no evident risk. To be very sure that anecdotal information may not be helpful to this woman, less traditional resources were used, including the National Institute for Occupational Safety and Health, Penn State Department of Poultry Science and the National Chicken Council. (Incidentally, the man at the Chicken Council seemed a little suspicious.). In the absence of data we concluded that minimizing maternal exposure ( through protective garments and techniques) was the prudent option to ensure the health of the baby and we provided those recommendations.

Case D. Immunosuppressant Drugs and Pregnancy:

From the desk of T. Snell – Genetic Counselor, Teratogen Information Specialist/ Pregnancy Risk Network

This case involved a call from a genetic counselor. This counselor had a client who had previously undergone two kidney transplants. She was currently taking two immunosuppressant drugs: Rapamycin and Tacrolimus. It is necessary for her to remain on these or related drugs for life. This client was not yet pregnant, but was considering pregnancy and wanted to learn more about the safety of these particular drugs in pregnancy. I reviewed the usual resources including TERIS, BRIGGS and REPROTOX. These are sources commonly referred to when researching a particular Teratogen. In general, I was able to find that the use of Tacrolimus and other immunosuppressive drugs in pregnancy have been associated with premature delivery, intrauterine growth retardation, neonatal hyperkalemia, pre-eclampsia and hypertension, and increased risk for spontaneous abortion (miscarriage). There was no pattern of birth defects identified. These resources all indicated that Rapamycin had not been well studied in pregnant women.

I decided to see if other Teratogen specialists had any additional input, so I posted my question on the Teratogen list-serve. I was able to get a response, which included information about a transplant registry and a detailed review article relating to Pregnancy in Female Pediatric Solid Organ Transplant Recipients. A second response on the list-serve included a summary sheet from another Teratogen counselor's research.

Next, I did a search of the medical literature and found another article relating to the Review of the Course and Outcome of 100 Pregnancies in 84 Women Treated with Tacrolimus. This article indicated nearly a 50% miscarriage rate and suggested that this drug be discontinued before pregnancy, if possible.

Unfortunately, I still was not finding out much regarding Rapamycin. I then called the National Transplantation Pregnancy Registry (NTPR). My contact at the NTPR confirmed that there was not enough data to extrapolate risk relating to the use of Rapamycin in pregnancy and an increased risk for congenital anomalies (only two pregnancies in database). She did tell me also that their data was indicating approximately a 50% risk for miscarriage for those using Tacrolimus in pregnancy, but that the risk for congenital anomalies (birth defects) did not seem to be increased (assuming the pregnancy did not end in miscarriage). Based on this, they were recommending that women discontinue this drug for a period of time before attempting pregnancy. They should discuss other options with their transplantation program. However, most important is their health and the drugs necessary to keep them healthy. They should also be at peak health before attempting pregnancy.

All of this information was relayed to the genetic counselor. I also faxed her a copy of the review article discussed above per her request.