HTB

Birth defects linked to use of certain drugs during pregnancy

10 January 2002. Related: Paediatric care.

Sean Hosein, for Canadian AIDS Treatment Information Exchange

In the past decade the use of anti-HIV drugs by HIV positive pregnant women has greatly increased in North America and Western Europe. These drugs can significantly reduce the risk of giving birth to an HIV positive baby.

While there are concerns that exposure to anti-HIV drugs during pregnancy, particularly during the first three months (first trimester), can significantly increase the risk of birth defects, so far this has not been the case.

Pregnant women with HIV sometimes also take the following antibiotics to prevent AIDS-related infections such as PCP and toxoplasmosis:

  • Bactrim/Septra
  • dapsone
  • pyrimethamine

Some pregnant women with HIV who are at high risk for having seizures may also be prescribed the following anti-seizure drugs:

  • carbamazepine
  • phenobarbital
  • phenytoin
  • primidone

Taken in combination, anti-HIV drugs, antibiotics and anti-seizure drugs could interfere with the growth and development of the foetus, resulting in birth defects. To find out about the impact of the combination of these drugs on the foetus, researchers in London, conducted a study. They reviewed the medical records of 195 HIV positive women and their children between 1994 and 1999.

  • average age of the mothers: 29 years
  • average CD4+ count during the first trimester: 255 cells

Increase in treatment use

The researchers found that the use of anti-HIV drugs during the first trimester of pregnancy has increased over the years, as follows:

  • 1994: 0%
  • 1998: 20%
  • 1999: 28%

They also noted that 22% of infants had been exposed to other drugs during the first trimester.

Birth defects

Mothers who received anti-HIV drugs and other medications during the first trimester were seven times more likely to have children with birth defects than mothers who did not use either group of drugs. Mothers who used either anti-HIV drugs or other medications during the first trimester did not have infants with birth defects. The occurrence of birth defects was not more common in women who had fewer than 200 CD4+ cells.

Drugs linked to birth defects

In HIV negative pregnant women, the use of such antibiotics as Bactrim/Septra, pyrimethamine or dapsone increases the risk of birth defects at least three-fold. These drugs work by interfering with the ability of germs to use the B-vitamin folic acid (folate). Unfortunately, they also affect the ability of the foetus to use folic acid, leading to birth defects. Thus it should come as no surprise that pregnant women who use these antibiotics as well as anti-HIV therapy during the first trimester are more likely to have children with birth defects.

What to do?

The London-based research team suggests that until further safety data are available, the need for taking preventative doses (prophylaxis) of drugs that interfere with folic acid “in women of childbearing age be reviewed and the benefits of folic acid supplementation emphasized during [pre-pregnancy] counselling.”

In Canada, the routine use of Bactrim/Septra in pregnant women is discouraged. If pregnant women must use these drugs then a supplement of folic acid, between 5 and 10 mg/day, is suggested.

Antiseizure drugs

Studies in HIV negative pregnant women indicate that low doses of folic acid (400 micrograms/day) may be protective against birth defects caused by the antibiotics previously mentioned. However, this low dose of folic acid does not help prevent birth defects in HIV negative pregnant women who are using anti-seizure drugs. Clearly, more research needs to be done to find ways of preventing birth defects in pregnant women who need to use anti-seizure drugs.

Comment

This is an issue that clearly deserves further attention to find out whether other cohorts corroborate the findings in London. The increased odds ratio of about eight is significant, but because these are rare events the possibility of a mother having a baby with a birth defect remains low even on these drugs. Therefore careful risk-benefit analysis is required, since PCP in pregnancy may be more detrimental to more mothers and their babies.

In the meantime the advice to use Bactrim/Septra judiciously in women is sensible. The Canadian policy of avoiding Bactrim/Septra during pregnancy seems reasonable, but have they extended this to women of child-bearing age? Since it is exposure in the first trimester that is relevant, there is a risk that by the time the pregnancy is recognised it would be too late.

References:

  1. Hernández-Díaz S, Werler MM, Walker AM and Mitchell AA. Folic acid antagonists during pregnancy and the risk of birth defects. New England Journal of Medicine 2000;343:1608-1614.
  2. Hernández-Díaz S, Werler MM, Walker AM and Mitchell AA. Neural tube defects in relation to use of folic acid antagonists during pregnancy. American Journal of Epidemiology 2001;153(10):961-968.
  3. Jungmann EM, Mercey D, DeRuiter A, Edwards S, et al. Is first trimester exposure to the combination of antiretroviral therapy and folate antagonists a risk factor for congenital abnormalities? Sexually Transmitted Infections 2001;77:441-443.
  4. Anonymous. Bactrim. Compendium of Pharmaceutical Specialties 2000;170.

Source: Canadian AIDS Treatment Information Exchange (CATIE). For more information visit CATIE’s Information Network at
http://www.catie.ca

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