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The Reproductive Health Needs of Women on Teratogenic Medications
The fundamental initial steps in caring for women of reproductive age who are candidates for teratogenic medications include recognition of a medication as a potential teratogen and assessing a woman's pregnancy status and fertility intentions.
Identifying Teratogens
Providers must consider teratogenicity each time they prescribe medications to women of reproductive age, just as they should counsel women about fertility goals and offer preconception or contraceptive counseling. Information resources available to providers include drug labels, which may draw on information from pregnancy registries, retrospective cohort studies, case–control studies and pregnancy surveillance programs. Commonly used drug information resources such as Micromedex® (Thomson Reuters, NY, USA) can be useful, as is information provided by the Organization of Teratology Information Specialists and Teratogen Information Service. Proposed mechanisms for improving provider education and access to information are described in the last section of this review.
Assessing Fertility Intentions
Any woman of reproductive age who is taking or considering taking a teratogenic medication should be encouraged to articulate her fertility goals. Particularly for women with chronic medical conditions, regardless of her stated fertility intentions, the implications of a patient's medical condition for her pregnancy, including the risk of teratogenic medications, must be regularly discussed. Pregnancy intentions should be assessed regularly as they may change with time. When possible, pregnancy intentions should be assessed in an open-ended way, which may be more consistent with women's actual experience. For example, questions can be phrased as 'How would you feel about becoming pregnant?' or 'Would you mind becoming pregnant?'. Ambivalence about becoming pregnant is common and is a risk factor for use of less effective contraceptive methods. If providers sense such ambivalence they should be aware that unplanned pregnancy is more likely and teratogenic medications should be avoided as much as possible.
Preconception Counseling & Pregnancy Testing
For women desiring pregnancy, the teratogenicity of a given medication must be discussed in detail and documented, with acknowledgement of the uncertainty surrounding these issues. In addition, the risks and benefits of stopping a given medication must be discussed. Of note, women who have depression or anxiety may be more likely to have inflated concerns about the teratogenic risks associated with medications. Providers should be particularly aware of this given the risk of depression during pregnancy; physician reassurance can often mitigate patients' concerns.
For patients of reproductive age who are sexually active and have no history of surgical sterilization, a pregnancy test should be conducted prior to initation of a teratogenic medication. Some experts recommend monthly pregnancy testing for sexually active women who are not using prescription contraception. For women desiring pregnancy, this will facilitate early diagnosis and appropriate monitoring as needed. Along with medication counseling, other preconception counseling, such as prescription of prenatal vitamins, and counseling about smoking cessation and nutrition, should be undertaken at the same time.
Prescribing for Women Who Are Pregnant or Desiring Pregnancy
For acute, relatively mild medical conditions that do not pose a significant risk to a woman or her pregnancy (e.g., a viral upper respiratory infection), medications should be avoided during the first trimester if possible. When the benefit of a medication is felt to outweigh potential risks, clinicians should consider prescribing the lowest effective dose of the medication with the most data on safety in pregnancy. Of note, the relationship between dose and teratogenicity has been primarily shown in animal studies; human studies rarely show variation in teratogenic responses by dose presumably because of the narrower therapeutic dose range in clinical use. Older medications with good safety records are generally preferred to newer medications with less supporting data. For chronic medical conditions or conditions that pose a risk to the woman or fetus if untreated, safer alternatives to a medication should be sought if they exist. For example, pregnant women or women desiring pregnancy with severe hypertension, oral agents of choice include methyldopa, labetalol and metoprolol. Some women with severe depression will need to continue receiving pharmacologic therapy while pregnant. Selective serotonin reuptake inhibitors are considered to be safer than tricyclic antidepressants, but paroxetine should be avoided since it has the strongest association with fetal cardiac malformations. Many women with rheumatoid arthritis are transitioned from disease-modifying antirheumatic drugs, such as methotrexate, to higher doses of steroids during, or in anticipation of, pregnancy. While steroids carry risks for pregnant women and fetuses, they are probably safer than many disease-modifying antirheumatic drugs.
Contraceptive Care
With typical use of condoms or fertility awareness-based methods, 15–25% of women become pregnant within the first year of use. With no contraception, 85% of sexually active women become pregnant within a year. Thus, to prevent birth defects, it is essential that women taking potentially teratogenic medications who do not desire pregnancy use effective contraception. If a woman declines contraception, the provider must document that the patient has expressed understanding of and willingness to accept an increased risk of a birth defect or other adverse outcome for her infant. For those women who are willing to use contraception, highly effective reversible contraceptive methods such as intrauterine devices and subdermal implants are preferred. For example, less than 1% of women using a Mirena® (Bayer, Leverkusen, Germany) or Paragard® (Teva Pharmaceutical, Petah Tikva, Israel) IUD will have an unintended pregnancy within the first year of use, whereas 8% of women using oral contraceptive pills will be pregnant within a year of typical use. Unfortunately, these highly effective methods remain underused in the USA; only 5.5% of contracepting US women currently use an IUD. This appears to be at least partly because of inadequate provider knowledge about these methods, as well as relatively high out-of-pocket costs for patients.
Many women on teratogenic medications have chronic medical conditions that may affect contraceptive recommendations. The US Medical Eligibility Criteria for Contraceptive Use (US MEC), a free resource available on the internet, provides a large amount of useful information when determining the safety of various contraceptive options in the setting of chronic medical conditions. The US MEC assigns each contraceptive a category from 1–4 for a large number of medical conditions, where 1 represents a condition for which there is no restriction to a given contraceptive method, 2 represents a condition for which the advantages of using the particular method generally outweigh the theoretical or proven risks, 3 indicates a condition for which the theoretical or proven risks usually outweigh the advantages and 4 indicates a condition that represents an unacceptable risk if the contraceptive method is used (Table 3). Importantly, IUDs and progesterone-only subdermal implants can be safely used with most chronic medical conditions. Table 4 outlines the effectiveness of various commonly used contraceptive methods and the US MEC category for selected medical conditions.
Women taking potentially teratogenic medications and oral contraceptives have been found to display similar rates of nonadherence to oral contraceptive pills compared with the general population. In situations in which nonadherence seems likely, methods that depend minimally on patient adherence should be recommended or, in discussion with the patient, teratogenic medications should be avoided. Pregnancy tests should be performed routinely for women for whom adherence is challenging. Particularly for women using less effective methods of contraception, emergency contraception should be provided in advance, since this has the potential to increase timely use and reduce the risk of unintended pregnancy.
Management of Unintended Pregnancy
For the substantial number of women who may become pregnant while taking a potentially teratogenic medication, options for management of the pregnancy must be presented in a compassionate and open-ended way. For those women who wish to terminate the pregnancy, whether because of concerns about the medication exposure or for other reasons, comprehensive pregnancy options counseling should be provided and when need be, the patient should be referred promptly for desired services. For those women who are ambivalent about continuing their pregnancy, referral to a teratogen information specialist (see ) or an obstetrician or gynecologist is indicated to explore the implications of use of specific medications during pregnancy, and conduct early fetal surveillance as needed or wherever possible, in order to guide decision-making.
Management of Desired Pregnancy
If a woman becomes pregnant while taking a teratogenic medication and wants to continue the pregnancy, referral to an obstetrician–gynecologist and preferably a maternal–fetal medicine specialist is important early in pregnancy in order to provide thorough counseling about the risks. While clinicians must present the scientific uncertainty that exists with regard to the teratogenic effects of most medications, patients must be aware of serious adverse effects that may be seen in the fetus. In addition, special monitoring or treatment may be warranted during pregnancy depending on the drug exposure. For example, if a medication is known to cause fetal cardiac defects, fetal echocardiography may be indicated. Higher doses of folic acid are prescribed for women taking some agents known to cause CNS deficits. In addressing the woman's own medical condition and providing any additional monitoring for the fetus, close communication and coordination of care between the patient's obstetrician/gynecologist, specialist provider and primary care are essential.
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