All women and men of reproductive age will achieve optimal health and wellness, fostering a healthy life course for them and any children they may have.- The period of organogenesis begins 2-3 days after the missed menstrual period. Teratogenic medication exposures can occur before a woman realizes she is pregnant.
- Primary care guidelines and quality measures for treating chronic conditions may include medications that have teratogenic potential (e.g., ACE-inhibitors for hypertension and renal protection in diabetes) (Frayne et al., 2016)
- The use of medications in the earliest weeks of pregnancy continues to increase:
- In a study of medication use in pregnancy between 2006-2008, over 80% of women reported taking at least one prescription or over-the-counter medicine in the first trimester (Mitchell et al., 2011)
- In a study of medication use in pregnancy between 2010 and 2013, over 95% of women took at least 1 prescription or over-the-counter medication during the first trimester (Haas et al., 2018)
- Clinical drug trials have historically excluded pregnant women, so there are insufficient data on maternal and fetal benefits versus risks of many medications commonly used during pregnancy (Shields and Lyerly, 2013)
- Dietary supplements and herbal remedies are not regulated in the same way as prescription medications, so even less reliable safety information is available for these products.
- Data have now emerged about birth defects associated with certain medications commonly used before and during pregnancy. For example,
- Antidepressants in early pregnancy, particularly venlafaxine, are associated with specific cardiac and non-cardiac birth defects. However, some risks associated with antidepressant use are attributable to underlying maternal conditions rather than the medication itself (Anderson et al. 2020; Venlafaxine During Early Pregnancy and Birth Defects | CDC)
- The benefits and risks of pharmacotherapy must be weighed against the benefits and risks of an untreated underlying condition (e.g., depression or anxiety)
- Teratogenic medications should be avoided to prevent associated congenital anomalies, which can result if medication exposure occurs early in pregnancy during the period of organogenesis
- The preconception period is a critical time for optimizing medication regimens. Because the period of organogenesis begins 2-3 days after the missed menstrual period, efforts to reduce avoidable teratogenic exposures must occur before the woman becomes pregnant
- The preconception period is also a critical time for counseling on over-the-counter medications, herbal medications, and substances that are not necessarily “safe” in pregnancy and may even impede fertility (e.g., cannabis Mumford et al. 2021)
Preconception strategies for minimizing exposure to potentially teratogenic medications in early pregnancy start with:
- Identification of the specific exposures and patterns of use for:
- Prescription medications
- Over-the-counter medications
- Dietary supplements
- Folk and herbal remedies
- Various resources are available to assist clinicians in their assessments of drug safety (see Clinical Tools tab)
- Limit use of essential medications to the smallest number of drugs at the lowest effective doses to manage chronic and acute needs.
- If possible, women planning a pregnancy should not be prescribed medications known or suspected to be teratogenic (Dunlop, et al. 2008, van Gelder et al. 2014, Götestam Skorpen et al. 2016). Some commonly prescribed medications with teratogenic potential include:
- ACE-Inhibitors
- Angiotensin II receptor blockers (ARBs)
- Spironolactone
- Warfarin
- Valproic acid
- Isotretinoin
- Carbamazepine
- Lithium
- Phenytoin
- Methotrexate and other disease-modifying antirheumatic drugs (DMARDs)
- For a patient being treated for a chronic condition who wants to become pregnant in the near future:
- Switch to the safest effective treatment regimen prior to conception
- If a specialist is helping to manage a chronic condition, collaborate with that specialist to determine the safest regimen before the patient discontinues her current family planning method.
- Advise of potential risks of any current medications or supplements (which some patients may not consider “medicine”)
- Educate the woman that she should never discontinue treatments for chronic disease without clinical guidance, even if she discovers she has become pregnant.
- Limit use of essential medications to the smallest number of drugs at the lowest effective doses to manage chronic and acute needs.
- Teratogenic medications should be avoided to the extent possible for women who desire/ have the potential to conceive.
- Every woman who could become pregnant while using a prescription or over-the-counter medication, herbal therapy, or substance that could affect fertility or fetal development should be aware of the importance of avoiding unnecessary exposures.
- A pregnancy is at greatest risk for adverse consequences of medication use during the earliest weeks of pregnancy (often before the woman even knows she is pregnant); therefore, all women who use a prescription medication should work with their providers to find the safest treatments for chronic diseases before becoming pregnant.
- A woman should never discontinue treatment for a chronic disease without clinical guidance, even if she thinks she has become pregnant.
Below are strategies for optimizing medication use for women who desire to conceive (Prepregnancy Counseling | ACOG Committee Opinion 762, 2019)
- Identify specific exposures and patterns of use for:
- Prescription medications
- Over-the-counter medications
- Dietary supplements
- Folk and herbal remedies
- If using any medications that could pose a teratogenic risk to a pregnancy (see Background: Risk Reduction Strategies)
- Discuss the specific medication, the known risks, and alternative for therapy
- Switch medications to safest known treatments (this is likely to be a process and may take some time to find the best and safest treatment regimens)
- If the patient has a specialist managing their chronic condition, collaborate with that specialist (phone call, written communication, etc.) to determine an appropriate preconception treatment plan. Ask about:
- What medications are safest while trying to conceive
- What medications to continue vs discontinue if conception were to occur
- Recommend that patients also share their plans to become pregnant with any specialists managing a chronic condition.
- Encourage the patient to postpone pregnancy until the safest possible drug profile has been achieved
- Educate the woman that she should never discontinue treatments for chronic diseases without clinical guidance even if she discovers she has become pregnant.
Treating for Two: Medicine and Pregnancy | CDC provides guidelines and recommendations for selecting the safest treatment options for various health conditions during pregnancy.
The LactMed® database contains information on the safety of drugs when breastfeeding, possible adverse effects in the nursing infant, and suggested therapeutic alternatives to those drugs when appropriate. All data are fully referenced and reviewed by a peer review panel.
Organization of Teratology Information Specialists (OTIS) Healthcare Professionals – MotherToBaby Resources feature easy-to-read fact sheets and free consultations with experts by phone/ text/ chat on how various exposures impact pregnancy and lactation.
Reprotox Information System for Exposures during Pregnancy https://www.reprotox.org/ (Paid Service) provides information for clinicians, scientists, and government agencies on the effects of medications, chemicals, and infections on pregnancy and reproduction.
The Infant Risk Center at Texas Tech University Health Sciences Center offers up-to-date information, resources, and an Infant Risk Call Center for expert advice on the safety of medications during lactation. See description of Infant Risk App for Health Care Professionals (paid service).
MotherToBaby, a service of the non-profit Organization of Teratology Information Specialists (OTIS), offers no-cost information and expert advice (by phone/ text/ e-mail/ chat) about medications and other exposures during pregnancy and while breastfeeding. See fact sheets on common medications in English and Spanish: https://mothertobaby.org
Treating for Two: Medicine and Pregnancy is a CDC program that offers patients tips and talking points for discussing medication use with healthcare providers when thinking about getting pregnant. Treating for Two: Medicine and Pregnancy | CDC
MommyMeds for Moms is a health & safety app from Texas Tech University Health Sciences Center that allows users to search or scan medication barcodes for easy-to-understand drug safety information during pregnancy and while breastfeeding http://mommymeds.com/
ACOG Committee Opinion No. 762. 2019. Prepregnancy Counseling. Obstet Gynecol;133(1):e78-e89. doi:10.1097/AOG.0000000000003013
Anderson KN, Lind JN, Simeone RM, et al. (2020). Maternal Use of Specific Antidepressant Medications During Early Pregnancy and the Risk of Selected Birth Defects. JAMA Psychiatry. 77(12):1246-1255. doi:10.1001/jamapsychiatry.2020.2453
Dunlop AL, Gardiner PM, Shellhaas CS, Menard MK, McDiarmid MA. (2008). The clinical content of preconception care: the use of medications and supplements among women of reproductive age. Am J Obstet Gynecol.199(6 Suppl 2):S367-372. doi:10.1016/j.ajog.2008.07.065
Frayne DJ, Verbiest S, Chelmow D, et al. Health Care System Measures to Advance Preconception Wellness: Consensus Recommendations of the Clinical Workgroup of the National Preconception Health and Health Care Initiative. Obstet Gynecol. 2016;127(5):863-872. doi:10.1097/AOG.0000000000001379
Haas DM, Marsh DJ, Dang DT, et al. Prescription and Other Medication Use in Pregnancy. Obstet Gynecol. 2018;131(5):789-798. doi:10.1097/AOG.0000000000002579
Mitchell AA, Gilboa SM, Werler MM, et al. (2011). Medication use during pregnancy, with particular focus on prescription drugs: 1976-2008. Am J Obstet Gynecol. 205(1):51.e1-8. doi:10.1016/j.ajog.2011.02.029
Mumford SL, Flannagan KS, Radoc JG, et al (2021). Cannabis use while trying to conceive: a prospective cohort study evaluating associations with fecundability, live birth and pregnancy loss. Hum Reprod. 36(5):1405-1415. doi:10.1093/humrep/deaa355
Shields KE, Lyerly AD (2013). Exclusion of pregnant women from industry-sponsored clinical trials. Obstet Gynecol. 122(5):1077-1081. doi:10.1097/AOG.0b013e3182a9ca67
Götestam Skorpen C, Hoeltzenbein M, Tincani A, et al (2016). The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis. 75(5):795-810. doi:10.1136/annrheumdis-2015-208840
Thorpe PG, Gilboa SM, Hernandez-Diaz S, et al. (2013). Medications in the first trimester of pregnancy: most common exposures and critical gaps in understanding fetal risk. Pharmacoepidemiol Drug Saf. 22(9):1013-1018. doi:10.1002/pds.3495
van Gelder MMHJ, de Jong-van den Berg LTW, Roeleveld N (2014). Drugs associated with teratogenic mechanisms. Part II: a literature review of the evidence on human risks. Hum Reprod. 29(1):168-183. doi:10.1093/humrep/det370
Background
- Approximately 10% to 15% of congenital anomalies in the U.S. are attributed to prescription medication use by the pregnant woman (Dunlop et al., 2008).
- Over the last three decades, the use of prescription medications in the earliest weeks of pregnancy has increased by more than 60%. (Mitchell et al., 2011).
- In 2008, 50% of women reported taking at least one prescription medication in the first trimester and 7.5% reported taking 4 or more (Mitchell et al., 2011).
- Another report covering the years 2006-2008 found over 80% of women reported taking at least one prescription or over-the-counter medicine in the first trimester (Thorpe, et al, 2013).
- National surveys estimate that 18-52% of the U.S. population, including a substantial proportion of women of childbearing age, use dietary supplements including vitamins, herbs, folk remedies, weight loss aids and sport enhancement substances (Gardiner et al., 2008).
- Clinical trials for approval of a new drug by the Food and Drug Administration (FDA) generally exclude pregnant women; trials generally include monitoring of reproductive performance in animals but the findings may not reflect the impact on human embryos and fetuses.
- There is insufficient data available to fully understand the fetal risk for medications commonly used during pregnancy (Thorpe et al., 2013).
- Prescription medications are assigned an FDA pregnancy category, but the categories offer limited and imprecise guidance placing clinicians at a disadvantage in their efforts to provide clear and accurate information to women who are, or may become, pregnant.
- Dietary supplements and herbal remedies are not regulated in the same way as prescription medications so even less reliable safety information is available for these products.
- Various resources are available to assist clinicians in their assessments of drug safety: see Clinical Tools. Of particular usefulness is the resource provided by the Organization of Teratology Information Specialists (OTIS) which provides information for women in both English and Spanish. This content can be reached at https://mothertobaby.org/fact-sheets-parent/
- Congenital anomalies caused by teratogenic exposures, such as certain medications, are considered preventable because they are linked to modifiable exposures during the period of organogenesis.
- Because the period of organogenesis begins 3 days after the first missed menstrual period, efforts to reduce avoidable exposures must be initiated before the woman becomes pregnant.
Preconception strategies for minimizing exposure to potentially teratogenic medications in early pregnancy start with
-
- Identification of the specific exposures and patterns of use for:
- Prescription medications
- Over-the-counter medications
- Dietary supplements
- Folk and herbal remedies
- Assessing the likelihood a woman is or will become pregnant while taking any of these drugs, supplements and remedies.
- Identification of the specific exposures and patterns of use for:
- A challenge for health care providers is to choose the most appropriate medication for treating a woman’s acute or chronic diseases given her desires and likelihood of conception.
- Before prescribing or refilling any medication, determine a woman’s likelihood of pregnancy while exposed to a medication:
- For a woman who wants to become pregnant in the near future and is not using contraception:
- If she is being treated for a chronic disease, switch medications to the safest known treatments prior to conception (this is likely to be a process, and it may take some time to find the best and safest treatment regimens);
- Advise of potential risks of any medications she currently takes;
- Counsel to avoid non-essential medications;
- Encourage to use a barrier method of contraception until the safest possible drug profile has been achieved;
- Educate about Plan B in case unprotected intercourse occurs;
- Educate the woman that she should NEVER discontinue treatments for chronic disease without clinical guidance even if she discovers she has become pregnant.
- For a woman who does not want to become pregnant but is having heterosexual intercourse with no, inconsistent, or user-dependent methods of contraception:
- Switch medications to safest known treatments (this is likely to be a process and may take some time to find the best and safest treatment regimens), because the woman is at risk for becoming pregnant;
- Advise her of specific and potential risks of any medications she currently takes;
- Encourage her to start and consistently use a hormonal method of contraception until she desires to become pregnant;
- In the meantime, she should avoid intercourse or use a barrier method of contraception while on potentially risky medication;
- Educate about Plan B in case unprotected intercourse occurs;
- Educate the woman that she should NEVER discontinue treatments for chronic disease without clinical guidance even if she discovers she has become pregnant.
- For a woman who wants to become pregnant in the near future and is not using contraception:
- If possible, women at risk of pregnancy should not be prescribed medications known or suspected to be harmful to the embryo. Some common medications contraindicated in pregnancy are (Dunlop, et al., 2008):
- Angiotensin-converting enzyme (ACE) inhibitors and angiotension II receptor blockers
- Statins
- Certain anticonvulsants including
- Carbamazepine
- Phenytoin
- Valproic acid
- Warfarin derivatives
- Folic acid antagonists
- Certain antibiotics including
- Streptomycin
- Kanamycin
- Tetracycline
- Isotretinoin (Accutane ™ )
- Thalidomide
- Lithium
- If a woman at risk of pregnancy is already on one of these medications consider changing the therapeutic regimen to a less risky choice, if one is available.
- Limit use of essential medications to the smallest number of drugs at the lowest effective doses to manage chronic and acute needs.
- In general, it is unwise to prescribe newer drugs to women of reproductive potential because the full effects of the drug on human reproduction may not yet have been revealed.
- Every woman who could become pregnant while using a prescription or over-the-counter medication or herbal therapy should be aware of the importance of avoiding unnecessary exposures in the earliest weeks of pregnancy.
- Women should be reassured that taking one multivitamin daily is without danger and offers protections against some birth defects; however, taking multiple vitamins may create nutritional imbalances which have the potential to cause problems for her and for future pregnancies.
- Women should be advised that herbal products and supplements are not regulated in the same way as prescription drugs making it impossible to assure the quality of the products and to assess their impact before or during pregnancy.
- Some over-the-counter medications also carry risks in and around pregnancy; the safest choice is to avoid these remedies if a woman could become pregnant.
- Every mother and fetus is different; therefore, it is impossible to say any drug will endanger all fetuses or will never endanger any fetus. The safest choice is to avoid those exposures that can be avoided safely if pregnancy is desired or a possibility.
- A pregnancy is at greatest risk for adverse consequences of medication use during the earliest weeks of pregnancy (often before the woman even knows she is pregnant); therefore, all women who use a prescription medication should work with their providers to find the safest treatments for chronic diseases before becoming pregnant.
- A woman should NEVER discontinue treatment for a chronic disease without clinical guidance even if she thinks she has become pregnant.
Clinical Guidance
- Identify specific exposures and patterns of use for:
- Prescription medications
- Over-the-counter medications
- Dietary supplements
- Folk and herbal remedies
- If using any medications that could pose a teratogenic risk to a pregnancy (see Background: Risk Reduction Strategies)
- Discuss the specific medication , the known risks and alternative for therapy;
- Switch medications to safest known treatments (this is likely to be a process and it may take some time to find the best and safest treatment regimens);
- If condition being managed by another provider, refer woman back to that provider with specific efforts to inform the provider about your concerns (phone call, written communication, etc.);
- Encourage to use a barrier method of contraception until the safest possible drug profile has been achieved;
- Educate about Plan B in case unprotected intercourse occurs.
- Other risk reduction strategies include:
- Avoidance of non-essential medications (including over-the-counter, herbal and dietary supplements).
- Educate the woman that she should NEVER discontinue treatments for chronic diseases without clinical guidance even if she discovers she has become pregnant.
- Emphasize that one multivitamin daily is highly recommended for her own health and the health of any future pregnancies but that more supplements are unnecessary and may pose some risks.
Clinical Tools
Treating for Two is CDC’s strategy to improve what we know about the safety of medication use in pregnancy and reduce harmful medication exposures. CDC is working with other federal agencies and non-federal partners to improve the quality and availability of information on the effects of medication use during pregnancy. This initiative will prevent birth defects and make mothers healthier by identifying the best treatments for managing health conditions during pregnancy and the childbearing years.
DART provides more than 200,000 journals references covering teratology and other aspects of developmental and reproductive toxicology. DART is funded by the U.S. Environmental Protection Agency, the National Institute of Environmental Health Sciences, the National Center for Toxicological Research of the Food and Drug Administration, and the NLM. DART has references from the early 1900s to the present. New references are added weekly.
The LactMed database contains information on drugs and other chemicals to which breastfeeding mothers may be exposed. It includes information on the levels of such substances in breast milk and infant blood, and the possible adverse effects in the nursing infant. Suggested therapeutic alternatives to those drugs are provided, where appropriate. All data are derived from the scientific literature and fully referenced. A peer review panel reviews the data to assure scientific validity and currency. LactMed is updated monthly.
OTIS: Fact sheets on common medications (in English and Spanish!)
https://mothertobaby.org/fact-sheets-parent/
Reprotox Information System for Exposures during Pregnancy (Paid Service) https://www.reprotox.org/
The InfantRisk Center is dedicated to providing up-to-date evidence-based information on the use of medications during pregnancy and breastfeeding.
Infant Risk Health Care Mobile App for Health Care Professionals: Medication Safety during Pregnancy (Paid Service) http://www.infantrisk.com/apps
Patient Resources
MotherToBaby, a service of the non-profit Organization of Teratology Information Specialists (OTIS), is dedicated to providing evidence-based information to mothers, health care professionals, and the general public about medications and other exposures during pregnancy and while breastfeeding. Fact sheets on common medications (in English and Spanish!) https://mothertobaby.org/fact-sheets-parent/
Treating for Two is CDC’s strategy to improve what we know about the safety of medication use in pregnancy and reduce harmful medication exposures. CDC is working with other federal agencies and non-federal partners to improve the quality and availability of information on the effects of medication use during pregnancy. This initiative will prevent birth defects and make mothers healthier by identifying the best treatments for managing health conditions during pregnancy and the childbearing years.
The LactMed database contains information on drugs and other chemicals to which breastfeeding mothers may be exposed. It includes information on the levels of such substances in breast milk and infant blood, and the possible adverse effects in the nursing infant. Suggested therapeutic alternatives to those drugs are provided, where appropriate. All data are derived from the scientific literature and fully referenced. A peer review panel reviews the data to assure scientific validity and currency. LactMed is updated monthly and is available as an iPhone and Android app.
The InfantRisk Center from Texas Tech University Health Sciences Center is dedicated to providing up-to-date evidence-based information on the use of medications during pregnancy and breastfeeding.
Mommy Meds from Texas Tech University Health Sciences Center http://mommymeds.com/
References
American College of Obstetricians and Gynecologists (2007). Guidelines for Women’s Health Care: A Resource Manual (3rd ed). Washington, DC: ACOG.
American Academy of Pediatrics and American College of Obstetricians and Gynecologists (2013). Guidelines for Perinatal Care (7th ed.), AAP/ACOG: Evansville, Ill.
Cragan J. et al., (2006) Ensuring the safe and effective use of medications during pregnancy: planning and prevention through preconception care. Maternal Child Health Journal. 10(Suppl 1): 129-135.
Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1592140/ .
Dunlop, A.L., et.al. (2008). The clinical content of preconception care: the use of medications and supplements among women of reproductive age. American Journal of Obstetrics & Gynecology, 199 (6B): 367-372.
Thorpe PG., et. al. (2013). Medications in the first trimester of pregnancy: most common exposures and critical gaps in understanding fetal risk. Pharmacoepidemiology and Drug Safety, 22, 1013-1018.
United States Medical Eligibility Criteria (USMEC) for Contraceptive Use. Centers for Disease Control and Prevention.
Available at: http://www.cdc.gov/reproductivehealth/unintendedpregnancy/usmec.htm.
