US Pharm. 2008;33(9):34-42.

Preconception care seeks to ensure optimal health for all women of childbearing age before a first pregnancy or between pregnancies (also known as interconception care). Preconception care involves identifying and managing health issues that may pose a risk to mothers or infants and that require action before conception or very early in pregnancy for maximal impact.1,2 As approximately half of all pregnancies in the United States are unplanned, preconception care (including risk screening, health promotion, and effective interventions) should be viewed as part of routine health care rather than a single clinical visit.3,4

Goals and Recommendations
In 2006, the Centers for Disease Control and Prevention (CDC) Preconception Care Work Group and the Select Panel on Preconception Care (SPPC) developed four overarching goals to improve preconception health and health care in the U.S. (TABLE 1) and 10 recommendations to achieve those four goals (TABLE 2).4,5 The recommendations utilize both clinical care and public health strategies to encourage the best possible health for a woman throughout her lifespan.4



Proven Interventions
Due to the many publications focusing on preconception care in the past few years, several sets of recommendations have emerged. Although each set is slightly different, there is significant overlap between them. Utilizing clinical practice guidelines and evidence-based data, the CDC and the SPPC compiled a list of 14 recommendations for preconception care (TABLE 3).4-6 The American College of Obstetricians and Gynecologists and the American Academy of Pediatrics have further defined four main categories for these 14 interventions: 1) maternal assessment, 2) screening, 3) vaccinations, and 4) counseling.6



Maternal Assessment
Diabetes: About one in 100 women of childbearing age in the U.S. has diabetes before pregnancy, referred to as pregestational diabetes. If the mother's pregestational diabetes is poorly controlled in early pregnancy, her baby is three to four times more likely to have a congenital heart defect or neural tube defect than the baby of a woman without diabetes. Other risks to the fetus include stillbirth, miscarriage, premature birth, and newborn complications such as jaundice. Because of the risks associated with poorly controlled pregestational diabetes, women should consult with their health care providers for optimal disease state management before conception, maintaining good glycemic control before and during pregnancy. These women should also receive nutritional counseling specific to the management of diabetes during pregnancy.5,

Hypothyroidism: Women with hypothyroidism should make their health care providers aware of their intention to conceive. Untreated overt hypothyroidism increases the likelihood of spontaneous abortion, stillbirth, low birth weight, and certain pregnancy complications such as maternal hypertension. While levothyroxine therapy is safe during pregnancy, the mother's dose of levothyroxine must be adjusted during pregnancy for proper fetal neurologic development. As a women's thyroid function may change during pregnancy, more frequent monitoring of serum thyroid-stimulating hormone (TSH) levels may be warranted. The American Association of Clinical Endocrinologists recommends routinely screening women for thyroid dysfunction by obtaining TSH measurements before pregnancy or during the first trimester.5,8

Maternal PKU: With newborn screening, most patients with phenylketonuria (PKU) are identified at a very early age and can successfully manage the disease through dietary restrictions. Approximately 3,000 women of childbearing age in the U.S. were diagnosed with PKU in infancy. Most of these women have relaxed their dietary restrictions in adulthood and therefore have increased levels of phenylalanine. It is essential that women with PKU adhere to the dietary restrictions at least three months prior to conception and throughout pregnancy to avoid negative consequences to the fetus, such as mental retardation, microcephaly, and congenital heart defects.5,7

Oral Anticoagulant Use: Warfarin is known to be teratogenic, with the potential to cause a characteristic embryopathy if exposure occurs during the first trimester. Exposure after the first trimester may result in fetal central nervous system (CNS) abnormalities or bleeding, although these complications occur less frequently. Before conception, each woman receiving warfarin should seek advice from her health care provider regarding the appropriate anticoagulation therapy required during her pregnancy, including the possibility of switching to a nonteratogenic agent to avoid exposure to warfarin during early pregnancy.5,9

Antiepileptic Drug Use: Epilepsy affects approximately 1% of the U.S. population, representing an estimated 1 million women of childbearing potential. Certain antiepileptic drugs (AEDs), such as valproic acid, are known teratogens. The risk of teratogenic effects also increases with polytherapy and higher doses of these drugs. Women with epilepsy should consult with their health care provider as to whether the AED regimen should be altered before conception.5,10 The CDC and the SPPC indicated that "recommendations suggest that women who are on a regimen of these drugs and who are contemplating pregnancy should be prescribed a lower dosage of these drugs."5

Isotretinoin Use: Isotretinoin, approved by the FDA for the treatment of severe recalcitrant nodular acne, is marketed under the brand names Accutane, Amnesteem, Claravis, and Sotret. Isotretinoin is contraindicated during pregnancy, as it has been shown to cause birth defects such as ear, eye, and heart abnormalities; cleft lip or palate; microcephaly; hydrocephalus; and mental retardation. Use during pregnancy also increases the risk of infant death, premature delivery, and miscarriage. Women of childbearing age who use isotretinoin should ensure effective pregnancy prevention by utilizing two forms of contraception. Men and women receiving isotretinoin must register with a risk management program known as iPLEDGE.5,7

Screening
HIV/AIDS: As part of routine medical care, the CDC recommends that all individuals aged 13 to 64 years be screened for HIV. There are approximately 120,000 to 160,000 women with HIV in the U.S.; about 80% are of childbearing age. Since many women do not realize that they are infected, routine screening assists in the identification of HIV before conception. As a result, appropriate treatment can be initiated and women can be educated regarding the timing of conception.5,7

Sexually Transmitted Infections: It is estimated that each year 19 million individuals in the U.S. contract a sexually transmitted infection (STI). STIs have the potential to cause fetal death, stillbirth, miscarriage, or physical and developmental disabilities such as mental retardation and blindness. Early screening and treatment can help to prevent these adverse outcomes.5,7

Vaccinations
Rubella: If a pregnant woman becomes infected with the rubella virus in the first or second trimester, her baby may be born with congenital rubella syndrome (birth defects of the eye, ear, heart, and/or CNS). The infection may also cause miscarriage or stillbirth. Most women of childbearing age in the U.S. are seropositive for rubella (either through vaccination or previous infection); about 10% are susceptible to the disease. Although the incidence of rubella in the U.S. has sharply decreased over the last few decades, cases continue to be introduced through international travel. Therefore, it is important that all women be tested for immunity to rubella before conception. Women without immunity should consider vaccination and should delay attempting to conceive for 28 days after vaccination. The vaccine is not recommended for pregnant women; rather, the woman should be closely monitored and instructed to avoid individuals with the disease and should be vaccinated after delivery.5,7

Hepatitis B: Prior to the availability of the hepatitis B virus (HBV) vaccine, an estimated 30% to 40% of chronic infections were believed to have resulted from perinatal or early childhood transmission. Therefore, it is advised that women (and men) who are at risk for contracting HBV infection through mucosal or percutaneous exposure to blood or through sexual transmission receive vaccination to avoid the long-term consequences of HBV and prevent transmission to the fetus.5,11

Counseling
Folic Acid: Adequate folic acid intake at least four weeks before conception and during the first trimester of pregnancy has been shown to reduce the risk of neural tube defects by 50% to 70%. Therefore, it is recommended that all women of childbearing potential consume 400 mcg (0.4 mg) of folic acid daily. Food sources include orange juice, peanuts, dark green leafy vegetables, and fortified grains and pastas. Since many times it is difficult to obtain the recommended amount from diet alone, women of childbearing potential should be encouraged to take a multivitamin with 400 mcg of folic acid daily. Women with a higher risk of having a baby with a neural tube defect may be advised to take up to 4,000 mcg of folic acid daily in the preconception period and during pregnancy.5,7

Smoking: Smoking has been associated with adverse perinatal outcomes such as preterm birth and low birth weight. Smoking also has well-documented negative consequences on maternal health. In the U.S., at least 10% of women smoke while pregnant. Only 20% of women who smoke at the time of conception are able to successfully quit smoking during pregnancy; therefore, women who smoke should be encouraged to stop before conception. Education is a key component, as data presented by the March of Dimes suggest that understanding the harmful effects of smoking is an important determinant of whether a woman will quit smoking during pregnancy. In addition, utilization of a counseling approach known as "The 5 As" (Ask, Advise, Assess, Assist, and Arrange) has demonstrated improved smoking cessation rates among pregnant women.5,7

Alcohol and Other Recreational Drug Misuse: Use of alcohol or other recreational drugs during pregnancy can harm the developing fetus. For example, alcohol intake during pregnancy may result in fetal alcohol spectrum disorder (effects such as birth defects; learning, emotional, or behavioral problems; or mental retardation). The most severe outcome is fetal alcohol syndrome. An estimated 13% of pregnant women consume alcohol, and up to 40,000 babies are born each year negatively impacted by a form of alcohol-related sequelae.5,7

It is important that women planning pregnancy refrain from drinking any amount of alcohol. If a woman suspects she is pregnant, she should also discontinue use of alcohol. Likewise, other recreational drugs should not be used at any time during pregnancy due to the potential negative consequences to the fetus.5,7

Obesity: About 20% of women of childbearing age in the U.S. are obese (body mass index >=30). Maternal obesity can lead to adverse perinatal outcomes such as fetal or infant death, birth defects (especially neural tube defects), or labor and delivery compilations, as well as maternal complications such as hypertension or gestational diabetes. Before conception, women should be counseled regarding appropriate weight loss and nutritional intake to reduce these risks.5,7



Preconception Health Issues in Men
There are considerations for men as well in the preconceptional period. A man's family health history is significant when planning pregnancy, as it, along with maternal family health history, allows for a comprehensive review of genetic risks. Men should be screened for STIs and treated appropriately to mitigate transmission to their partners. Men should not smoke around their partners to avoid the harmful effects of second-hand smoke. Occupational exposures to chemicals or toxins may affect spermatogenesis and male fertility; men should also be careful to avoid exposing their partners to these hazards. Men should be educated about these risks and about ways to reduce their impact in order to optimize pregnancy outcomes.12

Interconception Care
Interconception care--between pregnancies--is a subset of preconception care. As indicated in goal 3 and recommendation 5 from the CDC and the SPPC, interconception care should be provided to women who have previously experienced an adverse fetal outcome. During this period, targeted interventions should be performed.4

Conclusion
Through preconception care, women of childbearing age are encouraged to maintain good health for themselves. Preconception care also helps women prepare for a healthy pregnancy.4 As pharmacists, we have a unique opportunity to impact the provision of preconception care through counseling and educating women and prescribers about preconception health.

REFERENCES
1. Biermann J, Lang Dunlop A, Brady C, et al. Promising practices in preconception care for women at risk for poor health and pregnancy outcomes. Matern Child Health J. 2006;10:S21-S28.
2. Preconception health and care, 2006. Centers for Disease Control and Prevention. www.cdc.gov/ncbddd/preconception/documents/At-a-glance-4-11-06.pdf. Accessed April 20, 2008.
3. Henshaw SK. Unintended pregnancy in the United States. Fam Plan Perspect. 1998;30:24-29.
4. Centers for Disease Control and Prevention. Recommendations to improve preconception health and health care--United States: a report of the CDC/ATSDR Preconception Care Work Group and the Select Panel on Preconception Care. MMWR. 2006;55:1-22.
5. Kent H, Johnson K, Curtis M, et al. Proceedings of the preconception health and health care clinical, public health, and consumer workgroup meetings. Centers for Disease Control and Prevention; June 27-28, 2006; Atlanta, GA. www.cdc.gov/ncbddd/preconception/documents/Workgroup%20Proceedings%20June06.pdf. Accessed April 20, 2008.
6. Preconception care questions and answers. Professionals. CDC. www.cdc.gov/ncbddd/preconception/QandA_providers.htm. Accessed April 20, 2008.
7. Preconception risk reduction. March of Dimes. www.marchofdimes.com/professionals/19695.asp. Accessed April 29, 2008.
8. AACE Thyroid Task Force. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. 2006 amended version. www.aace.com/pub/pdf/guidelines/hypo_hyper.pdf. Accessed April 29, 2008.
9. Hirsh J, Fuster V, Ansell J, Halperin JL. American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. Circulation. 2003;107;1692-1711.
10. Practice parameter management issues for women with epilepsy. Summary statement, 1998. American Academy of Neurology. www.aan.com/professionals/practice/pdfs/pdf_1995_thru_1998/1998.51.944.pdf. Accessed April 29, 2008.
11. Centers for Disease Control and Prevention. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 2005;54:1-23.
12. Preconception care questions and answers. General public. CDC. www.cdc.gov/ncbddd/preconception/QandA.htm#5. Accessed April 20, 2008.

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