With specific medical conditions, general points include how pregnancy will affect maternal health and how a high-risk condition might affect the fetus. Afterward, advice for improving outcome is provided. Detailed preconceptional information regarding a few conditions is found in the next sections as well as in the other topic-specific chapters of this text.
Because maternal and fetal pathology associated with hyperglycemia is well known, diabetes is the prototype of a condition for which preconceptional counseling is beneficial. Diabetes-associated risks to both mother and fetus are discussed in detail in Chapter 57 (Types Of Diabetes). Many of these complications can be avoided if glucose control is optimized before conception. The American College of Obstetricians and Gynecologists (2012b) has concluded that preconceptional counseling for women with pregestational diabetes is both beneficial and cost-effective and should be encouraged. The American Diabetes Association has promulgated consensus recommendations for preconceptional care for diabetic women (Kitzmiller, 2008). These guidelines advise that a thorough inventory of disease duration and related complications be obtained and clinical and laboratory examination for end-organ damage be completed. Perhaps most importantly, they encourage a preconceptional goal of the lowest hemoglobin A1c level possible without undue hypoglycemic risk to the mother. In addition to assessing diabetic control during the preceding 6 weeks, hemoglobin A1c measurement can also be used to compute risks for major anomalies (Fig. 8-1). Although these data are from women with severe overt diabetes, the incidence of fetal anomalies in women who have gestational diabetes with fasting hyperglycemia is increased fourfold compared with that in normal women (Sheffield, 2002).
Relationship between first-trimester glycosylated hemoglobin values and risk for major congenital malformations in 320 women with insulin-dependent diabetes. (Data from Kitzmiller, 1991.)
Such counseling has been shown to be effective. In one review, Leguizamón and associates (2007) identified 12 studies that included more than 3200 pregnancies in women with insulin-dependent diabetes. Of the 1618 women without preconceptional counseling, 8.3 percent had a fetus with a major congenital anomaly, and this compared with a rate of 2.7 percent in the 1599 women who did have counseling. Tripathi and coworkers (2010) compared outcomes in 588 women with pregestational diabetes in whom about half had preconceptional counseling. Those women who received counseling had improved glycemic control before pregnancy and in the first trimester, had higher folate intake rates preconceptionally, and experienced lower rates of adverse outcomes—defined as a perinatal death or major congenital anomaly. These cited benefits are accompanied by reduced health-care costs in diabetic women. From their review, Reece and Homko (2007) found that each $1 expended for a preconceptional care program saved between $1.86 and $5.19 in averted medical costs. Despite such benefits, the proportion of diabetic women receiving preconceptional care is suboptimal. In their study of approximately 300 diabetic women in a managed-care plan, Kim and colleagues (2005) found that only about half had preconceptional counseling. Counseling rates are undoubtedly much lower among uninsured and indigent women.
Women who have epilepsy have an undisputed two- to threefold risk of having infants with structural anomalies compared with unaffected women (Wide, 2004). Some early reports indicated that epilepsy conferred an increased a priori risk for congenital malformations that was independent of any effects of anticonvulsant treatment. Although more recent publications have largely failed to confirm this increased risk in untreated women, it is difficult to refute entirely because women who are controlled without medication generally have less severe disease (Cassina, 2013). Fried and associates (2004) conducted a metaanalysis of studies comparing epileptic women, both treated and untreated, with controls. In this study, increased malformation rates could only be demonstrated in the offspring of women who had been exposed to anticonvulsant therapy. Veiby and coworkers (2009) used the Medical Birth Registry of Norway to compare pregnancy outcomes in 2861 deliveries by epileptic women with 369,267 control deliveries. They identified an increased malformation risk only in women who were exposed to valproic acid (5.6 percent) and polytherapy (6.1 percent). Untreated women had anomaly rates that were similar to those of nonepileptic controls.
Ideally, seizure control is optimized preconceptionally. Vajda and colleagues (2008) reported data from the Australian Register of Antiepileptic Drugs in Pregnancy. The risk of seizures during pregnancy was decreased by 50 to 70 percent if there were no seizures in the year preceding pregnancy. There were no further advantages that accrued if the seizure-free period exceeded a year.
Efforts should attempt to achieve seizure control with monotherapy and with medications considered less teratogenic (Aguglia, 2009; Tomson, 2009). As discussed in detail in Chapter 60 (Epilepsy During Pregnancy) and shown in Table 8-2, some one-drug regimens are more teratogenic than others. Valproic acid, in particular, should be avoided if possible, as this medication has consistently been associated with a greater risk for major congenital malformations than other antiepileptic drugs (Jentink, 2010). According to Jeha and Morris (2005), the American Academy of Neurology recommends consideration of antiseizure medication discontinuation before pregnancy in suitable candidates. These are women who satisfy the following criteria: have been seizure-free for 2 to 5 years, display a single seizure type, have a normal neurological examination and normal intelligence, and show electroencephalogram results that have normalized with treatment.
TABLE 8-2First-Trimester Antiepileptic Monotherapy and the Associated Congenital Malformation Risk ||Download (.pdf) TABLE 8-2 First-Trimester Antiepileptic Monotherapy and the Associated Congenital Malformation Risk
Epileptic women should be advised to take supplemental folic acid. However, it is not entirely clear that folate supplementation reduces the fetal malformation risk in pregnant women taking anticonvulsant therapy. In one case-control study, Kjær and associates (2008) reported that the congenital abnormality risk was reduced by maternal folate supplementation in fetuses exposed to carbamazepine, phenobarbital, phenytoin, and primidone. Conversely, from the United Kingdom Epilepsy and Pregnancy Register, Morrow and coworkers (2009) compared fetal outcomes of women who received preconceptional folic acid with those who did not receive it until later in pregnancy or not at all. In this study, a paradoxical increase in the number of major congenital malformations was observed in the group who received preconceptional folate. These investigators concluded that folate metabolism may be only a part of the mechanism by which malformations are induced in women taking these medications.
Preconceptional counseling includes assessment of immunity against common pathogens. Also, depending on health status, travel plans, and time of year, other immunizations may be indicated as discussed in Chapter 9 (Table 9-9, Obstetrical and Medical Risk Factors Detected During Prenatal Care in the United States in 2001). Vaccines that contain toxoids—for example, tetanus, or that consist of killed bacteria or viruses—such as influenza, pneumococcus, hepatitis B, meningococcus, and rabies—have not been associated with adverse fetal outcomes and are not contraindicated preconceptionally or during pregnancy. Conversely, live-virus vaccines—including varicella-zoster, measles, mumps, rubella, polio, chickenpox, and yellow fever—are not recommended during pregnancy. Moreover, 1 month or longer should ideally pass between vaccination and conception attempts. That said, inadvertent administration of measles, mumps, rubella (MMR) or varicella vaccines during pregnancy should not generally be considered indications for pregnancy termination. Most reports indicate that the fetal risk is only theoretical. Immunization to smallpox, anthrax, and other bioterrorist diseases should be discussed if clinically appropriate (Chap. 64, Travel Precautions During Pregnancy). Based on their study of approximately 300 women who received smallpox vaccination near the time of conception, Ryan and colleagues (2008) found that rates of pregnancy loss, preterm birth, and birth defects were not higher than expected.