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Chapter 10 Preconception evaluation
Scope of the problem
Preconception counseling affords the opportunity to identify, educate about, and modify risk factors for poor pregnancy outcome for both the woman and the child. In the United States, only about 50% of pregnancies are planned;[1] therefore, preconception counseling should be considered even if that is not the expressed purpose of the health-care encounter. Preconception counseling is not just for those with identified personal or family medical conditions, but also for “healthy women.” The thought “every woman, every time” for preconception counseling has been articulated and is a useful concept to keep in mind.[2] Pregnancy planning should also be incorporated into prenatal and postpartum health care, as well as visits for acute and chronic health conditions.
The concept of a reproductive life plan has been offered to help women make life and contraceptive decisions to optimize reproductive outcomes.[3] A woman should be encouraged to consider the timing, spacing, and number of children she plans, as well as barriers to this plan, such as age-related fertility changes. A woman should be encouraged to consider her readiness for pregnancy and her contraceptive options, if appropriate.
Planning for pregnancy may be a time of particular motivation for lifestyle and health choice changes. Some women may be motivated to make changes that were previously postponed or overlooked. Planning for pregnancy may also be a time to reassess family medical history issues that were previously considered intrusive or superfluous.
Including the partner in the preconception process can be helpful. Information about the partner’s family history may allow targeted genetic screening. Counseling the partner about pregnancy planning and lifestyle interventions such as smoking cessation and decreasing exposure to toxic substances may improve pregnancy outcomes. Vaccinating the partner and other newborn caregivers against influenza and pertussis reduces the rate of transmission of these diseases to the newborn.[4]
History
A preconception counseling visit may involve both the woman and her partner and may be facilitated by the use of questionnaires followed by questions to elicit a thorough history.
Menstrual history
An irregular or long menstrual cycle may indicate hypothyroidism, hyperprolactinemia, or polycystic ovarian syndrome. In the case of regular menstrual cycles, many couples appreciate a review of the menstrual cycle and ovulation to help plan timing of intercourse for conception. In general, ovulation proceeds the next menstrual cycle by 14 days. The most fertile time is thought to be the day of ovulation and the five prior days; however, this timing can be quite variable.[5] Advising a woman to maintain a menstrual diary can be very helpful in providing targeting counseling about maximizing chances of conception.
Past medical history
Assessment of preexisting medical conditions affords the opportunity to counsel patients about the implications of these disorders and to optimize these conditions prior to pregnancy thereby mitigating potential risks. Indeed, some conditions are especially associated with adverse outcomes of unintended or unplanned pregnancies (Table 10-1).
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Specific disorders
Diabetes mellitus
Women with diabetes should be counseled about optimum preconception and periconception blood glucose control. For instance, a hemoglobin A1c in the normal range is associated with a rate of congenital anomalies comparable to the nondiabetic population. However, a hemoglobin A1c of 10% is associated with a rate of congenital anomalies of about 20%, most commonly neural tube defects and congenital heart defects. Similarly, miscarriage is more common for women with poorly controlled glucose levels in early pregnancy. Controlling glucose levels before conception and in the early pregnancy period can reduce the number of birth defects and decrease the rate of spontaneous abortion.[6, 7] The preconception period is an optimal time for encouraging weight loss and lifestyle modifications for these women. For many women, converting to insulin instead of oral hypoglycemic agents is recommended prior to pregnancy. Education about the additional challenges of changing glucose metabolism due to the antagonistic effects of pregnancy hormones such as human placental lactogen (HPL) may help prepare the diabetic woman for the additional vigilance necessary in pregnancy. Diabetic women should be screened for coexistent renal and/or cardiac involvement. Women with pre-pregnancy diabetic nephropathy have a higher rate of preeclampsia.[8] Women with pre-pregnancy coronary artery disease have a higher rate of morbidity and mortality from pregnancy.[9]
Hypertension
Women with mild chronic hypertension are at increased maternal and fetal risks including perinatal mortality, placental abruption, and impaired fetal growth.[10] Women with hypertension for five years or more, or those who also have diabetes should have renal and cardiovascular function assessed.[11] Women with organ dysfunction or prior cerebrovascular accident, ventricular failure or myocardial infarction are at significantly increased risk for worsening during pregnancy or recurrence. Serum creatinine more than 1.4 mg/dL increases the risk of fetal loss and acceleration of renal disease.[12]
Consideration should also be given to underlying disease processes related to hypertension, for example, control of systemic lupus erythematosus. Women on angiotensin converting enzyme (ACE) or angiotensin receptor blocker (ARB) medications should be counseled on the risks of those medications in pregnancy and alternative medications should be prescribed. Optimization of factors that contribute to hypertension, including body mass index (BMI), glucose control if diabetic, nutrition, and activity, should be encouraged.
HIV/AIDS
If human immunodeficiency virus (HIV) infection is detected prior to conception, antiretroviral therapy and reduction of HIV viral load can be achieved prior to conception and the likelihood of transmission to the fetus/neonate can be thus reduced. Couples should be counseled about the risks of vertical transmission and the decreased rates of transmission with low or undetectable viral loads during pregnancy. For couples discordant for HIV infection, methods of conception to reduce transmission from one partner to the other should be discussed. The antiretroviral medications being used should be reviewed and altered if efavirenz is part of the regimen, as this drug may slightly increase the incidence of neural tube defects.[13] Screening and treatment of concurrent infections is recommended.
Epilepsy
Women with seizure disorders on medication prior to conception should be maintained at the lowest effective dose of the fewest medications prior to pregnancy,[14] especially if the last seizure was two or more years ago.[15] A number of anticonvulsant medications have teratogenic potential; for instance, the incidence of neural tube defects in the offspring of women taking valproic acid is 1%.[16] A woman should be made aware of this potential and the decision whether to continue or change medications is best be made prior to conception in consultation with the provider caring for her seizure disorder. Folic acid supplementation is recommended for all women prior to conception, but especially for those taking anticonvulsant medications.
Mental health disorders
For women on medical therapy for psychiatric disorders, the medication itself should be reviewed and the risks of unmedicated psychiatric disease compared to the risk of the specific medication. In the case of some medications, such as lithium, an alternate medication may be chosen. In other cases, the risk to that woman of stopping the medication may be substantial and the medication may be continued.[17]
Women with a history of depression, anxiety, and/or body image disorders may find pregnancy and the postpartum period a time of particular vulnerability to recurrence or worsening of these disorders. The couple should be given resources and counseled ahead of time to have support systems in place. Collaboration with the patient’s mental health provider prior to conception can reduce the likelihood of difficulty during pregnancy.
Systemic lupus erythematosus
Pregnancy outcomes such as preeclampsia and preterm delivery are generally reduced if lupus has been inactive or well controlled for six months or more prior to conception. The disease activity of lupus in pregnancy varies with the activity of the lupus prior to pregnancy, with 7%–33% of women with quiet disease in the six months prior to pregnancy having exacerbation or active disease compared to 61%–67% of those with active disease at the beginning of pregnancy.[18, 19] Methotrexate should be discontinued one month or more prior to conception due to its teratogenicity.[20]
Asthma
Unless asthma is severe, pregnancy outcomes for women with asthma are generally excellent.[21] Therapy and lifestyle changes to optimize pulmonary function should be started prior to conception, including objective evaluation of lung function, optimization of pharmacologic therapy, patient education, and avoidance of triggers. The woman should be encouraged to continue asthma therapy once pregnant.[22] Women should be reassured that there is no adverse safety data regarding use of albuterol, budesonide, or intranasal corticosteroids in pregnancy.[23]
Anemia
If iron deficiency anemia is found, iron supplementation should be started to replete iron stores prior to pregnancy. Iron deficiency anemia in pregnancy increases the chance of preterm labor, low birth weight babies, and the potential need for transfusion with delivery. If microcytic anemia is found, evaluation with hemoglobin electrophoresis to identify sickle cell or beta thalassemia or hemoglobin C carriers is recommended. Sickle cell testing alone will not identify carriers of these other hemoglobinopathies.
Cancer
Depending on the timing and the type of therapy for the cancer, fertility preserving options may be available, such as embryo cryopreservation, oocyte cryopreservation, ovarian cryopreservation, or pre-radiotherapy ovarian transposition.[24] The woman should be counseled on the potential impact of cancer therapy on her fertility since fertility may be diminished after radiation or chemotherapy.[25] Also, depending on the nature and prognosis of the cancer, the woman should be counseled on the potential impact of the pregnancy on her disease. Breast cancer survivors are typically advised to wait two years after completion of therapy to conceive after the highest risk of recurrence has passed; however, for women with localized disease, conception before this time has not been shown to adversely affect survival.[26] Similarly, women with previous melanoma may be advised to wait two years to conceive to have a better estimate of their chance of recurrence.[27]
Thyroid disease
Women with overt hypothyroidism often have difficulty conceiving. Screening for thyroid disease in women with a family history, obesity, type 1 diabetes mellitus, age over 35, or other risk factors followed by subsequent treatment with thyroid hormone replacement may facilitate conception. Untreated hypothyroidism is associated with an increase in preeclampsia and prematurity.[28, 29] Severe maternal hypothyroxinemia is associated with cognitive delay in early childhood.[30]
Obesity/low body weight
Women who are obese have more problems with infertility. Once pregnant, they are more prone to miscarriage, birth defects, gestational diabetes, hypertensive disorders of pregnancy, and stillbirth. Shoulder dystocia and cesarean deliveries are more common in obese women as are postpartum wound infection, hemorrhage, and thromboembolic disease. Trial of labor after prior cesarean is less likely to result in successful vaginal birth in obese women.[31] Preconception weight loss can reverse these tendencies. Obese women should be screened for diabetes and hypothyroidism. Offspring of obese women are more likely to have meconium aspiration, be large for gestational age, be admitted to the neonatal intensive care unit (NICU), and have childhood obesity, diabetes and heart disease later in life. Women who have previously undergone bariatric surgery should be screened for vitamin deficiencies such as B12, folate, and D and additionally supplemented for these vitamins.[32]
An underweight status prior to pregnancy increases a woman’s rate of infertility. Women who are underweight at the time of conception have higher incidences of pregnancy complications, such as low birth weight and preterm delivery. Babies born prematurely and/or small for gestation may have long-term development issues.
Cardiac disease
The prevalence of cardiovascular disease among women of childbearing age is increasing and can dramatically impact pregnancy outcome. Women with risk factors for cardiovascular disease, such as obesity, smoking, sedentary lifestyle, increasing maternal age, and comorbidities such diabetes, hypertension, and hyperlipidemia are at relatively higher risk of myocardial infarction in pregnancy and may benefit from assessment of cardiac function prior to pregnancy, although the absolute risk of myocardial infarction in pregnancy is low.
Some maternal cardiac conditions have a significant chance of worsening during pregnancy or of causing maternal mortality. For instance, women with Marfan’s syndrome and a dilated aortic root have a substantial risk of obstetric complications and death in pregnancy that may be lower in women with prior aortic root replacement. Women at especially high risk include those with New York Heart Association (NYHA) class III and IV disease. Pulmonary hypertension and cyanotic heart disease confer high risks of mortality during pregnancy. Women with prior mechanical cardiac valve replacement require anticoagulation during pregnancy. Women with a previously identified structural or functional cardiac defect may benefit from consultation with either a maternal fetal medicine specialist and/or cardiologist prior to pregnancy.[33]
Renal disease
Renal insufficiency confers increased risks of preeclampsia, low birth weight and preterm birth, and possibly further deterioration of renal function. Women with renal insufficiency should have optimal blood pressure management prior to conception.[34] Women with mild renal disease (creatinine 0.9 mL/dL–1.4 mL/dL) and normal blood pressure experience successful pregnancy outcome 90% of the time and have a low risk of progression of renal disease. Women with moderate (creatinine 1.4 mg/dL–2.5 mg/dL) or severe renal disease (creatinine >2.5 mg/dL) are at risk for worsening renal function during pregnancy.[35] Women on ACE or ARB medications should be counseled on the risks of those medications in pregnancy and alternative medications should be prescribed.
Phenylketonuria
Adults with phenylketonuria may have stopped dietary restrictions. The fetus of a patient with untreated phenylketonuria may demonstrate impaired brain development. Women who were diagnosed with phenylketonuria as infants can reduce their chances of delivering an impaired infant by following a reduced phenylalanine diet at least three months before and during pregnancy to reduce the circulating levels of phenylalanine, which can harm the developing fetus. Because many some women may not know that they were ever diagnosed with phenylketonuria, all women should be asked if they were ever placed on a special diet during childhood.[36]
Thromboembolic disease
For a personal or strong family history of thromboembolic disease, the woman should be counseled on the increased risk of venous thromboembolism during pregnancy. A personal history of thromboembolism, especially in the absence of risk factors such as immobilization, surgery, long-distance air travel or use of estrogens should prompt investigation of inherited thrombophilia. Similarly, a family history of recurrent thrombosis or sudden death due to pulmonary embolism should also prompt such testing.[37]
In some patients, anticoagulation may be recommended for pregnancy. Warfarin should be avoided due to its teratogenicity.
Myotonic dystrophy
Certain disorders, such as myotonic dystrophy, are transmitted to offspring with potentially increasing severity in subsequent generations. Although the parent may be only mildly affected, the children may be more profoundly disabled.[38]
Past obstetric history
Women with a history of preterm birth are at increased risk of having another premature delivery.[39] Gathering history about causes or contributing factors to prior preterm birth affords the opportunity address modifiable risk factors such as under- or overweight status, anemia, poorly controlled hypothyroidism or diabetes. Supplemental progesterone and/or cervical length monitoring in the next pregnancy can be offered to women with a history of preterm birth due to preterm rupture of membranes or preterm labor.
If a prior pregnancy was complicated by preeclampsia at less than 34 weeks gestation, or if preeclampsia was experienced in more than one pregnancy, treatment with low dose aspirin in a future pregnancy beginning late in the first trimester may reduce the chance of recurrent preeclampsia.[40]
For prior pregnancy complicated by stillbirth, an attempt should be made to learn the cause of that stillbirth. The woman should be counseled to make modifications to any amenable risk factors, such as smoking cessation, normalizing body weight, and controlling diabetes. Testing for antiphospholipid antibodies, lupus anticoagulant, anticardiolipin antibodies and beta 2 microglobin, should be performed, and if found, treatment with low dose aspirin and heparin for the next pregnancy should be offered.[41]
Prior unexplained recurrent pregnancy loss should prompt an investigation of uterine anomalies and parental karyotypes.
Interconception intervals of less than 18 months or more than 59 months are significantly associated with adverse pregnancy outcomes.[42] Short interpregnancy intervals of less than six months are associated with increased risks of low birth weight babies and preterm birth, compared to intervals of more than 18 months. Interconception intervals of 18 months or greater are associated with fewer uterine ruptures during trial of labor after previous cesarean delivery. Interconception intervals greater than 59 months are associated with higher rates of preeclampsia.
Family history/ethnicity
Family history of congenital anomalies
The family history of both the woman and the male partner should be obtained. In this way, there is the opportunity to counsel about inherited diseases. For instance, if the partner has a family history of neural tube defect, the woman should be advised to increase her folic acid intake to 4 mg daily. There is some evidence that folic acid may help reduce the incidence of other multifactoral birth defects such as orofacial clefts and congenital heart disease. The couple should be screened for consanguinity. A convenient tool for the couple to use to record family history is www.hhs.gov/familyhistory.[43]
Women with premature ovarian insufficiency or family history of predominantly male delayed development, mental retardation, or autism should have screening for fragile X premutation and be referred to a genetic counselor.
Some recessive genetic traits are prevalent in specific populations, and screening before conception for these traits can offer couples the chance to make informed decisions about conception. Some couples may choose to conceive and have diagnostic testing for these conditions once pregnant. Others may choose reproductive technologies that allow for embryo biopsy and transfer of only unaffected embryos. Some couples may choose not to conceive at all if they learn that they are both carriers. Preconception education allows all to understand their chances for an affected child.
Cystic fibrosis is prevalent among many populations, more so for those of Northern European ancestry. Cystic fibrosis screening should be offered to all women of Caucasian ancestry and made available to those of all genetic backgrounds. If there is a family history of cystic fibrosis, documentation of the particular mutations involved is helpful, as not all mutations are included in the current commercially available panels.
Beta thalassemia is prevalent in those of Mediterranean ancestry. Sickle cell trait is found in those of African and Latin American ancestry. Alpha thalassemia is found in the Asian population.
The Ashkenazi Jewish population carries genetic mutations for several recessive diseases with a carrier rate for Tay-Sachs disease of 1/30, Canavan disease 1/40, Gaucher disease 1/15, cystic fibrosis 1/29, Bloom syndrome 1/100, and so on. Several commercially available panels are available for detecting these mutations. French Canadian and Cajun populations have a prevalence of Tay-Sachs disease mutations of 1/30.[44]
Medications
One in 25 prescriptions written for women aged 15–45 is for a potentially teratogenic medication.[45] Ideally, all women of reproductive age should receive pregnancy counseling about the medications that they are prescribed at the time they initiate those medications, and medications with high likelihood of teratogenicity are best to only be prescribed to women with very low likelihood of conception, such as those using long-acting reversible contraception (LARC) or dual methods of contraception. Such medications would include isotretinoin (Acutane), lithium, trenotoin (Retin A), thalidomide, methotrexate, warfarin, ACE inhibitors, and ARBs. Other medications of lower teratogenicity that should also be avoided include the tetracyclines, which can cause discoloration of teeth when used after 25 weeks gestation. The decision to continue or change medications should involve a risk-benefit analysis of the medication and its alternative or absence on the medical condition being treated.
Maternal and paternal age
Pregnancy at a later maternal age confers increased risks for trisomies, especially trisomy 21, such that the rate of clinically significant aneuploidies at delivery is 5 per 1,000 for age 35 years, 15 per 1,000 at age 40 years, and 50 per 1,000 at age 45 years.[46] Pregnancy complications such as multiple gestation, hypertension, and diabetes also increase with advancing maternal age. Pregnancy after age 35 compared to before age 35 is more often complicated by outcomes such as maternal near miss morbidity, maternal death, preterm birth, stillbirth, low birth weight, perinatal mortality, and NICU admission.[47] Miscarriage is more common as maternal age increases.[48]
Later paternal age confers increased risks for single gene mutation, autosomal dominant disorders such as achondroplasia, and neurofibromatosis, although the incidence of these disorders is still low. Some studies have linked paternal age over 50 years to increased development of schizophrenia in offspring compared to paternal age less than 25 years.[49] Other studies have linked older paternal age more than 50 years to an increased risk of autism in offspring.[50]
