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]