Chronic Illnesses in Pregnancy

Allergic Rhinitis and Asthma

• Diagnosis and staging of asthma during pregnancy is the same as in nonpregnant women, but more frequent follow-up is necessary. The risks of medication use to the fetus are lower than the risks of untreated asthma.
• Treatment follows a six-step approach. As step 1, all pregnant patients with asthma should have access to a short-acting inhaled β2 -agonist (albuterol is the preferred agent).
• For persistent asthma (step 2 or higher), low, medium, or high doses of controller corticosteroids are foundational. Budesonide is preferred, but corticosteroids used before pregnancy can be continued. Long-acting β2 -agonists are safe.
• Cromolyn, leukotriene receptor antagonists, and theophylline are considered alternative agents, but they are not preferred.
• For patients with the most severe disease, systemic corticosteroids are recommended.
• First-line medications for allergic rhinitis during pregnancy include intranasal corticosteroids, nasal cromolyn, and first-generation antihistamines (e.g., chlorpheniramine and hydroxyzine). Intranasal corticosteroids are the most effective treatment and have a low risk for systemic effect. Beclomethasone and budesonide have been used most. Loratadine and cetirizine do not appear to increase fetal risk, but they have not been extensively studied.
• Use of an external nasal dilator, short-term topical oxymetazoline, or inhaled corticosteroids may be preferred over oral decongestants, especially during early pregnancy.

Diabetes

• Insulin is the drug of choice for patients with type 1 or 2 diabetes during pregnancy. Switch women receiving insulin glargine or detemir to NPH insulin. Glyburide and metformin may be alternatives but are not recommended by the American Diabetic Association.
• Goals for self-monitoring of blood glucose are the same as for GDM. EPILEPSY
• Major malformations are two to three times more likely in children born to women taking AEDs than to those who do not, but the risks of untreated epilepsy to the fetus are considered to be greater than those associated with the AEDs.
• Major malformations with valproic acid therapy are dose related and range from 6.2% to 10.7%. When possible, avoid valproic acid during pregnancy to minimize the risk of neural tube defects, facial clefts, and cognitive teratogenicity.
• Rates of major malformations associated with monotherapy of other AEDs are 2.9% to 3.6%. Polytherapy is associated with higher rates.
• Carbamazepine and lamotrigine may be the safest AEDs for use in pregnancy.
• Phenytoin, lamotrigine, and carbamazepine may cause cleft palate, and phenobarbital may cause cardiac malformations.
• Drug therapy should be optimized prior to conception, and AED monotherapy is recommended when possible.
• If drug withdrawal is planned, it should be done at least 6 months prior to conception.
• All women with epilepsy should take folic acid, 4 to 5 mg daily,starting before pregnancy and continuing through at least the first trimester. The American Academy of Pediatrics recommends that all neonates receive vitamin K at delivery.

Human Immunodeficiency Virus Infection

• Pregnant women infected with human immunodeficiency virus (HIV) should receive antiretroviral (ARV) therapy to decrease the risk of perinatal transmission of HIV. ARV therapy is selected from those recommended for nonpregnant adults (with consideration given to the teratogenic profiles of each drug). Women already taking ARV therapy should continue their regimen when possible.
• Women taking efavirenz should continue it, as neural tube defects usually occur through weeks 5 to 6 of gestation, and pregnancy often is not recognized until weeks 4 to 6.
• For ARV-naïve women, use of a three-drug combination regimen is recommended and usually contains two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) with high transplacental passage (preferred: zidovudine, lamivudine; alternatives: emtricitabine, tenofovir, abacavir) along with a protease inhibitor (preferred: atazanavir plus low-dose ritonavir, lopinavir/ritonavir; alternative: darunavir or saquinavir, both with low-dose ritonavir). Nevirapine, a nonnucleoside reverse transcriptase inhibitor (NNRTI), can be used as an alternative to a protease inhibitor but is associated with severe rash and life-threatening or fatal hepatotoxicity.
• Some women who do not require immediate therapy may choose to delay ARV therapy until after the first trimester to avoid potential teratogenicity.
• For women with HIV, cesarean section before the onset of labor (usually at 39 weeks’ gestation) is recommended to reduce the risk of perinatal HIV transmission. If maternal viral load is 400 copies/mL or more (400 × 103 /L or greater) or not known, IV zidovudine should be initiated with a 1-hour loading dose (2 mg/kg) followed by a continuous infusion (1 mg/kg) for 2 hours (cesarean) or until delivery (for vaginal delivery). Zidovudine IV should still be administered in the presence of resistance to oral zidovudine. Women with a viral load below 400 copies/mL (400 × 103 /L or less) near delivery do not require zidovudine IV but should continue their ARV regimen.

Hypertension

• Severe HTN (systolic blood pressure [sBP] = >160 mm Hg or diastolic blood pressure [dBP] ≥ 110 mm Hg) can cause maternal complications, hospital admission, and potential premature delivery. Drug therapy is indicated for women with BP of 160/110 mm Hg or more. BP should be lowered by a maximum of 25% in the first minutes to 1 hour with further reduction to below 160/100 mm Hg over a period of hours. Commonly used agents are labetalol and hydralazine, but hydralazine causes more fetal adverse effects. Oral nifedipine may also be used.
• Treatment of nonsevere HTN (sBP 140–159 mm Hg or dBP 90–109 mm Hg) reduces risks of severe HTN by 50% but does not substantially affect fetal outcomes. In the United States, treatment is started at BPs of 150 to 160/100 to110 mm Hg, with a goal of BP of less than 150/100 mm Hg. In Canada and the United Kingdom, the target goal is lower. No evidence exists for the superior efficacy of one antihypertensive agent versus another, but drugs commonly used include labetalol, methyldopa, and calcium channel blockers. β-Antagonists can be used except atenolol.
• ACE inhibitors, angiotensin receptor antagonists, and renin inhibitors are contraindicated throughout pregnancy.
• Thiazide diuretics can be used in women who were treated with them before pregnancy

Depression

• In general, monotherapy is preferred over polytherapy even if higher doses are required. If antidepressants are used, the lowest possible dose should be used for the shortest possible time to minimize adverse fetal and maternal pregnancy outcomes.
• In one study, pregnant women who stopped taking antidepressants were more likely to relapse than women who completed treatment.
• The selective serotonin reuptake inhibitors (SSRIs) are not considered major teratogens. The serotonin/norepinephrine reuptake inhibitors (SNRIs) are less well defined. Use of SSRIs and SNRIs in the latter part of pregnancy is associated with persistent pulmonary HTN of the newborn and prenatal antidepressant exposure syndrome (i.e., cardiac, respiratory, neurologic, gastrointestinal [GI], and metabolic complications from drug toxicity or withdrawal of drug therapy). Tricyclic antidepressants are not considered major teratogens but have been associated with neonatal withdrawal syndrome when used late in pregnancy an epidemiologic study suggests that first-trimester use of paroxetine may be associated with a 1.5- to 2-fold increased risk for cardiac defects in the infant.

Thyroid Disorders

• For hypothyroidism, give levothyroxine to attain a thyroid-stimulating hormone (TSH) of 0.1 to 2.5, 0.2 to 3, and 0.3 to 3 mIU/L in the first, second, and third trimesters, respectively. It can be started at 0.1 mg/day. Women receiving thyroid replacement therapy before pregnancy may require increased dosage during pregnancy. Monitor TSH levels every 4 weeks during the first half of pregnancy and at least once between 26 and 32 weeks of pregnancy to allow for dose titration.
• Hyperthyroidism therapy includes the thioamides (ie, methimazole, propylthiouracil [PTU]). Dose reductions are possible after attaining a euthyroid state. Some support a switch to PTU during the first trimester because of potential risks with methimazole followed by a subsequent switch to methimazole for the second and third trimesters to prevent hepatotoxicity from PTU. Iodine-131 is contraindicated. The goal of therapy is to attain free thyroxine concentrations near the upper limit of normal.