Safety of Systemic Immune Suppressive Drugs During Pregnancy and Lactation

Being pregnant while having an inflammatory/autoimmune dermatologic disease can be tough in terms of figuring out which medications can control your condition while keeping your growing baby safe and healthy. In this article, we will discuss a few medications commonly used to control a range of immune-mediated diseases during both pregnancy and lactation. Our goal is to keep you well informed during this important and exciting time in your life! 

This article will focus on systemic drugs, meaning medications which enter the bloodstream to target various organ systems in your body. Most of these medications are either taken orally, injected, or given through intravenous access. Each of the following medications will be discussed individually with regards to their safety during pregnancy and lactation: prednisone, hydroxychloroquine, dapsone, mycophenolate mofetil, azathioprine, intravenous immunoglobulin, and rituximab. These medications can be split into pregnancy category C and D drugs.

Pregnancy Category C Drugs

These drugs lack controlled clinical trials in pregnant women and may or may not have demonstrated adverse effects on the fetus in animal models.

Systemic corticosteroids

Prednisone is the preferred corticosteroid of all the systemic steroids during pregnancy since its transfer through the placenta to the growing fetus is limited.^[1] Corticosteroids are considered relatively safe, lacking any written reports of strong association with major birth anomalies. However, according to a 300 patient study published in 2004, there is a potential association between development of oral cleft abnormalities in the baby, a higher rate of preterm birth, and lower birth weight with the use of oral corticosteroids during pregnancy.^[2] The highest rates of oral cleft abnormalities have been reported when the medication is used in the period four weeks prior to and twelve weeks after conception, as this is the period when lip and palate formation occur.^[1] Because of this and the other listed abnormalities, it is frequently recommended that prolonged use of prednisone during pregnancy should not exceed 20 mg/day and preferably be 7.5mg/day or less. These medications are L2 in terms of lactation safety, meaning they are relatively safe. However, it is recommended that use of these agents be limited to less than three weeks while breastfeeding and that nursing should proceed four or more hours after the last dose is taken.^[1]

Hydroxychloroquine

This medication is considered a first-line agent for women with active lupus disease while pregnant. This medication has not been found to definitively increase the rate of birth defects over the general population.^[1] In fact, it is thought to be beneficial to both mother and baby. Hydroxychloroquine has been reported to reduce lupus flares in pregnant women as well as reduce the risk of clotting events and high lipid levels. The benefit to the baby is potential protection from the development of heart block, a fetal complication in lupus-diagnosed mothers with specific antibodies.^[3] Hydroxychloroquine is considered L2 in terms of lactation safety, but the lack of studies make it uncertain as to whether the medication should be recommended during breastfeeding.^[1]

Dapsone

Dapsone is used in the treatment of leprosy and pemphigus disease and as a chemoprophylactic agent for malaria. This medication is considered safe to use in pregnant patients. According to individual reports as well as animal studies, there has been no definite increase in the rate of birth defects over the general population in which high doses of dapsone were used
.^[4] However, there is a risk of maternal anemia (low hemoglobin) in mothers and hemolytic anemia (due to bursting and breakdown of red blood cells) in the baby, resulting in hyperbilirubinemia (too much bilirubin which is a breakdown product of red blood cells). Therefore, maternal G6PD (a metabolic enzyme in the body) should be checked to ensure levels are not low before starting therapy. Dapsone is considered L4 in terms of lactation safety, which indicates that it can be potentially hazardous. This is due to reported cases of hemolytic anemia (breakdown of red blood cells) in some babies with use of this medication while breastfeeding.^[1] If it is used during breastfeeding, signs of hemolytic anemia should be monitored in the baby.^[4]

Intravenous Immunoglobulin Therapy

IVIG therapy is used for a host of autoimmune diseases, including pemphigus and pemphigoid gestationis. This therapy is considered relatively safe in pregnancy even though the immunoglobulins do cross the placenta.^[1] There have been reports of this therapy being used safely in lupus and myasthenia gravis. The only special risks that should be considered in pregnant women are an increased clotting risk since pregnant women clot more easily, and volume overload in the mother’s circulation since this therapy relies on an infusion of the medication directly into the bloodstream.^[5] The therapy is considered L2 for lactation safety and can be used safely in breastfeeding mothers.^[1]

Rituximab

This medication is used as an effective therapy for a variety of autoimmune diseases. Although it is labeled as category C by the FDA, it should not be used during pregnancy if possible. This medication increasingly crosses the placenta over the duration of the pregnancy and has been associated with abnormalities in the development of the baby’s immune cells in the bloodstream.^[1] In a large study of 153 pregnant women on rituximab,10% of the babies who were born had abnormalities in their blood cells, which potentially contributed to infectious complications in around half of those babies.^[6] Women should avoid getting pregnant for 1 year after rituximab therapy. This drug has been categorized as L2, but should be avoided in lactating mothers since there is very limited data on its safety during breastfeeding.^[1]

Pregnancy Category D Drugs  

These drugs have shown adverse effects on the fetus in animal models, and no reliable human studies are available.

Mycophenolate mofetil

This drug should not be used in pregnancy due to the risk of miscarriage and multiple different structural and organ development abnormalities which can occur in the baby. It is L4 in lactation safety and should be avoided in breastfeeding mothers, as it very possibly enters the milk flow.^[1]

Azathioprine

This medication is frequently used for inflammatory bowel disease, rheumatic disease, and other autoimmune conditions. It does have reported use in pregnancy, but there are several known potential risks with use of this drug. Blood cell abnormalities, low birth weight, and heart defects in the baby have all been reported with maternal use,^[1] but there are conflicting reports based on the type of autoimmune condition being treated. For instance, azathioprine in lupus seems to demonstrate acceptable risk for the fetus.^[7] Overall, this drug should be used with caution in pregnant women, and doses should be reduced in the third trimester if the mother is found to be leukopenic (low white blood cell count). Caution should also be exercised while breastfeeding, as this drug is categorized L3. If breastfeeding is pursued while on this medication, the baby should be closely monitored for proper growth and ability to fight infection.^[1]