No adverse childhood outcomes through 17 years after prenatal hydroxychloroquine exposure

April Johnson, APRN, CNP

Systemic lupus erythematosus is commonly seen among minority women in their child-bearing years. It is imperative that practitioners are cognizant and sensitive to the family planning needs of these patients. Because of the high risk for birth defects and low birth weight in patients who take medications while pregnant, most mothers are very reluctant to take medications.

Rheumatology providers experience even more anxiety from pregnancy patients taking disease modifying anti-rheumatic drugs (DMARDs), such as hydroxychloroquine and azathioprine because of how these drugs work and the potential side effects to newborns. Historically, patients of color struggle with compliance to treatment regimens for fear of side effects to medications, lack of education regarding treatments, or because of a lack of trust in health care.

This patient population creates a unique opportunity for advanced practice providers to focus on these health care barriers to ensure both treatment compliance for SLE and surveillance of newborns to monitor for adverse effects.

David A. McLain, MD, MACR, FACP, FRCP

Medication use in pregnancy is a very serious concern. We are concerned about the health of the mother and the control of her underlying disease(s) — if any — as well as the health of the fetus and the medicolegal consequences of any problem tied to a medication that we prescribed for use during pregnancy.

In this analysis, the consequences of the use of hydroxychloroquine (HCQ) and azathioprine (AZA) in utero were observed long-term — up to the age of 17. The medicolegal aspect harkens back to Bendectin (pyridoxine, doxylamine and dicyclomine; Merrell Dow Pharmaceuticals), an antinausea combination medication for use during pregnancy.  Thirty-three million women took it, and 678 cases were settled for $120 million, the third highest class-action lawsuit at that time in 1984. Merrell Dow stopped production based on the litigation. No cause and effect for the birth defects and the medication were ever determined.

As we know, SLE is associated with multiple issues during pregnancy, including fetal loss, prematurity, low birth weight and lupus flares post pregnancy. I remember a case as a fellow where the patient was diagnosed with SLE but decided to ignore it. She delivered at a hospital in a neighboring state, had a severe SLE flare with seizures, among other signs and symptoms, and ended up in our university hospital ICU with a fatal outcome. The baby, fortunately, survived.

Studies have shown that women with SLE who continue HCQ throughout pregnancy have lower disease activity and lower corticosteroid doses at the end of pregnancy than those who discontinue HCQ. Mothers who have an anti-Ro antibody and a child with congenital heart block (CHB), have a more than 50% subsequent drop in the risk for CHB on HCQ. In the present study, many of these patients were exposed to low dose aspirin or low molecular weight heparin in addition to HCQ or AZA. No adverse outcomes were associated with hydroxychloroquine taken in pregnancy or breastfeeding in children followed for a median of 2.2 years post-delivery.   

Azathioprine is a prodrug of 6-mercaptopurine, an antimetabolite that inhibits de novo purine synthesis and acts as an antiproliferative agent by interfering with protein, DNA and RNA synthesis and promoting apoptosis. Xanthine oxidase metabolizes 6-mercaptopurine and simultaneous allopurinol use interferes with this metabolism and can lead to fatal blood dyscrasias. Use of AZA in this study was associated with premature delivery, lower birth weight and more childhood infections in children followed for a median of 4.4 years post-delivery.

This is important research as SLE is more common in young females at the peak childbearing years when SLE is often the most active. Nothing in rheumatology is more satisfying than helping a pregnant patient with SLE through a successful pregnancy!