In utero azathioprine exposure and increased utilization of special educational services in children born to mothers with systemic lupus erythematosus

Arthritis Care Res (Hoboken). 2013 May;65(5):759-66. doi: 10.1002/acr.21888.


Objective: Azathioprine (AZA) is recognized among immunosuppressive medications as relatively safe during pregnancy for women with systemic lupus erythematosus (SLE) requiring aggressive treatment. This pilot study aimed to determine whether SLE therapy during pregnancy was associated with developmental delays in offspring.

Methods: This cohort study included SLE patients with at least one live birth postdiagnosis. Medical histories were obtained via interviews and chart review. Multiple logistic regression was used to examine associations between SLE therapy during pregnancy and maternal report of special educational (SE) requirements (as proxy for developmental delays) among offspring. Propensity scoring (incorporating corticosteroid use, lupus flare, and lupus nephritis) was used to account for disease severity.

Results: Of 60 eligible offspring from 38 mothers, 15 required SE services, the most common indication for which was speech delay. Seven (54%) of the 13 children with in utero AZA exposure utilized SE services versus 8 (17%) of 47 nonexposed children (P < 0.01). After adjustment for pregnancy duration, small for gestational age, propensity score, maternal education level, and antiphospholipid antibody syndrome, AZA was significantly associated with SE utilization occurring from age 2 years onward (odds ratio 6.6, 95% confidence interval 1.0-43.3), and bordered on significance for utilization at any age or age <2 years.

Conclusion: AZA exposure during SLE pregnancy was independently associated with increased SE utilization in offspring, after controlling for confounders. Further research is indicated to fully characterize developmental outcomes among offspring with in utero AZA exposure. Vigilance and early interventions for suspected developmental delays among exposed offspring may be warranted.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Azathioprine / adverse effects*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Developmental Disabilities / diagnosis
  • Developmental Disabilities / epidemiology*
  • Developmental Disabilities / psychology
  • Education, Special / trends*
  • Female
  • Humans
  • Infant
  • Lupus Erythematosus, Systemic / drug therapy
  • Lupus Erythematosus, Systemic / epidemiology*
  • Male
  • Pilot Projects
  • Pregnancy
  • Pregnancy Complications / drug therapy
  • Pregnancy Complications / epidemiology*
  • Prenatal Exposure Delayed Effects / diagnosis
  • Prenatal Exposure Delayed Effects / epidemiology*
  • Prenatal Exposure Delayed Effects / psychology


  • Azathioprine