Table I.
Birth defect(s)a | Time of exposureb,c | Reported indication for methotrexate use | Gestational age (weeks) | Maternal age at delivery (years) | Maternal race/ethnicity | Maternal diabetes and pre-pregnancy BMI categoryd | Use of folic acid- containing multivitaminc |
---|---|---|---|---|---|---|---|
Perimembranous ventricular septal defect, atrial septal defect | Preconception | None | 37 | 26 | Non-Hispanic Black | No diabetes, overweight | Month 2 – end of pregnancy |
Secundum atrial septal defect | Preconception | Neoplasm of endocrine glands | 38 | 35 | Non-Hispanic White | No diabetes, overweight | Month 4 – end of pregnancy |
Tetralogy of Fallot | Preconception | None | 35 | 37 | Non-Hispanic White | No diabetes, normal weight | Preconception – Month 7 |
Total anomalous pulmonary venous return, atrial septal defect | Preconception | None | 36 | 36 | Asian/Pacific Islander | Gestational diabetes, obese | Preconception – end of pregnancy |
Valvar pulmonary stenosis, secundum atrial septal defect | Preconception | None | 40 | 29 | White, Native American | No diabetes, obese | Month 2 – end of pregnancy |
Secundum atrial septal defect | Preconception - Week 1 | None | 38 | 22 | Non-Hispanic White | No diabetes, normal weight | Preconception – end of pregnancy |
Cleft palate | Preconception - Week 2 | None | 38 | 24 | Non-Hispanic Black | No diabetes, overweight | Month 2 – end of pregnancy |
Tetralogy of Fallot | Preconception - Week 2 | Rheumatoid arthritis | 38 | 35 | Hispanic | No diabetes, normal weight | Month 3 – end of pregnancy |
Secundum atrial septal defect | Preconception - Week 3 | None | 38 | 33 | Non-Hispanic White | Gestational diabetes, overweight | Month 2 – end of pregnancy |
Multiple congenital diaphragmatic hernias (Bochdalek, Morgagni, hiatal) | Preconception - Week 4 | None | 22 | 26 | Non-Hispanic White | No diabetes, obese | Preconception – end of pregnancy |
Third degree hypospadias | Preconception - Week 6 | Systemic lupus erythematosus | 41 | 39 | Non-Hispanic Black | No diabetes, overweight | Preconception – end of pregnancy |
VACTER (thoracic hemivertebrae, tracheo- esophageal fistula, esophageal atresia, ectopic kidney, and cardiac [double-inlet left ventricle with mitral atresia, transposed great arteries, and hypoplastic ascending aorta]) | Preconception - Week 9 | None | 34 | 24 | Non-Hispanic White | No diabetes, normal weight | Month 2 – end of pregnancy |
Bilateral foot ectrodactyly, metopic craniosynostosis | Week 5 | None | 37 | 30 | White, Hispanic | No diabetes, normal weight | Preconception – end of pregnancy |
Third degree hypospadias | Week 5 | None | 29 | 29 | Non-Hispanic White | No diabetes, obese | Preconception – end of pregnancy |
Right microtia, muscular ventricular septal defect | 1 dose between weeks 6–10 | None | 33 | 31 | Hispanic | Gestational diabetes, obese | Month 1 – end of pregnancy |
Valvar pulmonary stenosis | Week 22 | None | 33 | 36 | Hispanic | No diabetes, normal weight | Preconception – end of pregnancy |
Control | Preconception | None | 35 | 34 | Non-Hispanic White | No diabetes, normal weight | Preconception – end of pregnancy |
Control | Preconception | Polyarticular juvenile rheumatoid arthritis | 39 | 33 | Non-Hispanic White | Gestational diabetes, obese | Preconception – end of pregnancy |
Control | Preconception - Week 1 | None | 36 | 36 | Non-Hispanic White | No diabetes, overweight | Preconception – end of pregnancy |
Control | Preconception - Week 2 | None | 39 | 29 | Non-Hispanic White | No diabetes, overweight | Preconception – end of pregnancy |
Birth defect diagnoses organized by cases appearing first followed by controls; within sub-group, cases and controls arranged chronologically by timing of exposure; congenital heart defects in bold
Exposure defined as any reported maternal use of methotrexate
Preconception defined as the period from three months prior to conception through the estimated date of conception. Week refers to gestational week. Month refers to gestational month.
Body mass index (BMI) categories: 18.5–24.9 mg/kg2 - normal, 25.0–29.9 - overweight, >29.9 - obese