Is Aminophylline (Theophylline) Teratogenic?
No, aminophylline/theophylline is not teratogenic and is classified as compatible for use during pregnancy. 1
Pregnancy Safety Profile
Theophylline carries a TGA Category A and FDA Category C classification, indicating it has been used extensively during pregnancy with no evidence of teratogenic effects. 1 The European Respiratory Society/Thoracic Society of Australia and New Zealand (ERS/TSANZ) 2020 guidelines explicitly state that theophylline is "compatible" for use throughout all trimesters of pregnancy and during breastfeeding. 1
Key Evidence Supporting Safety
No teratogenic effects have been documented in clinical use during pregnancy, despite decades of experience with this medication. 1
Animal studies confirm safety: Theophylline was not teratogenic in CD-1 mice at oral doses up to 400 mg/kg (approximately 2.0 times the human dose) or in CD-1 rats at oral doses up to 260 mg/kg (approximately 3.0 times the human dose). 2
The benefit of maintaining maternal asthma control far outweighs any theoretical risk, as uncontrolled maternal asthma with hypoxia poses well-documented adverse effects on the fetus. 1
Important Clinical Considerations
Monitoring Requirements
Blood theophylline levels must be monitored during pregnancy to maintain therapeutic concentrations and avoid toxicity. 1
If treatment continues until delivery, be aware that uterine contractions may be inhibited due to theophylline's smooth muscle relaxant properties. 1
Neonatal Monitoring
Neonates exposed to theophylline at term or during lactation should be observed for signs of toxicity or withdrawal, including:
- Tachycardia
- Irritability
- Vomiting 1
Breastfeeding Guidance
Theophylline is compatible with breastfeeding, though it is excreted into breast milk at concentrations approximately equivalent to maternal serum levels. 1, 2
Breastfeeding women should nurse immediately before taking their regular dose to minimize infant exposure. 1
An infant consuming 1 liter of breast milk containing 10-20 mcg/mL theophylline will receive approximately 10-20 mg/day, which is unlikely to cause serious adverse effects unless maternal serum concentrations are toxic. 2
Common Pitfalls to Avoid
Do not discontinue theophylline due to pregnancy concerns if it is required for maternal asthma control—the risk of uncontrolled asthma is greater than any medication risk. 1
Do not assume FDA Category C means "unsafe"—this classification reflects limited controlled human studies, not evidence of harm. The TGA Category A classification and extensive clinical experience support safety. 1
Do not forget to adjust monitoring frequency—pregnancy alters drug metabolism, requiring vigilant therapeutic drug monitoring. 1