Slow-release theophylline in pregnant asthmatics

Oral theophylline treatment may be helpful in controlling severe asthma during pregnancy. This treatment, however, has been suspected of causing both complications and malformations. The objective of this investigation was to study the influence of theophylline treatment on the course of pregnancy and delivery and on maternal and infant health.

Respiratory unit, antenatal outpatient departments, and labor and delivery rooms.

Case-control study.

The data of 212 pregnant asthmatics with theophylline treatment (AT) were compared with findings in 292 pregnant asthmatics without theophylline (A) and 237 nonasthmatic pregnant control subjects (C).

There were no significant differences among groups as to age, height, age of onset of asthma, lung function, parity, or smoking. In the AT group, 19% were treated for acute exacerbations of the asthma as compared with 6% in the A group (p < 0.001). The incidence of preeclampsia was higher in the AT (15.6%) than in the C (6.4%) group (p < 0.03). Theophylline treatment at term was not associated with premature contractions or premature rupture of membranes, hemorrhage, placenta previa, abruption of the placenta, abnormal fetus position, frequent induction or augmentation of labor, prolonged third phase of delivery, or increased hemorrhage post partum. No differences among groups were seen with regard to gestational age, birth weight, Apgar scores, or perinatal deaths. Jaundice in the newborn, necessitating treatment with blue light, was more common in the AT (15.0%) than in the C group (7.8%) (p < 0.05). Three infants of 121 patients treated with theophylline during the first trimester were born with malformations; in the 91 patients treated with theophylline only during the second and third trimester, and the asthmatic control group, the corresponding figures were 4 and 3.

During the second and third trimesters until term, theophylline treatment using moderate doses can be considered safe. The safety of theophylline treatment during the first trimester with regard to teratogenicity remains to be determined.