Objective: The Australian Collaborative Trial of Antenatal Thyrotropin-Releasing Hormone (ACTOBAT) assessed the efficacy of 200 microg of thyrotropin-releasing hormone (TRH) in combination with glucocorticoids in the prevention of neonatal lung disease. This paper reports the 12-month follow-up of the infants from the trial completed in 1994.
Design: This was a double-blinded randomized controlled trial.
Setting: Women were recruited from level 3 perinatal centers throughout Australia.
Participants: Mothers who had not withdrawn from treatment and whose infants were discharged alive (1262 infants). Extensive efforts were made to trace this entire cohort.
Outcome measures: A questionnaire was mailed to parents for self-completion immediately before their baby's/babies' first birthday. The questionnaire included a checklist to assess sensory, motor, language, and social development, and use of health services.
Results: Milestone scores were developed from items on the follow-up form. Treatment with TRH was associated with an increased risk of motor delay, social delay, fine motor delay, sensory impairment, and early language impairment. No differences were seen between treatment and placebo groups for motor impairment. Multivariate analyses were performed, adjusting for chronological age, duration of gestation at randomization, time from randomization to delivery, parity, history of perinatal death, history of preterm rupture of the membranes, infant sex, singleton or twin status, maternal age, and maternal blood pressure (systolic and diastolic) at randomization. For the total cohort (N = 1022), treatment with TRH was associated with motor delay (odds ratio [OR], 1.51; 95% confidence interval [CI] 1.11 to 2.05); social delay (OR 1.40; 95% CI 1.01 to 1.95); sensory impairment (OR, 2.00; 95% CI 1.06 to 3.74); severe impairment (OR, 1.75; 95% CI 1.07 to 2.87); and a trend toward motor impairment (OR, 1.50; 95% CI .97 to 2.33), early language impairment (OR, 1.27, 95% CI .90 to 1.79), and fine motor delay (OR, 1.15; 95% CI .83 to 1.60). There were no differences between the treatment groups in hospital admissions (OR, 1.08; 95% CI .83 to 1.42), doctors' visits (general practitioner OR adj, 1.09; 95% CI .79 to 1.50 or specialist OR adj 1.15; 95% CI .87 to 1.49), respiratory symptoms (OR adj, 1.16; 95% CI .88 to 1.53), or behavioral disturbances (OR adj, .93; 95% CI .71 to 1.21).
Conclusions: Because antenatal administration of TRH is associated with small, consistent deficits in major milestone achievements at 12 months of age, it is essential that additional planned trials make provision for long-term follow-up. Antenatal TRH should only be used in the context of a clinical trial.