AUSTRALIAN COLLABORATIVE TRIAL OF ANTENATAL THYROTROPIN-RELEASING-HORMONE - ADVERSE-EFFECTS AT 12-MONTH FOLLOW-UP

Objective. The Australian Collaborative Trial of Antenatal Thyrotropin -Releasing Hormone (ACTOBAT) assessed the efficacy of 200 mu g of thyr otropin-releasing hormone (TRH) in combination with glucocorticoids in the prevention of neonatal lung disease.(1) This paper reports the 12 -month follow-up of the infants from the trial completed in 1994. Desi gn. This was a double-blinded randomized controlled trial. Setting. Wo men 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 Mothers who had not withdrawn from treatment and whose infants were discharged alive (1262 infants).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 wa s mailed to parents for self-completion immediately before their baby' s/babies' first birthday. The questionnaire included a checklist to as sess sensory, motor, language, and social development, and use of heal th services. Results. Milestone scores were developed from items on th e follow-up form. Treatment with TRH was associated with an increased risk of motor delay, social delay, fine motor delay, sensory impairmen t, and early language impairment. No differences were seen between tre atment 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, histor y of perinatal death, history of preterm rupture of the membranes, inf ant sex, singleton or twin status, maternal age, and maternal blood pr essure (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 d elay (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), ea rly 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 betwe en the treatment groups in hospital admissions (OR, 1.08; 95% CI .83 t o 1.42), doctors' visits (general practitioner OR adj, 1.09; 95% CI .7 9 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 disturbance s (OR adj, .93; 95% CI .71 to 1.21). Conclusions. Because antenatal ad ministration of TRH is associated with small, consistent deficits in m ajor milestone achievements at 12 months of age, it is essential that additional planned trials make provision for long-term follow-up. Ante natal TRH should only be used in the context of a clinical trial.