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Fetal Monkey Surfactants After Intra-amniotic or Maternal Administration of Betamethasone and Thyroid Hormone

From the Department of Obstetrics and Gynecology, Pediatrics, Physiology, and the California Regional Research Primate Center, University of California, Davis, California; and Division of Pulmonary Biology and Neonatology Children’s Hospital, Cincinnati, Ohio

Address reprint requests to: William M. Gilbert, MD, Department of Obstetrics and Gynecology, University of California, Davis, 4860 Y Street, Suite 2500, Sacramento, CA 95817; E-mail: wmgilbert{at}ucdavis.edu.

OBJECTIVE: To compare direct intra-amniotic injection of betamethasone and thyroxine (T4) with maternal treatment and controls for accelerating pulmonary surfactant production.

METHODS: Twelve pregnant monkeys (Macaca mulatta) on gestational day 125 (term 165 ± 10 days) had surfactant protein A and B concentrations measured in amniotic fluid. In four controls, normal saline was injected into the amniotic fluid; four others (intra-amniotic) received intra-amniotic betamethasone (1 mg) and T4 (60 µg); and in four others (maternal), the dam was given betamethasone (12 mg) intramuscularly, repeated in 24 hours, plus TRH (400 µg) intravenously, repeated every 6 hours for 24 hours. Seventy-two hours after the initial amniocentesis, a hysterotomy was performed and fetal tissue and amniotic fluid harvested for determination of surfactant protein A and B concentrations and immunohistochemical staining for surfactant protein A.

RESULTS: Amniotic fluid surfactant protein A was higher with intra-amniotic injection than with maternal treatment (P < .04) or controls (P = .07). Amniotic fluid surfactant protein B was higher in the intra-amniotic group than in controls (P = .06). Immunohistochemical staining for surfactant protein A in the lung tissue was increased in the intra-amniotic group compared with controls (0.145 ± 0.01 versus 0.097 ± 0.001, percent positive staining for surfactant protein A cells per lung tissue cells; P < .03). Birth weight was greater in the intra-amniotic group compared with the maternal group (P < .03) although not different from the controls. Finally, gut motility and the presence of formed meconium were increased in the intra-amniotic group compared with the other groups (P < .05).

CONCLUSION: Intra-amniotic injection of betamethasone and T4 enhanced lung (and possibly intestinal) maturation of the preterm rhesus fetal monkey compared with maternal injections.