Experimental study concerning safety dosage of OK-432 for intrauterine treatment

Clinical intrauterine treatment for fetal cystic hygroma has so far been performed in a few patients; however, it is still difficult to evaluate the results. The aim of this study is to establish the safe dosage of OK-432 in the intrauterine treatment of fetal cystic hygroma.

OK-432 was injected either subcutaneously behind the neck of the fetuses or into the amniotic cavity through the uterine wall of pregnant Japanese white rabbits at 27 days of gestation. Saline was administered to the controls. The dosage and the site of injection were as follows: group 1, OK-432, 0.01 KE (0.25 KE/kg) in 0.2 mL saline per fetus, subcutis; group 2, OK-432, 0.02 KE (0.5 KE/kg) in 0.2 mL saline per fetus, subcutis; group 3, OK-432, 0.04 KE (1 KE/kg) in 0.2 mL saline per fetus, subcutis; group 4, OK-432, 0.01 KE in 0.2 mL saline per fetus, amniotic cavity; group 5, OK-432, 0.04 KE in 0.2 mL saline per fetus, amniotic cavity; group 6, saline, 0.2 mL per fetus, subcutis; group 7, saline, 0.2 mL per fetus, amniotic cavity. All fetuses were delivered at 29 days of gestation.

The mother's rectal temperature was mostly in the normal range throughout the experiment. There was no significant difference between any of the seven groups in fetal body weight. The C reactive protein values of all fetuses were negative. The appearance of the skin of all the fetuses was normal. The histopathological findings of the skin in the OK-432 groups showed a moderate infiltration of monocytes and plasma cells. No pathological changes were observed in the heart, lung, liver or kidneys of any of the fetuses.

Based on this rabbit experiment, we determined that OK-432 may be safely used at a dose of up to 1 KE/1 kg of fetal body weight as an intrauterine treatment for fetal cystic hygroma.