ABSTRACT. This study examines the effect of premature delivery on the switch from fetal (a2 72) to adult (a2 @2) Hb, in lambs in which premature parturition was induced by the intrafetal infusion of ACTH or corticotropin releasing hormone. Of 10 chronically cannulated ovine fetuses given ACTH at the rate of 79 ng/min for a 15 min period every 2 h starting at days 125 (n = 9) or 126 (n = 1) of gestation, three died in utero at days 131, 131, and 130, respectively. The remaining seven were born alive at 133 2 1.6 days. Five control fetuses, treated with vehicle (0.9% NaCl, wtlvol) only were delivered at 149 f 2.7 days of gestation, which is not significantly different from the duration of pregnancy in other chronically cannulated lambs in this flock. Hb switching, as measured by the globin synthesis ratio, @/a, was complete at term in the control lambs. The @/a globin synthesis ratio of the prematurely delivered lambs was not accelerated by birth, and was similar to that of control fetuses of the same gestational age still in utero. The four lambs surviving premature birth more than 70 days did not complete the switch to normal adult Hb until after 220 days postconception. (Pediatr Res 24: 688-692, 1988) Hb disappears from neonatal blood (9). It was reported that in lambs carrying the PA gene a small proportion of PC (~1 5 % of total p) appears transiently after birth and persists for several months (10). Many attempts have been made to influence the time of onset of the switch from fetal (7) to adult (P) Hb but these have been largely unsuccessful (8,9,11,12). Once commenced, the rate of the switching process has been shown to be able to be modulated. Hypophysectomy or bilateral adrenalectomy of the chronically cannulated fetus causes the completion of the switch to be delayed considerably (8, 9). In the adrenalectomized fetus replacement of cortisol in gradually increasing amounts returned the rate of adult Hb synthesis to normal (9).An increase in fetal cortisol production precedes and indeed induces parturition at normal term in sheep (13). Premature parturition can be induced by the treatment of immature ovine fetuses with cortisol, ACTH, or CRF some 3 wk or more before normal term (14, 15). These fetuses show accelerated lung maturation. The purpose of this study was to investigate the effect of premature activation of the fetal adrenal on Hb switching in the ovine fetus. The hypothesis was that premature parturition, induced by the fetal infusion of ACTH or CRF, would accelerate the completion of the switch from fetal to adult Hb. Abbreviations MATERIALS AND METHODS CRH, corticotrophin-releasing hormoneA total of 54 blood samples (1 ml) from 20 fetuses chronically cannulated as described previously (16, 17) was used to establish a, p, and 7 globin synthesis in normal intact animals from 103 days of gestation until term. Then 39 samples were collected For most of gestation sheep fetal red blood cells contain a fetal from birth until 30 days postpartum, and three samples from Hb, with two a and two 7 globi...

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This study was designed to investigate the effects of pulsatile infusion of ACTH into ovine fetuses on the endocrine changes that precede parturition, the timing of birth and the subsequent survival of the lamb. Where appropriate, these parameters were compared with fetuses infused with pulses of saline and uninfused normal term fetuses. Ten fetuses received a 15-min infusion of synthetic ACTH(1-24) (79 ng/min) from day 125 (n = 9) or day 126 (n = 1) of gestation. Seven fetuses were born prematurely within 174 +/- 14 h (mean +/- S.E.M.) after the commencement of the infusion, i.e. at 132 +/- 0.6 days, whilst three died in utero at 130-131 days. When born all lambs could breath, walk and suckle. Of the seven premature lambs, four died 2-10 days after parturition but three survived for at least 12 months after birth. Fetuses infused with pulses of ACTH exhibited intermittent but very large increases in plasma ACTH values, with the first pulse, on day 1, increasing ACTH values from 5.1 +/- 1.1 to 140 +/- 31.3 pmol/l (P less than 0.001). At the next sampling time, ACTH values were not significantly different from preinfusion values. A similar plasma ACTH profile was observed on each subsequent day of ACTH treatment. In contrast, fetuses (n = 4) infused with pulses of saline between 125 and 131 days exhibited fetal plasma concentrations of ACTH which ranged between 2 and 12 pmol/l for the majority of the time.(ABSTRACT TRUNCATED AT 250 WORDS)

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