The fetus is supplied from the placenta with
estradiol (E2) and
progesterone (P) in increasing amounts during gestation. After delivery of a premature infant, placental supply is disrupted, resulting in a rapid decrease in E2 and P. Replacement of these
placental hormones may restore intrauterine conditions and may be beneficial for bone
mineral accretion,
clinical course, and outcome. Thirty female infants with a median gestational age of 26.6 weeks (between 24.1-28.7) and a
birth weight of 675 g (370-990) were randomized to receive E2 and P replacement, aiming to maintain plasma levels equaling the intrauterine levels, or no replacement. The E2 and P replacement was started iv and was followed by transepidermal administration for a total duration of 6 weeks. Repeated measurements included plasma levels of E2, P, FSH, and LH; uterine volume;
calcium and
phosphorus in spot urine specimens; and bone
mineral accretion by single photon absorption densitometry. Further, the incidence of chronic
lung disease and various clinical outcome data were recorded. The plasma levels of E2 and P were within the intrauterine range with median replacements of 2.30 mg/kg x day E2 (1.13-6.23) and 21.20 mg/kg x day P (11.23-27.36), iv. Three- and 6-fold higher doses of E2 and P were needed via the transepidermal route. The uterine volumes increased, and FSH and LH as indicators for
biological effectiveness were significantly lowered with replacement. The bone
mineral accretion rates tended to be higher, and the incidence of chronic
lung disease tended to be lower (0% vs. 29%; P = 0.097). E2 and P replacement via iv and transepidermal routes is capable of maintaining plasma levels as high as those in utero with
biological effectiveness. Trends toward improved postnatal bone
mineral accretion and less chronic
lung disease were found with the
hormone replacement. Further and more extensive studies are warranted to address the role of this new approach in the care of extremely premature infants.