Effects of postnatal estradiol and progesterone replacement in extremely preterm infants

The fetus is supplied from the placenta with estradiol (E-2) and progestero ne (P) in increasing amounts during gestation. After delivery of a prematur e infant, placental supply is disrupted, resulting in a rapid decrease in E -2 and P. Replacement of these placental hormones may restore intrauterine conditions and may be beneficial for bone mineral accretion, clinical cours e, 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 rando mized to receive E-2 and P replacement, aiming to maintain plasma levels eq ualing the intrauterine levels, or no replacement. The E-2 and P replacemen t was started iv and was followed by transepidermal administration for a to tal duration of 6 weeks. Repeated measurements included plasma levels of E- 2, P, FSH, and LH; uterine volume; calcium and phosphorus in spot urine spe cimens; and bone mineral accretion by single photon absorption densitometry . Further, the incidence of chronic lung disease and various clinical outco me data were recorded. The plasma levels of E-2 and P were within the intra uterine range with median replacements of 2.30 mg/kg day E-2 (1.13-6.23) an d 21.20 mg/kg.day P(11.23-27.36), iv. Three- and 6-fold higher doses of E-2 and P were needed via the transepidermal route. The uterine volumes increa sed, and FSH and LH as indicators for biological effectiveness were signifi cantly 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). E-2 and P replacement via iv and transepidermal rout es is capable of maintaining plasma levels as high as those in utero with b iological effectiveness. Trends toward improved postnatal bone mineral accr etion and less chronic lung disease were found with the hormone replacement . Further and more extensive studies are warranted to address the role of t his new approach in the care of extremely premature infants.