During pregnancy, 17beta-estradiol (E2) and progesterone (P) plasma concentrations increase up to 100-fold. The fetus is exposed to these increasing amounts of E2 and P. Within 1 d after delivery, E2 and P concentrations fall to nonpregnancy concentrations in the mother and the infant. Extremely premature infants are cut off from the placental supply of E2 and P at a very early developmental stage, and therefore they suffer from this deprivation for a longer period than infants born at term. Nothing is known about the consequences of this deprivation. The purpose of this study was to investigate how intrauterine concentrations of E2 and P could be maintained after birth. In 13 infants with a median gestational age of 26.4 wk (24.1-28.7), a phospholipid-stabilized soybean oil emulsion available for parenteral nutrition that contains different amounts of E2 and P was continuously administered, starting within the first postnatal hours. The supplementation was continued as long as venous access was indicated but not longer than 6 wk (median 20 d, 12-44). To maintain intrauterine plasma concentrations of 2000-6000 pg/mL E2 and 300-600 ng/mL P, 2.30 mg x kg(-1) x d(-1) E2 (1.13-3.42 mg x kg(-1) x d(-1)) and 21.20 mg x kg(-1) x d(-1) P (11.23-27.36 mg x kg(-1) x d(-1)) were needed. We conclude that supplementation of E2 and P to maintain intrauterine concentrations in extremely premature infants is possible intravenously. The infants in this study are enrolled in a randomized, controlled pilot study to evaluate the potential benefits of E2 and P supplementation.