Elevated cardiac troponin I (cTnI), a myocardial damage biomarker, has been reported in cord blood of neonates delivered vaginally or by cesarean section. While the neonatal peak likely reflects the physiological adjustment to extrauterine life, a better understanding of serial prepartum changes is required to determine physiological causes of fetal cTnI release. METHODS We longitudinally sampled eight healthy lambs (20 days before spontaneous birth to 5 days postnatal), and from three fetuses receiving intravenous IGF-1. Samples were collected into heparin, and the plasma was stored at -80ºC for later determination of high-sensitivity (hs) cTnI levels (BeckmanCoulter UniCel DxI Access IA; log transformed detection limit=0.30, quantification limit=0.78, 99th%ile=1.78). Positive and negative control samples were drawn from an adult ewe during a terminal experiment (myocardial ischemia) and similarly assessed. hs-cTnI data were log transformed from ng/L. RESULTS Log(hs-cTnI) was 1.47±0.30 (mean±SD) at 20 days before birth and declined to 1.02±0.65 in fetuses 12±4 hour before birth (P<0.0001, R2=0.7869). Birth stimulated a delayed, transient peak in hs-cTnI (P=0.0058). Newborn (43±19 min postnatal) levels were 1.39±0.40 (P=0.0650 vs. fetus on day of birth) and 2.14±0.63 the day after birth (P=0.0331 vs. newborn). The second day after birth, levels declined to 1.65±0.48 (P=0.0238 vs. day 1). IGF-1 infusion increased hs-cTnI levels 25-50% over baseline (P=0.0252, R2=0.9938). Baseline adult ewe log(hs-cTnI) was below the limit of detection; three hours following coronary artery ligation, levels were 3.21. CONCLUSIONS We newly report that fetal hs-cTnI levels decline concomitant with reduced proliferation of cardiomyocytes towards term.