We report the cross-sectional pattern of first day urinary epidermal growth factor/creatinine (EGF/Cr) levels in 159 appropriate for gestational age infants born at 26-41 weeks gestation. EGF/Cr levels rose significantly earlier in female infants than levels in male infants. In female infants levels were similar to term levels beginning at 30-32 weeks. Mean EGF/Cr levels in male infants were similar to term values beginning at 32-34 weeks. We could not demonstrate any influence from acute perinatal events on EGF/Cr levels. In a subset of 28 infants, a weekly longitudinal study of urinary EGF/Cr levels was undertaken. The urinary EGF/Cr pattern correlated significantly with both corrected gestational and postnatal ages. A significant change in the EGF/Cr pattern was observed at a corrected gestational age of 32 weeks and at 4 weeks postnatal age. There was no significant difference in EGF/Cr levels between males and females. Our results demonstrated a significant difference in first day urinary EGF/Cr levels between female and male preterm infants during the early third trimester. This difference was seen at a time in gestation when other gender-specific maturational and growth differences are noted. When infants born at less than 32 weeks gestational age were followed longitudinally, the urinary EGF/Cr pattern, when expressed by corrected gestational age, was significantly modified from that in the cross-sectional study.

Fetal (20-21 day gestation) and neonatal (less than 5-day-old) rat islets were isolated from the glucagon-rich (dorsal) and glucagon-poor (ventral) pancreatic regions. After 1 or 2 wk in culture, groups of islets from each region were transferred to culture dishes containing Krebs-Ringer bicarbonate buffer with low (2.4 mM) and high (16.7 mM) glucose plus aminophylline. After 2 wk in culture, insulin released into medium was higher than after 1 wk, and more so if the islets originated from dorsal tissue (P less than .01). Glucagon release in response to alanine (10 mM) stimulation was also significantly higher in dorsal than in ventral islets (6.38 +/- 1.98 vs. 1.49 +/- 0.89 pg X islet-1 X h-1, respectively; P less than .02). Coincident with higher insulin and glucagon release, islet yield was greater in tissue from the dorsal neonatal pancreas than from that obtained in the fetal and neonatal ventral pancreas [range: dorsal, 131-180 (median, 153), vs. ventral, 53-127 (median, 84), islets obtained on day 5 of culture]. Neonatal islets of dorsal origin were transplanted intrasplenically (500-3000 islets) to streptozocin-induced diabetic inbred Lewis rats. Only rats receiving greater than 2500 islets were cured by transplantation. These experiments show that dorsal fetal islets secrete more insulin than do ventral islets and that islet yield is higher when islets are isolated from dorsal rather than from ventral perinatal pancreatic tissue. Despite their in vitro behavior, more neonatal dorsal islets are required to cure experimental diabetes than are reported with adult islets.

We have previously demonstrated that changes in urinary epidermal growth factor/creatinine ratios relate to gestational age and gender. It is unclear what controls this developmental pattern although chronic renal disease and thyroid aberrations have significant effects on epidermal growth factor and creatinine excretion in childhood and in adults. Therefore, we chose to explore the effects of these disease states on epidermal growth factor excretion during the perinatal time period. We collected urine samples from 8 infants with congenital renal disease and 45 infants with low T4 and normal TSH values who 'failed' the newborn screen.In addition, 2 infants with hypothyroidism and 2 infants with neonatal Grave's disease had urine samples examined. Values were compared with the epidermal growth factor and creatinine excretion from 190 infants. We demonstrated that epidermal growth factor excretion increased earlier in gestation than does creatinine excretion. In infants with renal disease or hypothyroidism, epidermal growth factor excretion was decreased while hyperthyroidism enhanced excretion. Epidermal growth factor excretion increased with relief of an obstruction but still remained low and creatinine excretion was unchanged. We confirm that in preterm infants as in childhood there are similar effects of thyroid and renal diseases on epidermal growth factor excretion.Little is known about concentrations of epidermal growth factor (EGF) in body fluids or tissues dur¬ ing human perinatal development although EGF is felt to be involved in many fetal maturational events (1-2). Evans et al. (3) demonstrated a signi¬ ficant increase in EGF excretion with gestation but did not explore the acute effects of delivery, gen¬ der nor creatinine changes on the EGF/creatinine ratio. We have demonstrated that urinary EGF concentrations in appropriate for gestational age premature infants significantly increase from 26 weeks postconceptional age, with female infants increasing their values earlier than seen in male in¬ fants (4). No acute affects from delivery were noted. The role of changes in creatinine excretion on this pattern was not described.On the basis of findings in children and adults, there are two groups of newborns which might be expected to have aberrations in their urinary EGF excretion, as well as creatinine excretion. The first group includes infants with chronic renal failure. Chronic renal failure is associated with a marked decrease in EGF levels in the child or adult (5). In this group, renal function does not improve so the effect of improvement of function on EGF values or the potential role of EGF in the improvement cannot be studied.A second group known to have alterations in EGF excretion are those with thyroid abnor¬ malities (6). Hypothyroid adults have decreased urinary EGF values and in the mouse, thyroid hor¬ mone concentrations directly alter EGF levels in the submandibular gland (7) as well as the urinary concentrations (8). Also, creatinine excretion is in¬ creased with hyperthyroidism (9) and...

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