Early Human Development, 29 (1992) 183-186 Elsevier Scientific Publishers Ireland Ltd.

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Fetal amino acids in normal pregnancies and in pregnancies complicated by intrauterine growth retardation I. Cetina, A.M. Marconia, C. Corbettab, A. Lanfranchia, A.M. Baggiania,F.C. BattagliaCand G. Pardi” “Clinica Ostetrico-Ginecologica. Universitk di Milano, Ospedale San Paolo, via A. di Rudini 8, 20142 Milano. bLuboratorio di Malattie Metaboliche. ICP, via Commend0 12, 20122 Milan0 (Italy) and ‘Division of Perinatal Medicine, UCHSC, 8200 E. Ninth Ave., 80262 Denver, CO, (USA)

Summary Plasma amino acid concentrations were measured in normal (AGA) and intrauterine growth retarded (IUGR) percutaneous umbilical blood sampling (PUBS) performed for prenatal diagnosis or at elective cesarean section. IUGR fetuses present significantly lower concentrations of most amino acids, with a significant reduction of the umbilical veno-arterial difference for total o-amino nitrogen. These findinigs are present early in grwoth retarded fetuses and may be potentially responsible for the growth retardation. Key words: intrauterine growth retardation; blood sampling (PUBS)

amino acids; percutaneous umbilical

Introduction During intrauterine life, the fetus receives its substrate supply through the umbilical circulation. The umbilical uptake of amino acids has been measured in chronically catheterized fetal lambs [ 11. There is a significant uptake of most neutral and basic amino acids, with a significant release of glutamic acid and serine from the fetus to the placenta. The uptake of amino acids by the fetus far exceeds the rate needed for protein synthesis, calculated from fetal accretion data [2]. This finding, together with the finding of a high rate of urea production by the fetus (31, has sugCorrespondence lo: I. Cetin, Clinica Ostetrico-Ginecologica, via A. di Rudini 8, 20142 Milano, Italy.

Universiki di Milano, Ospedale San Paolo,

0378-3782/92/$05.00 0 1992 Elsevier Scientific Publishers Ireland Ltd. Printed and Published in Ireland

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gested that amino acids are utilized during intrauterine life for oxidation purposes also. Recently, the availability of safe techniques for sampling fetal cord blood in utero, has made possible the study of fetal amino acid concentrations at different gestational ages. By this technique, umbilical venous blood is sampled under ultrasound visualization of the cord. Studies in normal (AGA) pregnancies In normal pregnancies, samples are obtained by PUBS (percutaneous umbilical blood sampling) during the II trimester for prenatal diagnosis of congenital diseases. More recently indications for fetal blood sampling have been extended to the third trimester in cases of suspected isoRh or maternal thrombocytopenia. It has long been known that amino acid concentrations in the fetus at term are higher than in the mother 141. This has been confirmed also in fetuses at mid gestation. Figure 1 presents plasma amino acid concentrations in maternal arterialized and in umbilical venous blood of normal fetuses sampled between 18 and 25 weeks for prenatal diagnosis. Concentrations are significantly higher in the fetus than in the mother. Amino acids are transported from the mother to the fetus by active transport systems. However, for the non-essential amino acids there is also the possibility of neo-synthesis within the fetus or the placenta. Veno-arterial amino acid concentration differences can be measured at cesarean section in normal pregnancies [5]. For most amino acids significantly positive differences were found at term gestation. Glutamic acid was released from the fetus to the placenta.

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ILE THRPHEMETLYS

hiAT.AR'IERY

q

HIS ARGGLNALAGLYSERTYRORNTAUASPGLUPRO

UMB.VElN

Fig. 1. Umbilical venous and maternal arterialized plasma amino acid concentrations in AGA fetuses sampled between 18 and 25 weeks gestation.

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Fig. 2. Umbilical veno-arterial difference for total a-amino nitrogen in AGA and IUGR fetuses sampled at elective cesarean section performed between 37 and 40 weeks gestation.

Studies in intrauterine growth retarded (IUGR) pregnancies Fetal blood sampling is performed in IUGR pregnancies for assessment of fetal well-being. This allows the study of fetal amino acid concentrations in IUGR fetuses of different gestational ages and also when parameters of oxygenation and acid-base balance are still normal. We also studied IUGR fetuses at cesarean section, in order to study whether these fetuses would present a reduction of amino acid uptake. Therefore, for this comparison we only considered those IUGR fetuses that were delivered at term, so that we could compare them to normal fetuses of the same gestational age. Fetal amino acid concentrations are significantly reduced in IUGR compared to AGA of both II and III trimesters. In particular, IUGR fetuses present significantly lower concentrations of total o-amino nitrogen and of the sum of the essential amino acids. IUGR fetuses present different fetal-maternal relationships and significantly lower fetal/maternal ratios from those found in AGA fetuses for most of the essential amino acids. The three branched chain amino acids valine, leucine and isoleucine were found to be particularly reduced in IUGR fetuses. These amino acids share a common transport system, system L. Studies in vitro have shown differences in placental transport systems of normal and IUGR placentas [6]. Therefore a reduction in umbilical concentrations can be due to an altered placental transport. The differences between normal and growth retarded fetuses become even more striking when we look at the umbilical venous-arterial differences. While in normal fetuses most amino acids present significantly positive amino acid differences, this is not true for IUGR fetuses and for some amino acids there is a negative mean value. This becomes most evident when looking at total N, whose umbilical difference is not significantly positive in IUGR fetuses, as shown in Fig. 2.

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Conclusions These results show that IUGR fetuses sampled in utero present significantly lower concentrations of most amino acids with a striking change in fetal-maternal relationships. Moreover, IUGR fetuses present significantly lower umbilical veno-arterial concentration differences of most essential amino acids and of total o-amino nitrogen, potentially responsible for the intrauterine growth retardation. These differences can be related to both alterations in placental transfer and changes in fetal and placental amino acid utilization. We speculate that further understanding of the metabolic differences found in IUGR fetuses will help in the future treatment, eventually by nutritional supplementation, of the growth retarded fetus. References Lemons, J.A, Adcock, E.W. III., Jones, M.D., Jr., Naughton, M.A., Meschia, G. and Battaglia, F.C. (1976): Umbilical uptake of amino acids in the unstressed fetal lamb. J. Clin. Invest., 58, 1428-1434. Battaglia, F.C. and Meschia, G. (1986): Fetal and placental metabolism. Part II. Amino acids and lipids. In: An Introduction to Fetal Physiology, pp. 100-135. Editors: F.C. Battaglia and G. Meschia. Academic Press, Orlando, Florida. Gresham, E.L., James, E.J., Raye, J.R., Battaglia, F.C., Makowski, E.L. and Meschia, G. (1972): Production and excretion of urea by the fetal lamb. Pediatrics, 50, 372-379. Cetin, I., Corbetta, C., Sereni, L.P., Marconi, A.M., Boxzetti, P., Pardi, G. and Battaglia, F.C. (1990): Umbilical amino acid concentrations in normal and growth retarded fetuses sampled in utero by cordocentesis. Am. J. Obstet. Gynecol., 162, 253-261. Cetin, I., Marconi, A.M., Bozxetti, P., Sereni, L.P., Corbetta, C., Pardi, G. and Battaglia, F.C. (1988): Umbilical amino acid concentrations in appropriate and small for gestational age infants: a biochemical difference present in utero. Am. J. Obstet. Gynecol., 158, 120-126. Dicke, J.M. and Henderson, G.I. (1988): Placental amino acid uptake in normal and complicated pregnancies. Am. J. Med. Sci., 295, 223-227.

Fetal amino acids in normal pregnancies and in pregnancies complicated by intrauterine growth retardation.

Plasma amino acid concentrations were measured in normal (AGA) and intrauterine growth retarded (IUGR) percutaneous umbilical blood sampling (PUBS) pe...
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