Steady State Maternal-Fetal Leucine Enrichments in Normal and Intrauterine Growth-Restricted Pregnancies

Abstract

The aim of this study was to compare the fetal/maternal (F/M) leucine-enrichment ratio in normal (AGA) and intrauterine growth-restricted (IUGR) pregnancies at the time of fetal blood sampling (FBS). A maternal primed-constant infusion of L-[1-13C]-leucine was given in six AGA and 14 IUGR pregnancies, divided into three groups according to the pulsatility index (PI) of the umbilical artery and to fetal heart rate (FHR): group 1 (normal FHR and PI, four cases); group 2 (normal FHR and abnormal PI, five cases); and group 3 (abnormal FHR and PI, five cases). Maternal arterialized samples were taken at time zero and every 20 min for 125+/-7 min. Umbilical venous samples were obtained after 114+/-42 min of infusion. Under steady state conditions, there was a significant linear relationship between maternal leucine disposal rate and maternal leucine concentration. The comparison of fetal to maternal leucine enrichment showed a progressive dilution of the fetal enrichment relative to the mother between AGA and IUGR of group 1 (0.89 versus 0.78, p < 0.02), group 2 (0.71, p < 0.001), and group 3 (0.62, p < 0.001), and also among the three IUGR groups. The F/M leucine molar percent enrichment (MPE) ratio showed a positive correlation with the umbilical venous oxygen content and an inverse correlation with fetal lactate concentration. We conclude that the dilution in the fetal/maternal leucine-enrichment ratio correlates with the severity of growth restriction and reflects decreased transplacental leucine flux and/or increased protein breakdown within the fetoplacental compartments.

SNAT2 expression and regulation in human growth-restricted placentas

“…Previous in vivo studies measured by stable isotope tracers found decreased essential amino acid placental transport rates (5,6), and in vitro experiments confirmed reduced activity of placental amino acid transport systems (10,11) in IUGR and small-for-gestational-age pregnancies as compared with normal pregnancies.…”

“…r educed oxygen and nutrient placental delivery has been clearly demonstrated in intrauterine growth-restricted (IUGR) pregnancies (1)(2)(3)(4)(5)(6)(7). Amino acids are needed during fetal growth for protein synthesis and also for energy production, supplying 20-40% of the fetal-placental unit energy requirements (8).…”

High protein intake in neonatal period induces glomerular hypertrophy and sclerosis in adulthood in rats born with IUGR

“…In the industrialized world, alterations in placental blood flow and preeclampsia are leading causes of IUGR so that IUGR due to maternal protein diet restriction may not be relevant. Recent studies, however, suggest that (i) both settings share some striking similarities, since impaired maternal-fetal amino-acid transfer has been observed in human IUGR of vascular origin and (ii) impairment in the placental transport of amino acids has been found precede growth alterations in a rat model of IUGR induced by protein diet restriction (36)(37)(38), implying decreased amino acid transport may be a cause, rather than a consequence, of IUGR in that model. Such evidence therefore argues for the potential relevance of the experimental model used in this study for human IUGR.…”

Lactate detection in the brain of growth-restricted fetuses with magnetic resonance spectroscopy

“…30 IUGR is a heterogeneous condition, associated with a specific placental phenotype and with different levels of severity. 31 We have previously shown that a definition of IUGR based on a reduction of growth rate of the abdominal circumference is able to identify fetuses that experience a significant reduction in nutrients delivery and utilization, 32,33 although not invariably hypoxemic and lactacidemic. 10 Moreover, whereas redistribution of blood flows with brain sparing occurs, preliminary data now suggest that the fetus adapts to an inadequate environment also with hypometabolism, reducing oxygen consumption on a per-kilogram basis.…”