Maternal Amino Acid Profiles to Distinguish Constitutionally Small versus Growth-Restricted Fetuses Defined by Doppler Ultrasound: A Pilot Study

Abstract

Objective Fetuses measuring below the 10th percentile for gestational age may be either constitutionally small for gestational age (SGA) or have pathologic fetal growth restriction (FGR). FGR is associated with adverse outcomes; however, identification of low-risk SGA cases is difficult. We performed a pilot study evaluating maternal markers of pathologic FGR, hypothesizing there are distinct amino acid signatures that might be used for diagnosis and development of new interventions. Study Design This was a cohort study of healthy women with sonographic fetal estimated fetal weight <5th percentile divided into two groups based upon umbilical artery (UmA) Doppler studies or uterine artery (UtA) Doppler studies. We collected maternal blood samples prior to delivery and used ion pair reverse phase liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry to assess 44 amino acids. Results Among 14 women included, five had abnormal UmA, and three had abnormal UtA Doppler results. Those with abnormal UmA showed elevated ornithine. Those with abnormal UtA had lower dimethylglycine, isoleucine, methionine, phenylalanine, and 1-methylhistidine. Conclusion We found several amino acids that might identify pregnancies affected by pathologic FGR. These findings support the feasibility of future larger studies to identify maternal metabolic approaches to accurately stratify risk for small fetuses.

Non-Targeted Metabolomic Study of Fetal Growth Restriction

“…When the concentration of amino acids is low, the downstream protein synthesis is reduced. The concentration of most amino acids in the umbilical artery and vein of FGR newborns is lower than that in healthy newborns [ 15 ], and the concentration of essential amino acids (such as valine, leucine, and isoleucine) in SGA fetuses is considerably lower [ 16 ]. Phenylalanine can promote the growth of malnourished children [ 17 ].…”

Cystathionine γ-lyase promotes estrogen-stimulated uterine artery blood flow via glutathione homeostasis

“…Amino acid concentration was measured after reaction with ninhydrin (Pickering) for 1 min at 570 nm with Chromeleon chromatographic software (Thermo Electron). To quantify 2-aminobutyrate, cystathionine, total and oxidized cysteine, dimethylglycine, glycine, total homocysteine, methionine, methylglycine, serine, and taurine, we performed capillary stable isotope dilution GC-MS on reduced samples using established methods [ 39 ]. The cysteine/cystine ratio was determined by dividing total (reduced) cysteine by oxidized cystine from assays of the same serum samples.…”

Metabolomics in Prenatal Medicine: A Review

“…Amino acid metabolism also appears to play a role in FGR, with several amino acids differing between the average for gestational age and FGR newborns (43,44) especially ornithine (45). A role for ornithine in fetal growth was also identified in maternal serum from pregnancies affected by extreme FGR (<5th %ile) and abnormal umbilical artery Dopplers (46). Correlations between ornithine and umbilical blood flow may be related to angiogenesis via polyamine pathways.…”