Review Article

Metabolomics of Pregnancy Complications: Emerging Application of Maternal Hair

Table 2

Examples of metabolomic studies associated with FGR/SGA.

Sample specimenParticipants (n)OutcomesAnalytical platformsMetabolitesStatistical analysisReferences

Cord blood: serum43 (22 IUGR)IUGR, AGA (appropriate for gest. Age)LC-HRMS (orbitrap)Phenylalanine, tryptophan, and glutamate to discriminate between IUGR and AGAP<0.05, ROC curve: sensitivity between 91-100% and specificity between 85-89%[54]
Fetal rabbit brain tissueLiving: 9 (4IUGR)
Stillborn: 7 (6 IUGR)
IUGR, controlLC-QTOF-MSN-acetylaspartylglutamic acid (NAAG), N-acetylaspartate (NAA), ornithine, L-lysine, asparagine, histidine, and leucine intermediate 2-keto-isovalerate, succinate, pantothenate, malondialdehyde and 3-nitrotyrosine, purine, 3,4-dihydroxybutyric acid, nucleotide GMP, docosahexaenoic acid (DHA), palmitoleic acid and oleic acidP<0.05[46]
Urine (end of the first trimester)464 (36 FGR, 19 SGA)FGR, SGA, ControlsNMRsignificant association FGR with decreased levels of acetate, formate, tyrosine and trimethylamine in urine adjusted for education, maternal age, parity, smoking during pregnancy; SGA was associated with leucine and N-acetyl neuraminic acid95% confi.int., AUC for FGR: 63.7-66.3%[45]
Urine of IUGR newborns56 (26 IUGR)IUGR, controlsNMRDiscrimination between IUGR and control neonates by myo-inositol, sarcosine, creatine and creatinine/[177]
(a) cord plasma
(b) early pregnancy maternal plasma
(a) 14 (8 SGA)
(b) 340 (73 SGA)
SGA, controlUPLC-MSPregnanediol-3-glucuronide OR 3alpha,20alpha-dihydroxy-5beta-pregnane 3-glucuronide, LysoPC(16:1) OR Cervonyl carnitine,6-hydroxysphingosine OR (4OH,8Z,t18:1) OR 3b-Allotetrahydrocortisol OR 15-methyl-15-PGD2 OR 15R-PGE2 methyl ester, Leucyl-leucyl-norleucine OR Sphingosine 1-phosphate, Cervonyl carnitine AND/OR 1R,25-dihydroxy-18-oxocholecalciferol, 17-[(Benzylamino)methyl]estra-1,3,5(10)-triene-3,17beta-diol, PC, phosphocholine; PGD, Prostaglandin D; PGE, prostaglandin E. significant different between SGA and controls in both studies associated with cord plasma and week 15 plasmaP<0.05, robust predictive model of 19 metabolites of presymptomatic SGA: AUC of 0.9[47]