Review Article

Metabolomics of Pregnancy Complications: Emerging Application of Maternal Hair

Table 4

Examples of metabolomic studies associated with gestational diabetes mellitus.

Sample specimenParticipants (n)OutcomesAnalytical platformsMetabolitesStatistical analysisReferences

Plasma31 (18 GDM)GDM vs controlsLC-ESI-QqQ-MS/MS L-asparagine (Asn), L-valine (Val), and L-ornithine (Orn) were decreased and L-citrulline (Cit) was elevated in GDM cases compared to controlsP<0.05[178]
Serum (3rd trimester)22 (12 GDM)GDM vs controlsUPLC-QTOF-MS9 metabolites were observed with AUC>0.7 to diagnose GDM from healthy controls which are 1- methyladenosine, glucosamine, L-tyrosine, phosphorylcholine, L-lactic acid, 3-methylthiopropionic acid, lysoPC(16:1), L-2- hydroxyglutaric acid, and trans-3-octenedioic acidP<0.05[64]
Serum (16 weeks of gestation)358 (178 GDM)GDM vs controlsGC-MS17 metabolites: linoleic acid, oleic acid, myristic acid, d-galactose, d-sorbitol, o-phosphoco- lamine, l-alanine, l-valine, 5-hydroxy-l-tryptophan, l-phenylalanine-phenyl, l-serine, sarcosine, l-pyroglutamic acid, and l-mimosine, l-lactic acid, glycolic acid, fumaric acid, and urea expressed differentiation between GDM cases and controlsRegression analysis, these metabolites together with GDM risk factors (maternal age, family history, prepregnancy BMI, ferritin, CRP, hep- cidin, and total vitamin D) gave rise to an AUC of 0.87[179]
Plasma (24-27 weeks of gestation, at OGTT test)24 (9 GDM)GDM vs controls at OGTT testFIA-MS/MS and LC-MS for amino acids, acylcarnitines, sphingomyelins, phosphatidylcholines, hexose (glucose) and biogenic amines; Fatty acids analysis by GC-MSreference model complemented by a clinical model(BMI, AUC of glucose and insulin) gave rise to 8 metabolites C18:0 carnitine, PC aa C34:4, PC aa C36:4, PC aa C38:5, PC ae C36:4, PC ae C36:5, LPC C20:4 and arachidonic acid which showed differences between GDM cases and controlsP<0.01, reference model: 96.4% AUC and clinical model: 99.3% AUC[63]
Serum (fasting)192 (96 GDM)GDM vs controlsLC-MSanthranilic acid, alanine, glutamate, allantoin and serine were increased and creatinine decreased in GDM cases compared to controlsP<0.05[180]
Serum (20 weeks)48 (22 GDM)GDM vs controlsGC-MSItaconic acid with P=0.0003 was significantly increased in women who developed GDM later on during pregnancy compared to controls, cis-aconitate levels were also higher in GDM cases and verging on statistical difference (P=0.013)P<0.01[74]
Urine and plasma (Fasting)40 (20 GDM)GDM vs controlsLC-QTOF-MS(plasma), GC-Q/MS(plasma), CE-TOF/MS(urine)After ROC analysis metabolites with a ROC area >0.94 and has shown a discriminative ability by 25 lysoglycerophospholipids, arachidonic 20:4) and docosahexaenoic (22:6) acid methyl esters, and taurine-conjugated bile acids. Lipoxin was another lipid which showed a high discriminative power and associated with diabetic outcome ROC area>0.94[65]
Urine (8-20 gest. week, week 28+/-2, 10-16 weeks after pregnancy)609 (13% GDM)GDM vs controlsNMRSignificant increase of citrate levels associated with GDM severityP<0.05, R2>95%[181]