Subgroup analysis of included studies according to which metabolomics technique was applied
| Authors, year | Metabolomics technique | Maternal sample/storage temperature | Prediction model* | Targeted compounds | Coefficient of variation/limits of quantitation | Predictive compounds | Sensitivity /Specificity | AUC |
| Nuclear magnetic resonance | ||||||||
| Luthra et al, 201838 | 1H-NMR 1D NOESY with presaturation and homonuclear 2D J-resolved at 300 K Bruker 600 MHz Advance III HD spectrometer | Urine/−80°C | Targeted | Tyrosine, acetate, formate, trimethylamine | NA | None | ||
| Gas chromatography coupled to mass spectrometry | ||||||||
| Costet et al, 201231 | GC-MS Simple headspace SPME-capillary GC | Urine/−20°C | Targeted | Trichloroacetic acid | <5%/0.01 mg/L | None | 0.1/0.93 | |
| Sulek et al, 201418 | GC-MS Thermo Trace GC Ultra system coupled to ISQ mass selective detector Capillary GC column: Phenomenex ZB-1701 (30 m × 250 µm id × 0.15 µm with 5 m guard column) | Hair/−20°C | Untargeted | NA | NA | ↓ Lactate ↓ Levulinate ↑2-methyloctadecanoate ↑Tyrosine ↓ Margarate | 0.998 | |
| Delplancke et al, 201828 | GC-MS Agilent 7890B gas chromatograph, capillary column ZB-1701 (30 m × 250 µm id × 0.15 µm with 5 m guard column) 5977A mass spectrometer, electron impact ionisation | Hair/−20°C | Untargeted | NA | NA | ↑ Margaric acid ↑ Pentadecanoic acid ↑ Myristic acid‡ | 0.72 0.73 0.73 | |
| Liquid chromatography coupled to mass spectrometry | ||||||||
| Grandone et al, 200633 | LC-MS/MS triple quadrupole Applera API 3000, TurboIonSpray ionisation | Amniotic fluid/−80°C | Targeted | Homocysteine | Unclear | ↑Homocysteine (1.29 µM; 1.05–1.51 µM) | ||
| Horgan et al, 201117 | UPLC-MS/MS Thermo Fisher LTQ Orbitrap, ESI | Plasma/−80°C | Untargeted | NA | NA | Hexacosanedioic acid, diglyceride, lyso-phosphocholine, sphinganine 1-phosphate, sphingosine 1-phosphate§ | 0.90 | |
| Ertl et al, 201232 | HPLC-MS/MS Shimadzu Prominence HPLC system with a column Phenomenex Luna C8 3×50 mm; AbSciex API-5000 triple quadrupole, ESI | Serum/−80°C | Targeted | 25(OH)D2; 25(OH)D3 | 6.3%*, 6.6%† (D2); 6.5%*, 7.3%† (D3)/unclear | ↓25,OH,vitamin D (12.16 ng/mL; 8.09–20.54 ng/mL) | 0.72/0.45 | |
| Gernand et al, 201340 | LC-MS/MS | Serum/−20°C | Targeted | 25(OH)D2; 25(OH)D3 | 8.2%* (D2) 5.9%* (D3)/<1 ng/mL | None | 0.39/0.66 | |
| Choi et al, 201634 | HPLC-MS/MS Waters HPLC system, Applied Biosystems API-4000 MS/MS mass spectrometer | Serum/−20°C | Targeted | Methylmalonic acid; homocysteine | <10%*; <10%†/unclear | None | ||
| Kiely et al, 201635 | UPLC-MS/MS Waters Acquity UPLC system, Waters Triple Quadrupole TQD mass spectrometer | Serum/−80°C | Targeted | 25(OH)D2; 25(OH)D3; 3-epi-25(OH)D3 | <6%*; <5%†/0.57 ng/mL (D2); 0.26 ng/mL (D3), 0.41 ng/mL (epi-D3) | None | ||
| Ong et al, 201637 | LC-MS/MS Applied Biosystems Thermo Hypersil BDS C8 reverse-phase column | Plasma/unclear | Targeted | 25(OH)D2; 25(OH)D3 | ≤10.3%*,†/<1.6 ng/mL | None | 0.12/0.87 | |
| Wang et al, 201636 | LC-MS Agilent HPLC system, Applied Biosystems Sciex API-4000 triple quadrupole mass spectrometer | Serum/unclear | Targeted | PFOA; long-chain PFCA | 0.83–7.94%*; 1.57–24.7%†/0.07–0.45 ng/mL¶ | PFDeA (OR 3.14; 95% CI 1.07 to 9.19), PFUnDA (OR 1.83; 95% CI 1.01 to 3.32)** | ||
| Gong et al, 201841 | LC-MS/MS Shimadzu UK Limited UPLC system, ACE Excel 2 C18-PFP LC-column, Thermo Fisher Scientific Exactive Orbitrap mass spectrometer | Serum/unclear | Untargeted | NA | ↑N1,N12-diacetylspermine** | |||
| Morillon et al, 201842 | UPLC-MS/MS Waters Acquity UPLC system, Waters Synapt G2-S mass spectrometer | Urine/−80°C | Untargeted | NA | None | |||
| Others | ||||||||
| van Eijsden et al, 200839 | GC-FID Solid phase extraction SPE, capillary GC | Plasma/−80°C | Semitargeted, lipid extraction | Elaidic, linoleic, alfa-linolenic, eicosatetraenoic, EPA, DPA, DHA DGLA, AA, adrenic, and Osbond acids | ≤2%–22%†/unclear | ↓ Eicosatetraenoic acid (OR 1.5; 95% CI 1.07 to 2.11), ↓DPA (OR 1.49; 95% CI 1.06 to 2.1) | ||
*Intra-assay coefficients of variation.
†Interassay coefficients of variation.
‡These metabolites were found in second-trimester hair segments.
§And more 14 metabolites that could not be identified certain based on chromatographic peak and mass: phenylacetylglutamine or formyl-N-acetyl-5-methroxykynurenamine; leucyl-leucyl-norleucine or sphingosine 1-phosphate; cervonyl carnitine and/or 1-alpha,25-dihydroxy-18-oxocholecalciferol; (15Z)-tetracosenoic acid or 10,13-dimethyl-11-docosyne-10,13-diol or trans-selacholeic acid; pencosenoic acid or cyclohexyl acetate or octanoic acid or methyl-heptenoic acid or 4-hydroxy-2-octenal or DL-2-aminooctanoic acid or 3-amino-octanoic acid; hydroxybutyrate or hydroxy-methylpropanoate or methyl methoxyacetate; lysophosphocoline and phosphocoline (more than 10 hits); phosphocoline (more than 20 hits); phosphocoline or ubiquinone-8; acetylleucil-leucil-norleucinal or oleoylglycerone phosphate or LPA(0:0/18:2(9Z,12Z)) or 1-16:1lysoPE or phosphocoline(O-11:1(10E)/2:0) or (3 s)−3,4-Di-N-hexanoyloxybutyl-1-phosphocoline or N-(3-hydroxy-propyl) arachidonoyl amine or N-methyl N-(2-hydroxy-ethyl) arachidonoyl amine or similar; lysophosphocholine (16:1) or cervonyl carnitine; preganediol-3-glucuronide or 3-alpha,20-alpha-dihydroxy-5-beta-pregnane-3-glucuronide; 6-hydroxyshingosine or (4OH,8Z,t18:1) sphingosine or 15-methyl-15-prostaglandin D2 or 15-R-prostaglandin E2 methyl ester.
¶Values for all studied metabolites.
**Predictive compounds only for female babies.
AA, arachidonic acid;AUC, area under the receiver operating characteristic curve; DGLA, dihomo-gamma-linolenic acid; DHA, docosahexaenoic acid; DPA, docosapentaenoic acid; EPA, eicosapentaenoic acid; ESI, electrospray ionisation; FID, flame ionisation detection; GC-MS, gas chromatography coupled to mass spectrometry;1H-NMR, hydrogen nuclear magnetic resonance; HPLC, high performance liquid chromatography; LC-MS, liquid chromatography coupled to mass spectrometry; NA, not applicable; NOESY, nuclear Overhauser effect spectroscopy; PFCA, perfluorocarboxylic acid; PFDeA, perfluorodecanoic acid; PFOA, perfluorooctanoic acid; PFUnDA, perfluoroundecanoic acid; SPME, solid phase microextraction; UPLC, ultra-performance liquid chromatography.