Table 4 Chemical identification of the metabolic features associated with phthalate exposure and NICU Net Neurobehavioral Scale (NNNS) outcome in the meet-in-the-middle analysis at visit 1 (n = 81) and visit 2 (n = 71) at p < 0.05 using generalized linear models
From: Impact of prenatal phthalate exposure on newborn metabolome and infant neurodevelopment
m/z | rt | Ontology level* | Metabolite | Exposure | Association with exposure (β) | Outcome | Association with outcome (β) | Pathways | Biological function |
|---|---|---|---|---|---|---|---|---|---|
Visit 1 (8–14 weeks) n = 81 | |||||||||
211.0845 | 2.84 | OL2b | 2-amino-3-(4-hydroxy-3-methoxyphenyl)propanoic acid | MBP | 0.0050 | Arousal | 0.1241 | Pharmaceutical (foodome) | Not enough information |
176.095 | 2.07 | OL1, OL2a | Cotinine, Serotonin | MECPP, MEHP, \(\Sigma\)DEHP | 0.0201, 0.0503, 2.036 | Arousal | −0.3115 | Biomarker (environmental) Tryptophan metabolism (endogenous) | Cotinine is a biomarker for tobacco use which can impact the nervous system33 Serotonin is a neurotransmitter28 |
235.0878 | 5.17 | OL2b | Acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine | MEP | −0.0002 | Arousal, Attention | −0.0873, −0.0929 | Biomarker (environmental) | Biomarker for tobacco use can impact the nervous system33,34 |
173.048 | 2.38 | OL2b | Quinaldic acid | MiBP | 0.0034 | Arousal | −0.0965 | Tryptophan metabolism (endogenous) | Not enough information |
196.074 | 8.59 | OL2a | 3,4,5-trimethoxybenzaldehyde | MiBP | −0.0021 | Arousal | 0.0655 | Pharmaceutical (foodome) | Not enough information |
416.329 | 15.04 | OL2b | Calcitriol | MBP | −0.0021 | Attention | −0.0484 | Steroid biosynthesis (endogenous) | Increases the amount of calcium in the body83 |
172.146 | 12.59 | OL2a | Decanoic acid | MEP | −0.0037 | Attention | −0.7346 | Fatty acid (endogenous) | Reduces oxidative stress in neuroblastoma cells84 |
194.08 | 5.94 | OL1 | Caffeine | MEP | 0.0001 | Attention | 0.0460 | Caffeine metabolism (drug) | Not enough information |
355.1936 | 15.44 | OL2b | JWH-019 | MEP | −0.0004 | Attention | −0.1770 | Biomarker (environmental) | Synthetic cannabinoid85 |
284.076 | 3.23 | OL1 | Xanthosine | MiBP | −0.0030 | Attention | 0.0736 | Purine metabolism (endogenous) | Involved in the synthesis and degradation of nucleic acids during rapid DNA/RNA turnover86 |
278.1518 | 14.36 | OL2b | Monoethylhexyl phthalic acid, Mono-n-octyl phthalate | MiBP | −0.0050 | Attention | −0.1130 | Biomarkers (environmental) | |
186.1256 | 10.1 | OL2a | 10-hydroxy-2-decenoic acid | MiBP | 0.0019 | Attention | 0.0486 | Fatty acid (endogenous) | Not enough information |
Visit 2 (24–30 weeks) n = 71 | |||||||||
105.043 | 0.57 | OL2b | Serine | MEHP, MiBP | −0.0222, −0.0051 | Attention | 0.0649 | Glycine, serine and threonine metabolism (endogenous) | Neurotransmitter precursor23 |
165.079 | 3.31 | OL2a | Phenylalanine | MEHP | −0.0209 | Attention | −0.0228 | Phenylalanine metabolism (endogenous) | Found in high levels in breastmilk and is a neurotransmitter precursor30 |
173.105 | 6.67 | OL2b | Acetylleucine, Hexanoyl Glycine | MEHHP, \(\Sigma\)DEHP | 0.0209, 1.9220 | Arousal | −0.2026 | Valine, leucine and isoleucine metabolism (endogenous) | Decreased neural inflammation in mouse models81 |
176.095 | 2.56 | OL1, OL2a | Cotinine, Serotonin | MiBP | −0.0188 | Arousal | −0.4044 | Biomarker (environmental) Tryptophan metabolism (endogenous) | Cotinine is a biomarker for tobacco use which can impact the nervous system33 Serotonin is a neurotransmitter28 |
179.0946 | 10.72 | OL2a | Propham | MiBP | 0.0022 | Attention | −0.0519 | Pesticide (environmental) | Not enough information |
180.0786 | 10.35 | OL2a | 4-hydroxy-3-methoxycinnamic alcohol | MiBP | 0.0022 | Attention | −0.0519 | Metabolite from fruits and vegetables (foodome) | Beneficial to gut microbiota and lipid metabolism89 |
181.074 | 1.56 | OL2a | Tyrosine | MEP | −0.0002 | Attention | −0.0608 | Tyrosine metabolism (endogenous) | Thyroid hormone; low level associated with increase illness and neurodevelopmental issues in newborns25 |
183.0895 | 0.77 | OL2b | Epinephrine | MBP | 0.0013 | Attention | −0.0427 | Tyrosine metabolism (endogenous) | Hormone and neurotransmitter90 |
186.1256 | 10.1 | OL2a | 10-hydroxy-2-decenoic acid | MBP | −0.0021 | Attention | 0.0629 | Fatty acid (endogenous) | Not enough information |
193.0739 | 7.21 | OL2a | 3-Methylhippuric acid | MEP | 0.0003 | Arousal | −0.1245 | Urinary metabolite (environmental) | A normal urine metabolite increased by consumption of phenolic compounds91 |
220.085 | 2.72 | OL2a | 5-Hydrotryptophan | MBP | −0.0017 | Arousal | −0.0543 | Tryptophan metabolism (endogenous) | Serotonin precursor29 |
229.0463 | 5.43 | OL1 | Flonicamid | MBP, MECPP, MEHHP, MEOHP, MEHP, MiBP, \(\Sigma\)DEHP | 0.0051, 0.0171, 0. 0210, 0.0277, 0.0343, 0.0077, 2.0323 | Arousal | −0.1524 | Pesticide (environmental) | Not enough information |
233.072 | 4.58 | OL2a | (R)-N-Acetyl-S-(1-(hydroxymethyl)-2-propen-1-yl)-L-cysteine | MECPP, MEHHP, MEOHP, \(\Sigma\)DEHP | −0.0105, −0.0124, −0.0177, −1.1830 | Arousal | −0.1781 | Acrylamide metabolite (environmental) | Acrylamide is classified as a possible human carcinogen; found in cigarettes or processed foods32 |
330.2559 | 16.54 | OL2a | Docosapentaenoic acid | MEP | −0.0004 | Arousal | 0.1572 | Fatty acid (endogenous) | Anti-inflammatory; Found in high concentrations in breastmilk74 |
376.2977 | 15.66 | OL2a | Lithocholic acid | MBP | 0.0036 | Attention | −0.1203 | Bile acid biosynthesis (endogenous) | Displays anti-neoplastic and anti-carcinogenic properties92 |
400.3341 | 16.1 | OL2b | Calcifediol, 7-Ketocholesterol | MBzP | 0.0297 | Attention | 0.0725 | Steroid biosynthesis (endogenous) | Increases the amount of calcium in the body83 Oxidation product of cholesterol93 |
406.2719 | 13.08 | OL1 | 7 & 12-Ketochenodeoxycholic acid | MBP, MiBP | −0.0101, −0.0038 | Attention | 0.4866 | Bile acid biosynthesis (endogenous) | Not enough information |
408.2876 | 14.13 | OL2b | Cholic acid | MBP, MEHP, MiBP | 0.0011, 0.0067, 0.0015 | Attention | −0.0228 | Bile acid biosynthesis (endogenous) | Not enough information |
