Quantitative metabolic profiles of 2nd and 3rd trimester human amniotic fluid using (1)H HR-MAS spectroscopy.
OBJECTIVE
To establish and compare normative metabolite concentrations in 2nd and 3rd trimester human amniotic fluid samples in an effort to reveal metabolic biomarkers of fetal health and development.


METHODS
Twenty-one metabolite concentrations were compared between 2nd (15-27 weeks gestation, N = 23) and 3rd (29-39 weeks gestation, N = 27) trimester amniotic fluid samples using (1)H high resolution magic angle spinning (HR-MAS) spectroscopy. Data were acquired using the electronic reference to access in vivo concentrations method and quantified using a modified semi-parametric quantum estimation algorithm modified for high-resolution ex vivo data.


RESULTS
Sixteen of 21 metabolite concentrations differed significantly between 2nd and 3rd trimester groups. Betaine (0.00846+/-0.00206 mmol/kg vs. 0.0133+/-0.0058 mmol/kg, P < 0.002) and creatinine (0.0124+/-0.0058 mmol/kg vs. 0.247+/-0.011 mmol/kg, P < 0.001) concentrations increased significantly, while glucose (5.96+/-1.66 mmol/kg vs. 2.41+/-1.69 mmol/kg, P < 0.001), citrate (0.740+/-0.217 mmol/kg vs. 0.399+/-0.137 mmol/kg, P < 0.001), pyruvate (0.0659+/-0.0103 mmol/kg vs. 0.0299+/-0.286 mmol/kg, P < 0.001), and numerous amino acid (e.g. alanine, glutamate, isoleucine, leucine, lysine, and valine) concentrations decreased significantly with advancing gestation. A stepwise multiple linear regression model applied to 50 samples showed that gestational age can be accurately predicted using combinations of alanine, glucose and creatinine concentrations.


CONCLUSIONS
These results provide key normative data for 2nd and 3rd trimester amniotic fluid metabolite concentrations and provide the foundation for future development of magnetic resonance spectroscopy (MRS) biomarkers to evaluate fetal health and development.
Department of Radiology & Biomedical Imaging, University of California, 1600 Divisadero Street, Room C-250, Box 1667, San Francisco, CA 94115, USA. brad.cohn@ucsf.edu
Brad R
BR
Cohn
Bonnie N
BN
Joe
Shoujun
S
Zhao
John
J
Kornak
Vickie Y
VY
Zhang
Rahwa
R
Iman
John
J
Kurhanewicz
Kiarash
K
Vahidi
Jingwei
J
Yu
Aaron B
AB
Caughey
Mark G
MG
Swanson
D000328:Adult; D000409:Alanine / Q000378:metabolism; D000653:Amniotic Fluid / Q000378:metabolism*; D001622:Betaine / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D019343:Citric Acid / Q000378:metabolism; D003404:Creatinine / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D055442:Metabolome; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000378:metabolism*; D011263:Pregnancy Trimester, Third / Q000378:metabolism*; D019289:Pyruvic Acid / Q000378:metabolism; D055815:Young Adult
D015415:Biomarkers; D019343:Citric Acid; D001622:Betaine; D019289:Pyruvic Acid; D003404:Creatinine; D005947:Glucose; D000409:Alanine