ObjectTo 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.Materials and methodsTwenty-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 1H 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.ResultsSixteen 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.ConclusionThese 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.

Purpose To determine the intra- and interobserver reproducibility of human amniotic fluid metabolite concentration measurements (including potential markers of fetal lung maturity) detectable by MR spectroscopy. Materials and Methods 1H high-resolution magic angle spinning (HR-MAS) spectroscopy was performed at 11.7T on 23 third-trimester amniotic fluid samples. Samples were analyzed quantitatively using 3-(trimethylsilyl)propionic-2,2,3,3-d4 acid (TSP) as a reference. Four observers independently quantified eight metabolite regions (TSP, lactate doublet and quartet, alanine, citrate, creatinine, choline, and glucose) twice from anonymized, randomized spectra using a semiautomated software program. Results Excellent inter- and intraobserver reproducibility was found for all metabolites. Intraclass correlation as a measure of interobserver agreement for the four readers ranged from 0.654 to 0.995. A high correlation of 0.973 was seen for choline in particular, a major component of surfactant. Pearson correlation as a measure of intraobserver reproducibility ranged from 0.478 to 0.999. Conclusion Quantification of choline and other metabolite concentrations in amniotic fluid by high-resolution MR spectroscopy can be performed with high inter- and intraobserver reproducibility. Demonstration of reproducible metabolite concentration measurements is a critical first step in the search for biomarkers of fetal lung maturity.

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