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BMC Pregnancy Childbirth. 2018 Feb 8;18(1):48. doi: 10.1186/s12884-018-1674-8.

First and second trimester urinary metabolic profiles and fetal growth restriction: an exploratory nested case-control study within the infant development and environment study.

Author information

Department of Maternal Fetal Medicine, University of Minnesota, 606 24th Ave S #400, Minneapolis, MN, 55454, USA.
Nuclear Magnetic Resonance Facility, Mayo Clinic, Stabile SL-035, 200 First Street SW, Rochester, MN, 55905, USA.
Clinical and Translational Science Institute, University of Minnesota, 717 Delaware Street SE, Second Floor, Minneapolis, MN, 55414, USA.
Department of Maternal Fetal Medicine, University of Minnesota, 606 24th Ave S #400, Minneapolis, MN, 55454, USA.
Division of Diabetes Endocrinology and Metabolism, 516 Delaware Street SE, MMC 101, Minneapolis, MN, 55455, USA.
Environmental and Occupational Health Sciences Institute, Rutgers School of Public Health, 170 Frelinghuysen Rd, Piscataway, NJ, 08854, USA.
Department of Pediatrics, University of Washington Seattle Children's Research Institute, CW8-6, PO Box 5371, Seattle, WA, 98145-5005, USA.
Division of Epidemiology and Community Health, University of Minnesota, 1300 S. 2nd Street, Suite 300, Minneapolis, MN, 55454, USA.
Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY, 10029, USA.
Metabolomics Core, Mayo Clinic Hospital, Saint Mary's Campus, Alfred Building, Fifth Floor, Room 417, 200 First St. SW, Rochester, MN, 55905, USA.



Routine prenatal care fails to identify a large proportion of women at risk of fetal growth restriction (FGR). Metabolomics, the comprehensive analysis of low molecular weight molecules (metabolites) in biological samples, can provide new and earlier biomarkers of prenatal health. Recent research has suggested possible predictive first trimester urine metabolites correlating to fetal growth restriction in the third trimester. Our objective in this current study was to examine urinary metabolic profiles in the first and second trimester of pregnancy in relation to third trimester FGR in a US population from a large, multi-center cohort study of healthy pregnant women.


We conducted a nested case-control study within The Infant Development and the Environment Study (TIDES), a population-based multi-center pregnancy cohort study. We identified 53 cases of FGR based on the AUDIPOG [Neonatal growth - AUDIPOG [Internet]. [cited 29 Nov 2016]. Available from: ] formula for birthweight percentile considering maternal height, age, and prenatal weight, as well as infant sex, gestational age, and birth rank. Cases were matched to 106 controls based on study site, maternal age (± 2 years), parity, and infant sex. NMR spectroscopy was used to assess concentrations of four urinary metabolites that have been previously associated with FGR (tyrosine, acetate, formate, and trimethylamine) in first and second trimester urine samples. We fit multivariate conditional logistic regression models to estimate the odds of FGR in relation to urinary concentrations of these individual metabolites in the first and second trimesters. Exploratory analyses of custom binned spectroscopy results were run to consider other potentially related metabolites.


We found no significant association between the relative concentrations of each of the four metabolites and odds of FGR. Exploratory analyses did not reveal any significant differences in urinary metabolic profiles. Compared with controls, cases delivered earlier (38.6 vs 39.8, p < 0.001), and had lower birthweights (2527 g vs 3471 g, p < 0.001). Maternal BMI was similar between cases and controls.


First and second trimester concentrations of urinary metabolites (acetate, formate, trimethylamine and tyrosine) did not predict FGR. This inconsistency with previous studies highlights the need for more rigorous investigation and data collection in this area before metabolomics can be clinically applied to obstetrics.


Fetal growth restriction; NMR spectroscopy; Obstetrics

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