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

Gauri Luthra, Ivan Vuckovic, A. Bangdiwala, H. Gray, J. B. Redmon, E. S. Barrett, S. Sathyanarayana, R. H.N. Nguyen, S. H. Swan, S. Zhang, P. Dzeja, S. I. Macura, K. S. Nair

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: 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. Methods: 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: http://www.audipog.net/courbes_morpho.php?langue=en ] 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Article number48
JournalBMC Pregnancy and Childbirth
Volume18
Issue number1
DOIs
StatePublished - Feb 8 2018

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Metabolome
Second Pregnancy Trimester
First Pregnancy Trimester
Fetal Development
Child Development
Case-Control Studies
formic acid
Metabolomics
Maternal Age
Third Pregnancy Trimester
Tyrosine
Acetates
Cohort Studies
Logistic Models
Urine
Pregnancy
Prenatal Care
Parity
Internet
Population

Keywords

  • Fetal growth restriction
  • NMR spectroscopy
  • Obstetrics

PubMed: MeSH publication types

  • Journal Article
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Cite this

First and second trimester urinary metabolic profiles and fetal growth restriction : An exploratory nested case-control study within the infant development and environment study. / Luthra, Gauri; Vuckovic, Ivan; Bangdiwala, A.; Gray, H.; Redmon, J. B.; Barrett, E. S.; Sathyanarayana, S.; Nguyen, R. H.N.; Swan, S. H.; Zhang, S.; Dzeja, P.; Macura, S. I.; Nair, K. S.

In: BMC Pregnancy and Childbirth, Vol. 18, No. 1, 48, 08.02.2018.

Research output: Contribution to journalArticle

Luthra, Gauri ; Vuckovic, Ivan ; Bangdiwala, A. ; Gray, H. ; Redmon, J. B. ; Barrett, E. S. ; Sathyanarayana, S. ; Nguyen, R. H.N. ; Swan, S. H. ; Zhang, S. ; Dzeja, P. ; Macura, S. I. ; Nair, K. S. / First and second trimester urinary metabolic profiles and fetal growth restriction : An exploratory nested case-control study within the infant development and environment study. In: BMC Pregnancy and Childbirth. 2018 ; Vol. 18, No. 1.
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abstract = "Background: 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. Methods: 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: http://www.audipog.net/courbes_morpho.php?langue=en ] 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. Results: 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. Conclusions: 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.",
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T2 - An exploratory nested case-control study within the infant development and environment study

AU - Luthra, Gauri

AU - Vuckovic, Ivan

AU - Bangdiwala, A.

AU - Gray, H.

AU - Redmon, J. B.

AU - Barrett, E. S.

AU - Sathyanarayana, S.

AU - Nguyen, R. H.N.

AU - Swan, S. H.

AU - Zhang, S.

AU - Dzeja, P.

AU - Macura, S. I.

AU - Nair, K. S.

PY - 2018/2/8

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N2 - Background: 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. Methods: 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: http://www.audipog.net/courbes_morpho.php?langue=en ] 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. Results: 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. Conclusions: 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.

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