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A Maternal Serum Metabolite Ratio Predicts Large for Gestational Age Infants at Term: A Prospective Cohort Study.

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Peer-reviewed

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Article

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Abstract

CONTEXT: Excessive birth weight is associated with maternal and neonatal complications. However, ultrasonically estimated large for gestational age (LGA; >90th percentile) predicts these complications poorly. OBJECTIVE: To determine whether a maternal serum metabolite ratio developed for fetal growth restriction (FGR) is predictive of birth weight across the whole range, including LGA at birth. METHODS: Metabolites were measured using ultrahigh performance liquid chromatography-tandem mass spectroscopy. The 4-metabolite ratio was previously derived from an analysis of FGR cases and a random subcohort from the Pregnancy Outcome Prediction study. Here, we evaluated its relationship at 36 weeks of gestational age (wkGA) with birth weight in the subcohort (n = 281). External validation in the Born in Bradford (BiB) study (n = 2366) used the metabolite ratio at 24 to 28 wkGA. RESULTS: The inverse of the metabolite ratio at 36 wkGA predicted LGA at term [the area under the receiver operating characteristic curve (AUROCC) = 0.82, 95% CI 0.73 to 0.91, P = 6.7 × 10-5]. The ratio was also inversely associated with birth weight z score (linear regression, beta = -0.29 SD, P = 2.1 × 10-8). Analysis in the BiB cohort confirmed that the ratio at 24 to 28 wkGA predicted LGA (AUROCC = 0.60, 95% CI 0.54 to 0.67, P = 8.6 × 10-5) and was inversely associated with birth weight z score (beta = -0.12 SD, P = 1.3 × 10-9). CONCLUSIONS: A metabolite ratio which is strongly predictive of FGR is equally predictive of LGA birth weight and is inversely associated with birth weight across the whole range.

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Keywords

large for gestational age, macrosomia, metabolomics, prediction, pregnancy, Birth Weight, Cohort Studies, Female, Fetal Growth Retardation, Fetal Macrosomia, Gestational Age, Humans, Infant, Newborn, Pregnancy, Pregnancy Outcome, Prospective Studies

Journal Title

J Clin Endocrinol Metab

Conference Name

Journal ISSN

0021-972X
1945-7197

Volume Title

Publisher

The Endocrine Society
Sponsorship
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Medical Research Council (G1100221)
Medical Research Council (G1100221/1)
The work was supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (Women’s Health theme), the Medical Research Council (United Kingdom; 1100221 to G.C.S.S. and D.S.C.-J., MR/N024397/1 to D.A.L.), the Wellcome Trust (WT101597MA), National Institutes of Health (R01 DK10324), the European Research Council (669545), and the NIHR Biomedical Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol (Reproductive and Perinatal Health theme), which funds N.M.’s PhD studentship. N.G., N.M. and D.A.L. work in a unit that receives support from the MRC (MC_UU_00011/6) and University of Bristol. D.A.L. is an NIHR Senior Investigator (NF-SI-0611-10196).
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