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Urinary metabolic profiles in early pregnancy associated with preterm birth

Study published in BMC Medicine

Tuesday, July 15th, 2014

Urinary metabolic profiles in early pregnancy associated with preterm birth

Urinary metabolites measured at the end of the first trimester are associated with increased risk of negative birth outcomes, and provide novel information about the possible mechanisms leading to adverse pregnancies in the Rhea cohort. This study, published in BMC Medicine, emphasizes the potential of metabolic profiling of urine as a means to identify novel non-invasive biomarkers of PB and FGR risk.

Preterm birth (PB) and fetal growth restriction (FGR) convey the highest risk of perinatal mortality and morbidity, as well as increasing the chance of developing chronic disease in later life. Identifying early in pregnancy the unfavourable maternal conditions that can predict poor birth outcomes could help their prevention and management. Here we used an exploratory metabolic profiling approach (metabolomics) to investigate the association between birth outcomes and metabolites in maternal urine collected early in pregnancy as part of the prospective mother–child cohort Rhea study. Metabolomic techniques can simultaneously capture information about genotype and its interaction with the accumulated exposures experienced by an individual from their diet, environment, physical activity or disease (the exposome). As metabolic syndrome has previously been shown to be associated with PB in this cohort, we sought to gain further insight into PB-linked metabolic phenotypes and to define new predictive biomarkers.

The researchers analyzed the metabolites – molecules excreted in urine – of 438 pregnant women in the Rhea cohort. They found that elevated levels of the amino acid lysine were associated with spontaneous premature birth. In contrast, increased levels of the glycoprotein – a molecule consisting of a carbohydrate and protein – is linked with women who had to be induced early. Decreased levels of a third group of molecules: acetate, formate, tyrosine and trimethylamine were associated with poor fetal development.

Acording Manolis Kogevinas, CREAL researcher who had participated in this study, “ our findings imply that it could be possible to improve the identification of women at higher risk of delivering smaller babies or premature delivery using non-invasive metabolic profiling technology early in pregnancy”. Researchers confirmed that N-acetyl glycoprotein and IPB were significantly associated in overweight and obese women only.

It was a case–control study nested within the Rhea cohort. Major metabolites in maternal urine samples collected at the end of the first trimester were measured using proton nuclear magnetic resonance spectroscopy. In addition to PB, we used FGR in weight and small for gestational age as study endpoints. The researchers have observed significant associations between FGR and decreased urinary acetate, formate, tyrosine and trimethylamine adjusting for maternal education, maternal age, and smoking during pregnancy.


Léa Maitre, Eleni Fthenou, Toby Athersuch, Muireann Coen, Mireille B Toledano, Elaine Holmes, Manolis Kogevinas, Leda Chatzi and Hector C Keun. Urinary metabolic profiles in early pregnancy are associated with preterm birth and fetal growth restriction in the Rhea mother–child cohort study. BMC Medicine 2014.

Picture: Ing Jorge (Flickr)



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