• The impact of maternal celiac disease on birthweight and preterm birth: a Danish population-based cohort study.

      Khashan, A S; Henriksen, T B; Mortensen, P B; McNamee, R; McCarthy, F P; Pedersen, M G; Kenny, L C; Anu Research Centre, Department of Obstetrics and Gynecology, University College , Cork, Cork University Maternity Hospital, Cork, Ireland. a.khashan@ucc.ie (2012-01-31)
      BACKGROUND: Adverse pregnancy outcomes have been associated with maternal celiac disease (CD). In this study, we investigate the effect of treated and untreated maternal CD on infant birthweight and preterm birth. METHODS: A population-based cohort study consisted of all singleton live births in Denmark between 1 January 1979 and 31 December 2004 was used. A total of 1,504,342 babies were born to 836,241 mothers during the study period. Of those, 1105 babies were born to women with diagnosed CD and 346 were born to women with undiagnosed CD. Women with diagnosed CD were considered as treated with a gluten free diet while women with undiagnosed CD were considered as untreated. The outcome measures were: birthweight, small for gestational age (SGA: birthweight <10th centile), very small for gestational age (VSGA: birthweight <5th centile) and preterm birth. We compared these measures in treated and untreated women with those of a reference group (no history of CD). RESULTS: Women with untreated CD delivered smaller babies [difference = -98 g (95% CI: -130, -67)], with a higher risk of SGA infants [OR = 1.31 (95% CI: 1.06, 1.63)], VSGA infants [OR = 1.54 (95% CI: 1.17, 2.03)] and preterm birth [OR = 1.33 (95% CI: 1.02, 1.72)] compared with women without CD. Women with treated CD had no increased risk of reduced mean birthweight, risk of delivering SGA and VSGA infants or preterm birth compared with women without CD. CONCLUSION: Untreated maternal CD increases the risk of reduced birthweight, the risk of delivering SGA and VSGA infants and preterm birth. Diagnosis and presumed treatment of maternal CD with a gluten-free diet appeared to result in a birthweight and preterm birth rate similar to those in women without CD.
    • Metabolic profiling uncovers a phenotypic signature of small for gestational age in early pregnancy.

      Horgan, Richard P; Broadhurst, David I; Walsh, Sarah K; Dunn, Warwick B; Brown, Marie; Roberts, Claire T; North, Robyn A; McCowan, Lesley M; Kell, Douglas B; Baker, Philip N; et al. (2012-01-31)
      Being born small for gestational age (SGA) confers increased risks of perinatal morbidity and mortality and increases the risk of cardiovascular complications and diabetes in later life. Accumulating evidence suggests that the etiology of SGA is usually associated with poor placental vascular development in early pregnancy. We examined metabolomic profiles using ultra performance liquid chromatography-mass spectrometry (UPLC-MS) in three independent studies: (a) venous cord plasma from normal and SGA babies, (b) plasma from a rat model of placental insufficiency and controls, and (c) early pregnancy peripheral plasma samples from women who subsequently delivered a SGA baby and controls. Multivariate analysis by cross-validated Partial Least Squares Discriminant Analysis (PLS-DA) of all 3 studies showed a comprehensive and similar disruption of plasma metabolism. A multivariate predictive model combining 19 metabolites produced by a Genetic Algorithm-based search program gave an Odds Ratio for developing SGA of 44, with an area under the Receiver Operator Characteristic curve of 0.9. Sphingolipids, phospholipids, carnitines, and fatty acids were among this panel of metabolites. The finding of a consistent discriminatory metabolite signature in early pregnancy plasma preceding the onset of SGA offers insight into disease pathogenesis and offers the promise of a robust presymptomatic screening test.