Strengths and limitations
The strengths of this study are the novel approach and the use of high-quality prospective clinical and biobank data incorporating a large number of early pregnancy biomarkers. To our knowledge, this is the first study to investigate a range of metabolic and inflammatory-related biomarkers in a multi-centre cohort of low-risk nulliparous women, by ethnicity. The main limitation of this study was the relatively small number of Indian participants in SCOPE. Stratification by ethnicity did therefore not allow us to investigate the association between early pregnancy biomarkers and adverse pregnancy outcome. We did, however, observe remarkable differences in metabolic profile by ethnicity and further research is therefore needed to investigate this relationship. It should be noted that the reported mean values for some biomarkers may be different than expected, as we did not exclude outliers from this study; however, data was transformed prior to analysis and checked for normality. Secondly, as Indian women are more likely to have various types of anaemia and are more likely to be vegetarian,42 it would have been helpful to investigate the association between ferritin and biomarker profile. Unfortunately ferritin testing was not routinely performed in the SCOPE study, and only 37% of Indian women were tested. Similarly, over a quarter of women were not routinely screened for GDM. Finally, while biomarkers were significantly different between ethnicities, many were correlated. This is to be expected as an inflammatory response encompasses multiple pathways that lead to an overall adverse milieu, which can consequently result in poor outcomes. Each biomarker, therefore, is unlikely to exert influence on outcomes independently of other biomarkers. The presented biomarker profiles rather show an overall picture of inflammation and/or adverse metabolic health.