{
  "abstract": "Purpose Adverse pregnancy and perinatal outcomes (APPOs), including pre-term birth, pre-eclampsia and gestational diabetes, can result in maternal and neonatal morbidity and mortality, parental anxiety and increased healthcare costs. A better understanding of the causes of APPOs is essential to inform lifestyle and pharmaceutical interventions for their prevention and management. Given the difficulty of undertaking randomised controlled trials in pregnant women, triangulating evidence from across methods with different sources of bias may improve causal inference for APPOs. The purpose of the Mendelian randomisation in pregnancy (MR-PREG) collaboration is to support such triangulation using genetic (eg, Mendelian randomisation (MR)) and non-genetic (eg, partner negative controls) approaches to investigate the causal effects of maternal exposures on a comprehensive set of APPOs.Participants The MR-PREG collaboration includes individual participant data from three birth cohorts (two from the UK and one from Norway) and UK Biobank, as well as summary data from FinnGen and publicly available genome-wide association studies (GWAS). Data have been harmonised across studies and currently include information on up to 35 APPOs in up to 707 797 women.Findings to date The main aims of MR-PREG are to strengthen the evidence base for (1) prevention, by advancing understanding of maternal lifestyle factors on APPOs, (2) the role of pre-conceptional health, by improving understanding of the effect of maternal pre-existing conditions on APPOs, and (3) treatments, by evaluating the efficacy and safety of existing medications used for pre-existing conditions, and by identifying and testing novel or repurposed therapies for APPOs. To date, our published work has mainly addressed aims 1 and 3. Examples include triangulation of evidence from MR, conventional multivariable regression and paternal negative control, showing that higher maternal body mass index increases the risk of multiple APPOs, as well as the identification of maternal circulating metabolites and proteins that may influence birth weight.Future plans Future priorities include increasing diversity within the MR-PREG collaboration by expanding representation of participants from non-European ancestries. We are also integrating molecular data, including circulating protein levels and placental transcriptomics, to better characterise the molecular mechanisms underlying APPOs. Additionally, we are using whole-exome and whole-genome sequencing to identify novel causal genes and to inform the prioritisation of candidate therapeutic targets for APPOs.",
  "authors": [
    {
      "affiliations": [
        "MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK",
        "Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK"
      ],
      "name": "Nancy McBride"
    },
    {
      "affiliations": [
        "MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK",
        "Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK"
      ],
      "name": "Gemma L Clayton"
    },
    {
      "affiliations": [
        "MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK",
        "Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK"
      ],
      "name": "Ana Goncalves Soares"
    },
    {
      "affiliations": [
        "MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK",
        "Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK",
        "Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China",
        "Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Lifecycle Health Management Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Qian Yang"
    },
    {
      "affiliations": [
        "MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK",
        "Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK",
        "Frazer Institute, University of Queensland, Woolloongabba, Queensland, Australia"
      ],
      "name": "Tom A Bond"
    },
    {
      "affiliations": [
        "MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK",
        "Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK",
        "Division of Surgery and Interventional Science, University College London, London, UK"
      ],
      "name": "Amy Taylor"
    },
    {
      "affiliations": [
        "MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK",
        "Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK"
      ],
      "name": "Charikleia Chatzigeorgiou"
    },
    {
      "affiliations": [
        "MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK",
        "Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK"
      ],
      "name": "Elisabeth Aiton"
    },
    {
      "affiliations": [
        "Population Health, School of Medicine and Population Health, University of Sheffield, Sheffield, UK",
        "Bradford Institute for Health Research, Bradford Teaching Hospitals, Bradford, UK"
      ],
      "name": "Jane West"
    },
    {
      "affiliations": [
        "Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway"
      ],
      "name": "Maria C Magnus"
    },
    {
      "affiliations": [
        "MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK",
        "Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK"
      ],
      "name": "Deborah A Lawlor"
    },
    {
      "affiliations": [
        "MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK",
        "Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK"
      ],
      "name": "Maria Carolina Borges"
    }
  ],
  "title": "Cohort profile: the Mendelian randomisation in pregnancy (MR-PREG) collaboration – improving evidence for prevention and treatment of adverse pregnancy and perinatal outcomes",
  "uid": "9f310750-43b9-52a2-a271-948f6b52dbfd"
}