Early pregnancy events and impact on pregnancy outcomes: the EPOS study
Creators: name: Al-Memar, Maya
Publisher: name: Imperial College London
Year: 2018

description: Early pregnancy events, such as pain and bleeding, are common. Their influence on pregnancy outcomes remains unclear. I aimed to assess the impact of early pregnancy events (pain, bleeding, nausea and vomiting, intrauterine haematoma) on short-term and long-term pregnancy outcomes. The metabolome, specific biomarkers and the vaginal microbiome were also assessed in the first trimester of viable pregnancies and compared with first trimester miscarriages. A prospective longitudinal cohort study was conducted, recruiting from March 2014 to March 2016. Participants with intrauterine pregnancies were recruited and underwent serial ultrasound scans and bio-fluid sampling (blood, urine and vaginal swabs) in the first trimester. Symptoms were recorded using validated scores for vaginal bleeding, pelvic pain and nausea and vomiting. Participants underwent routine follow up and an additional sonographic assessment of fetal growth in the third trimester. Pregnancy outcomes were collected using the hospital database. Over 1000 women were recruited to the study. From this cohort, five separate analyses were conducted to meet our aims: Study 1. Participants experiencing first trimester miscarriage were compared with controls. A multivariate model to predict viability was developed based on maternal age, gestational age discrepancy, presence of fetal heart pulsations and mean gestation sac diameter and the multiple of the median of progesterone. Study 2. The metabolic profile of pregnancies in the first trimester was assessed. This demonstrated a relationship between metabolite changes in the first trimester and gestational age, allowing development of a model to predict gestational age. This relationship was altered in pregnancies that subsequently miscarried. A model using the metabolic profile to predict miscarriage did not perform as well as clinical data based on gestational age discrepancy. Study 3. The vaginal microbiota composition in participants who experienced first and second trimester miscarriages and controls was analysed. This demonstrated reduced Lactobacillus spp. abundance in pregnancies affected by first trimester miscarriage that was independent of vaginal bleeding and preceded miscarriage diagnosis. Study 4. The impact of early pregnancy events (pain, vaginal bleeding, nausea and vomiting) on long-term pregnancy outcomes was assessed. Pain and/or bleeding in the first trimester were associated with increased risk of overall antenatal but not delivery or neonatal complications. Nausea and vomiting in pregnancy was not associated with adverse outcomes. Study 5. Pregnancy outcomes in those with intrauterine haematoma (IUH) diagnosed on ultrasound scan in the first trimester were compared to those without IUH. The presence of an IUH was associated with an increased risk of preterm birth, but not first trimester miscarriage. In conclusion, early pregnancy events impact both short-term and long-term pregnancy outcomes. This information can be used to develop models to predict adverse outcomes, as has been demonstrated within this thesis for first trimester miscarriage, as well as provide insights into the mechanisms of disease. Pregnancies at higher risk of complications could then be identified and additional antenatal surveillance recommended.