Predicting Gestational Diabetes from the First Trimester - an exploration of alternative screening processes

Gestational diabetes is recognised to be an increasingly common and treatable cause of maternal and infant morbidity. Screening and formal diagnosis of gestational diabetes have been at the centre of much of the scientific debate. This thesis aims to explore the ability of a panel of biomarkers in the first trimester of pregnancy to predict gestational diabetes and examines their link with the clinical complications of GDM. 248 women with known risk factors for GDM were recruited in the first trimester and had serum samples taken for c-reactive protein, sex hormone binding globulin, adiponectin anhydroglucitol. They underwent oral glucose tolerance testing at 28 weeks gestation and had prospectively collected perinatal outcome data. Cord blood c-peptide levels were drawn as an indicator of fetal hyperglycaemia. Our study found that adiponectin and SHBG demonstrated a correlation to the risk of onset of GDM in the univariate analysis. However, after adjustment for BMI, family history and ethnicity in the multivariate analysis SHBG loses significance. Following adjustment for BMI, family history and ethnicity 1st trimester 1,5 AG becomes a significant predictor of GDM. Mean 1,5 AG levels are significantly lower in the first trimester in women that will go on to develop GDM. However, none of these biomarkers exhibited a specific threshold value at which onset of GDM could be predicted absolutely with acceptable sensitivity and specificity. Our analysis of the relationship between sex hormone binding globulin values in the first trimester and neonatal hyperinsulinaemia (cord blood c-peptide> 90th centile/1.7µL) shows that in women with a high SHBG (>350nmol/L) early in pregnancy have an odds ratio of 2.7 to have a non-hyperinsulinaemic neonate. Our study also explored the patient experience of the OGTT. We found that despite the OGTT having adverse physical effects and being inconvenient, most women find it an acceptable test and would agree to be screened again in the future. BMI >30kg/m2 and non-Caucasian ethnicity remain as independent predictors of GDM status in the adjusted analysis of the history-identified risk factors. Adiponectin and 1,5 AG remain independent predictors of GDM status after adjusting for all other variables.</p

Immunological assessment of SARS-CoV-2 infection in pregnancy from diagnosis to delivery: a multicentre prospective study

Background: Background Population-based data on SARS-CoV-2 infection in pregnancy and assessment of passive immunity to the neonate, is lacking. We profiled the maternal and fetal response using a combination of viral RNA from naso-pharyngeal swabs and serological assessment of antibodies against SARS-CoV-2.Methods: This multicentre prospective observational study was conducted between March 24th and August 31st 2020. Two independent cohorts were established, a symptomatic SARS-CoV-2 cohort and a cohort of asymptomatic pregnant women attending two of the largest maternity hospitals in Europe. Symptomatic women were invited to provide a serum sample to assess antibody responses. Asymptomatic pregnant women provided a nasopharyngeal swab and serum sample. RT-PCR for viral RNA was performed using the Cobas SARS-CoV-2 6800 platform (Roche). Umbilical cord bloods were obtained at delivery. Maternal and fetal serological response was measured using both the Elecsys® Anti-SARS-CoV-2 immunoassay (Roche), Abbott SARS-CoV-2 IgG Assay and the IgM Architect assay. Informed written consent was obtained from all participants.Results: Ten of twenty three symptomatic women had SARS-CoV-2 RNA detected on nasopharyngeal swabs. Five (5/23, 21.7%) demonstrated serological evidence of anti-SARS-CoV-2 IgG antibodies and seven (30.4%, 7/23) were positive for IgM antibodies. In the asymptomatic cohort, the prevalence of SARS-CoV-2 infection in RNA was 0.16% (1/608). IgG SARS-CoV-2 antibodies were detected in 1·67% (10/598, 95% CI 0·8%-3·1%) and IgM in 3·51% (21/598, 95% CI 2·3-5·5%). Nine women had repeat testing post the baseline test. Four (4/9, 44%) remained IgM positive and one remained IgG positive. 3 IgG anti-SARS-CoV-2 antibodies were detectable in cord bloods from babies born to five seropositive women who delivered during the study. The mean gestation at serological test was 34 weeks. The mean time between maternal serologic positivity and detection in umbilical cord samples was 28 days.Conclusion: Using two independent serological assays, we present a comprehensive illustration of the antibody response to SARS-CoV-2 in pregnancy, and show a low prevalence of asymptomatic SARS-CoV2. Transplacental migration of anti-SARS-CoV-2 antibodies was identified in cord blood of women who demonstrated antenatal anti-SARS-CoV-2 antibodies, raising the possibility of passive immunity.</p