Methods

This was a prospective, observational, longitudinal study conducted in an inner London Hospital between April 2018 to June 2020. Pregnant women without significant co-morbidities, including chronic hypertension or kidney disease, with a singleton pregnancy were recruited soon after their first trimester scan and seen at three time points during pregnancy; 12-14, 20-24 and 30-32 weeks of gestation. Participants were allocated to the following groups: Group 1 – Pregnant women with BMI ≥30kg/m2 and Group 2 – Pregnant women with BMI 20-24.9kg/m2. The study protocol has been described before and none of the participants had a history of bariatric surgery.17 All participants gave a written consent form and the study was approved by the National Health Service Research Ethics Committee (No: 14/LO/0592). Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines were used throughout.
Blood pressure (BP) measurements were performed twice, electronically (Microlife WatchBP, Switzerland),18 and mean arterial pressure (MAP) was calculated as Systolic BP + (2 x Diastolic BP)]/3.19 The maternal cardiac function was assessed using transthoracic echocardiography and two-dimensional, M-mode and tissue Doppler imaging (TDI) were used (iE33 Philips Ultrasound system) according to European and American guidelines. 20, 21All echocardiographic studies were performed by experienced operators (DP and NB).
Cardiac output (ml or L/min) was calculated as stroke volume (SV) x heart rate (HR). 22 Stroke volume (ml) was calculated as the cross-sectional area of the left ventricular outflow tract x velocity time integral. 22 Peripheral vascular resistance (dynes/sec/ per cm5) was calculated as MAP × 80/CO. 19, 23 Left ventricular mass (g) was calculated as (0.8 x (1.04x [(interventricular septum diameter (mm) + left ventricle internal diameter (mm) + posterior wall thickness (mm))3) − left ventricle internal diameter3 (mm)]) + 0.6g. 20Relative wall thickness was calculated as (2 x posterior wall thickness (mm)) / left ventricle internal diameter (mm). All measurements were taken in diastole. Body surface area (BSA) was calculated as (weight (kg)0.425 x height (cm)0.725) x 0.007184. 24 Haemodynamic function was assessed by systolic BP, diastolic BP, HR, SV, CO and PVR. Cardiac geometry was assessed by left atrial (LA) diameter (end-systole), interventricular septum thickness (IVS) (end-diastole), left ventricle diameter (LVEDD) (end-diastole), posterior wall thickness (PWT) (end-diastole), relative wall thickness (RWT) and left ventricular mass. Diastolic function was assessed by mitral flow velocity (E/A ratio), TDI lateral and medial mitral annular velocity (E’) and left atrial volume. Systolic function was assessed by end-diastolic volume, end-systolic volume, ejection fraction and TDI s’ at the lateral tricuspid annulus. Longitudinal function was assessed by mitral annular plane systolic excursion (MAPSE) at the septal and lateral annulus. All echocardiographic data were stored for offline analysis, which was performed by experienced operators (DP and NB) who were blinded to the allocation of the study participants. We have previously shown that the inter- and intra-observer variability in our Unit is >0.8, indicating good reliability. 17
Women were followed up in pregnancy and all of them underwent a full oral glucose tolerance test at 28-30 weeks of gestation. Gestational diabetes was defined according to the National Institute of Health and Care Excellence (NICE) guidelines of fasting plasma glucose level ≥5.6 mmol/L and/or a 2-hour plasma glucose level ≥7.8 mmol/L.25 Information on pregnancy outcomes were obtained from the Hospital’s perinatal database. Birthweight (BW) was recorded at birth and BW percentiles were calculated. 26Hypertension was defined as persistent maternal BP ≥140/90 mmHg and pre-eclampsia was defined as hypertension with significant proteinuria.27