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