Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT04858386 |
| Other study ID # |
17024UG-SW |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
November 1, 2017 |
| Est. completion date |
August 4, 2020 |
Study information
| Verified date |
April 2021 |
| Source |
Belfast Health and Social Care Trust |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The association of hyperglycaemia in pregnancy (gestational diabetes mellitus; GDM) with
adverse maternal and fetal outcomes is clearly recognised. Traditionally the diagnosis is
made at 28 weeks gestation at which stage children of affected women already have a two-fold
rate of excessive weight gain (abdominal circumference > 90th percentile). This is attributed
to fetal exposure to undiagnosed high blood glucose earlier in pregnancy. Indeed almost 25%
of women with GDM develop the condition before 20 weeks gestation. Interventional studies in
women diagnosed in the late second trimester have shown benefits in reducing fetal
macrosomia. It is unknown whether screening in the first trimester would predict fetal
macrosomia and allow more timely and effective intervention. To examine this question, we
propose a prospective cohort study of 1,662 women at increased risk of GDM to determine if an
elevated HbA1c (39-48mmool/l) in early pregnancy (<14 weeks) can identify babies at risk of
excessive weight gain in later pregnancy, as determined by ultrasound measurement of
abdominal circumference at 28 weeks gestation. The study will be largely integrated into
routine clinical practice enabling a large number of women to participate. Study participants
will all undergo formal screening (75g oral glucose tolerance test) for GDM at 28 weeks
gestation. Secondary outcomes, namely the ability of early pregnancy HbA1c to predict later
maternal GDM, and fetal and maternal complications of pregnancy will also be evaluated. The
results of this study, if positive, are likely to impact upon patient care almost immediately
following study completion. In addition, given the stability of the Northern Ireland
population, the relatively unique data set will facilitate future work on predictive markers
for cardiovascular disease, and prospective studies on the cardiovascular consequences of GDM
on both mother and baby.
Description:
Study Aim: The overall aim of this study is to identify a feasible, easily adopted, early
screening method for excessive fetal weight gain; a known risk factor for childhood obesity
and type 2 diabetes.
Primary objective: To examine the effect of increased (39-48mmol/mol) maternal HbA1c,
measured before 14 weeks gestation, on the ultrasound finding of fetal abdominal
circumference greater than the 90th percentile at 28 weeks gestation. We hypothesise that
women with a high early pregnancy HbA1c (39-48mmol/mol) will have a significantly increased
risk of excessive weight gain in their babies.
Secondary objectives:
1. To establish ability of maternal HbA1c in early pregnancy (< 14 weeks) to predict the
diagnosis of GDM in the late second trimester (28 weeks)
2. To determine the effect of an increased (39-48mmol/mol) maternal HbA1c, measured before
14 weeks gestation, on fetal, maternal and neonatal complications of pregnancy
(stillbirth, preterm delivery, birth weight >90th percentile, shoulder dystocia, birth
injury, neonatal hypoglycaemia, neonatal intensive care, caesarean delivery,
preeclampsia, gestational hypertension) taking account of any GDM intervention.
3. To determine dietary patterns among women with and without a diagnosis of GDM.
Study Outline: Prospective cohort study of women at increased risk of GDM presenting for
obstetric care at the Royal Jubilee Maternity Hospital Belfast; the largest maternity unit in
Northern Ireland with some 5000-6000 deliveries per year. The study will be conducted over
three years by healthcare staff with support from the research team. The study will largely
be integrated into routine clinical practice thus enabling a large number of women to take
part in the study.
Participants: 1,828 women in early pregnancy (≤ 14 weeks gestation) will be recruited,
following informed consent, during their booking visit at the Royal Jubilee Maternity
Hospital, Belfast. Inclusion criteria include age ≥ 18yrs, and NICE risk factors for glucose
intolerance namely body mass index ≥ 30kg/m2, family history of diabetes (first-degree
relative), previous macrosomic baby (>4.5kg) and minority ethnic family origin with a high
prevalence of diabetes14. Exclusion criteria will include pre-existing type 1 or type 2
diabetes mellitus, a previous history of GDM, booking HbA1c ≥ 48mmol/mol (6.5%), anaemia
diagnosed on booking full blood count, booking diagnosis of a multiple pregnancy, and use of
corticosteroids or metformin within two weeks of booking.
Booking visit: Participants at 10-14 weeks gestation will be consented at their booking
visit. At this visit patient demographics such as height, weight and blood pressure, are
recorded on the Northern Ireland Maternity Information System (NIMATS) by the booking
midwife. Study blood samples (14 mls) will be taken alongside routine antenatal bloods by the
booking midwife, and plasma analysed for HbA1c (4mls) in the Regional Haematology Laboratory
as outlined below. Serum and urine will also be collected (10mls whole blood, 10mls urine),
processed and stored at -80°C for future work. Sample processing (as outlined below) will be
carried out immediately following venesection/urine collection. Women with HbA1c ≥ 48mmol/mol
(6.5%) will informed of their result by telephone (RD); referred for ongoing care at the
Diabetes Antenatal Clinic and excluded from the study. Women with HbA1c < 48mmol/mol (6.5%)
will be recruited to the study but will continue to be managed according to their routine
obstetric care pathway. Women booking at the Royal Jubilee Maternity Hospital will also be
offered ultrasound measurement of visceral/subcutaneous fat depth. This will be performed at
the end of their routine booking ultrasound (RD) and measurements will be recorded in the
study database.
Nested Observational Study In a subset of women, visceral adipose tissue depth and
subcutaneous adipose tissue depth will be measured using the technique described by Martin et
al following booking ultrasonography. Measurements will be taken with the participant
recumbent and measurements taken approximately 1cm above the umbilicus in triplicate. These
measurements will be added to the dataset.
28 weeks: Oral Glucose Tolerance Test: All participants will be invited to attend for a 75g
oral glucose tolerance test at 28 weeks gestation as part of their routine clinical care14.
Testing will be performed by clinical midwives in the Day Obstetric Unit. The test will take
place in the morning following an overnight fast from 10pm the evening before. Maternal
weight will be recorded at this visit. Baseline bloods (24mls in total) will be taken for
glucose (4mls) and storage (20mls). Following a drink containing 75g glucose, blood will be
taken after 60min and 120mins for glucose (4mls) and storage (4mls). Samples for storage will
be processed following collection. Glucose will be analysed in the Regional Biochemistry
Laboratory immediately.
Plasma glucose results will available within 4 hours of each OGTT. World Health Organisation
criteria will be used to diagnose GDM (fasting glucose ≥ 5.1mmol/l; 1-hr ≥ 10.0mmol/l; 2-hr
8.5mmol/l)15. Each woman will be contacted with the results of their OGTT as per our routine
practice with immediate referral to the Diabetes Antenatal Clinic for those diagnosed with
GDM. Glucose results will be inputted to the study dataset on a daily basis using a unique
patient identifier. Samples for storage will be processed as outlined below. Participant
weights will also be entered into a database on a daily basis and linked to
clinical/biochemical data via a unique patient identifier.
28 weeks: Fetal ultrasound: At the time of their OGTT, participants will also attend the
study ultrasonographer for their study ultrasound scan. Abdominal circumference, head
circumference, femur length and estimated fetal weight will be measured using the ellipse
function on a Voluson E8 ultrasound scanner at the recommended anatomical sites25. The
ultrasonographer will be experienced in fetal ultrasound and blinded to early pregnancy HbA1c
results. The same scanner will be used for all study participants. Ultrasound measurements
will be recorded initially on a study case report form and transferred daily to the
electronic study database.
28 weeks: Food Frequency Questionnaire: Each participant will be asked to complete a food
frequency questionnaire whilst waiting for blood sampling during their OGTT. This is to
evaluate dietary patterns of women with and without GDM and will provide a basis from which
future dietary interventions can be formed. The questionnaire used is a validated
questionnaire used recently in the Avon Longitudinal Study of Pregnancy and Children
(http://www.bristol.ac.uk/alspac)
Delivery: Each participant will continue their usual obstetric care following their 28 week
appointment. At the end of the study, obstetric outcome information will be extracted from
the Northern Ireland Maternity Information System (NIMATS) and, if necessary, paper records.
This will include gestational age at delivery, mode of delivery and the fetal, maternal and
early neonatal complications as outlined above in the objectives. Delivery outcomes will be
linked to the study data using matched unique participant identifiers.
