Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000985684
Ethics application status
Approved
Date submitted
29/08/2014
Date registered
12/09/2014
Date last updated
4/08/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Screening Tests to identify poor Outcomes in Pregnancy (STOP) Study
Scientific title
Prospective cohort study on nulliparous women with the aim of developing screening tests to identify adverse pregnancy outcomes
Secondary ID [1] 285245 0
Nil Known
Universal Trial Number (UTN)
U1111-1160-9802
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Preeclampsia 292883 0
Small for gestational age birth 292884 0
Preterm birth 292885 0
Gestational diabetes mellitus 292886 0
Condition category
Condition code
Reproductive Health and Childbirth 293177 293177 0 0
Fetal medicine and complications of pregnancy

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This is a prospective cohort study where women with a singleton pregnancy less than 12 weeks’ gestation attending the first antenatal clinic, their partners and babies will be recruited. The women will be monitored throughout pregnancy and pregnancy complications will be diagnosed using current international guidelines as follows.

1. Preeclampsia is defined as Systolic blood pressure greater than or equal to 140 mmHg and/or diastolic blood pressure greater than or equal to 90mmHg (Korotkoff V) on at least
2 occasions 4hours apart, after 20 weeks’ gestation, but before the onset of labour and Proteinuria greater than or equal to 300 mg/24h or spot urine protein:creatinine ratio greater than or equal to 30 mg/mmol creatinine or urine dipstick protein greater than or equal to plus 2 or any multi-system
complication of preeclampsia including

a. Haematological abnormalities consisting of thrombocytopenia (platelet count less than100 x 109/L), disseminated intravascular coagulation (DIC), haemolysis (diagnosed by features on blood film such as fragmented cells, helmet cells) and reduced haptoglobin

b. Liver disease demonstrated by increased aspartate transaminase and/or alanine transaminase greater than 45 IU/L and/or severe right upper quadrant or epigastric pain, liver rupture,

c. Neurological problems including eclampsia, imminent eclampsia (severe headache with hyperreflexia and persistent visual disturbance), cerebral haemorrhage

d. Acute renal insufficiency demonstrated by new increase in serum creatinine to greater than 100 umol/L antepartum or greater than 130 umol/L postpartum

e. Pulmonary oedema confirmed by chest x-ray

2. Small for gestational age birth defined as birthweight less than 10th percentile using customized centiles, adjusted for maternal weight, height, parity, ethnicity and infant sex

3. Spontaneous preterm birth defined as spontaneous preterm labour or preterm premature rupture of membranes resulting in
preterm birth at less than 37 weeks

4. Gestational diabetes mellitus diagnosed by any of,

Glucose tolerance test (GTT) fasting glucose greater than or equal to 5.5 mmol/L and/or 2 hour glucose greater than or equal to 7.8 mmol/L
Polycose and no GTT available: 1h glucose greater than 11.0 mmol/l
Fasting Glucose and no polycose or GTT available fasting glucose greater than or equal to 5.5 mmol/L
Random Glucose and no polycose, GTT or fasting glucose, random glucose greater than 11.0 mmol/L

Women with a singleton pregnancy less than 12 weeks’ gestation attending the first antenatal clinic will be invited to participate in the STOP study.
At 12 weeks’, information will be obtained regarding baseline demographic characteristics including age, ethnicity, level of education, employment and income; medical/surgical and obstetric history, complications during the current pregnancy including hyperemesis and vaginal bleeding; family history of any medical or obstetric disorders; diet; exercise; intake of alcohol and recreational drugs and smoking. The height, weight and blood pressure will be measured and 20ml of peripheral blood and a sample of urine will be collected. Plasma will be used to assess selected biomarkers and micronutrients including folate, vitamin D, zinc and selenium. HbA1c will be measured in whole blood. A Doppler scan will be performed to assess the uterine artery blood flow. The women will also be given a lifestyle questionnaire to assess their level of anxiety and stress.

At 18-20 weeks, at the time of the routine morphology ultrasound scan, a transvaginal ultrasound scan will be performed to measure the cervical length and a Doppler scan will be performed to assess the uterine and umbilical artery blood flow.
At 28 weeks, an oral glucose tolerance test will be performed to screen for gestational diabetes mellitus.
The women will be followed up throughout the pregnancy. If a pregnancy complication develops, a blood and a urine sample will be collected at the time of diagnosis of any complication for assessment of changes in the levels of the selected biomarkers. One in seven women who have uncomplicated pregnancies will be selected as late gestation controls and will be requested to give a blood and a urine sample for comparison.
We will request the permission of the recruited women, to invite their partners to the STOP study. Consenting partners will be recruited at a time convenient to the participants. Information will be obtained regarding baseline demographic characteristics including age, ethnicity, level of education, employment and income; medical and surgical history, family history of any medical or obstetric disorders; diet; exercise; intake of alcohol and recreational drugs and smoking. The height, weight and blood pressure will be measured and 10ml of peripheral will be collected. Those who do not wish to provide a blood sample will be given the opportunity to provide a sample of saliva.
We will request the permission of the women to obtain a sample of the placenta at delivery. 5ml of cord blood will also be collected at delivery. If a cord blood sample cannot be collected at delivery, a saliva sample or a buccal swab will be collected from the baby within 72 hours of delivery. We will obtain the baby’s length, weight, APGAR score and information on the presence/absence of any congenital malformations from clinical records. Babies that are admitted to a neonatal intensive care or special care unit will be followed up until discharge to identify the outcome.
We will use the blood collected from women at the 12 weeks’ visit, the blood or saliva samples collected from the partners and the cord blood or buccal swabs collected from babies to extract DNA. Genotyping for selected polymorphisms will be performed using the Life Technologies Quant Studio Open Array system. We expect to validate our previous associations, as well as identify other candidate gene polymorphisms/haplotypes that are associated with pregnancy complications. We will identify clinical/lifestyle and environmental factors collected at 12 weeks’ gestation that interact with these polymorphisms to modify the risk of pregnancy complications.
Intervention code [1] 290127 0
Not applicable
Comparator / control treatment
Uncomplicated pregnancy - Normotensive pregnancy, delivered after 37 weeks, resulting in a liveborn baby who is not small for gestational age (SGA)
Control group
Uncontrolled

Outcomes
Primary outcome [1] 293042 0
Composite primary outcome of pregnancy including uncomplicated pregnancy or pregnancy complications including preeclampsia, small for gestational age birth, spontaneous preterm birth or gestational diabetes mellitus (the pregnancy complications have been defined earlier)
Timepoint [1] 293042 0
The period of gestation at which the complication is diagnosed for preeclampsia, spontaneous preterm birth and gestational diabets mellitus and at birth for small for gestational age birth
Secondary outcome [1] 310228 0
Birthweight
Timepoint [1] 310228 0
At the time of delivery
Secondary outcome [2] 310323 0
Customised birthweight centile
Timepoint [2] 310323 0
At the time of delivery
Secondary outcome [3] 310324 0
Placental weight
Timepoint [3] 310324 0
At the time of delivery
Secondary outcome [4] 310325 0
Gestational age at delivery
Timepoint [4] 310325 0
At the time of delivery

Eligibility
Key inclusion criteria
Women with a singleton pregnancy less than 12 weeks’ gestation attending the first antenatal clinic, their partners and babies
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Women with,

1. Multiple pregnancy
2. Major fetal anomalies
3. Known essential hypertension pre-pregnancy, whether or
not on anti hypertensive medication OR
Women who are not known to have hypertension, but have
severe hypertension (blood pressure greater than 160/110mmHg) at booking
4. Type I or II diabetes
5. Renal disease
6. Systemic lupus erythematosus and anti-phospholipid
syndrome
7. Known major uterine anomaly
8. Cervical cone biopsy
9. More than 3 miscarriages more than 3 terminations
10. Treatment with low dose aspirin, calcium greater than 1g/24h, heparin, low molecular weight heparin, antioxidants (vitamin C and E) in a trial setting

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
This is a prospective cohort study with the aim of developing screening tests to predict the risk of preeclampsia, small for gestational age birth, spontaneous preterm birth and gestational diabets mellitus. These pregnancy complications together affect approximately 25% of pregnant women. Our aim is to identify a combination of genetic, clinical and biochemical markers that can predict the risk of these pregnancy complications as early as during the 12th week of pregnancy. On the basis of prevalence of a polymorphism in 10% in the general population and a ratio of 1 control subject to 1 case, we will need 344 cases and 344 controls to achieve a power of 80% to detect an odds ratio of 2.0 (beta = 80%, alpha = 0.05). Based on the above calculation, we will need a minimum sample size of 1400 to achieve the above number of cases. Therefore, we expect to recruit 1500 to the study.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/10/2014
Actual
5/03/2015
Date of last participant enrolment
Anticipated
29/12/2017
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
1500
Accrual to date
1172
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 2942 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [2] 2943 0
Womens and Childrens Hospital - North Adelaide
Recruitment postcode(s) [1] 8675 0
5112 - Elizabeth Vale
Recruitment postcode(s) [2] 8676 0
5006 - North Adelaide

Funding & Sponsors
Funding source category [1] 289874 0
University
Name [1] 289874 0
The University of Adelaide
Country [1] 289874 0
Australia
Primary sponsor type
University
Name
The University of Adelaide
Address
The University of Adelaide, Adelaide, South Australia 5005
Country
Australia
Secondary sponsor category [1] 288554 0
None
Name [1] 288554 0
Address [1] 288554 0
Country [1] 288554 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291596 0
Women’s and Children’s Health Network Human Research Ethics Committee
Ethics committee address [1] 291596 0
Ethics committee country [1] 291596 0
Australia
Date submitted for ethics approval [1] 291596 0
11/08/2014
Approval date [1] 291596 0
16/10/2014
Ethics approval number [1] 291596 0
HREC/14/WCHN/90

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 51042 0
Prof Claire Roberts
Address 51042 0
Discipline of Obsterics and Gynaecology, School of Paediatrics and Reproductive Health, The University of Adelaide, Level 6, Medical School North, Frome Road, Adelaide, SA 5005
Country 51042 0
Australia
Phone 51042 0
+61 8 8313 3118
Fax 51042 0
+61 8 8313 4099
Email 51042 0
[email protected]
Contact person for public queries
Name 51043 0
Claire Roberts
Address 51043 0
Discipline of Obsterics and Gynaecology, School of Paediatrics and Reproductive Health, The University of Adelaide, Level 6, Medical School North, Frome Road, Adelaide, SA 5005
Country 51043 0
Australia
Phone 51043 0
+61 8 8313 3118
Fax 51043 0
+61 8 8313 4099
Email 51043 0
[email protected]
Contact person for scientific queries
Name 51044 0
Claire Roberts
Address 51044 0
Discipline of Obsterics and Gynaecology, School of Paediatrics and Reproductive Health, The University of Adelaide, Level 6, Medical School North, Frome Road, Adelaide, SA 5005
Country 51044 0
Australia
Phone 51044 0
+61 8 8313 3118
Fax 51044 0
+61 8 8313 4099
Email 51044 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseSafety and protective effects of maternal influenza vaccination on pregnancy and birth outcomes: A prospective cohort study.2020https://dx.doi.org/10.1016/j.eclinm.2020.100522
EmbaseGestational diabetes mellitus and cardio-metabolic risk factors in women and children at 3 years postpartum.2022https://dx.doi.org/10.1007/s00592-022-01914-y
EmbasePlacental Inflammasome mRNA Levels Differ by Mode of Delivery and Fetal Sex.2022https://dx.doi.org/10.3389/fimmu.2022.807750
EmbaseThe association of breast feeding for at least six months with hemodynamic and metabolic health of women and their children aged three years: an observational cohort study.2023https://dx.doi.org/10.1186/s13006-023-00571-3
N.B. These documents automatically identified may not have been verified by the study sponsor.