ANZCTR - Registration

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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]

Nil Known

Universal Trial Number (UTN)

U1111-1160-9802

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Preeclampsia

Small for gestational age birth

Preterm birth

Gestational diabetes mellitus

Condition category

Condition code

Reproductive Health and Childbirth

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]

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]

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]

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]

Birthweight

Timepoint [1]

At the time of delivery

Secondary outcome [2]

Customised birthweight centile

Timepoint [2]

At the time of delivery

Secondary outcome [3]

Placental weight

Timepoint [3]

At the time of delivery

Secondary outcome [4]

Gestational age at delivery

Timepoint [4]

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)

Recruitment hospital [1]

Lyell McEwin Hospital - Elizabeth Vale

Recruitment hospital [2]

Womens and Childrens Hospital - North Adelaide

Recruitment postcode(s) [1]

5112 - Elizabeth Vale

Recruitment postcode(s) [2]

5006 - North Adelaide

Funding & Sponsors

Funding source category [1]

University

Name [1]

The University of Adelaide

Address [1]

The University of Adelaide, Adelaide, South Australia 5005

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Women’s and Children’s Health Network Human Research Ethics Committee

Ethics committee address [1]

Level 2, Samuel Way Building, The Women's and Children's Hospital, 72, King William Road, North Adelaide, South Australia 5006

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

11/08/2014

Approval date [1]

16/10/2014

Ethics approval number [1]

HREC/14/WCHN/90

Summary

Brief summary

The four major pregnancy complications, preeclampsia, preterm birth, intrauterine growth restriction and gestational diabetes mellitus, afflict 25% of first pregnancies and are life-threatening to the mother and/or her baby in more than 6% of pregnancies. Although many aetiological risk factors have been identified, at present we cannot effectively
predict which women will develop pregnancy complications.
Our previous research has identified a combination of potential clinical and lifestyle factors and genetic and biochemical biomarkers that predict the risk of these
pregnancy complications at 15 weeks of gestation. We aim to validate our algorithms in a new cohort of participants and
expect to be able to predict the risk of development of pregnancy complications as early as at the 12th week of
gestation. Those found to be at increased risk can be managed with a combination of preventive strategies and
early targeted interventions that would reduce the risk of developing these complications.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Claire Roberts

Address

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

Australia

Phone

+61 8 8313 3118

Fax

+61 8 8313 4099

[email protected]

Contact person for public queries

Name

Prof Claire Roberts

Address

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

Australia

Phone

+61 8 8313 3118

Fax

+61 8 8313 4099

[email protected]

Contact person for scientific queries

Name

Prof Claire Roberts

Address

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

Australia

Phone

+61 8 8313 3118

Fax

+61 8 8313 4099

[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

Source	Title	Year of Publication	DOI
Embase	The 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.	2023	https://dx.doi.org/10.1186/s13006-023-00571-3
Embase	Placental Inflammasome mRNA Levels Differ by Mode of Delivery and Fetal Sex.	2022	https://dx.doi.org/10.3389/fimmu.2022.807750
Embase	Gestational diabetes mellitus and cardio-metabolic risk factors in women and children at 3 years postpartum.	2022	https://dx.doi.org/10.1007/s00592-022-01914-y
Embase	Safety and protective effects of maternal influenza vaccination on pregnancy and birth outcomes: A prospective cohort study.	2020	https://dx.doi.org/10.1016/j.eclinm.2020.100522

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically