IMproved PRegnancy Outcome by Early Detection

NCT01891240 | Unknown

• 2 other identifiers: Study Protocol v. 8.0 20122013Project no: 305169
• Study Type: observational
• Target: 5,000
• Locations: 4 countries
• Sites: 6

Brief Summary

The overall objective of the IMPROvED project is to develop a sensitive, specific, high-throughput and economically viable early pregnancy screening test for preeclampsia. This will involve a multicentre, phase IIa clinical predictive study to assess and refine novel and innovative prototype tests based on emerging metabolomic and proteomic technologies developed by SMEs (small to medium size enterprise) within the consortium. The study will i) recruit 5000 first-time pregnant women; ii) establish a high calibre biobank, augmented by accurate clinical metadata; iii) determine whether prototype predictive assays and algorithms translate to the clinical environment; iv) assess potential synergy of a combined metabolomic and proteomic approach and v) progress regulatory approval and development of the selected test into the clinical arena.

Conditions

Pre-eclampsia; Pregnancy; Pregnancy, High-risk; Pregnancy Complications

Keywords

Diagnostic; Pre-eclampsia; Pregnancy outcome; Mass screening; Diagnostic Techniques and Procedures

Outcome Measures

Primary Outcomes (3)

• Pre-eclampsia.

  Preeclampsia is defined as gestational hypertension defined as systolic BP ≥140mmHg and/or diastolic BP ≥90mmHg (Korotkoff V) on at least 2 occasions 4h apart after 20 weeks' gestation, but before the onset of labour or postpartum systolic BP ≥140mmHg and/or diastolic BP ≥90mmHg on at least 2 occasions 4h apart with either proteinuria ≥300mg/24h or spot urine protein:creatinine ratio ≥30mg/mmol creatinine or urine dipstick protein ≥++.

  7 days after birth

• Spontaneous pre-term birth

  Spontaneous pre-term birth is defined as spontaneous preterm labour or preterm premature rupture of the membranes resulting in preterm birth at \<37+0 weeks' gestation.

  Up to 37+0 weeks´ gestation

• Small for gestational age (SGA)

  The birth weight is converted to a customized centile, adjusting for gestation, maternal weight, height, parity, ethnicity and infant sex. SGA is defined as \<10th customised centile.

  Within 24 hours after birth

Secondary Outcomes (13)

• Early onset pre-eclampsia

  Followed for the duration of hospital stay, an expected average of 6 weeks

• Multisystem complications of pre-eclampsia

  Between 20 weeks´gestation and 6 weeks after birth

• Pre-eclampsia with severe fetal or neonatal complications

  Followed for the duration of hospital stay, an expected average of 6 weeks

• Major neonatal morbidity in preterm infants

  Followed for the duration of hospital stay, an expected average of 6 weeks

• Major neonatal morbidity in term infants

  Followed for the duration of hospital stay, an expected average of 6 weeks

Study Arms (1)

First time, low risk mothers

The study population will consist of first time, low risk mothers attending for antenatal care in one of the participating clinical centres.

Eligibility Criteria

• Age: 16 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

First time, low risk mothers attending antenatal care units. Women will be referred to IMPROvED through a number of routes including referral by their midwife, obstetrician or general practitioner and self-referral following exposure to the study through friends, posters, advertisements, website and news stories. Maternity caregivers in each centre will provide information about the study to eligible women in early pregnancy.

You may qualify if:

• Nulliparous.
• Singleton pregnancy, between 9+0 and 16+6 weeks' gestation.
• Signed informed consent.

You may not qualify if:

• Unsure of last menstrual period (LMP) and unwilling to have ultrasonography screening (USS) at ≤ 20 weeks.
• ≥ 3 miscarriages.
• ≥3 terminations of pregnancy.
• Known or suspected major fetal anomaly/abnormal karyotype.
• Essential hypertension treated pre-pregnancy.
• Moderate-severe hypertension at booking (BP \>160/100 mmHg).
• Diabetes mellitus.
• Renal disease.
• Systemic lupus erythematosus.
• Anti-phospholipid syndrome.
• Sickle cell disease.
• HIV positive.
• Hepatitis B or C positive.
• Major uterine anomaly.
• Cervical suture in situ.

Sponsors & Collaborators

• Louise Kenny: lead
• Keele University: collaborator
• University of Liverpool: collaborator
• Karolinska University: collaborator
• Erasmus Medical Center: collaborator
• Copenhagen Trial Unit, Center for Clinical Intervention Research: collaborator
• MedSciNet AB, Stockholm, Sweden: collaborator
• MyCartis, Ghent, Belgium: collaborator
• Metabolomic Diagnostics Ltd, Cork, Ireland: collaborator
• Accelopment AG: collaborator
• University of Groningen, The Netherlands: collaborator
• INFANT centre, University College Cork, Republic of Ireland: collaborator

Study Sites (6)

Cork University Maternity Hospital, University College Cork

Wilton, Cork, Ireland

RECRUITING

Erasmus Medical Center Rotterdam

Rotterdam, Netherlands

RECRUITING

Karolinska University Hospital Huddinge, Karolinska Institute

Stockholm, Sweden

RECRUITING

Liverpool Women's Hospital, University of Liverpool

Liverpool, Merseyside, United Kingdom

RECRUITING

Keele University School of Medicine, Shrewsbury and Telford Hospital NHS Trust

Shrewsbury, Shropshire, United Kingdom

COMPLETED

Keele University School of Medicine, University Hospital of North Midlands

Stoke-on-Trent, Staffordshire, United Kingdom

COMPLETED

Related Publications (3)

• McCarthy EK, Schneck D, Basu S, Xenopoulos-Oddsson A, McCarthy FP, Murray DM, Georgieff MK, Kiely ME. Impact of Maternal Iron Deficiency in Early Pregnancy on Neonatal Iron Status and Neurodevelopment at Two Years of Age: a Prospective, Maternal-Infant Cohort Study. J Nutr. 2026 Jan;156(1):101240. doi: 10.1016/j.tjnut.2025.11.009. Epub 2025 Nov 12.

  PMID: 41238120 DERIVED

• McCarthy EK, Schneck D, Basu S, Xenopoulos-Oddsson A, McCarthy FP, Kiely ME, Georgieff MK. Longitudinal evaluation of iron status during pregnancy: a prospective cohort study in a high-resource setting. Am J Clin Nutr. 2024 Nov;120(5):1259-1268. doi: 10.1016/j.ajcnut.2024.08.010. Epub 2024 Sep 26.

  PMID: 39510727 DERIVED

• Navaratnam K, Alfirevic Z, Baker PN, Gluud C, Gruttner B, Kublickiene K, Zeeman G, Kenny LC. A multi-centre phase IIa clinical study of predictive testing for preeclampsia: improved pregnancy outcomes via early detection (IMPROvED). BMC Pregnancy Childbirth. 2013 Dec 7;13:226. doi: 10.1186/1471-2393-13-226.

  PMID: 24314209 DERIVED

Related Links

• Official website of IMPROvED

Biospecimen

Retention: SAMPLES WITH DNA

EDTA plasma and serum. Optional urine, hair and baby cord samples

MeSH Terms

Conditions

Pre-Eclampsia; Pregnancy Complications; Disease

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-Induced; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Louise Kenny, Professor

  INFANT Centre, University College Cork, Ireland

  PRINCIPAL INVESTIGATOR

• Philip N Baker, Professor

  Keele Univeristy School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 20, 2013
• First Posted: July 3, 2013
• Study Start: November 1, 2013
• Primary Completion: October 1, 2017
• Study Completion: April 1, 2018
• Last Updated: November 8, 2016

Record last verified: 2016-11

Locations

GB (3); IE (1); SE (1); NL (1)