Study for Improving Maternal, Pregnancy and Child Outcomes

Pre-Eclampsia Clinical Trial

— IMPACT  

Official title:

IMPACT - Study for Improving Maternal, Pregnancy and Child Outcomes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03831490
• Other study ID #: Dnr 2018-231
• Status: Completed
• Start date: November 9, 2018
• Est. completion date: December 31, 2022

Study information

• Verified date: May 2024
• Source: Uppsala University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The overall aims of this proposal are to improve, facilitate, optimize and equalize the existing screening system for adverse pregnancy outcomes in early pregnancy in order to limit adverse consequences for both the mother and infant, by:

1. Creating a Swedish prediction model with population-specific risk factors, optimized for the Swedish health care system, identifying high-risk women for preterm preeclampsia and validate the model within the cohort. This would give us the possibility to start aspirin prophylaxis in time, which has been proven to reduce the risk of developing preterm preeclampsia by 50%.

2. Validating the Fetal Medicine Foundation prediction model for detection of preterm (< 37 gestational weeks) preeclampsia in a Swedish population.

3. Creating a prediction model identifying high-risk women for overall preeclampsia during pregnancy and birth of a small for gestational age infant in order to plan individualized surveillance for early detection, which has been proven beneficial for both the mother and infant.

4. Creating a national pregnancy biobank with blood samples and individual clinical registry data, including pregnancy outcomes, enabling future research on prevention and early detection for various adverse pregnancy outcomes which could be such as preterm birth and intrauterine growth restriction.

Description:

Preeclampsia is a pregnancy-specific syndrome that affects 3-5% of all pregnancies and traditionally defined as new onset hypertension (blood pressure ≥ 140/90) and proteinuria after gestational week 20. The syndrome is one of the leading causes of maternal and perinatal acute morbidity and long-term disability and accounts for about 50 000 maternal deaths annually worldwide. Morbidity risks for the mother include seizures, intracranial hemorrhage, kidney failure, heart failure and pulmonary edema. Risks for the fetus include fetal growth restriction, preterm birth and hypoxia. Generally preterm preeclampsia (delivery before 37 weeks) is more severe than term preeclampsia.

Risk assessment for preeclampsia enables both prevention and early prediction of the disease.

Swedish risk assessment for preeclampsia in early pregnancy is still obtained by maternal history and characteristics, without medical examinations, which only detects about 30% of women that will develop preeclampsia. Risk factors are evaluated individually without being incorporated into a combined model that would allow multivariable analysis. This approach has been proven to be poor due to low specificity and sensitivity. Lately a more complex prediction model has been developed by the Fetal Medicine Foundation, using multivariable analysis and including serum biomarkers and physiological measurements reflecting maternal adaption to pregnancy. Intervention with aspirin given to identified high-risk pregnancies according this model has been shown to decrease the incidence of preterm (< 37 gestational weeks) preeclampsia (OR: 0.38; 95% CI 0.20-0.74), compared to placebo. Detection rates and cut-off values have been shown to vary between populations, depending on differences in population characteristics and incidence of disease, overfitting of the original model and differences in healthcare systems. Therefore, the model needs to be validated in Sweden. Further, the Fetal Medicine Foundation prediction model includes expensive covariates such as several biochemical markers and uterine artery Doppler. There is a need to create, validate and implement a cost-effective prediction model for first trimester screening for preeclampsia in a Swedish population, with the purpose to select who might benefit from aspirin prophylaxis to prevent preterm preeclampsia. We will study preeclampsia both according to the definition used in Sweden prior to 2020 and the definition used hereafter.

Early detection of preeclampsia remains one of the major focuses of maternal health care and is emphasized by the WHO, since it has proven to be beneficial for both the mother and unborn child. Small-for-gestational-age fetuses not identified before delivery have an increased risk of adverse perinatal outcomes, compared to those identified during pregnancy. Identification of high-risk pregnancies is therefore important in early pregnancy not only to plan for prophylactic interventions, but also to optimize surveillance and to plan deliveries. Today most Swedish women attend the same maternal health care program with increasing number of visits in the end of pregnancy. By risk identification in early pregnancy we can individualize maternal health care and target women at high risk early in pregnancy. High-risk pregnancies can be referred to specialized health care and normal pregnancies followed at the basic maternal health care.

The Swedish registry data is unique and combining it with a biobank containing blood samples from the first trimester could improve maternal healthcare and in the long run reduce adverse outcomes for Swedish women. A national first trimester pregnancy biobank would facilitate future research on prevention and prediction of pregnancy complications.

A total of 13000 enrolled individuals will be needed for creating the model and for validation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13000
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Women with a Swedish personal identity number, who adhere to maternal care program before the end of the first trimester and have a planned first trimester scan (weeks 11-13) are eligible for the study.

Exclusion Criteria:

• Maternal age <18 years or language-barrier despite interpreter and written information.

Related Conditions & MeSH terms

• Eclampsia
• Pre-Eclampsia

Intervention

Diagnostic Test:
• history
combining these 4 interventions will great an algorithm predicting preeclampsia

Locations

Country	Name	City	State
Sweden	Södra Älvsborgs sjukhus	Borås	Västra Götalandsregionen
Sweden	Eskilstuna hospital	Eskilstuna	Sörmland
Sweden	County Council Dalarna	Falun
Sweden	Gothenburg University, Sahlgrenska academy, dept of obstetrics and gynecology	Gothenburg
Sweden	Lund University Hospital, dept of obstetrics and gynecology	Lund
Sweden	Örebro University Hospital	Örebro
Sweden	Karolinska Institute	Stockholm
Sweden	Norra Älvsborgs sjukhus	Trollhättan	Västra Götalandsregionen
Sweden	Uppsala University Hopsital, department of women's and children's health	Uppsala

Sponsors (4)

Lead Sponsor	Collaborator
Uppsala University	Perkin Elmer Inc., Roche Pharma AG, Thermo Fisher Scientific, Inc

Country where clinical trial is conducted

Sweden, 

References & Publications (13)

Akolekar R, Syngelaki A, Poon L, Wright D, Nicolaides KH. Competing risks model in early screening for preeclampsia by biophysical and biochemical markers. Fetal Diagn Ther. 2013;33(1):8-15. doi: 10.1159/000341264. Epub 2012 Aug 16. Erratum In: Fetal Diag — View Citation

Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol. 2009 Jun;33(3):130-7. doi: 10.1053/j.semperi.2009.02.010. — View Citation

Lindqvist PG, Molin J. Does antenatal identification of small-for-gestational age fetuses significantly improve their outcome? Ultrasound Obstet Gynecol. 2005 Mar;25(3):258-64. doi: 10.1002/uog.1806. — View Citation

Mol BWJ, Roberts CT, Thangaratinam S, Magee LA, de Groot CJM, Hofmeyr GJ. Pre-eclampsia. Lancet. 2016 Mar 5;387(10022):999-1011. doi: 10.1016/S0140-6736(15)00070-7. Epub 2015 Sep 2. — View Citation

Mosimann B, Pfiffner C, Amylidi-Mohr S, Risch L, Surbek D, Raio L. First trimester combined screening for preeclampsia and small for gestational age - a single centre experience and validation of the FMF screening algorithm. Swiss Med Wkly. 2017 Aug 25;14 — View Citation

O'Gorman N, Wright D, Syngelaki A, Akolekar R, Wright A, Poon LC, Nicolaides KH. Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 11-13 weeks gestation. Am J Obstet Gynecol. 2016 Jan;214(1):103.e1-103.e12. doi: 10. — View Citation

Oliveira N, Magder LS, Blitzer MG, Baschat AA. First-trimester prediction of pre-eclampsia: external validity of algorithms in a prospectively enrolled cohort. Ultrasound Obstet Gynecol. 2014 Sep;44(3):279-85. doi: 10.1002/uog.13435. Epub 2014 Aug 13. — View Citation

Rolnik DL, Wright D, Poon LC, O'Gorman N, Syngelaki A, de Paco Matallana C, Akolekar R, Cicero S, Janga D, Singh M, Molina FS, Persico N, Jani JC, Plasencia W, Papaioannou G, Tenenbaum-Gavish K, Meiri H, Gizurarson S, Maclagan K, Nicolaides KH. Aspirin ve — View Citation

Sreeja Sarojini AG, Andrew Pecora and K. Stephen Suh. Proactive Biobanking to Improve Research and Health Care. Journal of Tissue Science & Engineering.

Stephansson O, Petersson K, Bjork C, Conner P, Wikstrom AK. The Swedish Pregnancy Register - for quality of care improvement and research. Acta Obstet Gynecol Scand. 2018 Apr;97(4):466-476. doi: 10.1111/aogs.13266. Epub 2017 Dec 14. — View Citation

WHO Recommendations for Prevention and Treatment of Pre-Eclampsia and Eclampsia. Geneva: World Health Organization; 2011. Available from http://www.ncbi.nlm.nih.gov/books/NBK140561/ — View Citation

Wikstrom AK, Larsson A, Eriksson UJ, Nash P, Norden-Lindeberg S, Olovsson M. Placental growth factor and soluble FMS-like tyrosine kinase-1 in early-onset and late-onset preeclampsia. Obstet Gynecol. 2007 Jun;109(6):1368-74. doi: 10.1097/01.AOG.0000264552 — View Citation

Wright D, Syngelaki A, Akolekar R, Poon LC, Nicolaides KH. Competing risks model in screening for preeclampsia by maternal characteristics and medical history. Am J Obstet Gynecol. 2015 Jul;213(1):62.e1-62.e10. doi: 10.1016/j.ajog.2015.02.018. Epub 2015 F — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Preterm Preeclampsia	Preeclampsia according to the Swedish definition, currently new onset hypertension (blood pressure = 140/90) and proteinuria after gestational week 20.	delivery <37 gestational weeks
Secondary	Small for gestational age	birthweight = - 2 SD according to the Swedish reference curve	at delivery
Secondary	Overall preeclampsia	Preeclampsia according to the Swedish definition, currently new onset hypertension (blood pressure = 140/90) and proteinuria after gestational week 20.	At delivery
Secondary	Preterm preeclampsia	Preeclampsia according to the Swedish definition prior to 2020 as well as the definition hereafter	delivery <37 gestational weeks
Secondary	Term preeclampsia	Preeclampsia according to the Swedish definition prior to 2020 as well as the definition hereafter	delivery >/=37 gestational weeks