Pre-EclampsiaNCT06115122

PEPPI Study: Identification of Women at Risk for Placental Dysfunction

An observational study of Pre-Eclampsia and Intrauterine Growth Restriction, run by Oulu University Hospital at 1 site in Finland.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial summary

The main purpose of this study is to evaluate Fetal Medicine Foundation's pre-eclampsia risk calculator using maternal characteristics, first trimester serum placental growth factor (PlGF) and mean arterial pressure (MAP) in a Finnish general population. Read more about this study

Who is it for?: Any ageHealthy volunteers can take part
Conditions the study is for: Pre-Eclampsia, Intrauterine Growth Restriction, Polycystic Ovary Syndrome
What is being tested?: Pre-eclampsia screening program
How many people: 3,000 participants
Where: 1 siteFinland
Study dates: 15 Feb 2022to 31 Dec 2041
How long will I take part?: 15 Years
Phase: Observational
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Any age
All sexes
Healthy volunteers accepted
Child, Adult, Older adult

Study population: All pregnant women eligible for the study will be invited to participate the study during their first visit to maternity care. Children born to these women and children's fathers will be asked to participate in the study at the labor hospital.

Who may be able to join

Pregnant (first trimester)
Understands Finnish
≥18 years
Signed informed consent
Participates in PEPPI-study (criteria above)
Blood samples at first and third trimester of pregnancy

Show all 15Show fewer

Permits blood sampling from the umbilical cord when the baby is born
Biological father to the child born for the mother who participated in PEPPI study
≥18 years
Signed informed consent
Born to mother who participated in PEPPI study
Signed informed consent from parent(s)
Signed informed consent from parent(s)
Mother has blood samples taken at first and third trimester (iron status)
Child has blood samples taken at birth and at 3 months of age

Who cannot join

Multiple pregnancy
Miscarriage/termination of the index pregnancy
No first trimester blood sampling
No first or third trimester blood sampling
No umbilical cord blood sample after baby is born
Fathers

Show all 14Show fewer

Does not understand Finnish
Children
No consent from parent(s)
Inclusion Criteria for PEPPI-offspring study • Mother in risk-, control-, or PCOS group during PEPPI-study with ultrasound information at gestational weeks 30-32 or a mother who developed pre-eclampsia during the pregnancy regardless of their study group during PEPPI-study
Mother/father declines participation
No consent from parent(s)
No blood samples from mother
No blood samples from child

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Jaana E Nevalainen, Assoc prof contact

+358405801857

jaana.nevalainen@oulu.fi

Terhi Piltonen, Professor contact

+358405008266

terhi.piltonen@oulu.fi

Finland1 site, 1 recruiting

The Wellbeing Services County of North Ostrobothnia
Oulu, 90100
Jaana E Nevalainen, Assoc Prof, +358405801857, jaana.nevalainen@oulu.fi
Terhi Piltonen, Professor, +358405008266, terhi.piltonen@oulu.fi
Recruiting

Other trials in Finland

About this study

Official title: PEPPI Study: Identification of Women at Risk for Placental Dysfunction During the First and Third Trimesters of Pregnancy

Condition or disease: pre-eclampsia, intrauterine growth restriction, polycystic ovary syndrome

Read the detailed description

According to power calculations, altogether 3000 pregnant women will be recruited into PEPPI-study in Oulu area. Women will be recruited during their first visit to maternity care. Women will have blood samples for study purposes at first and third trimester of pregnancy. Participants will be divided into risk-, control- and polycystic ovary syndrome (PCOS) groups according to pre-eclampsia risk calculation program and questionnaire (PCOS: Rotterdam criteria) (N=300/group). Half of the women in risk- and control groups and all women in PCOS group will have a pregnancy ultrasound scan at 30-32 weeks of gestation. Fathers and children will be recruited at the Oulu University Hospital when the child is born.

Studies within PEPPI-study:

PEPPI-offspring: Children born for those 600 women in risk-, control and PCOS groups who have an extra ultrasound at gestational weeks 30-32 during PEPPI-study and children whose mother developed pre-eclampsia during the pregnancy regardless of her study group during PEPPI-study are recruited into PEPPI-offspring study. PEPPI-offspring study investigates the short- and long-term consequences of placental insufficiency/pre-eclampsia on the health of the children.

PEPPI-PCOS: Investigates pregnancy characteristics of women with PCOS. Women with PCOS form PCOS study group, have additional ultrasound scan at gestational weeks 30-32 and their children are recruited into PEPPI-offspring study.

FERPPI: FERPPI study investigates the possible connection between placental insufficiency and iron deficiency with or without anemia in both pregnant women and their children after birth.

Conditions: Pre-Eclampsia, Intrauterine Growth Restriction, Polycystic Ovary Syndrome, Iron-deficiency, Cardiovascular Diseases, Hypertensive Disorder of Pregnancy
Being tested: Pre-eclampsia screening program
Medical subject headings: Pre-Eclampsia, Fetal Growth Retardation, Polycystic Ovary Syndrome, Anemia, Iron-Deficiency, Cardiovascular Diseases, Toxemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Pre-eclampsia screening programOther
Pregnant women will be devided into risk-, control- and PCOS groups according to first trimester screening program.

Study groups in NCT06115122
Study group	Role	What they receive
Pre-eclampsia risk group		Approximately 300 women will be enrolled into a risk group according to a pre-eclampsia risk calculator. Receives: Other: Pre-eclampsia screening program
PCOS group		Women enrolled into study who fulfill ≥2 Rotterdam criteria. Women with PCOS may be included in risk- or control groups. Receives: Other: Pre-eclampsia screening program
Control group		Approximately 300 women in low risk for pre-eclampsia according to a pre-eclampsia risk calculator. Receives: Other: Pre-eclampsia screening program
Follow up group		Approximately 2100 women who are not enrolled into risk-, control- or PCOS groups. Receives: Other: Pre-eclampsia screening program
Children		Mothers and fathers will be asked for permission to follow the child's health information from national registers until the age of 15 years. Approximately 300 children will be recruited to PEPPI-offspring follow up study (including also PCOS offspring).
Fathers		The role of fathers in the development of pregnancy complications and on the health of the offspring.

What is being measured

The primary outcome is the main question the study is designed to answer.

Composite of Pregnancy-associated Hypertension and Serious Adverse Outcomes in the Mother or Fetus or Neonate
Severe hypertension (blood pressure [BP]≥ 160/110) or mild hypertension (BP≥140/90) ≥ 20 weeks gestation in conjunction with one of the following: elevated liver enzymes, thrombocytopenia, elevated serum creatinine levels, eclamptic seizure, an indicated preterm birth before 32 weeks of gestation owing to hypertension-related disorders, a fetus that was small for gestational age (SGA, below 3rd percentile) adjusted for sex and race or ethnic group, fetal death after 20 weeks of gestation, or neonatal death
Measured: 20 weeks through discharge following delivery
Severe Hypertension
Women who had severe hypertension only and those who had severe hypertension with elevated liver enzyme levels, thrombocytopenia, elevated serum creatinine levels, eclamptic seizure, medically indicated preterm birth, fetal-growth restriction, or fetal death after 20 weeks of gestation, or neonatal death.
Measured: 20 weeks through discharge following delivery
Severe or Mild Pregnancy-associated Hypertension With Elevated Liver Enzyme Levels
Elevated liver enzyme levels are specified as an aspartate aminotransferase level of ≥ 100 U/l. Women who met more than one component of the primary outcome are counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
Measured: 20 weeks through discharge following delivery
Severe or Mild Pregnancy-associated Hypertension With Thrombocytopenia
Thrombocytopenia defined as a platelet count of <100 × 109/l. Women who meet more than one component of the primary outcome are counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
Measured: 20 weeks through discharge following delivery
Severe or Mild Pregnancy-associated Hypertension With an Elevated Serum Creatinine Level
Elevated serum creatinine defined as ≥90 µmol/l. Women who meet more than one component of the primary outcome are counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
Measured: 20 weeks through discharge following delivery
Severe or Mild Pregnancy-associated Hypertension With an Eclamptic Seizure
Women who meet more than one component of the primary outcome are counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
Measured: 20 weeks through discharge following delivery
Severe or Mild Pregnancy-associated Hypertension With an Indicated Preterm Birth Before 32-34-37 Weeks of Gestation Owing to Hypertension-related Disorders
Women who meet more than one component of the primary outcome are counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
Measured: 20 weeks through discharge following delivery
Severe or Mild Pregnancy-associated Hypertension With a Fetus That Was Small for Gestational Age (Below the - 2 SD) Adjusted for Sex and Race or Ethnic Group
Women who meet more than one component of the primary outcome are counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
Measured: 20 weeks through discharge following delivery
Severe or Mild Pregnancy-associated Hypertension With a Fetal Death After 20 Weeks of Gestation or Neonatal Death
Women who meet more than one component of the primary outcome are counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
Measured: 20 weeks through discharge or prior to discharge following delivery admission
Prevalence of high pre-eclampsia risk score in women with PCOS compared to non-PCOS women
Pre-eclampsia risk score is calculated with LifeCycle risk calculation program and a risk of 1:100 or higher is considered as high risk for pre-eclampsia.
Measured: at 13 gestational weeks
11. All the above mentioned outcomes (1-10) in PCOS group compared to non-PCOS group.
As described above.
Measured: 13 gestational weeks through discharge following delivery
The height of the child during the first year of life.
Measurement of height (cm)
Measured: At 0, 3 and 6-12 months of age
The weight of the child during the first year of life.
Measurement of weight (g, kg)
Measured: At 0, 3 and 6-12 months of age
The body mass index (BMI) of the child during the first year of life.
Measurements of height (cm) and weight (kg) combined as BMI (kg/m2)
Measured: At 0, 3 and 6-12 months of age
Basic blood count
B-Hb, B-Leuk, B-Hkr, B-Eryt, E-MCV, E-RDW, E-MCH, E-MCHC, B-Trom
Measured: At 0, 3 and 6-12 months of age
Ferritin
Measured: At 0, 3 and 6-12 months of age
Hepcidin
Measured: At 0, 3 and 6-12 months of age
Saturation of transferrin
Measured: At 0, 3 and 6-12 months of age
Hypersensitive-C-reactive protein
Measured: At 0, 3 and 6-12 months of age
Anti-mullerian hormone
Measured: At 3 and 6-12 months of age
Cortisol
Measured: At 3 and 6-12 months of age
Corticotropin
Measured: At 3 and 6-12 months of age
Dehydroepiandrosterone
Measured: At 3 and 6-12 months of age
Progesterone
Measured: At 3 and 6-12 months of age
Inhibin-B
Measured: At 3 and 6-12 months of age
Luteinizing hormone
Measured: At 3 and 6-12 months of age
Follicle stimulating hormone
Measured: At 3 and 6-12 months of age
Testosterone (boys)
Measured: At 3 and 6-12 months of age
Estradioli (girls)
Measured: At 3 and 6-12 months of age
Vitamin D
Measured: At 3 and 6-12 months of age
Calcium
Measured: At 3 and 6-12 months of age
Phosphate
Measured: At 3 and 6-12 months of age
Alkaline phosphatase
Measured: At 3 and 6-12 months of age
Parathyroid hormone
Measured: At 3 and 6-12 months of age
Clinical examination of genitals
Measurement of perineum with centimeters (cm)
Measured: At 0, 3 and 6-12 months of age
Clinical examination of mammary glands
Measurement with millimeters (mm)
Measured: At 3 and 6-12 months of age
Sebum measurement
Measurement is done with Sebumeter ®. The cassette is placed on the skin for a defined length of time and then returned to the aperture. The change in the amount of light transmission represents the sebum content of the tape, which is displayed in units from 0-350.
Measured: At 3 and 6-12 months of age
Heart auscultation with stethoscope.
Measured: At 3 and 6-12 months of age
Ultrasound scan of the heart (echo)
Measured: At 3 and 6-12 months of age
Birth Weight
Grams
Measured: At birth
Small for Gestational Age
A baby whose birth weight is less than the - 2 standard deviations is considered to be small for gestational age (adjusted for sex and race or ethnic group)
Measured: At birth
Large for gestational age
A baby whose birth weight is more than the + 2 standard deviations is considered to be small for gestational age (adjusted for sex and race or ethnic group)
Measured: At birth
Admission to NICU
NICU denotes neonatal intensive care unit.
Measured: Delivery through discharge up to 18 weeks
Apgar Score ≤3 at 5 Minutes
Measured: At birth
Fetal iron deficiency
Fetal iron deficiency defined by reticulocyte hemoglobin < 29 pg from umbilical cord blood collected at birth
Measured: At birth
Iron deficiency during third trimester of pregnancy
Iron deficiency defined as serum ferritin < 30 µg/l at gestational weeks 30-32 with or without anemia defined as Hb ≤ 110 g/l.
Measured: At 30-32 weeks of gestation
Severe iron deficiency during third trimester of pregnancy
Iron deficiency defined as serum ferritin < 15 µg/l at gestational weeks 30-32 with or without anemia defined as Hb ≤ 110 g/l.
Measured: At 30-32 weeks of gestation

Secondary outcomes (38)

Pre-eclampsia (Mild, Severe, HELLP Syndrome, Eclampsia).
HELLP denotes hemolytic anemia, elevated liver enzymes, and low platelet count.
Measured: 20 weeks through discharge following delivery.
Superimposed Pre-eclampsia (Mild, Severe, HELLP Syndrome, Eclampsia).
Women with Hypertension before pregnancy week 20. HELLP denotes hemolytic anemia, elevated liver enzymes, and low platelet count.
Measured: 20 weeks through discharge following delivery.
Pregnancy Associated Hypertension.
Women with Hypertension after pregnancy week 20.
Measured: 20 weeks through discharge following delivery.
Medically Indicated Delivery Because of Hypertension.
Measured: 20 weeks through discharge following delivery.
Fetal Weight Estimation under 3rd percentile at gestational weeks 30-32 ultrasound scan.
Measured: 30-32 weeks.
Abnormal uterine artery pulsatility index at gestational weeks 30-32 ultrasound scan
According to calculator provided by Fetal Medicine Foundation (https://fetalmedicine.org/research/utpi).
Measured: At 30-32 weeks.
Aspartate Aminotransferase ≥100 U/Liter.
Measured: 20 weeks through discharge.
Creatinine ≥90 µmol/l.
Measured: 20 weeks through discharge.
Massive postpartum hemorrhage.
Massive postpartum hemorrhage defined≥ 1000ml blood loss within 24 hours after child birth.
Measured: From delivery to 24 hours after child birth
Premature Rupture of Membranes.
If the water breaks before the 37th week of pregnancy, it is called preterm premature rupture of membranes (PPROM).
Measured: From 22nd gestational week until delivery
Placental Abruption.
Defined as the placenta separates from the inner wall of the uterus before birth.
Measured: From 22nd gestational week until delivery
Gestational Diabetes.
Defined as abnormal glucose tolerance test during pregnancy (≥ 5.3 mmol/l (0 h), ≥ 10.0 mmol/l (1 h) and/or ≥ 8.6 mmol/l (2 h). Treatment either with diet or medicine (metformin and/or insulin therapy).
Measured: From gestation until delivery
Cesarean Delivery.
Measured: At Birth.
Vacuum Extraction Delivery.
Measured: At Birth.
Maternal Death.
Measured: During pregnancy or within 42 days after delivery
Postpartum Pulmonary Edema.
Measured: Within 42 days after delivery
Hematocrit ≤24% With Transfusion.
Measured: Within 42 days after delivery
Maternal Hospital Stay.
Duration of the time spend at the hospital after delivery (measured as days and weeks)
Measured: Within 42 days after delivery
Gestational Age at Delivery.
Measured: At Delivery.
Perineal Lacerations.
Defined as first, second, third or fourth degree lacerations during birth.
Measured: At Birth.
Number of Visits to Maternity Health Care During Pregnancy.
Measured: From gestation until delivery, on average during 9 months
Number of Visits at Tertiary Maternity Care Hospital.
Measured: From gestation until delivery, on average during 9 months
Fetal Death.
Measured: From 22nd gestational week until delivery
Neonatal Death.
Measured: Birth until 4 weeks' of age
Respiratory Distress Syndrome.
Measured: Birth until 4 weeks' of age
Intraventricular Hemorrhage, Grade III or IV.
Measured: Birth until 4 weeks' of age
Neonatal sepsis.
Measured: Birth until 4 weeks' of age
Necrotizing Enterocolitis.
Measured: Birth until 4 weeks' of age
Retinopathy of Prematurity.
Measured: Birth until 4 weeks' of age
Neonatal Hospital Stay.
Measured: Birth until 18 weeks' of age
Umbilical artery pulsatility index
Measured with Doppler ultrasound
Measured: At 30-32 gestational weeks
Mean cerebral artery pulsatility index
Measured with Doppler ultrasound
Measured: At 30-32 gestational weeks
Ductus venousus pulsatility index
Measured with Doppler ultrasound
Measured: At 30-32 gestational weeks
Fetal weight estimation
Measured with ultrasound using fetal BPD, HC, AC and FL measurements (Hadlock)
Measured: At 30-32 gestational weeks
Amniotic fluid measurement
Ultrasound measurements of maximum velocity pocket (cm) and amniotic fluid index (cm)
Measured: At 30-32 gestational weeks
Estimation of fetal movement during ultrasound scan
Estimated as a whole with inspection of body movements, limb movements and breathing movement
Measured: At 30-32 gestational weeks
Apgar Score ≤7 at 5 minutes.
Measured: At birth.
Blood transfusion.
Defined as red blood cell transfusion received by patient (mother or child).
Measured: From 22nd pregnancy week until four weeks after delivery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Feb 202231 Dec 2041

First posted2 Nov 2023
Study start15 Feb 2022
Primary completion31 Dec 2027 (estimated)
Study completion31 Dec 2041 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (23)Papers the sponsor has linked to this study.
Other trials for Pre-EclampsiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Cohort
Time perspective: Prospective
Enrolment: 3,000 participants (estimated)
Target duration: 15 Years

IDs, dates and publications

ClinicalTrials.gov ID: NCT06115122
Sponsor's protocol ID: OuluUH_PEPPI
Status last verified: Jul 2025
First submitted: 28 Nov 2022
Last updated: 5 Aug 2025
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: Data will deposited into Oulu University Hospital's and Oulu University's data bank.

Publications

Ashraf UM, Hall DL, Rawls AZ, Alexander BT. Epigenetic processes during preeclampsia and effects on fetal development and chronic health. Clin Sci (Lond). 2021 Oct 15;135(19):2307-2327. doi: 10.1042/CS20190070.
PubMed 34643675
Bahri Khomami M, Joham AE, Boyle JA, Piltonen T, Silagy M, Arora C, Misso ML, Teede HJ, Moran LJ. Increased maternal pregnancy complications in polycystic ovary syndrome appear to be independent of obesity-A systematic review, meta-analysis, and meta-regression. Obes Rev. 2019 May;20(5):659-674. doi: 10.1111/obr.12829. Epub 2019 Jan 23.
PubMed 30674081
Becker M, Hesse V. Minipuberty: Why Does it Happen? Horm Res Paediatr. 2020;93(2):76-84. doi: 10.1159/000508329. Epub 2020 Jun 29.
PubMed 32599600
Binder NK, Evans J, Salamonsen LA, Gardner DK, Kaitu'u-Lino TJ, Hannan NJ. Placental Growth Factor Is Secreted by the Human Endometrium and Has Potential Important Functions during Embryo Development and Implantation. PLoS One. 2016 Oct 6;11(10):e0163096. doi: 10.1371/journal.pone.0163096. eCollection 2016.
PubMed 27711226
Chockalingam UM, Murphy E, Ophoven JC, Weisdorf SA, Georgieff MK. Cord transferrin and ferritin values in newborn infants at risk for prenatal uteroplacental insufficiency and chronic hypoxia. J Pediatr. 1987 Aug;111(2):283-6. doi: 10.1016/s0022-3476(87)80088-4.
PubMed 3612404
Dewey KG, Oaks BM. U-shaped curve for risk associated with maternal hemoglobin, iron status, or iron supplementation. Am J Clin Nutr. 2017 Dec;106(Suppl 6):1694S-1702S. doi: 10.3945/ajcn.117.156075. Epub 2017 Oct 25.
PubMed 29070565
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.
PubMed 19464502
Duley L, Henderson-Smart DJ, Meher S, King JF. Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD004659. doi: 10.1002/14651858.CD004659.pub2.
PubMed 17443552
Guy GP, Leslie K, Diaz Gomez D, Forenc K, Buck E, Khalil A, Thilaganathan B. Implementation of routine first trimester combined screening for pre-eclampsia: a clinical effectiveness study. BJOG. 2021 Jan;128(2):149-156. doi: 10.1111/1471-0528.16361. Epub 2020 Jul 1.
PubMed 32613730
Henley D, Brown S, Pennell C, Lye S, Torpy DJ. Evidence for central hypercortisolism and elevated blood pressure in adolescent offspring of mothers with pre-eclampsia. Clin Endocrinol (Oxf). 2016 Oct;85(4):583-9. doi: 10.1111/cen.13092. Epub 2016 May 26.
PubMed 27144974
Kalousova M, Muravska A, Zima T. Pregnancy-associated plasma protein A (PAPP-A) and preeclampsia. Adv Clin Chem. 2014;63:169-209. doi: 10.1016/b978-0-12-800094-6.00005-4.
PubMed 24783354
Koster MP, de Wilde MA, Veltman-Verhulst SM, Houben ML, Nikkels PG, van Rijn BB, Fauser BC. Placental characteristics in women with polycystic ovary syndrome. Hum Reprod. 2015 Dec;30(12):2829-37. doi: 10.1093/humrep/dev265. Epub 2015 Oct 25.
PubMed 26498178
Nevalainen J, Korpimaki T, Kouru H, Sairanen M, Ryynanen M. Performance of first trimester biochemical markers and mean arterial pressure in prediction of early-onset pre-eclampsia. Metabolism. 2017 Oct;75:6-15. doi: 10.1016/j.metabol.2017.07.004. Epub 2017 Jul 18.
PubMed 28964327
Nevalainen J, Skarp S, Savolainen ER, Ryynanen M, Jarvenpaa J. Intrauterine growth restriction and placental gene expression in severe preeclampsia, comparing early-onset and late-onset forms. J Perinat Med. 2017 Oct 26;45(7):869-877. doi: 10.1515/jpm-2016-0406.
PubMed 28593875
O'Gorman N, Wright D, Rolnik DL, Nicolaides KH, Poon LC. Study protocol for the randomised controlled trial: combined multimarker screening and randomised patient treatment with ASpirin for evidence-based PREeclampsia prevention (ASPRE). BMJ Open. 2016 Jun 28;6(6):e011801. doi: 10.1136/bmjopen-2016-011801.
PubMed 27354081

Interested in taking part?

Jaana E Nevalainen, Assoc prof

+358405801857

jaana.nevalainen@oulu.fi

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 5 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: PEPPI Study: Identification of Women at Risk for Placental Dysfunction During the First and Third Trimesters of Pregnancy
ClinicalTrials.gov ID: NCT06115122
Acronym / sponsor ID: OuluUH_PEPPI
Conditions: Pre-Eclampsia, Intrauterine Growth Restriction, Polycystic Ovary Syndrome, Iron-deficiency, Cardiovascular Diseases, Hypertensive Disorder of Pregnancy
Study type: Observational
Recruitment status: Recruiting
Enrolment: 3,000 participants (estimated)
Lead sponsor: Oulu University HospitalUniversity, hospital or other
Collaborators: PerkinElmer, Inc., Roche Diagnostics GmbH, Academy of Finland, Sigrid Jusélius Foundation, Finnish Medical Foundation, University of Oulu
Study start: 15 Feb 2022 (actual)
Primary completion: 31 Dec 2027 (estimated)
Study completion: 31 Dec 2041 (estimated)
First posted: 2 Nov 2023 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Condition or disease: pre-eclampsia, intrauterine growth restriction, polycystic ovary syndrome

Detailed description

Studies within PEPPI-study:

FERPPI: FERPPI study investigates the possible connection between placental insufficiency and iron deficiency with or without anemia in both pregnant women and their children after birth.

Study design

Observational model: Cohort
Time perspective: Prospective
Target follow-up: 15 Years
Number of arms: 6

Arm	Type	Receives
Pre-eclampsia risk group	–	Other: Pre-eclampsia screening programApproximately 300 women will be enrolled into a risk group according to a pre-eclampsia risk calculator.
PCOS group	–	Other: Pre-eclampsia screening programWomen enrolled into study who fulfill ≥2 Rotterdam criteria. Women with PCOS may be included in risk- or control groups.
Control group	–	Other: Pre-eclampsia screening programApproximately 300 women in low risk for pre-eclampsia according to a pre-eclampsia risk calculator.
Follow up group	–	Other: Pre-eclampsia screening programApproximately 2100 women who are not enrolled into risk-, control- or PCOS groups.
Children	–	–Mothers and fathers will be asked for permission to follow the child's health information from national registers until the age of 15 years. Approximately 300 children will be recruited to PEPPI-offspring follow up study (including also PCOS offspring).
Fathers	–	–The role of fathers in the development of pregnancy complications and on the health of the offspring.

Who may qualify

Sex: All
Healthy volunteers: Accepted
Age groups: Child, Adult, Older adult
Study population: All pregnant women eligible for the study will be invited to participate the study during their first visit to maternity care. Children born to these women and children's fathers will be asked to participate in the study at the labor hospital.

Key inclusion criteria (15 listed)

Pregnant (first trimester)
Understands Finnish
≥18 years
Signed informed consent
Participates in PEPPI-study (criteria above)

Key exclusion criteria (14 listed)

Multiple pregnancy
Miscarriage/termination of the index pregnancy
No first trimester blood sampling
No first or third trimester blood sampling
No umbilical cord blood sample after baby is born

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Pre-eclampsia screening programPregnant women will be devided into risk-, control- and PCOS groups according to first trimester screening program.	Other	Control group, Follow up group, PCOS group, Pre-eclampsia risk group

Primary outcome

Composite of Pregnancy-associated Hypertension and Serious Adverse Outcomes in the Mother or Fetus or Neonate
Time frame: 20 weeks through discharge following delivery
Severe hypertension (blood pressure [BP]≥ 160/110) or mild hypertension (BP≥140/90) ≥ 20 weeks gestation in conjunction with one of the following: elevated liver enzymes, thrombocytopenia, elevated serum creatinine levels, eclamptic seizure, an indicated preterm birth before 32 weeks of gestation owing to hypertension-related disorders, a fetus that was small for gestational age (SGA, below 3rd percentile) adjusted for sex and race or ethnic group, fetal death after 20 weeks of gestation, or neonatal death
Severe Hypertension
Time frame: 20 weeks through discharge following delivery
Women who had severe hypertension only and those who had severe hypertension with elevated liver enzyme levels, thrombocytopenia, elevated serum creatinine levels, eclamptic seizure, medically indicated preterm birth, fetal-growth restriction, or fetal death after 20 weeks of gestation, or neonatal death.
Severe or Mild Pregnancy-associated Hypertension With Elevated Liver Enzyme Levels
Time frame: 20 weeks through discharge following delivery
Elevated liver enzyme levels are specified as an aspartate aminotransferase level of ≥ 100 U/l. Women who met more than one component of the primary outcome are counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
Severe or Mild Pregnancy-associated Hypertension With Thrombocytopenia
Time frame: 20 weeks through discharge following delivery
Thrombocytopenia defined as a platelet count of <100 × 109/l. Women who meet more than one component of the primary outcome are counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
Severe or Mild Pregnancy-associated Hypertension With an Elevated Serum Creatinine Level
Time frame: 20 weeks through discharge following delivery
Elevated serum creatinine defined as ≥90 µmol/l. Women who meet more than one component of the primary outcome are counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
Severe or Mild Pregnancy-associated Hypertension With an Eclamptic Seizure
Time frame: 20 weeks through discharge following delivery
Women who meet more than one component of the primary outcome are counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
Severe or Mild Pregnancy-associated Hypertension With an Indicated Preterm Birth Before 32-34-37 Weeks of Gestation Owing to Hypertension-related Disorders
Time frame: 20 weeks through discharge following delivery
Women who meet more than one component of the primary outcome are counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
Severe or Mild Pregnancy-associated Hypertension With a Fetus That Was Small for Gestational Age (Below the - 2 SD) Adjusted for Sex and Race or Ethnic Group
Time frame: 20 weeks through discharge following delivery
Women who meet more than one component of the primary outcome are counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
Severe or Mild Pregnancy-associated Hypertension With a Fetal Death After 20 Weeks of Gestation or Neonatal Death
Time frame: 20 weeks through discharge or prior to discharge following delivery admission
Women who meet more than one component of the primary outcome are counted for each component. Therefore, the number of women for all individual components combined is greater than the number of women with the primary outcome.
Prevalence of high pre-eclampsia risk score in women with PCOS compared to non-PCOS women
Time frame: at 13 gestational weeks
Pre-eclampsia risk score is calculated with LifeCycle risk calculation program and a risk of 1:100 or higher is considered as high risk for pre-eclampsia.
11. All the above mentioned outcomes (1-10) in PCOS group compared to non-PCOS group.
Time frame: 13 gestational weeks through discharge following delivery
As described above.
The height of the child during the first year of life.
Time frame: At 0, 3 and 6-12 months of age
Measurement of height (cm)
The weight of the child during the first year of life.
Time frame: At 0, 3 and 6-12 months of age
Measurement of weight (g, kg)
The body mass index (BMI) of the child during the first year of life.
Time frame: At 0, 3 and 6-12 months of age
Measurements of height (cm) and weight (kg) combined as BMI (kg/m2)
Basic blood count
Time frame: At 0, 3 and 6-12 months of age
B-Hb, B-Leuk, B-Hkr, B-Eryt, E-MCV, E-RDW, E-MCH, E-MCHC, B-Trom
Ferritin
Time frame: At 0, 3 and 6-12 months of age
Hepcidin
Time frame: At 0, 3 and 6-12 months of age
Saturation of transferrin
Time frame: At 0, 3 and 6-12 months of age
Hypersensitive-C-reactive protein
Time frame: At 0, 3 and 6-12 months of age
Anti-mullerian hormone
Time frame: At 3 and 6-12 months of age
Cortisol
Time frame: At 3 and 6-12 months of age
Corticotropin
Time frame: At 3 and 6-12 months of age
Dehydroepiandrosterone
Time frame: At 3 and 6-12 months of age
Progesterone
Time frame: At 3 and 6-12 months of age
Inhibin-B
Time frame: At 3 and 6-12 months of age
Luteinizing hormone
Time frame: At 3 and 6-12 months of age
Follicle stimulating hormone
Time frame: At 3 and 6-12 months of age
Testosterone (boys)
Time frame: At 3 and 6-12 months of age
Estradioli (girls)
Time frame: At 3 and 6-12 months of age
Vitamin D
Time frame: At 3 and 6-12 months of age
Calcium
Time frame: At 3 and 6-12 months of age
Phosphate
Time frame: At 3 and 6-12 months of age
Alkaline phosphatase
Time frame: At 3 and 6-12 months of age
Parathyroid hormone
Time frame: At 3 and 6-12 months of age
Clinical examination of genitals
Time frame: At 0, 3 and 6-12 months of age
Measurement of perineum with centimeters (cm)
Clinical examination of mammary glands
Time frame: At 3 and 6-12 months of age
Measurement with millimeters (mm)
Sebum measurement
Time frame: At 3 and 6-12 months of age
Measurement is done with Sebumeter ®. The cassette is placed on the skin for a defined length of time and then returned to the aperture. The change in the amount of light transmission represents the sebum content of the tape, which is displayed in units from 0-350.
Heart auscultation with stethoscope.
Time frame: At 3 and 6-12 months of age
Ultrasound scan of the heart (echo)
Time frame: At 3 and 6-12 months of age
Birth Weight
Time frame: At birth
Grams
Small for Gestational Age
Time frame: At birth
A baby whose birth weight is less than the - 2 standard deviations is considered to be small for gestational age (adjusted for sex and race or ethnic group)
Large for gestational age
Time frame: At birth
A baby whose birth weight is more than the + 2 standard deviations is considered to be small for gestational age (adjusted for sex and race or ethnic group)
Admission to NICU
Time frame: Delivery through discharge up to 18 weeks
NICU denotes neonatal intensive care unit.
Apgar Score ≤3 at 5 Minutes
Time frame: At birth
Fetal iron deficiency
Time frame: At birth
Fetal iron deficiency defined by reticulocyte hemoglobin < 29 pg from umbilical cord blood collected at birth
Iron deficiency during third trimester of pregnancy
Time frame: At 30-32 weeks of gestation
Iron deficiency defined as serum ferritin < 30 µg/l at gestational weeks 30-32 with or without anemia defined as Hb ≤ 110 g/l.
Severe iron deficiency during third trimester of pregnancy
Time frame: At 30-32 weeks of gestation
Iron deficiency defined as serum ferritin < 15 µg/l at gestational weeks 30-32 with or without anemia defined as Hb ≤ 110 g/l.

38 secondary outcomes

Pre-eclampsia (Mild, Severe, HELLP Syndrome, Eclampsia).
Time frame: 20 weeks through discharge following delivery.
Superimposed Pre-eclampsia (Mild, Severe, HELLP Syndrome, Eclampsia).
Time frame: 20 weeks through discharge following delivery.
Pregnancy Associated Hypertension.
Time frame: 20 weeks through discharge following delivery.
Medically Indicated Delivery Because of Hypertension.
Time frame: 20 weeks through discharge following delivery.
Fetal Weight Estimation under 3rd percentile at gestational weeks 30-32 ultrasound scan.
Time frame: 30-32 weeks.
Abnormal uterine artery pulsatility index at gestational weeks 30-32 ultrasound scan
Time frame: At 30-32 weeks.
Aspartate Aminotransferase ≥100 U/Liter.
Time frame: 20 weeks through discharge.
Creatinine ≥90 µmol/l.
Time frame: 20 weeks through discharge.
Massive postpartum hemorrhage.
Time frame: From delivery to 24 hours after child birth
Premature Rupture of Membranes.
Time frame: From 22nd gestational week until delivery
Placental Abruption.
Time frame: From 22nd gestational week until delivery
Gestational Diabetes.
Time frame: From gestation until delivery
Cesarean Delivery.
Time frame: At Birth.
Vacuum Extraction Delivery.
Time frame: At Birth.
Maternal Death.
Time frame: During pregnancy or within 42 days after delivery
Postpartum Pulmonary Edema.
Time frame: Within 42 days after delivery
Hematocrit ≤24% With Transfusion.
Time frame: Within 42 days after delivery
Maternal Hospital Stay.
Time frame: Within 42 days after delivery
Gestational Age at Delivery.
Time frame: At Delivery.
Perineal Lacerations.
Time frame: At Birth.
Number of Visits to Maternity Health Care During Pregnancy.
Time frame: From gestation until delivery, on average during 9 months
Number of Visits at Tertiary Maternity Care Hospital.
Time frame: From gestation until delivery, on average during 9 months
Fetal Death.
Time frame: From 22nd gestational week until delivery
Neonatal Death.
Time frame: Birth until 4 weeks' of age
Respiratory Distress Syndrome.
Time frame: Birth until 4 weeks' of age
Intraventricular Hemorrhage, Grade III or IV.
Time frame: Birth until 4 weeks' of age
Neonatal sepsis.
Time frame: Birth until 4 weeks' of age
Necrotizing Enterocolitis.
Time frame: Birth until 4 weeks' of age
Retinopathy of Prematurity.
Time frame: Birth until 4 weeks' of age
Neonatal Hospital Stay.
Time frame: Birth until 18 weeks' of age
Umbilical artery pulsatility index
Time frame: At 30-32 gestational weeks
Mean cerebral artery pulsatility index
Time frame: At 30-32 gestational weeks
Ductus venousus pulsatility index
Time frame: At 30-32 gestational weeks
Fetal weight estimation
Time frame: At 30-32 gestational weeks
Amniotic fluid measurement
Time frame: At 30-32 gestational weeks
Estimation of fetal movement during ultrasound scan
Time frame: At 30-32 gestational weeks
Apgar Score ≤7 at 5 minutes.
Time frame: At birth.
Blood transfusion.
Time frame: From 22nd pregnancy week until four weeks after delivery

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2025.
Background: PubMed 34643675Ashraf UM, Hall DL, Rawls AZ, Alexander BT. Epigenetic processes during preeclampsia and effects on fetal development and chronic health. Clin Sci (Lond). 2021 Oct 15;135(19):2307-2327. doi: 10.1042/CS20190070.
Background: PubMed 30674081Bahri Khomami M, Joham AE, Boyle JA, Piltonen T, Silagy M, Arora C, Misso ML, Teede HJ, Moran LJ. Increased maternal pregnancy complications in polycystic ovary syndrome appear to be independent of obesity-A systematic review, meta-analysis, and meta-regression. Obes Rev. 2019 May;20(5):659-674. doi: 10.1111/obr.12829. Epub 2019 Jan 23.
Background: PubMed 32599600Becker M, Hesse V. Minipuberty: Why Does it Happen? Horm Res Paediatr. 2020;93(2):76-84. doi: 10.1159/000508329. Epub 2020 Jun 29.
Background: PubMed 27711226Binder NK, Evans J, Salamonsen LA, Gardner DK, Kaitu'u-Lino TJ, Hannan NJ. Placental Growth Factor Is Secreted by the Human Endometrium and Has Potential Important Functions during Embryo Development and Implantation. PLoS One. 2016 Oct 6;11(10):e0163096. doi: 10.1371/journal.pone.0163096. eCollection 2016.
Background: PubMed 3612404Chockalingam UM, Murphy E, Ophoven JC, Weisdorf SA, Georgieff MK. Cord transferrin and ferritin values in newborn infants at risk for prenatal uteroplacental insufficiency and chronic hypoxia. J Pediatr. 1987 Aug;111(2):283-6. doi: 10.1016/s0022-3476(87)80088-4.
Background: PubMed 29070565Dewey KG, Oaks BM. U-shaped curve for risk associated with maternal hemoglobin, iron status, or iron supplementation. Am J Clin Nutr. 2017 Dec;106(Suppl 6):1694S-1702S. doi: 10.3945/ajcn.117.156075. Epub 2017 Oct 25.
Background: PubMed 19464502Duley 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.
Background: PubMed 17443552Duley L, Henderson-Smart DJ, Meher S, King JF. Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD004659. doi: 10.1002/14651858.CD004659.pub2.
Background: PubMed 32613730Guy GP, Leslie K, Diaz Gomez D, Forenc K, Buck E, Khalil A, Thilaganathan B. Implementation of routine first trimester combined screening for pre-eclampsia: a clinical effectiveness study. BJOG. 2021 Jan;128(2):149-156. doi: 10.1111/1471-0528.16361. Epub 2020 Jul 1.
Background: PubMed 27144974Henley D, Brown S, Pennell C, Lye S, Torpy DJ. Evidence for central hypercortisolism and elevated blood pressure in adolescent offspring of mothers with pre-eclampsia. Clin Endocrinol (Oxf). 2016 Oct;85(4):583-9. doi: 10.1111/cen.13092. Epub 2016 May 26.
Background: PubMed 24783354Kalousova M, Muravska A, Zima T. Pregnancy-associated plasma protein A (PAPP-A) and preeclampsia. Adv Clin Chem. 2014;63:169-209. doi: 10.1016/b978-0-12-800094-6.00005-4.
Background: PubMed 26498178Koster MP, de Wilde MA, Veltman-Verhulst SM, Houben ML, Nikkels PG, van Rijn BB, Fauser BC. Placental characteristics in women with polycystic ovary syndrome. Hum Reprod. 2015 Dec;30(12):2829-37. doi: 10.1093/humrep/dev265. Epub 2015 Oct 25.
PEPPI-study's webpageLink provided by the sponsor.
Individual participant dataSharing planned: Yes. Data will deposited into Oulu University Hospital's and Oulu University's data bank.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Jaana E Nevalainen, Assoc prof contact

+358405801857

jaana.nevalainen@oulu.fi

Terhi Piltonen, Professor contact

+358405008266

terhi.piltonen@oulu.fi

Jaana Nevalainen, Assoc prof principal investigator

The Wellbeing Services County of North Ostrobothnia

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Pre-Eclampsia and Intrauterine Growth Restriction, run by Oulu University Hospital at 1 site in Finland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 5 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Jaana E Nevalainen, Assoc prof (+358405801857, jaana.nevalainen@oulu.fi), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite of Pregnancy-associated Hypertension and Serious Adverse Outcomes in the Mother or Fetus or Neonate (time frame: 20 weeks through discharge following delivery). The study lists 47 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06115122, which also lists 23 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2025; AzTrials last refreshed its copy on 26 Oct 2026.