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NCT Number: NCT06115122

PEPPI Study: Identification of Women at Risk for Placental Dysfunction

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.

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

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Key information

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Mothers

Inclusion criteria

for PEPPI-study

  • Pregnant (first trimester)
  • Understands Finnish
  • ≥18 years
  • Signed informed consent

Exclusion criteria

  • Multiple pregnancy
  • Miscarriage/termination of the index pregnancy
  • No first trimester blood sampling

Inclusion criteria

for FERPPI-study

  • Participates in PEPPI-study (criteria above)
  • Blood samples at first and third trimester of pregnancy
  • Permits blood sampling from the umbilical cord when the baby is born

Exclusion criteria

  • No first or third trimester blood sampling
  • No umbilical cord blood sample after baby is born

Fathers

Inclusion criteria

  • Biological father to the child born for the mother who participated in PEPPI study
  • ≥18 years
  • Signed informed consent

Exclusion criteria

  • Does not understand Finnish

Children

Inclusion criteria

for PEPPI-study

  • Born to mother who participated in PEPPI study
  • Signed informed consent from parent(s)

Exclusion criteria

  • 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

Exclusion criteria

  • Mother/father declines participation

Inclusion criteria

for FERPPI-study

  • 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

Exclusion criteria

  • No consent from parent(s)
  • No blood samples from mother
  • No blood samples from child

Treatment and study plan

Pre-eclampsia screening program

Other

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

Primary outcomes

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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. 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.

  12. 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)

  13. 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)

  14. 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)

  15. 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

  16. Ferritin

    Time frame: At 0, 3 and 6-12 months of age

  17. Hepcidin

    Time frame: At 0, 3 and 6-12 months of age

  18. Saturation of transferrin

    Time frame: At 0, 3 and 6-12 months of age

  19. Hypersensitive-C-reactive protein

    Time frame: At 0, 3 and 6-12 months of age

  20. Anti-mullerian hormone

    Time frame: At 3 and 6-12 months of age

  21. Cortisol

    Time frame: At 3 and 6-12 months of age

  22. Corticotropin

    Time frame: At 3 and 6-12 months of age

  23. Dehydroepiandrosterone

    Time frame: At 3 and 6-12 months of age

  24. Progesterone

    Time frame: At 3 and 6-12 months of age

  25. Inhibin-B

    Time frame: At 3 and 6-12 months of age

  26. Luteinizing hormone

    Time frame: At 3 and 6-12 months of age

  27. Follicle stimulating hormone

    Time frame: At 3 and 6-12 months of age

  28. Testosterone (boys)

    Time frame: At 3 and 6-12 months of age

  29. Estradioli (girls)

    Time frame: At 3 and 6-12 months of age

  30. Vitamin D

    Time frame: At 3 and 6-12 months of age

  31. Calcium

    Time frame: At 3 and 6-12 months of age

  32. Phosphate

    Time frame: At 3 and 6-12 months of age

  33. Alkaline phosphatase

    Time frame: At 3 and 6-12 months of age

  34. Parathyroid hormone

    Time frame: At 3 and 6-12 months of age

  35. Clinical examination of genitals

    Time frame: At 0, 3 and 6-12 months of age

    Measurement of perineum with centimeters (cm)

  36. Clinical examination of mammary glands

    Time frame: At 3 and 6-12 months of age

    Measurement with millimeters (mm)

  37. 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.

  38. Heart auscultation with stethoscope.

    Time frame: At 3 and 6-12 months of age

  39. Ultrasound scan of the heart (echo)

    Time frame: At 3 and 6-12 months of age

  40. Birth Weight

    Time frame: At birth

    Grams

  41. 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)

  42. 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)

  43. Admission to NICU

    Time frame: Delivery through discharge up to 18 weeks

    NICU denotes neonatal intensive care unit.

  44. Apgar Score ≤3 at 5 Minutes

    Time frame: At birth

  45. Fetal iron deficiency

    Time frame: At birth

    Fetal iron deficiency defined by reticulocyte hemoglobin < 29 pg from umbilical cord blood collected at birth

  46. 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.

  47. 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.

Secondary outcomes

  1. Pre-eclampsia (Mild, Severe, HELLP Syndrome, Eclampsia).

    Time frame: 20 weeks through discharge following delivery.

    HELLP denotes hemolytic anemia, elevated liver enzymes, and low platelet count.

  2. Superimposed Pre-eclampsia (Mild, Severe, HELLP Syndrome, Eclampsia).

    Time frame: 20 weeks through discharge following delivery.

    Women with Hypertension before pregnancy week 20. HELLP denotes hemolytic anemia, elevated liver enzymes, and low platelet count.

  3. Pregnancy Associated Hypertension.

    Time frame: 20 weeks through discharge following delivery.

    Women with Hypertension after pregnancy week 20.

  4. Medically Indicated Delivery Because of Hypertension.

    Time frame: 20 weeks through discharge following delivery.

  5. Fetal Weight Estimation under 3rd percentile at gestational weeks 30-32 ultrasound scan.

    Time frame: 30-32 weeks.

  6. Abnormal uterine artery pulsatility index at gestational weeks 30-32 ultrasound scan

    Time frame: At 30-32 weeks.

    According to calculator provided by Fetal Medicine Foundation (https://fetalmedicine.org/research/utpi).

  7. Aspartate Aminotransferase ≥100 U/Liter.

    Time frame: 20 weeks through discharge.

  8. Creatinine ≥90 µmol/l.

    Time frame: 20 weeks through discharge.

  9. Massive postpartum hemorrhage.

    Time frame: From delivery to 24 hours after child birth

    Massive postpartum hemorrhage defined≥ 1000ml blood loss within 24 hours after child birth.

  10. Premature Rupture of Membranes.

    Time frame: From 22nd gestational week until delivery

    If the water breaks before the 37th week of pregnancy, it is called preterm premature rupture of membranes (PPROM).

  11. Placental Abruption.

    Time frame: From 22nd gestational week until delivery

    Defined as the placenta separates from the inner wall of the uterus before birth.

  12. Gestational Diabetes.

    Time frame: From gestation until delivery

    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).

  13. Cesarean Delivery.

    Time frame: At Birth.

  14. Vacuum Extraction Delivery.

    Time frame: At Birth.

  15. Maternal Death.

    Time frame: During pregnancy or within 42 days after delivery

  16. Postpartum Pulmonary Edema.

    Time frame: Within 42 days after delivery

  17. Hematocrit ≤24% With Transfusion.

    Time frame: Within 42 days after delivery

  18. Maternal Hospital Stay.

    Time frame: Within 42 days after delivery

    Duration of the time spend at the hospital after delivery (measured as days and weeks)

  19. Gestational Age at Delivery.

    Time frame: At Delivery.

  20. Perineal Lacerations.

    Time frame: At Birth.

    Defined as first, second, third or fourth degree lacerations during birth.

  21. Number of Visits to Maternity Health Care During Pregnancy.

    Time frame: From gestation until delivery, on average during 9 months

  22. Number of Visits at Tertiary Maternity Care Hospital.

    Time frame: From gestation until delivery, on average during 9 months

  23. Fetal Death.

    Time frame: From 22nd gestational week until delivery

  24. Neonatal Death.

    Time frame: Birth until 4 weeks' of age

  25. Respiratory Distress Syndrome.

    Time frame: Birth until 4 weeks' of age

  26. Intraventricular Hemorrhage, Grade III or IV.

    Time frame: Birth until 4 weeks' of age

  27. Neonatal sepsis.

    Time frame: Birth until 4 weeks' of age

  28. Necrotizing Enterocolitis.

    Time frame: Birth until 4 weeks' of age

  29. Retinopathy of Prematurity.

    Time frame: Birth until 4 weeks' of age

  30. Neonatal Hospital Stay.

    Time frame: Birth until 18 weeks' of age

  31. Umbilical artery pulsatility index

    Time frame: At 30-32 gestational weeks

    Measured with Doppler ultrasound

  32. Mean cerebral artery pulsatility index

    Time frame: At 30-32 gestational weeks

    Measured with Doppler ultrasound

  33. Ductus venousus pulsatility index

    Time frame: At 30-32 gestational weeks

    Measured with Doppler ultrasound

  34. Fetal weight estimation

    Time frame: At 30-32 gestational weeks

    Measured with ultrasound using fetal BPD, HC, AC and FL measurements (Hadlock)

  35. Amniotic fluid measurement

    Time frame: At 30-32 gestational weeks

    Ultrasound measurements of maximum velocity pocket (cm) and amniotic fluid index (cm)

  36. Estimation of fetal movement during ultrasound scan

    Time frame: At 30-32 gestational weeks

    Estimated as a whole with inspection of body movements, limb movements and breathing movement

  37. Apgar Score ≤7 at 5 minutes.

    Time frame: At birth.

  38. Blood transfusion.

    Time frame: From 22nd pregnancy week until four weeks after delivery

    Defined as red blood cell transfusion received by patient (mother or child).

Study contacts

Contact information is provided by the study sponsor or research team.

Jaana E Nevalainen, Assoc prof

CONTACT

[email protected]

+358405801857

Terhi Piltonen, Professor

CONTACT

[email protected]

+358405008266

Sponsors and collaborators

Lead sponsor

Oulu University Hospital

Other

Collaborators

  • Academy of Finland
  • Finnish Medical Foundation
  • PerkinElmer, Inc.
  • Roche Diagnostics GmbH
  • Sigrid Jusélius Foundation
  • University of Oulu

Registry information

Official study title

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

Important dates

Study start
2022
Primary completion
2027
Study completion
2041
First posted
Nov 2, 2023
Registry last updated
Aug 5, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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