PEPPI Study: Identification of Women at Risk for Placental Dysfunction
- Conditions
- Pre-EclampsiaIron-deficiencyHypertensive Disorder of PregnancyCardiovascular DiseasesIntrauterine Growth RestrictionPolycystic Ovary SyndromeProteinuria in Pregnancy
- Interventions
- Other: Pre-eclampsia screening program
- Registration Number
- NCT06115122
- Lead Sponsor
- Oulu University Hospital
- Brief 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.
Condition or disease: pre-eclampsia, intrauterine growth restriction, polycystic ovary syndrome
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 3000
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Pre-eclampsia risk group Pre-eclampsia screening program Approximately 300 women will be enrolled into a risk group according to a pre-eclampsia risk calculator. Control group Pre-eclampsia screening program Approximately 300 women in low risk for pre-eclampsia according to a pre-eclampsia risk calculator. PCOS group Pre-eclampsia screening program Women enrolled into study who fulfill ≥2 Rotterdam criteria. Women with PCOS may be included in risk- or control groups. Follow up group Pre-eclampsia screening program Approximately 2100 women who are not enrolled into risk-, control- or PCOS groups.
- Primary Outcome Measures
Name Time Method Cortisol At 3 and 6-12 months of age Severe or Mild Pregnancy-associated Hypertension With Thrombocytopenia 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.
The weight of the child during the first year of life. At 0, 3 and 6-12 months of age Measurement of weight (g, kg)
Luteinizing hormone At 3 and 6-12 months of age Testosterone (boys) At 3 and 6-12 months of age Sebum measurement 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.
Birth Weight At birth Grams
Hepcidin At 0, 3 and 6-12 months of age Dehydroepiandrosterone At 3 and 6-12 months of age Inhibin-B At 3 and 6-12 months of age Estradioli (girls) At 3 and 6-12 months of age Parathyroid hormone At 3 and 6-12 months of age Heart auscultation with stethoscope. At 3 and 6-12 months of age Small for Gestational Age 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)
Severe Hypertension 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 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 a Fetus That Was Small for Gestational Age (Below the - 2 SD) Adjusted for Sex and Race or Ethnic Group 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.
Prevalence of high pre-eclampsia risk score in women with PCOS compared to non-PCOS women 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.
The height of the child during the first year of life. At 0, 3 and 6-12 months of age Measurement of height (cm)
Basic blood count 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
Severe or Mild Pregnancy-associated Hypertension With an Elevated Serum Creatinine Level 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 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 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 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.
Ferritin At 0, 3 and 6-12 months of age Saturation of transferrin At 0, 3 and 6-12 months of age Anti-mullerian hormone At 3 and 6-12 months of age Alkaline phosphatase At 3 and 6-12 months of age Clinical examination of mammary glands At 3 and 6-12 months of age Measurement with millimeters (mm)
Composite of Pregnancy-associated Hypertension and Serious Adverse Outcomes in the Mother or Fetus or Neonate 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
11. All the above mentioned outcomes (1-10) in PCOS group compared to non-PCOS group. 13 gestational weeks through discharge following delivery As described above.
The body mass index (BMI) of the child during the first year of life. At 0, 3 and 6-12 months of age Measurements of height (cm) and weight (kg) combined as BMI (kg/m2)
Hypersensitive-C-reactive protein At 0, 3 and 6-12 months of age Corticotropin At 3 and 6-12 months of age Progesterone At 3 and 6-12 months of age Follicle stimulating hormone At 3 and 6-12 months of age Vitamin D At 3 and 6-12 months of age Calcium At 3 and 6-12 months of age Phosphate At 3 and 6-12 months of age Clinical examination of genitals At 0, 3 and 6-12 months of age Measurement of perineum with centimeters (cm)
Ultrasound scan of the heart (echo) At 3 and 6-12 months of age Admission to NICU Delivery through discharge up to 18 weeks NICU denotes neonatal intensive care unit.
Apgar Score ≤3 at 5 Minutes At birth Iron deficiency during third trimester of pregnancy 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.
Large for gestational age 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)
Fetal iron deficiency At birth Fetal iron deficiency defined by reticulocyte hemoglobin \< 29 pg from umbilical cord blood collected at birth
Severe iron deficiency during third trimester of pregnancy 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 Outcome Measures
Name Time Method Fetal weight estimation At 30-32 gestational weeks Measured with ultrasound using fetal BPD, HC, AC and FL measurements (Hadlock)
Necrotizing Enterocolitis. Birth until 4 weeks' of age Massive postpartum hemorrhage. From delivery to 24 hours after child birth Massive postpartum hemorrhage defined≥ 1000ml blood loss within 24 hours after child birth.
Premature Rupture of Membranes. 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).
Placental Abruption. From 22nd gestational week until delivery Defined as the placenta separates from the inner wall of the uterus before birth.
Cesarean Delivery. At Birth. Fetal Death. From 22nd gestational week until delivery Pre-eclampsia (Mild, Severe, HELLP Syndrome, Eclampsia). 20 weeks through discharge following delivery. HELLP denotes hemolytic anemia, elevated liver enzymes, and low platelet count.
Fetal Weight Estimation under 3rd percentile at gestational weeks 30-32 ultrasound scan. 30-32 weeks. Gestational Diabetes. 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).
Maternal Death. During pregnancy or within 42 days after delivery Perineal Lacerations. At Birth. Defined as first, second, third or fourth degree lacerations during birth.
Intraventricular Hemorrhage, Grade III or IV. Birth until 4 weeks' of age Neonatal sepsis. Birth until 4 weeks' of age Medically Indicated Delivery Because of Hypertension. 20 weeks through discharge following delivery. Aspartate Aminotransferase ≥100 U/Liter. 20 weeks through discharge. Postpartum Pulmonary Edema. Within 42 days after delivery Hematocrit ≤24% With Transfusion. Within 42 days after delivery Maternal Hospital Stay. Within 42 days after delivery Duration of the time spend at the hospital after delivery (measured as days and weeks)
Number of Visits at Tertiary Maternity Care Hospital. From gestation until delivery, on average during 9 months Respiratory Distress Syndrome. Birth until 4 weeks' of age Apgar Score ≤7 at 5 minutes. At birth. Superimposed Pre-eclampsia (Mild, Severe, HELLP Syndrome, Eclampsia). 20 weeks through discharge following delivery. Women with Hypertension before pregnancy week 20. HELLP denotes hemolytic anemia, elevated liver enzymes, and low platelet count.
Pregnancy Associated Hypertension. 20 weeks through discharge following delivery. Women with Hypertension after pregnancy week 20.
Abnormal uterine artery pulsatility index at gestational weeks 30-32 ultrasound scan At 30-32 weeks. According to calculator provided by Fetal Medicine Foundation (https://fetalmedicine.org/research/utpi).
Gestational Age at Delivery. At Delivery. Number of Visits to Maternity Health Care During Pregnancy. From gestation until delivery, on average during 9 months Neonatal Hospital Stay. Birth until 18 weeks' of age Amniotic fluid measurement At 30-32 gestational weeks Ultrasound measurements of maximum velocity pocket (cm) and amniotic fluid index (cm)
Estimation of fetal movement during ultrasound scan At 30-32 gestational weeks Estimated as a whole with inspection of body movements, limb movements and breathing movement
Creatinine ≥90 µmol/l. 20 weeks through discharge. Vacuum Extraction Delivery. At Birth. Umbilical artery pulsatility index At 30-32 gestational weeks Measured with Doppler ultrasound
Ductus venousus pulsatility index At 30-32 gestational weeks Measured with Doppler ultrasound
Blood transfusion. From 22nd pregnancy week until four weeks after delivery Defined as red blood cell transfusion received by patient (mother or child).
Neonatal Death. Birth until 4 weeks' of age Retinopathy of Prematurity. Birth until 4 weeks' of age Mean cerebral artery pulsatility index At 30-32 gestational weeks Measured with Doppler ultrasound
Trial Locations
- Locations (1)
The Wellbeing Services County of North Ostrobothnia
🇫🇮Oulu, Finland