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Approximately 300 women will be enrolled into a risk group according to a pre-eclampsia risk calculator.

Women enrolled into study who fulfill ≥2 Rotterdam criteria. Women with PCOS may be included in risk- or control groups.

Approximately 300 women in low risk for pre-eclampsia according to a pre-eclampsia risk calculator.

Approximately 2100 women who are not enrolled into risk-, control- or PCOS groups.

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).

The role of fathers in the development of pregnancy complications and on the health of the offspring.

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

Pre-eclampsia screening program

Jaana E Nevalainen, Assoc prof

Terhi Piltonen, Professor

Jaana E Nevalainen, Assoc Prof

Marja Ojaniemi, Assoc Prof

Liisa Laatio, PhD

Hilkka Nikkinen, PhD

Pekka Pinola, PhD

Tiina Kantomaa, MD

Jaana Nevalainen, Assoc prof

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

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.

Blood samples will be taken at first and third trimesters from pregnant women. At birth, blood samples will be taken from umbilical cord, placental samples and umbilical cord samples will be taken also. DNA samples from mothers, fathers and children will be taken. Approximately 900 children will have blood samples at the age of 3 and 6-12 months.

Participants recruited for PEPPI are pregnant women (females), their partners (males) and babies (female/male).

PEPPI Study: Identification of Women at Risk for Placental Dysfunction

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

Data will deposited into Oulu University Hospital's and Oulu University's data bank.

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

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.

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.

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.

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.

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.

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.

Measurements of height (cm) and weight (kg) combined as BMI (kg/m2)

B-Hb, B-Leuk, B-Hkr, B-Eryt, E-MCV, E-RDW, E-MCH, E-MCHC, B-Trom

Measurement of perineum with centimeters (cm)

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.

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)

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)

NICU denotes neonatal intensive care unit.

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

Iron deficiency defined as serum ferritin \< 30 µg/l at gestational weeks 30-32 with or without anemia defined as Hb ≤ 110 g/l.

Iron deficiency defined as serum ferritin \< 15 µg/l at gestational weeks 30-32 with or without anemia defined as Hb ≤ 110 g/l.

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

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

Women with Hypertension after pregnancy week 20.

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

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

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

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

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).

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

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

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

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

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

Spots Global Cancer Trial Database for intrauterine growth restriction