PEPPI Study: Identification of Women at Risk for Placental Dysfunction

Официальное название

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

Обзор

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

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Composite of Pregnancy-associated Hypertension and Serious Adverse Outcomes in the Mother or Fetus or Neonate [Срок оценки: 20 weeks through discharge following delivery]
• Severe Hypertension [Срок оценки: 20 weeks through discharge following delivery]
• Severe or Mild Pregnancy-associated Hypertension With Elevated Liver Enzyme Levels [Срок оценки: 20 weeks through discharge following delivery]
• Severe or Mild Pregnancy-associated Hypertension With Thrombocytopenia [Срок оценки: 20 weeks through discharge following delivery]
• Severe or Mild Pregnancy-associated Hypertension With an Elevated Serum Creatinine Level [Срок оценки: 20 weeks through discharge following delivery]
• Severe or Mild Pregnancy-associated Hypertension With an Eclamptic Seizure [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 20 weeks through discharge following delivery]
• Severe or Mild Pregnancy-associated Hypertension With a Fetal Death After 20 Weeks of Gestation or Neonatal Death [Срок оценки: 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 [Срок оценки: at 13 gestational weeks]

Вторичные конечные точки (12)

• Pre-eclampsia (Mild, Severe, HELLP Syndrome, Eclampsia). [Срок оценки: 20 weeks through discharge following delivery.]
• Superimposed Pre-eclampsia (Mild, Severe, HELLP Syndrome, Eclampsia). [Срок оценки: 20 weeks through discharge following delivery.]
• Pregnancy Associated Hypertension. [Срок оценки: 20 weeks through discharge following delivery.]
• Medically Indicated Delivery Because of Hypertension. [Срок оценки: 20 weeks through discharge following delivery.]
• Fetal Weight Estimation under 3rd percentile at gestational weeks 30-32 ultrasound scan. [Срок оценки: 30-32 weeks.]
• Abnormal uterine artery pulsatility index at gestational weeks 30-32 ultrasound scan [Срок оценки: At 30-32 weeks.]
• Aspartate Aminotransferase ≥100 U/Liter. [Срок оценки: 20 weeks through discharge.]
• Creatinine ≥90 µmol/l. [Срок оценки: 20 weeks through discharge.]
• Massive postpartum hemorrhage. [Срок оценки: From delivery to 24 hours after child birth]
• Premature Rupture of Membranes. [Срок оценки: From 22nd gestational week until delivery]
• Placental Abruption. [Срок оценки: From 22nd gestational week until delivery]
• Gestational Diabetes. [Срок оценки: From gestation until delivery]

Критерии участия

Mothers

Inclusion Criteria for PEPPI-study

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

Критерии исключения

• 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

Критерии исключения

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

Fathers

Критерии включения

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

Критерии исключения

• Does not understand Finnish

Children

Inclusion Criteria for PEPPI-study

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

Критерии исключения

• 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

Критерии исключения

• 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

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Финляндия · 1 центр

• The Wellbeing Services County of North Ostrobothnia — Oulu

Публикации

• 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. PMID 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. PMID 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. PMID 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. PMID 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. PMID 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. PMID 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. PMID 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. PMID 17443552

Идентификаторы

NCT: NCT06115122 · OuluUH_PEPPI

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗