FORgenomics: Fetal, Obstetrics and Reproduction Genomics

Sponsor

Fundación Ginemed (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05720169

Collaborator

Hospitales Universitarios Virgen del Rocío (Other), University of Seville (Other), Clínicas Ginemed (Other), FIRST - Fetal, IVF and Reproduction Simulation Training Center (Other)

400

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the impact of a clinical screening strategy and genomic analysis of the factors involved in Placental Dysfunction (Preeclampsia and IUGR) in women of advanced maternal age undergoing assisted reproduction techniques (ART), specifically, in vitro fertilization (IVF) and oocyte donation.

Condition or Disease	Intervention/Treatment	Phase
Preeclampsia Intrauterine Growth Restriction Placental Disease	Diagnostic Test: Doppler ultrasound Diagnostic Test: Blood sample Diagnostic Test: Blood sample Diagnostic Test: Doppler ultrasound

Detailed Description

Given society's shift towards later childbearing, partly related to increased career development, women are increasingly delaying childbearing and, as a result, face declining biological fertility and increased maternal morbidity and adverse perinatal pregnancy outcomes, as well as increased use of ART. Preeclampsia (PE) complicates 2% of pregnancies and is a leading cause of severe maternal and perinatal complications. There is no curative treatment, and the only recognized beneficial primary prevention is low-dose aspirin. Finding an effective method of predicting and preventing placental dysfunction (PD) in women of advanced maternal age undergoing ART remains a challenge.

The investigators believe that maternal and perinatal complications in this group of pregnant women could be detected preclinically and allow early preventive actions.

On the other hand, establishing a differentiated genomic pattern in this group of patients would allow preventive actions both pregestational and during gestation. Furthermore, FORgenomics can be used to externally validate a prediction model for the development of PE and IUGR in pregnancy after IVF/ovodon. Our results could be applicable in most healthcare settings and have important implications for maternal-fetal health.

The justification and hypothesis of this proposal is: (1) maternal and perinatal complications in this group of pregnant women could be detected preclinically and allow preventive actions by systematic screening based on Doppler ultrasound of uterine arteries and anti-angiogenic factors (sFlt-1/PlGF ratio) at 13, 16, 20 and 26 weeks to identify pregnant women at high risk for developing PE; (2) morphological ultrasound at 13, 16 and 20 weeks would help to establish a standardized procedure for early detection of congenital anomalies and (3) establishing a differentiated genomic pattern in this group of patients would allow preventive actions both pregestational and during gestation.

Study Design

Study Type:

Observational

Anticipated Enrollment :

400 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Fetal, Obstetrics and Reproduction Genomics

Anticipated Study Start Date :

Feb 1, 2023

Anticipated Primary Completion Date :

Dec 31, 2024

Anticipated Study Completion Date :

Dec 31, 2024

Outcome Measures

Primary Outcome Measures

Number of Participants with preeclampsia (PE) during pregnancy [≥20 weeks to <37 weeks of gestation]
Defined as systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90mmHg with an interval of at least 4 h after 20 weeks' gestation plus any of the following: (i) proteinuria (>300 mg/24 h) or a urine protein/creatinine ratio > 0.3 mg/mmol); (ii) end-organ dysfunction: systolic blood pressure > 160 mmHg, diastolic blood pressure >110 mmHg, platelet count <100x109/L, blood alanine and aspartate transaminases >70 IU/L, serum creatinine >1. 1 mg/dL, lactate dehydrogenase >700 IU/L, right upper quadrant or epigastric pain, dyspnea and/or cerebral/visual disturbances. Or (iii) utero-placental dysfunction (estimated fetal weight <3rd centile or <10th centile with abnormal uterine or umbilical Doppler [pulsatility index >95th centile]) as defined by the International Society for the Study of Hypertension in Pregnancy (ISSHP) with minor adaptations for study purposes.
Number of fetuses diagnosed with intrauterine growth restriction (IUGR) during pregnancy [≥20 weeks to <37 weeks of gestation]
IUGR will be defined by the following criteria: Estimated fetal weight (EFW) between percentile (p) 3 and p 10 with Doppler alteration (uterine arteries > p 95 or cerebroplacental index < p 5, or middle cerebral artery < p 5, or umbilical artery > p 95). PFE < p 3 independently of feto-maternal Doppler.

Secondary Outcome Measures

Number of fetuses and newborns with severe perinatal morbidity [From birth up to 7 days of life]
Defined by a composite including any of the following: premature placental abruption, severe fetal growth restriction (birth weight <3rd centile), perinatal mortality, an Apgar score at 5'< 7.0, arterial pH less than 7.10, need for respiratory support within 72 hours of birth, neonatal intraventricular hemorrhage grade III/IV, necrotizing, periventricular leukomalacia, sepsis, bronchopulmonary dysplasia or encephalopathy due to hypoxic ischemic enterocolitis. Days of admission to ICU.
Cesarean section rate [During birth]
Type of delivery and cesarean section rate will be recorded.
Number of Participants with pregnancy-related maternal morbidity [From conception up to 4 days after birth]
defined by a composite including any of the following: (i) HELLP syndrome (lactate dehydrogenase [LDH] >700 IU/L, AST at twice normal values, and platelet count <100x109/L); (ii) central nervous system dysfunction (eclampsia, Glasgow Coma Score <13, stroke, reversible ischemic neurologic deficit, or cortical blindness); (iii) hepatic dysfunction (INR >1. 2 in the absence of disseminated intravascular coagulation, MELD score >10, or hepatic hematoma or rupture); (iv) renal dysfunction (dialysis, serum creatinine concentration greater than 150 μmol/L, or diuresis <0.5 mL/kg/h for 12 hours, according to renal failure by RIFLE criteria; or need for furosemide treatment to maintain diuresis >0. 5 mL/kg/h for 3 hours); (v) respiratory dysfunction (pulmonary edema, need for invasive or noninvasive mechanical ventilation, need for oxygen concentration greater than 50% for more than 1 hour, or severe respiratory distress [without pulmonary edema criteria but with presence of dyspnea,
Maternal experience and psychological impact [From conception up to 4 days after birth]
It will be assessed by: - WHO Five Well-Being Index (WHO), Spanish version of 1998, applied at week 26. A brief self-assessment questionnaire on a person's perception of well-being over a specific period of time.
Maternal anxiety and psychological impact [From conception up to 4 days after birth]
It will be assessed by: - Spielberger State-Trait Anxiety Questionnaire (STAI), in its Spanish adaptation applied in the 26th week of gestation. One of the first instruments validated in Spain and one of the most widely used by many researchers, it comprises two differentiated self-assessment scales: State Anxiety (SA), referring to a transitory anxious state that a person may feel in specific situations; and Trait Anxiety (RA), which characterizes a more or less stable anxious tendency that distinguishes people in their tendency to perceive situations as threatening.

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Singleton pregnancy
Age ≥40 years
Signed informed consent
Gestation obtained by IVF or ovodonation

Exclusion Criteria:

Non-ongoing pregnancy
Gestation obtained by artificial insemination
Naturally obtained gestation, without ART
Multiple pregnancy
Pregnancies complicated by major fetal abnormality identified at the first-trimester ultrasound
Age <18 years
Poor understanding of the Spanish or English languages
Refusal in informed consent to participate in the study
Participation in another intervention study that could modify follow-up