ART, Pre-Eclampsia
Conditions
Brief summary
This study seeks to validate the hypothesis that nulliparous pregnant women after Assisted Reproductive Technology (ART) are at high risk of preeclampsia and perinatal complications and represent a subgroup for which aspirin prophylaxis during pregnancy may be effective in the prevention of preterm preeclampsia and other perinatal adverse outcomes.
Detailed description
Preeclampsia (PE) affects 2% of pregnancies in France and is an important cause of maternal and perinatal mortality and morbidity. Aspirin is currently the only prophylactic therapy for PE in high-risk women when initiated before 16 weeks of gestation and at a daily dose of 100-160 mg, with a reduction in the incidence of preterm preeclampsia of 60-70% in recent meta-analysis. Latest data also demonstrate a potential beneficial effect of aspirin on spontaneous preterm birth. A major challenge in modern obstetrics is early identification of pregnant women at high-risk of PE who could benefit from aspirin treatment. In France, the College National des Gynécologues et Obstétriciens Français and the Société Française d'HyperTension Artérielle have restrictive recommendation of aspirin to be prescribed only to women with a history of PE or vascular intra-uterine growth restriction, thus leaving out all nulliparous women (including those with multiple risk factors). Other countries (USA, United Kingdom (UK), Canada) have much broader recommendations with aspirin prescription for patients with one high or 2 moderate risk factors, but exposing nearly 30% of pregnant women to aspirin (leading to unnecessary exposure to treatment). The Fetal Medicine Foundation provides a screening test combining clinical parameters, uterine artery Doppler, and biomarkers; but this strategy has high false-positive rate and the reproducibility needs to be confirmed in clinical practice. It seems necessary to be able to better target women at risk, especially in nulliparous women. Nulliparity and assisted reproductive technology (ART) are independent risk factors for PE. Currently the proportion of pregnancy after ART in France is roughly 6.9% and is rising. Nulliparous ART pregnant women have a higher risk of PE and preterm birth. Indeed, they commonly cumulate risk factors including age\>35years in association with nulliparity and ART. The rate of PE in this population can rise up to 10%. Our hypothesis is that nulliparous pregnant women after ART are at high risk of preeclampsia and perinatal complications and represent a subgroup for which aspirin prophylaxis during pregnancy may be effective in the prevention of preterm preeclampsia and other perinatal adverse outcomes.
Interventions
DRUGAspirin
Experimental drug administrated orally
DRUGPlacebo
Treatment for the control group
Sponsors
University Hospital, Toulouse
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Nulliparous women aged 18 years or more * Pregnancy following ART, including in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), oocyte donation or intrauterine insemination with sperm donor * Singleton pregnancy * Evolutive pregnancy between 9 and 14 weeks of gestation * Women affiliated to a French Social Security Insurance or equivalent social protection * Written informed consent
Exclusion criteria
* Major fetal abnormality * Regular treatment with aspirin (including antiphospholipid syndrome) * Aspirin contraindications (allergy, von Willebrand disease, peptic ulceration, hemophilia) * Women protected by law. * Women included in another interventional study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of aspirin 150mg daily initiated between 9 and 14 weeks of gestation versus placebo in the prevention of preterm (<37 weeks of gestation) preeclampsia | Up to 9 months | Occurrence of preterm (\<37 weeks of gestation) preeclampsia (binary variable yes/no) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compare the effect of aspirin 150mg daily initiated between 9 and 14 weeks of gestation versus placebo on spontaneous and total preterm birth <34 weeks of gestation | Up to 8 months | Occurrence of spontaneous and total preterm birth (defined by delivery at \<34 weeks of gestation) |
| Compare the effect of aspirin 150mg daily initiated between 9 and 14 weeks of gestation versus placebo on spontaneous and total preterm birth <37 weeks of gestation | Up to 9 months | Occurrence of spontaneous and total preterm birth (defined by delivery at \<37weeks of gestation) |
| Compare the effect of aspirin 150mg daily initiated between 9 and 14 weeks of gestation versus placebo on occurrence of preeclampsia <34 weeks of gestation, term preeclampsia (≥ 37 weeks of gestation) | Up to 8 months | Occurrence of term (≥37 weeks) preeclampsia |
| Compare the effect of aspirin 150mg daily initiated between 9 and 14 weeks of gestation versus placebo on occurrence of cesarean delivery | Up to 9 months | Occurrence of cesarean delivery |
| Compare the effect of aspirin 150mg daily initiated between 9 and 14 weeks of gestation versus placebo on occurrence of postpartum hemorrhage (>500ml) | Up to 9 months | Occurrence of postpartum hemorrhage (\>500ml) |
| Compare the effect of aspirin 150mg daily initiated between 9 and 14 weeks of gestation versus placebo on occurrence of placental abruption | Up to 9 months | Occurrence of placental abruption |
| Compare the effect of aspirin 150mg daily initiated between 9 and 14 weeks of gestation versus placebo on neonatal adverse outcome. | Up to 9 months | Occurrence of neonatal adverse outcomes: still birth, neonatal death, neonatal complications |
Countries
France
Contacts
CONTACTPaul GUERBY, MD
CONTACTDelphine DUCHANOIS, Midwife
PRINCIPAL_INVESTIGATORChristophe VAYSSIERE, MD
University Hospital, Toulouse
Outcome results
None listed