Preeclampsia and intrauterine growth restriction (IUGR) are two principal complications of pregnancy. These diseases are related to placental dysfunction nevertheless knowledge of its pathophysiological mechanisms remains inadequate.

No etiological treatment for these pathologies is available. Inducing birth is the only way to prevent the occurrence of these complications (such as fetal death in utero.

Therefore, a better understanding of placental vascularization under pathological and physiological conditions is necessary. This placental vascularization evolves throughout gestation. Histological studies have improved our knowledge of placental vascular pathologies; however, these are ex vivo data that only provide an incomplete reflection of placental function. In vivo placental studies are therefore essential to understand the mechanisms of placental perfusion. Currently, these studies are limited because the available tools (such as placental Doppler) do not allow for the separate study of maternal placental flow from fetal flow. However, histological evidence clearly establishes maternal placental vascular involvement in IUGR. It would therefore be interesting to study maternal and fetal placental vascularization separately. The development of new in vivo imaging exploration techniques will help to better understand placental pathologies.

In obstetrics, CES would offer the opportunity to study in vivo placental vascularization in a segmented manner (maternal versus fetal side independently) since the microbubbles do not cross the placental barrier. Animal studies show no toxic effects on fetal development nor any crossing of the placental barrier. In humans, the innovative use of this contrast agent has allowed for a better understanding of placental vascularization in the first trimester of pregnancy.

The primary objective is to compare placental contrast ultrasound in patients with medical termination of pregnancy at gestational age 16 weeks - 38 weeks+ 6 days between two groups: the fetal growth restriction one and the no fetal growth restriction.

Methods and analysis: This is a monocentric, prospective comparative, non-randomized, feasibility, open and interventional study. The investigators will include 30 women with medical termination of pregnancy divided in two groups: fetal growth restriction one and the no fetal growth restriction. Women are informed and recruited in the Fetal Medicine units in Nancy, over a period of 48 months.

Inclusion Criteria:

• Adult woman (age ≥18 years),
• Gestational age between 16 GW + 0 days and 38 GW + 6 days,
• Singleton pregnancy,
• Whose request of a medical termination of pregnancy (IMG) has been formulated and accepted in a written form by the Centre Pluridisciplinaire de Diagnostic Prénatal (CPDPN) of the Centre Hospitalier Régional Universaitaire (CHRU) de Nancy,
• Affiliated to the social security system or benefit from such a system,
• Having received full information and having signed an informed consent form.

Criteria specific to patients in the "growth restriction" group:

- Severe growth restriction defined by an estimation of foetal weight below the 3rd percentile using ultrasound performed no more than 15 days prior to the IMG (the diagnosis must be established at the time of the request for IMG in routine care).

Exclusion Criteria:

• Person who do not speak French

• Any medical condition contraindicating the administration of SonoVue, in particular:

  • Hypersensitivity to sulfur hexafluoride or to one of the other components of SonoVue® such as polyethylene glycol (PEG),
  • Women with recent acute coronary syndrome or unstable ischaemic heart disease,
  • Women with a right-to-left shunt, severe pulmonary arterial hypertension (pulmonary arterial pressure > 90 mmHg), uncontrolled systemic hypertension and women suffering from respiratory distress syndrome.

• Persons covered by articles L. 1121-5, L. 1121-7 and L1121-8 of the French Public Health Code:

  • Breast-feeding mother
  • Minor (not emancipated)
  • An adult subject to a legal protection (guardianship, curatorship, safeguard of justice)
  • An adult unable to give consent

• Persons deprived of their liberty by a judicial or administrative decision, persons under psychiatric care by virtue of articles L. 3212-1 and L. 3213-1

Individual participant data (IPD) will be made available upon reasonable request, after de-identification.

Additional documents such as the statistical analysis plan may also be available.

Data will be available starting 3 months after publication and for a period of 5 years.

Researchers must submit a methodologically sound proposal reviewed and approved by an independent ethics committee.

Data will be shared via a secure online platform and under a data access agreement.

Requests should be addressed to the corresponding author: Dr. Matthieu Dap (m.dap@chru-nancy.fr)