Background:

Pre-eclampsia, defined by the association of an arterial hypertension and significant proteinuria after 20 weeks of gestation, complicates 1 to 2% of pregnancies in France. Its pathophysiology involves angiogenesis impairment, upregulated maternal systemic inflammatory response, activation of oxidative stress and endothelial dysfunction.

In a recent Danish nation-wide cohort study, pre-eclampsia was associated with a 69% increased risk of later developing scleroderma.

Type of study: prospective observational case-control study. Primary objective of the study: to determine if a history of pre-eclampsia before systemic sclerosis diagnosis is an independent risk factor for vascular phenotype in sclerodermic women.

Secondary objective: to describe all risk factors for vascular phenotype in sclerodermic women with a previous pregnancy longer than 6 months before scleroderma diagnosis.

Background :

Pre-eclampsia is defined by the association of an arterial hypertension and significant proteinuria after 20 weeks of gestation. It complicates 1 to 2% of pregnancies in France. Its pathophysiology involves angiogenesis impairment, upregulated maternal systemic inflammatory response, activation of oxidative stress and endothelial dysfunction.

In a recent Danish nation-wide cohort study, pre-eclampsia was associated with a 69% increased risk of later developing scleroderma. A case-control study on 103 women with systemic sclerosis compared to 103 control women had already found an increased incidence of previous vasculoplacental disorders in women with systemic sclerosis. Women developed systemic sclerosis on average 27 years after their first pregnancy.

Primary objective of the study : to determine if a history of pre-eclampsia before systemic sclerosis diagnosis is an independent risk factor for vascular phenotype in sclerodermic women.

Secondary objective: to describe all risk factors for vascular phenotype in sclerodermic women with a previous pregnancy longer than 6 months before scleroderma diagnosis.

Conduct of the study:

It is a prospective observational case-control study. Cases will be defined as women with systemic sclerosis, specific vascular complications (digital ulcers, specific cardiac involvement of systemic sclerosis including pulmonary arterial hypertension, renal crisis) and with a previous pregnancy longer than 6 months before systemic sclerosis diagnosis.

Controls will be defined as women with systemic sclerosis, no specific vascular complication and with a previous pregnancy longer than 6 months before systemic sclerosis diagnosis.

Conduct of the study:

A self-administered " pregnancy " questionnaire will be given to each women with systemic sclerosis of the cohort group during the annual follow-up consultation. A case report form will be completed at the same time by the physician in charge of the patient.

The " pregnancy " questionnaire will consist of two parts :

• A part " pre-eclampsia questionnaire ", derived from the translation in French of a questionnaire validated in English.
• A second part with additional questions on pregnancies. The duration of participation to the study will be of one day. The duration of the inclusion period will be of 24 months. Needed number of patients : 378 women, 126 "cases" and 252 "control" .

Perspectives of the study :

If this study demonstrates that a previous pre-eclampsia is an independent risk factor for vascular phenotype in women with systemic sclerosis, it will be mandatory to look for a history of pre-eclampsia in women at the time of systemic sclerosis diagnosis. Besides, the women with a history of pre-eclampsia should be monitored more frequently for vascular complications related to systemic sclerosis.

Inclusion Criteria:

• General:

Women with a diagnosis of systemic sclerosis according to EULAR 2013 diagnostic criteria AND with a history of pregnancy longer than 6 months (28 weeks of gestation (WG)) before systemic sclerosis diagnosis.

• Specific:

For the women of the " case " group :

Women with vascular complications specific of systemic sclerosis (digital ulcers, specific cardiac involvement of systemic sclerosis including pulmonary arterial hypertension, renal crisis).

For the women of the " control " group :

Women with no vascular complications specific of systemic sclerosis.

Non inclusion criteria :

• Refusal to participate to the study
• Minor women
• Women under tutorship
• Women with no pregnancy history or with a history of pregnancy(ies) below 6 months length.

Exclusion Criteria:

• Women aged of less than 18 years
• Women on legal protection
• Women with no history of pregnancy of more than 6 months
• Women unable to fill out a questionnaire in French
• Women who refuse to participate to the study

Women with a diagnosis of systemic sclerosis according to EULAR 2013 diagnostic criteria AND with a history of pregnancy longer than 6 months (28 WG) before systemic sclerosis diagnosis

followed in one of the French centers of expertise for systemic sclerosis will be offered to participate to the study during the annual follow-up consultation with her referring physician.

All collected data that underlie results in a publication

Data will be available beginning two year and ending five years following the end study

Data access requests will be reviewed by the internal committee of Brest UH. Requestors will be required to sign and complete a data access agreement.