Complementary projects

Several projects complementary to the Epipage 2 study are being conducted among subgroups of the cohort. Additional investigations were performed to meet the particular objectives of these projects.

The recruitment of these subgroups took place in centers that volunteered to participate in these studies. The staff recruiting subjects provided specific information about them to the families before asking them if they were willing to participate.

All these complementary projects can use all of the cohort data collected at recruitment and during follow-up.

Recruitment for some of these projects continued beyond December 31, 2011, to include a large enough number of subjects.



Principal investigator: Pr Elie SALIBA, UCH Tours

Despite progress in the survival of very preterm children, their neurological development remains worrisome. These children are at greater risk than others of behavioral problems and learning disorders, which may be explained by disorders in executive functions (cerebral functions that allow individuals to adapt their behavior to changes in their environment) that are manifested by difficulties in problem solving and in working memory.

The objective of this study is to investigate, at the age of 3 years, during a specific examination set up as part of this project, the appearance of impairments in executive functions in these children and its relation to structural brain aberrations observed during magnetic resonance imaging (MRI) performed at birth.

This study includes 581 children.

One specific 3-year follow-up stage is ongoing to collect informations about children neurodevelopment.

To find out more about EPIRMEX study, click here icone-pdf


Principal investigator: Pr Pascal BOILEAU, IHC Poissy-St-Germain

Although the survival of preterm children has increased in recent years, the complication rates associated with very preterm birth remain high (40% have respiratory complications, 20% infectious complications, and 40% cerebral complications) and are associated with a high risk of disabilities (40%). The issue for the years to come is to reduce the frequency of these complications by implementing prevention strategies.

As part of this study, samples of cord blood and maternal blood were taken at birth. The results of the genetic analyses of these blood samples will be combined with the child's health data collected at birth and during the Epipage 2 follow-up, to examine whether early modifications of some genes may be associated with and, possibly, predict specific complications of very preterm birth.

This study includes 145 children.

To find out more about BIOPAG study, click here icone-pdf


Principal investigator: Pr Alexandre LAPILLONNE, Necker Hospital, Paris

French studies have recently suggested that preterm children's diets may be a decisive factor for their outcome. Accordingly, the quantity of milk received in the first weeks of life, its origin, its composition, and additional lipid and iron intake are factors that might significantly influence neurological outcome in children born before 33 weeks of gestation.

The objective of this study is to study the influence of the quantity and composition of the milk received in the first weeks of life on neurological outcome at the age of 2 years.

This study includes 329 children.

To find out more about EPINUTRI study, click here icone-pdf

Specific follow-up of children at 1 year - Practical procedures

The self-administered questionnaire for the EPINUTRI study supplemented the questionnaire sent to parents as part of Epipage 2 and collected information about breastfeeding between 6 and 12 months, consumption of fish and egg yolks (sources of DHA intake), and possible iron supplementation. This questionnaire was not available online, but was mailed to parents.


Intestinal ecosystem of very and extremely preterm infants: Analysis of the microbiota and its short- and long-term clinical implications

Principal investigator: Pr Marie-José BUTEL, Paris Descartes University

Associated group: MICALIS, INRA, Jouy-en-Josas

Studies have shown that development of the gut flora (all the microorganisms present in the intestines) during the first weeks of preterm babies' lives is aberrant and may affect the child's health in both the short term (intestinal complications during the initial hospitalization) and the long term (obesity, diabetes, allergies, etc.).

This study examines:

  • The relation between the development of intestinal flora and the risk of subsequent complications in very premature infants
  • The relation between intestinal flora and complications of intestinal origins observed during hospitalization
  • The factors occurring arround birth that may influence the establishment of intestinal flora in the very premature.

This study includes 731 children.

One specific 3-year follow-up stage is ongoing using a parental self-administered questionnaire and a collect of faeces sample.

To find out more about EPIFLORE study, click here icone-pdf


Observation of the Mother-Preterm Baby Bond

Principal investigator: Dr Jean-Baptiste MULLER, UCH Nantes

Recent data about child development suggest that the establishment of the mother-child bond can influence the quality of the child's growth (height and weight), motor progress (development and coordination of movements), and intellectual and language development. In preterm births, the negative experiences around the birth, by including particular mother-child interactions, may have a durable influence on the child's outcome.

The objectives of this study are:

  • To study the impact of the quality of early mother-child interactions on the intellectual, behavioral, and emotional outcome of preterm children at 2 and 5 years of age
  • To search for the factors that might cause early relational difficulties between the mother and her child.

This study includes 192 children.

To find out more about OLIMPE study, click here icone-pdf


Impact of histologic chorioamnionitis on neonatal prognosis in preterm deliveries

Principal investigators:
Pr Gilles KAYEM, UCH Louis-Mourier, AP-HP, Colombes
Pr Damien SUBTIL, UHC Lille

Histological and/or clinical chorioamnionitis (inflammation of the placenta, whether or not accompanied by clinical signs) is considered to aggravate neonatal prognosis or, more particularly, to increase neurological and pulmonary morbidity in the cases of preterm delivery. Inflammatory/ infectious phenomena appear to increase the risk of the white-matter diseases that cause cerebral palsy. The clinical studies thus far performed have nonetheless yielded discordant results about the association between histological chorioamnionitis and cerebral palsy or bronchopulmonary dysplasia.

The objective of this study is to study, in the context of current practices and with a long-term follow-up, the role of perinatal inflammation in the neurodevelopmental and pulmonary outcome of very preterm infants.

This study included 1406 births and enabled specific data collection for 1360 placentas.

To find out more about CHORHIST study, click hereicone-pdf


Palliative care decisions and practices around extremely preterm birth: role of the healthcare professionals and involvement of parents 

Principal investigator: Dr Laurence FOIX L'HELIAS, GH Armand Trousseau-La Roche Gouyon

Extremely preterm children, born between 22 and 26 weeks of gestation, account for 0.2 to 0.3% of births and require particular care. This care varies from one country to another and even from one hospital to another. Depending on their gestational age, their birth weight, and other criteria often associated with medical staff, some receive intensive care, while others do not. .

The objectives of this study are to:

  • Describe the situations of therapeutic abstention (where no treatment is administered to the child) and those where intensive care was initiated and then subsequently continued or limited, and identify the decision criteria that led to each of these situations
  • Assess parents' participation in this decision-making
  • Study the palliative care (care provided to preterm babies not responding to treatment to support their end-of-life period) set up in cases of very preterm birth.

This study includes 430 births.

To find out more about ETHICS study, click here icone-pdf

Epippain 2

Epidemiology of painful procedures in the NIC

Principal investigator: Pr Ricardo CARBAJAL, GH Armand Trousseau-La Roche Guyon

In France, the EPIPPAIN study performed in 2005-2006 in 13 NICUs in the Ile-de-France region showed that such procedures are performed extremely frequently in newborns admitted in the NICU, and that the use of methods for managing pain varied highly between the units.

The objectives of this second phase of EPIPPAIN are to:

  • describe the frequency of painful or stressful procedures in newborns receiving care in neonatal and pediatric ICUs and assess trends in these practices;
  • look at the influence of the painful or stressful procedures experienced and the anti-pain treatments received during the neonatal period on the children's subsequent neurological development;
  • describe the frequency of painful or stressful procedures and their management during the transport of newborns by the pediatric emergency and intensive care ambulance service (SMUR) in Ile-de-France.

This study includes 592 children. Among these 592 newborns, 332 are also participating in Epipage 2.

To find out more about EPIPPAIN 2 study, click here  icone-pdf






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