Complementary projects

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

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

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 

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 

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 

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



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

To find out more about CHORHIST study, click here

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  

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  

Principal investigator: Professor Marie Laure CHARKALUK, Hospital Saint Vincent de Paul, Lille (GHICL)

Despite the reduction in mortality of very preterm babies, their neurocognitive — and especially language — development remains worrisome. Preterm children are at higher risk of language delays. Moreover, their interactions with the external environment and especially with their parents are determinant in the process of language acquisition. There are not currently any guidelines in France for the management of language disorders in children younger than 3 years. Accordingly, a speech and language program implemented by parents with expert guidance might improve children's language skills.

The objective of this study was to assess the effect on language performance at age 3 of such a program conducted between 30 and 36 months of corrected age for very preterm babies with a language delay at 30 months of corrected age.

To learn more about the EPILANG study, click here   .

Principal investigator: Dr Catherine Gire, AP-HM

Although severe impairments have stabilized, most children born very preterm present apparently moderate neuropsychological disorders and behavioral problems that nonetheless have important family, school, and social repercussions that sometimes persist in adulthood. Executive functions, generally, and working memory, in particular, are frequently impaired in very preterm infants compared with control children born at term. Working memory is essential for the development of the mechanisms of reasoning, planning, and attention.

Intervention programs known as cognitive remediation have been set up to retrain the working memory; one of these is the Cogmed program. The hypothesis is that preschool cognitive remediation for children born very preterm with working memory deficits can improve their global intellectual performance and school integration. Several scientific studies have indicated that the Cogmed program has a significant and sustained effect on working memory, but its benefits for a large population remain to be proven.

The EPIREMED project is a randomized controlled study comparing 2 strategies: remediation versus standard management. Its objective is to assess the long-term (after 18 months) effect of a cognitive remediation intervention (Cogmed) at preschool age on intellectual function and language but also on behavior, quality of life, and schooling.

The children included in this project are those detected to have a working memory deficiency at the neuropsychological examination at age 5½ years.

Overall, 150 children participated in this study: 75 in the control group, and 75 in the group receiving the Cogmed intervention.

Principal investigator: Professor Jean-Christophe Rozé, UHC Nantes

The objectives of the Epivarec project are to study:

• The influence of variations in early nutritional/feeding practices "in the neonatal period" on metabolic status at age 5½ years
• The association between metabolic status and the growth trajectory during the first 5 years of life
• The association between neurocognitive development and the growth trajectory during the first 5 years of life.

At the 5½-year follow-up, supplementary investigations took place for children whose families agreed to participate in this project (estimation of body fat percentage, pulse wave velocity, albuminuria, and evaluation of physical activity).

401 children participated in this project.

Principal investigator: Professor Laurent Storme (UHC Lille), Professor Philippe Froguel (Institute Pasteur Lille)

Several studies have shown possible associations between various in utero exposures and the onset of chronic diseases during adulthood. These exposures may modify the functioning of our genetic material and consequently the development of our organism.

Preterm birth may also lead to such modifications, which are known as epigenetic modifications. They may eventually explain why some adults develop diseases such as obesity or type 2 diabetes. The objective is to detect these modifications to be able to determine if they might be associated, in the medium term, with the onset of particular diseases.

The EPIPRETERM project is a collaboration between the Epipage 2 team and the Institut Pasteur de Lille, which has the expertise required to perform these genetic analyses. This project does not require the collection of any new data. It is based on the use of the cord blood samples collected, with your consent, at your child's birth, as part of the supplemental BIOPAG project. This project, conducted in several regions, concerns only 150 children.

Genetic material (RNA and DNA), extracted from these blood samples, will be analyzed by Prof Philippe FROGUEL's team at the Institut Pasteur de Lille (http://www.good.cnrs.fr). These analyses will be performed in a confidential manner. They will therefore not lead to any individual results; they will only enable the identification of a global association between the frequencies of given genetic modifications and a given disease.

If you do not want these samples, taken at your child's birth, to be used for this project, contact us by telephone (01 56 01 71 85) or email ( This email address is being protected from spambots. You need JavaScript enabled to view it. ).