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The EPIPAGE Study

Catherine Arnaud, MD; Laetitia Daubisse-Marliac, MD; Mélanie White-Koning, PhD; Véronique Pierrat, MD; Béatrice Larroque, MD, PhD; Hélène Grandjean, MD, PhD; Corine Alberge, MD; Stéphane Marret, MD, PhD; Antoine Burguet, MD, PhD; Pierre-Yves Ancel, MD, PhD; Karine Supernant, DUT; Monique Kaminski, MSc

Arch Pediatr Adolesc Med. 2007;161(11):1053-1061.

Objectives  To assess the frequency of minor neuromotor dysfunctions (MNDs) at age 5 years according to gestational age, to test their association with behavioral and learning difficulties, and to find determining neonatal factors.

Design  Prospective population-based cohort study of children born in 1997 and followed up from birth to age 5 years.

Setting  All maternity wards in 9 regions of France.

Participants  A total of 1662 children born before 33 completed weeks of gestation and 2 control groups including 245 children born at 33 to 34 weeks and 332 children born at 39 to 40 weeks.

Main Exposure  Birth before 33 weeks.

Main Outcome Measure  Short version of the Touwen neurological examination classifying children as healthy, having mild MND (MND-1), or having moderate MND (MND-2) depending on the number of abnormal neuromotor signs found.

Results  Of children born before 33 weeks, 41.4% had MND-1 and 3.0% had MND-2. These proportions were 30.8% and 0.5%, respectively, for children born at 33 to 34 weeks and 22.0% and 0.7%, respectively, for children born at 39 to 40 weeks. Minor neuromotor dysfunction was independently associated with learning difficulties at age 5 years (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1-2.2). In very preterm children, factors associated with MND-1 were postnatal corticotherapy (OR, 1.8; 95% CI, 1.3-2.6), multiple births (OR, 0.7; 95% CI, 0.6-0.9), and, in singletons, breastfeeding (OR, 0.8; 95% CI, 0.6-0.99). Being a boy (OR, 3.1; 95% CI, 1.5-6.4), having had acute fetal distress (OR, 2.8; 95% CI, 1.4-5.5) or severe abnormalities on early cranial ultrasonography (OR, 2.7; 95% CI, 1.2-6.2), and having had postnatal corticotherapy (OR, 2.7; 95% CI, 1.2-6.1) increased the risk of MND-2.

Conclusions  The high rate of MNDs and their association with an increased risk for learning difficulties justify their screening in case of (even moderate) prematurity.

Author Affiliations: Institut National de la Santé et de la Recherche Médicale Unit 558, Research Unit on Perinatal Epidemiology, Child Health, and Development, University Toulouse III (Drs Arnaud, Daubisse-Marliac, White-Koning, and Grandjean) and Neonatal Care Unit, Children Hospital (Dr Alberge), Toulouse, France; Jeanne de Flandre Hospital, Lille, France (Dr Pierrat); Institut National de la Santé et de la Recherche Médicale Unit 149, Institut Fédératif de Recherche 169, Epidemiological Research on Perinatal Health and Women's Health, Villejuif, France (Drs Larroque, Burguet, and Ancel and Mss Supernant and Kaminski); Charles Nicolle Hospital, Rouen, France (Dr Marret); and Pediatric Unit, University Hospital, Poitiers, France (Dr Burguet).