Effect of Intra- and Extrauterine Growth on Long-Term Neurologic Outcomes of Very Preterm Infants.
To determine whether extrauterine growth is associated with neurologic outcomes and if this association varies by prenatal growth profile.



For 1493 preterms from the EPIPAGE (Étude Épidémiologique sur les Petits Âges Gestationnels [Epidemiological Study on Small Gestational Ages]) cohort, appropriate for gestational-age (AGA) was defined by birth weight >-2 SD and small for gestational-age (SGA) by birth weight ≤-2 SD. Extra-uterine growth was defined by weight gain or loss between birth and 6 months by z-score change. Growth following-the-curve (FTC) was defined as weight change -1 to +1 SD, catch-down-growth (CD) as weight loss ≥1 SD, and catch-up-growth (CU) as weight gain ≥1 SD. At 5 years, a complete medical examination (n = 1305) and cognitive evaluation with the Kauffman Assessment Battery for Children (n = 1130) were performed. Behavioral difficulties at 5 years and school performance at 8 years were assessed (n = 1095).



Overall, 42.5% of preterms were AGA-FTC, 20.2% AGA-CD, 17.1% AGA-CU, 5.6% SGA-FTC, and 14.5% SGA-CU. Outcomes did not differ between CU and FTC preterm AGA infants. Risk of cerebral palsy was greater for AGA-CD compared with AGA-FTC (aOR 2.26 [95% CI 1.37-3.72]). As compared with children with SGA-CU, SGA-FTC children showed no significant increased risk of cognitive deficiency (aOR 1.41[0.94-2.12]) or school difficulties (aOR 1.60 [0.84-3.03]). Compared with AGA-FTC, SGA showed increased risk of cognitive deficiency (SGA-FTC aOR 2.19 [1.25-3.84]) and inattention-hyperactivity (SGA-CU aOR 1.65 [1.05-2.60]).



Deficient postnatal growth was associated with poor neurologic outcome for AGA and SGA preterm infants. CU growth does not add additional benefits. Regardless of type of postnatal growth, SGA infants showed behavioral problems and cognitive deficiency.
Obstetrical, Perinatal, and Pediatric Epidemiology Team, Epidemiology and Biostatistics Sorbonne Paris Cité Research Center (U1153), INSERM, Paris, France. Electronic address: isabelle.guellec@trs.aphp.fr.
Isabelle
I
Guellec
APHP, Neonatology Unit, Necker Hospital, Paris, France.
Alexandre
A
Lapillonne
Rouen University Hospital, Neonatal Medicine, Rouen; Institute of Biomedical Research, University, Inserm Avenir Research Group, IFR 23, Rouen, France.
Stephane
S
Marret
Department of Neonatology, Human Nutrition Research Center, Hospital E. Herriot, Lyon, France.
Jean-Charles
JC
Picaud
APHP, Neonatology Unit, Trousseau Hospital, Paris, France.
Delphine
D
Mitanchez
Obstetrical, Perinatal, and Pediatric Epidemiology Team, Epidemiology and Biostatistics Sorbonne Paris Cité Research Center (U1153), INSERM, Paris, France.
Marie-Laure
ML
Charkaluk
Obstetrical, Perinatal, and Pediatric Epidemiology Team, Epidemiology and Biostatistics Sorbonne Paris Cité Research Center (U1153), INSERM, Paris, France; Clinical Epidemiology and Biostatistics Department, CHRU Nancy, Nancy, France.
Jeanne
J
Fresson
Paul Sabatier University, Toulouse, France.
Catherine
C
Arnaud
Department of Neonatology, CHU Nantes, Nantes, France.
Cyril
C
Flamant
Montpellier University Hospital Center, Neonatal and Pediatric Intensive Care Unit, Montpellier, France.
Gilles
G
Cambonie
Obstetrical, Perinatal, and Pediatric Epidemiology Team, Epidemiology and Biostatistics Sorbonne Paris Cité Research Center (U1153), INSERM, Paris, France.
Monique
M
Kaminski
Department of Neonatology, CHU Nantes, Nantes, France.
Jean-Christophe
JC
Roze
Obstetrical, Perinatal, and Pediatric Epidemiology Team, Epidemiology and Biostatistics Sorbonne Paris Cité Research Center (U1153), INSERM, Paris, France.
Pierre-Yves
PY
Ancel
D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000209:etiology*; D002547:Cerebral Palsy / Q000175:diagnosis / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology*; D005260:Female; D047109:Fetal Development; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature / Q000254:growth & development* / Q000523:psychology; D007236:Infant, Small for Gestational Age / Q000254:growth & development* / Q000523:psychology; D007859:Learning Disabilities / Q000175:diagnosis / Q000209:etiology*; D008297:Male; D009483:Neuropsychological Tests; D015430:Weight Gain
extrauterine growth restriction; neurological outcome; preterm; small-for-gestational age