Effect of Intra- and Extrauterine Growth on Long-Term Neurologic Outcomes of Very Preterm Infants

J Pediatr. 2016 Aug:175:93-99.e1. doi: 10.1016/j.jpeds.2016.05.027. Epub 2016 Jun 16.


Objective: To determine whether extrauterine growth is associated with neurologic outcomes and if this association varies by prenatal growth profile.

Study design: 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).

Results: 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]).

Conclusion: 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.

Keywords: extrauterine growth restriction; neurological outcome; preterm; small-for-gestational age.

MeSH terms

  • Attention Deficit Disorder with Hyperactivity / diagnosis
  • Attention Deficit Disorder with Hyperactivity / etiology*
  • Cerebral Palsy / diagnosis
  • Cerebral Palsy / etiology*
  • Child
  • Child, Preschool
  • Cognition Disorders / diagnosis
  • Cognition Disorders / etiology*
  • Female
  • Fetal Development*
  • Follow-Up Studies
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Premature / growth & development*
  • Infant, Premature / psychology
  • Infant, Small for Gestational Age / growth & development*
  • Infant, Small for Gestational Age / psychology
  • Learning Disabilities / diagnosis
  • Learning Disabilities / etiology*
  • Male
  • Neuropsychological Tests
  • Weight Gain