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Pediatr Res. 2013 Mar;73(3):362-70. doi: 10.1038/pr.2012.188. Epub 2012 Dec 7.

Two-hit model of brain damage in the very preterm newborn: small for gestational age and postnatal systemic inflammation.

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Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.



We sought to disentangle the contributions of perinatal systemic inflammation and being small for gestational age (SGA) to the occurrence of low Bayley Mental Development Indices (MDIs) at the age of 2 y.


We measured the concentration of 25 inflammation-related proteins in blood obtained during the first two postnatal weeks from 805 infants who were born before the 28th wk of gestation and who had MDI measurements at the age of 2 y and were able to walk independently.


SGA newborns who did not have systemic inflammation (a concentration of an inflammation-related protein in the top quartile for gestational age on two days a week apart) were at a greater risk of an MDI <55, but not 55-69, than their peers who had neither SGA nor systemic inflammation. SGA infants who had elevated blood concentrations of interleukin (IL)-1β, tumor necrosis factor-α, or IL-8 during the first 2 postnatal weeks were at even higher risk of an MDI <55 than their SGA peers without systemic inflammation and their non-SGA peers with systemic inflammation.


SGA appears to place very preterm newborns at an increased risk of a very low MDI. Systemic inflammation adds considerably to the increased risk.

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