Systemic Inflammation in the First 2 Weeks after Birth as a Determinant of Physical Growth Outcomes in Hospitalized Infants with Extremely Low Gestational Age

Objective: To examine associations of systemic inflammation with growth outcomes at neonatal intensive care unit discharge or transfer among infants with extremely low gestational ages. Study design: We studied 850 infants at born at 23-27 weeks of gestation. We defined inflammatory protein elevation as the highest quartile of C-reactive protein (CRP), Interleukin (IL)-6, tumor necrosis factor-∝, or IL-8 on postnatal days 1, 7, and 14. We compared z-scores of weight, length, and head circumference at neonatal intensive care unit discharge or transfer between infants with vs without inflammatory protein elevation, adjusting in linear regression for birth size z-score, sex, gestational age, diet, comorbidities, medications, and length of hospitalization. Results: The mean gestational age was 25 weeks (range, 23-27 weeks) and birth weight z-score 0.14 (range, −2.73 to 3.28). Infants with a high CRP on day 7 had lower weights at discharge or transfer (−0.17 z-score; 95% CI, −0.27 to −0.06) than infants without CRP elevation, with similar results on day 14. Infants with CRP elevation on day 14 were also shorter (−0.21 length z-scores; 95% CI, −0.38 to −0.04), and had smaller head circumferences (−0.18 z-scores; 95% CI, −0.33 to −0.04) at discharge or transfer. IL-6 elevation on day 14 was associated with lower weight (−0.12; 95% CI, −0.22 to −0.02); IL-6 elevation on day 7 was associated with shorter length (−0.27; 95% CI, −0.43 to −0.12). Tumor necrosis factor-∝ and IL-8 elevation on day 14 were associated with a lower weight at discharge or transfer. Conclusions: Postnatal systemic inflammation may contribute to impaired nutrient accretion during a critical period in development in infants with extremely low gestational ages.