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

Abstract

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.

Keywords: epidemiology; growth; inflammation; preterm infant.

Figure.

Inflammatory protein elevation and infant size at NICU discharge or transfer in infants with extremely low gestational ages (<28 weeks). Weight is shown in Panel A, length in Panel B, and head circumference in Panel C. Beta coefficients from Model 3 (indicated by squares for weight, triangles for length, diamonds for head circumference) represent the estimated mean differences in weight, length, or head circumference z-score at discharge/transfer for infants in the top quartile for each inflammatory protein compared with a reference group of infants not in the top quartile. ‘Sustained’ elevation indicates being in the top quartile on at least 2 of 3 available days (1, 7, and/or 14).