Early Elevation in Interleukin-6 is Associated with Reduced Growth in Extremely Low Birth Weight Infants

Abstract

Objective To determine whether reduced growth velocity (GV) in extremely low birth weight infants is preceded by elevated inflammatory cytokines.

Study Design GV was determined at 36 weeks' postmenstrual age (PMA) in 768 infants 401 to 1,000 g birth weight (BW). Association between blood cytokines measured through day of life 21 and GV was explored using linear regression models that adjusted for late-onset sepsis (LOS), BW, small for gestational age (SGA), gender, race, energy intake, and center.

Results Serum interleukin-6 (IL-6) was increased at days 14 and 21 in LOS infants. LOS was associated with reduced energy intake and GV for weight (weight-GV) at 36 weeks' PMA. Linear regression analysis controlling for LOS and energy intake showed significant relationships between increased IL-6 at days 14 and 21 with reduced weight-GV at 36 weeks' PMA (p < 0.0001). The relationship between day 21 IL-6 and weight-GV was not associated with LOS (p = 0.12) when controlling for BW and energy intake. Both BW (p = 0.02) and energy intake (p = 0.003) influenced the relationship between day 14 IL-6 and weight-GV.

Conclusion IL-6 elevation during the first month of life is associated with lower weight-GV at 36 weeks' PMA and may have a direct effect upon energy balance and postnatal growth.

Keywords

cytokines - growth retardation - growth velocity - preterm infant - sepsis

Funding

The authors have no financial arrangement(s) with a company whose product figures prominently in the submitted manuscript or with a company making a competing product.

The study was supported by United States Public Health Service grants to the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network and NIH grant R01 DK058259 to Dr. Denson.

The National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the Centers for Disease Control and Prevention provided grant support for recruitment for 1999–2001 and data analysis for the Neonatal Research Network's Cytokines Study. In addition, Dr. Denson received support from National Institutes of Health through grant R01 DK058259. The funding agencies provided overall oversight for study conduct, but all data analyses and interpretation were independent of the funding agencies. We are indebted to our medical and nursing colleagues and the infants and their parents who agreed to take part in this study.

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