Enteral feeding advancement and growth until 5 years in extremely preterm infants.

BACKGROUND: In-utero weight gain can be achieved in very preterm infants through rapid advancement of enteral feeds without increasing risk of necrotizing enterocolitis. There are concerns, however, that such rapid weight gain may lead to an increased childhood adiposity risk, although long-term data are sparse. DESIGN: This retrospective observational study included two well-characterized cohorts comprising 145 infants born at < 28 weeks or with < 1000 g birth weight. We investigated associations between advancing enteral feeding volumes in daily increments of 15-20 ml/kg (Cohort 1, n = 84, born in 2006/2007) vs. 25-30 ml/kg (Cohort 2, n = 61, born in 2010) and growth up to 5 years of age. RESULTS: There was no significant difference in anthropometric parameters post discharge to 5 years between both cohorts. Standard deviation score (SDS) weight and SDS BMI at the age of 5 years remained lower than in the reference population. SDS weight decreased from discharge to about 10-12 months postnatal age and returned to birth values by age 5 years. There was a catch-up for SDS length/height from discharge to 5 years; SDS head circumference decreased from birth to 5 years. Multiple regression analyses revealed that for all anthropometric parameters SDS at birth was the most important predictor for SDS at 5 years. Early parenteral protein intake may be another important factor, at least for head growth. CONCLUSIONS: Growth was similar in both cohorts without benefit from more accelerated feeding advancement in cohort 2. In both cohorts, early enteral nutrition was associated with in-hospital weight gain as in utero, a drop in weight SDS post discharge and catch-up to birth SDS until age 5 years, remaining below the reference population. Length showed catch-up form discharge to 5 years, whereas head circumference progressively deviated from the reference population. Increased parenteral protein supplementation may be needed to accompany early enteral feeding advancements.

Reticulocyte haemoglobin content as a marker of iron deficiency.

OBJECTIVE: To evaluate reticulocyte haemoglobin content (CHr), compared with ferritin, transferrin saturation (TS) and mean corpuscular volume (MCV), as a marker of iron deficiency (ID). DESIGN: Retrospective analysis of clinically indicated blood samples taken between February 2010 and October 2012. SETTING: Single-centre neonatal care unit. PATIENTS: 210 very preterm (gestational age <32 weeks) or very low birthweight infants (birth weight <1500 g) at 3-4 months corrected age. MAIN OUTCOME MEASURES: Complete blood count, CHr, ferritin and TS determined as part of a standard follow-up examination. To detect the optimal CHr cut-off, ID was defined by the presence of more than two of the following three criteria: MCV <75 fL, TS <10%, ferritin <30 µg/L. RESULTS: 210 preterm infants were included at a corrected age of (median (IQR)) 3.5 (3.0-4.0) months and with a CHr of 29.7 (28.6-30.7) pg. There were correlations between CHr and MCV (r=0.54, p <0.0001) and between CHr and TS (r=0.44, p <0.0001). There were 27 (13.4%) iron-deficient infants, and two infants (1%) fulfilled criteria of ID-anaemia. CHr was lower in infants with ID (26.4 (23.8-28.7) pg) than in those without (29.9 (29.0-30.8) pg, p <0.0001). The optimal CHr cut-off for detecting ID was 29 pg (sensitivity 85%, specificity 73%). Areas under the receiver operating characteristic curve for detection of ID tended to be higher for CHr compared with ferritin (0.92 vs 0.75), TS (0.90 vs 0.82) and MCV (0.81 vs 0.72). CONCLUSIONS: CHr seems to be a suitable marker for latent ID in preterm infants at 3-4 months corrected age and may be superior to ferritin, TS and MCV.

MHC class II molecules enhance Toll-like receptor mediated innate immune responses.

BACKGROUND: Major histocompatibility complex (MHC) class II molecules play crucial roles in immune activation by presenting foreign peptides to antigen-specific T helper cells and thereby inducing adaptive immune responses. Although adaptive immunity is a highly effective defense system, it takes several days to become fully operational and needs to be triggered by danger-signals generated during the preceding innate immune response. Here we show that MHC class II molecules synergize with Toll-like receptor (TLR) 2 and TLR4 in inducing an innate immune response. METHODOLOGY/PRINCIPAL FINDINGS: We found that co-expression of MHC class II molecules and TLR2 or TLR4 in human embryonic kidney (HEK) cells 293 leads to enhanced production of the anti-microbial peptide human-beta-defensin (hBD) 2 after treatment with TLR2 stimulus bacterial lipoprotein (BLP) or TLR4 ligand lipopolysaccharide (LPS), respectively. Furthermore, we found that peritoneal macrophages of MHC class II knock-out mice show a decreased responsiveness to TLR2 and TLR4 stimuli compared to macrophages of wild-type mice. Finally, we show that MHC class II molecules are physically and functionally associated with TLR2 in lipid raft domains of the cell membrane. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that MHC class II molecules are, in addition to their central role in adaptive immunity, also implicated in generating optimal innate immune responses.