Objective There is increasing awareness that allogeneic transfusion is potentially harmful in preterm neonates secondary to transfusion related immunomodulation (TRIM). Non-transferrin bound iron (NTBI) may contribute to TRIM by promoting oxidative damage and pro-inflammatory cytokine release. The current study aimed to determine if transfusion early in the neonatal period resulted in an increase in circulating NTBI, oxidative stress and immune activation. Design Prospective observational study. Setting One transfusion event was studied in infants ≤28 weeks gestation between 2 and 6 weeks postnatal age (n=33) admitted to a tertiary neonatal intensive care unit. Methods Serum NTBI, inflammatory cytokines and malondialdehyde (MDA) were measured from the donor pack, prior to and at 2–4 and 24 h post-transfusion. Results Median (range) age at transfusion was 17 (14–39) days with the pretransfusion haemoglobin level 9.6 (7.4–10.4) g/dl. NTBI was detectable in 18 (51%) of the transfusion packs. NTBI levels were higher after transfusion (p<0.01) returning to pretransfusion levels by 24 h. Post-transfusion NTBI level correlated with the age of transfused blood (p<0.001) and was positively correlated with plasma MDA (p=0.01) but not IL-1β, IL-6, IL8 or TNFα. Conclusions Circulating NTBI is transiently elevated following blood transfusion in preterm newborns. This increase was related to the age of blood transfused and correlated with increases in oxidative stress but not pro-inflammatory cytokines. While further studies are necessary to determine whether these transient effects influence clinical outcome, the current data do not support a significant role in the very preterm neonate for NTBI in TRIM.

Objective. Dysregulated vascular resistance contributes to hypotension following preterm birth with sex-specific differences in microvascular function conferring a male disadvantage. We hypothesized that glucocorticoid mediated, sex-specific differences in the endogenous catecholamine norepinephrine and endothelially derived endothelin-1 (ET-1) contribute to microvascular dysfunction in preterm neonates in the immediate newborn period. Methods. Umbilical and plasma ET-1 and normetanephrine, in 24 h urine samples, were determined at 24, 72, and 120 h of age in 24–34 week infants (n = 60). Microvascular blood flow was determined by laser Doppler flowmetry. Results. In infants born within 72 h of antenatal glucocorticoid exposure, normetanephrine was higher in females than males (p = 0.048). Normetanephrine was inversely correlated with both microvascular blood flow at 24 h (p = 0.025) and CRIB II (p = 0.001). While umbilical arterial ET-1 was higher in females delivered <72 h after antenatal betamethasone (p = 0.006), plasma ET-1 did not correlate with microvascular blood flow or illness severity. Only sex and normetanephrine contributed significantly to both microvascular blood flow and endothelium dependant vasodilatation. Conclusions. These data support glucocorticoid mediated, sex-specific differences in mediators of vascular tone that may contribute to the impaired mechanisms compromising successful hemodynamic adaption to neonatal life and resulting in excess male morbidity and mortality.

Docosahexaenoic acid (DHA) supplementation in pregnancy may confer some clinical benefits; however, this compound can exert pro-oxidant effects. In this study, we investigated the effects of DHA on pro-oxidant/antioxidant balance in term and preterm placental explants, assessing oxidative stress marker concentrations, antioxidant capacity and pro-inflammatory cytokine production. Term (n=8) and preterm (n=9) placental explants were exposed to lipopolysaccharide (LPS, 1 ng/ml), DHA (1, 10 and 100 μM), and DHA and LPS simultaneously or pre-treated with DHA for 24 h prior to LPS treatment. The production of malondialdehyde (MDA, lipid peroxidation), 8-hydroxy-2-deoxy guanosine (8-OHdG, oxidative DNA damage) and pro-inflammatory cytokines (tumour necrosis factor α (TNFα), interleukin 6 and interferon-γ) and total antioxidant capacity were measured. DHA at a concentration of 100 μM induced oxidative stress in term placentas, while at all the three concentrations, it induced oxidative stress in preterm placentas. DHA and LPS resulted in reduced MDA levels in term (P<0.005) and preterm (P=0.004) placentas and reduced 8-OHdG levels in preterm placentas (P=0.035). DHA pre-treatment, but not co-treatment with LPS, reduced 8-OHdG levels (P<0.001) in term placentas. DHA increased antioxidant capacity only in term placentas (P<0.001), with lower antioxidant capacity being observed overall in preterm placentas compared with term placentas (P≤0.001). In term placentas, but not in preterm ones, DHA co-treatment and pre-treatment reduced LPS-induced TNFα levels. The ability of DHA to alter placental pro-oxidant/antioxidant balance is dependent on the DHA concentration used and the gestational age of the placental tissue. DHA has a greater capacity to increase oxidative stress in preterm placentas, but it offers greater protection against inflammation-induced oxidative stress in term placentas. This appears to be a result of DHA altering placental antioxidant capacity. These data have implications for the timing and concentration of DHA supplementation in pregnancy.

The aim of this study was to assess the effect of feeding high protein human milk fortifier (HMF) on growth in preterm infants. In this single-centre randomised trial, 60 infants born 28–32 weeks’ gestation were randomised to receive a higher protein HMF providing 1.8 g protein (n = 31) or standard HMF providing 1 g protein per 100 mL expressed breast milk (EBM) (n = 29). The primary outcome was rate of weight gain. Baseline characteristics were similar between groups. There was no difference between high and standard HMF groups for weight gain (mean difference (MD) −14 g/week; 95% CI −32, 4; p = 0.12), length gain (MD −0.01 cm/week; 95% CI −0.06, 0.03; p = 0.45) or head circumference gain (MD 0.007 cm/week; 95% CI −0.05, 0.06; p = 0.79), despite achieving a 0.7 g/kg/day increase in protein intake in the high protein group. Infants in the high protein group had a higher proportion of lean body mass at trial entry; however, there was no group by time effect on lean mass gains over the study. Increasing HMF protein content to 1.8 g per 100 mL EBM does not improve growth in preterm infants born 28–32 weeks’ gestation.