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Background: Composition of leukocyte populations in the first month of life remains incompletely characterised, particularly in preterm infants who go on to develop late-onset sepsis (LOS). Aim: To characterise and compare leukocyte populations in preterm infants with and without LOS during the first month of life. Study design: Single-centre prospective observational cohort study. Participants: Infants born <30 weeks gestational age (GA). Outcome measures: Peripheral blood samples were collected at 1, 7, 14, 21 and 28 days of life. Leukocyte populations were characterised using 5-fluorophore-6-marker flow cytometry. Absolute leukocyte counts and frequency of total CD45+ leukocytes of each population were adjusted for GA, birth weight z-scores, sex and total leukocyte count. Results: Of 119 preterm infants enrolled, 43 (36%) had confirmed or clinical LOS, with a median onset at 13 days (range 6–26). Compared to infants without LOS, the adjusted counts and frequency of neutrophils, basophils and non-cytotoxic T lymphocytes were generally lower and immature granulocytes were higher over the first month of life in infants who developed LOS. Specific time point comparisons identified lower adjusted neutrophil counts on the first day of life in those infants who developed LOS more than a week later, compared to those without LOS, albeit levels were within the normal age-adjusted range. Non-cytotoxic T lymphocyte counts and/or frequencies were lower in infants following LOS on days 21 and 28 when compared to those who did not develop LOS. Conclusion: Changes in non-cytotoxic T lymphocytes occurred following LOS suggesting sepsis-induced immune suppression. [ABSTRACT FROM AUTHOR]

Objective: We aimed to study fatigue and sleep in registrars working 12-hour rotating shifts in our tertiary neonatal intensive unit. Methods and participants: This study involved neonatal registrar's working day (08:00–21:00) and night (20:30–08:30) shifts. Participants maintained a sleep diary, answered a self-reported sleepiness questionnaire assessing subjective sleepiness, and performed a 10-minute psychomotor vigilance task (PVT) at the start and end of each shift. Primary outcomes: (1) Fatigue at the (i) "start vs end" of day and night shifts, (ii) end of the "day vs night" shifts, and (iii) end of "first vs last shift" in block of day and night shifts. (2) Duration and quality of sleep before the "day vs night" shifts. Mean reaction time (RTM), relative coefficient of variation (RTCV), and lapses (reaction time > 500ms) were used as measures of fatigue on PVT. Secondary outcome: Subjective sleepiness (self-reported sleepiness questionnaire) at the 'start vs end" of day and night shifts. Results: Fifteen registrars completed the study. Acuity was comparable for all shifts. (1) Psychomotor responses were impaired at the end vs start of day shifts [RTM (p = 0.014), lapses (p = 0.001)], end vs start of night shifts [RTM (p = 0.007), RTCV (p = 0.003), lapses (p<0.001)] and end of night vs day shifts [RTM (p = 0.007), RTCV (p = 0.046), lapses (p = 0.001)]. Only lapses were significantly increased at the end of the last (p = 0.013) vs first shift (p = 0.009) in a block of day and night shifts. (2) Duration of sleep before the night (p = 0.019) and consecutive night shifts was decreased significantly (p = 0.034). Subjective sleepiness worsened after day (p = 0.014) and night shifts (p<0.001). Conclusion: Fatigue worsened after the 12-hour day and night shifts with a greater change after night shifts. Lapses increased after block of day and night shifts. Sleep was decreased before night shifts. Our findings need to be confirmed in larger studies. [ABSTRACT FROM AUTHOR]

Background: In 2014, a whole-of-population and multi-faceted preterm birth prevention program was introduced in Western Australia with the single aim of safely lowering the rate of preterm birth. The program included new clinical guidelines, print and social media, and a dedicated new clinic. In the first full calendar year the rate of preterm birth fell by 7.6% and the reduction extended from the 28–31 week gestational age group upwards. Objective: The objective of this study was to evaluate outcomes in greater depth and to also include the first three years of the program. Study design: This was a prospective population-based cohort study of perinatal outcomes in singleton pregnancies before and after commencement of the program. Results: There was a significant reduction in preterm birth in the tertiary center which extended from 28 weeks gestation onwards and was ongoing. In non-tertiary centers there was an initial reduction, but this was not sustained past the first year. The greatest reduction was observed in pregnancies classified at first attendance as low risk. No benefit was observed in the private sector, but a significant reduction was seen in the remote region of the Kimberley where the program was first launched and vaginal progesterone had been made free-of-charge. Conclusion: Preterm birth rates can be safely reduced by a multi-faceted and whole-of-population program but the effectiveness requires continuing effort and will be greatest where the strategies are most targeted. [ABSTRACT FROM AUTHOR]

Background: Systematic reviews of randomised controlled trials report that probiotics reduce the risk of necrotising enterocolitis (NEC) in preterm neonates. Aim: To determine whether routine probiotic supplementation (RPS) to preterm neonates would reduce the incidence of NEC. Methods: The incidence of NEC ≥ Stage II and all-cause mortality was compared for an equal period of 24 months ‘before’ (Epoch 1) and ‘after’ (Epoch 2) RPS with Bifidobacterium breve M-16V in neonates <34 weeks. Multivariate logistic regression analysis was conducted to adjust for relevant confounders. Results: A total of 1755 neonates (Epoch I vs. II: 835 vs. 920) with comparable gestation and birth weights were admitted. There was a significant reduction in NEC ≥ Stage II: 3% vs. 1%, adjusted odds ratio (aOR) = 0.43 (95%CI: 0.21–0.87); ‘NEC ≥ Stage II or all-cause mortality’: 9% vs. 5%, aOR = 0.53 (95%CI: 0.32–0.88); but not all-cause mortality alone: 7% vs. 4%, aOR = 0.58 (95% CI: 0.31–1.06) in Epoch II. The benefits in neonates <28 weeks did not reach statistical significance: NEC ≥ Stage II: 6% vs. 3%, aOR 0.51 (95%CI: 0.20–1.27), ‘NEC ≥ Stage II or all-cause mortality’, 21% vs. 14%, aOR = 0.59 (95%CI: 0.29–1.18); all-cause mortality: 17% vs. 11%, aOR = 0.63 (95%CI: 0.28–1.41). There was no probiotic sepsis. Conclusion: RPS with Bifidobacterium breve M-16V was associated with decreased NEC≥ Stage II and ‘NEC≥ Stage II or all-cause mortality’ in neonates <34 weeks. Large sample size is required to assess the potential benefits of RPS in neonates <28 weeks. [ABSTRACT FROM AUTHOR]

Background: Extremely preterm infants are highly susceptible to bacterial infections but breast milk provides some protection. It is unknown if leukocyte numbers and subsets in milk differ between term and preterm breast milk. This study serially characterised leukocyte populations in breast milk of mothers of preterm and term infants using multicolour flow cytometry methods for extended differential leukocyte counts in blood. Methods: Sixty mothers of extremely preterm (<28 weeks gestational age), very preterm (28–31 wk), and moderately preterm (32–36 wk), as well as term (37–41 wk) infants were recruited. Colostrum (d2–5), transitional (d8–12) and mature milk (d26–30) samples were collected, cells isolated, and leukocyte subsets analysed using flow cytometry. Results: The major CD45+ leukocyte populations circulating in blood were also detectable in breast milk but at different frequencies. Progression of lactation was associated with decreasing CD45+ leukocyte concentration, as well as increases in the relative frequencies of neutrophils and immature granulocytes, and decreases in the relative frequencies of eosinophils, myeloid and B cell precursors, and CD16- monocytes. No differences were observed between preterm and term breast milk in leukocyte concentration, though minor differences between preterm groups in some leukocyte frequencies were observed. Conclusions: Flow cytometry is a useful tool to identify and quantify leukocyte subsets in breast milk. The stage of lactation is associated with major changes in milk leukocyte composition in this population. Fresh preterm breast milk is not deficient in leukocytes, but shorter gestation may be associated with minor differences in leukocyte subset frequencies in preterm compared to term breast milk. [ABSTRACT FROM AUTHOR]

Objective: We investigated the levels and antimicrobial activity of antimicrobial proteins and peptides (AMPs) in breast milk consumed by preterm infants, and whether deficiencies of these factors were associated with late-onset neonatal sepsis (LOS), a bacterial infection that frequently occurs in preterm infants in the neonatal period. Study design: Breast milk from mothers of preterm infants (≤32 weeks gestation) was collected on days 7 (n = 88) and 21 (n = 77) postpartum. Concentrations of lactoferrin, LL-37, beta-defensins 1 and 2, and alpha-defensin 5 were measured by enzyme-linked immunosorbent assay. The antimicrobial activity of breast milk samples against Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, and Streptococcus agalactiae was compared to the activity of infant formula, alone or supplemented with physiological levels of AMPs. Samples of breast milk fed to infants with and without subsequent LOS were compared for levels of AMPs and inhibition of bacterial growth. Results: Levels of most AMPs and antibacterial activity in preterm breast milk were higher at day 7 than at day 21. Lactoferrin was the only AMP that limited pathogen growth >50% when added to formula at a concentration equivalent to that present in breast milk. Levels of AMPs were similar in the breast milk fed to infants with and without LOS, however, infants who developed LOS consumed significantly less breast milk and lower doses of milk AMPs than those who were free from LOS. Conclusions: The concentrations of lactoferrin and defensins in preterm breast milk have antimicrobial activity against common neonatal pathogens. [ABSTRACT FROM AUTHOR]

Background: Probiotic supplementation significantly reduces the risk of necrotising enterocolitis (NEC) and all cause mortality in preterm neonates. Independent quality assessment is important before introducing routine probiotic supplementation in this cohort. Aim: To assess product quality, and confirm that Bifidobacterium breve (B. breve) M-16V supplementation will increase fecal B. breve counts without adverse effects. Methods and Participants: Strain identity (16S rRNA gene sequencing), viability over 2 year shelf-life were confirmed, and microbial contamination of the product was ruled out. In a controlled trial preterm neonates (Gestation <33 weeks) ready to commence or on feeds for <12 hours were randomly allocated to either B. breve M-16V (3×109 cfu/day) or placebo (dextrin) supplementation until the corrected age 37 weeks. Stool samples were collected before (S1) and after 3 weeks of supplementation (S2) for studying fecal B. breve levels using quantitative PCR (Primary outcome). Secondary outcomes included total fecal bifidobacteria and NEC≥Stage II. Categorical and continuous outcomes were analysed using Chi-square and Mann-Whitney tests, and McNemar and Wilcoxon signed-rank tests for paired comparisons. Results: A total of 159 neonates (Probiotic: 79, Placebo: 80) were enrolled. Maternal and neonatal demographic characteristics were comparable between the groups. The proportion of neonates with detectable B. breve increased significantly post intervention: Placebo: [S1:2/66 (3%), S2: 25/66 (38%), p<0.001] Probiotic: [S1: 29/74 (40%), S2: 67/74 (91%), p<0.001]. Median S1 B. breve counts in both groups were below detection (<4.7 log cells.g−1), increasing significantly in S2 for the probiotic group (log 8.6) while remaining <4.7 log in the control group (p<0.001). There were no adverse effects including probiotic sepsis and no deaths. NEC≥Stage II occurred in only 1 neonate (placebo group). Conclusion: B. breve M-16V is a suitable probiotic strain for routine use in preterm neonates. Trial Registration: Australia New Zealand Clinical Trial Registry ACTRN 12609000374268 [ABSTRACT FROM AUTHOR]

Background: The relationship between histological chorioamnionitis and haematological and biochemical markers in mothers and infants at delivery, and in infants postnatally, is incompletely characterised. These markers are widely used in the diagnosis of maternal and neonatal infection. Our objective was to investigate the effects of histological chorioamnionitis (HCA) on haematological and biochemical inflammatory markers in mothers and infants at delivery, and in infants post-delivery. Methods: Two hundred and forty seven mothers, delivering 325 infants, were recruited at the only tertiary perinatal centre in Western Australia. Placentae were assessed for evidence of HCA using a semi-quantitative scoring system. Maternal high sensitivity C-reactive protein (hsCRP), procalcitonin, and umbilical cord hsCRP, procalcitonin, white cell count and absolute neutrophil count were measured at delivery. In infants where sepsis was clinically suspected, postnatal CRP, white cell count and absolute neutrophil count were measured up to 48 hours of age. The effect of HCA on maternal, cord and neonatal markers was evaluated by multivariable regression analysis. Results: The median gestational age was 34 weeks and HCA was present in 26 of 247 (10.5%) placentae. Mothers whose pregnancies were complicated by HCA had higher hsCRP (median 26 (range 2-107) versus 5.6 (0-108) mg/L; P<0.001). Histological chorioamnionitis was associated with higher umbilical cord hsCRP (75th percentile 2.91 mg/L (range 0-63.9) versus 75th percentile 0 mg/L (0-45.6); P<0.001) and procalcitonin (median 0.293 (range 0.05-27.37) versus median 0.064 (range 0.01-5.24) ug/L; P<0.001), with a sustained increase in neonatal absolute neutrophil count (median 4.5 (0.1- 26.4)6109/L versus 3.0 (0.1-17.8)6109/L), and CRP up to 48 hours post-partum (median 10 versus 6.5 mg/L) (P<0.05 for each). Conclusion: Histological chorioamnionitis is associated with modest systemic inflammation in maternal and cord blood. These systemic changes may increase postnatally, potentially undermining their utility in the diagnosis of early-onset neonatal infection. [ABSTRACT FROM AUTHOR]