This systematic review and meta-analysis synthesised the post-1990 literature examining the effect of human milk on morbidity, specifically necrotising enterocolitis (NEC), late onset sepsis (LOS), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD) and neurodevelopment in infants born ≤28 weeks’ gestation and/or publications with reported infant mean birth weight of ≤1500 g. Online databases including Medline, PubMed, CINAHL, Scopus, and the Cochrane Central Register of Controlled Trials were searched, and comparisons were grouped as follows: exclusive human milk (EHM) versus exclusive preterm formula (EPTF), any human milk (HM) versus EPTF, higher versus lower dose HM, and unpasteurised versus pasteurised HM. Experimental and observational studies were pooled separately in meta-analyses. Risk of bias was assessed for each individual study and the GRADE system used to judge the certainty of the findings. Forty-nine studies (with 56 reports) were included, of which 44 could be included in meta-analyses. HM provided a clear protective effect against NEC, with an approximate 4% reduction in incidence. HM also provided a possible reduction in LOS, severe ROP and severe NEC. Particularly for NEC, any volume of HM is better than EPTF, and the higher the dose the greater the protection. Evidence regarding pasteurisation is inconclusive, but it appears to have no effect on some outcomes. Improving the intake of mother’s own milk (MOM) and/or donor HM results in small improvements in morbidity in this population.

Concern that mild iodine deficiency in pregnancy may adversely affect neurodevelopment of offspring has led to recommendations for iodine supplementation in the absence of evidence from randomised controlled trials. The primary objective of the study was to investigate the effect of iodine supplementation during pregnancy on childhood neurodevelopment. Secondary outcomes included pregnancy outcomes, maternal thyroid function and general health. Women with a singleton pregnancy of fewer than 20 weeks were randomly assigned to iodine (150 μg/d) or placebo from trial entry to birth. Childhood neurodevelopment was assessed at 18 months by using Bayley Scales of Infant and Toddler Development (Bayley-III). Iodine status and thyroid function were assessed at baseline and at 36 weeks’ gestation. Pregnancy outcomes were collected from medical records. The trial was stopped after 59 women were randomly assigned following withdrawal of support by the funding body. There were no differences in childhood neurodevelopmental scores between the iodine treated and placebo groups. The mean cognitive, language and motor scores on the Bayley-III (iodine versus placebo, respectively) were 99.4 ± 12.2 versus 101.7 ± 8.2 (mean difference (MD) −2.3, 95 % confidence interval (CI) −7.8, 3.2; P = 0.42), 97.2 ± 12.2 versus 97.9 ± 11.5 (MD −0.7, 95 % CI −7.0, 5.6; P = 0.83) and 93.9 ± 10.8 versus 92.4 ± 9.7 (MD 1.4, 95 % CI −4.0, 6.9; P = 0.61), respectively. No differences were identified between groups in any secondary outcomes. Iodine supplementation in pregnancy did not result in better childhood neurodevelopment in this small trial. Adequately powered randomised controlled trials are needed to provide conclusive evidence regarding the effect of iodine supplementation in pregnancy. The trial was registered with the Australian New Zealand Clinical Trials Registry at http://www.anzctr.org.au . The registration number of this trial is ACTRN12610000411044 . The trial was registered on 21 May 2010.

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.

Low Protein Kinase C zeta (PKCζ) levels in cord blood T cells (CBTC) have been shown to correlate with the development of allergic sensitization in childhood. However, little is known about the mechanisms responsible. We have examined the relationship between the expression of different levels of PKCζ in CBTC and their development into mature T cell cytokine producers that relate to allergy or anti-allergy promoting cells. Maturation of naïve CBTC was initiated with anti-CD3/-CD28 antibodies and recombinant human interleukin-2 (rhIL-2). To stimulate lymphocyte proliferation and cytokine production the cells were treated with Phytohaemagglutinin (PHA) and Phorbol myristate acetate (PMA). Irrespective of the PKCζ levels expressed, immature CBTC showed no difference in lymphocyte proliferation and the production of T helper 2 (Th2) cytokine interleukin-4 (IL-4) and Th1 cytokine, interferon-gamma (IFN-γ), and influenced neither their maturation from CD45RA⁺ to CD45RO⁺ cells nor cell viability/apoptosis. However, upon maturation the low PKCζ expressing cells produced low levels of the Th1 cytokines, IFN-γ, IL-2 and tumour necrosis factor-alpha (TNF), no changes to levels of the Th2 cytokines, IL-4, IL-5 and IL-13, and an increase in the Th9 cytokine, IL-9. Other cytokines, lymphotoxin-α (LT-α), IL-10, IL-17, IL-21, IL-22 and Transforming growth factor-beta (TGF-β) were not significantly different. The findings support the view that low CBTC PKCζ levels relate to the increased risk of developing allergic diseases.

Protein intakes of preterm infants are frequently below recommendations, but few studies report accurate intakes due to the difficulty of analysing human milk clinically. This observational analysis from a randomised trial of infants born <31 weeks’ gestation, investigating two levels of protein fortification, reports protein intakes compared with requirements and determines the association of direct breastfeeding on growth. Ninety-two infants (median gestational age 28 weeks, Interquartile range (IQR) 26–29; mean birth weight 1040 g, SD 300 g) were studied. Infants born weighing <1000 g were underfed protein compared with recommendations (median (IQR) intake of 3.0 (2.0–3.7) g/kg/day in week 2 versus recommendation of 4–4.5 g/kg/day), while those born weighing ≥1000 g met recommended protein intakes after the first week of life (median (IQR) intake of 3.7 (3.0–4.0) g/kg/day in week 2 versus recommendation of 3.5–4.5 g/kg/day). A moderate, negative correlation between the mean number of breast feeds and change in rate of weight gain (r = −0.37, p = 0.001) was found. Protein intakes of infants <1000 g did not meet recommendations and all infants were underfed protein and energy in the first week of life. Current protein fortification is inadequate for infants born <1000 g. Exploratory analysis showed faltering rate weight gain associated with increasing number of breast feeds and these results warrant confirmation.

Introduction: Milk fat globule membrane (MFGM) is a complex lipid–protein structure in mammalian milk and human milk that is largely absent from breastmilk substitutes. The objective of this trial is to investigate whether providing infant formula enriched with MFGM versus standard infant formula improves cognitive development at 12 months of age in exclusively formula-fed full-term infants.Methods and analysis: This is a randomised, controlled, clinician-blinded, researcher-blinded and participant-blinded trial of two parallel formula-fed groups and a breastfed reference group that were recruited in the suburban Adelaide (Australia) community by a single study centre (a medical research institute). Healthy, exclusively formula-fed, singleton, term-born infants under 8 weeks of age were randomised to either an MFGM-supplemented formula (intervention) or standard infant formula (control) from enrolment until 12 months of age. The reference group was not provided with formula. The primary outcome is the Cognitive Scale of the Bayley Scales of Infant Development, Fourth Edition (Bayley-IV) at 12 months. Secondary outcomes are the Bayley-IV Cognitive Scale at 24 months, other Bayley-IV domains (language, motor, emotional and behavioural development) at 12 and 24 months of age, infant attention at 4 and 9 months of age, parent-rated language at 12 and 24 months of age, parent-rated development at 6 and 18 months of age as well as growth, tolerance and safety of the study formula. To ensure at least 80% power to detect a 5-point difference in the mean Bayley-IV cognitive score, >200 infants were recruited in each group.Ethics and dissemination: The Women’s and Children Health Network Human Research Ethics Committee reviewed and approved the study (HREC/19/WCHN/140). Caregivers gave written informed consent prior to enrolling in the trial. Findings of this study will be disseminated through peer-reviewed publications and conference presentations.Trial registration number: ACTRN12620000552987; Australian and New Zealand Clinical Trial Registry: anzctr.org.au.