Long-term outcomes of prenatally diagnosed ventriculomegaly — 10 years of Polish tertiary centre experience

Objectives: To estimate the prevalence, associated anomalies, and postnatal outcomes in infants prenatally diagnosed with ventriculomegaly.  Material and methods: All cases of ventriculomegaly that were examined and treated by the 1st Department of Obstet- rics and Gynecology, at the Medical University of Warsaw, from August 2007 until November 2017 were included in this study. Ultrasound data, and information on perinatal outcomes and long-term postnatal follow up were retrospectively collected by a standardised telephone survey. Ventriculomegaly was diagnosed when the atrial width of the lateral ventri- cles was ≥ 10 mm. The cases analyzed were divided into two subgroups: isolated ventriculomegaly (IVM) and non-isolated ventriculomegaly (NIVM). Neurodevelopmental complications were differentiated as either moderate or severe and were compared within each group and between groups.  Results: There were 118 cases of prenatally diagnosed ventriculomegaly. Complete follow up records were collected for 54 cases (45.8%). IVM was diagnosed in 29/54 (53.7%) cases, while NIVM was diagnosed in the remaining 25 (46.3%). The mean ventricular width for IVM was 16.93 mm (range 10.0 mm–73.0 mm) and 14.08 mm (range 9.0 mm–27.1 mm) for NIVM (p = 0.28). The mean gestational age at delivery for the IVM cases was 36 + 4 weeks and in the NIVM group 33 + 4 weeks (p = 0.022). Mild VM (10–12 mm) was diagnosed in 22/54 cases (40.7%), moderate VM (13–15 mm) in 12/54 (22.3%) and severe (≥ 15 mm) in 20/54 (37%). Among the infants with IVM the rate of severe medical complications was 29.6% (8/28) and for NIVM 667% (8/12) (p = 0.041). Less severe medical conditions affected 6/28 of the infants with IVM (21.4%) vs 9/12 NIVM cases (75%) (p = 0.012).  Conclusions: In terms of prenatal diagnosis, treatment of ventriculomegaly remains challenging due to a lack of specific prognostic factors and the significant risk of neurodevelopmental disorders. Nevertheless, isolated ventriculomegaly has significantly better long-term outcomes compared with non-isolated ventriculomegaly. In our material, the rate of severe neurodevelopmental disorders in the non-isolated ventriculomegaly cases was associated with a 52% rate of adverse perinatal outcomes. On the other hand, less severe medical conditions occurred in 21.4% of the infants with IVM and in 75% of the NIVM cases. Furthermore, obstetrical data suggest that the risks of premature delivery and caesarean section are significantly higher in cases of non-isolated ventriculomegaly.

New Achievements in High-Pressure Processing to Preserve Human Milk Bioactivity

High-pressure processing (HPP) is a non-thermal technology that is being increasingly applied in food industries worldwide. It was proposed that this method could be used as an alternative to holder pasteurization (HoP; 62.5°C, 30 min) in milk banks but its impact on the immunologic, enzymatic and hormonal components of human milk has not yet been evaluated in detail. The aim of our study was to compare the effects of HPP in variants: (1) 600 MPa, 10 min (2) 100 MPa, 10 min, interval 10 min, 600 MPa, 10 min (3) 200 MPa, 10 min, interval 10 min, 400 MPa, 10 min (4) 200 MPa, 10 min, interval 10 min, 600 MPa, 10 min in temperature range 19–21°C and HoP on the leptin, adiponectin, insulin, hepatocyte growth factor (HGF), lactoferrin and IgG contents in human milk. HoP was done at the Regional Human Milk Bank in Warsaw at the Holy Family Hospital on S90 Eco pasteurizer (Sterifeed, Medicare Colgate Ltd). Apparatus U4000/65 (Unipress Equipment, Poland) was used for pascalization. Milk samples were obtained from women during 2–6 weeks of lactation. Post-treatment culture showed no endogenous bacterial contamination in any tested option. Concentrations of selected components were determined using ELISA tests. The level of all analyzed components were significantly decreased by HoP: leptin 77.86%, adiponectin 32.79%, insulin 32.40%, HGF 88.72%, lactoferrin 60.31@.%, IgG 49.04%. All HPP variants caused an increase in leptin concentration, respectively (1) 81.79% (2) 90.01% (3) 86.12% (4) 47.96%. Retention of insulin after HPP was (1) 88.20% (2) 81.98% (3) 94.76% (4) 90.31% HGF (1) 36.15% (2) 38.81% 97.15% (3) 97.15% (4) 43.02%, lactoferrin (1) 55.78% (2) 57.63% (3) 78.77% (4) 64.75%. Moreover, HPP variant as 200 + 400 MPa preserved IgG (82.24%) better than HoP and resulted not statistically significant change of adiponectin level (38.55%) compare to raw milk. Our results showed that HPP leads to preservation of adipokines, growth factor, and lactoferrin, IgG much better or comparable with HoP

Recommendations for the Establishment and Operation of Human Milk Banks in Europe: A Consensus Statement From the European Milk Bank Association (EMBA)

Objectives: To develop recommendations from the European Milk Bank Association (EMBA) for the establishment and operation of human milk banks (HMB) in Europe.Method: A working group comprising members of the EMBA was convened in 2015 to develop Europe-wide recommendations for milk banks. Each member had experience of guideline development and/or milk banking operations. An initial survey was agreed using collated published global recommendations. A total of 108 potential recommendations were included in the survey; responders noted which were included in their national guidelines. The responses were collated, compared, and discussed and the group determined where there was consensus and where substantial or minor differences were identified. Where there was consensus or robust published evidence on which to base recommendations these were included. When there was no consensus and no clear evidence base, a statement of explanation based on collective expert opinion was agreed.Results: Published, internationally available guidelines with recommendations for human milk banks from France, Italy, and the UK, together with guidelines from Austria, Denmark, Germany, Norway, Slovakia, Spain, Sweden, and Switzerland were included as source materials. These covered: General recommendations; Donor recruitment and screening; Expression, handling, and storage of donor human milk (DHM); Pooling of DHM; Milk screening; Milk treatment (pasteurization); Delivery of DHM to recipients.Conclusions: Evidence based recommendations and consensus statements from the EMBA will now be published on the EMBA website to assist in the safe establishment and operation of HMBs throughout Europe. These have also been used to inform the chapter on human milk to be included in the 2019 edition of the Guide to the quality and safety of tissues and cells for human application, published by the European Directorate for the Quality of Medicines & HealthCare (EDQM)

Barley malt-based composition as a galactagogue — a randomized, controlled trial in preterm mothers

Objectives: Delayed or insufficient breast milk production, as well as low milk supply, is still a challenging problem toovercome, particularly in the case of preterm delivery. Herbal galactagogues might be a good way to increase milk supply,however, there is a lack of clinical studies confirming their efficacy and safety.The aim of this study was to verify the safety and effectiveness as a galactagogue of the unique galactagogue compositionbased on barley malt with β -glucan and lemon balm.Material and methods: The study included 117 mothers of preterm infants randomly divided into the GalactagogueGroup given galactagogue and the Placebo Group. A complete data set was obtained for 80 participants, divided equallybetween two groups.Volume of milk expressed by mothers during the first two weeks after delivery was the primary outcome and safetyof the product was the secondary outcome.Results: Volume of milk recorded on participants’ last visit in the Galactagogue Group was significantly higher than in thePlacebo Group (95 mL vs 62.5 mL, p = 0.049). The total expressed milk volume during the study was 4209 ± 335 mLin the Placebo Group vs 6036 ± 498 mL (p = 0.003) in the Galactagogue Group.Conclusions: Supplementation with unique Galactagogue composition was safe and increased milk output which allowedachieving target minimal volume of 500 mL per day in first week of lactation in preterm mothers

Fortification of Human Milk for Preterm Infants: Update and Recommendations of the European Milk Bank Association (EMBA) Working Group on Human Milk Fortification

Evidence indicates that human milk (HM) is the best form of nutrition uniquely suited not only to term but also to preterm infants conferring health benefits in both the short and long-term. However, HM does not provide sufficient nutrition for the very low birth weight (VLBW) infant when fed at the usual feeding volumes leading to slow growth with the risk of neurocognitive impairment and other poor health outcomes such as retinopathy and bronchopulmonary dysplasia. HM should be supplemented (fortified) with the nutrients in short supply, particularly with protein, calcium, and phosphate to meet the high requirements of this group of babies. In this paper the European Milk Bank Association (EMBA) Working Group on HM Fortification discusses the existing evidence in this field, gives an overview of different fortification approaches and definitions, outlines the gaps in knowledge and gives recommendations for practice and suggestions for future research. EMBA recognizes that “Standard Fortification,” which is currently the most utilized regimen in neonatal intensive care units, still falls short in supplying sufficient protein for some VLBW infants. EMBA encourages the use of “Individualized Fortification” to optimize nutrient intake. “Adjustable Fortification” and “Targeted Fortification” are 2 methods of individualized fortification. The quality and source of human milk fortifiers constitute another important topic. There is work looking at human milk derived fortifiers, but it is still too early to draw precise conclusions about their use. The pros and cons are discussed in this Commentary in addition to the evidence around use of fortifiers post discharge

Characteristics of the Alternative Phenotype of Microglia/Macrophages and its Modulation in Experimental Gliomas

Microglia (brain resident macrophages) accumulate in malignant gliomas and instead of initiating the anti-tumor response, they switch to a pro-invasive phenotype, support tumor growth, invasion, angiogenesis and immunosuppression by release of cytokines/chemokines and extracellular matrix proteases. Using immunofluorescence and flow cytometry, we demonstrate an early accumulation of activated microglia followed by accumulation of macrophages in experimental murine EGFP-GL261 gliomas. Those cells acquire the alternative phenotype, as evidenced by evaluation of the production of ten pro/anti-inflammatory cytokines and expression profiling of 28 genes in magnetically-sorted CD11b+ cells from tumor tissues. Furthermore, we show that infiltration of implanted gliomas by amoeboid, Iba1-positive cells can be reduced by a systematically injected cyclosporine A (CsA) two or eight days after cell inoculation. The up-regulated levels of IL-10 and GM-CSF, increased expression of genes characteristic for the alternative and pro-invasive phenotype (arg-1, mt1-mmp, cxcl14) in glioma-derived CD11b+ cells as well as enhanced angiogenesis and tumor growth were reduced in CsA-treated mice. Our findings define for the first time kinetics and biochemical characteristics of glioma-infiltrating microglia/macrophages. Inhibition of the alternative activation of tumor-infiltrating macrophages significantly reduced tumor growth. Thus, blockade of microglia/macrophage infiltration and their pro-invasive functions could be a novel therapeutic strategy in malignant gliomas

TGF beta signalling and its role in tumour pathogenesis.

Transforming growth factor beta (TGF-β) is a multifunctional cytokine involved in the regulation of cell proliferation, differentiation and survival/or apoptosis of many cells. Knock-out experiments in mice for the three isoforms of TGF-β have demonstrated their importance in regulating inflammation and tissue repair. TGF-β is implicated in the pathogenesis of human diseases, including tissue fibrosis and carcinogenesis. TGF-β receptors act through multiple intracellular pathways. Upon binding of TGF-β with its receptor, receptor-regulated Smad2/3 proteins become phosphorylated and associate with Smad4. Such complex translocates to the nucleus, binds to DNA and regulates transcription of specific genes. Negative regulation of TGF-β/Smad signalling may occur through the inhibitory Smad6/7. Furthermore, TGF-β-activated kinase-1 (TAK1) is a component of TGF-β signalling and activates stress-activated kinases: p38 through MKK6 or MKK3 and c-Jun N-terminal kinases (JNKs) via MKK4. In the brain TGF-β, normally expressed at the very low level, increases dramatically after injury. Increased mRNA levels of the three TGF-β isoforms correlate with the degree of malignancy of human gliomas. TGF-βs are secreted as latent precursors requiring activation into the mature form. TGF-β may contribute to tumour pathogenesis by direct support of tumour growth and influence on local microenvironment, resulting in immunosuppression, induction of angiogenesis, and modification of the extracellular matrix. TGF-β1,2 may stimulate production of vascular endothelial growth factor (VEGF) as well as plasminogen activator inhibitor (PAI-I), that are involved in vascular remodelling occurring during angiogenesis. Blocking of TGF-β action inhibits tumour viability, migration, metastases in mammary cancer, melanoma and prostate cancer model. Reduction of TGF-β production and activity may be a promising target of therapeutic strategies to control tumour growth

Carotenoid Content in Breastmilk in the 3rd and 6th Month of Lactation and Its Associations with Maternal Dietary Intake and Anthropometric Characteristics

Carotenoids are diet-dependent milk components that are important for the visual and cognitive development of an infant. This study determined β-carotene, lycopene and lutein + zeaxanthin in breastmilk and its associations with dietary intake from healthy Polish mothers in the first six months of lactation. Concentrations of carotenoids in breastmilk were measured by HPLC (high-performance liquid chromatography) (first, third, sixth month of lactation) and dietary intake was assessed based on a three-day dietary record (third and sixth month of lactation). The average age of participants (n = 53) was 31.4 ± 3.8 years. The breastmilk concentrations of carotenoids were not changed over the progress of lactation. Lycopene was a carotenoid with the highest content in breastmilk (first month 112.2 (95% CI 106.1–118.3)—sixth month 110.1 (103.9–116.3) nmol/L) and maternal diet (third month 7897.3 (5465.2–10329.5) and sixth month 7255.8 (5037.5–9474.1) µg/day). There was a positive correlation between carotenoids in breastmilk and dietary intake (lycopene r = 0.374, r = 0.338; lutein + zeaxanthin r = 0.711, r = 0.726, 3rd and 6th month, respectively) and an inverse correlation with maternal BMI in the third month of lactation (β-carotene: r = −0.248, lycopene: r = −0.286, lutein + zeaxanthin: r = −0.355). Adjusted multivariate regression models confirmed an association between lutein + zeaxanthin intake and its concentration in breastmilk (third month: β = 0.730 (0.516–0.943); 6th: β = 0.644 (0.448–0.840)). Due to the positive associations between dietary intake and breastmilk concentrations, breastfeeding mothers should have a diet that is abundant in carotenoids

Association between Breastmilk LC PUFA, Carotenoids and Psychomotor Development of Exclusively Breastfed Infants

The first months of infant life are crucial for proper neurodevelopment, which may be influenced by several factors, including nutrition and nutrients (e.g., long-chain polyunsaturated fatty acids (LC PUFA) and carotenoids) of which the concentration in breastmilk is diet-dependent. This study analysed the relationship between the average concentrations of selected LC PUFA and carotenoids in breastmilk samples from the first and third months of lactation and the psychomotor development of exclusively breastfed infants at the sixth month of life. Infant psychomotor development was assessed using the Children Development Scale (DSR). The average age of infants during the assessment was 6.6 ± 0.2 months and 30.9 ± 3.8 years for mothers (n = 39 mother–infant pairs). The average concentration of docosahexaenoic acid (DHA) was 0.50% of fatty acids. The average concentration of carotenoids was 33.3 nmol/L for β-carotene, 121 nmol/L for lycopene and 33.3 nmol/L for lutein + zeaxanthin. The total results of the Performance scale and Motor subscale were 39 centiles and 4.1 points, respectively. Adjusted multivariate regression models revealed associations between breastmilk DHA and motor development (β = 0.275; p ≤ 0.05), α-linolenic acid (ALA; β = 0.432; p ≤ 0.05), n-3 LC PUFA (β = 0.423; p ≤ 0.05) and β-carotene (β = 0.359; p ≤ 0.05). In addition, an association between the Perception subscale and DHA was observed (β = 0.316; p ≤ 0.05; model 2). There were no significant associations between the overall Performance scale scores. Due to the positive association between concentrations of n-3 LC PUFA (ALA and DHA) and β-carotene in breastmilk and infant motor development, it is important to provide these nutrients with breastmilk. According to the diet-dependent concentration of these compounds in breastmilk, breastfeeding mothers should have a diet abundant in dietary sources of these nutrients, e.g., fish, nuts, seeds, vegetable oils, vegetables and fruits

Microbiological Quality of Milk Donated to the Regional Human Milk Bank in Warsaw in the First Four Years of Activity

As the survival rate for preterm infants increases, more emphasis is placed on improving health-related quality of life through optimal nutritional management. Human Milk Banks (HMBs) provide bioactive nutrients and probiotic microorganisms to premature newborns, especially in the first year of life. Donated milk screening and selection of potential donors ensures the quality and microbiological safety of the donated milk. Therefore we reviewed the basic characteristics of donors and the amounts and contamination of breast milk donated to the Regional Human Milk Bank (RHMB) in Warsaw. In four years, the RHMB collected 1445.59 L of milk, of which 96.60% was distributed among hospitalised infants. Additionally, breastmilk from donor candidates (139 samples from 96 women) was tested at least once in the first year of lactation. First analyses showed that 18 women’s milk samples were microbiologically pure, and 78 samples had one or more species of commensal and/or potentially pathogenic bacteria. In human milk samples from 10 women, the bacteria level was above the standard required by the RHMB; therefore, donors were re-educated, and further samples were tested. Most women followed the recommendations on hygienic expression and storage of milk before transfer to the RHMB. Our analysis will help to increase the accessibility and quality of raw donor milk and to meet the needs of more newborns