Monitoring the Use of Human Milk, the Ideal Food for Very Low-Birth-Weight Infants-A Narrative Review.

Aware of the utmost importance of feeding premature babies-especially those of lower weight-with human milk, as well as the need to monitor this important element of neonatal care, we focused on four aspects in this review. First of all, we reviewed the beneficial effects of feeding premature infants with breast milk in the short and long term. Secondly, we performed a quantitative evaluation of the rates of breastfeeding and feeding with human milk in Very-Low-Birth-Weight infants (VLBWs) during hospitalization in the Neonatal Intensive Care Unit (NICU) and at discharge. Our aim was to take a snapshot of the current status of human milk-feeding care and track its trends over time. Then we analyzed, on the one hand, factors that have been proven to facilitate the use of maternal milk and, on the other hand, the risk factors of not feeding with breast milk. We also considered the spread of human milk banking so as to assess the availability of donated milk for the most vulnerable category of premature babies. Finally, we proposed a protocol designed as a tool for the systematic monitoring of actions that could be planned and implemented in NICUs in order to achieve the goal of feeding even more VLBWs with human milk.

Trend and Predictors of Breastmilk Feeding among Very-Low-Birth-Weight Infants in NICU and at Discharge.

Mothers' own milk (MOM) for premature babies is considered a life-saving drug for its proven protective action against the complications of prematurity and for effects on outcome in the short and long term, especially neurological ones. We studied the use of MOM for infants weighing <1500 g for a period of 5 years, evaluating the trend over time and the impact of some variables on human milk feeding performance. Statistical comparisons concerned the rate of feeding with breast milk during a stay in an NICU and at discharge with respect to two types of variables: (1) maternal and neonatal characteristics (gestational age, birth weight, type of pregnancy (whether single or twin), maternal age) and (2) feeding characteristics (time of the start of minimal enteral feeding and availability of MOM, days until the achievement of full enteral feeding). Group comparisons were performed using ANOVA or t-test for continuous variables and Pearson chi-squared test or Fisher exact test for categorical variables. We observed an increase, between 2017 and 2021, in MOM use (p = 0.003). The availability of the own mothers' milk occurred, on average, on the fourth day of life and improved over the years. The start of minimal enteral feeding (MEF) with human milk averaged 1.78 days, and 54.3% of VLBWs received MEF with donor milk on the first day of life. The average percentage of feeding with the mothers' milk at discharge was 47.6%, with 36.1% of exclusive MOM and an increase from 45.8% in 2017 (33.3% exclusive) to 58.82% (41.18% exclusive) in 2021. The mean average daily growth of the weight improved (p < 0.001) during this period, and there was no statistical difference between infants fed with maternal milk and those fed with bank milk. Older maternal age, early-start feeding with maternal milk and low gestational age had a statistically significant impact on feeding with MOM at discharge.

Feeding Twins with Human Milk and Factors Associated with Its Duration: A Qualitative and Quantitative Study in Southern Italy.

BACKGROUND: Over the past year, there has been a rise in twin births. The current scientific consensus recommended breast-feed milk for all newborns for at least 6 months. They stated that it is possible to meet the nutritional needs of two or more newborns with only one mother's milk. More information would be desirable about the factors that influence or lead to the initiation and interruption of breastfeeding. The quality of the evidence available from multiple studies has been inconclusive and therefore led to controversial interpretations and practices. AIMS: The first aim of this study was to analyze the extent of the feeding of multiples with breast milk in the experience of our clinical unit in terms of incidence and duration. The second objective was to evaluate the correlation between maternal, perinatal and neonatal variables with breast milk feeding rates and duration. METHODS: The study was conducted between 2015 and 2020, in a NICU in Southern Italy (San Giovanni Rotondo, Foggia). Sixty-one women who have given birth to multiples were enrolled into the study. Newborn data were retrospectively collected by informatic database and breastfeeding information were collected by a questionnaire. RESULTS: In our centre, the percentage of twins out of the total number of births over the years has almost doubled from 1.28% in 2015 to 2.48% in 2020 and the 88% of twins are premature. 18.1% received breast milk for more than 6 months and 6.3% received it for more than 12 months. Infants of lower gestational age and weight, born to multiparous, more mature and medium-high schooling mothers received breast milk for a longer period. 35% of women explained that the interruption of breastfeeding was due to the insufficient milk production and 41% to the stress and difficulties in managing the twins. Qualitative analysis of maternal narrative revealed, for many of them, the awareness of the importance of breastfeeding and the efforts made to try to give breast milk, but also fears about the quantity of milk and satiety of their children. CONCLUSIONS: It is important to identify the factors both favoring and obstructing maternal milk feeding of multiples and it would be desirable the activation of a network of training and support for mothers after discharge, with particular regard to the categories found to be less inclined.

Exploring the Role of Matrix Metalloproteinases as Biomarkers in Sporadic Lymphangioleiomyomatosis and Tuberous Sclerosis Complex. A Pilot Study.

Background: Lymphangioleiomyomatosis can develop in a sporadic form (S-LAM) or in women with tuberous sclerosis complex (TSC). The matrix metalloproteinases (MMPs) are extracellular matrix-degrading enzymes potentially involved in cystic lung destruction, and in the process of migration of LAM cells. The aim of the study was to explore the role of MMP-2 and MMP-7, such as vascular endothelial growth factor (VEGF) -C and -D in women with LAM, including patients with minor pulmonary disease (i.e., <10 lung cysts), and TSC with or without LAM. Methods: We evaluated 50 patients: 13 individuals affected by S-LAM, 20 with TSC-LAM, of whom six with minor pulmonary disease, and 17 with TSC without pulmonary involvement. Sixteen healthy women were used as controls. Results: MMP-2 resulted higher in LAM compared to healthy volunteers, and TSC patients (p = 0.040). MMP-7 was higher in TSC-LAM patient, with even greater values in patients with TSC-LAM minor pulmonary disease, than in S-LAM patients, and in controls (p = 0.001). VEGF-D level was lower than 800 pg/mL in all healthy controls and resulted higher in S-LAM and TSC-LAM than in TSC patients and controls (p < 0.001). VEGF-C values were not statistically different in the study population (p = 0.354). The area under ROC curves (AUCs) of MMP-2, and MMP-7 for predicting LAM diagnosis were of 0.756 ± 0.079 (p = 0.004), and 0.828 ± 0.060 (p < 0.001), respectively. Considering only patients with TSC, the AUCs for MMP-2, and MMP-7 in predicting LAM were 0.694 ± 0.088 (p = 0.044), and 0.713 ± 0.090 (p = 0.027), respectively. Conclusions: Our data suggest that MMP-2 and MMP-7 could be promising biomarkers for LAM diagnosis.

The Revolution of Breast Milk: The Multiple Role of Human Milk Banking between Evidence and Experience-A Narrative Review.

The review recalls the importance of breast milk and deepens the theme of human milk banking, a virtuous reality that is expanding all over the world but is still little known. In the last 15 years, modern biological technologies have crystallized the concept of uniqueness and irreproducibility of human milk, by establishing three new principles: first: human milk: a "life-saving" drug; second: human milk: the best food for preterm infants; and third: human milk: the main component of premature infant care. Our experience teaches us that human milk banking plays many roles that need to be known and shared.

X(-rays) sometimes mark the spot: A case of occult central venous catheter embolization.

INTRODUCTION: Breakage and fragment embolization is a rare but feared complication of peripherally inserted central catheter use. While chest radiographs are no longer the gold standard for determining peripherally inserted central catheter tip position, their use in diagnosing complications is still warranted. We report a case of occult catheter embolization discovered by routine chest X-ray. CASE DESCRIPTION: A patient with a right brachial vein peripherally inserted central catheter was admitted to our Emergency Department for palpitations and dyspnea. The peripherally inserted central catheter was not visible at presentation, and she was unclear as to what had happened; she left the Emergency Department before workup was performed. Catheter embolization was discovered upon implantation of a new peripherally inserted central catheter. CONCLUSION: Although routine chest radiographs are no longer necessary after peripherally inserted central catheter implantation, they are in diagnosing peripherally inserted central catheter-related complications even in asymptomatic patients. We discuss their use and the possible role of securement devices in preventing some instances of catheter embolization.

Natural history of incidental sporadic and tuberous sclerosis complex associated lymphangioleiomyomatosis.

Lymphangioleiomyiomatosis (LAM) is a rare disease affecting women in childbearing age. A sporadic form (S-LAM) affecting previously healthy women, and a form associated with Tuberous Sclerosis Complex (TSC-LAM) are described. Some data suggested that TSC-LAM could be a milder disease compared to S-LAM. To investigate whether the different disease behavior is real or due to overdiagnosis of screened TSC women, we compared the natural history of S-LAM and TSC-LAM in patients with incidental diagnosis. Clinical, and functional data from 52 patients (23 with S-LAM and 29 with TSC-LAM) were analysed. At diagnosis functional impairment was mild without differences between groups [FEV1 % pred was 97% (88-105) and 94% (82-106) in TSC-LAM and S-LAM, respectively, p = 0.125]. Patients with S-LAM had less renal angiomyolipoma, and lower VEGF-D serum levels than TSC-LAM. There was no difference in the baseline extent of pulmonary cysts on CT scan and no difference in yearly rate of functional decline between TSC-LAM, and S-LAM patients [e.g. yearly rate of decline of FEV1 % pred was -0.51 (-1.59-2.24) and -0.90 (-1.92--0.42) in TSC-LAM and S-LAM, respectively, p = 0.265]. In conclusion, the natural history of TSC-LAM and S-LAM, when a potential selection bias due to screening in the latter group is balanced, is similar. Our study suggests that the prevalence of S-LAM can be significantly underestimated due to a tendency to diagnosis more frequently patients with more severe impairment, without identifying several ones with asymptomatic disease.

If it looks like a catheter and winds like a catheter . . . fibroblastic sheath mimicking a central venous catheter fragment: A case report.

INTRODUCTION: Fibroblastic sheath formation is a well-known complication of long-term central venous catheters. When calcified, fibroblastic (formerly known as "fibrin") sheaths may be easily mistaken for retained catheter fragments. We describe one such case and how imaging was used to recognize the sheath and avoid unnecessary interventions. CASE DESCRIPTION: A patient with systemic sclerosis was referred for port removal because of suspected infection. A later computed tomography scan showed a persistent tubular structure coursing behind the right clavicle, which was also seen in an anteroposterior chest radiograph. Three-dimensional reconstruction and analysis of the structure's lumen in comparison to previous imaging studies allowed us to confirm that it was, in fact, a calcified fibroblastic sheath. The patient's course was uneventful thereafter. CONCLUSION: Three-dimensional computed tomography reconstruction, as well as the hollow appearance of a tubular structure after removal of a central catheter may help differentiate a fibroblastic sheath from a retained catheter fragment. Accurate surgical notes mentioning the length of the catheter at implant and explant are also of paramount importance.

Analytical Study of Donor's Milk Bank Macronutrients by Infrared Spectroscopy. Correlations With Clinic-Metabolic Profile of 100 Donors.

For its specific qualitative characteristics human donor milk (DM) is the main alternative to preterm infants nutrition and growing. How several studies suggest child's physical and mental development is influenced by breastfeeding that prevents the necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), and sepsis common in preterm newborns. Our research was conducted in NICU's Human Milk Bank (HMB) "Allattiamolavita." Our study was based on macronutrients analysis (MA) of 100 DM samples taken until 10 days since childbirth and analyzed by spectroscopic infrared innovative method (MIRIS). This is a specific method to analyse fat (F), crude proteins (CP), true proteins (TP), carbohydrate (CHO), and total solids (TS). We also analyzed the 100 donors' clinic-metabolic profile by blood tests (PMT). Both data was collected between September 2015 and February 2018. The research was structured in two parts. In the first part we compared PMT with qualitative and quantitative characteristics of MA while in the second one we studied every DM macronutrient finding furthermore possible relations between them. Statistical Package for Social Sciences (SPSS-IBM 24) was used to compare data and reporting coefficient of determination using Spearman's Rho and Kendall's Tau. We also analyzed samples using Kolmogorov-Smirnov test, Student T-test, ANOVA, Whitney U-test, and chi-square test. Statistically significant correlations were noted between maternal serum proteins and CP-TP of DM. The research showed also significant correlations between azotaemia and TP and an inverse correlation between serum creatinine and CP. No statistically significant correlation was observed between donors' glycaemia and CHO. Mineral concentrations of DM emerged independent of blood minerals (P, Ca, Fe, Na). We also calculated a normal range for individual macronutrient of human transitional milk (TM) that was not established in literature yet. Our experience allowed us to underline that human milk is a privileged site compared to donors' clinical and metabolic disorders. Our analysis showed the major role of the HMB to provide DM to improve clinical status, growing, and neurocognitive short and long term outcome of preterm infants.

Might the Mothers of Premature Babies Feed Them and Devote Some Milk to the Milk Bank?

The breast milk is the gold standard food for the feeding of the premature baby: it is the natural way to provide excellent nutritional, immunological, and biological nutriment so as to facilitate a healthy growth and the development of the infants. When the breast milk is not available, the alternative is represented by the donated milk. The mothers of premature infants are important opportunity if we consider the fact that they could devote some milk both because they provide a food which is closer to the needs of the vulnerable category of newborns and because it is, for the mothers, a way to overcome the detachment and the psychological trauma of a premature birth. There are no data on this kind of donation. The aim of the study is to evaluate the contribution of the milk donation to the HMB of CSS by women who gave birth to premature infants of gestational age <35 weeks and to analyze the macronutrient composition of the "preterm" donated milk. The CSS HMB has recruited 659 donors totalling 2236 liters of donated milk over a period of 7 years. 38 donors (5.7%) gave birth to a gestational age <35 weeks. Almost 20% of the donated milk comes from mothers of premature babies and this is a very important fact because it shows the huge potential belonging to this category of mothers. Taking into account the parameter regarding the birth weight, it was found that VLBW mothers contributed for 56% to preterm donation while ELBW mothers contributed for 41%. By evaluating the variable gestational age, about 40% of the average total donation derives from mothers who gave birth before the 25 weeks, while a contribution of 46% is attributable to the category of newborns with a GA between 25 and 32 weeks. Besides, some other exceptional examples can be outlined. Regarding the correlation analysis DM resulted in negative correlation with GA weeks (r=-0.31, p=0.058) and with BW g (r=-0.30, p=0.068) achieving values which are very close to the significance. The comparison between the donor volume averages of the preterm and full-term groups is statistically significant. The composition data are in line with the literature: there is an increase by 18 % in the protein component of the milk deriving from the mothers of the premature infants; the gap in carbohydrates is less significant (5-6%) and the gap in calories is similarly low being only 2% higher than the single donor milk and 11% more than the pooled milk. The data on the lipids line up to single donor term milk, while it grows by 24% compared to the pooled one. The study shows that even at very low or extreme gestational age it is possible to obtain an appropriate production of breast milk. This awareness becomes a fundamental starting point for the activation in a standardized way of all the strategies of promotion and support of food that have proven effective with the HM in NICU.

Lymphangioleiomyomatosis, multifocal micronodular pneumocyte hyperplasia, and sarcoidosis: more pathological findings in the same chest CT, or a single pathological pathway?

BACKGROUND: Autoimmune hepatitis/primary biliary cirrhosis overlap syndrome, lymphangioleiomyomatosis/tuberous sclerosis complex (LAM-TSC), and sarcoidosis are three rare diseases. Here we present, to the best of our knowledge, the first description of a patient with the coexistence of these three diseases. CASE PRESENTATION: A 47-year-old woman affected by LAM-TSC and primary biliary cirrosis/autoimmune hepatitis overlap syndrome. During her follow up a high resolution chest CT scan (HRTC) confirmed the presence of both multiple cysts and micronodular opacities consistent with multifocal micronodular pneumocytes hyperlasia (MMPH), and revealed multiple hilar-mediastinal symmetrical lymphadenopathies suggestive of sarcoidosis. Simultaneously, subcutaneous nodules appeared on her forearm bilaterally. Cutaneous biopsy showed granulomatous dermatitis with sarcoid-like granulomas. A diagnosis of stage I pulmonary sarcoidosis was made. No treatment for sarcoidosis was initiated since the patient had neither systemic involvement, nor respiratory impairment. CONCLUSIONS: The presence of more than one rare disease should challenge the concept of a potential common underlying mechanism, since the a priori probability of the concomitant presence of different conditions with different pathogenic mechanisms - especially if rare diseases - is low. We speculate that the dysregulation of the pathway involving mTOR and MAPK and their interaction might play a role in the pathogenesis of other diseases, including sarcoidosis.

Women with TSC: Relationship between Clinical, Lung Function and Radiological Features in a Genotyped Population Investigated for Lymphangioleiomyomatosis.

The advent of pharmacological therapies for lymphangioleiomyomatosis (LAM) has made early diagnosis important in women with tuberous sclerosis complex (TSC), although the lifelong cumulative radiation exposure caused by chest computer tomography (CT) should not be underestimated. We retrospectively investigated, in a cohort of TSC outpatients of San Paolo Hospital (Milan, Italy) 1) the role of pulmonary function tests (PFTs) for LAM diagnosis, 2) the association between LAM and other features of TSC (e.g. demography, extrapulmonary manifestations, genetic mutations, etc.), and 3) the characteristics of patients with multifocal micronodular pneumocyte hyperplasia (MMPH). Eighty-six women underwent chest CT scan; pulmonary involvement was found in 66 patients (77%; 49% LAM with or without MMPH, and 28% MMPH alone). LAM patients were older, with a higher rate of pneumothorax, presented more frequently with renal and hepatic angiomyolipomas, and tended to have a TSC2 mutation profile. PFTs, assessed in 64% of women unaffected by cognitive impairments, revealed a lower lung diffusion capacity in LAM patients. In multivariate analysis, age, but not PFTs, resulted independently associated with LAM diagnosis. Patients with MMPH alone did not show specific clinical, functional or genetic features. A mild respiratory impairment was most common in LAM-TSC patients: In conclusions, PFTs, even if indicated to assess impairment in lung function, are feasible in a limited number of patients, and are not significantly useful for LAM diagnosis in women with TSC.