Exclusive human milk feeding and prevalence of early adiposity rebound in ELBW infants: a retrospective cohort study.

The purpose of the present study was to evaluate the prevalence of early adiposity rebound (EAR) and factors associated with its occurrence in a cohort of extremely low birth weight infants (ELBW). We conducted a retrospective longitudinal study including ELBW infants followed-up for up to 10 years after discharge. EAR was defined as occurring before 5 years of age. A multivariate binary logistic regression analysis was performed to evaluate maternal and perinatal variables independently associated with EAR. Out of 212 ELBW infants included in the analysis, 40.6% developed EAR and 21.5% showed it before 4 years of age. Only formula milk feeding at discharge was independently associated with a higher risk of EAR. The mean BMI of children with EAR was higher than that of children without EAR. Furthermore, the prevalence of overweight and obesity was higher in the EAR group than in the timely AR group.  Conclusions: ELBW infants in our cohort developed EAR in a relatively high percentage of cases. In this already at-risk population, EAR may represent a further risk factor for an adverse metabolic outcome. Monitoring preterm infants' growth within a long-term follow-up program and promoting and supporting human milk feeding is advisable. What is Known: • Preterm-born infants are at high risk for long-term adverse health outcomes, especially cardiovascular and metabolic. • The occurrence of early adiposity rebound (EAR) is associated with the risk of later obesity and metabolic syndrome. What is New: • The occurrence of EAR in ELBW infants may represent an additional risk factor for later adverse metabolic outcomes in an already vulnerable population. • Future preventive strategies should include a long-term follow-up and the promotion of exclusive breastfeeding.

Human Bone Marrow-Derived Mesenchymal Stromal Cells Reduce the Severity of Experimental Necrotizing Enterocolitis in a Concentration-Dependent Manner.

Necrotizing enterocolitis (NEC) is a devastating gut disease in preterm neonates. In NEC animal models, mesenchymal stromal cells (MSCs) administration has reduced the incidence and severity of NEC. We developed and characterized a novel mouse model of NEC to evaluate the effect of human bone marrow-derived MSCs (hBM-MSCs) in tissue regeneration and epithelial gut repair. NEC was induced in C57BL/6 mouse pups at postnatal days (PND) 3-6 by (A) gavage feeding term infant formula, (B) hypoxia/hypothermia, and (C) lipopolysaccharide. Intraperitoneal injections of PBS or two hBM-MSCs doses (0.5 × 106 or 1 × 106) were given on PND2. At PND 6, we harvested intestine samples from all groups. The NEC group showed an incidence of NEC of 50% compared with controls (p < 0.001). Severity of bowel damage was reduced by hBM-MSCs compared to the PBS-treated NEC group in a concentration-dependent manner, with hBM-MSCs (1 × 106) inducing a NEC incidence reduction of up to 0% (p < 0.001). We showed that hBM-MSCs enhanced intestinal cell survival, preserving intestinal barrier integrity and decreasing mucosal inflammation and apoptosis. In conclusion, we established a novel NEC animal model and demonstrated that hBM-MSCs administration reduced the NEC incidence and severity in a concentration-dependent manner, enhancing intestinal barrier integrity.

Congenital diaphragmatic hernia in Coffin Siris syndrome: Further evidence from two cases.

Coffin-Siris Syndrome (CSS) is a rare multi-system dominant condition with a variable clinical presentation mainly characterized by hypoplasia/aplasia of the nail and/or distal phalanx of the fifth digit, coarse facies, hirsutism/hypertrichosis, developmental delay and intellectual disability of variable degree and growth impairment. Congenital anomalies may include cardiac, genitourinary and central nervous system malformations whereas congenital diaphragmatic hernia (CDH) is rarely reported. The genes usually involved in CSS pathogenesis are ARID1B (most frequently), SMARCA4, SMARCB1, ARID1A, SMARCE1, DPF2, and PHF6. Here, we present two cases of CSS presenting with CDH, for whom Whole Exome Sequencing (WES) identified two distinct de novo heterozygous causative variants, one in ARID1B (case 1) and one in SMARCA4 (case 2). Due to the rarity of CDH in CSS, in both cases the occurrence of CDH did not represent a predictive sign of CSS but, on the other hand, prompted genetic testing before (case 1) or independently (case 2) from the clinical hypothesis of CSS. We provide further evidence of the association between CSS and CDH, reviewed previous cases from literature and discuss possible functional links to related conditions.

Postnatal growth of small for gestational age late preterm infants: determinants of catch-up growth.

BACKGROUND: Failure to recover growth is a risk reported in late preterm population. This study aimed to evaluate the auxological outcome of late preterm infants and identify factors associated with failure to recover growth. METHODS: We enrolled late preterm infants with birth weight ≤10th percentile, followed up at High-Risk Infant Follow-up Service. We collected data at birth and at follow-up visits. A logistic regression analysis was performed to assess variables independently associated with growth failure. RESULTS: The population consisted of 175 preterms. The percentage of children showing no weight recovery was 34% at 36 months. At logistic regression analysis, infants who had not regained weight at 12 months had a higher risk of not regaining weight even at 36 months. The same risk factor was highlighted for length catch-up growth. Moreover, infants fed any human milk at discharge were protected from not achieving both weight and length catch-up growth at 36 months. CONCLUSION: These results indicate that children born late preterm and small for gestational age could fail to recover weight and stature growth in the first 36 months. The protective effect of human milk on failure to thrive highlights the importance of promoting breastfeeding in this population. IMPACT: A significant number of SGA late preterms show a failure to recover weight and statural growth. Having experienced intrauterine growth restriction is associated with a greater chance of achieving statural catch-up growth. Being born singleton represents a risk factor for slower weight and height growth velocity. Breastmilk has a protective effect on failure to recover adequate weight and length in preterm SGA infants. This finding highlights the importance of promoting breastfeeding in this population.

Prenatal overgrowth and polydramnios: Would you think about Noonan syndrome?

We report on a child with prenatal findings of increased nuchal translucency, polydramnios, ascites, and overgrowth. At birth, she presented length >97° centile, minor facial anomalies, megalencephaly, and Wolff-Parkinson-White syndrome. Whole-exome sequencing showed a pathogenic variant in the NRAS gene, but no mutations were found in PI3K/AKT/mTOR pathway genes.

The hidden universe of human milk microbiome: origin, composition, determinants, role, and future perspectives.

Although traditionally considered sterile, human milk is currently recognized as an alive ecosystem that harbors not only bacteria, but also viruses, fungi and yeasts, and minor genera, collectively known as the human milk microbiome (HMM). The seeding of HMM is a complex phenomenon whose dynamics are still a matter of research. Many factors contribute to its determination, both maternal, neonatal, environmental, and related to human milk itself. The transmission of microorganisms to the infant through breastfeeding may impact its present and future health, mainly shaping the GI tract microbiome and immune system. The existence and persistence of HMM as a conserved feature among different species may also have an evolutionary meaning, which will become apparent only in evolutionary times. CONCLUSION: The complexities of HMM warrant further research in order to deepen our knowledge on its origin, determinants, and impact on infants' health. The practical and translational implications of research on HMM (e.g., reconstitution of donor human milk through inoculation of infant's own mother milk, modulation of HMM through maternal dietary supplementation) should not be overlooked. WHAT IS KNOWN: • Human milk harbors a wide variety of microorganisms, ranging from bacteria to viruses, fungi and yeasts, and minor genera. • Human milk microbiome is shaped over time by many factors: maternal, neonatal, environmental, and related to human milk itself. • The transmission of microorganisms through breastfeeding may impact the infant's present and future health. WHAT IS NEW: • We provide an overview on human milk microbiome, hopefully encouraging physicians to consider it among the other better-known breastfeeding benefits. • Further studies, with standardized and rigorous study designs to enhance accuracy and reproducibility of the results, are needed to deepen our knowledge of the human milk microbiota and its role in newborn and infant's health.

Human Milk, More Than Simple Nourishment.

Human breast milk not only has nutritional properties but also holds a functional role. It contains various bioactive factors (lactoferrin, lysozyme, leukocytes, immunoglobulins, cytokines, hormones, human milk oligosaccharides, microbiome, microRNAs and stem cells) shown to contribute to several short- and long-term health outcomes. Some of these factors appear to be involved in the infant's neuro-cognitive development, anti-oncogenic processes, cellular communication and differentiation. Furthermore, breast milk is increasingly recognized to have dynamic characteristics and to play a fundamental role in the cross-talking mother-neonate. This narrative review aims to provide a summary and an update on these bioactive substances, exploring their functions mainly on immunomodulation, microbiome and virome development. Although the knowledge about breast milk potentiality has significantly improved, leading to discovering unexpected functions, the exact mechanisms with which breast milk exercises its bioactivity have not been completely clarified. This can represent a fertile ground for exploring and understanding the complexity behind these functional elements to develop new therapeutic strategies.

The Antiviral Properties of Human Milk: A Multitude of Defence Tools from Mother Nature.

The anti-infective properties of breast milk have been known for decades. In recent years, an increasing number of papers have described the variety of bioactive compounds that are present in breast milk with varying degrees of antiviral activity. However, to date, the totality of the properties of these compounds is not fully understood and, above all, their synergistic interaction is not yet known. The purpose of this review is to describe the current knowledge about the antiviral compounds in breast milk, both with specific and non-specific action against pathogens. Due to the current pandemic situation from SARS-CoV-2 (Severe acute respiratory syndrome Coronavirus-2), research has focused on a multitude of potential antiviral substances, taking breast milk as a biological model of reference. Future research is needed to expand the knowledge of these compounds, which will hopefully assist in the development of therapies applicable even at later ages.

The Triad Mother-Breast Milk-Infant as Predictor of Future Health: A Narrative Review.

The benefits of human milk for both mother and infant are widely acknowledged. Human milk could represent a link between maternal and offspring health. The triad mother-breast milk-infant is an interconnected system in which maternal diet and lifestyle might have effects on infant's health outcome. This link could be in part explained by epigenetics, even if the underlining mechanisms have not been fully clarified yet. The aim of this paper is to update the association between maternal diet and human milk, pointing out how maternal diet and lifestyle could be associated with breast-milk composition, hence with offspring's health outcome.

Human Milk Feeding and Preterm Infants' Growth and Body Composition: A Literature Review.

Preterm infants may show a higher risk of adverse health outcomes, such as the development of metabolic syndrome and cognitive impairment. The most recent evidence highlights that nutrition, body composition development, and early postnatal growth may play a role in the programming of these processes. Human milk feeding has been recommended as the natural feeding for preterm infants and as a cost-effective strategy for reducing disease and economic burden. Considering that the postnatal growth retardation and aberrant body composition shown by preterm infants at the time of hospital discharge still remain important issues, we performed a literature review, aiming to provide an update about the effect of human milk feeding on these processes. On the basis of our findings, human milk feeding in preterm infants, although related to a slower weight gain than formula feeding, is associated with a better recovery of body composition through the promotion of fat-free mass deposition, which may ultimately lead to better metabolic and neurodevelopmental outcomes. Promotion and support of human milk feeding should be considered a priority in preterm infants' care.

Overcoming Rooming-In Barriers: A Survey on Mothers' Perspectives.

Background: The importance of rooming-in in promoting breastfeeding initiation and continuation within the 10 Steps for Successful Breastfeeding is widely acknowledged. However, adherence to this practice by healthcare facilities is lower than that of other Steps. A deeper knowledge of maternal rooming-in experience has been advocated to identify the most effective rooming-in policies, thus enabling mothers to have a positive experience when practicing it in the postpartum period. Aim: To investigate maternal knowledge of rooming-in and the most frequently encountered barriers and possible facilitators of adherence to the practice, according to their experience. Study Design and Methods: We enrolled mothers who delivered healthy term or late preterm infants during the month of January 2019 in a tertiary referral center for neonatal care in Milan, Italy. At discharge, a structured interview about mothers' rooming-in experience was administered by healthcare professionals. Basic subjects' characteristics and mode of feeding were recorded. Results: The enrolled population included 328 mothers and 333 neonates. The great majority of mothers knew of rooming-in and 48.2% practiced it continuously. The 86.3% of mothers was aware of the beneficial effects of rooming-in; promotion of mother-infant bonding, increased confidence in taking care of the baby and ability to recognize baby's feeding cues were the most frequently cited, whereas improving breastfeeding was reported by a limited number of mothers, unless they were asked a specific question about it. The main reported obstacles were fatigue (40.5%) and cesarean section related difficulties (15.5%); night was the most critical time of the day for rooming-in. Strategies suggested by mothers for improving rooming-in were increased assistance to the dyad, organizational and structural changes and the possibility to have a family member during the night. Additionally, mothers who adhered to rooming-in practice continuously during hospital stay had a higher exclusive breastfeeding rate at discharge compared to mothers who did not. Conclusions: Our study contributes to a deeper knowledge of maternal rooming-in experience in an Italian tertiary maternity. We underline the importance of providing a tailored support to the mother-infant dyad in order to overcome rooming-in barriers perceived by mothers and promote a positive rooming-in experience.