Peptidomic profile of human milk as influenced by fortification with different protein sources: An in vitro dynamic digestion simulation.

Fortification of human milk (HM) is often necessary to meet the nutritional requirements of preterm infants. The present experiment aimed to establish whether the supplementation of HM with either an experimental donkey milk-derived fortifier containing whole donkey milk proteins, or with a commercial bovine milk-derived fortifier containing hydrolyzed bovine whey proteins, affects peptide release differently during digestion. The experiment was conducted using an in vitro dynamic system designed to simulate the preterm infant's digestion followed by digesta analysis by means of LC-MS-MS. The different fortifiers did not appear to influence the cumulative intensity of HM peptides. Fortification had a differential impact on the release of either donkey or bovine bioactive peptides. Donkey milk peptides showed antioxidant/ACE inhibitory activities, while bovine peptides showed opioid, dipeptil- and propyl endo- peptidase inhibitory and antimicrobial activity. A slight delay in peptide release from human lactoferrin and α-lactalbumin was observed when HM was supplemented with donkey milk-derived fortifier.

Cord blood transfusions in extremely low gestational age neonates to reduce severe retinopathy of prematurity: results of a prespecified interim analysis of the randomized BORN trial.

BACKGROUND: Preterm infants are at high risk for retinopathy of prematurity (ROP), with potential life-long visual impairment. Low fetal hemoglobin (HbF) levels predict ROP. It is unknown if preventing the HbF decrease also reduces ROP. METHODS: BORN is an ongoing multicenter double-blinded randomized controlled trial investigating whether transfusing HbF-enriched cord blood-red blood cells (CB-RBCs) instead of adult donor-RBC units (A-RBCs) reduces the incidence of severe ROP (NCT05100212). Neonates born between 24 and 27 + 6 weeks of gestation are enrolled and randomized 1:1 to receive adult donor-RBCs (A-RBCs, arm A) or allogeneic CB-RBCs (arm B) from birth to the postmenstrual age (PMA) of 31 + 6 weeks. Primary outcome is the rate of severe ROP at 40 weeks of PMA or discharge, with a sample size of 146 patients. A prespecified interim analysis was scheduled after the first 58 patients were enrolled, with the main purpose to evaluate the safety of CB-RBC transfusions. RESULTS: Results in the intention-to-treat and per-protocol analysis are reported. Twenty-eight patients were in arm A and 30 in arm B. Overall, 104 A-RBC units and 49 CB-RBC units were transfused, with a high rate of protocol deviations. A total of 336 adverse events were recorded, with similar incidence and severity in the two arms. By per-protocol analysis, patients receiving A-RBCs or both RBC types experienced more adverse events than non-transfused patients or those transfused exclusively with CB-RBCs, and suffered from more severe forms of bradycardia, pulmonary hypertension, and hemodynamically significant patent ductus arteriosus. Serum potassium, lactate, and pH were similar after CB-RBCs or A-RBCs. Fourteen patients died and 44 were evaluated for ROP. Ten of them developed severe ROP, with no differences between arms. At per-protocol analysis each A-RBC transfusion carried a relative risk for severe ROP of 1.66 (95% CI 1.06-2.20) in comparison with CB-RBCs. The area under the curve of HbF suggested that HbF decrement before 30 weeks PMA is critical for severe ROP development. Subsequent CB-RBC transfusions do not lessen the ROP risk. CONCLUSIONS: The interim analysis shows that CB-RBC transfusion strategy in preterm neonates is safe and, if early adopted, might protect them from severe ROP. TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.gov on October 29, 2021. Identifier number NCT05100212.

Presepsin in Human Milk Is Delivery Mode and Gender Dependent.

Breast milk (BM) is a unique food due to its nutritional composition and anti-inflammatory characteristics. Evidence has emerged on the role of Presepsin (PSEP) as a reliable marker of early sepsis diagnosis. In the present study, we aimed to investigate the measurability of PSEP in BM according to different maturation stages (colostrum, C; transition, Tr; and mature milks, Mt) and corrected for delivery mode and gender. We conducted a multicenter prospective case-control study in women who had delivered 22 term (T) and 22 preterm (PT) infants. A total of 44 human milk samples were collected and stored at -80 °C. BM PSEP (pg/mL) levels were measured by using a rapid chemiluminescent enzyme immunoassay. PSEP was detected in all samples analyzed. Higher (p < 0.05) BM PSEP concentrations were observed in the PT compared to the T infants. According to the grade of maturation, higher (p < 0.05) levels of PSEP in C compared to Tr and Mt milks were observed in the whole study population. The BM subtypes' degrees of maturation were delivery mode and gender dependent. We found that PSEP at high concentrations supports its antimicrobial action both in PT and T infants. These results open the door to further studies investigating the role of PSEP.

Effect of in-line filtration in newborns: study protocol of the Intravenous Neonatal Central Access Safety (INCAS) randomized controlled trial.

BACKGROUND: Particulate contamination due to infusion therapy (administration of parenteral nutrition and medications) carries a potential health risk for infants in neonatal intensive care units (NICUs). This particulate consists of metals, drug crystals, glass fragments, or cotton fibers and can be generated by drug packaging, incomplete reconstitution, and chemical incompatibilities. In-line filters have been shown to remove micro-organisms, endotoxin, air, and particles in critically ill adults and older infants, but its benefits in newborn remain to be demonstrated. Moreover, 50% of inflammatory episodes in the setting of NICUs are blood culture-negative. These episodes could be partly related to the presence of particles in the infusion lines. METHODS: A multicenter randomized single-blind controlled trial was designed. All infants admitted to NICUs for which prolonged infusion therapy is expected will be enrolled in the study and randomized to the Filter or Control arm. All patients will be monitored until discharge, and data will be analyzed according to a "full analysis set." The primary outcome is the frequency of patients with at least one sepsis-like event, defined by any association of suspected sepsis symptoms with a level of c-reactive protein (CRP) > 5 mg/L in a negative-culture contest. The frequency of sepsis, phlebitis, luminal obstruction, and the duration of mechanical ventilation and of catheter days will be evaluated as secondary outcomes. The sample size was calculated at 368 patients per arm. DISCUSSION: This is the first multicenter randomized control trial that compares in-line filtration of parenteral nutrition and other intravenous drugs to infusion without filters. Sepsis-like events are commonly diagnosed in clinical practice and are more frequent than sepsis in a positive culture contest. The risk of these episodes in the target population is estimated at 30-35%, but this data is not confirmed in the literature. If the use of in-line filters results in a significant decrease in sepsis-like events and/or in any other complications, the use of in-line filters in all intravenous administration systems may be recommended in NICUs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05537389, registered on 12 September 2022 ( https://classic. CLINICALTRIALS: gov/ct2/show/results/NCT05537389?view=results ).

Italian neonatal birthweight charts derived from INeS not separated by birth order.

BACKGROUND: Identifying high-risk neonates with abnormal fetal growth is crucial for health risk prediction and early intervention. Small for gestational age (SGA) and large for gestational age (LGA) classifications highlight neonates having a higher risk for postnatal diseases. Accurate diagnosis depends on precise anthropometric measurements and appropriate reference data. In 2010, specific neonatal charts for Italian singletons (INeS charts) were published, tracing separately for first- and later-born neonates due to a 3% birth weight difference. We present INeS charts for birth weight non-separated by first- and later-born babies useful when information on parity is unavailable or unreliable, or for better comparisons with other neonatal charts that are not separated by birth-order. METHODS: INeS charts were traced using a parametric function. Starting with the parameters estimates published in a different paper, INeS charts not separated by birth order were traced for the gestational age range of 23 to 42 weeks. In a second step the charts were parametrized as Cole and Green Lambda Mu and Sigma (LMS) model, allowing computation of standard deviation scores. RESULTS: The centiles of non-separated INeS charts follow between first- and later-born charts. Distances varied due to changing first-born proportions with gestational age, Max differences of about 100g with later born and 70g with first-born were observed at term. S and L functions have a similar shape for boys and girls. S function shows a pick at about 29 weeks, L function has positive values in all the range of gestational age with a pick at 39 weeks. CONCLUSIONS: The study presents non-separated Birth Weight INeS charts, bridging the gap when parity information is unavailable. Differences with separated charts were generally small, making them reliable for neonatal health assessment. Insights from L and S parameters contribute to standardized birth weight and adjust it by sex and Gestational Age, useful for defining SGA or LGA neonates. The paper enhances neonatal care tools, showcasing INeS chart flexibility in different clinical scenarios and supporting neonatology research.

The Use of a Novel Donkey Milk-Derived Human Milk Fortified in the Neonatal Period Had No Effect on the Frequency of Allergic Manifestations During the First Years of Life: The "Fortilat Trial" Follow-Up.

Background: Since human milk contents does not meet the high need of very low birth weight infants, fortification of breast milk is a standard practice for this population. As donkey milk has been long considered for children allergic to cow's milk proteins due to its low allergic properties, a new donkey milk-derived fortifier (DF) has been recently evaluated as a valid alternative to bovine milk-derived fortifier (BF). It seems to improve feeding tolerance when compared with standard BF, with similar neurodevelopmental and auxological outcome at 18 months of age. The aim of this study is to evaluate the development of allergic manifestations occurring in the population of the "Fortilat Trial" at 6-8 years of age. Methods: Allergic manifestations were assessed by an ad hoc questionnaire administered to families. The occurrence of asthma, allergic rhinitis and oculorhinitis, rashes and atopic dermatitis, food allergies, accesses to an emergency department for allergic reactions, and the need of antihistamine have been investigated. Results: In total, 113 infants were enrolled in the study (BF arm: n = 60, DF arm: n = 53). No difference in risk was observed between the two groups for all the considered outcomes. In conclusion, our data suggest that DF does not impact the development of allergic manifestations in the first years of life. Clinical Trial Registration number: ISRCT N70022881.

Effects of a valved infant-bottle with ergonomic teat on the coordination of sucking, swallowing, and respiration in late-preterm infants. The Safe Oral Feeding randomized Trial.

Introduction: Breastfeeding naturally enables the coordination of sucking, swallowing, and respiration patterns for safe feeding. When breastfeeding is not possible a feeding device that releases milk in response to intra-oral vacuum could potentially offer improved coordination of sucking, swallowing, and breathing patterns compared to conventional devices. The aim of the study is to evaluate the effect of a valved infant-bottle with an ergonomic teat compared to a standard infant-bottle. Methods: This unblinded randomized controlled trial focused on late preterm infants fed by bottle for at least three meals over the day, admitted to the Neonatal Unit of Sant'Anna Hospital (Turin, Italy). Infants were randomized to be fed with a valved infant-bottle with an ergonomic teat (B-EXP arm) or with a standard infant-bottle (B-STD arm). Monitoring included a simultaneous synchronized recording of sucking, swallowing and respiration. The main outcome was the swallowing/breathing ratio. Results: Forty infants (20 B-EXP arm; 20 B-STD arm) with a median gestational age of 35.0 weeks (IQR 35.0-36.0 weeks) completed the study. Four infants were censored for the presence of artifacts in the polygraphic traces. The median swallowing/breathing ratio was 1.11 (1.03-1.23) in the B-EXP arm and 1.75 (1.21-2.06) in the B-STD (p = .003). A lower frequency of swallowing events during the inspiratory phase of breathing was observed in B-EXP arm compared with B-STD arm (p = 0.013). Discussion: The valved infant-bottle with an ergonomic teat improves the coordination of sucking-swallowing-respiration and limits the risk of inhalation reducing the frequency of swallowing during the inspiratory phase.

SARS-CoV-2 perinatal transmission and neonatal outcomes across four different waves of COVID-19 pandemic: A nationwide prospective cohort study from the Italian Society of Neonatology.

OBJECTIVES: To describe how SARS-CoV-2 infection at the time of delivery affected maternal and neonatal outcomes across four major waves of the COVID-19 pandemic in Italy. METHODS: This is a large, prospective, nationwide cohort study collecting maternal and neonatal data in case of maternal peripartum SARS-CoV-2 infection between February 2020 and March 2022. Data were stratified across the four observed pandemic waves. RESULTS: Among 5201 COVID-19-positive mothers, the risk of being symptomatic at delivery was significantly higher in the first and third waves (20.8-20.8%) than in the second and fourth (13.2-12.2%). Among their 5284 neonates, the risk of prematurity (gestational age <37 weeks) was significantly higher in the first and third waves (15.6-12.5%). The risk of intrauterine transmission was always very low, while the risk of postnatal transmission during rooming-in was higher and peaked at 4.5% during the fourth wave. A total of 80% of positive neonates were asymptomatic. CONCLUSION: The risk of adverse maternal and neonatal outcomes was significantly higher during the first and third waves, dominated by unsequenced variants and the Delta variant, respectively. Postnatal transmission accounted for most neonatal infections and was more frequent during the Omicron period. However, the paucity of symptoms in infected neonates should lead us not to separate the dyad.

The Gestational Pathologies Effect on the Human Milk Redox Homeostasis: A First Step towards Its Definition.

BACKGROUND: Human Milk (HM) is a dynamic nourishment; its composition is influenced by several conditions such as gestational age, maternal diet and ethnicity. It appears important to evaluate the impact that gestational pathologies have on HM components and if their presence, as a source of oxidative stress in the mother, influence milk's redox homeostasis. To assess the effect of Preeclampsia (PE) and Gestational Diabetes Mellitus (GDM) on some aspects of human milk redox homeostasis, we chose to investigate both oxidative and antioxidant aspects, with, respectively, Lipid hydroperoxides (LOOHs) and Glutathione (GSH). METHODS: Women with PE, GDM and who were healthy were recruited for this study. Colostrum, transitional and mature milk samples were collected. GSH and LOOHs levels were measured using a spectrophotometric test. To investigate the effect of pathology on redox homeostasis, a mixed linear model with unistructural covariance structure was performed. RESULTS: A total of 120 mothers were recruited. The GSH concentration results were significantly lower in GDM women than in healthy women only in colostrum (p < 0.01). No other differences emerged. LOOHs was not detectable in almost all the samples. DISCUSSION: Our study is the first to extensively evaluate these components in the HM of women with these gestational pathologies. The main observation is that GDM can alter the GSH level of HM, mainly in colostrum.

Preeclampsia and Its Impact on Human Milk Activin A Concentration.

BACKGROUND: It is known that preeclampsia affects lactogenesis. However, data on the effects of this pathology on human milk neurobiomarker composition are not available. The aim of this study is to investigate the effects of this gestational pathology on activin A levels, a neurobiomarker known to play an important role in the development and protection of the central nervous system. METHODS: The women recruited were divided in two different study groups: preeclamptic or normotensive women. All the human milk samples were collected using the same procedure. Activin A was quantified using an Enzyme-linked immunosorbent assay (ELISA) test. To investigate the effect of preeclampsia on the activin A concentration in the three lactation phases, a mixed linear model with a unistructural covariance structure, with the mother as the random effect, and fixed effects were performed. RESULTS: Activin A was detected in all samples. There were no significant differences between preeclamptic and normotensive women. The only significant effect is related to the lactation phase: the difference between colostrum and mature milk (p < 0.01) was significant. In conclusion, these results allow us to affirm that breast milk's beneficial properties are maintained even if preeclampsia occurs.

Viruses and Human Milk: Transmission or Protection?

Human milk (HM) is considered the best source of nutrition for infant growth and health. This nourishment is unique and changes constantly during lactation to adapt to the physiological needs of the developing infant. It is also recognized as a potential route of transmission of some viral pathogens although the presence of a virus in HM rarely leads to a disease in an infant. This intriguing paradox can be explained by considering the intrinsic antiviral properties of HM. In this comprehensive and schematically presented review, we have described what viruses have been detected in HM so far and what their potential transmission risk through breastfeeding is. We have provided a description of all the antiviral compounds of HM, along with an analysis of their demonstrated and hypothesized mechanisms of action. Finally, we have also analyzed the impact of HM pasteurization and storage methods on the detection and transmission of viruses, and on the antiviral compounds of HM. We have highlighted that there is currently a deep knowledge on the potential transmission of viral pathogens through breastfeeding and on the antiviral properties of HM. The current evidence suggests that, in most cases, it is unnecessarily to deprive an infant of this high-quality nourishment and that the continuation of breastfeeding is in the best interest of the infant and the mother.

Effect of Nasal Continuous Positive Airway Pressure vs Heated Humidified High-Flow Nasal Cannula on Feeding Intolerance in Preterm Infants With Respiratory Distress Syndrome: The ENTARES Randomized Clinical Trial.

Importance: Respiratory distress syndrome and feeding intolerance are common conditions that are often associated with preterm infants. Showing similar efficacy, nasal continuous positive airway pressure (NCPAP) and heated humidified high-flow nasal cannula (HHHFNC) are the most widespread noninvasive respiratory support (NRS) in neonatal intensive care units, but their effect on feeding intolerance is unknown. Objective: To evaluate the effect of NCPAP vs HHHFNC on high-risk preterm infants with respiratory distress syndrome. Design, Setting, and Participants: This multicenter randomized clinical trial involved infants who were born in 1 of 13 neonatal intensive care units in Italy between November 1, 2018, and June 30, 2021. Preterm infants with a gestational age of 25 to 29 weeks, who were suitable for enteral feeding and who proved to be medically stable on NRS for at least 48 hours were enrolled in the study within the first week of life and randomized to receive either NCPAP or HHHFNC. Statistical analysis was performed according to the intention-to-treat approach. Intervention: NCPAP or HHHFNC. Main Outcomes and Measures: The primary outcome was the time to full enteral feeding (FEF), defined as an enteral intake of 150 mL/kg per day. Secondary outcomes were the median daily increment of enteral feeding, signs of feeding intolerance, effectiveness of the assigned NRS, peripheral oxygen saturation (SpO2)-fraction of inspired oxygen (FIO2) ratio at changes of NRS, and growth. Results: Two-hundred forty-seven infants (median [IQR] gestational age, 28 [27-29] weeks; 130 girls [52.6%]) were randomized to the NCPAP group (n = 122) or the HHHFNC group (n = 125). There were no differences in the primary and secondary nutritional outcomes between the 2 groups. The median time to reach FEF was 14 days (95% CI, 11-15 days) in the NCPAP group and 14 days (95% CI, 12-18 days) in the HHHFNC group, and similar results were observed in the subgroup of infants with less than 28 weeks' gestation. On the first NRS change, higher SpO2-FIO2 ratio (median [IQR], 4.6 [4.1-4.7] vs 3.7 [3.2-4.0]; P < .001) and lower rate of ineffectiveness (1 [4.8%] vs 17 [73.9%]; P < .001) were observed in the NCPAP vs HHHFNC group. Conclusions and relevance: This randomized clinical trial found that NCPAP and HHHFNC had similar effects on feeding intolerance, despite different working mechanisms. Clinicians may tailor respiratory care by selecting and switching between the 2 NRS techniques on the basis of respiratory effectiveness and patient compliance, without affecting feeding intolerance. Trial Registration: ClinicalTrials.gov Identifier: NCT03548324.

Beyond survival: the lasting effects of premature birth.

Preterm birth, defined as birth before 37 weeks of gestation, is a major public health concern. It affects about 10% of all newborns globally and is the main cause of infant death and morbidity. Prematurity increases the likelihood of respiratory distress syndrome, cerebral palsy, and developmental abnormalities. Furthermore, premature newborns are at risk of acquiring chronic noncommunicable diseases later in life due to interference with organ system development during the in-utero and perinatal period. Because of the greater risk of long-term repercussions, preterm birth should be considered a chronic disorder, and gestational age and other birth histories should be included in all medical records for patients of all ages, especially when assessing the risk of multiple chronic diseases. Conventional methods for assessing preterm infant development, as well as reliable and precise growth monitoring, can lead to the early detection of growth decline and the adjustment of feeding regimens as needed. Because of its unique composition and useful components, human milk is a powerful tool for mitigating the negative outcomes associated with prematurity. It contains a variety of growth factors that promote the development of organs and systems, counteracting the negative effects of the abrupt interruption of intrauterine development and promoting better outcomes in all altered functions. Despite its multiple benefits, human milk cannot totally restore the lasting damage caused by premature birth. Premature infants cannot be completely overcome by nutrition alone, and yet adequate nutritional intake and human milk feeding are critical to their health and development.

Replication properties and immunomodulatory effects of human cytomegalovirus infection impact the clinical presentation in congenital patients: A case series.

BACKGROUND: Human cytomegalovirus (HCMV) is the leading cause of congenital infections resulting in severe morbidity and mortality among newborns worldwide. Although both the host's and the virus' genetic backgrounds contribute to the outcome of infections, significant gaps remain in our understanding of the exact mechanisms that determine disease severity. OBJECTIVES: In this study, we sought to identify a correlation between the virological features of different HCMV strains with the clinical and pathological features of congenitally infected newborns, therefore proposing new possible prognostic factors. STUDY DESIGN: This short communication presents five newborns with congenital cytomegalovirus infection, whose clinical phenotype during fetal, neonatal, and follow-up periods is correlated with in-vitro growth properties, immunomodulatory abilities and genome variability of HCMV strains isolated from organic samples (urine) of the patients. RESULTS: The five patients described in this short communication displayed a heterogeneous clinical phenotype and different virus replication properties, immunomodulatory abilities, and genetic polymorphisms. Interestingly, we observed that an attenuate viral replication in-vitro influences the immunomodulatory abilities of HCMV, leading to more severe congenital infections and long-term sequelae. Conversely, infection with viruses characterized by aggressive replicative behavior in-vitro resulted in asymptomatic patients' phenotypes. CONCLUSIONS: Overall, this case series suggests the hypothesis that genetic variability and differences in the replicative behavior of HCMV strains result in clinical phenotypes of different severity, most likely due to different immunomodulatory properties of the virus.

Safety and tolerability of ozonated-oils in liposome eyedrop in preterm eye examination.

BACKGROUND: Eye examinations for ROP screening in preterm newborns are characterized by two main problems: infection control and poor tear secretion. Therefore, in order to reduce the risk of ocular infection and to protect the ocular surface, netilmicin eye drops are usually used after the exams. The purpose of our study was to evaluate the safety and tolerability of ozonated-oils eyedrops during the eye examination of preterm babies in the screening for ROP, sparing the use of antibiotics eyedrops. METHODS: All newborn infants that needed to be screened for ROP were divided into two groups: in group A we used topical netilmicin eye drops and in group B ozonated-oils eyedrops. We looked for any sign of conjunctival injection and chemosis, infectious conjunctivitis, blepharoconjunctivitis, erythema, and edema of the eyelids. RESULTS: A total of 162 adverse effects out of 3546 examinations (4,5%) were reported acutely: in group A (1778 examinations), they consisted of 47 reactive conjunctivitis, 3 cases of blepharoconjunctivitis, 30 of eyelids swelling, and 3 infectious conjunctivitis, compared to 39 cases of conjunctival injection, 3 blepharoconjunctivitis, 33 eyelids swelling and 4 infectious conjunctivitis in group B (1768 examinations). No significant differences were found in the comparison of the two groups. CONCLUSIONS: Ozonated-oils eyedrops should be considered a valid and safe alternative for the lubrification of the ocular surface and an adjuvant strategy to further minimize the risk of microbial contamination during screening for ROP.

Fetal and post-natal growth in infants of mothers with multiple sclerosis: A case-control stud.

BACKGROUND: Multiple sclerosis does not seem to adversely affect fetal and neonatal outcomes, although some studies reported a possible reduction in mean birth weight and length, and a higher incidence of preterm delivery, mainly in relation to the exposure to disease-modifying drugs (DMDs) during pregnancy. Few data are available on intrauterine fetal growth and postnatal somatic development of newborns from mothers with multiple sclerosis compared to those from healthy women. For these reasons, we decided to investigate fetal growth, neonatal anthropometric parameters, and postnatal somatic development up to 12 months of life in offsprings from MS mothers. METHODS: This retrospective cohort study included 211 women with multiple sclerosis, and 384 healthy women paired for maternal age and parity as controls. Fetal biometric parameters (biparietal diameter, head circumference, abdominal circumference, and femur length) measured during the third trimester of pregnancy (30-34 weeks' gestation) were retrieved from the computerized database of the Department (EcoPlus*) where the results of ultrasound exams performed in the hospital are stored. Newborn measurements (weight, length and head circumference) at birth were obtained from the hospital's computerized obstetric and neonatal database (Trackare* and Remote* data base); measurements at 6 and 12 months of life were obtained from the regional database (ECWMED*) of family pediatricians of our region. RESULTS: No differences between the two groups were observed for all the fetal parameters considered, expressed as centiles of growth according to gestational age (biparietal diameter: p = 0.40; head circumference: p = 0.40; abdominal circumference: p = 0.32; femur length: p = 0.32). No differences in gestational age at delivery, birthweight, and in the incidence of low birthweight and small for gestational age newborns were observed between the two groups. In the multiple sclerosis group a significantly higher incidence of caesarean section (p = 0.01) and late preterm delivery (at less than 37 weeks'gestation, p = 0.001) were registered. The trends of postnatal growth in weight (F = 0.53; p-value = 0.590) and length (F = 0.44; p-value = 0.645) were superimposable between the two groups. The trends of growth for head circumference showed a slightly, not significantly greater head circumference of infants from mothers with multiple sclerosis at 6 months of life, but the values at twelve months of life in the two groups were similar (F = 0.85; p-value = 0.427) . Moreover, the trends of postnatal increase of weight (F = 1.016; p-value = 0.331), length (F = 2.001; p-value = 0.146) and head circumference (F = 1.591; p-value = 0.212) of newborns/infants (from birth to twelve months of life) born to mothers with multiple sclerosis who breastfed, mothers who did not, and in the control group were similar. CONCLUSION: Multiple sclerosis in pregnancy does not seem to affect fetal growth and postnatal development during the first year of the offspring life. We think that these results represent an important and reassuring information to provide the patients with during preconception counseling.

Moral Distress and Burnout in Neonatal Intensive Care Unit Healthcare Providers: A Cross-Sectional Study in Italy.

Moral distress (MD) in healthcare providers is widely recognized as a serious issue in critical care contexts. It has the potential to have negative impacts on both personal and professional wellbeing, the quality of care provided and staff turnover. The aim of this study was to investigate the relationship between MD and burnout among neonatal intensive care unit (NICU) healthcare professionals and identify the possible factors associated with its occurrence. Participants were asked to complete an online survey, which covered sociodemographic and professional information and included two self-report questionnaires (Italian Moral Distress Scale-Revised and Maslach Burnout Inventory). The sample comprised 115 healthcare providers (nurses and physiotherapists: 66.1%; physicians: 30.4%; healthcare assistants: 3.5%) working in four NICUs located within the province of Turin, Italy. The results revealed overall low levels of MD, with no significant differences between nurses/physiotherapists and physicians. Nurses/physiotherapists showed a statistically significant higher percentage of personal accomplishment burnout (32.9%) compared with physicians (8.6%; p = 0.012). MD was associated with the emotional exhaustion dimension of burnout. Spirituality and/or religiousness was shown to be a moderating variable. Further research is needed to deepen our understanding of the correlation between MD and burnout and the role of spirituality and/or religiousness as moderators.

Supplementing human milk with a donkey or bovine milk derived fortifier: Consequences on proteolysis, lipolysis and particle structure under in vitro dynamic digestion.

Fortification of human milk (HM) is often necessary to meet the nutritional requirements of preterm infants. This study sought to establish whether HM supplemented with an experimental donkey milk-derived fortifier (DMF) or a commercial bovine milk-derived fortifier (BMF) affected digestion, using an in vitro dynamic system at the preterm stage. Particle size in gastric phase was higher in DMF than in BMF, due to protein aggregates surrounding lipid globules. Before digestion, BMF, with its extensively hydrolysed proteins, had a higher degree of proteolysis (30%) than DMF (11%), which contained intact proteins. After digestion, this difference was reduced concomitantly to a similar net degree of proteolysis (33%). DMF, with a higher proportion of ω3, resulted in a lower ω6/ω3 free PUFA ratio than BMF throughout digestion, although the final degree of lipolysis was similar (54%). In summary, DMF could represent a better source of proteins and lipids for the preterm infant.

Perinatal outcomes in twin late preterm pregnancies: results from an Italian area-based, prospective cohort study.

BACKGROUND: Multiple gestations represent a considerable proportion of pregnancies delivering in the late preterm (LP) period. Only 30% of LP twins are due to spontaneous preterm labor and 70% are medically indicated; among this literature described that 16-50% of indicated LP twin deliveries are non-evidence based. As non-evidence-based delivery indications account for iatrogenic morbidity that could be prevented, the objective of our observational study is to investigate first neonatal outcomes of LP twin pregnancies according to gestational age at delivery, chorionicity and delivery indication, then non evidence-based delivery indications. METHODS: Prospective cohort study among twins infants born between 34 + 0 and 36 + 6 weeks, in Emilia Romagna, Italy, during 2013-2015. The primary outcome was a composite of adverse perinatal outcomes. RESULTS: Among 346 LP twins, 84 (23.4%) were monochorionic and 262 (75.7%) were dichorionic; spontaneous preterm labor accounted for 85 (24.6%) deliveries, preterm prelabor rupture of membranes for 66 (19.1%), evidence based indicated deliveries were 117 (33.8%), while non-evidence-based indications were 78 (22.5%). When compared to spontaneous preterm labor or preterm prelabor rupture of membranes, pregnancies delivered due to maternal and/or fetal indications were associated with higher maternal age (p <  0.01), higher gestational age at delivery (p <  0.01), Caucasian race (p 0.04), ART use (p <  0.01), gestational diabetes (p <  0.01), vaginal bleeding (p <  0.01), antenatal corticosteroids (p <  0.01), diagnosis of fetal growth restriction (FGR) (p <  0.01), and monochorionic (p <  0.01). Two hundred twenty-six pregnancies (65.3%) had at least one fetus experiencing one composite of adverse perinatal outcome. Multivariate analysis confirmed that delivery indication did not affect the composite of adverse perinatal outcomes; the only characteristic that affect the outcome after controlling for confounding was gestational age at delivery (p <  0.01). Moreover, there was at least one adverse neonatal outcome for 94% of babies born at 34 weeks, for 73% of those born at 35 weeks and for 46% of those born at 36 weeks (p <  0.01). CONCLUSION: Our study suggests that the decision to deliver or not twins in LP period should consider gestational age at delivery as the main determinant infants' prognosis. Delivery indications should be accurately considered, to avoid iatrogenic early birth responsible of preventable complications.

Delivery indication matters for perinatal outcomes in late preterm newborns.

BACKGROUND: The late preterm (LP) rate in Western countries is 3-6% of all births, accounting for about two-thirds of the entire preterm population. However, all LP babies are not the same. AIMS: To identify pregnancies at risk for adverse outcomes in the LP period, we investigated how gestational age (GA) at delivery, delivery indication and prenatal risk factors may affect neonatal outcomes. STUDY DESIGN: Prospective cohort study among singleton infants born between 34 + 0 and 36 + 6 weeks, in Emilia Romagna, Italy, during 2013-2015. OUTCOMES MEASURES: The primary outcome was a composite of adverse perinatal outcomes. Multivariate logistic regression models were used to, respectively, investigate the effects of GA at delivery, circumstances at parturition and prenatal risk factors, on study outcomes after controlling for confounding variable. RESULTS: Among 1867 births, 302, 504, and 1061 infants were born at 34, 35, and 36 weeks, respectively. There were no neonatal deaths. An increased risk of composite neonatal outcome was observed among 34 and 35 weeks deliveries compared with 36 weeks, and among indicated deliveries compared with spontaneous. When studying prenatal risk factors, neonatal morbidity was associated with pre gestational diabetes, preterm premature rupture of membranes (pPROM), maternal obesity, bleeding and polyhydramnios; instead, preeclampsia had a protective effect. CONCLUSION: LP with indicated deliveries at 34 or 35 weeks, or with specific prenatal risk factors have worse neonatal outcome when compared to 36. Such differences should be considered when counseling patients and planning interventions such as timing of delivery in LP period.