Extrauterine Growth Restriction (EUGR) refers to inadequate growth during hospitalization. Current definitions for EUGR are varied and can be classified as cross-sectional (weight at a given t-time 1SD). Different t-times are also considered in literature, such as 36 weeks of gestational age (GA) or age at discharge. The aim of this study is to investigate whether EUGR could predict the auxological outcome at 24–30 months, and to evaluate the agreement between cross-sectional and longitudinal definitions. In total, 1589 infants with GA <30 weeks or birthweight ≤ 1500 g and without major congenital anomalies were included in this study. Cross-sectional and longitudinal EUGR were calculated at 36 and 40 weeks of GA, at discharge, and at 28 days. The concordance between the two definitions was estimated by Kappa coefficient. At 24–30 months, 803 infants were measured again. The agreement between the two definitions of EUGR was low. Both EUGR and not-EUGR groups were at lower centiles for weight, but at higher centiles for head circumference at 24–30 months than at birth. Longitudinal EUGR was associated with a poorer growth outcome for weight and height circumference than cross-sectional EUGR. No differences were observed for length. An agreed definition of EUGR is highly desirable in clinical practice to assess medical and nutritional interventions in preterm neonates. Based on the results of this study, we recommend the use of the longitudinal evaluation, that proved to better predict the auxological long-term outcome with respect to the cross-sectional one.

Aim: To assess the effect of maternal age, height, early pregnancy body mass index (BMI) and ethnicity on birth weight. Subjects and methods: A cross-sectional study was conducted on more than 42,000 newborns. Ethnicity was defined by maternal country of birth or, when missing (<0.6% of records), by citizenship. The effect of maternal characteristics on birth weight was evaluated with general linear models. Results: Maternal height and BMI, although not age, significantly affected birth weight. Among Italian babies, 4.7% of newborns were classified as appropriate-for-gestational age (AGA) (birth weight between the 10^th and the 90^th centile) according to the country-specific Italian Neonatal Study (INeS) charts and were re-classified as either large-(LGA) (birth weight >90^th centile) or small-(SGA) (birth weight <10^th centile) for gestational age (GA) after adjustment for maternal characteristics. On the contrary, 1.6% of Italian newborns were classified as SGA or LGA according to the INeS charts and re-classified as AGA after adjustment. Maternal ethnicity had a significant impact on birth weight. Specifically, babies born to Senegalese mothers were the lightest, whilst babies born to Chinese mothers were the heaviest. Conclusions: Maternal height and early pregnancy BMI, should be considered in the evaluation of birth weight. The effect of ethnicity suggests the appropriateness of ethnic-specific charts. Further studies are necessary to determine if changes in birth weight classification, may translate into improved detection of subjects at risk of adverse outcomes.

Fortification of human milk is a standard practice for feeding very low birth weight infants. However, preterm infants often still experience suboptimal growth and feeding intolerance. New fortification strategies and different commercially available fortifiers have been developed. Commercially available fortifiers are constituted by a blend of ingredients from different sources, including plant oils and bovine milk proteins, thus presenting remarkable differences in the quality of macronutrients with respect to human milk. Based on the consideration that donkey milk has been suggested as a valid alternative for children allergic to cow’s milk proteins, due to its biochemical similarity to human milk, we hypothesized that donkey milk could be a suitable ingredient for developing an innovative human milk fortifier. The aim of the study is to evaluate feeding tolerance, growth and clinical short and long-term outcomes in a population of preterm infants fed with a novel multi-component fortifier and a protein concentrate derived from donkey milk, in comparison to an analogous population fed with traditional fortifier and protein supplement containing bovine milk proteins. The study has been designed as a randomized, controlled, single-blind clinical trial. Infants born <1500 g and <32 weeks of gestational age were randomized to receive for 21 days either a combination of control bovine milk-based multicomponent fortifier and protein supplement, or a combination of a novel multicomponent fortifier and protein supplement derived from donkey milk. The fortification protocol followed is the same for the two groups, and the two diets were designed to be isoproteic and isocaloric. Weight, length and head circumference are measured; feeding tolerance is assessed by a standardized protocol. The occurrence of sepsis, necrotizing enterocolitis and adverse effects are monitored. This is the first clinical study investigating the use of a human milk fortifier derived from donkey milk for the nutrition of preterm infants. If donkey milk derived products will be shown to improve the feeding tolerance or either of the clinical, metabolic, neurological or auxological outcomes of preterm infants, it would be an absolute innovation in the field of feeding practices for preterm infants. ISRCTN - ISRCTN70022881 .

In the context of suspected neonatal sepsis, early diagnosis and stratification of patients according to clinical severity is not yet effectively achieved. In this diagnostic trial, we aimed to assess the accuracy of presepsin (PSEP) for the diagnosis and early stratification of supposedly septic neonates. PSEP, C-reactive protein (CRP), and procalcitonin (PCT) were assessed at the onset of sepsis suspicion (T0), every 12–24 h for the first 48 h (T1–T4), and at the end of antibiotic therapy (T5). Enrolled neonates were stratified into three groups (infection, sepsis, septic shock) according to Wynn and Wong’s definitions. Sensitivity, specificity, and area under the ROC curve (AUC) according to the severity of clinical conditions were assessed. We enrolled 58 neonates with infection, 77 with sepsis, and 24 with septic shock. PSEP levels were higher in neonates with septic shock (median 1557.5 pg/mL) and sepsis (median 1361 pg/mL) compared to those with infection (median 977.5 pg/mL) at T0 (p < 0.01). Neither CRP nor PCT could distinguish the three groups at T0. PSEP’s AUC was 0.90 (95% CI: 0.854–0.943) for sepsis and 0.94 (95% CI: 0.885–0.988) for septic shock. Maximum Youden index was 1013 pg/mL (84.4% sensitivity, 88% specificity) for sepsis, and 971.5 pg/mL for septic shock (92% sensitivity, 86% specificity). However, differences in PSEP between neonates with positive and negative blood culture were limited. Thus, PSEP was an early biomarker of neonatal sepsis severity, but did not support the early identification of neonates with positive blood culture.

To construct monochorionic (MC) twin-specific longitudinal Doppler references for umbilical artery pulsatility index (UA-PI), middle cerebral artery (MCA) PI and peak systolic velocity (PSV) and ductus venosus (DV) PI derived from a strictly selected cohort of uncomplicated MC twins. The secondary aim of the study was to compare our findings with singleton reference charts. A retrospective evaluation was made of all consecutive uncomplicated MC twin pregnancies referred to our Unit from 2010 to 2018. Fortnightly serial examinations were performed of UA-PI, MCA-PI, MCA-PSV and DV-PI, according with the clinical protocol, from 20 to 37 weeks of gestation. We included cases with at least four ultrasound examinations, delivery at our hospital and complete neonatal follow up. A two-step method was used to trace the estimated centile curves: estimation of the median was performed with appropriate fractional polynomials by a multilevel model and estimation of the external centiles through the residuals (quantile regression). The comparison with singletons was made by plotting the references derived from the present study on the referred charts commonly used for singletons. The study group comprised 150 uncomplicated MC twin pairs. Estimated centiles (3^rd, 5^th, 10^th, 50^th, 90^th, 95^th, 97^th) of UA-PI, MCA-PI, MCA-PSV and DV-PI in function of the gestational age are presented. The comparison with singletons showed substantial differences, with higher UA-PI and lower MCA-PI and PSV median values in MC twins. Median DV PI values were similar to the values for singletons, while the upper centiles were higher in MC twins. This study sets out MC twin-specific longitudinal references for UA-PI, MCA-PI, MCA-PSV and DV-PI derived from the largest series of uncomplicated MC twin pregnancies presently available. The comparison with singleton reference values underscores the deviation from physiology that is intrinsic to these unique pregnancies and supports the need for MC twin-specific charts.

Respiratory distress syndrome (RDS) and feeding intolerance are common conditions in preterm infants and among the major causes of neonatal mortality and morbidity. For many years, preterm infants with RDS have been treated with mechanical ventilation, increasing risks of acute lung injury and bronchopulmonary dysplasia. In recent years non-invasive ventilation techniques have been developed. Showing similar efficacy and risk of bronchopulmonary dysplasia, nasal continuous positive airway pressure (NCPAP) and heated humidified high-flow nasal cannula (HHHFNC) have become the most widespread techniques in neonatal intensive care units. However, their impact on nutrition, particularly on feeding tolerance and risk of complications, is still unknown in preterm infants. The aim of the study is to evaluate the impact of NCPAP vs HHHFNC on enteral feeding and to identify the most suitable technique for preterm infants with RDS. A multicenter randomized single-blind controlled trial was designed. All preterm infants with a gestational age of 25–29 weeks treated with NCPAP or HHHFNC for RDS and demonstrating stability for at least 48 h along with the compliance with inclusion criteria (age less than 7 days, need for non-invasive respiratory support, suitability to start enteral feeding) will be enrolled in the study and randomized to the NCPAP or HHHFNC arm. All patients will be monitored until discharge, and data will be analyzed according to an intention-to-treat model. The primary outcome is the time to reach full enteral feeding, while parameters of respiratory support, feeding tolerance, and overall health status will be evaluated as secondary outcomes. The sample size was calculated at 141 patients per arm. The identification of the most suitable technique (NCPAP vs HHHFNC) for preterm infants with feeding intolerance could reduce gastrointestinal complications, improve growth, and reduce hospital length of stay, thus improving clinical outcomes and reducing health costs. The evaluation of the timing of oral feeding could be useful in understanding the influence that these techniques could have on the development of sucking-swallow coordination. Moreover, the evaluation of the response to NCPAP and HHHFNC could clarify their efficacy as a treatment for RDS in extremely preterm infants. ClinicalTrials.gov, NCT03548324 . Registered on 7 June 2018.