Hearing Loss and Risk Factors in Very Low Birth Weight Infants.

The incidence of sensorineural hearing loss (SNHL) is still high in very low birth weight (VLBW) infants. The purpose of our study was to provide the prevalence rates of SNHL and to analyze the risk factors of hearing impairment and changes in hearing thresholds in a cohort of VLBW infants. A retrospective observational study was conducted in our neonatal intensive care unit (NICU) from 2012 to 2016. All VLBW infants included were screened by transient evoked otoacoustic emissions (TEOAEs) and diagnostic auditory brainstem response (ABR). In total, we enrolled 316 infants and SNHL was diagnosed in 68, leading to an early incidence of 21.5% as 36 infants out of 68 improved. Finally, SNHL was confirmed in 20 patients (6.3%) who needed hearing aids. They were significantly smaller, sicker, had longer hospitalizations, and received more ototoxic therapies. Logistic regression analysis showed that gestational age (GA) influenced the association between drugs and SNHL. The results underlined how the total exposure to antibiotics is significantly associated with SNHL, even after GA correction. In conclusion, GA, birth weight and, above all, the length and complexity of NICU stay quantify the risk of SNHL and should be considered at the individual level for parent counseling.

Early Respiratory Physiotherapy versus an Individualized Postural Care Program for Reducing Mechanical Ventilation in Preterm Infants: A Randomised Controlled Trial.

BACKGROUND: Tactile stimulation manoeuvres stimulate spontaneous breathing in preterm newborns. The aim of this study is to evaluate the effect of early respiratory physiotherapy on the need for mechanical ventilation during the first week of life in preterm infants with respiratory failure. METHODS: This is a monocentric, randomised controlled trial. Preterm infants (gestational age ≤ 30 weeks) not intubated in the delivery room and requiring non-invasive respiratory support at birth were eligible for the study. The intervention group received early respiratory physiotherapy, while the control group received only a daily physiotherapy program (i.e., modifying the infant's posture in accordance with the patient's needs). RESULTS: between October 2019 and March 2021, 133 preterm infants were studied, 68 infants in the study group and 65 in routine care. The study group showed a reduction in the need for mechanical ventilation (not statistically significant) and a statistically significant reduction in hemodynamically significant patent ductus arteriosus with respect to the control group (19/68 (28%) vs. 35/65 (54%), respectively, p = 0.03). CONCLUSIONS: early respiratory physiotherapy in preterm infants requiring non-invasive respiratory support at birth is safe and has proven to be protective against haemodynamically significant PDA.

Securement of Umbilical Venous Catheter Using Cyanoacrylate Glue: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the role of cyanoacrylate glue in reducing dislodgement of umbilical venous catheters (UVCs). STUDY DESIGN: This was a single-center, randomized, controlled, nonblinded trial. All infants requiring an UVC according to our local policy were included in the study. Infants with a UVC with a centrally located tip as verified by real-time ultrasound examination were eligible for the study. Primary outcome was the safety and efficacy of securement by cyanoacrylate glue plus cord-anchored suture (SG group) vs securement by suture alone (S group), as measured by reduction in dislodgment of the external tract of the catheter. Secondary outcomes were tip migration, catheter-related bloodstream infection, and catheter-related thrombosis. RESULTS: In the first 48 hours after UVC insertion, dislodgement was significantly higher in the S group than in the SG group (23.1% vs 1.5%; P < .001). The overall dislodgement rate was 24.6% in the S group vs 7.7% in the SG group (P = .016). No differences were found in catheter-related bloodstream infection and catheter-related thrombosis. The incidence of tip migration was similar in both groups (S group 12.2% vs SG group 11.7%). CONCLUSIONS: In our single-center study, cyanoacrylate glue was safe and effective for securement of UVCs, and particularly effective in decreasing early catheter dislodgments. TRIAL REGISTRATION: UMIN-CTR Clinical Trial; Registration number: R000045844.

Real-Time Ultrasound Tip Location Reduces Malposition and Radiation Exposure during Epicutaneo-Caval Catheter Placement in Neonates.

OBJECTIVE: Epicutaneo-caval catheters (ECCs) are essential for the care of sick infants who require long-term medical and nutritional management. The aim of this study was to investigate the use of real-time ultrasound as an alternative to X-rays to reduce the incidence of primary malpositions during catheter insertion. STUDY DESIGN: Data on ECCs were retrospectively collected in a tertiary neonatal intensive care unit. Catheter were analyzed considering the tip location technique (standard chest-abdominal radiograph vs real-time ultrasound) RESULTS: A total of 248 ECCs were analyzed. Of these, 118 catheters had primary malposition (47.6%). The tip of 165 catheters was assessed using standard chest-abdominal X-rays and 107 (64.8%) were found to be in an inappropriate location. In the group of 83 catheters that were placed using real-time ultrasound for tip location, only 11 catheters (13.2%) had primary malposition. The rate of malposition among the two groups showed a statistically significant difference (p < 0.001). Hypothetically, 300 chest X-rays could have been saved if real-time ultrasound had been used to locate the tip, reducing radiation exposure to infants. CONCLUSION: The use of a real-time ultrasound may be beneficial in reducing primary catheter malpositions compared with conventional radiography. In addition, secondary malpositions and catheter-related complications can be monitored over time. KEY POINTS: · Conventional radiology cannot be considered the "gold standard" for ECC tip location.. · Ultrasound is more accurate and reduces insertion time reducing the rate of primary malposition.. · Ultrasound can be performed in real time and it is the best technique for ECC tip location in infants..

pCO2 values in asphyxiated infants under therapeutic hypothermia after tailored respiratory management: a retrospective cohort study.

Background: Hypoxic-ischemic encephalopathy (HIE) represents one of the major causes of neonatal death and long-term neurological disability. Both hypoxic-ischemic insults and therapeutic hypothermia (TH) can affect respiratory function. Currently, there is no evidence regarding optimal respiratory management in these infants. Methods: This is a retrospective cohort study examining newborns with HIE treated with TH between January 2015 and September 2020. The study population was divided into two groups based on different respiratory assistance during TH: spontaneous breathing (Group A) or mechanical ventilation (Group B). The primary outcome of the study was the mean pCO2 ± SD evaluation during TH in ventilated and non-ventilated asphyxiated infants. The secondary outcome was the correlation between ventilation strategy and short-term neurologic outcome according to Rutherford et al.'s MRI scoring system. Results: A total of 126 newborns were enrolled, 75 in Group A and 51 in Group B. Respiratory management was individualized, and volume guarantee (VG) ventilation was the first choice for ventilated infants. Group B infants showed more severe conditions at birth. During TH, ventilated infants showed optimal mean pCO2 comparable with those breathing spontaneously (40.6 mmHg vs. 42.3 mmHg, respectively, p 0.091), with no significant difference in pCO2 standard deviation between (7.7 mmHg vs. 8.1 mmHg, respectively, p 0.522). Mean pH, pH standard deviation, mean pO2, pO2 standard deviation, and mean respiratory rate also did not differ between groups. MRI patterns of brain injury predictive of abnormal neurodevelopmental outcomes were similar in both groups. Logistic regression analysis demonstrated that only umbilical cord arterial blood pH-affected MRI lesions were associated with poor neurodevelopmental outcomes (OR 1.505; CI 95% 1.069-2.117). Conclusions: Infants cooled after HIE should receive individualized respiratory management, not necessarily involving intubation. In those infants requiring mechanical ventilation, a volume-targeted strategy appeared to be effective in maintaining stable blood gas levels. Short-term neurological outcomes appeared comparable in ventilated and non-ventilated infants.

Maternal Ureaplasma/Mycoplasma colonization during pregnancy and neurodevelopmental outcomes for preterm infants.

Introduction: Ureaplasma (U.) and Mycoplasma (M.) species have been related to pregnancy complications (including preterm birth) and worse neonatal outcomes. The aim of our work is to evaluate neurodevelopmental outcomes in preterm infants born to mothers with Ureaplasma/Mycoplasma colonization during pregnancy. Methods: Preterm infants with gestational age (GA) of ≤ 30 weeks were included in a retrospective follow-up study. To evaluate the effects of maternal vaginal colonization, we divided preterm infants into two groups: exposed and unexposed infants. All infants were assessed at 24 ± 3 months of age using Griffith's Mental Developmental Scales (GMDS). Results: Among 254 preterm infants, only 32 infants (12.6%) were exposed to U. /M. colonization during pregnancy. Exposed infants and unexposed ones had a similar Griffith's Developmental Quotient (106 ± 27.2 vs. 108.9 ± 19.5, respectively), without significant differences (p = 0.46). However, exposed infants had a significantly poorer outcome than their unexposed peers in terms of locomotor abilities (100.7 ± 28.3 exposed vs. 111.5 ± 26.1 unexposed, p = 0.03). Conclusion: For visual and hearing impairment, exposed and unexposed infants had similar incidences of cognitive and motor impairment. However, exposed infants had significantly lower locomotor scores than unexposed peers.

Hammersmith Infant Neurological Examination in low-risk infants born very preterm: a longitudinal prospective study.

AIM: To describe the profile of global and single items of the Hammersmith Infant Neurological Examination (HINE) in a population of low-risk infants born very preterm during the first year of life. METHOD: The HINE was performed at 3, 6, 9, and 12 months' corrected age in a population of low-risk infants born preterm with a gestational age of fewer than 32 weeks and with normal or minimal changes on neuroimaging. RESULTS: A total of 174 infants born preterm (96 males, 78 females; mean gestational age = 27 weeks [SD = 1.8], range 23-31 weeks) fulfilled the inclusion criteria. The 10th centile cut-off score with median and range was reported for the HINE global and subsection scores. A progressive increase in global HINE scores was observed. Most of the single items, especially those related to tone, posture, and reflexes, showed progressive maturation. INTERPRETATION: Our results, which provide longitudinal data for single-item and global scores in a population of low-risk infants born very preterm, can be used as a reference in both clinical and research settings to monitor early neurological signs in these infants. These data could be used as normative data when examining low-risk infants born preterm.

Hammersmith Infant Neurological Examination in infants born at term: Predicting outcomes other than cerebral palsy.

AIM: We explored the ability of the Hammersmith Infant Neurological Examination (HINE) to identify cognitive performance delay at 2 years in a large cohort of infants born at term. METHOD: We conducted a retrospective study of infants born at term at risk of neurodevelopmental impairments assessed using the HINE between 3 and 12 months post-term age and compared them with a cohort of typically developing infants born at term. All infants performed a neurodevelopmental assessment at 2 years of age using the Mental Development Index (MDI) of the Bayley Scales of Infant Development, Second Edition; the presence of cerebral palsy (CP) was also reported. The infants were classified as being cognitively normal/mildly delayed or significantly delayed (MDI < 70). The predictive validity of HINE scores for significantly delayed cognitive performance, in infants with and without CP, was calculated using specific cut-off scores according to age at assessment. RESULTS: A total of 446 at-risk and 235 typically developing infants (345 males, 336 females; mean [SD] gestational age 38.7 weeks [1.4], range 37-43 weeks) were included. Of the at-risk infants, 408 did not have CP at 2 years; 243 had a normal/mild delayed MDI and 165 had an MDI less than 70. Of the at-risk infants, 38 developed CP. HINE scores showed a good sensitivity and specificity, mainly after 3 months, for identifying significantly delayed cognitive performance in infants without CP. In those with CP, the score was associated with their cognitive performance. The comparison group had the highest HINE scores. INTERPRETATION: The HINE provides evidence about the risk of delayed cognitive performance at age 2 years in infants born at term with and without CP.

EXAMEN NEUROLÓGICO INFANTIL DE HAMMERSMITH EN BEBÉS NACIDOS A TÉRMINO: SU USO PARA PREDECIR OTRAS CONDICIONES ADEMÁS DE LA PARÁLISIS CEREBRAL: OBJETIVO: Valoramos la capacidad del examen neurológico infantil de Hammersmith (HINE) para identificar el retraso en el rendimiento cognitivo a los 2 años en una cohorte grande de bebés nacidos a término. MÉTODO: Realizamos un estudio retrospectivo de bebés nacidos a término con riesgo de trastornos del desarrollo neurológico evaluados mediante el HINE entre los 3 y los 12 meses de edad postérmino y los comparamos con una cohorte de bebés nacidos a término con un desarrollo típico. Todos los bebés realizaron una evaluación del desarrollo neurológico a los 2 años de edad utilizando el Índice de Desarrollo Mental (MDI) de las Escalas de Desarrollo Infantil de Bayley, Segunda Edición; también se informó la presencia de parálisis cerebral (PC). Los bebés se clasificaron como cognitivamente normales/levemente con retreaso o significativamente con retraso (MDI < 70). La validez predictiva de las puntuaciones HINE para el rendimiento cognitivo con retraso significativo, en bebés con y sin parálisis cerebral, se calculó utilizando puntuaciones de corte específicas según la edad en la evaluación. RESULTADOS: Se incluyeron un total de 446 lactantes en riesgo y 235 con desarrollo normal (345 varones, 336 mujeres; edad gestacional media [DE] 38,7 semanas [1,4], rango de 37 a 43 semanas). De los lactantes en riesgo, 408 no tenían parálisis cerebral a los 2 años; 243 tenían un MDI con retraso normal/leve y 165 tenían un MDI inferior a 70. De los bebés en riesgo, 38 desarrollaron PC. Las puntuaciones HINE mostraron una buena sensibilidad y especificidad, principalmente después de 3 meses, para identificar un rendimiento cognitivo severo en lactantes sin PC. En aquellos con PC, la puntuación se asoció con su rendimiento cognitivo. El grupo de comparación tuvo las puntuaciones HINE más altas. INTERPRETACIÓN: El HINE proporciona evidencia sobre el riesgo de retraso en el rendimiento cognitivo a los 2 años de edad en bebés nacidos a término con y sin parálisis cerebral.

Strict glycaemic control in very low birthweight infants using a continuous glucose monitoring system: a randomised controlled trial.

OBJECTIVE: To evaluate the efficacy of a strict glycaemic control protocol using a continuous glucose monitoring (CGM) in infants at high risk of dysglycaemia with the aim of reducing the number of dysglycaemic episodes. DESIGN: Randomised controlled trial. SETTING: Neonatal intensive care unit, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome. PATIENTS: All infants <1500 g fed on parental nutrition (PN) since birth were eligible. A total of 63 infants were eligible and 48 were randomised. INTERVENTION: All participants wore a CGM sensor and were randomised in two arms with alarms set at different cut-off values (2.61-10 mmol/L (47-180 mg/dL) vs 3.44-7.78 mmol/L (62-140 mg/dL)), representing the operative threshold requiring modulation of glucose infusion rate according to an innovative protocol. MAIN OUTCOME MEASURES: The primary outcome was the number of severe dysglycaemic episodes (<2.61 mmol/L (47 mg/dL) or >10 mmol/L (180 mg/dL)) in the intervention group versus the control group, during the monitoring time. RESULTS: We enrolled 47 infants, with similar characteristics between the two arms. The number of dysglycaemic episodes and of infants with at least one episode of dysglycaemia was significantly lower in the intervention group (strict group): respectively, 1 (IQR 0-2) vs 3 (IQR 1-7); (p=0.005) and 12 (52%) vs 20 (83%); p=0.047. Infants managed using the strict protocol had a higher probability of having normal glycaemic values: relative risk 2.87 (95% CI 1.1 to 7.3). They spent more time in euglycaemia: 100% (IQR 97-100) vs 98% (IQR 94-99), p=0.036. The number needed to treat to avoid dysglycaemia episodes is 3.2 (95% CI 1.8 to 16.6). CONCLUSION: We provide evidence that CGM, combined with a protocol for adjusting glucose infusion, can effectively reduce the episodes of dysglycaemia and increase the percentage of time spent in euglycaemia in very low birthweight infants receiving PN in the first week of life.

Lutein supplementation and retinopathy of prematurity: a meta-analysis.

BACKGROUND: Retinopathy of prematurity (ROP) is a multifactorial retinal disorder characterized by an abnormal vascular development of the retina of the preterm infants. Carotenoids are natural pigments that are synthesized by all plants and some microorganisms where they play a role in photoprotection and coloration. Lutein and zeaxanthin (L/Z) are two carotenoids identified as the major components of the macular pigment. Recently it has been suggested that lutein and its isomer zeaxanthin may act as antioxidant agents and that they may prevent ROP. OBJECTIVE: The primary objective of this study is to assess the safety and effectiveness of oral lutein in the prevention of retinopathy of prematurity in preterm neonates. STUDY DESIGN: We conducted a systematic search for randomized or quasi-randomized controlled trials without any language or publication year restriction. The studies have to recruit preterm neonates ≤32 completed weeks of gestation and to compare the administration of oral L/Z at any dosage or duration, versus placebo in order to prevent ROP. RESULT: Data from three RCT with a total of 406 participants failed to show any reduction in ROP incidence nor the risk of BPD, sepsis, NEC and mortality. It may reduce the number of transfusions but this result has to be assessed in a separate ad hoc trial.

Neurodevelopmental Outcomes in Preterm Infants Receiving a Multicomponent vs. a Soybean-Based Lipid Emulsion: 24 Month Follow-Up of a Randomized Controlled Trial.

BACKGROUND: Few studies in the literature have analyzed the long-term neurodevelopmental outcomes of the administration of a multicomponent versus a soybean-based lipid emulsion (LE) in preterm infants receiving parenteral nutrition (PN). A recent randomized controlled trial conducted in our unit provided evidence of better growth in head circumference during the hospital stay in those who received a multicomponent LE. METHODS: This is a 24 month follow-up study of preterm infants, previously enrolled in a randomized trial, who received a multicomponent LE (SMOFlipid®) or a standard soybean-based one (Intralipid®). We evaluated neurodevelopmental outcomes at 24 months of corrected age (CA) in the two groups. RESULTS: Ninety-three children were followed up to the age of 24 months CA. Due to the peculiar time frame of the SARS-CoV-2 pandemic, neurodevelopmental outcomes were evaluated only in 77 children: 37 in the SMOFlipid® group and 40 in the Intralipid® group. No differences in major disability rates or in Griffith's evaluation were found between the two groups. CONCLUSIONS: In our population study, the administration of a multicomponent LE containing fish oil, compared to a soybean-based LE, had no significant effects on neurodevelopmental outcomes in preterm infants at 24 months CA.

Extra-uterine growth restriction in preterm infants: Neurodevelopmental outcomes according to different definitions.

AIM: Extra-uterine Growth Restriction (EUGR) is common among preterm infants. Two types of EUGR definitions are still now available: cross-sectional definitions and longitudinal ones. In a cohort of very preterm infants, we aimed to evaluate which definition could better predict neurodevelopmental outcomes at 2 years of corrected age. We used Italian Neonatal Study Charts (INeS) growth charts and INTERGROWTH-21st (IG-21) standard charts and compared results. METHOD: We restrospectively collected data from clinical charts of 324 preterm newborns with a gestational age ≤30 weeks born from 2012 to 2017. Then we compared forty-eight definitions (24 cross-sectional and 24 longitudinal) of EUGR, in term of neurodevelopmental outcomes at 2 years of corrected age. RESULTS: We included in the study 254 preterm infants, whose clinical information met the enrolment criteria. Nineteen out of 48 definitions of EUGR were significantly predictive both for Griffith's Development Quotient (GDQ) and Neurodevelopment Impairment (NDI). Among these, longitudinal definitions appeared to have a higher negative predictive value for NDI than cross-sectional ones. Furthermore, infants with EUGR appeared to have a lower cognitive score than their peers without EUGR. INTERPRETATION: A loss of Zs > 1 SDS in weight and head circumference, calculated from when physiological weight loss is over and identified as soon as possible rather than at discharge, better predicts neurodevelopmental outcomes of preterm infants.

Effects of early respiratory physiotherapy on spontaneous respiratory activity of preterm infants: study protocol for a randomized controlled trial.

BACKGROUND: Tactile maneuvers stimulating spontaneous respiratory activity in preterm infants are recommended since birth, but data on how and how often these maneuvers are applied in clinical practice are unknown. In the last years, most preterm newborns with respiratory failure are preferentially managed with non-invasive respiratory support and by stimulating spontaneous respiratory activity from the delivery room and in neonatal intensive care unit (NICU), in order to avoid the risks of intubation and prolonged mechanical ventilation. METHODS: Preterm infants with gestational age < 31 weeks not intubated in the delivery room and requiring non-invasive respiratory support at birth will be eligible for the study. They will be randomized and allocated to one of two treatment groups: (1) the study group infants will be subject to the technique of respiratory facilitation within the first 24 h of life, according to the reflex stimulations, by the physiotherapist. The newborn is placed in supine decubitus and a slight digital pressure is exerted on a hemithorax. The respiratory facilitation technique will be performed for about three minutes and repeated for a total of 4/6 times in sequence, three times a day until spontaneous respiratory activity is achieved; thus, no respiratory support is required; (2) the control group infants will take part exclusively in the individualized postural care program. They will perform the technique of respiratory facilitation and autogenous drainage. OBJECTIVE: To evaluate the efficacy of early respiratory physiotherapy in reducing the incidence of intubation and mechanical ventilation in the first week of life (primary outcome). DISCUSSION: The technique of respiratory facilitation is based on reflex stimulations, applied early to preterm infant. Slight digital pressure is exerted on a "trigger point" of each hemithorax, to stimulate the respiratory activity with subsequent increase of the ipsilateral pulmonary minute ventilation and to facilitate the contralateral pulmonary expansion. This mechanism will determine the concatenation of input to all anatomical structures in relation to the area being treated, to promote spontaneous respiratory activity and reducing work of breathing, avoiding or minimizing the use of invasive respiratory support. TRIAL REGISTRATION: UMIN-CTR Clinical Trial UMIN000036066. Registered on March 1, 2019. Protocol 1. https://www.umin.ac.jp/ctr.

Developmental dysplasia of the hip: real world data from a retrospective analysis to evaluate the effectiveness of universal screening.

AIMS: Developmental dysplasia of the hip is an important cause of disability in children and young adult and it also has a significant socio-economic impact in our society. The main objective of our study is to evaluate, in our hospital, the effectiveness of a universal ultrasound screening protocol and to assess the general knowledge about the theme of pediatricians and neonatologists. METHODS: Retrospective study of infants born from January 2016 to April 2019, evaluated with hip ultrasound (Graf method). Risk factors assessed were female gender, breech presentation at birth, positive family history and twin birth. For the secondary objective, an anonymous and validated questionnaire was distributed to all pediatricians and neonatologists. RESULTS: Among the 4000 hips analyzed, on ultrasound examination, 98.8% hips resulted mature or immature but appropriate for age, while 1,2% hips were pathological. Analyzing the mature or immature hips, 2,4% were positive on clinical examination and 97,6% were negative. In relation to ultrasound pathological hips, 33,3% have positive clinical examination, while 66,7% negative. From the analysis of risk factors a significant association emerged between female sex, breech presentation and family history with the ultrasound pathological findings. The results of Survey showed that inadequate training about developmental dysplasia of the hip is done during medical school. CONCLUSIONS: A universal ultrasound screening allowed us to identify developmental dysplasia of the hip in a number of children with normal clinical examination and no risk factors. Specific training courses should be implemented regarding Developmental Dysplasia of the Hip for neonatologists and pediatricians.

Lung recruitment before surfactant administration in extremely preterm neonates with respiratory distress syndrome (IN-REC-SUR-E): a randomised, unblinded, controlled trial.

BACKGROUND: The importance of lung recruitment before surfactant administration has been shown in animal studies. Well designed trials in preterm infants are absent. We aimed to examine whether the application of a recruitment manoeuvre just before surfactant administration, followed by rapid extubation (intubate-recruit-surfactant-extubate [IN-REC-SUR-E]), decreased the need for mechanical ventilation during the first 72 h of life compared with no recruitment manoeuvre (ie, intubate-surfactant-extubate [IN-SUR-E]). METHODS: We did a randomised, unblinded, controlled trial in 35 tertiary neonatal intensive care units in Italy. Spontaneously breathing extremely preterm neonates (24 + 0 to 27 + 6 weeks' gestation) reaching failure criteria for continuous positive airway pressure within the first 24 h of life were randomly assigned (1:1) with a minimisation algorithm to IN-REC-SUR-E or IN-SUR-E using an interactive web-based electronic system, stratified by clinical site and gestational age. The primary outcome was the need for mechanical ventilation in the first 72 h of life. Analyses were done in intention-to-treat and per-protocol populations, with a log-binomial regression model correcting for stratification factors to estimate adjusted relative risk (RR). This study is registered with ClinicalTrials.gov, NCT02482766. FINDINGS: Of 556 infants assessed for eligibility, 218 infants were recruited from Nov 12, 2015, to Sept 23, 2018, and included in the intention-to-treat analysis. The requirement for mechanical ventilation during the first 72 h of life was reduced in the IN-REC-SUR-E group (43 [40%] of 107) compared with the IN-SUR-E group (60 [54%] of 111; adjusted RR 0·75, 95% CI 0·57-0·98; p=0·037), with a number needed to treat of 7·2 (95% CI 3·7-135·0). The addition of the recruitment manoeuvre did not adversely affect the safety outcomes of in-hospital mortality (19 [19%] of 101 in the IN-REC-SUR-E group vs 37 [33%] of 111 in the IN-SUR-E group), pneumothorax (four [4%] of 101 vs seven [6%] of 111), or grade 3 or worse intraventricular haemorrhage (12 [12%] of 101 vs 17 [15%] of 111). INTERPRETATION: A lung recruitment manoeuvre just before surfactant administration improved the efficacy of surfactant treatment in extremely preterm neonates compared with the standard IN-SUR-E technique, without increasing the risk of adverse neonatal outcomes. The reduced need for mechanical ventilation during the first 72 h of life might facilitate implementation of a non-invasive respiratory support strategy. FUNDING: None.

Neurodevelopmental outcomes in very preterm infants: The role of severity of Bronchopulmonary Dysplasia.

OBJECTIVE: Bronchopulmonary dysplasia is a chronic respiratory disease that still affects preterm neonates; its association with neurodevelopmental (ND) impairment is already known. Different studies investigated neurodevelopmental outcomes in infants with BPD, often using the old dichotomous definition (BPD vs Non-BPD). This retrospective study aims to evaluate the role of different BPD severity grades on ND outcomes at 24 months of corrected age (CA). METHODS: All preterm infants born between 2011 and 2015 in the study hospital with a gestational age (GA) ≤ 30 weeks and discharged from our NICU were included and were divided in infants with and without BPD. Infants with BPD were divided into three severity groups as defined by NICHD/NHLBI Workshop in 2001, and were compared to their Non-BPD peers, matching them according to the same GA and year of birth. At 24 months postmenstrual age, we assessed general outcomes (growth and hospital readmissions) and neurodevelopmental outcomes (motor, developmental and sensory outcomes) with a standardized assessment. RESULTS: We enrolled 89 patients affected by BPD of different grades of severity and a control group of 89 preterm infants without BPD. Infants with Moderate and Severe BPD showed a significantly higher corrected odds ratio (OR) for cognitive impairment compared to controls. Within the group of infants without severe disability (regarding Griffiths' scales), infants with Moderate and Severe BPD as well as infants with Mild BPD showed a significantly higher risk of a lower total Developmental Quotient (DQ) score, even after correction for confounding factors. CONCLUSIONS: Our study evidenced that not only Severe BPD infants, but also Moderate ones showed a higher risk of overall cognitive impairment at 24 months CA. Within the group of infants without severe disability, also those with Mild BPD had lower Griffiths DQ scores than those without. This would suggest that infants with BPD, regardless of severity, warrant neurodevelopmental follow-up.

Hammersmith Infant Neurological Examination for infants born preterm: predicting outcomes other than cerebral palsy.

AIM: We explored the ability of the Hammersmith Infant Neurological Examination (HINE) to identify typical and delayed cognitive performance in a large population of infants born preterm, both with and without cerebral palsy (CP). METHOD: We conducted a retrospective study of infants born preterm who had repeated HINEs between 3 and 12 months corrected age. At 2 years, cognition was assessed using the Mental Development Index (MDI; from the Bayley Scales of Infant Development, Second Edition) and the presence and severity of CP was determined. All children were classified as cognitively typical/mildly delayed or significantly delayed (MDI <70) and CP. The predictive validity of HINE scores for significantly delayed cognitive performance, in children with and without CP, was calculated using specific cut-off scores according to age at assessment. RESULTS: Of 1229 eligible infants (gestational age 25-36wks, mean [SD] 34.9 [2.3]; 646 males, 583 females), 1108 did not develop CP, 891 had an MDI that was typical/mildly delayed, and 217 had an MDI less than 70. Of the 121 infants who developed CP, the MDI was typical in 28, mildly delayed in 27, and less than 70 in 66. HINE scores showed a good sensitivity and specificity, especially after 3 months, for detecting significantly delayed cognitive performance in infants without CP. In those who developed CP, the score was associated with their cognitive level. INTERPRETATION: The HINE provides information about the risk of delayed cognitive performance in infants born preterm with and without CP. What this paper adds The Hammersmith Infant Neurological Examination (HINE) can be used in the first year to identify infants born preterm at risk for delayed cognitive performance. Age-dependent HINE cut-off scores are proposed for detecting increased risk of delayed cognitive performance.

Sleep disorders in low-risk preschool very preterm children.

OBJECTIVES: (i) to assess the presence of sleep disorders in a population of very preterm children (ie, with a gestational age [GA] ≤ 31 weeks) of preschool age with no history of neurological disabilities using a questionnaire standardized for this age group and (ii) to identify possible differences in a control group of term-born children. METHODS: A total of 146 low-risk preterm children (mean gestational age 28 weeks; range: 25-30), were assessed at a preschool age (mean age 3.8 years; range 3-6 years) using the sleep disturbance scale for children (SDSC) to assess sleep problems. As controls, 146 typically developing children matched for age and gender were also evaluated using the SDSC. RESULTS: An abnormal total sleep score (>70) was found in 7% of preterm children, while 21% had an abnormal score on at least one SDSC factor. No significant differences were reported according to the age of assessment or gestational age. The preterm group reported higher significant median scores on SDSC total, sleep-disordered breathing, sleep hyperhidrosis and difficulty in initiating and maintaining sleep factors. CONCLUSIONS: Low-risk very preterm children showed only a slightly higher incidence of sleep disorders than term-born peers at preschool age, with higher scores in specific sleep factors. These data could be useful to clinicians for screening those preterm children at risk for sleep disorders who need a more detailed assessment for a conclusive diagnosis and treatment.

Tolerance of preterm formula versus pasteurized donor human milk in very preterm infants: a randomized non-inferiority trial.

BACKGROUND: Human milk (HM) is the best feeding for premature infants. When own mother's milk (OMM) is insufficient or unavailable, pasteurized donor human milk (PDHM) and preterm formula (PF) are the alternative nutritional sources, but the benefits of donor milk over formula are not defined. This study aimed to assess whether, in the absence of OMM, the PF could guarantee a feeding tolerance not inferior to that seen with the use of PDHM during the first two weeks of life of very preterm infants. METHODS: Infants with gestational age (GA) of ≤32 weeks who started enteral feeding within the first 7 days of life were randomized to receive PDHM or PF as a supplement to the OMM insufficient or unavailable. The primary outcome was the day of life when full enteral feeding (FEF) of 150 mL/Kg/d was achieved. RESULTS: Seventy infants were randomized, 35 in the PF group (GA 30.2 ± 1.7 weeks; BW 1342 ± 275 g), 35 in the PDHM group (GA 30 ± 1.9 weeks; BW 1365 ± 332 g). The time to achieve FEF was the same for infants fed with PF and for infants fed with PDHM (12.3 ± 7.0 days vs 12.8 ± 6.5). CONCLUSIONS: This trial shows that PF could be a valid alternative for the early feeding of very preterm infants when OMM is insufficient or unavailable. TRIAL REGISTRATION: UMIN000013922 . Date of formal registration: December 31, 2014.