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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 25–36 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.

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

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.

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. Keywords: cognitive; motor outcomes; motor performance; neonate; neurodevelopment; newborn; pregnant; prematurity—risk assessment and prevention.

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.

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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.

Background: Hypenatremic dehydration is a complication of preterm infants with reportedly high morbility. In preterm infants, this happens due to a combination of low fluid intake, transepidermal water loss (TEWL), and immaturity of kidney function. Semipermeable membranes are self-adhesive membranes that can be applied as an artificial skin to reduce TEWL.Aims: To test the hypothesis that early application of a semipermeable membrane (Tegaderm(TM)) in preterm infants <= 30 weeks could result in a significant reduction of hypenatremia (serum Na > 145 mEq/l) during the first 15 days of life.Study design: Randomized controlled trial (UMIN000010515).Subjects: 164 consecutive newborns with gestational ages <= 30 weeks, absence of congenital skin defects, and duration of admission a 15 days. Patients were randomized to receive semipermeable membrane (n = 82) or no membrane (n =82) for the first 15 days of life.Outcome measures: The primary endpoint of the study was the incidence reduction of hypernatremia (Na > 145 mEq/l). Secondary endpoints included: postnatal weight loss (WL) and time to birth weight (BW) recovery.Results: Incidence of hypernatremia in the control and semipermeable membrane group was 59.7% and 41.6%, respectively (p = 0.030). Postnatal WL was larger in the control group (13.9 +/- 5.6% vs 11.1 +/- 3.4%, p = 0.005) and occurred later than the semipermeable membrane group (5.4 +/- 2.3 vs 4.5 +/- 1.4 days, p = 0.005). Time to BW recovery was also longer for control group (13.5 +/- 4.3 vs 11.9 +/- 3.2 days, p = 0.016).Conclusions: Early application of skin semipermeable membrane to <= 30 week preterm is associated with decreased incidence of hypernatremia, decreased %WL, and earlier BW recovery. No complications were observed with membrane application.

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.

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.

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 (

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.

This study investigated hearing threshold changes during the first year of corrected age (CA) in infants admitted in a neonatal intensive care unit (NICU). In 5 years, 239 infants with birth weight (BW) ≤ 1,000 gm and/or gestational age (GA) ≤ 30 weeks were enrolled. Hearing was evaluated by oto-acoustic emission (OAEs) before discharge and auditory brainstem response (ABR) within 3 months of CA. Infants affected by unilateral or bilateral hearing loss were addressed to audiological follow-up until definitive diagnosis (within 6 months of CA). Changes in hearing threshold were also carefully analysed. 207 (86.6%) infants had normal hearing while 32 infants (13.4%) showed hearing loss (HL) at the confirmative ABR evaluation (9 mild, 16 moderate, 4 severe, 3 profound). The latter showed lower GA (27.7 ± 2 vs 28.4 ± 1.2; p = 0.0061) and BW (950 ± 390 vs 1,119 ± 326 gm; p = 0.0085). At final evaluation, 15 infants (47%) recovered a normal hearing. HL was confirmed in 17 patients. Among these, 3 infants were addressed to audiological follow-up (one case of mild unilateral hearing loss (UHL) and two with moderate UHL), while in 14 cases (44%) with bilateral sensory neural hearing loss (SNHL) (7 moderate, 4 severe, 3 profound) hearing aids were prescribed. They showed significantly lower GA and longer hospital stay in the NICU in comparison with infants without indication for audiological habilitation (18 infants) (GA 26.2 ± 2.2 weeks vs 28.4 ± 2.4; p = 0.01; NICU stay 132 ± 67 vs 59 ± 7; p = 0.0002). Definitive diagnosis was obtained at 5.9 ± 1.3 months of CA. Our study confirms the importance of audiological surveillance in preterm newborns. Hearing thresholds of preterm infants with hearing loss can change during the first year of CA and we observed normalisation in 47% of our patients. Most vulnerable to permanent SNHL were very preterm infants with a longer NICU stay, while a shorter stay represents a favourable prognostic factor for hearing improvement.

Background: Fibreoptic Phototherapy (FPT) allows to lower total serum bilirubin (TSB) levels in healthy neonates maintained in rooming-in with their mothers. The 2004 Cochrane review showed that, differently from preterm neonates, FPT was not as effective as traditional phototherapy in term neonates (TN), unless the simultaneous utilization of two FPT devices. Aim of this study was to compare the efficacy of two FPT devices, both equipped with a single light-emitting diode (LED): the first one has a single large pad wrapped around the infant body (Bilisoft, GE Health Care) (device A), the second one is a double-pad phototherapy device (BiliCocoon, CremascolieIris) (device B). Methods: We studied 172 healthy neonates with non-hemolytic hyperbilirubinaemia: 57 TN and 57 late preterm neonates (LPN) treated with device A (Group 1); 47 TN and 11 LPN treated with device B (Group 2). We evaluated the differences between groups by the Student's t-test for continuous variables and by chi square test for categorical data. A two tailed p < 0.05 was considered significant. Results: There were no differences in term of duration of FPT, TSB hourly reduction, percentage of TSB reduction after FPT, TSB maximum rebound, percentage of TSB increase after FPT discontinuation and number of after-discharge checks. Two neonates treated with device B showed no decrease in TSB values during FPT. Seven infants treated with device B experienced hyperpyrexia. Conclusions: The two LED FPT devices were both effective in lowering TSB either in TN or LPN. Device A was effective in all treated neonates without negative side effects during treatment; device B was effective in all but 2 infants and 12% of the neonates in the same group experienced hyperpyrexia. According to our results, the single big pad wrapped around the infant body has the same efficacy as a double FPT device in TN and LPN.

Objective: To evaluate the prevalence of joint laxity in children born preterm assessed in the first 2 years, the relationship between joint laxity and motor performance at preschool age, and possible changes over time in a subgroup of children followed longitudinally. Study design: The revised scale of Beighton Score was used to evaluate joint laxity in a population of 132 preschool children born preterm between 24 and 32 weeks of gestational age. All were assessed for joint laxity between 12 and 24 months of age. Children also performed the Movement Assessment Battery for Children-Second Edition between the age of 3 years and 6 months and 4 years; the age at onset of independent walking also was recorded. Results: The total Beighton Score ranged between 0 and 8. Twenty percent of the cohort showed joint laxity. No differences related to sex or gestational age were observed. Children born preterm with joint laxity achieved later independent walking and achieved lower scores on Movement Assessment Battery for Children-Second Edition than those without joint laxity. In 76 children born preterm, an assessment for joint laxity was repeated once between 25 and 36 months and again after >36 months. No statistically significant difference was observed between the 3 assessments. Conclusions: The Beighton Score can be used to assess generalized joint laxity in children born preterm. As the presence of joint laxity influenced motor competences, the possibility to early identify these infants in the first 2 years is of interest to benefit from early intervention and potentially improve gross motor skills and coordination.

BACKGROUND: The influence of gestational age and gender in the neurodevelopment of infants during the first year of age is not yet fully elucidated. AIMS: The purpose of this study was to identify the early occurrence of neurodevelopmental differences, between very preterm, late preterm and term born infants and the possible influence of the gender on the neurodevelopment in early infancy. METHODS: A total of 188 low-risk infants, 69 very preterms, 71 late-preterms, and 48 term infants were assessed at 3, 6, 9, 12 months corrected age using the Hammersmith Infant Neurological Examination (HINE). At two years of age infants performed the Mental Developmental Index (MDI) of the Bayley Scales of Infant Development. RESULTS: The main results indicate that both very preterms and late-preterms showed significant lower global scores than term born infants at each evaluation (p < 0.001) at HINE and namely, at 3 months for the subsections "cranial nerve" and "posture" and at every age for "tone"; no gender differences has been evidenced in neurological performances. At the MDI, very preterms showed significant lower scores (p < 0.01) than both late-preterm and term born infants; gender differences were observed for preterms only (very and late), with best performances for females. CONCLUSIONS: Our results point out the presence of gestational age and gender-dependent differences in the development of infants assessed during the first 2 years of life.

We aimed to estimate the frequency of sleep disorders in children with cerebral palsy (CP) using the Sleep Disturbance Scale for Children (SDSC) and to evaluate the relations between sleep disorders and motor, cognitive, and behavioral problems. METHODS: One hundred and sixty-five children with CP ages 6-16 years (mean age, 11years) were assessed using the SDSC, the Gross Motor Function Classification System (GMFCS), the Wechsler Intelligence Scale for Children and the Child Behavior Check List (CBCL) to assess sleep, motor, cognitive, and behavioral problems, respectively. RESULTS: An abnormal total sleep score was found in 19% of children with CP; more than 40% of children had an abnormal score on at least one SDSC factor. The SDSC total score was significantly associated (P<.01) with mental retardation, epilepsy, CBCL scores, and level 5 on the GMFCS. CONCLUSIONS: Our results confirm that sleep disorders are common in children with cerebral palsy. The relationship between motor and cognitive behavior and epilepsy should be further explored to better understand how these factors influence one another to identify effective treatments and to improve the well-being of the child.