The General Movement Optimality Score-Revised (GMOS-R) with Socioeconomically Stratified Percentile Ranks.

Background: The general movement optimality score (GMOS) quantifies the details of general movements (GMs). We recently conducted psychometric analyses of the GMOS and developed a revised scoresheet. Consequently, the GMOS-Revised (GMOS-R) instrument necessitated validation using new percentile ranks. This study aimed to provide these percentile ranks for the GMOS-R and to investigate whether sex, preterm birth, or the infant's country of birth and residence affected the GMOS-R distribution. Methods: We applied the GMOS-R to an international sample of 1983 infants (32% female, 44% male, and 24% not disclosed), assessed in the extremely and very preterm period (10%), moderate (12%) and late (22%) preterm periods, at term (25%), and post-term age (31%). Data were grouped according to the World Bank's classification into lower- and upper-middle-income countries (LMICs and UMICs; 26%) or high-income countries (HICs; 74%), respectively. Results: We found that sex and preterm or term birth did not affect either GM classification or the GMOS-R, but the country of residence did. A lower median GMOS-R for infants with normal or poor-repertoire GMs from LMICs and UMICs compared with HICs suggests the use of specific percentile ranks for LMICs and UMICs vs. HICs. Conclusion: For clinical and scientific use, we provide a freely available GMOS-R scoring sheet, with percentile ranks reflecting socioeconomic stratification.

Neurodevelopmental Outcome after Culture-Proven or So-Called Culture-Negative Sepsis in Preterm Infants.

(1) Background: Prematurity is a serious condition associated with long-term neurological disability. This study aimed to compare the neurodevelopmental outcomes of preterm neonates with or without sepsis. (2) Methods: This single-center retrospective case-control study included infants with birth weight < 1500 g and/or gestational age ≤ 30 weeks. Short-term outcomes, brain MRI findings, and severe functional disability (SFD) at age 24 months were compared between infants with culture-proven or culture-negative sepsis or without sepsis. A chi-squared test or Mann-Whitney U test was used to compare the clinical and instrumental characteristics and the outcomes between cases and controls. (3) Results: Infants with sepsis (all sepsis n = 76; of which culture-proven n = 33 and culture-negative n = 43) were matched with infants without sepsis (n = 76). Compared with infants without sepsis, both all sepsis and culture-proven sepsis were associated with SFD. In multivariate logistic regression analysis, SFD was associated with intraventricular hemorrhage (OR 4.7, CI 1.7-13.1, p = 0.002) and all sepsis (OR 3.68, CI 1.2-11.2, p = 0.021). (4) Conclusions: All sepsis and culture-proven sepsis were associated with SFD. Compared with infants without sepsis, culture-negative sepsis was not associated with an increased risk of SFD. Given the association between poor outcomes and culture-proven sepsis, its prevention in the neonatal intensive care unit is a priority.

Neurodevelopmental outcome of neonatal seizures: A longitudinal study.

INTRODUCTION: Neonatal seizures (NS) are the most common neurological emergency in the neonatal period. The International League Against Epilepsy (ILAE) proposed a new classification of NS based on semiology and highlighted the correlation between semiology and aetiology. However, neurodevelopmental outcomes have not been comprehensively evaluated based on this new classification. AIMS: To evaluate neurodevelopmental outcomes and potential risk factors for severe outcomes in NS. METHODS: Patients with video electroencephalogram confirmed NS were evaluated. Seizure aetiology, cerebral magnetic resonance imaging (MRI) data, background electroencephalograms data, general movements, and neurodevelopmental outcomes were analysed. Severe outcomes were one of the following: death, cerebral palsy, Griffiths developmental quotient <70, epilepsy, deafness, or blindness. RESULTS: A total of 74 neonates were evaluated: 62 (83.8 %) with acute provoked NS (primarily hypoxic-ischaemic encephalopathy), and 12 (16.2 %) with neonatal-onset epilepsies (self-limited neonatal epilepsy, developmental and epileptic encephalopathy, cerebral malformations). Of these, 32 (43.2 %) had electrographic seizures, while 42 (56.7 %) had electroclinical seizures - 38 (90.5 %) were motor (42.1 % clonic) and 4 (9.5 %) were non-motor phenomena. Severe outcomes occurred in 33 of the 74 (44.6 %) participants. In multivariate analysis, neonatal-onset epilepsies (odds ratio [OR]: 1.3; 95 % confidence interval [CI]: 1.1-1.6), status epilepticus (OR: 5.4; 95 % CI: 1.5-19.9), and abnormal general movements (OR: 3.4; 95 % CI: 1.9-7.6) were associated with severe outcomes. CONCLUSIONS: At present, hypoxic-ischaemic encephalopathy remains the most frequent aetiology of NS. The prognosis of neonatal-onset epilepsies was worse than that of acute provoked NS, and status epilepticus was the most predictive factor for adverse outcomes.

Fetal hepatic calcification in severe KAT6A (Arboleda-Tham) syndrome.

Arboleda-Tham syndrome (ARTHS, MIM 616268) is a rare genetic disease, due to a pathogenic variant of Lysine (K) Acetyltransferase 6A (KAT6A) with autosomal dominant inheritance. Firstly described in 2015, ARTHS is one of the more common causes of undiagnosed syndromic intellectual disability. Due to extreme phenotypic variability, ARTHS clinical diagnosis is challenging, mostly at early stage of the disease. Moreover, because of the wide and unspecific spectrum of ARTHS, identification of the syndrome during prenatal life rarely occurs. Therefore, reported cases of KAT6A syndrome have been identified primarily through clinical or research exome sequencing in a gene-centric approach. In order to expands the genotypic and phenotypic spectrum of ARTHS, we describe prenatal and postnatal findings in a patient with a novel frameshift KAT6A pathogenic variant, displaying a severe phenotype with previously unreported clinical features.

Perinatal and postnatal exposure to phthalates and early neurodevelopment at 6 months in healthy infants born at term.

Background: Phthalates are non-persistent chemicals largely used as plasticizers and considered ubiquitous pollutants with endocrine disrupting activity. The exposure during sensible temporal windows as pregnancy and early childhood, may influence physiological neurodevelopment. Aims and Scope: The aim of this study is to analyze the relationship between the urinary levels of phthalate metabolites in newborn and infants and the global development measured by the Griffiths Scales of Children Development (GSCD) at six months. Methods: Longitudinal cohort study in healthy Italian term newborn and their mothers from birth to the first 6 months of life. Urine samples were collected at respectively 0 (T0), 3 (T3), 6 (T6) months, and around the delivery for mothers. Urine samples were analyzed for a total of 7 major phthalate metabolites of 5 of the most commonly used phthalates. At six months of age a global child development assessment using the third edition of the Griffith Scales of Child Development (GSCD III) was performed in 104 participants. Results: In a total of 387 urine samples, the seven metabolites analyzed appeared widespread and were detected in most of the urine samples collected at any time of sampling (66-100%). At six months most of the Developmental Quotients (DQs) falls in average range, except for the subscale B, which presents a DQ median score of 87 (85-95). Adjusted linear regressions between DQs and urinary phthalate metabolite concentrations in mothers at T0 and in infants at T0, T3 and T6 identified several negative associations both for infants' and mothers especially for DEHP and MBzP. Moreover, once stratified by children's sex, negative associations were found in boys while positive in girls. Conclusions: Phthalates exposure is widespread, especially for not regulated compounds. Urinary phthalate metabolites were found to be associated to GSCD III scores, showing inverse association with higher phthalate levels related to lower development scores. Our data suggested differences related to the child's sex.

Early Skin-to-Skin Contact in Preterm Infants: Is It Safe? An Italian Experience.

BACKGROUND: Skin-to-skin contact (SSC) is one of the four components of kangaroo care (KC) and is also a valued alternative to incubators in low-income countries. SSC has also become a standard of care in high-income countries because of its short- and long-term benefits and its positive effect on infant growth and neurodevelopmental outcome. However, barriers in the implementation of SSC, especially with preterm infants, are common in NICUs because parents and health care professionals can perceive it as potentially risky for the clinical stability of preterm infants. Previous studies have assessed safety before and during SSC by monitoring vital parameters during short-time intervals. AIMS: To demonstrate the safety of early SSC in preterm infants during at least 90 min intervals. DESIGN: Prospective observational monocentric study. METHODS: Preterm infants born between June 2018 and June 2020 with a gestational age of ≤33 weeks and a birth weight of <2000 g were monitored while performing an SSC session during the first three weeks of life. Infants with necrotizing enterocolitis, sepsis, and congenital malformations on mechanical ventilation or with more than five apneas in the hour before SSC were excluded. Continuous oxygen saturation (SaO2), heart rate (HR), and respiratory rate (RR) were registered during an SSC session and in the hour before. The minimum duration of an SSC session was 90 min. Information regarding postmenstrual age (PMA), body weight, respiratory support, presence of a central venous catheter and the onset of sepsis within 72 h after a session was collected. Two physicians, blinded to infant conditions and the period of analysis (before or during SSC), evaluated desaturation episodes (SaO2 < 85%, >15 s), bradycardia (HR < 100, >15 s) and apneas (pause in breathing > 20 s associated with desaturation and/or bradycardia). A Wilcoxon rank sum test was used for the statistical analysis. RESULTS: In total, 83 episodes of SSC were analyzed for a total of 38 infants. The mean gestational age at birth was 29 weeks (range 23-33 weeks). Median PMA, days of life, and body weight at SSC were 31 weeks (range 25-34 weeks), 10 days (range 1-20 days), and 1131 g (range 631-2206 g), respectively. We found that 77% of infants were on respiratory support and 47% of them had a central venous catheter (umbilical or peripherally inserted central catheter) during SSC. The total duration of desaturation, bradycardia, and the number of apneas were not statistically different during the SSC session and the hour before. No catheter dislocation or ruptures were reported. CONCLUSIONS: These findings highlighted the safety of early SSC in preterm infants and the possibility of performing it in an intensive care setting in the first weeks of life. In addition, these findings should reassure health care professionals offering this practice as a standard of care. SSC plays a key role in the care of preterm infants due to its short- and long-term positive benefits, and it deserves to be increasingly offered to infants and their parents.

Therapeutic hypothermia is associated with changes in prognostic value of general movements.

BACKGROUND AND AIMS: General movements (GMs) have been recognized as the most accurate clinical tools for predicting cerebral palsy (CP). This study aimed to compare the type and prognostic value of abnormal GMs in infants with hypoxic ischemic encephalopathy treated or not with therapeutic hypothermia (TH). MATERIALS AND METHODS: This was a single-center retrospective study. We compared GMs of 55 cooled term infants versus 30 non-cooled term infants with hypoxic ischemic encephalopathy (HIE) and their motor outcome at 24 months of age. We also included data regarding early brain MRI scans. RESULTS: Rates of cerebral palsy was 5.4% and 46.7% in cooled and non-cooled infants respectively (p < 0.001). None of cooled infants showed cramped-synchronized GMs, whereas among non-cooled infants the cramped-synchronized pattern was present in 17.2% and 20% of infants at 1 and 3 months of age respectively. Hypokinesis was never seen in cooled infants and it was present in 23.3% of non-cooled ones. Absent fidgety correlated with CP in 14% and 73% of cooled and non-cooled infants respectively. At brain MRI cooled infants had fewer and less severe cerebral lesions compared to non-cooled infants (p = 0.003). CONCLUSIONS: Abnormal GMs are reduced in infants treated with TH. Hypokinesis and cramped-synchronized GMs are not observed in cooled infants and the associations between absent fidgety movements and CP it is largely abolished. TH is associated with changes in prognostic value of GMs.

Neurodevelopmental Outcome and Neuroimaging of Very Low Birth Weight Infants from an Italian NICU Adopting the Family-Centered Care Model.

BACKGROUND: Improvements in perinatal care have substantially decreased mortality rates among preterm infants, yet their neurodevelopmental outcomes and quality of life persist as a pertinent public health concern. Family-centered care has emerged as a holistic philosophy that promotes effective alliances among patients, families, and healthcare providers to improve the quality of care. AIMS: This longitudinal prospective study aims to evaluate the neurodevelopmental outcomes and brain MRI findings in a cohort of preterm newborns admitted to a neonatal intensive care unit (NICU) adopting a family-centered care model. METHODS: Very low birth weight (VLBW) infants admitted to the NICU of Modena between 2015 and 2020 were enrolled. Infants who underwent conventional brain magnetic resonance imaging (MRI) at term-equivalent age were included. Neurodevelopmental follow-up was performed until the age of 24 months by a multidisciplinary team using the Amiel-Tison neurological assessment and the Griffiths Mental Developmental Scales (GMDS-R). Neurodevelopmental outcomes were classified as major sequelae (cerebral palsy, DQ ≤ 70, severe sensory impairment), minor sequelae (minor neurological signs such as clumsiness or DQ between 71 and 85), and normal outcomes (no neurological signs and DQ > 85). Risk factors for severe outcomes were assessed. RESULTS: In total, 49 of the 356 infants (13.8%) died before hospital discharge, and 2 were excluded because of congenital disorders. Of the remaining 305 infants, 222 (72.8%) completed the 24 month follow-up and were included in the study. Neurodevelopmental outcomes were classified as normal (n = 173, 77.9%), minor (n = 34, 15.3%), and major sequelae (n = 15, 6.8%). Among 221 infants undergoing brain MRI, 76 (34.4%) had major lesions (intraventricular hemorrhage, hemorrhagic parenchymal infarction, periventricular leukomalacia, and large cerebellar hemorrhage). In the multivariate regression model, the retinopathy of prematurity (OR 1.8; p value 0.016) and periventricular-intraventricular hemorrhage (OR 5.6; p value < 0.004) were associated with major sequelae. CONCLUSIONS: We reported low rates of severe neurodevelopmental outcomes in VLBW infants born in an Italian NICU with FCC. Identifying the risk factors for severe outcomes can assist in tailoring and optimizing early interventions on an individual basis, both within the NICU and after discharge.

Parents' Experience in an Italian NICU Implementing NIDCAP-Based Care: A Qualitative Study.

Background: The birth of a preterm infant and his/her immediate admittance to the Neonatal Intensive Care Unit (NICU) are sudden, unexpected, stressful and painful events for parents. In the last decade, in response to the increased awareness of the stressful experiences of parents, much attention has been paid to Family-Centered Care (FCC) and the implementation of the Newborn Individualized Developmental Care and Assessment Program (NIDCAP). According to the NIDCAP model, the infant-parents' dyad is the core of the care provided by the NICU professionals to reduce the stress experienced by parents. So far, the literature does not show a clear correlation between parental experiences and the NICU practices according NIDCAP principles. Aims: To explore how parents of preterm infants experienced the NIDCAP-based care from admission to discharge, in particular, their relationships with NICU professionals and with other parents, and the organization of the couple's daily activities during this process. Design: Qualitative exploratory study. Methods: Twelve parents of preterm infants born between January 2018 and December 2020 at the NICU of Modena, with a gestational age at birth of less than 30 weeks and/or a birth weight of less than 1250 g, were recruited. Three couples had twins, and the total number of infants was 15. All infants were followed for up to 24 months post-term age (PTA) for neurological outcomes. Each couple was given a semi-structured online interview about their experience during their infant's hospitalization in the NICU up to discharge. The interview was developed around three time points: birth, hospitalization and discharge. The data analysis was conducted according to the template analysis method. Results: The admission to the NICU was unexpected and extraordinary, and its impact was contained by the skilled staff who were capable of welcoming the parents and making them feel they were involved and active collaborators in the care of their infant. The emotional experience was compared to being in a blender; they were overwhelmed by changing emotions, ranging from terrible fear to extreme joy. The couple's activities of daily life were reorganized after the infant's birth and admission to the NICU. Fathers felt unbalanced and alone in taking care of their partners and their children. Conclusions: This is the first study in Italy to explore parental experience in an NICU implementing NIDCAP-based care. The NIDCAP approach in the NICU of Modena helps parents to be involved early, to develop parental skills, and to be prepared for the transition home; and it also facilitates and enhances the relationship between parents and NICU staff.

Polygraphic EEG Can Identify Asphyxiated Infants for Therapeutic Hypothermia and Predict Neurodevelopmental Outcomes.

Background: Neonatal encephalopathy due to perinatal asphyxia is one of the leading causes of neonatal death and morbidity worldwide. The neurodevelopmental outcomes of asphyxiated neonates have considerably improved after therapeutic hypothermia (TH). The current challenge is to identify all newborns with encephalopathy at risk of cerebral lesions and subsequent disability within 6 h of life and who may be within the window period for treatment with TH. This study evaluated the neurodevelopmental outcomes in surviving asphyxiated neonates who did and did not receive TH, based on clinical and polygraphic electroencephalographic (p-EEG) criteria. Methods: The study included 139 asphyxiated newborns divided into two groups: 82 who received TH and 57 who were not cooled. TH was administered to asphyxiated newborns (gestational age ≥ 35 weeks, birth weight ≥ 1800 g) with encephalopathy of any grade and moderate-to-severe p-EEG abnormalities or seizures. Neurodevelopmental outcomes between the groups at 24 months of life and the risk factors for severe outcomes were assessed. Results: Severe neurodevelopmental impairment occurred in 10 (7.2%) out of the 139 enrolled neonates. Nine out of the 82 cooled neonates (11.0%) had severe neurodevelopmental impairment. All but one neonate (98.2%) who did not receive TH had normal outcomes. The multivariate logistic regression analysis showed that abnormal p-EEG patterns (OR: 27.6; IC: 2.8-267.6) and general movements (OR: 3.2; IC: 1.0-10.0) were significantly associated with severe neurodevelopmental impairment (area under ROC curve: 92.7%). Conclusion: The combination of clinical and p-EEG evaluations in hypoxic-ischemic encephalopathy contributed to a more accurate selection of patients treated with therapeutic hypothermia. When administered to infants with moderate to severe p-EEG abnormalities, TH prevents approximately 90% of severe neurodevelopmental impairment after any grade of hypoxic-ischemic encephalopathy.

Subtle impairment of neurodevelopment in infants with late fetal growth restriction.

INTRODUCTION: Children with late fetal growth restriction (FGR) are at high risk of being born small for gestational age (SGA). These categories of newborns are at increased risk for neurodevelopment impairment. The general movements assessment, in particular at fidgety age, has been used to predict neurological dysfunctions. This study aimed to evaluate growth recovery, presence of fidgety movements at 3 months, and neurodevelopmental outcome at 2 years of age in term late FGR infants and adequate for gestational age (AGA) controls. METHODS: Prospective clinical evaluation. At 3 months auxological parameters (AP) and neurological examination were evaluated while at 24 months neurodevelopment outcome by Griffiths Mental Development Scales (GMDS-R) was evaluated. RESULTS: 38 late FGR and 20 AGA controls completed the study. Despite a significant catch up, at 3 months 13% of late FGR presented at least one auxological parameter <3° percentile. Moreover, 23.7% of late FGR infants did not show fidgety movements compared to 100% AGA controls (p < .001). Cranial circumference at birth resulted a positive predictive factor for FMs (p = .039). At 2 years of age, a difference statistically significant between late FGR and AGA was detected in GMDS-R. CONCLUSION: Independently from growth recovery, fidgety movements resulted less expressed in late FGR infants, and at 2 years of age the neurodevelopmental assessment revealed differences in each domain of evaluation between late FGR and AGA infants, although within normal ranges.

Neuroprem 2: An Italian Study of Neurodevelopmental Outcomes of Very Low Birth Weight Infants.

Background: Despite the increased survival of preterm newborns worldwide, the risk of neurodevelopmental disabilities remains high. Analyzing the outcomes of the preterm population can identify risk factors and enable specific early interventions. Aims: Neuroprem is a prospective cohort study of very low birth weight (VLBW) infants that aims to evaluate the neurodevelopmental outcomes and risk factors for severe functional disability at 2 years of corrected age. Methods: Nine Italian neonatal intensive care units participated in the network. The Griffiths Mental Developmental Scales (GMDS-R) or the Bayley Scales of Infant and Toddler Development (BSDI III) and a neuro-functional evaluation (according to the International Classification of Disability and Health and Neuro-Functional Assessment, or NFA ICF-CY) were administered to VLBW infants at 24 months of corrected age. The primary outcome measure was severe functional disability, defined as cerebral palsy, bilateral blindness, deafness, an NFA ICF-CY of >2, a BSDI III cognitive composite score of <2 SD, or a GMDS-R global quotient score of <2 SD. Perinatal risk factors for severe functional disability were assessed through multivariate logistic regression analysis. Results: Among 502 VLBW survivors who completed the 24-month follow-up, 48 (9.6%) presented severe functional disability, of whom 27 had cerebral palsy (5.4%). Rates of severe functional disability and cerebral palsy were higher in neonates with a lower gestational age (p < 0.001). Overall, 147 infants (29.3%) were referred to neuromotor intervention. In the multivariate regression model, gestational age at birth OR 0.79; 95% CI 0.67-0.90; p = 0.001) and periventricular-intraventricular hemorrhage (OR 2.51; 95% CI 1.19-5.26; p = 0.015) were significantly associated with severe functional disability. Conclusion: Neuroprem 2 provides updated information on the neurodevelopmental outcomes of VLBW infants in a large Italian cohort. The overall rate of neurodevelopmental disabilities was quite lower than reported in the previous literature. These data indicate the need for structured follow-up programs from a national neonatal network perspective.

The ontogeny of limbs movements towards midline in healthy infants born at term.

BACKGROUND: Movements towards midline are part of the age-adequate motor repertoire of infants. They develop contemporaneously to general movements, changing from occasional simple contact to proper midline motor patterns. AIM: The aim of this study is to describe the ontogeny of movements towards midline in full term healthy infants. STUDY DESIGN: Parents were asked to record their infant every second week, from term age to 22 weeks post-term. SUBJECTS: 25 healthy full-term infants. RESULTS: Three main epochs of development were detected: in the first one, between birth and 4 weeks post-term, movements towards midline were occasional, apparently due to the dominant flexed posture of elbow and knees and the adducted posture of shoulders and hips. In the second epoch, from 4 to 8 weeks, the limbs movements towards midline markedly decreased. In the third one, after 8 weeks, movements towards midline increased again in frequency, first appearing in lower limbs then in upper limbs, first solely as contact and thereafter as manipulation. A temporal overlapping with the occurrence of intermittent or continual fidgety movements was detected. CONCLUSIONS: Movements towards midline progressively change, through a defined timeline, in full term healthy infants. The increased knowledge about the normal age-adequate motor repertoire can help physicians in clinical assessment of high risk infants.

Foot-to-Foot Contact Among Initial Goal-Directed Movements Supports the Prognostic Value of Fidgety Movements in HIE-Cooled Infants.

Background: Few studies conducted to date have observed general movements in infants affected by hypoxic-ischemic encephalopathy (HIE) who underwent therapeutic hypothermia. We investigated whether foot-to-foot contact (FF) could support the predictive value of fidgety movements (FMs) in infants affected by HIE and treated with brain cooling. Methods: Spontaneous motility was video recorded for 3-5 min at 12 weeks post-term age in 58 full-term newborn infants affected by perinatal asphyxia who were cooled due to moderate to severe HIE. FF and FMs were blindly scored by three independent observers. At 24 months, each patient underwent a neurological examination by Amiel-Tison and Grenier. Results: At 24 months, 47 infants had developed typically at neurological examination, eight had developed mild motor impairment, and three developed cerebral palsy (CP). At 12 weeks, 34 (58.6%) infants had shown normal FMs, four of whom developed mild motor impairment. Twenty-four infants (41.4%) exhibited abnormal or no FMs, four of whom developed mild motor impairment and three developed CP. FF was present in 20 infants (34.5%), two of whom developed mild motor impairment. FF was absent in 38 infants (65.5%), six of whom developed mild motor impairment and three developed CP. Both FMs and FF, considered separately, were 100% sensitive for predicting CP at 24 months, but only 61 and 36%, respectively, were specific. Summing the two patterns together, the specificity increases to 73%, considering only CP as an abnormal outcome, and increases to 74% when considering CP plus mild motor impairment. Unexpectedly, fidgety movements were absent in 24 infants with typical motor outcomes, 17 of whom showed a typical motor outcome. Conclusions: FF is already part of motor repertoire at 12 weeks and allows a comparison of spontaneous non-voluntary movements (FMs) to pre-voluntary movements (FF). FF supports FMs for both sensitivity and specificity. A second video recording at 16-18 weeks, when pedipulation is present in healthy infants, is suggested: it may better define the presence or absence of goal-directed motility.

Endocrine-Disrupting Chemicals and Their Effects during Female Puberty: A Review of Current Evidence.

Puberty is the process of physical changes between childhood and adulthood during which adolescents reach sexual maturity and become capable of reproduction. It is considered one of the main temporal windows of susceptibility for the influence of the endocrine-disrupting chemicals (EDCs). EDCs may act as single chemical agents or as chemical mixtures; they can be pubertal influencers, accelerating and anticipating the processing of maturation of secondary sexual characteristics. Moreover, recent studies have started to point out how exposure to EDCs during puberty may predispose to breast cancer later in life. In fact, the estrogen-mimicking endocrine disruptors (EEDs) may influence breast tissue development during puberty in two main ways: the first is the action on the proliferation of the breast stromal cells, the second concerns epigenetic mechanisms. The aim of this mini-review was to better highlight what is new and what is not completely known regarding the role of EDCs during puberty.

Neuroprem: the Neuro-developmental outcome of very low birth weight infants in an Italian region.

INTRODUCTION: The survival of preterm babies has increased worldwide, but the risk of neuro-developmental disabilities remains high, which is of concern to both the public and professionals. The early identification of children at risk of neuro-developmental disabilities may increase access to intervention, potentially influencing the outcome. AIMS: Neuroprem is an area-based prospective cohort study on the neuro-developmental outcome of very low birth weight (VLBW) infants that aims to define severe functional disability at 2 years of age. METHODS: Surviving VLBW infants from an Italian network of 7 neonatal intensive care units (NICUs) were assessed for 24 months through the Griffiths Mental Developmental Scales (GMDS-R) or the Bayley Scales of Infant and Toddler Development (BSDI III) and neuro-functional evaluation according to the International Classification of Disability and Health (ICF-CY). The primary outcome measure was severe functional disability at 2 years of age, defined as cerebral palsy, a BSDI III cognitive composite score < 2 standard deviation (SD) or a GMDS-R global quotients score < 2 SD, bilateral blindness or deafness. RESULTS: Among 211 surviving VLBW infants, 153 completed follow-up at 24 months (72.5%). Thirteen patients (8.5%) developed a severe functional disability, of whom 7 presented with cerebral palsy (overall rate of 4.5%). Patients with cerebral palsy were all classified with ICF-CY scores of 3 or 4. BSDI III composite scores and GMDS-R subscales were significantly correlated with ICF-CY scores (p < 0.01). CONCLUSION: Neuroprem represents an Italian network of NICUs aiming to work together to ensure preterm neuro-developmental assessment. This study updates information on VLBW outcomes in an Italian region, showing a rate of cerebral palsy and major developmental disabilities in line with or even lower than those of similar international studies. Therefore, Neuroprem provides encouraging data on VLBW neurological outcomes and supports the implementation of a preterm follow-up programme from a national network perspective.

Cerebral Palsy: Early Markers of Clinical Phenotype and Functional Outcome.

The Prechtl General Movement Assessment (GMA) has become a cornerstone assessment in early identification of cerebral palsy (CP), particularly during the fidgety movement period at 3-5 months of age. Additionally, assessment of motor repertoire, such as antigravity movements and postural patterns, which form the Motor Optimality Score (MOS), may provide insight into an infant's later motor function. This study aimed to identify early specific markers for ambulation, gross motor function (using the Gross Motor Function Classification System, GMFCS), topography (unilateral, bilateral), and type (spastic, dyskinetic, ataxic, and hypotonic) of CP in a large worldwide cohort of 468 infants. We found that 95% of children with CP did not have fidgety movements, with 100% having non-optimal MOS. GMFCS level was strongly correlated to MOS. An MOS > 14 was most likely associated with GMFCS outcomes I or II, whereas GMFCS outcomes IV or V were hardly ever associated with an MOS > 8. A number of different movement patterns were associated with more severe functional impairment (GMFCS III-V), including atypical arching and persistent cramped-synchronized movements. Asymmetrical segmental movements were strongly associated with unilateral CP. Circular arm movements were associated with dyskinetic CP. This study demonstrated that use of the MOS contributes to understanding later CP prognosis, including early markers for type and severity.

Motor and Postural Patterns Concomitant with General Movements Are Associated with Cerebral Palsy at Term and Fidgety Age in Preterm Infants.

General movements (GMs) in combination with neurological examination and magnetic resonance imaging at term age can accurately determine the risk of cerebral palsy. The present study aimed to assess whether 11 motor and postural patterns concomitant with GMs were associated with cerebral palsy. Video recordings performed after birth in 79 preterm infants were reviewed retrospectively. Thirty-seven infants developed cerebral palsy at 2 years corrected age and the remaining 42 showed typical development. GMs were assessed from preterm to fidgety age and GM trajectories were defined. The 11 motor and postural patterns were evaluated at each age and longitudinally, alone and in combination with GM trajectories. A logistic regression model was used to assess the association between GMs, concomitant motor and postural patterns, and cerebral palsy. We confirmed that high-risk GM trajectories were associated with cerebral palsy (odds ratio = 44.40, 95% confidence interval = 11.74-167.85). An association between concomitant motor and postural patterns and cerebral palsy was found for some of the patterns at term age and for all of them at fidgety age. Therefore, at term age, concomitant motor and postural patterns can support GMs for the early diagnosis of cerebral palsy.

Shifting of the body center of gravity in low-risk preterm infants: A video-pedoscope study.

AIM: To evaluate whether there is any developmental course of the shifting of the center of gravity (COG) in healthy preterm infants. METHODS: Eleven healthy preterm infants were assessed on a computerized pedoscope from early preterm to term age. Data from the pedoscope and the videorecorder were analyzed with a special software for the assessment of the COG shifting. Infants were placed on the pedoscope in supine position for 5 min. We scored the positions of the COG during its shifting, the body parts most frequently involved in its shifting and the shifting' amplitude at each epoch. We scored the frequency of the COG shifting in head, trunk and bottom, its direction and amplitude using a semi-quantitative scale. RESULTS: A developmental course of the COG shifting from preterm throughout post-term ages was demonstrated, with COG position displaced from head to bottom. The shifting amplitude decreased with increasing age. Lateral shifting were never observed. INTERPRETATION: The developmental course of the COG shifting suggests the maturation of postural behaviour in healthy preterm infants. The displacement of the COG from head to bottom and the reduced amplitude of the COG shifting from preterm to post-term age indicates a more stable body position.

Validity of the General Movement Optimality List in Infants Born Preterm.

PURPOSE: To examine concurrent and predictive validity of the optimality list "Detailed Assessment of General Movements (GMs) During Preterm and Term Age." METHODS: Video clips of general movements were analyzed for 20 infants born preterm without severe brain lesions. Concurrent validity of the optimality list compared with the General Movement Assessment (GMA) was examined. The General Movement Optimality Scores (GMOSs) between infants with normal and poor repertoire GMA were examined. Estimates of diagnostic accuracy were calculated. RESULTS: The GMOS correlated with the GMA and differed between infants with normal and poor repertoire GMA. The area under the curve was below 0.53 with respect to normal or abnormal general movements at 3 months' corrected age. CONCLUSIONS: Concurrent validity of the optimality list was moderate to high compared with the GMA, but its predictive validity for general movements at 3 months' corrected age was low.