Camilla Pisoni

Objectives: The aim of the study is to describe the neurodevelopmental profile at 24 months of corrected age (CA) measured by Griffiths’ Developmental Scale of a cohort of extremely low birth weight preterm infants born and admitted to an Italian single tertiary care center from 2005 to 2015. Content: Methods: All consecutive infants born with a birth weight of <1,000 g and admitted within 6 hours from birth to the neonatal intensive care unit (NICU) of the “Fondazione IRCCS Policlinico San Matteo” hospital in Pavia from January 1, 2005, to December 31, 2015, were enrolled. All patients with congenital malformations and/or genetic disorders were excluded. Obstetric and neonatological data were collected. Ultrasound scans’ findings at 40 weeks of gestational age were summarized and classified according to Rademaker. Each patient was examined at term age by a child neuropsychiatrist unaware of the U.S. findings and neonatal neurological examination according to the Amiel-Tison was performed. At 24 months of CA, every patient underwent neurological examination and Griffiths’ Developmental Scale obtaining scores for general quotient (GQ) and for five subscales (locomotor, personal–social, hearing and speech, eye and hand coordination, and performance). Results: Griffiths’ Developmental Scale scores were available for 174 of 176 patients enrolled. The median GQ was 95.98 (25th: 88, 75th: 106). The median scores obtained on the subscales were the following: locomotor, 98.05 (25th: 88, 75th: 108); personal–social, 99.28 (25th: 90, 75th: 111); hearing speech, 89.65 (25th: 77, 75th: 103); eye–hand coordination, 97.37 (25th: 92, 75th: 105); and performance 97.13 (25th: 85, 75th: 107). A statistically significant difference between the median score obtained on the hearing-speech subscale and on all the other subscales emerged (p < 0.001). Statistical significance persisted after restriction of the analysis to the children with GQ within the normal range, to children with a birth weight of ≤500 g and to children with a gestational age of ≤24 weeks of gestation. Conclusion: Preterm infants performed significantly lower on language assessment compared with term peers but also scored lower on measures of general cognitive functions. This study confirmed a peculiar developmental profile in preterm infants characterized by a selective deficit in language domain that is maintained regardless GQ, birth weight, and gestational age. Further investigations are needed to understand the pathophysiological mechanisms leading to this selective developmental vulnerability to create early intervention program able to sustain language development in preterm infants. Publication Date: 16 March 2022 (online) © 2022. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Background: SARS-CoV-2 infection can present with a broad clinical spectrum, from asymptomatic to lethal. Different risk factors have been recognized. Socio-economic status and educational level may affect access to the healthcare system and therefore COVID-19 infection outcome. Objectives: The aim of this study was to assess the association between socio-demographic status and educational level and SARS-CoV-2 outcomes, such as hospitalization, ICU admission, need for mechanical ventilation and death, in Argentinean patients with rheumatic diseases from the SAR-COVID Registry. Methods: We performed a cross-sectional study of consecutive adult patients with rheumatic diseases and SARS-CoV-2 infection included in the multicentric Argentinean SAR-COVID Registry. The following variables were included: gender, ethnicity, age, health insurance, educational level (under or over 12 years of education), socio-economic level according to Graffar Scale in high, medium-high, medium, medium-low, low; underlying rheumatic disease, its duration and treatment at the time of infection. SARS-CoV-2 infection outcomes were: hospitalization, admission to ICU, mechanical ventilation requirement and death. Statistical analysis was performed using Chi², Fisher, T-test, ANOVA. Results: Five hundred and twenty-five patients were included, 422 (80.4%) were female, with a mean age of 51.3 years (SD 15.2). Most of them were caucasians (48%) or mestizos (43%) and 96.8% lived in an urban environment. Almost half of the patients (47%) were categorized as middle-class, 24% middle-high or high class, 21% middle-low or low. 48.4% of the patients were employed. Regarding educational level, 54% had more than 12 years of education. The most prevalent rheumatic disease was Rheumatoid Arthritis (40.4%), followed by Systemic Lupus Erythematosus (14.9%), Sjögren (5.5%) and Psoriatic Arthritis (5.5%). Treatments used at the time of SARS-CoV-2 infection were corticosteroids (19%), cs-DMARDs (49%), and b- and ts-DMARDs (16%). Overall hospitalization frequency was 35%, median hospital stay was 10 days (IQR 10 days), 11.6% were admitted to the ICU, 10% required mechanical ventilation and the global mortality was 8%. Notably, patients with less than 12 years of education required mechanical ventilation more frequently than the more educated ones (11.9% vs. 5.6%, p=0.026) and showed a higher mortality due to COVID-19 (9% vs. 2.8%, p=0.0004). Patients categorized as upper social classes (middle-high and high) were admitted to the hospital on a more frequent basis (74.4% of cases), when compared with middle class (64.4%) and middle-low and low class (58%) (p=0.77). Median duration of hospitalization for the aforementioned groups was 12.5 (IQR 17.3), 10 (IQR 9) and 10.5 (IQR 9.3) days respectively (p=0.60). Patients with health insurance were found to be hospitalized more frequently in comparison to those without insurance (42.4% vs. 33.7%, p=0.14), but showed similar admission rates to the ICU (11.8% vs. 12.8%; p=0.78), need for mechanical ventilation (10.7% vs. 8.7%; p=0.70) and mortality (7.1% vs. 6.5%; p=0.99). Caucasian patients had fewer hospital admissions when compared against other ethnicities (mestizos mostly) (26.1% vs. 43.4%; pConclusion: Patients with lower educational level needed twice the frequency of mechanical ventilation, and showed thrice the mortality than those with more than 12 years of education. Albeit patients in upper social stratus and those with health insurance were admitted to the hospital in a more frequent manner, no statistically significant differences were found regarding the need for ICU, mechanical ventilation or mortality. Caucasians were hospitalized less frequently than mestizos, but had no significant differences in the other measured outcomes. Disclosure of Interests: Laura Sorrentino Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Jonathan Rebak Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Federico Maldonado Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Vanessa Viviana Castro Coello Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Alejandro Brigante Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Adriana Hamaui Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Diana Dubinsky Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Roberto Baez Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Cecilia Pisoni Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Carla Gobbi Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Leandro Carlevaris Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Romina Tanten Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Adriana Karina Cogo Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Maria DeLaVega Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Rodolfo Perez Alamino Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Maria Alicia Lazaro Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Mariana Pera Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Susana Isabel Pineda Vidal Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Maria Elena Calvo Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Debora Guaglianone Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Carla G Alonso Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Mara Guinsburg Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Cinthya Retamozo Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Carolina Aeschlimann Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Rosana Quintana Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Karen Roberts Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Carolina Ayelen Isnardi Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data., Guillermo Pons Estel Grant/research support from: Unrestricted grants: Pfizer, Abbvie, Elea Phoenix. None of them have access to patient data.

Background: Prevention of neurodevelopmental impairment due to preterm birth is a major health challenge. Despite advanced obstetric and neonatal care, to date there are few neuroprotective molecules available. Melatonin has been shown to have anti-oxidant/anti-inflammatory effects and to reduce brain damage, mainly after hypoxic ischemic encephalopathy. The planned study will be the first aiming to evaluate the capacity of melatonin to mitigate brain impairment due to premature birth. Method: In our planned prospective, multicenter, double-blind, randomized vs placebo study, we will recruit, within 96 h of birth, 60 preterm newborns with a gestational age ≤ 29 weeks + 6 days; these infants will be randomly allocated to oral melatonin, 3 mg/kg/day, or placebo for 15 days. After the administration period, we will measure plasma levels of malondialdehyde, a lipid peroxidation product considered an early biological marker of melatonin treatment efficacy (primary outcome). At term-equivalent age, we will evaluate neurological status (through cerebral ultrasound, cerebral magnetic resonance imaging, vision and hearing evaluations, clinical neurological assessment, and screening for retinopathy of prematurity) as well as the incidence of bronchodysplasia and sepsis. We will also monitor neurodevelopmental outcome during the first 24 months of corrected age (using the modified Fagan Test of Infant Intelligence at 4–6 months and standardized neurological and developmental assessments at 24 months). Discussion: Preterm birth survivors often present long-term neurodevelopmental sequelae, such as motor, learning, social-behavioral, and communication problems. We aim to assess the role of melatonin as a neuroprotectant during the first weeks of extrauterine life, when preterm infants are unable to produce it spontaneously. This approach is based on the supposition that its anti-oxidant mechanism could be useful in preventing neurodevelopmental impairment. Considering the short- and long-term morbidities related to preterm birth, and the financial and social costs of the care of preterm infants, both at birth and over time, we suggest that melatonin administration could lead to considerable saving of resources. This would be the first study addressing the role of melatonin in very low birth weight preterm newborns, and it could provide a basis for further studies on melatonin as a neuroprotection strategy in this vulnerable population. Trial registration: ClinicalTrials.gov NCT04235673. Prospectively registered on 22 January 2020.

Aim: Although parenting is key to promoting healthy development of at‐risk preterm infants, parents have often restricted access to neonatal intensive care units (NICUs). This study aimed to assess the effect of an early parenting intervention on the psychomotor outcome in preterm children at 24 months of corrected age.Methods: Forty‐two preterm children and their parents were consecutively recruited at a level III NICU in Northern Italy and randomly allocated to early intervention (two educational peer‐group sessions and four individual infant observation sessions) or care as usual (no educational or infant observation sessions). During NICU stay, parents provided information on daily holding and skin‐to‐skin. Psychomotor development was measured at 24 months of corrected age using the Griffith Mental Development Scales.Results: There were no significant differences in socio‐demographic and clinical variables between early intervention (n = 21; 13 females) and care as usual (n = 21; 12 females) groups. At 24 months of corrected age, children in the early intervention arm had greater scores for global psychomotor development as well as for Hearing‐Speech and Personal‐Social sub‐scales, compared to those in the care as usual group.Conclusion: The present NICU parenting intervention was found to be associated with better psychomotor outcomes in preterm children at 24‐month age. The effects were especially evident for domains related to language and socio‐emotional functioning. Results are promising and should be retested with more heterogeneous and representative preterm sample.

Objective Little is known about the process of becoming a mother in women who experienced a breast cancer diagnosis (BC). In this qualitative study, we investigated maternal representations in pregnant women with experience of BC and those with no oncological history. Methods A total of 38 women were recruited, 19 women who experienced a BC diagnosis and 19 who had not. To explore maternal representations, semi‐structured interviews were conducted and analysed through thematic analysis. Results Four main themes were identified: fears and worries, meaning of motherhood, mother–foetus relationship and partner support. Across themes, differences between primiparous and multiparous are reported. Women with gestational breast cancer (GBC) described fear for their own and their child's survival. Women with previous BC recall contrasting emotions. All women with experience of BC perceived breastfeeding as fundamental and inability to do so provoked worry. Relationship with the partner was considered central, while healthy women were projected towards the future triadic relationship. Conclusions Finding a mental space during pregnancy for the representation of the future child could be hard for women with GBC. Dissimilarities in the experience of motherhood in cancer patients provide insight into psychological aspects that should be taken into account in clinical practice.

Young cancer survivors often wish to bear a child after oncological treatments, as they might not have started or completed their families. As young cancer survivors have a higher risk of developing psychological difficulties, this study investigated whether there were significant differences in psychological aspects between pregnant women who received a cancer diagnosis in the past and pregnant women without a history of cancer. A total of 123 pregnant women, of which 36 were cancer survivors and 87 women without a history of cancer, were recruited during their last trimester at different hospitals in Northern Italy. Patients were asked to complete a socio-demographic profile and questionnaires measuring mood states, post-traumatic symptoms, centrality of the pregnancy and cancer event, quality of life, and prenatal attachment. Cancer survivors had significantly higher levels of PTSD symptoms, perceived pregnancy as more central to their identity and life story, perceived lower quality of life and had lower intensity of prenatal attachment compared with the control group. Centrality of the cancer event did not correlate with any psychological variables. Preliminary results suggest that a past cancer diagnosis can influence the mother’s psychological functioning and the development of the relationship with their child.

Background: The literature shows that parents of preterm infants are at risk of psychological distress and that this may impact on the quality of the parent–child relationship and on the child’s development. Aim: This longitudinal study was conducted to examine in preterm infants relationships between maternal psychological variables, parental protective factors, perinatal infant variables, and neurodevelopmental outcome. Furthermore, we explored the impact of these variables on the quality of the mother–infant relationship (dyadic synchrony). Subjects and methods: A total of 29 preterm infants (GA < 34 weeks) and their mothers were evaluated twice: at t₀, during the infant’s hospitalization in the neonatal intensive care unit (NICU), and at 12 months of infant corrected age (t2). Results: With the exception of decreases in anxiety and perceived social support and an increase in the rate of severe depression at follow-up, there were no significant changes between t₀ and t₁ assessments. The infant’s perinatal risk status was the variable that impacted most on maternal psychopathology. Furthermore, our data revealed that baseline maternal stress related to the appearance of the child and to the mother’s perception of her parenting role represent a risk factor in relation to developmental outcome at 12 months of corrected age. Finally, no correlations emerged between dyadic synchrony and infant perinatal data, maternal psychological variables (at t₀ and at t₁), or child developmental outcome at t₁. Conclusions: Our results underline the need to identify negative maternal affective states early in the mother–child relationship and to provide mothers with adequate support in the NICU, to enhance their parental role.

Introduction From the prognostic perspective, the quality of the mother–child relationship during the first months of life has been variously associated with different factors such as the child's psychomotor/cognitive development and emotional–behavioral disorders. Methods The main aim of this study was to describe, at term age and 3 months of corrected age, the features and the prevalent patterns of the mother–child relationship in a group of 20 mother–preterm infant dyads and to compare them with those of a group of 20 mother–term infant dyads. Results A relatively high rate of inadequate dyadic synchrony was found in our sample of preterms at 40 weeks of gestational age (half of the sample analyzed). The quality of the dyadic relationship and the prevalent patterns of the mother–child relationship were found to differ between the two groups we studied; moreover, the subjects at risk of relational problems remained substantially the same during the first 3 months of life. Discussion These data underline that in preterm children, the first weeks of life, coinciding with their hospitalization, represent a crucial time for establishing a valid dyadic relationship and for considering and planning any preventive interventions; after all, the earlier the risk of relational problems becomes a real possibility, the more likely it is to negatively impact on a child's overall development.