Effect of an early music intervention on emotional and neurodevelopmental outcomes of preterm infants at 12 and 24 months.

Background: Few studies have found long-term effects of early musical environmental enrichment in the NICU on preterm infant's development. This study examines how early music enrichment affects emotional development and effortful control abilities in 12- and 24-month-old very preterm (VPT) infants. Methods: One hundred nineteen newborns were recruited, including 83 VPTs and 36 full-term (FT) infants. The VPT infants were randomly assigned to the music intervention (44 VPT-Music) or control (39 VPT-control) groups. VPT-Music infants listened specifically designed music intervention from the 33rd week of gestation until hospital discharge. At 12 and 24 months, children were clinically evaluated using the Bayley-III Scales of Infant and Toddler Development and the Laboratory Temperament Assessment Battery, and at 24 months, with 3 additional episodes of the Effortful Control Battery. Results and discussion: Our analysis showed that during a fear eliciting task, the VPT-Music group expressed lower level of fear reactivity and higher positive motor actions than VPT-controls and FT infants. At 24 months, the VPT-music group had lower scores for negative motor actions in the joy task, compared to both VPT-control and FT groups. In addition, both FT and VPT-music had higher scores of sustained attention compared to VPT-controls, but the contrasts were not significant. No significant effects on mental, language and motor outcomes were identified and for all three dimensions of the ECBQ. Conclusion: The present study suggests that an early music intervention in the NICU might influence preterm children's emotional processing at 12 and 24 months. Limitations and suggestions for future research are highlighted.

Newborn's neural representation of instrumental and vocal music as revealed by fMRI: A dynamic effective brain connectivity study.

Music is ubiquitous, both in its instrumental and vocal forms. While speech perception at birth has been at the core of an extensive corpus of research, the origins of the ability to discriminate instrumental or vocal melodies is still not well investigated. In previous studies comparing vocal and musical perception, the vocal stimuli were mainly related to speaking, including language, and not to the non-language singing voice. In the present study, to better compare a melodic instrumental line with the voice, we used singing as a comparison stimulus, to reduce the dissimilarities between the two stimuli as much as possible, separating language perception from vocal musical perception. In the present study, 45 newborns were scanned, 10 full-term born infants and 35 preterm infants at term-equivalent age (mean gestational age at test = 40.17 weeks, SD = 0.44) using functional magnetic resonance imaging while listening to five melodies played by a musical instrument (flute) or sung by a female voice. To examine the dynamic task-based effective connectivity, we employed a psychophysiological interaction of co-activation patterns (PPI-CAPs) analysis, using the auditory cortices as seed region, to investigate moment-to-moment changes in task-driven modulation of cortical activity during an fMRI task. Our findings reveal condition-specific, dynamically occurring patterns of co-activation (PPI-CAPs). During the vocal condition, the auditory cortex co-activates with the sensorimotor and salience networks, while during the instrumental condition, it co-activates with the visual cortex and the superior frontal cortex. Our results show that the vocal stimulus elicits sensorimotor aspects of the auditory perception and is processed as a more salient stimulus while the instrumental condition activated higher-order cognitive and visuo-spatial networks. Common neural signatures for both auditory stimuli were found in the precuneus and posterior cingulate gyrus. Finally, this study adds knowledge on the dynamic brain connectivity underlying the newborns capability of early and specialized auditory processing, highlighting the relevance of dynamic approaches to study brain function in newborn populations.

Perinatal arterial ischemic stroke: how informative is the placenta?

Neuroplacentology is an expanding field of interest that addresses the placental influence on fetal and neonatal brain lesions and on further neurodevelopment. The objective of this study was to clarify the link between placental pathology and perinatal arterial ischemic stroke (PAIS). Prior publications have reported different types of perinatal stroke with diverse methodologies precluding firm conclusions. We report here the histological placental findings in a series of 16 neonates with radiologically confirmed PAIS. Findings were grouped into 3 categories of lesions: (1) inflammation, (2) placental and fetal hypoxic lesions, and (3) placentas with a high birthweight/placenta weight ratio. Matched control placentas were compared to the pathological placentas when feasible. The eight term singleton placentas were compared to a series of 20 placentas from a highly controlled amniotic membrane donation program; in three twin pregnancies, the placental portions from the affected twin and unaffected co-twin were compared. Slightly more than half (9/16, 56%) had histopathological features belonging to more than one category, a feature shared by the singleton control placentas (13/20, 65%). More severe and extensive lesions were however observed in the pathological placentas. One case occurring in the context of SARS-CoV-2 placentitis further expands the spectrum of COVID-related perinatal disease. Our study supports the assumption that PAIS can result from various combinations and interplay of maternal and fetal factors and confirms the value of placenta examination. Yet, placental findings must be interpreted with caution given their prevalence in well-designed controls.

Newborn phosphocalcic metabolism after intravenous iron administration during pregnancy.

OBJECTIVE: Iron deficiency anemia is a very common health problem during pregnancy and intravenous (IV) iron substitution has become part of routine management. However, recent studies have raised concerns about the association of IV iron infusion and the development of secondary transitory hypophosphatemia (HP) in adults, including pregnant women. We aimed to evaluate the impact of IV iron administration during pregnancy on the phosphocalcic metabolism of newborns. METHODS: A prospective, single-center, observational study was performed from December 2022 to May 2023 at the maternity facility of Geneva University Hospitals. We included women treated with either IV or oral iron during pregnancy. At delivery, a maternal blood sample was collected to assess hemoglobin, hematocrit, and levels of ferritin, phosphate and calcium, as well as an umbilical cord blood sample to assess levels of phosphate and calcium. Univariate and multivariate analyses were performed to evaluate the contribution of IV iron substitution on cord blood phosphatemia and calcemia, considering potential confounding factors. Neonatal HP was defined as a phosphate level <1.3 mmol/L. RESULTS: Forty-three pregnant women were included in our study. Among these, 22 were treated with ferric carboxymaltose and 21 with oral iron. There were three cases of maternal HP in the IV iron group (13.6%) and one (4.8%) in the control group (p value for the difference= .607). We observed one case (4.5%) of neonatal HP in the IV iron group and no cases in the control group. Median cord blood phosphatemia and calcemia were 1.7 mmol/L vs. 1.71 mmol/L and 2.67 mmol/L vs. 2.64 mmol/L in the IV iron and oral groups, respectively. After adjustment, IV iron administration had no impact on cord blood phosphate (p= .919) and calcium (p= .891) levels. CONCLUSION: No impact of IV iron administration during pregnancy was observed on the newborn phosphocalcic metabolism.

Music impacts brain cortical microstructural maturation in very preterm infants: A longitudinal diffusion MR imaging study.

Preterm birth disrupts important neurodevelopmental processes occurring from mid-fetal to term-age. Musicotherapy, by enriching infants' sensory input, might enhance brain maturation during this critical period of activity-dependent plasticity. To study the impact of music on preterm infants' brain structural changes, we recruited 54 very preterm infants randomized to receive or not a daily music intervention, that have undergone a longitudinal multi-shell diffusion MRI acquisition, before the intervention (at 33 weeks' gestational age) and after it (at term-equivalent-age). Using whole-brain fixel-based (FBA) and NODDI analysis (n = 40), we showed a longitudinal increase of fiber cross-section (FC) and fiber density (FD) in all major cerebral white matter fibers. Regarding cortical grey matter, FD decreased while FC and orientation dispersion index (ODI) increased, reflecting intracortical multidirectional complexification and intracortical myelination. The music intervention resulted in a significantly higher longitudinal increase of FC and ODI in cortical paralimbic regions, namely the insulo-orbito-temporopolar complex, precuneus/posterior cingulate gyrus, as well as the auditory association cortex. Our results support a longitudinal early brain macro and microstructural maturation of white and cortical grey matter in preterm infants. The music intervention led to an increased intracortical complexity in regions important for socio-emotional development, known to be impaired in preterm infants.

Parents' Views with Music Therapy in the Pediatric Intensive Care Unit: A Retrospective Cohort Study.

PURPOSE: Music therapy intervention (MT) could be used as an adjunctive therapy in PICU for anxiety and pain management. The aim of the study was to examine the perception of MT by children's parents in a PICU of a tertiary care teaching hospital. METHODS: This is a retrospective cohort study summarizing the results of an institutional quality improvement initiative. Questionnaires were distributed to parents whose children were exposed to MT. RESULTS: From April 2019 to July 2021, 263 patients received a total of 603 h of MT. Twenty-five questionnaires were distributed to parents over a 4-month period (February-June 2021). A total of 19 (76%) parents completed the questionnaire. The majority of parents thought that MT helped their child to communicate (89%), feel less isolated (100%) and cope with stress during hospitalization (100%). The majority of parents also thought that MT contributed to physical recovery (90%) and alleviated feelings of anxiety (90%). Parents also believed that MT should be offered as an out-patient service. CONCLUSIONS: Our study agrees with other studies on the positive potentials of MT in PICU. Music therapy intervention could be used to promote children's and parents' psychological well-being. Further studies are warranted to evaluate the impact of MT on long-term post-ICU outcomes.

Early arterial pressure monitoring and term-equivalent age MRI findings in very preterm infants.

INTRODUCTION: Variability of arterial blood pressure (ABP) has been associated with intraventricular hemorrhage in very preterm neonates (VPT) and may predict other brain lesions assessed at term-equivalent of age (TEA). METHODS: This was a prospective single-center study including VPT with early invasive continuous ABP monitoring and assessed at TEA using brain magnetic resonance imaging (TEA-MRI). The association between early mean ABP (MABP) and TEA-MRI findings was modeled by multivariate logistic regression analysis using covariates selected by the LASSO method. RESULTS: Among 99 VPT, the LASSO procedure selected consecutive periods of lowest MABP of 30 min on day 1 (d1) and 10 min on day 2 (d2) as the most relevant durations to predict TEA-MRI findings (OR [95% CI], 1.11 [1.02-1.23], p = 0.03 and 1.13 [1.01-1.27], p = 0.03, respectively). ROC curve analysis showed optimal thresholds at 30.25 mmHg on d1 and 33.25 mmHg on d2. This significant association persisted after adjustment with covariates including birthweight, gestational age, sex, and inotrope exposure. Final models selected by LASSO included the decile of the birthweight and lowest MABP for 30 min on d1 and 10 min on d2, for which the areas under the ROC curve were 74% and 75%, respectively. CONCLUSION: Early continuous ABP monitoring may predict brain TEA-MRI findings in VPT. IMPACT: Early arterial blood pressure monitoring may contribute to predicting brain damage upon MRI at term-equivalent of age for infants born very preterm. Careful blood pressure continuous monitoring in very preterm infants may identify infants at risk of long-term brain damage. Umbilical artery catheterization provides the best option for continuously monitoring arterial blood pressure in very preterm infants.

Maternal Stress, Depression, and Attachment in the Neonatal Intensive Care Unit Before and During the COVID Pandemic: An Exploratory Study.

The main aim of the present study was to investigate the effects of the COVID-19 pandemic on the mothers' postnatal depression, stress, and attachment during their stay in the Neonatal Intensive Care Unit (NICU). Twenty mothers of very premature infants born before 32weeks of gestational age were recruited at the Geneva University Hospital between January 2018 and February 2020 before the COVID-19 pandemic started. Mothers were screened for postnatal depression after their preterm infant's birth (Edinburgh Postnatal Depression Scale, EPDS), then for stress (Parental Stressor Scale: Neonatal Intensive Care Unit, PSS:NICU), and attachment (Maternal Postnatal Attachment Scale, MPAS) at infant's term-equivalent age. Data were compared with 14 mothers recruited between November 2020 and June 2021 during the COVID-19 pandemic. No significant differences were found in the scores for depression, stress, and attachment between the two groups. However, a non-statistically significant trend showed a general increase of depression symptoms in mothers during the COVID-19 pandemic, which significantly correlated to the attachment and stress scores. Moreover, the PSS:NICU Sights and Sounds score was significantly positively correlated with EPDS scores and negatively with the MPAS score only in the During-COVID group. To conclude, we discussed a possible dampened effect of the several protective family-based actions that have been adopted in the Geneva University Hospital during the health crisis, and we discussed the most appropriate interventions to support parents in this traumatic period during the COVID-19 pandemic.

Post-Burn Infantile Hemangioma in an Extremely Premature Neonate.

Infantile hemangioma (IH) is the most common vascular tumor in infancy, and its physiopathology is not fully understood. Nevertheless, a hypoxic insult may be an essential element for the formation of an IH. Herein, we describe a case of a 25-week premature newborn who developed an IH after a post-burn scar and its evolution.