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.

Association of growth with neurodevelopment in extremely low gestational age infants: a population-based analysis.

To assess the association between postnatal growth and neurodevelopment at the age of 2 years in extremely low gestational age newborns (ELGAN, < 28 weeks' gestation). Retrospective population-based cohort study including all live born ELGAN in 2006-2012 in Switzerland. Growth parameters (weight, length, head circumference, body mass index) were assessed at birth, at hospital discharge home, and 2-year follow-up (FU2). Unadjusted and adjusted regression models assessed associations between growth (birth to hospital discharge and birth to FU2) and neurodevelopment at FU2. A total of 1244 infants (mean GA 26.5 ± 1.0 weeks, birth weight 853 ± 189 g) survived to hospital discharge and were included in the analyses. FU2 was documented for 1049 (84.3%) infants. The mean (± SD) mental and a psychomotor development index at 2FU were 88.9 (± 18.0) and 86.9 (± 17.7), respectively. Moderate or severe neurodevelopmental impairment was documented in 23.2% of patients. Changes of z-scores between birth and discharge and between birth and FU2 for weight were - 1.06 (± 0.85) and - 0.140 (± 1.15), for length - 1.36 (± 1.34), and - 0.40 (± 1.33), for head circumference - 0.61 (± 1.04) and - 0.76 (± 1.32) as well as for BMI 0.22 (± 3.36) and - 0.006 (± 1.45). Unadjusted and adjusted analyses showed that none of the four growth parameters was significantly associated with any of the three outcome parameters of neurodevelopment. This was consistent for both time intervals. CONCLUSION: In the present population-based cohort of ELGAN, neither growth between birth and hospital discharge nor between birth and FU2 were significantly associated with neurodevelopment at age of 2 years. WHAT IS KNOWN: • Studies assessing the association between growth and neurodevelopment in extremely low gestational age newborns (28 weeks' gestation) show conflicting results. WHAT IS NEW: • Neither growth between birth and hospital discharge nor between birth and corrected age of 2 years were significantly associated with neurodevelopment at age of 2 years. • The role of postnatal growth as a predictor of neurodevelopmental outcome during infancy might be smaller than previously assumed.

Outcomes for Infants Born in Perinatal Centers Performing Fewer Surgical Ligations for Patent Ductus Arteriosus: A Swiss Population-Based Study.

OBJECTIVE: To assess patent ductus arteriosus treatment variation between Swiss perinatal centers and to determine its effect on outcome in a population-based setting. STUDY DESIGN: This was a retrospective cohort study of infants born less than 28 weeks of gestation between 2012 and 2017. Outcomes between surgically ligated and pharmacologically treated infants as well as infants born in centers performing ≤10% ligation ("low" group) and >10% ("high" group) were compared using logistic regression and 1:1 propensity score matching. Matching was based on case-mix and preligation confounders: intraventricular hemorrhages grades 3-4, necrotizing enterocolitis, sepsis, and ≥28 days' oxygen supply. RESULTS: Of 1389 infants, 722 (52%) had pharmacologic treatment and 156 (11.2%) received surgical ligation. Compared with infants who received pharmacologic treatment, ligated infants had greater odds for major morbidities (OR 2.09, 95% CI 1.44-3.04) and 2-year neurodevelopmental impairment (OR 1.81, 95% CI 1.15-2.84). Mortality was comparable after restricting the cohort to infants surviving at least until day 10 to avoid survival bias. In the "low" group, 34 (4.9%) of 696 infants were ligated compared with 122 (17.6%) of 693 infants in the "high" group. Infants in the "high" group had greater odds for major morbidities (OR 1.49, 95% CI 1.11-2.0). CONCLUSIONS: Our analysis identified a burden on infants receiving surgical ligation vs pharmacologic treatment in a population-based setting where there was no agreed-on common procedure. These results may guide a revision of patent ductus arteriosus treatment practice in Switzerland.

[SSRI antidepressant use during pregnancy and the assessment of the risk-benefit ratio]. / Bon usage des antidépresseurs ISRS durant la grossesse--le défi de l'évaluation de la balance bénéfice-risque.

Studies report that between 6 and 13% of women experience symptoms of depression during pregnancy and the postpartum period. The abundant data available make selective serotonin reuptake inhibitors (SSRIs) the first line treatment in pregnancy when a pharmacological treatment is required. Risks associated with the use of SSRIs during pregnancy are limited (moderate effect size) and are often not distinguishable from those inherent to the mother's disease. Yet, several questions regarding the SSRI safety profile for the unborn child are still under debate or require additional epidemiological data. The decision of SSRI use during pregnancy needs an individual evaluation of the risk-benefit balance.

Emotional and effortful control abilities in 42-month-old very preterm and full-term children.

BACKGROUND: Very preterm (VP) infants are at greater risk for cognitive difficulties that may persist during school-age, adolescence and adulthood. Behavioral assessments report either effortful control (part of executive functions) or emotional reactivity/regulation impairments. AIMS: The aim of this study is to examine whether emotional recognition, reactivity, and regulation, as well as effortful control abilities are impaired in very preterm children at 42 months of age, compared with their full-term peers, and to what extent emotional and effortful control difficulties are linked. STUDY DESIGN: Children born very preterm (VP; < 29 weeks gestational age, n=41) and full-term (FT) aged-matched children (n=47) participated in a series of specific neuropsychological tests assessing their level of emotional understanding, reactivity and regulation, as well as their attentional and effortful control abilities. RESULTS: VP children exhibited higher scores of frustration and fear, and were less accurate in naming facial expressions of emotions than their aged-matched peers. However, VP children and FT children equally performed when asked to choose emotional facial expression in social context, and when we assessed their selective attention skills. VP performed significantly lower than full terms on two tasks of inhibition when correcting for verbal skills. Moreover, significant correlations between cognitive capacities (effortful control) and emotional abilities were evidenced. CONCLUSIONS: Compared to their FT peers, 42 month-olds who were born very preterm are at higher risk of exhibiting specific emotional and effortful control difficulties. The results suggest that these difficulties are linked. Ongoing behavioral and emotional impairments starting at an early age in preterms highlight the need for early interventions based on a better understanding of the relationship between emotional and cognitive difficulties.

Intrauterine growth restriction affects the preterm infant's hippocampus.

The hippocampus is known to be vulnerable to hypoxia, stress, and undernutrition, all likely to be present in fetal intrauterine growth restriction (IUGR). The effect of IUGR in preterm infants on the hippocampus was studied using 3D magnetic resonance imaging at term-equivalent age Thirteen preterm infants born with IUGR after placental insufficiency were compared with 13 infants with normal intrauterine growth age matched for gestational age. The hippocampal structural differences were defined using voxel-based morphometry and manual segmentation. The specific neurobehavioral function was evaluated by the Assessment of Preterm Infants' Behavior at term and at 24 mo of corrected age by a Bayley Scales of Infant and Toddler Development. Voxel-based morphometry detected significant gray matter volume differences in the hippocampus between the two groups. This finding was confirmed by manual segmentation of the hippocampus with a reduction of hippocampal volume after IUGR. The hippocampal volume reduction was further associated with functional behavioral differences at term-equivalent age in all six subdomains of the Assessment of Preterm Infants' Behavior but not at 24 mo of corrected age. We conclude that hippocampal development in IUGR is altered and might result from a combination of maternal corticosteroid hormone exposure, hypoxemia, and micronutrient deficiency.

Early alteration of structural and functional brain development in premature infants born with intrauterine growth restriction.

Placental insufficiency with fetal intrauterine growth restriction (IUGR) is an important cause of perinatal mortality and morbidity and is subsequently associated with significant neurodevelopmental impairment in cognitive function, attention capacity, and school performance. The underlying biologic cause for this association is unclear. Twenty-eight preterm infants (gestational age 32.5 +/- 1.9 wk) were studied by early and term magnetic resonance imaging (MRI). An advanced quantitative volumetric three-dimensional MRI technique was used to measure brain tissue volumes in 14 premature infants with placental insufficiency, defined by abnormal antenatal Doppler measurements and mean birth weights <10(th) percentile (1246 +/- 299 g) (IUGR) and in 14 preterm infants matched for gestational age with normal mean birth weights 1843 +/- 246 g (control). Functional outcome was measured at term in all infants by a specialized assessment scale of preterm infant behavior. Premature infants with IUGR had a significant reduction in intracranial volume (mean +/- SD: 253.7 +/- 29.9 versus 300.5 +/- 43.5 mL, p < 0.01) and in cerebral cortical gray matter (mean +/- SD: 77.2 +/- 16.3 versus 106.8 +/- 24.6 mL, p < 0.01) when measured within the first 2 wk of life compared with control premature infants. These findings persisted at term with intracranial volume (mean +/- SD: 429.3 +/- 47.9 versus 475.9 +/- 53.4 mL, p < 0.05) and cerebral cortical gray matter (mean +/- SD: 149.3 +/- 29.2 versus 189 +/- 34.2 mL, p < 0.01). Behavioral assessment at term showed a significantly less mature score in the subsystem of attention-interaction availability in IUGR infants (p < 0.01). Cerebral cortical gray matter volume at term correlated with attention-interaction capacity measured at term (r = 0.45, p < 0.05). These results suggest that placental insufficiency with IUGR have specific structural and functional consequences on cerebral cortical brain development. These findings may provide insight into the structural-functional correlate for the developmental deficits associated with IUGR.