Myriam Bickle Graz

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.

Gentamicin Exposure and Sensorineural Hearing Loss in Preterm Infants

Objective To evaluate the impact of gentamicin exposure on sensorineural hearing loss (SNHL) in very low birth weight (VLBW) infants. Methods Exposure to gentamicin was determined in infants born between 1993 and 2010 at a gestational age < 32 weeks and/or with a birthweight < 1500 g, who presented with SNHL during the first 5 years of life. For each case, we selected two controls matched for gender, gestational age, birthweight, and year of birth. Results We identified 25 infants affected by SNHL, leading to an incidence of SNHL of 1.58% in our population of VLBW infants. The proportion of infants treated with gentamicin was 76% in the study group and 70% in controls (p = 0.78). The total cumulated dose of gentamicin administered did not differ between the study group (median 10.2 mg/kg, Q1-Q3 1.6–13.2) and the control group (median 7.9 mg/kg, Q1-Q3 0–12.8, p = 0.47). The median duration of gentamicin treatment was 3 days both in the study group and the control group (p = 0.58). Maximum predicted trough serum levels of gentamicin, cumulative area under the curve and gentamicin clearance were not different between cases and controls. Conclusion The impact of gentamicin on SNHL can be minimized with treatments of short duration, monitoring of blood levels and dose adjustment.

Being Small for Gestational Age: Does it Matter for the Neurodevelopment of Premature Infants? A Cohort Study

Background Whether being small for gestational age (SGA) increases the risk of adverse neurodevelopmental outcome in premature infants remains controversial. Objective to study the impact of SGA (birthweight < percentile 10) on cognition, behavior, neurodevelopmental impairment and use of therapy at 5 years old. Methods This population-based prospective cohort included infants born before 32 weeks of gestation. Cognition was evaluated with the K-ABC, and behavior with the Strengths and Difficulties Questionnaire (SDQ). Primary outcomes were cognitive and behavioral scores, as well as neurodevelopmental impairment (cognitive score < 2SD, hearing loss, blindness, or cerebral palsy). The need of therapy, an indirect indicator of neurodevelopmental impairment, was a secondary outcome. Linear and logistic regression models were used to analyze the association of SGA with neurodevelopment. Results 342/515 (76%) premature infants were assessed. SGA was significantly associated with hyperactivity scores of the SDQ (coefficient 0.81, p < 0.04), but not with cognitive scores, neurodevelopmental impairment or the need of therapy. Gestational age, socio-economic status, and major brain lesions were associated with cognitive outcome in the univariate and multivariate model, whereas asphyxia, sepsis and bronchopulmonary dysplasia were associated in the univariate model only. Severe impairment was associated with fetal tobacco exposition, asphyxia, gestational age and major brain lesions. Different neonatal factors were associated with the use of single or multiple therapies: children with one therapy were more likely to have suffered birth asphyxia or necrotizing enterocolitis, whereas the need for several therapies was predicted by major brain lesions. Discussion In this large cohort of premature infants, assessed at 5 years old with a complete panel of tests, SGA was associated with hyperactive behavior, but not with cognition, neurodevelopmental impairment or use of therapy. Birthweight <10th percentile alone does not appear to be an independent risk factor of neurodevelopmental adverse outcome in preterm children.

Neurodevelopment outcome of newborns with cerebral subependymal pseudocysts at 18 and 46 months: a prospective study

Objectives Subependymal pseudocysts (SEPC) are cerebral periventricular cysts located on the floor of the lateral ventricle and result from regression of the germinal matrix. They are increasingly diagnosed on neonatal cranial ultrasound. While associated pathologies are reported, information about long-term prognosis is missing, and we aimed to investigate long-term follow-up of these patients. Study design Newborns diagnosed with SEPC were enrolled for follow-up. Neurodevelopment outcome was assessed at 6, 18 and 46 months of age. Results 74 newborns were recruited: we found a high rate of antenatal events (63%), premature infants (66% <37 weeks, 31% <32 weeks) and twins (30%). MRI was performed in 31 patients, and cystic periventricular leukomalacia (c-PVL) was primarily falsely diagnosed in 9 of them. Underlying disease was diagnosed in 17 patients, 8 with congenital cytomegalovirus (CMV) infection, 5 with genetic and 4 with metabolic disease. Neurological examination (NE) at birth was normal for patients with SEPCs and no underlying disease, except one. Mean Developmental Quotient and IQ of these patients was 98.2 (±9.6SD; range 77–121), 94.6 (±14.2SD; 71–120) and 99.6 (±12.3SD; 76–120) at 6, 18 and 46 months of age, respectively, with no differences between the subtypes of SEPC. A subset analysis showed no outcome differences between preterm infants with or without SEPC, or between preterm of <32 GA and ≥32 GA. Conclusions Neurodevelopment of newborns with SEPC was normal when no underlying disease was present. This study suggests that if NE is normal at birth and congenital CMV infection can be excluded, then no further investigations are needed. Moreover, it is crucial to differentiate SEPC from c-PVL which carries a poor prognosis.

Comparison of Griffiths-II and Bayley-II tests for the developmental assessment of high-risk infants.

INTRODUCTION Two important risk factors for abnormal neurodevelopment are preterm birth and neonatal hypoxic ischemic encephalopathy. The new revisions of Griffiths Mental Development Scale (Griffiths-II, [1996]) and the Bayley Scales of Infant Development (BSID-II, [1993]) are two of the most frequently used developmental diagnostics tests. The Griffiths-II is divided into five subscales and a global development quotient (QD), and the BSID-II is divided into two scales, the Mental scale (MDI) and the Psychomotor scale (PDI). The main objective of this research was to establish the extent to which developmental diagnoses obtained using the new revisions of these two tests are comparable for a given child. MATERIAL AND METHODS Retrospective study of 18-months-old high-risk children examined with both tests in the follow-up Unit of the Clinic of Neonatology of our tertiary care university Hospital between 2011 and 2012. To determine the concurrent validity of the two tests paired t-tests and Pearson product-moment correlation coefficients were computed. Using the BSID-II as a gold standard, the performance of the Griffiths-II was analyzed with receiver operating curves. RESULTS 61 patients (80.3% preterm, 14.7% neonatal asphyxia) were examined. For the BSID-II the MDI mean was 96.21 (range 67-133) and the PDI mean was 87.72 (range 49-114). For the Griffiths-II, the QD mean was 96.95 (range 60-124), the locomotors subscale mean was 92.57 (range 49-119). The score of the Griffiths locomotors subscale was significantly higher than the PDI (p<0.001). Between the Griffiths-II QD and the BSID-II MDI no significant difference was found, and the area under the curve was 0.93, showing good validity. All correlations were high and significant with a Pearson product-moment correlation coefficient >0.8. CONCLUSIONS The meaning of the results for a given child was the same for the two tests. Two scores were interchangeable, the Griffiths-II QD and the BSID-II MDI.

Nutrient Intake in the First Two Weeks of Life and Brain Growth in Preterm Neonates

In this preterm cohort study, we investigate the relationship between early macronutrient intake and brain macro- and microstructural growth, the influence of neonatal morbidity, and subsequent neurodevelopment. BACKGROUND: Optimizing early nutritional intake in preterm neonates may promote brain health and neurodevelopment through enhanced brain maturation. Our objectives were (1) to determine the association of energy and macronutrient intake in the first 2 weeks of life with regional and total brain growth and white matter (WM) maturation, assessed by 3 serial MRI scans in preterm neonates; (2) to examine how critical illness modifies this association; and (3) to investigate the relationship with neurodevelopmental outcomes. METHODS: Forty-nine preterm neonates (21 boys, median [interquartile range] gestational age: 27.6 [2.3] weeks) were scanned serially at the following median postmenstrual weeks: 29.4, 31.7, and 41. The total brain, basal nuclei, and cerebellum were semiautomatically segmented. Fractional anisotropy was extracted from diffusion tensor imaging data. Nutritional intake from day of life 1 to 14 was monitored and clinical factors were collected. RESULTS: Greater energy and lipid intake predicted increased total brain and basal nuclei volumes over the course of neonatal care to term-equivalent age. Similarly, energy and lipid intake were significantly associated with fractional anisotropy values in selected WM tracts. The association of ventilation duration with smaller brain volumes was attenuated by higher energy intake. Brain growth predicted psychomotor outcome at 18 months’ corrected age. CONCLUSIONS: In preterm neonates, greater energy and enteral feeding during the first 2 weeks of life predicted more robust brain growth and accelerated WM maturation. The long-lasting effect of early nutrition on neurodevelopment may be mediated by enhanced brain growth. Optimizing nutrition in preterm neonates may represent a potential avenue to mitigate the adverse brain health consequences of critical illness.

Emotion, attention, and effortful control in 24-month-old very preterm and full-term children

The literature reports behavioral and socio-emotional problems in children born preterm that persist throughout adolescence and early adulthood. However, no study has simultaneously investigated emotion, attention, and effortful control. In the present study, we compared these abilities between children born very preterm (<29 weeks of gestation) and full-term children at 24 months of age by parental questionnaire and experimental design. Results on the questionnaire showed that very preterm children were rated by parents as having a higher level of negative affect and lower sustained attention than full-term children. Results on the experimental tasks revealed a distinct attention pattern between the two groups: The full-term children showed a peak of attention in the second trial while preterm children exhibited an unchanged level of attention throughout the task. The preterm children also exhibited greater difficulties in maintaining inhibitory control compared with full-term children. Taken together, the results observed in very preterm children clearly showed difficulties in key abilities which allow a voluntary self-regulation behavior and consequently, they should be considered to improve early intervention strategies.

Clinical characteristics, audiological and neurodevelopmental outcomes of newborns with congenital cytomegalovirus infection

BACKGROUND Congenital cytomegalovirus (cCMV) infections are the leading nongenetic cause of congenital sensorineural hearing loss (SNHL); however the true impact of cCMV infections remains unknown. AIMS OF THE STUDY (1) To identify the number of asymptomatic and symptomatic cCMV infections diagnosed between 1999 and 2014 at the Lausanne University Hospital; (2) to describe the audiological and neurodevelopmental outcomes of infants with cCMV infection; and (3) to compare clinical outcomes between infants born to mothers with primary versus nonprimary infection. METHODS This was a single-centre, observational, exploratory, retrospective study of newborns diagnosed with cCMV infection at the Lausanne University Hospital between 1999 and 2014. RESULTS Fifty newborns with cCMV infection were identified; 39 (78%) were symptomatic at birth, of whom 29 (74%) were neurologically symptomatic. Twelve children (24%) presented with subsequent abnormal audiological and/or neurodevelopmental outcomes. Newborns born to mothers with a nonprimary infection were more often symptomatic at birth than those born to mothers with a primary infection. CONCLUSIONS All infants with subsequent SNHL or abnormal neurodevelopment were symptomatic at birth. Similar long-term neurodevelopmental and audiological outcomes were observed in infants born to mothers with a primary and nonprimary infection.

The prospective relationship between postpartum PTSD and child sleep: A 2-year follow-up study

BACKGROUND The main aim of this study was to examine the prospective impact of maternal postpartum PTSD on several standardized child sleep variables two years postpartum in a large, population-based cohort of mothers. Moreover, we investigated the influence of numerous potential confounding maternal and child factors. Finally, we tested potential reverse temporal associations between child sleep eight weeks postpartum and maternal PTSD symptoms two years postpartum. METHODS This study is part of the population-based Akershus Birth Cohort, a prospective cohort study at Akershus University Hospital, Norway. Data from the hospitals birth record, from questionnaires at 17 weeks gestation, eight weeks and two years postpartum were used. At two years postpartum, 39% of the original participants could be retained, resulting in a study population of n = 1480. All child sleep variables significantly correlated with postpartum PTSD symptoms were entered into multiple linear regression analyses, adjusting for confounding factors. RESULTS Postpartum PTSD symptoms were related to all child sleep variables, except daytime sleep duration. When all significant confounding factors were included into multivariate regression analyses, postpartum PTSD symptoms remained a significant predictor for number and duration of night wakings (β = 0.10 and β = 0.08, respectively), duration of settling time (β = 0.10), and maternal rating of their childs sleep problems (β = 0.12, all p<.01. Child sleep at eight weeks postpartum was not significantly related to maternal sleep two years postpartum when controlling for postpartum PTSD at eight weeks. LIMITATIONS Child outcomes were based on maternal reporting and might be influenced by maternal mental health. CONCLUSIONS Our results showed for the first time that maternal postpartum PTSD symptoms were prospectively associated with less favorable child sleep, thus increasing the risk of developmental or behavioral problems through an indirect, but treatable pathway. Early detection and treatment of maternal postpartum PTSD may prevent or improve sleep problems and long-term child development.

PROCEDURAL PAIN AND ORAL GLUCOSE IN PRETERM NEONATES: BRAIN DEVELOPMENT AND SEX-SPECIFIC EFFECTS

Abstract Our objectives were to determine whether procedural pain and glucose exposure are associated with altered structural and functional brain development differently in preterm males and females, and neurodevelopment at 18-month corrected age. Fifty-one very preterm neonates (22 males; median [interquartile range] gestational age 27.6 [2.0] weeks) underwent 3 serial scans including T1-weighted and resting-state functional magnetic resonance imaging (MRI) at median postmenstrual weeks: 29.4, 31.9, and 41.1. Thalamus, basal ganglia, and total brain volumes were segmented. Functional resting-state MRI data were extracted from the independent-components maps. Pain was operationalized as the total number of neonatal intensive care unit–administered invasive procedures. Neurodevelopmental outcomes at 18-month corrected age were assessed with the Bayley Scales of Infant Development, second edition. Generalized estimating equations assessed the association of pain and glucose exposure with brain structural and functional development. More invasive procedures were independently associated with slower growth of thalamic (P < 0.001), basal ganglia (P = 0.028), and total brain volumes (P = 0.001), particularly in females. Similar relationships were observed between glucose exposure and brain volumes. Functional connectivity between thalamus and sensorimotor cortices was negatively associated with number of invasive procedures. Greater procedural pain and higher glucose exposure were related to poorer neurodevelopmental outcomes. These findings suggest that structural and functional brain development is vulnerable to procedural pain. Glucose used for analgesia does not appear to mitigate the adverse impact of pain on brain development. The vulnerability of brain development in females towards early pain is distinct from other neonatal morbidities. The link between pain and glucose with neurodevelopment suggests that these factors have long-lasting impact.