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MILD PERIVENTRICULAR LEUKOMALACIA DOES NOT PREDICT POOR MOTOR SKILLS IN CHILDREN BORN EXTREMELY PRETERM AT 12 YEARS OF AGE
Background and aim
Neonatal cystic periventricular leukomalacia (PVL) is a strong predictor of future impairments in children born extremely preterm (EPT). Today this condition is rare. However mild PVL is a common finding and little is known about if it persists and affects the motor performance in children born EPT at school-age.
Our aim was to investigate the relationship between mild PVL changes on MRI and white matter volume, motor performance, visual-motor integration and minor neurological dysfunction (MND) in children born EPT at 12y.
MRI was performed in 67 children born EPT at age 9-11y. Mild PVL was defined as an abnormally high signal intensity in the periventricular white matter. DTI was done and analyzed by TBSS. Brain volumes were calculated. Fifty children also accepted to participate in follow-up assessment at 12y including the simplified version of Touwen, Movement ABC-2 (MABC-2) and Beery VIM.
Thirty-four children had mild PVL, 1 had cystic PVL, 6 had unspecified signal changes and 26 had normal MRI. No differences in white matter volumes were found in children born EPT with mild PVL compared to children born EPT without PVL, but TBSS showed significant clusters posteriorly in major white matter tracts. Mild PVL did not relate to the severity of MND or to the total score of MABC-2 and Berry VMI.
Mild PVL is a common finding in children born EPT at age 9-11. These abnormalities were not related to white matter volumes or neuromotor outcomes. We are currently investigating cognitive outcomes.
NEURODEVELOPMENTAL OUTCOME AT THE CORRECTED AGE OF 24 MONTHS’ IN EXTREMELY PRETERM INFANTS BORN IN THE NETHERLANDS: AN INTERIM ANALYSIS OF THE EPI-DAF STUDY
Background/aim: In 2010, a new guideline on perinatal treatment of spontaneous extremely preterm (EP) birth was implemented in the Netherlands, lowering the threshold for supporting active treatment from 25 to 24 completed weeks’ gestation. The EPI-DAF study (Extremely Preterm Infants – Dutch Analysis on Follow-up) was developed to collect nationwide data on long-term neurodevelopmental outcome of these EP infants.
Methods: National cohort study in all ten perinatal centers in the Netherlands, including all live born infants <27 weeks’ gestation who reach the corrected age (CA) of 24 months in 2018, 2019 and 2020. This abstract presents data in the first year of data collection. The primary outcome measurement is neurodevelopmental impairment (NDI), classified using cognitive score (Bayley-III-NL), neurological assessment (Gross Motor Function Classification System) and the presence of visual and/or hearing impairment.
Results: A total of 231 infants survived to 24 months' CA. Data is available for 191 infants (83%). Mean cognitive scores for children born at 24, 25 and 26 weeks’ gestation were 93 (±12) , 94 (±15) and 99 (±12), respectively (p=0.078). At 24 months’ CA, 128 infants (67%) had no NDI, 41 infants (22%) had mild NDI and 17 infants (8.9%) had moderate/severe NDI (Table 1). Results were comparable between infants born at 24, 25 and 26 weeks’ gestation (p=0.328).
Conclusion: In this first year of the planned three years data collection, approximately two-third of the EP infants had no neurodevelopmental impairment at 24 months’ CA. Outcome is comparable between 24, 25 and 26 weeks’ gestation.
MOVEMENTS AND POSTURES IN INFANTS BORN EXTREMELY PRETERM AND THE PREDICTION OF NEURODEVELOPMENTAL OUTCOME AT 12 YEARS OF AGE
BACKGROUND AND AIMS
In children born extremely preterm early motor development may be altered and the relation to later neurodevelopmental outcome is unclear. The aim was to evaluate General Movements (GMs, Fidgety Movements, FMs) and the Motor Optimality Score-Revised and their predictive value for neurodevelopmental outcomes at 12 years.
GMs and MOS-R were evaluated from video recordings at 3 months corrected age. Outcome was assessed by the modified Touwen’s neurological examination and the Movement Assessment Battery for Children-2. Subjects were classified into two groups; normal and adverse outcome (Cerebral Palsy, Developmental Coordination Disorder, Minor Neurological Dysfunction, Epilepsy, Attention Deficit Hyperactivity Disorder, Autism Spectrum Disorder, Intellectual Disability, Blindness).
53 infants (33 boys, gestational age mean 25 (23-26 w), body weight mean 805±156 g), were included in the study, of which 42 (79%) participated in the follow up (mean age 12.3 ± 0.4). Of these, 26 (62%) were defined as having an adverse outcome. A significant difference in MOS-R between children with normal vs. adverse outcome were found (p=0.007). Predictive values of GMs and MOS-R (cut-off 21) for adverse outcome at 12 years are presented below (Table 1).
Aberrant FMs predict an overall adverse neurodevelopment with a high PPV and specificity, however the sensitivity to detect adverse outcome per se is low. The combination with MOS-R increases the sensitivity substantially.
SLEEP ARCHITECTURE OF MID TO LATE PRETERM INFANTS OVER A 12 HOUR PERIOD IN AN NICU
Sleep is a prerequisite for normal growth, development, cognitive function and memory creation at any age but particularly for preterm infants who are in a phase of critical brain development. Sleep architecture in healthy newborns is characterised by regular cycling between periods of active sleep, quiet sleep and wakefulness, sleep-wake cycling (SWC). Continuous video encephalography (vEEG) and polygraphy allows for the accurate identification of SWC patterns
To describe the sleep architecture of mid to late preterm (MLP) infants in the NICU.
To quantify the number of SWC interruptions and the purpose of these interruptions
This was a single centre observational study of clinically stable MLP infants (n=98). All infants had overnight multichannel vEEG recorded with sleep-wake states annotated and quantified. Wakeful periods were identified as either spontaneous or interrupted (Fig1).
103 infants were included in this study; recordings from 98 infants were suitable for analysis. A total of 589 sleep cycles were identified with a median of 6 and interquartile range (IQR: 5-7) SWC per infant. Periods of wakefulness occurred with a median frequency of 4 (IQR: 3-4) and median duration of 136 minutes (IQR: 91-169). 137/589 (23%) of sleep periods were purposefully interrupted and occurred during both active (77%) and quiet (23%) sleep.
Healthy MLP infants have well developed SWCs. We have also shown that 23% of SWCs were interrupted. Preserving preterm sleep architecture may help improve outcomes but presents a real operational challenge for NICU caregivers.
A LONGITUDINAL ELECTROPHYSIOLOGICAL MONITORING STUDY IN PRETERM INFANTS: THE PHASE LAG INDEX AS MEASURE FOR BRAIN MATURATION
Background and aims: In a previous cross-sectional study we showed that the phase lag index (PLI), an electroencephalographic (EEG) measure of functional connectivity between different brain regions, is an indicator of brain maturation. However, knowledge on how the PLI develops longitudinally in preterm infants is lacking. The aim of this study was to investigate longitudinal functional connectivity development in very preterm infants with normal follow-up at age five.
Methods: In 18 very preterm infants, EEGs were recorded at weekly intervals, resulting in 4-5 recordings per subject at the postconceptional age (PCA) between 27.6-36.1 weeks. The final dataset consisted of 76 EEGs. Functional connectivity was assessed by the phase lag index (PLI), and global functional connectivity was explored in the broadband frequency (0.5-30 Hz) and delta (0.5-4 Hz) band. Furthermore, the influence of delta power and suppression periods on PLI calculations was studied.
Results: We found negative correlations between PLI and PCA in both broadband (R=–0.67; p<.001) and delta (R=–0.60; p<.001). In addition, the amount of artificially added suppression periods substantially influenced functional connectivity analysis, with a strong correlation between suppression and PLI outcome (R=.91, p<.001).
Conclusions: In preterm infants with normal follow-up, PLI correlates strongly with PCA. The evolution of the background pattern, more specifically the change in amount of suppression periods, may play a crucial role in the observed trend of functional connectivity results in preterm infants. PLI calculations from serial EEGs might be useful as a neurophysiological marker for normal brain development in preterm infants.
NEURODEVELOPMENTAL OUTCOMES OF PRETERM NEONATES
Peri/Intraventricular haemorrhage (PIVH) is relatively frequent among preterm neonates and may compromise normal neuronal and glial cells development, affecting short/long-term neurodevelopment.
The authors aimed to compare the neurodevelopment at 24-36 months of corrected age of neonates <32 weeks of GA with/without PIVH, searching for risk factors for worst prognosis.
Retrospective longitudinal case-control study including the 161 neonates <32 weeks gestational age born between 2011-2017 in a tertiary care Hospital, with no major congenital malformations and evaluated for HPIV by transfontanelar ultrasound. Outcomes assessed included ophthalmologic and auditive evaluations, cerebral palsy, and a global neurodevelopment evaluation using Schedules of Growing Skills (SGS) assessment tool.
PIVH was detected in 24,8%: n=15 gradeI, n=10 gradeII and n=15 gradeIII; n=10 had parenchymal extension. Mortality accounted for n=7 controls vs n=10 PIVH (p=0,001), particularly higher grades (p<0,05). Lower GA/birth weight, vaginal/nocturnal birth, mechanical ventilation, pulmonary haemorrhage, hypotension and significant patent ductus arteriosus were risk factors for PIVH(p<0,050). At 24-36 months (n=124), PIVH patients developed more cerebral palsy (20,7% vs 3,2%, p=0,005), visual dysfunction (44,4 vs 11,4%, p=0,001), audition deficit (20,8 vs 2,5%, p=0,007), and gross motor (24,1 vs 4,4% (p=0,004)) and language (24,1 vs 7,8% (p=0,040)) development delay. No statistically significant differences were found between IPVH I vs controls or PIVH II vs III.
The authors highlight the comparable prognosis associated with PIVH I vs controls, although not obviating regular long-term surveillance to detect later-onset ND disorders. Additionally, PIVH II may carry a comparable poor prognosis as PIVH III, reinforcing surveillance and early intervention in this group.
PERINATAL METABOLIC-ENDOCRINE DISRUPTION: WHY MODERN NEONATAL INTENSIVE CARE CANNOT ACHIEVE RECOMMENDED BODY COMPOSITION IN PRETERM INFANTS AT TERM AGE.
Despite optimized nutrition, preterm-born infants grow slowly and over-accumulate body fat postnatally, leading to significant alterations in body composition compared to term-born counterparts. We hypothesize that the premature metabolic-endocrine disruption, caused by the withdrawal of the materno-placental unit, generates these alterations. This review highlights endocrine interactions during gestation and the early perinatal period, and reports on intervention studies aiming to compensate for preterm-borns hormonal deficiencies.
Thirty-seven papers on maternal/placental hormonal impact on fetal development were studied. Additionally, 43 papers about postnatal endocrine status, early nutritional practices and their impact on postnatal growth in preterm and term-borns were reviewed. Nine interventional studies were examined.
Compared to term-borns, preterm infants show lower levels of insulin-like growth factors 1 and 2. Preterm birth prematurely terminates the placental production of IGF-2 and hPL (stimulates fetal IGF-1) and concludes the maternal support with estrogens (stimulate fetal prolactin) and thyroid hormones. Neonatal morbidities and perinatal-stress inhibit the fetal IGF-1 production. As the postnatal regulation of IGF-1 via growth hormone is still immature, the mismatch between low IGF-1 (premature disruption of the materno-placento-fetal unit) and energy-dense nutrition leads to the development of an undesired body composition with increased fat-mass and low lean-mass. First clinical studies, supplementing IGF-1, resulted in improvements of neonatal morbidity and growth.
In conclusion, the premature metabolic-endocrine disruption of the materno-placental unit leads to multiple endocrine deficiencies in preterm-borns, resulting in impairment of growth, unfavorable body composition and neonatal outcome. The need for hormonal substitution in preterm-borns should be tested.