Neurodevelopmental outcomes following preterm birth and the association with postmenstrual age at discharge

Objective: To 1) define the prevalence of motor, cognitive, and language delays in preterm infants born < 32 weeks estimated gestational age (EGA) and 2) identify the relationship between the timing of discharge from the NICU and neurodevelopmental outcome in early childhood. Study Design: This retrospective study of 176 preterm infants born < 32 weeks EGA and hospitalized in a level IV NICU captured medical factors, including timing of discharge, from the NICU stay. Standardized developmental testing at 1-2 years corrected age was conducted in the newborn follow-up clinic. Results: At 1-2 years corrected age, the sample had an average cognitive composite score of 91.5 ± 17.4, language composite score of 84.5 ± 17.3, and motor composite score of 88.9 ± 18.4. Lower EGA at birth, necrotizing enterocolitis, patent ductus arteriosus, and oxygen requirement for > 28 days were independently associated with higher postmenstrual age (PMA) at NICU discharge. After controlling for known risk factors, higher PMA at discharge was associated with poorer cognitive outcome [p < 0.001, (-0.16, -0.07), β = -0.35], poorer language outcome [p = 0.049 (-0.10, 0.00), β = -0.15] and poorer motor outcome [p < 0.001, (-0.14, -0.05), β = -0.30]. Conclusion: Poorer cognitive, language, and motor outcomes were associated with longer hospitalization, even after controlling for medical risk factors known to be associated with poorer outcome. This provides further evidence for the potential role of the environment that may be impacting the developmental outcomes of infants hospitalized in the NICU.

Harnessing the power of telemedicine to accomplish international pediatric outcome research during the COVID-19 pandemic

The COVID-19 pandemic occurred during planned neurodevelopmental follow-up of Colombian children with antenatal Zika-virus exposure. The objective of the study was to leverage the institution's telemedicine infrastructure to support international clinical child outcome research. In a prospective cohort study of child neurodevelopment (NCT04398901), we used synchronous telemedicine to remotely train a research team and perform live observational assessments of children in Sabanalarga, Colombia. An observational motor and conceptional standardized tool kit was mailed to Colombia; other materials were translated and emailed; team training was done virtually. Children were recruited by team on the ground. Synchronous activities were video-recorded directly to two laptops, each with a telehealth Zoom link to allow simultaneous evaluation of “table” and “standing” activities, and backup recordings were captured directly on the device in Colombia. The U.S. team attended live over Zoom from four states and five distinct locations, made observational notes, and provided real-time feedback. Fifty-seven, 3–4-year-old children with Zika-virus exposure and 70 non-exposed controls were studied during 10 daytrips. Direct laptop recording ensured complete record of child activities due to internet outages. Telemedicine can be used to successfully perform international neurodevelopmental outcome research in children during the COVID-19 pandemic. Telemedicine can benefit global health studies.

First-line noninvasive management of cytomegalovirus primary infection in pregnancy

Objectives To introduce a first-line noninvasive antenatal management of maternal cytomegalovirus (CMV) primary infection based on ultrasound (US) and magnetic resonance imaging (MRI). Amniocentesis (AC) is used as a second-line tool in cases of abnormalities compatible with fetal CMV infection on US and/or MRI screening. Methods Between January 2011 and October 2018, pregnant women referred with a CMV primary infection on antibody screening were followed up by monthly US scans and a brain MRI at approximately 32 weeks. In cases with US and/or MRI abnormalities compatible with congenital CMV infection, AC was performed to confirm the diagnosis. Results Ninety pregnant women with a primary CMV infection were included (89 singleton and one twin pregnancy). The first-line screening by US and/or MRI was normal for 72 of 91 fetuses (79%). At birth, 19 of these 72 neonates (26%) had a positive urine sample for CMV but were asymptomatic. US and/or MRI abnormalities were identified in 19 fetuses (21%). AC confirmed a fetal CMV infection in 16 fetuses (84%); 12 pregnancies were terminated, and four were continued, with three symptomatic neonates at birth and one poor neurodevelopmental outcome at postnatal follow-up. Conclusions First-line noninvasive management of maternal CMV primary infection based on serial US scans and brain MRI can be offered to identify fetuses with severe symptomatic congenital CMV infection and reduce the number of ACs without compromising the fetal outcome.

Outcome of non-cooled asphyxiated infants with under-recognised or delayed-onset encephalopathy

ObjectiveTo describe the clinical characteristics, MRI findings and neurodevelopmental outcome of infants with documented perinatal asphyxia and seizure onset within 24 hours after birth who were not selected for therapeutic hypothermia (TH).DesignRetrospective cohort study.Setting and patients(Near-)term infants with documented perinatal asphyxia referred to two Dutch level III neonatal units with neonatal encephalopathy (NE) and seizures <24 hours after birth not treated with TH. Infants with a diagnosis other than NE following perinatal asphyxia causing the seizures were excluded.Main outcome measuresClinical characteristics, findings on cranial MRI performed within 8 days after birth and neurodevelopmental outcome assessed using the Griffiths Mental Development Scales at 18 months or Bayley Scales of Infant and Toddler Development–Third Edition at 2 years of age.Results39 infants were included. All had abnormalities on MRI. Predominant white matter/watershed injury was the most common pattern of injury, 23 (59%). 7 (18%) infants had predominant basal ganglia/thalamus injury, 3 (8%) near total brain injury, 5 (13%) arterial ischaemic stroke, 1 (3%) an intraventricular haemorrhage. Adverse outcome was seen in 51%: 6 died, 11 developed cerebral palsy (spastic n=8, dyskinetic n=3), 2 had neurodevelopmental delay, 1 had severe hearing impairment.ConclusionsAll infants with documented perinatal asphyxia and seizure onset within 24 hours after birth who did not receive TH had abnormalities on MRI. 51% had an adverse outcome. Better methods for recognition of infants who might benefit from TH and careful neurodevelopmental follow-up are urgently needed.

Impact of antenatal glucocorticoid exposure on the activity of the stress system, cognition and behavior in 8 to 9-year-old children: a clinical cohort study

Objective: To determine stress-sensitivity and neurodevelopmental outcome in 8- to 9-year-old children following antenatal exposure to glucocorticoid (GC) prophylaxis for neonatal respiratory distress syndrome. Design: Clinical cohort study. Setting: University-based obstetric clinic in Central Germany. Population: 31 term or near-term born children whose mothers received single or multiple courses of betamethasone (BM) to induce fetal lung maturation in threatened preterm birth compared to 39 non-exposed children. Methods: Multi-system assessment of the individual stress response together with an analysis of cognitive, behavioral and electrocortical functioning. Main Outcome Measures: Activity of the hypothalamus-pituitary-adrenal axis (HPAA, primary outcome domain) and the autonomic nervous system (ANS, secondary outcome domain) including markers of heart rate variability (HRV). Additional endpoints were the cognitive performance (IQ) and attention-deficit/hyperactivity disorder (ADHD) core symptoms. Results: HPAA activity was not affected by antenatal GC-exposure. ANS activity in GC-exposed children shifted towards a higher parasympathetic tone reflected by a higher overall high-frequency band power of HRV (1313 vs. 762 msec2/Hz, p=0.03). BM-exposed children had lower cognitive performance (IQ 96.9 vs. 108.0, p<0.01) and a marginally higher ADHD score (FBB-ADHD scale 5.5 vs. 4.6 points, p=0.04). A monotonic dose-response relationship between GC-exposure and stress-induced activity of the ANS and IQ was estimated post-hoc. Conclusions: Antenatal exposure to supraphysiological concentrations of BM in the context of threatened preterm birth was associated with multidimensional changes in stress-sensitivity and neurodevelopment in later life. As these changes may be dose-dependent, antenatal GC prophylaxis should be used at the minimum effective dose after a careful risk-benefit assessment.

Predicting neurodevelopmental outcomes in fetuses with isolated mild ventriculomegaly

BackgroundFetal ventriculomegaly is the the most common intracranial abnormality detected antenatally. When ventriculomegaly is mild and the only, isolated, abnormality detected (isolated mild ventriculomegaly (IMVM)) the prognosis is generally considered to be good. We aim to determine if there are features on in utero MRI (iuMRI) that can identify fetuses with IMVM who have lower risks of abnormal neurodevelopment outcome.MethodsWe studied cases recruited into the MRI to enhance the diagnosis of fetal developmental brain abnormalities in utero (MERIDIAN) study, specifically those with: confirmed IMVM, 3D volume imaging of the fetal brain and neurodevelopmental outcomes at 3 years. We explored the influence of sex of the fetus, laterality of the ventriculomegaly and intracranial compartmental volumes in relation to neurodevelopmental outcome.FindingsForty-two fetuses met the criteria (33 male and 9 female). There was no obvious correlation between fetal sex and the risk of poor neurodevelopmental outcome. Unilateral IMVM was present in 23 fetuses and bilateral IMVM in 19 fetuses. All fetuses with unilateral IMVM had normal neurodevelopmental outcomes, while only 12/19 with bilateral IMVM had normal neurodevelopmental outcomes. There was no obvious correlation between measure of intracranial volumes and risk of abnormal developmental outcomes.InterpretationThe most important finding is the very high chance of a good neurodevelopmental outcome observed in fetuses with unilateral IMVM, which is a potentially important finding for antenatal counselling. There does not appear to be a link between the volume of the ventricular system or brain volume and the risk of poor neurodevelopmental outcome.

Favorable Response to “Memantine” in a Child with GRIN2B Epileptic Encephalopathy

GRIN2B is a gene encoding GluN2B subunit under the family of N-methyl D-aspartate (NMDA) receptors, which is responsible for neurogenesis and cognitive processes. The role of NMDA receptor antagonists like memantine is being explored for therapies in drug-resistant epilepsies. Here, we present a case of a 20-month-old boy who presented with refractory epileptic spasms. Upon failure of multiple antiepileptic drugs, he was started on oral memantine. There was a significant reduction in average seizure episodes by ∼80%. The use of memantine along with antiepileptic drug polytherapy has proved to be beneficial in our case. Our experience with memantine and favorable outcome opens up the scope of more research into the use of NMDA receptor antagonist as a drug option for refractory epilepsies with proven genetic mutation and hence improves the overall neurodevelopmental outcome and survival chance.