Post-hemorrhagic ventricular dilatation affects white matter maturation in extremely preterm infants.

BACKGROUND: Data on microstructural white matter integrity in preterm infants with post-hemorrhagic ventricular dilatation (PHVD) using diffusion tensor imaging (DTI) are limited. Also, to date, no study has focused on the DTI changes in extremely preterm (EP) infants with PHVD. METHODS: A case-control study of EP infants <28 weeks' gestation with PHVD was conducted. Diffusivity and fractional anisotropy (FA) values of corticospinal tracts (CST) and corpus callosum (CC) were measured using DTI at term-equivalent age. Outcomes were assessed at 2-years-corrected age. RESULTS: Twenty-one infants with PHVD and 21 matched-controls were assessed. FA values in the CC were lower in infants with PHVD compared with controls (mean difference, 0.05 [95% confidence interval (CI), 0.02-0.08], p < 0.001). In infants with periventricular hemorrhagic infarction, FA values in the CC were lower than in controls (mean difference, 0.05 [95% CI, 0.02-0.09], p = 0.005). The composite cognitive and motor scores were associated with the FA value of the CC (coefficient 114, p = 0.01 and coefficient 147, p = 0.004; respectively). CONCLUSIONS: Extremely preterm infants with PHVD showed lower FA values in CC. A positive correlation was also shown between the composite cognitive and motor scores and FA value of the CC at 2-years-corrected age. IMPACT: Extremely preterm infants with post-hemorrhagic ventricular dilatation showed lower fractional anisotropy values in their corpus callosum compared with controls reflecting the impaired microstructure of these commissural nerve fibers that are adjacent to the dilated ventricles. Impaired microstructure of the corpus callosum was shown to be associated with cognitive and motor scores at 2-years-corrected age.

Social Media Recruitment Strategies to Recruit Pregnant Women Into a Longitudinal Observational Cohort Study: Usability Study.

BACKGROUND: Use of social media for study recruitment is becoming increasingly common. Previous studies have typically focused on using Facebook; however, there are limited data to support the use of other social media platforms for participant recruitment, notably in the context of a pregnancy study. OBJECTIVE: Our study aimed to evaluate the effectiveness of Facebook, Twitter, and Instagram in recruiting a representative sample of pregnant women in a longitudinal pregnancy cohort study in Calgary, Alberta, between September 27, 2021, and April 24, 2022. METHODS: Paid advertisements were targeted at 18- to 50-year-old women in Calgary, with interests in pregnancy. Data regarding reach, link clicks, and costs were collected through Facebook Ads Manager (Meta Platforms, Inc) and Twitter Analytics (Twitter, Inc). The feasibility of each platform for recruitment was assessed based on the recruitment rate and cost-effectiveness. The demographic characteristics of the participants recruited through each source were compared using the chi-square test. RESULTS: Paid advertisements reached 159,778 social media users, resulting in 2390 link clicks and 324 participants being recruited. Facebook reached and recruited the highest number of participants (153/324, 47.2%), whereas Instagram saw the highest number of link clicks relative to the number of users who saw the advertisement (418/19,764, 2.11%). Facebook and Instagram advertisements were cost-effective, with an average cost-per-click of CAD $0.65 (US $0.84; SD $0.27, US $0.35) and cost-per-completer of CAD $7.89 (US $10.25; SD CAD $4.08, US $5.30). Twitter advertisements were less successful in terms of recruitment and costs. Demographic characteristics of participants did not differ based on recruitment source, except for education and income, where more highly educated and higher-income participants were recruited through Instagram or Twitter. Many issues related to fraudulent responses were encountered throughout the recruitment period. CONCLUSIONS: Paid social media advertisements (especially Facebook and Instagram) are feasible and cost-effective methods for recruiting a large sample of pregnant women for survey-based research. However, future research should be aware of the potential for fraudulent responses when using social media for recruitment and consider strategies to mitigate this problem.

Post-hemorrhagic ventricular dilatation: inter-observer reliability of ventricular size measurements in extremely preterm infants.

BACKGROUND: Post-hemorrhagic ventricular dilatation (PHVD) in preterm infants can be assessed with ventricular size indices from cranial ultrasound. We explored inter-observer reliability of these indices for prediction of severe PHVD. METHODS: For all 139 infants with IVH, serial neonatal ultrasound at 3 time points (days 4-7, day 14, 36 weeks PMA) were assessed independently by 3 observers with differing levels of training/experience. Ventricular index (VI), anterior horn width (AHW), and fronto-temporal horn ratio (FTHR) were measured and used to diagnose PHVD. For all, inter-observer reliability and predictive values for receipt of surgical intervention were calculated. RESULTS: Inter-observer reliability for all observers varied from poor to excellent, with higher reliability for VI/AHW (ICC 0.49-0.84/0.51-0.81) than FTHR (0.41-0.82), particularly from the second week. Good-excellent inter-expertise reliability was found between observers with ample experience/training (0.65-0.99), particularly for VI and AHW, while poor-moderate when comparing with an inexperienced observer (0.28-0.88). Slightly higher predictive value for PHVD intervention (n = 12) was found for AHW (AUC 0.86-0.96) than for VI and FTHR (0.80-0.96/0.80-0.95). CONCLUSIONS: AHW and VI are highly reproducible in experienced hands compared to FTHR, with AHW from the second week onwards being the strongest predictor for receiving surgical intervention for severe PHVD. AHW may aid in early PHVD diagnosis and decision-making on intervention. IMPACT: While ventricular size indices from serial cUS are superior to clinical signs of increased intracranial pressure to assess PHVD, questions remained on their inter-observer reproducibility and reliability to predict severity of PHVD. AHW and VI are highly reproducible when performed by experienced clinicians. AHW from the second week of birth is the strongest predictor of PHVD onset and severity. AHW, combined with VI, may aid in early PHVD diagnosis and decision-making on need for surgical intervention. Consistent use of these indices has the potential to improve PHVD management and therewith the long-term outcomes in preterm infants.

Antenatal diagnosis of fetal intraventricular hemorrhage: systematic review and meta-analysis.

AIM: To determine how the severity of antenatally diagnosed germinal matrix-intraventricular hemorrhage (GMH-IVH) relates to morbidity and mortality, and to explore potential risk factors. METHOD: We conducted a systematic review and individual patient data meta-analysis of antenatally diagnosed fetal GMH-IVH. The primary outcomes were mortality and morbidity. Potential associations with clinical factors during pregnancy were explored. Analysis employed Fisher's exact test and logistic regression. RESULTS: We included 240 cases from 80 studies. Presence of venous infarction was associated with mortality (odds ratio [OR] 4.3, 95% confidence interval [CI] 1.4-13.25), motor impairment (OR 103.2, 95% CI 8.6-1238), epilepsy (OR 6.46, 95% CI 2.64-16.06), and developmental delay (OR 8.55, 95% CI 2.12-48.79). Shunt placement was associated with gestational age at GMH-IVH diagnosis and in utero progression. Many cases had uncomplicated pregnancies but possible co-occurring conditions included twin gestation, small for gestational age, and congenital anomalies. INTERPRETATION: Severity of fetal GMH-IVH, specifically venous infarction, is associated with overall mortality and morbidity. Risk factors for fetal GMH-IVH are poorly understood and controlled studies are required. WHAT THIS PAPER ADDS: Preterm germinal matrix-intraventricular hemorrhage (GMH-IVH) grading can be applied to fetuses. Many fetal germinal matrix hemorrhages occur in otherwise typical pregnancies. Half of fetuses with post-hemorrhagic ventricular dilatation receive a shunt after delivery. Fetuses with grade I or II GMH-IVH have few sequelae. Fetuses with periventricular hemorrhagic infarction have a high burden of motor impairment.

Periventricular Hemorrhagic Infarction in Very Preterm Infants: Characteristic Sonographic Findings and Association with Neurodevelopmental Outcome at Age 2 Years.

OBJECTIVE: To describe the sonographic characteristics of periventricular hemorrhagic infarction (PVHI) and their association with mortality and neurodevelopmental disability in very preterm infants born in 2008-2013. STUDY DESIGN: Retrospective multicenter observational cohort study. Diagonal PVHI size was measured and severity score assessed. PVHI characteristics were scored and temporal trends were assessed. Neurodevelopmental outcome at 2 years of corrected age was assessed using either the Bayley Scales of Infant and Toddler Development, Third Edition or the Griffiths Mental Development Scales. Multigroup analyses were applied as appropriate. RESULTS: We enrolled 160 infants with median gestational age of 26.6 weeks. PVHI was mostly unilateral (90%), associated with an ipsilateral grade III intraventricular hemorrhage (84%), and located in the parietal lobe (51%). Sixty-four (40%) infants with PVHI died in the neonatal period. Of the survivors assessed at 2 years of corrected age, 65% had normal cognitive and 69% had normal motor outcomes. The cerebral palsy rate was 42%. The composite outcome of death or severe neurodevelopmental disability was observed in 58%, with no trends over the study period (P = .6). Increasing PVHI severity score was associated with death (P < .001). Increasing PVHI size and severity score were negatively associated with gross motor scores (P = .01 and .03, respectively). Trigone involvement was associated with cerebral palsy (41% vs 14%; P = .004). Associated posthemorrhagic ventricular dilation (36%) was an independent risk factor for poorer cognitive and motor outcomes (P < .001 for both). CONCLUSIONS: Increasing PVHI size and severity score were predictive of less optimal gross motor outcome and death in very preterm infants.

Prognostic value of gradient echo T2* sequences for brain MR imaging in preterm infants.

BACKGROUND: Gradient echo T2*-W sequences are more sensitive than T2-W spin-echo sequences for detecting hemorrhages in the brain. OBJECTIVE: The aim of this study is to correlate presence of hemosiderin deposits in the brain of very preterm infants (gestational age <32 weeks) detected by T2*-W gradient echo MRI to white matter injury and neurodevelopmental outcome at 2 years. MATERIALS AND METHODS: In 101 preterm infants, presence and location of hemosiderin were assessed on T2*-W gradient echo MRI performed around term-equivalent age (range: 40-60 weeks). White matter injury was defined as the presence of >6 non-hemorrhagic punctate white matter lesions (PWML), cysts and/or ventricular dilatation. Six infants with post-hemorrhagic ventricular dilatation detected by US in the neonatal period were excluded. Infants were seen for follow-up at 2 years. Univariate and regression analysis assessed the relation between presence and location of hemosiderin, white matter injury and neurodevelopmental outcome. RESULTS: In 38/95 (40%) of the infants, hemosiderin was detected. Twenty percent (19/95) of the infants were lost to follow-up. There was a correlation between hemosiderin in the ventricular wall with >6 PWML (P < 0.001) and cysts (P < 0.001) at term-equivalent age, and with a lower psychomotor development index (PDI) (P=0.02) at 2 years. After correcting for known confounders (gestational age, gender, intrauterine growth retardation and white matter injury), the correlation with PDI was no longer significant. CONCLUSION: The clinical importance of detecting small hemosiderin deposits is limited as there is no independent association with neurodevelopmental outcome.

Small cerebellar hemorrhage in preterm infants: perinatal and postnatal factors and outcome.

The objective of the study is to determine perinatal and postnatal factors that may affect the occurrence of small cerebellar hemorrhage (CBH) and to evaluate the effect of small CBH on neurodevelopmental outcome in very preterm infants. This prospective study in an unselected cohort of very preterm infants was approved by the medical ethics committee, and informed parental consent was obtained. Presence of small CBH (<4 mm) was assessed with magnetic resonance imaging around term equivalent age in 108 preterm infants (<32 weeks gestation). We compared infants with and without small CBH for perinatal and postnatal factors, supratentorial brain injury, and for neurodevelopmental outcome at 2 years corrected age. Follow-up consisted of a neurological examination, mental and developmental assessment (Bayley Scales of Infant Development), and behavior checklist. Univariate and multivariate logistic regression analyses were performed to examine the relationships between variables. Small CBH was diagnosed in 16/108 very preterm infants. Univariate analyses identified gestational age, high-frequency oscillation (HFO) ventilation, and grade 3-4 intraventricular hemorrhage (IVH) as factors associated with small CBH. HFO ventilation and severe IVH were independent predictors of small CBH. We found no association between small CBH and neurodevelopmental outcome at 2 years of age. Small CBH is a frequent finding in preterm infants. These hemorrhages are independently associated with HFO ventilation and severe supratentorial hemorrhage and seem to have a favorable short-term prognosis.

Tractography of white-matter tracts in very preterm infants: a 2-year follow-up study.

AIM: The aim of this study was to determine whether tractography of white-matter tracts can independently predict neurodevelopmental outcome in very preterm infants. METHOD: Out of 84 very preterm infants admitted to a neonatal intensive care unit, 64 (41 males, 23 females; median gestational age 29.1 weeks [range 25.6-31.9]; birthweight 1163 g [range 585-1960]) underwent follow-up at 2 years. Diffusion tensor imaging (DTI) values obtained around term were associated with a neurological examination and mental and psychomotor developmental index scores at 2 years based on the Bayley Scales of Infant Development (version 3). Univariate and logistic regression analyses tested for associations between DTI values and follow-up parameters. Cut-off values predicting motor delay and cerebral palsy (CP) were determined for fractional anisotropy, apparent diffusion coefficient (ADC), and fibre lengths. RESULTS: Infants with psychomotor delay and CP had significantly lower fractional anisotropy values (p=0.002, p=0.04 respectively) and shorter fibre lengths (p=0.02, p=0.02 respectively) of the posterior limb of the internal capsule. Infants with psychomotor delay also had significantly higher ADC values (p=0.03) and shorter fibre lengths (p=0.002) of the callosal splenium. Fractional anisotropy values of the posterior limb of the internal capsule independently predicted motor delay and CP, with sensitivity between 80 and 100% and specificity between 66 and 69%. ADC values of the splenium independently predicted motor delay with sensitivity of 100% and specificity of 65%. INTERPRETATION: Diffusion tensor imaging tractography at term-equivalent age independently predicts psychomotor delay at 2 years of age in preterm infants.

Practical Stepwise Approach to Performing Neonatal Brain MR Imaging in the Research Setting.

Magnetic resonance imaging (MRI) is a non-invasive imaging technique that is commonly used for the visualization of newborn infant brains, both for clinical and research purposes. One of the main challenges with scanning newborn infants, particularly when scanning without sedation in a research setting, is movement. Infant movement can affect MR image quality and therewith reliable image assessment and advanced image analysis. Applying a systematic, stepwise approach to MR scanning during the neonatal period, including the use of the feed-and-bundle technique, is effective in reducing infant motion and ensuring high-quality images. We provide recommendations for one such systematic approach, including the step-by-step preparation and infant immobilization, and highlight safety precautions to minimize any potential risks. The recommendations are primarily focused on scanning newborn infants for research purposes but may be used successfully for clinical purposes as well, granted the infant is medically stable. Using the stepwise approach in our local research setting, our success rate of acquiring high-quality, analyzable infant brain MR images during the neonatal period is as high as 91%.

Comparing Three Methods of Therapeutic Hypothermia Among Transported Neonates with Hypoxic-Ischemic Encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) and associated multiorgan injury are significant causes of morbidity and mortality in term and near-term neonates. Therapeutic hypothermia (TH) is the current standard of care for neuroprotection in neonates with HIE. In our experience, the majority of babies born with HIE were found in nontertiary care facilities in our region, where effective methods of cooling during transport to tertiary care centers are desirable. Most centers initiate passive TH at referral hospitals, while active cooling is typically initiated during transport. The objective of this study was to evaluate the effectiveness of three methods of cooling during transport of neonates with HIE in southern Alberta. In this prospective cohort study, 186 neonates with HIE were transported between January 2013 and December 2021. Among the 186 neonates, 47 were passively cooled, 36 actively cooled with gel packs, and 103 cooled with a servo-controlled cooling device. The clinical characteristics were comparable for the three groups, with no difference in adverse events. Fifteen neonates (8%) died and 54 neonates (29%) suffered radiologically determined brain injury. Servo-controlled cooling was found to be superior to other methods in maintaining a target temperature without significant fluctuation during transport and with temperature in the target range on arrival at tertiary care facilities. The rate of overcooling was also lower in the servo-controlled group compared with other groups. There were no statistically significant differences between the groups in relation to mortality and brain MRI changes associated with HIE. Adjusting for GA, 10-minute Apgar score, base excess, HIE stage, and need for intubation during transport, passive cooling increased the odds of temperature fluctuation outside the range by 12-fold and gel pack cooling by 13-fold compared with servo-controlled cooling. The use of servo-controlled TH devices should be the preferred practice wherever feasible. (REB17-1334_REN3).

Feeding during therapeutic hypothermia is safe and may improve outcomes in newborns with perinatal asphyxia.

OBJECTIVE: We assessed the impact of early enteral feeding introduction during therapeutic hypothermia on time to reach full enteral feeding (FEF) and other feeding related outcomes in infants born at ≥35 weeks gestational age and diagnosed with moderate to severe Hypoxic-Ischemic Encephalopathy. METHODS: A prospective cohort with historical control study, conducted on infants admitted to the Alberta Children's Hospital level III NICU in Calgary between January 2013 and December 2018. Infants were divided into 2 groups: (1) unfed group (UG), which was kept nil per os during the 72 h of therapeutic Hypothermia (TH), with subsequent introduction of feeding and gradual increase to FEF; (2) fed group (FG), which received feeding at 10 mL/kg/day during TH then increased gradually to FEF. Groups were compared for time to FEF and the type of milk they were being fed on discharge. Other gut related health risks such as NEC and sepsis were examined. RESULTS: During the study period, 146 infants received therapeutic hypothermia, of whom 75 in the UG and 71 in the FG. The FG compared to the UG received the first feed sooner after TH initiation (median 57 vs. 86.5 h, p < .001), reached FEF earlier (median 6 vs. 8 days, p = .012), had a higher rate of being fully fed in the first week of life (70 vs. 53%, p < .035), was kept NPO for shorter duration (median 2 vs. 4 days, p < .001), and had a higher rate of breast milk feeding at discharge (41 vs. 13%, p < .001). There were no cases of necrotizing enterocolitis or late onset sepsis in either group during the hospital stay. CONCLUSION: Minimal enteral feeding during therapeutic hypothermia appears to be safe and leads to a shorter time to FEF and higher rates of breast milk feeding at discharge.

Neurological Surveillance in Moderate-Late Preterm Infants-Results from a Dutch-Canadian Survey.

Preterm birth remains an important cause of abnormal neurodevelopment. While the majority of preterm infants are born moderate-late preterm (MLPT; 32-36 weeks), international and national recommendations on neurological surveillance in this population are lacking. We conducted an observational quantitative survey among Dutch and Canadian neonatal level I-III centres (June 2020-August 2021) to gain insight into local clinical practices on neurological surveillance in MLPT infants. All centres caring for MLPT infants designated one paediatrician/neonatologist to complete the survey. A total of 85 out of 174 (49%) qualifying neonatal centres completed the survey (60 level I-II and 25 level III centres). Admission of MLPT infants was based on infant-related criteria in 78/85 (92%) centres. Cranial ultrasonography to screen the infant's brain for abnormalities was routinely performed in 16/85 (19%) centres, while only on indication in 39/85 (46%). In 57/85 (67%) centres, neurological examination was performed at least once during admission. Of 85 centres, 51 (60%) followed the infants' development post-discharge, with follow-up duration ranging from 1-52 months of age. The survey showed a wide variety in neurological surveillance in MLPT infants among Dutch and Canadian neonatal centres. Given the risk for short-term morbidity and long-term neurodevelopmental disabilities, future studies are required to investigate best practices for in-hospital care and follow-up of MLPT infants.

Neuroprotection care bundle implementation is associated with improved long-term neurodevelopmental outcomes in extremely premature infants.

OBJECTIVE: To study the impact of an evidence-based neuroprotection care (NPC) bundle on long-term neurodevelopmental impairment (NDI) in infants born extremely premature. STUDY DESIGN: An NPC bundle targeting predefined risk factors for acute brain injury in extremely preterm infants was implemented. We compared the incidence of composite outcome of death or severe neurodevelopmental impairment (sNDI) at 21 months adjusted age pre and post bundle implementation. RESULTS: Adjusting for confounding factors, NPC bundle implementation associated with a significant reduction in death or sNDI (aOR, 0.34; 95% CI 0.17-0.68; P = 0.002), mortality (aOR, 0.31; 95% CI (0.12-0.79); P = 0.015), sNDI (aOR, 0.37; 95% CI: 0.12-0.94; P = 0.039), any motor, language, or cognitive composite score <70 (aOR, 0.48; 95% CI: 0.26-0.90; P = 0.021). CONCLUSION: Implementation of NPC bundle targeting predefined risk factors is associated with a reduction in mortality or sNDI in extremely preterm infants.

Diffuse hyperechogenicity of basal ganglia and thalami in preterm neonates: a physiologic finding?

PURPOSE: To elucidate whether echogenicity (EG) of the basal ganglia and thalami (BGT) represents a physiologic phenomenon in preterm neonates (<32 weeks gestation). MATERIALS AND METHODS: The study was approved by the medical ethics committee, and informed consent was obtained from the parents. Sequential neonatal cranial ultrasonographic (US) images obtained in 130 preterm neonates were evaluated for EG of the BGT. In 110 of the 130 neonates, MR imaging was performed around or within the first months after term-equivalent age to assess myelination and changes in BGT signal. Cranial US studies obtained in 83 low-risk near-term neonates were used for comparison. RESULTS: Diffuse homogeneous bilateral EG of the BGT was seen in 120 (92%) of 130 preterm neonates and in seven (8%) of 83 low-risk neonates (P < .001). In preterm neonates, EG of the BGT faded with age and was no longer seen 1 month after delivery. This finding was associated with frontal echodensity, which is a normal prematurity-related cranial US phenomenon that occurs in the white matter (P < .001). No association with changes on MR images was found. CONCLUSION: In preterm neonates, diffuse homogeneous EG of the BGT is a frequent and normal prematurity-related finding.

Clinical implications of MR imaging findings in the white matter in very preterm infants: a 2-year follow-up study.

PURPOSE: To explore the association between diffuse excessive high signal intensity (DEHSI), punctate white matter (WM) lesions, and ventricular dilatation around term-equivalent age (TEA) and at clinical follow-up at 2 years in very preterm infants and the effect on neurodevelopment. MATERIALS AND METHODS: Ethical approval for this prospective study was given by the institutional review board, and informed parental consent was obtained. An unselected cohort of 110 preterm infants (gestational age, < 32 weeks) was imaged around or after TEA. Clinical follow-up was performed at a corrected age of 2 years and consisted of a neurologic examination and a mental and developmental assessment (Bayley Scales of Infant Development). Univariate analyses and logistic and linear regression were performed to examine the relationships between variables. RESULTS: DEHSI was found in 58 of 65 (89%) infants imaged around TEA. DEHSI was never detected in infants imaged after postmenstrual age of 50 weeks and showed no association with neurodevelopmental outcome. Punctate WM lesions and ventricular dilatation were significantly associated with mental (P = .02 for punctate WM lesions) and psychomotor developmental delay (P < .001 and P = .03, respectively), motor delay (P = .002 and P = .02, respectively), and cerebral palsy (P = .01 and P = .03, respectively). CONCLUSION: Because of its high incidence in preterm infants around TEA, its absence after a postmenstrual age of 50 weeks, and its association with normal neurologic outcome at a corrected age of 2 years, DEHSI should not be considered part of the spectrum of WM injury, but rather a prematurity-related developmental phenomenon.

Tractography of developing white matter of the internal capsule and corpus callosum in very preterm infants.

OBJECTIVES: To investigate in preterm infants associations between Diffusion Tensor Imaging (DTI) parameters of the posterior limb of the internal capsule (PLIC) and corpus callosum (CC) and age, white matter (WM) injury and clinical factors. METHODS: In 84 preterm infants DTI was performed between 40-62 weeks postmenstrual age on 3 T MR. Fractional anisotropy (FA), apparent diffusion coefficient (ADC) values and fibre lengths through the PLIC and the genu and splenium were determined. WM injury was categorised as normal/mildly, moderately and severely abnormal. Associations between DTI parameters and age, WM injury and clinical factors were analysed. RESULTS: A positive association existed between FA and age at imaging for fibres through the PLIC (r = 0.48 p < 0.001) and splenium (r = 0.24 p < 0.01). A negative association existed between ADC and age at imaging for fibres through the PLIC (r = -0.65 p < 0.001), splenium (r = -0.35 p < 0.001) and genu (r = -0.53 p < 0.001). No association was found between DTI parameters and gestational age, degree of WM injury or categorical clinical factors. CONCLUSIONS: These results indicate that in our cohort of very preterm infants, at this young age, the development of the PLIC and CC is ongoing and independent of the degree of prematurity or WM injury.

Ultrasound detection of white matter injury in very preterm neonates: practical implications.

AIM: Diffuse white matter injury is not well detected by cranial ultrasonography (CUS). The aim of this study was twofold: (1) to assess in very preterm neonates the predictive values of individual CUS abnormalities for white matter injury on MRI and neurological outcome; (2) to develop a strategy optimizing CUS detection of white matter injury. METHOD: Very preterm neonates (n=67; 44 males, 23 females) underwent serial CUS and single MRI. Predictive values of CUS findings for a white matter classification on MRI, individual MRI findings, and neurological outcome at 2 years corrected age were calculated. The effects of timing and frequency of CUS were evaluated. RESULTS: Periventricular echodensities (PVEs) predicted abnormal white matter on MRI, but absence of PVEs did not predict absence of white matter changes. Peri- and intraventricular haemorrhage (P/IVH) was highly predictive of abnormal white matter on MRI. Frequency and timing of CUS did not influence predictive values. P/IVH and abnormal ventricular size/shape were reasonably predictive of unfavourable outcome, whereas absence of CUS abnormalities predicted a favorable outcome. INTERPRETATION: (1) If PVEs are present, there is a significant chance of abnormal white matter on MRI. (2) Increasing frequency of CUS does not increase its diagnostic performance for white matter injury. (3) P/IVH is highly predictive of abnormal white matter on MRI and reasonably predictive of unfavourable outcome. (4) Absence of PVEs and P/IVH on CUS does not guarantee normal white matter, but predicts a favourable outcome.

Cord Blood Cytokine Levels Correlate With Types of Placental Pathology in Extremely Preterm Infants.

Background: Placental abnormalities are associated with inflammation and have been linked to brain injury in preterm infants. We studied the relationship between placental pathology and the temporal profiles of cytokine levels in extremely pre-term infants. Study Design: We prospectively enrolled 55 extremely preterm infants born between June 2017 and July 2018. Levels of 27 cytokines were measured in blood drawn from the umbilical artery at birth and from infants at 1-3 and 21-28 days of life. Placental pathology was grouped as normal (N), inflammation (I), vasculopathy (V), or combined vasculopathy and inflammation (V+I). Results: Complete data was available from 42 patients. Cord blood median levels of cytokines differed between groups with the highest levels observed in group V+I as compared to groups N, I and V for the following: Eotaxin (p = 0.038), G-CSF (p = 0.023), IFN-γ (p = 0.002), IL-1ra (p < 0.001), IL-4 (p = 0.005), IL-8 (p = 0.010), MCP-1 (p = 0.011), and TNFα (p = 0.002). Post-hoc analysis revealed sex differences between and within the placental pathology groups. Conclusion: Specific types of placental pathology may be associated with differential cytokine profiles in extremely pre-term infants. Sampling from cord blood may help assess the pathological status of the placenta and potentially infer outcome risks for the infant.

Consensus Approach for Standardizing the Screening and Classification of Preterm Brain Injury Diagnosed With Cranial Ultrasound: A Canadian Perspective.

Acquired brain injury remains common in very preterm infants and is associated with significant risks for short- and long-term morbidities. Cranial ultrasound has been widely adopted as the first-line neuroimaging modality to study the neonatal brain. It can reliably detect clinically significant abnormalities that include germinal matrix and intraventricular hemorrhage, periventricular hemorrhagic infarction, post-hemorrhagic ventricular dilatation, cerebellar hemorrhage, and white matter injury. The purpose of this article is to provide a consensus approach for detecting and classifying preterm brain injury to reduce variability in diagnosis and classification between neonatologists and radiologists. Our overarching goal with this work was to achieve homogeneity between different neonatal intensive care units across a large country (Canada) with regards to classification, timing of brain injury screening and frequency of follow up imaging. We propose an algorithmic approach that can help stratify different grades of germinal matrix-intraventricular hemorrhage, white matter injury, and ventricular dilatation in very preterm infants.

Is sequential cranial ultrasound reliable for detection of white matter injury in very preterm infants?

INTRODUCTION: Cranial ultrasound (cUS) may not be reliable for detection of diffuse white matter (WM) injury. Our aim was to assess in very preterm infants the reliability of a classification system for WM injury on sequential cUS throughout the neonatal period, using magnetic resonance imaging (MRI) as reference standard. METHODS: In 110 very preterm infants (gestational age <32 weeks), serial cUS during admission (median 8, range 4-22) and again around term equivalent age (TEA) and a single MRI around TEA were performed. cUS during admission were assessed for presence of WM changes, and contemporaneous cUS and MRI around TEA additionally for abnormality of lateral ventricles. Sequential cUS (from birth up to TEA) and MRI were classified as normal/mildly abnormal, moderately abnormal, or severely abnormal, based on a combination of findings of the WM and lateral ventricles. Predictive values of the cUS classification were calculated. RESULTS: Sequential cUS were classified as normal/mildly abnormal, moderately abnormal, and severely abnormal in, respectively, 22%, 65%, and 13% of infants and MRI in, respectively, 30%, 52%, and 18%. The positive predictive value of the cUS classification for the MRI classification was high for severely abnormal WM (0.79) but lower for normal/mildly abnormal (0.67) and moderately abnormal (0.64) WM. CONCLUSION: Sequential cUS during the neonatal period detects severely abnormal WM in very preterm infants but is less reliable for mildly and moderately abnormal WM. MRI around TEA seems needed to reliably detect WM injury in very preterm infants.