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Children born very preterm (≤32 weeks gestational age) show poorer cognitive and language development compared with their term-born peers. The importance of supportive maternal responses to the child's cues for promoting neurodevelopment is well established. However, little is known about whether supportive maternal behavior can buffer the association of early brain dysmaturation with cognitive and language performance.Infants born very preterm (N = 226) were recruited from the neonatal intensive care unit for a prospective, observational cohort study. Chart review (e.g., size at birth, postnatal infection) was conducted from birth to discharge. Magnetic resonance imaging, including diffusion tensor imaging, was acquired at approximately 32 weeks postmenstrual age and again at term-equivalent age. Fractional anisotropy, a quantitative measure of brain maturation, was obtained from 11 bilateral regions of interest in the cortical gray matter. At 3 years (n = 187), neurodevelopmental testing (Bayley Scales of Infant and Toddler Development-III) was administered, and parent-child interaction was filmed. Maternal behavior was scored using the Emotional Availability Scale-IV. A total of 146 infants with neonatal brain imaging and follow-up data were included for analysis. Generalized estimating equations were used to examine whether maternal support interacted with mean fractional anisotropy values to predict Cognitive and Language scores at 3 years, accounting for confounding neonatal and maternal factors.Higher maternal support significantly moderated cortical fractional anisotropy values at term-equivalent age to predict higher Cognitive (interaction term β = 2.01, p = .05) and Language (interaction term β = 1.85, p = .04) scores.Findings suggest that supportive maternal behavior following early brain dysmaturation may provide an opportunity to promote optimal neurodevelopment in children born very preterm.

Background and objectiveNeonatal outcome research and clinical follow-up principally focus on neurodevelopmental impairment (NDI) after extremely preterm birth, as defined by the scientific community, without parental input. This survey aimed to investigate parental perspectives about the health and development of their preterm children.MethodsParents of children aged 18 months to 7 years born Results248 parents of 213 children (mean gestational age 26.6±1.6 weeks, 20% with severe NDI) were recruited. Parents evaluated their children’s health at a median of 9/10. Parental priorities for health improvements were (1) development, mainly behaviour, emotional health and language/communication (55%); (2) respiratory heath and overall medical fragility (25%); and (3) feeding/growth issues (14%). Nineteen per cent explicitly mentioned ‘no improvements’. Parents were more likely to state ‘no improvements’ if child had no versus severe NDI OR 4.33 (95% CI 1.47 to 12.75)) or if parents had no versus at least a high school diploma (OR 4.01 (95% 1.99 to 8.10)).ConclusionsParents evaluate the health of their preterm children as being very good, with positive perspectives. Parental concerns outside the developmental sphere should also be addressed both in clinical follow-up and research.

Rationale: Bronchopulmonary dysplasia increases the risk of disability in extremely preterm infants. Although the pathophysiology remains uncertain, prior exposure to intermittent hypoxemia may pla...

ObjectivesHealth status (HS)/ health-related quality of life measures, completed by self or proxy, are important outcome indicators. Most HS literature on children born preterm includes adolescents and adults with limited data at preschool age. This study aimed to describe parent-reported HS in a large national cohort of extreme preterm children at preschool age and to identify clinical and sociodemographic variables associated with HS.MethodsInfants born before 29 weeks’ gestation between 2009 and 2011 were enrolled in a prospective longitudinal national cohort study through the Canadian Neonatal Network (CNN) and the Canadian Neonatal Follow-Up Network (CNFUN). HS, at 36 months’ corrected age (CA), was measured with the Health Status Classification System for Pre-School Children tool completed by parents. Information about HS predictors was extracted from the CNN and CNFUN databases.ResultsOf 811 children included, there were 79, 309 and 423 participants in 23–24, 25–26 and 27–28 weeks’ gestational age groups, respectively. At 36 months’ CA, 78% had a parent-reported health concern, mild in >50% and severe in 7%. Most affected HS attributes were speech (52.1%) and self-care (41.4%). Independent predictors of HS included substance use during pregnancy, infant male sex, Score for Neonatal Acute Physiology-II, bronchopulmonary dysplasia, severe retinopathy of prematurity, caregiver employment and single caregiver.ConclusionMost parents expressed no or mild health concerns for their children at 36 months’ CA. Factors associated with health concerns included initial severity of illness, complications of prematurity and social factors.

To evaluate neurodevelopment and growth in extremely preterm infants with or without necrotizing enterocolitis or spontaneous intestinal perforation.We conducted a retrospective cohort study of infants admitted to Canadian neonatal intensive care units in 2010 to 2011. We assessed outcomes at 18 to 24 months' corrected ages for preterm infants29 weeks of gestational age at birth with spontaneous intestinal perforation or non-perforated or perforated necrotizing enterocolitis, and for preterm infants with none of these gastrointestinal complications. The primary outcome was a composite of death or significant neurodevelopmental impairment at 18 to 24 months' corrected age. We used multivariable logistic regression models to adjust for gestational age, small for gestational age, prenatal steroids, cesarean section, multiple gestations, and SNAP-II score.Of 2,019 infants total, 39 (1.9%) had spontaneous intestinal perforation, 61 (3%) had perforated necrotizing enterocolitis, and 115 (5.7%) had non-perforated necrotizing enterocolitis. Infants with spontaneous intestinal perforation (aOR 2.11; 95% CI 1.01-4.42), necrotizing enterocolitis (aOR 2.58; 95% CI 1.81-3.68), or any bowel perforation (aOR 3.97; CI 2.43-6.48) had higher odds of death or significant neurodevelopmental impairment compared to infants with none of these bowel diseases.Spontaneous intestinal perforation, necrotizing enterocolitis, or any bowel perforation are risk factors for death or significant neurodevelopmental impairment in extremely preterm infants.Study type: prognosis study (cohort study: retrospective) LEVEL OF EVIDENCE RATING: II.

OBJECTIVES To determine whether maternal supplementation with high-dose docosahexaenoic acid (DHA) in breastfed, very preterm neonates improves neurodevelopmental outcomes at 18 to 22 months’ corrected age (CA). METHODS Planned follow-up of a randomized, double-blind, placebo-controlled, multicenter trial to compare neurodevelopmental outcomes in breastfed, preterm neonates born before 29 weeks’ gestational age (GA). Lactating mothers were randomized to receive either DHA-rich algae oil or a placebo within 72 hours of delivery until 36 weeks’ postmenstrual age. Neurodevelopmental outcomes were assessed with the Bayley Scales of Infant and Toddler Development third edition (Bayley-III) at 18 to 22 months’ CA. Planned subgroup analyses were conducted for GA ( RESULTS Among the 528 children enrolled, 457 (86.6%) had outcomes available at 18 to 22 months’ CA (DHA, N = 234, placebo, N = 223). The mean differences in Bayley-III between children in the DHA and placebo groups were −0.07 (95% confidence interval [CI] −3.23 to 3.10, P = .97) for cognitive score, 2.36 (95% CI −1.14 to 5.87, P = .19) for language score, and 1.10 (95% CI −2.01 to 4.20, P = .49) for motor score. The association between treatment and the Bayley-III language score was modified by GA at birth (interaction P = .07). Neonates born CONCLUSIONS Maternal DHA supplementation did not improve neurodevelopmental outcomes at 18 to 22 months’ CA in breastfed, preterm neonates, but subgroup analyses suggested a potential benefit for language in preterm neonates born before 27 weeks’ GA.

To predict adverse neurodevelopmental outcome of very preterm neonates. A total of 166 preterm neonates born between 24–32 weeks’ gestation underwent brain MRI early in life. Radiomics features were extracted from T1- and T2- weighted images. Motor, cognitive, and language outcomes were assessed at a corrected age of 18 and 33 months and 4.5 years. Elastic Net was implemented to select the clinical and radiomic features that best predicted outcome. The area under the receiver operating characteristic (AUROC) curve was used to determine the predictive ability of each feature set. Clinical variables predicted cognitive outcome at 18 months with AUROC 0.76 and motor outcome at 4.5 years with AUROC 0.78. T1-radiomics features showed better prediction than T2-radiomics on the total motor outcome at 18 months and gross motor outcome at 33 months (AUROC: 0.81 vs 0.66 and 0.77 vs 0.7). T2-radiomics features were superior in two 4.5-year motor outcomes (AUROC: 0.78 vs 0.64 and 0.8 vs 0.57). Combining clinical parameters and radiomics features improved model performance in motor outcome at 4.5 years (AUROC: 0.84 vs 0.8). Radiomic features outperformed clinical variables for the prediction of adverse motor outcomes. Adding clinical variables to the radiomics model enhanced predictive performance.

Infants born extremely preterm are at high risk for early feeding difficulties, as well as poor neurodevelopmental outcomes in childhood. Feeding, a complex motor skill, may be predictive of later neuromotor outcomes.To determine the relationship between feeding behaviours of extremely preterm-born infants (28 weeks gestational age) at 4-months corrected age (CA) and neurodevelopmental outcomes at 4-5 years.Retrospective cohort design with prospectively collected data.Infants born extremely preterm from September 1999 - October 2013 [n = 412, mean gestational age 25.4 (1.3) weeks; mean birth weight 771 (168) grams]. Oral feeding was assessed at 4-months CA by an experienced occupational therapist; infants were classified as either having poor suck-swallow ('feeding difficulties') or no feeding difficulties.Motor outcomes were assessed at 4-5 years using the Movement Assessment Battery for Children (MABC). Children were categorized as: (1) typical motor development (TMD; n = 214); (2) Developmental Coordination Disorder (DCD; n = 116); or (3) major neurodevelopmental disorder (MND; n = 82).Feeding behaviour at 4-months CA predicted DCD (OR = 2.95, CI 1.13-7.68) and MND (OR = 3.67, CI 1.35-9.96) after controlling for confounders. Infants with feeding difficulties were more likely to be diagnosed with DCD (40 % of poor feeders) or MND (36 %) at 4-5 years, compared to infants without feeding issues.Early feeding behaviours significantly predicted motor outcomes at 4-5 years. Infants born extremely preterm with early feeding difficulties should be identified as at high risk for poor motor outcomes later in childhood and screened for early diagnosis and intervention.

To evaluate the relationship of quantitative ventricular volume with brain maturation and neurodevelopmental outcomes at age 4.5 years in children born very preterm.T1-weighted imaging, diffusion tensor imaging, and magnetic resonance spectroscopy were performed shortly after birth (n = 212) and at term-equivalent age (TEA) (n = 194). Intraventricular hemorrhage (IVH) grade and white matter injury (WMI) volume were measured on early T1-weighted magnetic resonance imaging (MRI) scans. Total cerebral volume and ventricular volume were quantified using the Multiple Automatically Generated Templates-Brain pipeline. At age 4.5 years, 178 children (84%) underwent cognitive and motor assessments. Multivariable linear regression was used to examine the relationships between ventricular volume and neurodevelopmental outcomes. Generalized estimating equations were used to account for repeated measures when analyzing neonatal MRI data. All models accounted for sex, postmenstrual age at scan, WMI volume, IVH grade, and total cerebral volume and were corrected for multiple comparisons.On early MRI, 97 infants had IVH (grade 1, n = 22; grade 2, n = 66; grade 3, n = 9), and 68 had WMI (median, 44 mmIn children born very preterm, neonatal ventricular size was associated with 4.5-year neurodevelopmental outcomes. Our findings suggest that white matter maturation may be abnormal in the setting of enlarged ventricular size beyond that expected from concurrent brain injuries.

OBJECTIVE The purpose of this study was to determine how preterm white matter injury (WMI) and long-term thalamic growth interact to predict 8-year neurodevelopmental outcomes. METHODS A prospective cohort of 114 children born at 24 to 32 weeks' gestational age (GA) underwent structural and diffusion tensor magnetic resonance imaging early in life (median 32 weeks), at term-equivalent age and at 8 years. Manual segmentation of neonatal WMI was performed on T1-weighted images and thalamic volumes were obtained using the MAGeT brain segmentation pipeline. Cognitive, motor, and visual-motor outcomes were evaluated at 8 years of age. Multivariable regression was used to examine the relationship among neonatal WMI volume, school-age thalamic volume, and neurodevelopmental outcomes. RESULTS School-age thalamic volumes were predicted by neonatal thalamic growth rate, GA, sex, and neonatal WMI volume (p

The ability to definitively diagnose cerebral palsy (CP) at 18-24 months is unknown.To describe very preterm children who, at 19 months, have suspected CP defined as neither having a definitive diagnosis of CP nor no CP and compare them with children with and without CP.Longitudinal national cohort study of births29 weeks' gestation with linked Canadian Neonatal Network and Canadian Neonatal Follow-up Network data with 19 month assessments and 3-year questionnaires (Ages and Stages-3 and Health Status Classification System-Preschool). CP, no CP and suspected CP groups, classified at 19 months, were compared using chi square and ANOVA.Of 3086 survivors, 2280 had complete 19-month corrected age (CA) and 1261 had 3-year CA data. Suspected CP (3.6%), CP (6.4%) and no CP (90%) groups differed (p 0.05) in birth weight, gestational age, complications of prematurity and NICU length of stay. Children with suspected CP had Bayley-III motor, cognitive and language composite scores at 18 months midway between CP and no CP, had the lowest sensory impairment rates and highest hospital readmission rates. At 3 years, gross motor, fine motor, problem-solving, communication and social skill abilities differed: abnormal outcomes were intermediate for children with suspected CP (p 0.01).CP incidence varied from 6.4% to 10% with exclusion or inclusion of children with suspected CP. Children with suspected CP have characteristics mostly midway between those with and without CP and developmental concerns persist to 3 years and require surveillance beyond 19 months.

Genetic disorders are one of the leading causes of infant mortality and are frequent in neonatal intensive care units (NICUs). Rapid genome-wide sequencing (GWS; whole genome or exome sequencing (ES)), due to its diagnostic capabilities and immediate impacts on medical management, is becoming an appealing testing option in the NICU setting. RAPIDOMICS was a trio-based rapid ES pilot study of 25 babies with suspected genetic disorders in the BC Women's Hospital NICU. ES and bioinformatic analysis were performed after careful patient ascertainment. Trio analysis was performed using an in-house pipeline reporting variants in known disease-causing genes. Variants interpreted by the research team as definitely or possibly causal of the infant's phenotype were Sanger validated in a clinical laboratory. The average time to preliminary diagnosis was 7.2 days. Sanger validation was pursued in 15 patients for 13 autosomal dominant and 2 autosomal recessive disorders, with an overall diagnostic rate (partial or complete) of 60%.Conclusion: In total, 72% of patients enrolled had a genomic diagnosis achieved through ES, multi-gene panel testing or chromosomal microarray analysis. Among these, there was an 83% rate of significant and immediate impact on medical decision-making directly related to new knowledge of the diagnosis. Health service implementation challenges and successes are discussed. What is Known: • Rapid genome-wide sequencing in the neonatal intensive care setting has a greater diagnostic hit rate and impact on medical management than conventional genetic testing. However, the impact of consultation with genetics and patient ascertainment requires further investigation. What is New: • This study demonstrates the importance of genetic consultation and careful patient selection prior to pursuing exome sequencing (ES). • In total, 15/25 (60%) patients achieved a diagnosis through ES and 18/25 (72%) through ES, multi-gene panel testing or chromosomal microarray analysis with 83% of those having immediate effects on medical management.

To compare neurodevelopmental outcomes of preterm infants at 18–21 months corrected age (CA) whose mothers smoked during pregnancy to those whose mothers did not smoke. Preterm infants born at

Quality improvement initiatives in neonatology have yielded positive results; however, few programs have demonstrated sustainability. We evaluated an ongoing, national quality improvement initiative (Evidence-based Practice for Improving Quality Phase 3 (EPIQ-3)) on outcomes of preterm neonates with a gestational age (GA) of 220–286weeks (i.e., from 22 weeks and 0 days of gestation to 28 weeks and 6 days of gestation). Data from 7459 neonates admitted to 25 Canadian centers between 2013 and 2017 were studied. Trends in mortality and major morbidities were evaluated. The number of neonates with a GA of 220–236weeks increased from 90 in 2013 to 139 in 2017 without a significant change in any other GA categories. In the entire cohort, the odds of composite outcome of mortality or any major morbidity (adjusted odds ratio (AOR) 0.72, 95% confidence interval (CI) 0.61–0.84) and of necrotizing enterocolitis (AOR 0.66, 95% CI 0.49–0.89) were lower in 2017 than in 2013. When calculated per year, the odds of composite outcome (AOR 0.93, 95% CI 0.89–0.97) and odds of necrotizing enterocolitis (AOR 0.89, 95% CI 0.82–0.96) decreased significantly. Among the subgroup of neonates with a GA of 260–286weeks, the odds of composite outcome (AOR 0.63, 95% CI 0.51–0.79), necrotizing enterocolitis (AOR 0.44, 95% CI 0.26–0.73), and nosocomial infection (AOR 0.64, 95% CI 0.49–0.84) were reduced. The collaborative, multidisciplinary, nationwide EPIQ-3 program improved outcomes of preterm neonates, and the improvement was sustainable over 5 years.

ImportanceInternalizing (anxiety and/or depressive) behaviors are prevalent in children born very preterm (24-32 weeks’ gestation). Procedural pain-related stress in the neonatal intensive care unit (NICU) is associated with long-term internalizing problems in this population; however, whether positive parenting during toddlerhood attenuates development of internalizing behaviors across childhood is unknown.ObjectiveTo investigate whether neonatal pain-related stress is associated with trajectories of internalizing behaviors across 1.5, 3.0, 4.5, and 8.0 years, and whether supportive parenting behaviors and lower parenting stress at 1.5 and 3.0 years attenuate this association.Design, Setting, and ParticipantsIn this prospective longitudinal cohort study, preterm neonates (born at 24-32 weeks’ gestation) were recruited from August 16, 2006, to September 9, 2013, with follow-up visits at ages 1.5, 3.0, 4.5, and 8.0 years. The study was conducted at BC Women’s Hospital, Vancouver, Canada, with recruitment from a level III neonatal intensive care unit and sequential developmental assessments performed in a Neonatal Follow-up Program. Data analysis was performed from August to December 2021.Main Outcomes and MeasuresParental report of child internalizing behaviors on the Child Behavior Checklist at 1.5, 3.0, 4.5, and 8.0 years.ResultsA total of 234 neonates were recruited, and 186 children (101 boys [54%]) were included in the current study across ages 1.5 (159 children), 3.0 (169 children), 4.5 (162 children), and 8.0 (153 children) years. After accounting for clinical factors associated with prematurity, greater neonatal pain-related stress was associated with more internalizing behaviors across ages (B = 4.95; 95% CI, 0.76 to 9.14). Higher parenting stress at age 1.5 years (B = 0.17; 95% CI, 0.11 to 0.23) and a less supportive parent environment (less sensitivity, structure, nonintrusiveness, nonhostility, and higher parenting stress; B = −5.47; 95% CI, −9.44 to −1.51) at 3.0 years were associated with greater internalizing problems across development to age 8.0 years.Conclusions and RelevanceIn this cohort study of children born very preterm, exposure to repetitive neonatal pain-related stress was associated with persistent internalizing behavior problems across toddlerhood to age 8.0 years. Supportive parenting behaviors during early childhood were associated with better long-term behavioral outcomes, whereas elevated parenting stress was associated with more child anxiety and/or depressive behaviors in this population. These findings reinforce the need to prevent pain in preterm neonates and inform future development of targeted parent-led behavioral interventions.

To evaluate changes in mortality or significant neurodevelopmental impairment (NDI) in children born at29 weeks of gestation in association with national quality improvement initiatives.This longitudinal cohort study included children born at 22The 4426 children included 1895 (43%) born in epoch 1 and 2531 (57%) born in epoch 2. Compared with epoch 1, in epoch 2 more mothers received magnesium sulfate (56% vs 28%), antibiotics (69% vs 65%), and delayed cord clamping (37% vs 31%) and fewer infants had a Score for Neonatal Acute Physiology, version II20 (31% vs 35%) and late-onset sepsis (23% vs 27%). Death or significant NDI occurred in 30% of children in epoch 2 versus 32% of children in epoch 1 (aOR, 0.86; 95% CI, 0.75-0.99). In epoch 2, there were reductions in the need for hearing aids or cochlear implants (1.4% vs 2.6%; aOR, 0.50; 95% CI, 0.31-0.82) and in blindness (0.6% vs.1.4%; aOR, 0.38; 95% CI, 0.18-0.80).Among preterm infants born at29 weeks of gestation, composite rates of death or significant NDI and rates of visual and hearing impairment were significantly lower in 2013-2016 compared with 2009-2012.

IntroductionHaving an infant admitted to the neonatal intensive care unit (NICU) is associated with increased parental stress, anxiety and depression. Enhanced support for parents may decrease parental stress and improve subsequent parent and child outcomes. The Coached, Coordinated, Enhanced Neonatal Transition (CCENT) programme is a novel bundled intervention of psychosocial support delivered by a nurse navigator that includes Acceptance and Commitment Therapy-based coaching, care coordination and anticipatory education for parents of high-risk infants in the NICU through the first year at home. The primary objective is to evaluate the impact of the intervention on parent stress at 12 months.Methods and analysisThis is a multicentre pragmatic randomised controlled superiority trial with 1:1 allocation to the CCENT model versus control (standard neonatal follow-up). Parents of high-risk infants (n=236) will be recruited from seven NICUs across three Canadian provinces. Intervention participants are assigned a nurse navigator who will provide the intervention for 12 months. Outcomes are measured at baseline, 6 weeks, 4, 12 and 18 months. The primary outcome measure is the total score of the Parenting Stress Index Fourth Edition Short Form at 12 months. Secondary outcomes include parental mental health, empowerment and health-related quality of life for calculation of quality-adjusted life years (QALYs). A cost-effectiveness analysis will examine the incremental cost of CCENT versus usual care per QALY gained. Qualitative interviews will explore parent and healthcare provider experiences with the intervention.Ethics and disseminationResearch ethics approval was obtained from Clinical Trials Ontario, Children’s Hospital of Eastern Ontario Research Ethics Board (REB), The Hospital for Sick Children REB, UBC Children’s and Women’s REB and McGill University Health Centre REB. Results will be shared with Canadian level III NICUs, neonatal follow-up programmes and academic forums.Trial registration numberClinicalTrials.gov Registry (NCT03350243).

ObjectiveTo compare mortality and rates of significant neurosensory impairment (sNSI) at 18–36 months’ corrected age in infants born extremely preterm across three international cohorts.DesignRetrospective analysis of prospectively collected neonatal and follow-up data.SettingThree population-based observational cohort studies: the Australian and New Zealand Neonatal Network (ANZNN), the Canadian Neonatal and Follow-up Networks (CNN/CNFUN) and the French cohort Etude (Epidémiologique sur les Petits Ages Gestationnels: EPIPAGE-2).PatientsExtremely preterm neonates of Main outcome measuresPrimary outcome was composite of mortality or sNSI defined by cerebral palsy with no independent walking, disabling hearing loss and bilateral blindness.ResultsOverall, 3055 infants (ANZNN n=960, CNN/CNFUN n=1019, EPIPAGE-2 n=1076) were included in the study. Primary composite outcome rates were 21.3%, 20.6% and 28.4%; mortality rates were 18.7%, 17.4% and 26.3%; and rates of sNSI among survivors were 4.3%, 5.3% and 3.3% for ANZNN, CNN/CNFUN and EPIPAGE-2, respectively. Adjusted for gestational age and multiple births, EPIPAGE-2 had higher odds of composite outcome compared with ANZNN (OR 1.71, 95% CI 1.38 to 2.13) and CNN/CNFUN (OR 1.72, 95% CI 1.39 to 2.12). EPIPAGE-2 did have a trend of lower odds of sNDI but far short of compensating for the significant increase in mortality odds. These differences may be related to variations in perinatal approach and practices (and not to differences in infants’ baseline characteristics).ConclusionsComposite outcome of mortality or sNSI for extremely preterm infants differed across high-income countries with similar baseline characteristics and access to healthcare.

Altered sensory processing is commonly reported in children born very preterm (≤32 weeks' gestational age [GA]). The immature nervous system, particularly the development of connections from the thalamus to the cortex, may show enhanced vulnerability to excessive sensory stimulation, and may contribute to altered sensory processing. Our objective was to determine whether sensory processing assessed at preschool-aged in children born very preterm was predicted by neonatal procedural pain and thalamic development.In a prospective longitudinal cohort study, N = 140 very preterm infants (median GA at birth 28 weeks) underwent MRI early-in-life and again at term-equivalent age. Children returned for assessment at 4.5 years. Parents reported on child sensory processing behaviors on the Short Sensory Profile. General linear models were used to assess factors associated with sensory processing behaviors, adjusting for clinical and demographic factors.Among extremely preterm neonates (born 24-28 weeks' GA), but not very-preterm neonates (29-32 weeks' GA), more invasive procedures were associated with poorer sensory processing (B = -0.09, 95%CI [-0.17, -0.01] p = 0.03). In the overall cohort, fewer sensory processing problems were associated with greater thalamic growth between birth and term-equivalent age (B = 0.3, 95%CI [0.11, 0.42], p 0.001). Extremely preterm neonates exposed to a high number of skin-breaking procedures who exhibited slower neonatal thalamic growth displayed the highest sensory processing problems (B = -26.2, 95%CI [-45.96, -6.38], p = 0.01).Early exposure to pain and related alterations in the developing thalamus may be a key factor underlying later sensory problems in children born extremely preterm.

ObjectivesTo assess the association of head circumference (HC) DesignIn a prospective cohort, semiautomatically segmented TCV and manually segmented white matter injury (WMI) volumes were obtained. Multivariable regressions were used to study the association of HC and TCV with neurodevelopmental outcomes, accounting for birth gestational age, WMI and postnatal illness.SettingParticipants born in 2006–2013 at British Columbia Women’s Hospital were recruited.Patients168 neonates had HC measurements at birth and discharge and MRI at term-equivalent age (TEA). 143 children were assessed at 4.5 years.Main outcome measuresMotor, cognitive and language outcomes at 4.5 years were assessed using the Movement Assessment Battery for Children Second Edition (M-ABC) and Wechsler Preschool and Primary Scale of Intelligence Third Edition Full Scale IQ (FSIQ) and Verbal IQ (VIQ).ResultsSmall birth HC was associated with lower M-ABC and FSIQ scores. In children with small birth HC, small discharge HC was associated with lower M-ABC, FSIQ and VIQ scores, while normal HC at discharge was no longer associated with adverse outcomes. HC strongly correlated with TCV at TEA. TCV did not correlate with outcomes.ConclusionsSmall birth HC is associated with poorer neurodevelopment, independent of postnatal illness and WMI. Normalisation of HC during NICU care appears to moderate this risk.

There have been concerns about the development of children conceived through assisted reproductive technology. Despite multiple studies investigating the outcomes of assisted conception, data focusing specifically on the neurodevelopmental outcomes of infants conceived through assisted reproductive technology and born preterm are limited.This study aimed to evaluate and compare the neurodevelopmental outcomes of preterm infants born at29 weeks' gestation at 18 to 24 months' corrected age who were conceived through assisted reproductive technology and those who were conceived naturally.This retrospective cohort study included inborn, nonanomalous infants, born at29 weeks' gestation between January 1, 2010, and December 31, 2016, who had a neurodevelopmental assessment at 18 to 24 months' corrected age at any of the 10 Canadian Neonatal Follow-Up Network clinics. The primary outcome was neurodevelopmental impairment at 18 to 24 months, defined as the presence of any of the following: cerebral palsy; Bayley-III cognitive, motor, or language composite score of85; sensorineural or mixed hearing loss; and unilateral or bilateral visual impairment. Secondary outcomes included mortality, composite of mortality or neurodevelopmental impairment, significant neurodevelopmental impairment, and each component of the primary outcome. We compared outcomes between infants conceived through assisted reproductive technology and those conceived naturally, using bivariate and multivariable analyses after adjustment.Of the 4863 eligible neonates, 651 (13.4%) were conceived using assisted reproductive technology. Maternal age; education level; and rates of diabetes mellitus, receipt of antenatal corticosteroids, and cesarean delivery were higher in the assisted reproduction group than the natural conception group. Neonatal morbidity and death rates were similar except for intraventricular hemorrhage, which was lower in the assisted reproduction group (33% [181 of 546] vs 39% [1284 of 3318]; P=.01). Of the 4176 surviving infants, 3386 (81%) had a follow-up outcome at 18 to 24 months' corrected age. Multivariable logistic regression adjusting for gestational age, antenatal steroids, sex, small for gestational age, multiple gestations, mode of delivery, maternal age, maternal education, pregnancy-induced hypertension, maternal diabetes mellitus, and smoking showed that infants conceived through assisted reproduction was associated with lower odds of neurodevelopmental impairment (adjusted odds ratio, 0.67; 95% confidence interval, 0.52-0.86) and the composite of death or neurodevelopmental impairment (adjusted odds ratio, 0.67; 95% confidence interval, 0.54-0.84). Conception through assisted reproductive technology was associated with decreased odds of a Bayley-III composite cognitive score of85 (adjusted odds ratio, 0.68; 95% confidence interval, 0.48-0.99) and composite language score of85 (adjusted odds ratio, 0.67; 95% confidence interval, 0.50-0.88).Compared with natural conception, assisted conception was associated with lower odds of adverse neurodevelopmental outcomes, especially cognitive and language outcomes, at 18 to 24 months' corrected age among preterm infants born at29 weeks' gestation. Long-term follow-up studies are required to assess the risks of learning disabilities and development of complex visual-spatial and processing skills in these children as they reach school age.

ObjectiveTo examine whether the family integrated care (FICare) programme, a multifaceted approach which enables parents to be engaged as primary caregivers in the neonatal intensive care unit, impacts infant neurodevelopment and growth at 18 months’ corrected age.Design/MethodsProspective cohort study of infants born ResultsOf 756 infants ConclusionsVery preterm infants exposed to FICare had no significant difference in incidence of cognitive or language delay but had better motor development.Trial registration numberParticipants in this cohort study were previously enrolled in a registered trial: NCT01852695

OBJECTIVE To compare neurodevelopmental outcomes of large and appropriate for gestational age (LGA, AGA) infants

Importance Maternal docosahexaenoic acid (DHA) supplementation may prevent bronchopulmonary dysplasia, but evidence remains inconclusive. Objective To determine whether maternal DHA supplementation during the neonatal period improves bronchopulmonary dysplasia–free survival in breastfed infants born before 29 weeks of gestation. Design, Setting, and Participants Superiority, placebo-controlled randomized clinical trial at 16 Canadian neonatal intensive care units (June 2015-April 2018 with last infant follow-up in July 2018). Lactating women who delivered before 29 weeks of gestation were enrolled within 72 hours of delivery. The trial intended to enroll 800 mothers, but was stopped earlier. Interventions There were 232 mothers (273 infants) assigned to oral capsules providing 1.2 g/d of DHA from randomization to 36 weeks’ postmenstrual age and 229 mothers (255 infants) assigned to placebo capsules. Main Outcomes and Measures The primary outcome was bronchopulmonary dysplasia–free survival in infants at 36 weeks’ postmenstrual age. There were 22 secondary outcomes, including mortality and bronchopulmonary dysplasia. Results Enrollment was stopped early due to concern for harm based on interim data from this trial and from another trial that was published during the course of this study. Among 461 mothers and their 528 infants (mean gestational age, 26.6 weeks [SD, 1.6 weeks]; 253 [47.9%] females), 375 mothers (81.3%) and 523 infants (99.1%) completed the trial. Overall, 147 of 268 infants (54.9%) in the DHA group vs 157 of 255 infants (61.6%) in the placebo group survived without bronchopulmonary dysplasia (absolute difference, –5.0% [95% CI, –11.6% to 2.6%]; relative risk, 0.91 [95% CI, 0.80 to 1.04],P = .18). Mortality occurred in 6.0% of infants in the DHA group vs 10.2% of infants in the placebo group (absolute difference, –3.9% [95% CI, –6.8% to 1.4%]; relative risk, 0.61 [95% CI, 0.33 to 1.13],P = .12). Bronchopulmonary dysplasia occurred in 41.7% of surviving infants in the DHA group vs 31.4% in the placebo group (absolute difference, 11.5% [95% CI, 2.3% to 23.2%]; relative risk, 1.36 [95% CI, 1.07 to 1.73],P = .01). Of 22 prespecified secondary outcomes, 19 were not significantly different. Conclusions and Relevance Among breastfed preterm infants born before 29 weeks of gestation, maternal docosahexaenoic acid supplementation during the neonatal period did not significantly improve bronchopulmonary dysplasia–free survival at 36 weeks’ postmenstrual age compared with placebo. Study interpretation is limited by early trial termination. Trial Registration ClinicalTrials.gov Identifier:NCT02371460

Background Very preterm children (VPT) are at high risk for developmental coordination disorder (DCD). The Movement Assessment Battery for Children-2 (MABC-2) Test is commonly used to identify children with DCD, but little is known about the predictive validity of this assessment in this population. Aims The aims of this study were to determine if MABC-2 scores at 3 years can predict DCD at 4.5 years and if DCD can be reliably identified in VPT children at 3 years. Methods and procedures In a retrospective sample of 165 VPT children, logistic regression was used to determine if the MABC-2 score at 3 years is predictive of DCD at 4.5 years. Cross-tabulations were used to determine the relationship between scores at 3 years and DCD at 4.5 years. Outcomes and results MABC-2 scores at age 3 were a significant predictor (OR = 0.82, p = 0.001) of DCD diagnosis at 4.5 years. The MABC-2 has excellent sensitivity (90%), moderate specificity (69%), small to moderate positive predictive value (38%) and high negative predictive value (97%). Conclusions and implications The MABC-2 is highly sensitive in identifying VPT children with DCD, but also has many false positives. MABC-2 scores can reliably predict VPT children who are not at risk of DCD.

We present a new method to identify anatomical subnetworks of the human connectome that are optimally predictive of targeted clinical variables, developmental outcomes or disease states. Given a training set of structural or functional brain networks, derived from diffusion MRI (dMRI) or functional MRI (fMRI) scans respectively, our sparse linear regression model extracts a weighted subnetwork. By enforcing novel backbone network and connectivity based priors along with a non-negativity constraint, the discovered subnetworks are simultaneously anatomically plausible, well connected, positively weighted and reasonably sparse. We apply our method to (1) predicting the cognitive and neuromotor developmental outcomes of a dataset of 168 structural connectomes of preterm neonates, and (2) predicting the autism spectrum category of a dataset of 1013 resting-state functional connectomes from the Autism Brain Imaging Data Exchange (ABIDE) database. We find that the addition of each of our novel priors improves prediction accuracy and together outperform other state-of-the-art prediction techniques. We then examine the structure of the learned subnetworks in terms of topological features and with respect to established function and physiology of different regions of the brain.

Background Behaviour problems are prevalent among children born very preterm (≤ 32 weeks gestation), and have been associated with morphine exposure. Morphine accumulation in the brain is determined by genetic variations related to morphine biotransformation. The objective of the study was to investigate whether morphine-biotransformation genotypes contribute to individual differences in long-term effects of morphine on behaviour at 18 months corrected age (CA). Methods 198 children born very preterm (24–32 weeks gestation) were followed from birth and seen at 18 months CA. Relationships between child behavior (Internalizing, Externalizing on the Child Behavior Checklist), morphine exposure, neonatal clinical variables, and morphine biotransformation gene variants in ABCB1, UGT1A9, UGT 2B7*2, ABCC2, ABCC3, SLCO1B1, CYP3A4, COMT were examined. Findings Neonatal clinical predictors and genotypes accounted for 39% of the overall variance in behaviour. In children with the minor allele of UGT1A9 rs17863783 (marker of UGT1A6*4, UDP-glucuronosyltransferase), greater morphine exposure (p = ·0011) was associated with more Internalizing behaviour. More Externalizing behaviour was predicted by greater morphine exposure in children with the COMT rs4680 Met/Met genotype (p = ·0006). Interpretation Genetic variations that affect relative accumulation of morphine in the brain, together with neonatal clinical factors, are differentially related to anxiety and depressive symptoms (internalizing) and to acting out (externalizing) behaviours at 18 months CA in children born very preterm. Fund NIH/NICHD HD039783 (REG); CIHR MOP86489 (REG), MOP68898 (SPM), MOP79262 (SPM, REG).

Children born preterm display altered sensory processing, which may manifest as hyper- and/or hypo-sensitivity to sensory information. In this vulnerable population, exposure to neonatal pain-related stress is associated with altered stress regulation, as indexed by alterations in cortisol levels. It is unknown whether sensory processing behaviors are also affected by early life adversity, and whether dysregulated cortisol is related to sensory processing problems in preterm children. We examined relationships between neonatal pain-related stress, sensory processing profiles and cortisol levels at age 4 years, and whether pathways were sex-specific. In a longitudinal prospective cohort study, N = 146 infants born 24-32 weeks gestational age were recruited from BC Women's Hospital, Vancouver, BC, Canada; neonatal factors were collected from daily chart review. At age 4 years, saliva to assay cortisol was collected three times across cognitive assessment (pre-test, during, end) and parents completed the Short Sensory Profile questionnaire. Using generalized linear modeling, independent of other neonatal factors, higher number of invasive procedures (pain/stress) was associated with more sensory processing problems (total, hypo- and hyper-sensitivity) for girls only. After accounting for neonatal factors, greater cortisol output across the assessment was associated with more total sensory processing problems in girls only, and hypersensitivity to sensory input in both boys and girls. Findings suggest that in children born very preterm, how a child responds to sensory input and cortisol reactivity to stress are related but may have different precursors. Girls may be somewhat more susceptible to neonatal pain-related stress exposure in relation to sensory processing at preschool age.

Objective To examine the association between cerebellar hemorrhage (CBH) size and location and preschool-age neurodevelopment in very preterm neonates. Methods Preterm magnetic resonance images of 221 very preterm neonates (median gestational age = 27.9 weeks) were manually segmented for CBH quantification and location. Neurodevelopmental assessments at chronological age 4.5 years included motor (Movement Assessment Battery for Children, 2nd Edition [MABC-2]), visuomotor integration (Beery-Buktenica Developmental Test of Visual-Motor Integration, 6th Edition), cognitive (Wechsler Primary and Preschool Scale of Intelligence, 3rd Edition), and behavioral (Child Behavior Checklist) outcomes. Multivariable linear regression models examined the association between CBH size and 4.5-year outcomes accounting for sex, gestational age, and supratentorial injury. Probabilistic maps assessed CBH location and likelihood of a lesion to predict adverse outcome. Results Thirty-six neonates had CBH: 14 (6%) with only punctate CBH and 22 (10%) with ≥1 larger CBH. CBH occurred mostly in the inferior aspect of the posterior lobes. CBH total volume was independently associated with MABC-2 motor scores at 4.5 years (β = -0.095, 95% confidence interval = -0.184 to -0.005), with a standardized β coefficient (-0.16) that was similar to that of white matter injury volume (standardized β = -0.22). CBH size was similarly associated with visuomotor integration and externalizing behavior but not cognition. Voxelwise odds ratio and lesion-symptom maps demonstrated that CBH extending more deeply into the cerebellum predicted adverse motor, visuomotor, and behavioral outcomes. Interpretation CBH size and location on preterm magnetic resonance imaging were associated with reduced preschool motor and visuomotor function and more externalizing behavior independent of supratentorial brain injury in a dose-dependent fashion. The volumetric quantification and localization of CBH, even when punctate, may allow opportunity to improve motor and behavioral outcomes by providing targeted intervention. ANN NEUROL 2020;88:1095-1108.

Background Very preterm infants are at high risk of death or severe morbidity. The objective was to determine the significance of severe congenital heart defects ( CHDs ) for these risks. Methods and Results This cohort study included infants from 10 countries born from 2007–2015 at 24 to 31 weeks’ gestation with birth weights CHDs were defined by International Classification of Diseases, Ninth Revision ( ICD‐9 ) and Tenth ( ICD‐10 ) codes and categorized as those compromising systemic output, causing sustained cyanosis, or resulting in congestive heart failure. The primary outcome was in‐hospital mortality. Secondary outcomes were neonatal brain injury, necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy of prematurity. Adjusted and propensity score–matched odds ratios ( ORs ) were calculated. Analyses were stratified by type of CHD , gestational age, and network. A total of 609 (0.77%) infants had severe CHD and 76 371 without any malformation served as controls. The mean gestational age and birth weight were 27.8 weeks and 1018 g, respectively. The mortality rate was 18.6% in infants with CHD and 8.9% in controls (propensity score–matched OR , 2.30; 95% CI , 1.61–3.27). Severe CHD was not associated with neonatal brain injury, necrotizing enterocolitis, or retinopathy of prematurity, whereas the OR for bronchopulmonary dysplasia increased. Mortality was higher in all types, with the highest propensity score–matched OR (4.96; 95% CI, 2.11–11.7) for CHD causing congestive heart failure. While mortality did not differ between groups at OR for mortality in infants with CHD increased to 10.9 (95% CI, 5.76–20.70) at 31 weeks’ gestational age. Rates of CHD and mortality differed significantly between networks. Conclusions Severe CHD is associated with significantly increased mortality in very preterm infants.

To assess whether Family Integrated Care (FICare) in the neonatal intensive care unit improves maternal chronic physiological stress and child behavior at 18 months of corrected age for infants born preterm.Follow-up of a multicenter, prospective cluster-randomized controlled trial comparing FICare and standard care of children born at33 weeks of gestation and parents, stratified by tertiary neonatal intensive care units, across Canada. Primary outcomes at 18 months of corrected age were maternal stress hormones (cortisol, ie, hair cumulative cortisol [HCC], dehydroepiandrosterone [DHEA]) assayed from hair samples. Secondary outcomes included maternal reports of parenting stress, child behaviors (Internalizing, Externalizing, Dysregulation), and observer-rated caregiving behaviors. Outcomes were analyzed using multilevel modeling.We included 126 mother-child dyads from 12 sites (6 FICare sites, n = 83; 6 standard care sites, n = 43). FICare intervention significantly lowered maternal physiological stress as indicated by HCC (B = -0.22 [-0.41, -0.04]) and cortisol/DHEA ratio (B = -0.25 [-0.48, -0.02]), but not DHEA (B = 0.01 [-0.11, 0.14]). Enrollment in FICare led to lower child Internalizing (B = -0.93 [-2.33, 0.02]) and Externalizing behavior T scores (B = -0.91 [-2.25, -0.01]) via improvements to maternal HCC (mediation). FICare buffered the negative effects of high maternal HCC on child Dysregulation T scores (B = -11.40 [-23.01, 0.21]; moderation). For mothers reporting high parenting stress at 18 months, FICare was related to lower Dysregulation T scores via maternal HCC; moderated mediation = -0.17 (-0.41, -0.01).FICare has long-term beneficial effects for mother and child, attenuating maternal chronic physiological stress, and improving child behavior in toddlerhood.NCT01852695.

Neonatal fungemia is associated with adverse neonatal outcomes and higher overall healthcare expenditure. Our objective is to review the epidemiology of invasive fungal infections (IFIs) in neonates in Canada.A retrospective cohort study using data collected by the Canadian Neonatal Network (CNN) was conducted. Using a nested matched cohort study design, risk factors and outcomes of neonates born33 weeks gestation (n = 39,305) during 2003-2013 were compared between neonates diagnosed with an IFI during their stay to infection-free controls.Overall incidence of IFI among all admitted neonates was 0.22% (n = 286), while the incidence of IFI in the group of neonates born33 weeks gestation was 0.64%. Of the isolates, 170 (59%) had Candida albicans and 59 (21%) had Candida parapsilosis. Risk factors for IFI were lower gestation, male sex, Apgar score7 at 5 minutes, higher severity of illness score, maternal diabetes and vaginal birth. Neonates with IFI had higher odds of mortality [adjusted odds ratio (aOR): 1.60; 95% confidence interval (CI): 1.06-2.43], necrotizing enterocolitis (aOR: 2.97; 95% CI: 1.76-5.01) and severe retinopathy of prematurity (aOR: 2.15; 95% CI: 1.26-3.67).The overall incidence of IFI in neonates was low in Canada in comparison to other large population cohort studies; however, the mortality and morbidity remained high.

Despite improved survival of preterm infants, there has not been an equivalent improvement in long-term neurodevelopmental outcomes. Adverse neurodevelopmental outcome rates and severity are inversely related to the degree of prematurity, but only 1.6% are born very preterm and the motor, cognitive, behavioral, and psychiatric disabilities in the large moderate and late preterm population have a greater impact. The disability-free preterm adult has a lower educational achievement and income but similar health-related quality of life to term controls. Reducing the long-term neurodevelopmental impact of prematurity is the next frontier of neonatal care.

Objective The aim of this study was to evaluate the association between neonatal seizure and neurodevelopmental impairment (NDI) at 18 to 24 months in extremely preterm neonates. The association between anticonvulsants use and NDI was also assessed. Study Design In this retrospective cohort study of infants born at Results Of the 2,762 eligible neonates, 133 (4.8%) had seizures. Infants who had seizures were of lower gestation (25.2 vs. 26.2 weeks) and birth weight (819 vs. 920 g) and had higher rates of adverse outcomes. Neonatal seizure was associated with higher odds of composite outcome of death or significant NDI (74 vs. 27%; adjusted odds ratio [OR]: 3.4; 95% confidence interval [CI]: 2.2–5.4). Death or significant NDI was higher in infants with seizures treated with anticonvulsants than those without treatment (89 vs. 70%); however, when adjusted for confounders, it was not significantly different (adjusted OR: 3.5; 95% CI: 0.83–14.6). Conclusion Neonatal seizures were independently associated with higher odds of death or significant NDI at 18 to 24 months of age. Relationship of anticonvulsant and neurodevelopmental outcomes needs further studies.

Preterm infants are at higher risk of developing hypothermia and complications from cold stress, resulting in high mortality and short-term morbidity. Our objective is to evaluate the association between admission temperatures of extremely low-gestational age neonates (ELGAN) (

BACKGROUND:Brain injury (BI) is reported in 60% of newborns with critical congenital heart disease as white matter injury (WMI) or stroke. Neurodevelopmental (ND) impairments are reported in these patients. The relationship between neonatal BI and ND outcome has not been established. OBJECTIVES:This study sought to determine the association between peri-operative BI and ND outcomes in infants with single ventricle physiology (SVP) and d-transposition of the great arteries (d-TGA). METHODS:Term newborns with d-TGA and SVP had pre-operative and post-operative brain magnetic resonance imaging and ND outcomes assessed at 12 and 30months with the Bayley Scales of Infant Development-II. BI was categorized by the brain injury severity score and WMI was quantified by volumetric analysis. RESULTS:A total of 104 infants had follow-up at 12months and 70 had follow-up at 30months. At 12months, only clinical variables were associated with ND outcome. At 30months, subjects with moderate-to-severe WMI had significantly lower Psychomotor Development Index (PDI) scores (13 points lower) as compared with those with none or minimal WMI for d-TGA and SVP (p=0.03 and p=0.05, respectively) after adjusting for various factors. Quantitative WMI volume was likewise associated. Stroke was not associated with outcome. The Bland-Altman limits of agreement for PDI scores at 12 and 30months were wide (-40.3 to 31.2) across the range of mean PDI values. CONCLUSIONS:Increasing burden of WMI is associated with worse motor outcomes at 30months for infants with criticalcongenital heart disease, whereas no adverse association was seen between small strokes and outcome. Theseresults support the utility of neonatal brain magnetic resonance imaging in this population to aid in predictinglateroutcomes and the importance of ND follow-up beyond 1 year of age.

Objective The objective is to evaluate the association between antibiotic utilization and neurodevelopmental outcomes at 18 to 21 months' corrected age among extremely low gestational age neonates without culture-proven sepsis or necrotizing enterocolitis (NEC). Study Design We conducted a retrospective cohort study of infants born between April 2009 and September 2011 at Result There were 1,373 infants who fulfilled our inclusion criteria. Compared with infants in the lowest AUR quartile (Q1), those in the highest quartile (Q4) had higher odds of death or sNDI (adjusted odds ratio [AOR] = 7.44; 95% confidence interval [CI]: 4.55, 12.2) and death (AOR = 39.3; 95% CI: 16.1, 95.9). Conclusion Our results indicate an association between high AUR and a composite outcome of death or adverse neurodevelopmental outcomes at 18 to 21 months' corrected age.

KEY POINTS Congenital diaphragmatic hernia (CDH), which occurs in about 1 in 3300 live births, is a congenital defect in the diaphragm that allows herniation of abdominal viscera into the thorax.[1][1] The resulting abnormal lung development leads to pulmonary hypoplasia and pulmonary hypertension

To examine rates and determinants of mother's own milk (MOM) feeding at hospital discharge in a cohort of infants born very preterm within the Canadian Neonatal Network (CNN).This was a population-based cohort study of infants born at33 weeks of gestation and admitted to neonatal intensive care units (NICUs) participating in the CNN between January 1, 2015, and December 31, 2018. We examined the rates and determinants of MOM use at discharge home among the participating NICUs. We used multivariable logistic regression analysis to identify independent determinants of MOM feeding.Among the 6404 infants born very preterm and discharged home during the study period, 4457 (70%) received MOM or MOM supplemented with formula. Rates of MOM feeding at discharge varied from 49% to 87% across NICUs. Determinants associated with MOM feeding at discharge were gestational age 29-32 weeks compared with26 weeks (aOR 1.56, 95% CI 1.25-1.93), primipara mothers (aOR 2.12, 95% CI 1.86-2.42), maternal diabetes (aOR 0.79, 95% CI 0.66-0.93), and maternal smoking (aOR 0.27, 95% CI 0.19-0.38). Receipt of MOM by day 3 of age was the major predictor of breast milk feeding at discharge (aOR 3.61, 95% CI 3.17-4.12).Approximately two-thirds of infants born very preterm received MOM at hospital discharge, and rates varied across NICUs. Supporting mothers to provide breast milk in the first 3 days after birth may be associated with improved MOM feeding rates at discharge.

BackgroundHuman studies investigating the link between postnatal polyunsaturated fatty acids and preterm brain growth are limited, despite emerging evidence of potential effects on outcomes.MethodsSixty preterm neonates

To compare the neurodevelopmental outcomes at 18 to 21 months corrected age (CA) of infants born at29 weeks that received room air, an intermediate oxygen concentration or 100% oxygen at the initiation of resuscitation.In this retrospective cohort study, we compared neonatal and neurodevelopmental outcomes at 18 to 21 months CA among inborn infants born before 29 weeks' gestation that received room air, intermediate oxygen concentration or 100% oxygen at the initiation of resuscitation.Of 1509 infants, 445 received room air, 483 received intermediate oxygen concentrations and 581 received 100% oxygen. Compared to infants that received room air, the primary outcome of death or neurodevelopmental impairment (NDI) was not different in intermediate oxygen (adjusted odds ratio (aOR) 1.01; 95% confidence interval (CI) 0.77, 1.34) or 100% oxygen (aOR 1.03; 95% CI 0.78, 1.35). Compared to room air, there was no difference in odds of death or severe NDI in intermediate oxygen (aOR 1.14; 95% CI 0.82, 1.58) or 100% oxygen group (aOR 1.22; 95% CI 0.90, 1.67). The odds of severe NDI among survivors were significantly higher in infants that received 100% oxygen as compared to room air (aOR 1.57, 95% CI 1.05, 2.35).We observed no significant difference in the primary composite outcomes of death or NDI and death or severe NDI at 18 to 21 months CA between infants that received room air, intermediate oxygen concentration or 100% oxygen at the initiation of resuscitation. However, use of 100% oxygen was associated with increased odds of severe NDI among survivors as compared to room air.

Objectives The objective of this study was to describe survival, short-term, and long-term morbidities of neonates with birth weight Study Design Retrospective cohort studies to calculate survival, short-term, and long-term morbidity rates of neonates born weighing Results Of 549 inborn neonates with birth weight Conclusion Only 4% of births

To compare neonatal outcomes of twins delivered33 weeks' gestation in tertiary centers in Canada according to the mode of birth and presentation.This retrospective cohort from the Canadian Neonatal Network database studied preterm twins born from 24 + 0 to 32 + 6 weeks' gestation between 2005 and 2012. Twins were grouped by the mode of birth: both vaginal, combined vaginal/cesarean section (CS), and both CS. Additionally, twins were grouped by the mode of presentation: both vertex, vertex/breech, breech/vertex, and both breech. The primary outcome was a composite of mortality or severe neonatal morbidity (severe neurological injury [intraventricular hemorrhage grade 3/4 or periventricular leukomalacia], bronchopulmonary dysplasia, retinopathy of prematurity, and necrotizing enterocolitis).Of the 6636 twins, 1934 (29%) were delivered vaginally, 418 (6%) by combined vaginal birth/CS, and 4284 (65%) were born by CS. The composite did not differ between the groups. However, severe neurological injury was decreased (adjusted odds ratio [AOR], 0.77; 95% confidence interval [CI], 0.61-0.98) and respiratory distress syndrome (AOR, 1.34; 95%CI, 1.15-1.56) was increased when both the twins were delivered by CS.Preterm twin infants born via CS experienced less severe neurological injury when compared to those delivered vaginally, but had an increase in respiratory distress syndrome.

Background Antenatal exposure to selective serotonin reuptake inhibitors (SSRIs) is associated with an enhanced risk of preterm birth. Very preterm-born neonates (

BACKGROUND: Preterm birth is the leading cause of morbidity and mortality in children younger than 5 years. We report the changes in neonatal outcomes and care practices among very preterm infants in Canada over 14 years within a national, collaborative, continuous quality-improvement program. METHODS: We retrospectively studied infants born at 23–32 weeks’ gestation who were admitted to tertiary neonatal intensive care units that participated in the Evidence-based Practice for Improving Quality program in the Canadian Neonatal Network from 2004 to 2017. The primary outcome was survival without major morbidity during the initial hospital admission. We quantified changes using process-control charts in 6-month intervals to identify special-cause variations, adjusted regression models for yearly changes, and interrupted time series analyses. RESULTS: The final study population included 50 831 infants. As a result of practice changes, survival without major morbidity increased significantly (56.6% [669/1183] to 70.9% [1424/2009]; adjusted odds ratio [OR] 1.08, 95% confidence interval [CI] 1.06–1.10, per year) across all gestational ages. Survival of infants born at 23–25 weeks’ gestation increased (70.8% [97/137] to 74.5% [219/294]; adjusted OR 1.03, 95% CI 1.02–1.05, per year). Changes in care practices included increased use of antenatal steroids (83.6% [904/1081] to 88.1% [1747/1983]), increased rates of normothermia at admission (44.8% [520/1160] to 67.5% [1316/1951]) and reduced use of pulmonary surfactant (52.8% [625/1183] to 42.7% [857/2009]). INTERPRETATION: Network-wide quality-improvement activities that include better implementation of optimal care practices can yield sustained improvement in survival without morbidity in very preterm infants.

Objectives To examine the association between mortality or neurodevelopmental impairment at 18-24 months of corrected age and the Transport Risk Index of Physiologic Stability (TRIPS) score on admission to the neonatal intensive care unit (NICU) in extremely premature infants. Study design Retrospective cohort study of extremely premature infants (inborn and outborn) born at 22-28 weeks of gestational age and admitted to NICUs in the Canadian Neonatal Network between April 2009 and September 2011. TRIPS scores and clinical data were collected from the Canadian Neonatal Network database. Follow-up data at 18-24 months of corrected age were retrieved from the Canadian Neonatal Follow-Up Network database. Neurodevelopment was assessed using the Bayley Scales of Infant and Toddler Development, Edition III. The primary outcome was death or significant neurodevelopmental impairment at 18-24 months of corrected age. The secondary outcomes were individual components of the Bayley Scales of Infant and Toddler Development, Edition III assessment. Results A total of 1686 eligible infants were included. A TRIPS score of ≥20 on admission to the NICU was significantly associated with mortality (aOR 2.71 [95% CI, 2.02-3.62]) and mortality or significant neurodevelopmental impairment (aOR 1.91 [95% CI, 1.52-2.41]) at 18-24 months of corrected age across all gestational age groups of extremely premature infants. Conclusion The TRIPS score on admission to the NICU can be used as an adjunctive, objective tool for counselling the parents of extremely premature infants early after their admission to the NICU.

BackgroundHospitalized infants undergo multiple painful procedures daily. Despite the significant evidence, procedural pain assessment and management continues to be suboptimal. Repetitive and untreated pain at this vital developmental juncture is associated with negative behavioral and neurodevelopmental consequences. To address this knowledge to practice gap, we developed the web-based Implementation of Infant Pain Practice Change (ImPaC) Resource to guide change in healthcare professionals’ pain practice behaviors. This protocol describes the evaluation of the intervention effectiveness and implementation of the Resource and how organizational context influences outcomes.MethodsAn effectiveness-implementation hybrid type 1 design, blending a cluster randomized clinical trial and a mixed-methods implementation study will be used. Eighteen Neonatal Intensive Care Units (NICUs) across Canada will be randomized to intervention (INT) or standard practice (SP) groups. NICUs in the INT group will receive the Resource for six months; those in the SP group will continue with practice as usual and will be offered the Resource after a six-month waiting period. Data analysts will be blinded to group allocation. To address the intervention effectiveness, the INT and SP groups will be compared on clinical outcomes including the proportion of infants who have procedural pain assessed and managed, and the frequency and nature of painful procedures. Data will be collected at baseline (before randomization) and at completion of the intervention (six months). Implementation outcomes (feasibility, fidelity, implementation cost, and reach) will be measured at completion of the intervention. Sustainability will be assessed at six and 12 months following the intervention. Organizational context will be assessed to examine its influence on intervention and implementation outcomes.DiscussionThis mixed-methods study aims to determine the effectiveness and the implementation of a multifaceted online strategy for changing healthcare professionals’ pain practices for hospitalized infants. Implementation strategies that are easily and effectively implemented are important for sustained change. The results will inform healthcare professionals and decision-makers on how to address the challenges of implementing the Resource within various organizational contexts.Trial registrationClinicalTrials.gov,NCT03825822. Registered 31 January 2019.

To develop and validate an itemized costing algorithm for in-patient neonatal intensive care unit (NICU) costs for infants born prematurely that can be used for quality improvement and health economic analyses.We sourced patient resource use data from the Canadian Neonatal Network database, with records from infants admitted to 30 tertiary NICUs in Canada. We sourced unit cost inputs from Ontario hospitals, schedules of benefits, and administrative sources. Costing estimates were generated by matching patient resource use data to the appropriate unit costs. All cost estimates were in 2017 Canadian dollars and assigned from the perspective of a provincial public payer. Results were validated using previous estimates of inpatient NICU costs and hospital case-cost estimates.We assigned costs to 27 742 infants born prematurely admitted from 2015 to 2017. Mean (SD) gestational age and birth weight of the cohort were 31.8 (3.5) weeks and 1843 (739) g, respectively. The median (IQR) cost of hospitalization before NICU discharge was estimated as $20 184 ($9739-51 314) for all infants; $11 810 ($6410-19 800) for infants born at gestational age of 33-36 weeks; $30 572 ($16 597-$51 857) at gestational age of 29-32 weeks; and $100 440 ($56 858-$159 3867) at gestational age of29 weeks. Cost estimates correlated with length of stay (r = 0.97) and gestational age (r = -0.65). The estimates were consistent with provincial resource estimates and previous estimates from Canada.NICU costs for infants with preterm birth increase as gestation decreases and length of stay increases. Our cost estimates are easily accessible, transparent, and congruent with previous cost estimates.

ObjectivesTo identify the probability of survival and severe neurodevelopmental impairment (sNDI) at which perinatal physicians would or would not offer or recommend resuscitation at birth for extremely preterm infants.MethodsA Delphi process consisting of five rounds was implemented to seek consensus (>80% agreement) amongst British Columbia perinatal physicians. The first-round consisted of neonatal and maternal-fetal-medicine Focus Groups. Rounds two to five surveyed perinatal physicians, building upon previous rounds. Draft guidelines were developed and agreement sought.ResultsBased on 401 responses across all rounds, consensus was obtained that resuscitation should not be offered if survival probability 70 to 90% and resuscitation standard care if survival without sNDI >90%.ConclusionsThis physician consensus-based, objective framework for the management of an anticipated extremely preterm infant is a transparent alternative to existing guidelines, minimizing gestational-ageism and allowing for individualized management utilizing up-to-date data. Further input from other key stakeholders will be required prior to guideline implementation.