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Introduction:Young adults born very preterm have increased cardiovascular risks. While intima-media thickness of the common carotid artery is an early marker of atherosclerosis in adults, the most reliable method of its measurement is not established in this population. The purpose of this study is to compare manual and semi-automated B-mode ultrasound intima-media thickness measurement techniques in adults born very preterm and full-term. Methods:Intima-media thickness was measured in adults 18 to 29 years born very preterm (<30 weeks’ gestation) or full-term (≥37 weeks’ gestation) using B-mode ultrasound. Analyses included intraclass correlation coefficient (ICC) and relationships with prematurity status, age, body mass index, and metabolic and respiratory comorbidities. Results:There were 86 preterm-born participants (58% women) and 85 full-term (56% women), mean age 23 ± 2 years. Intra-observer agreement was better using semi-automated (ICC = 0.89; 95% confidence interval (CI) = [0.86-0.91]) than manual measurement (ICC = 0.73; 95% CI = [0.65-0.79]). Measures obtained using both techniques did not detect any differences according to prematurity status, did not correlate with age, and moderately correlated with body mass index. The semi-automated technique showed higher intima-media thickness values in men vs women and overall gave higher values. Results obtained through both techniques moderately correlated with each other when looking at subgroups: preterm group ICC of 0.53, full-term group ICC of 0.62. Conclusion:Manual and semi-automated intima-media thickness measurements moderately correlate in young adults. The semi-automated technique is more reproducible. Both techniques are useful in discriminating intima-media thickness according to weight. This study identifies variance of results according to different techniques of measurements. Adherence to a single technique is recommended in young adults born prematurely. Clinical implication includes adherence to the same technique for risk stratification and for follow-up of these patients.

The primary objective of this study was to evaluate the feasibility and acceptability of the study design of a randomized controlled trial, and an experimental neonatal nursing intervention.

ObjectivesExtremely preterm babies have a significant risk of neurodevelopmental impairment (NDI). There has been little investigation regarding the impact of prematurity on families. The objective of this study was to explore parental perspectives regarding the impact of prematurity on themselves/their family.MethodsOver 1 year, parents of children born <29 weeks’ gestational age (GA) who were between 18 months old and 7 years old and came for their follow-up visit were invited to participate. They were asked to categorise the impacts of prematurity on their life and their family as positive, negative or both and to describe those impacts in their own words. Thematic analysis was performed by a multidisciplinary group, including parents. Logistic regression was performed to compare parental responses.ResultsAmong parents (n=248, 98% participation rate), most (74%) reported that their child’s prematurity had both positive and negative impacts on their life or their family’s life, while 18% reported only positive impacts and 8% only negative impacts. These proportions were not correlated with GA, brain injury, nor level of NDI. The positive impacts reported included: an improved outlook on life, such as gratitude and perspective (48%), stronger family relationships (31%) and the gift of the child (28%). The negative themes were stress and fear (42%), loss of equilibrium due to medical fragility (35%) and concerns about developmental outcomes including the child’s future (18%).ConclusionParents report both positive and negative impacts after an extremely preterm birth, independent of disability. These balanced perspectives should be included in neonatal research, clinical care and provider education.

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 <28 weeks’ gestation in year 2011.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.

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 <29 weeks’ gestational age presenting at a neonatal follow-up clinic over a 1-year period were asked to evaluate their children’s health and development. They were also asked the following question: ‘if you could improve two things about your child, what would they be?’ Responses were analysed using mixed methods. Logistic regressions were done to compare parental responses.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.

Objective: To assess the association of maternal illicit drug abuse before or during pregnancy with future fractures in offspring.Methods: We performed a longitudinal cohort study of 792,022 infants born in hospitals of Quebec, Canada, between 2006 and 2016, with 5,457,634 person-years of follow-up. The main exposure was maternal substance abuse before or during pregnancy, including cocaine, opioid, cannabis, and other illicit drugs. The main outcome measure was hospitalization for traumatic fracture in offspring up to 12 years of age. We used adjusted Cox regression models to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association of maternal drug abuse with the subsequent risk of fracture in children.Results: The incidence of child fractures was higher for maternal illicit drug abuse than no drug abuse (21.2 vs. 15.4 per 10,000 person-years). Maternal drug abuse before or during pregnancy was associated with 2.35 times the risk of assault-related fractures (95% CI, 1.29 to 4.27) and 2.21 times the risk of transport accident-related fractures (95% CI, 1.34 to 3.66), compared with no drug abuse. Associations were strongest before 6 months of age for assault-related fractures (HR = 2.14; 95% CI, 0.97 to 4.72) and after 6 years for transport-related fractures (HR = 2.86; 95% CI, 1.35 to 6.05). Compared with no drug abuse, associations with assault and transport-related fractures were elevated for all drugs including cocaine, opioids, and cannabis.Conclusions: Maternal illicit drug abuse is associated with future child fractures due to assault and transport accidents.

Background:Risk factors for severe outcomes of SARS-CoV-2 infection are not well established in children. We sought to describe pediatric hospital admissions associated with SARS-CoV-2 infection in Canada and identify risk factors for more severe disease.Methods:We conducted a national prospective study using the infrastructure of the Canadian Paediatric Surveillance Program (CPSP). Cases involving children who were admitted to hospital with microbiologically confirmed SARS-CoV-2 infection were reported from Apr. 8 to Dec. 31 2020, through weekly online questionnaires distributed to the CPSP network of more than 2800 pediatricians. We categorized hospital admissions as related to COVID-19, incidental, or for social or infection control reasons and determined risk factors for disease severity in hospital.Results:Among 264 hospital admissions involving children with SARS-CoV-2 infection during the 9-month study period, 150 (56.8%) admissions were related to COVID-19 and 100 (37.9%) were incidental infections (admissions for other reasons and found to be positive for SARS-CoV-2 on screening). Infants (37.3%) and adolescents (29.6%) represented most cases. Among hospital admissions related to COVID-19, 52 (34.7%) had critical disease, 42 (28.0%) of whom required any form of respiratory or hemodynamic support, and 59 (39.3%) had at least 1 underlying comorbidity. Children with obesity, chronic neurologic conditions or chronic lung disease other than asthma were more likely to have severe or critical COVID-19.Interpretation:Among children who were admitted to hospital with SARS-CoV-2 infection in Canada during the early COVID-19 pandemic period, incidental SARS-CoV-2 infection was common. In children admitted with acute COVID-19, obesity and neurologic and respiratory comorbidities were associated with more severe disease.

RésuméContexte:Les facteurs de risque de complications graves de l’infection par le SRAS-CoV-2 n’ont pas été bien établis chez les enfants. Nous avons voulu décrire les hospitalisations pédiatriques associées au SRAS-CoV-2 au Canada et identifier les facteurs de risque de maladie grave.Méthodes:Nous avons procédé à une étude prospective nationale en utilisant l’infrastructure du Programme canadien de surveillance pédiatrique (PCSP). Les hospitalisations d’enfants ayant contracté une infection par le SRAS-CoV-2 confirmée en laboratoire de microbiologie ont été rapportées du 8 avril au 31 décembre 2020 au moyen de questionnaires hebdomadaires en ligne distribués au réseau du PCSP, qui compte plus de 2800 pédiatres. Nous avons catégorisé les hospitalisations comme suit : liées à la COVID-19, infections découvertes fortuitement, ou hospitalisations pour des raisons sociales ou de contrôle des infections, et dégagé les facteurs de risque associés à la gravité de la maladie chez les patients hospitalisés.Résultats:Sur les 264 hospitalisations d’enfants ayant contracté le SRAS-CoV-2 au cours de la période de l’étude de 9 mois, 150 (56,8 %) ont été associées à la COVID-19 et 100 (37,9 %) étaient des cas découverts fortuitement (admission pour d’autres raisons et découverte fortuite du SRAS-CoV-2 par dépistage positif). Les nourrissons (37,3 %) et les adolescents (29,6 %) représentaient la majorité des cas. Parmi les hospitalisations liées à la COVID-19, 52 patients (34,7 %) étaient atteints d’une forme grave de la maladie, dont 42 (28,0 % des cas liés à la COVID-19) ont eu besoin d’une forme d’assistance respiratoire ou hémodynamique, et 59 (39,3 %) présentaient au moins 1 comorbidité sous-jacente. Les enfants atteints d’obésité, de maladies neurologiques chroniques ou de maladies pulmonaires chroniques, à l’exclusion de l’asthme, étaient plus susceptibles de présenter une forme grave ou critique de la COVID-19.Interprétation:Parmi les enfants hospitalisés au Canada chez lesquels on a diagnostiqué une infection par le SRAS-CoV-2 au début de la pandémie de COVID-19, la découverte fortuite du SRAS-CoV-2 a été fréquente. Chez les enfants hospitalisés pour une COVID-19 aiguë, l’obésité et les comorbidités neurologiques et respiratoires ont été associées à une gravité accrue.

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BackgroundAlthough erythropoiesis is impaired and anaemia frequent in neonates born preterm, haematopoiesis in adults born preterm has not been previously studied.ObjectiveWe, thus, aimed to evaluate haemoglobin and erythropoietin levels in young adults born preterm, to identify neonatal events associated with erythropoiesis in adulthood and to examine the relationships of haemoglobin levels with respiratory function and blood pressure.MethodsWe assessed a cohort of 101 young adults (ages 18–29) born preterm (≤29 weeks of gestation), in comparison to 105 full-term controls. We measured haemoglobin, erythropoietin levels and blood pressure. We also assessed respiratory function using spirometry.ResultsCompared with controls, tobacco use and sex-adjusted haemoglobin levels were 5.3 (95% CI 2.9 to 7.7) g/L higher in preterm-born individuals, but erythropoietin levels were similar. Duration of oxygen supplementation in the neonatal period was independently associated with higher haemoglobin levels in the preterm group. In young adults born preterm with bronchopulmonary dysplasia, airflow limitation was associated with higher haemoglobin levels. Both systolic (SBP) and diastolic (DBP) blood pressure were increased in individuals born preterm (p=0.042 and p=0.0008, respectively). Higher haemoglobin levels were associated with higher SBP and DBP, independently of term or preterm status. Mediation analysis suggests that haemoglobin increase contributes to 37% and 32% of the effect of preterm birth on SBP and DBP, respectively.ConclusionsHaemoglobin levels are higher in young adults born preterm, while erythropoietin levels are similar, especially in case of bronchopulmonary dysplasia and airflow limitation, and haemoglobin increase is associated with elevated blood pressure in this population.

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BACKGROUND:Neonatal abstinence syndrome is increasingly prevalent, and may be related to opioid use disorders caused by postoperative prescriptions for pain control. We assessed the association of maternal prepregnancy surgery with risk of neonatal abstinence syndrome from opioid use disorders in future pregnancies.METHODS:We conducted a longitudinal retrospective cohort study of 2 182 365 deliveries in Quebec, Canada, between 1989 and 2016. The main exposure was maternal prepregnancy surgery. The main outcome measure was neonatal abstinence syndrome in offspring. We adjusted associations for maternal comorbidity and pregnancy characteristics using log-binomial regression models.RESULTS:The prevalence of neonatal abstinence syndrome in the cohort was 10.7 per 10 000 births. Compared with no surgery, prepregnancy surgery was associated with a risk ratio (RR) of neonatal abstinence syndrome of 1.63 (95% confidence interval [CI] 1.49–1.78). Risk was greater for 3 or more prepregnancy surgeries (RR 2.34, 95% CI 2.07–2.63) and age < 15 years at first surgery (1 surgery: RR 2.08, 95% CI 1.71–2.54; 2 or more surgeries: RR 2.79, 95% CI 2.32–3.37). Nearly all surgical specialties increased the risk of neonatal abstinence syndrome, but associations were strongest for cardiothoracic surgery (RR 4.45, 95% CI 2.87–6.91), neurosurgery (RR 3.00, 95% CI 1.56–5.77) and urologic surgery (RR 3.03, 95% CI 2.16–4.26).INTERPRETATION:Prepregnancy surgery is associated with the risk of neonatal abstinence syndrome in future pregnancies. Prescription opioids for postsurgical pain may result in opioid use disorders during future pregnancies, inadvertently increasing the risk of neonatal abstinence syndrome in offspring.

Survivors of extremely preterm birth are at risk of re-hospitalization but risk factors in the Canadian population are unknown. Our objective is to identify neonatal, sociodemographic, and geographic characteristics that predict re-hospitalization in Canadian extremely preterm neonates.

Extremely preterm babies are exposed to various sources of injury during critical stages of development. The extremely preterm infant faces premature transition to ex utero physiology and undergoes adaptive mechanisms that may be deleterious in the long term because of permanent alterations in organ structure and function. Perinatal events can also directly cause structural injury. These disturbances induce morphologic and functional changes in their organ systems that might heighten their risks for later adult chronic diseases. This review examines the pathophysiology of programming of long-term health and diseases after preterm birth and associated perinatal risk factors.

Preterm birth severely disrupts the normal developmental maturation of organ systems, resulting in lasting adverse effects. High blood pressure, cardiac dysfunction, obstructive lung disease, elevated blood glucose, and mental health problems occur earlier and at higher rates in the preterm-born than in the term populations. Disadvantageous health conditions may have a significant impact on the well-being of preterm-born individuals from childhood through adulthood. This review summarizes the impact of preterm birth on neurodevelopment and on cardiovascular, renal, metabolic, and pulmonary health.

Bronchopulmonary dysplasia, the most common pulmonary complication of extremely preterm (EPT) birth, has longstanding multiorgan repercussions, with increasing reports of emphysema and cardiac disease in early adulthood. There are currently no clear recommendations pertaining to best practices for optimal multidisciplinary cardiorespiratory follow-up of EPT children. We report the outcomes of a 2-day consensus workshop involving a Canadian panel of 31 multidisciplinary experts with the goal of improvement and standardization of the cardiopulmonary follow-up care of EPT infants (i.e., born at <28 weeks' gestation), from neonatal discharge to mid childhood. The most relevant and important clinical outcomes to evaluate were identified. Practical aspects of integrating cardiopulmonary follow-up into ambulatory care clinics were explored. This article summarizes the discussions from this workshop and provides the panel's recommendations for clinical follow-up and research priorities.

Preterm birth is associated with alteration of the vascular tree that can result in disease states such as bronchopulmonary dysplasia and retinopathy of prematurity during the neonatal period and emphysema and hypertension in adulthood. Studies have suggested a potential role for endothelial progenitor cells in the pathophysiology of prematurity‐related complications involving blood vessels; however, this knowledge has never been synthesized. We conducted a systematic review of the published data to examine the characteristics of endothelial progenitor cells in relation to preterm birth in humans. Preterm infants compared with term controls displayed similar or increased circulating/cord blood endothelial progenitor cell counts. However, the preterm endothelial progenitor cells were more vulnerable to exogenous factors such as oxidative stress. A reduced number, in particular of endothelial colony‐forming cells, was associated with bronchopulmonary dysplasia. No studies have examined endothelial progenitor cells beyond the neonatal period. These findings could prove useful in the identification of biomarkers for prognostication or therapeutic strategies for vascular‐related diseases in preterm‐born individuals. StemCellsTranslationalMedicine2017;6:7–13

Twinning is currently considered a complex multifactorial trait. Few studies have explored how the unique genetic and environmental influences that create twinning affect phenotypes and outcomes. Previous data has shown that twins account for a significant proportion of preterm and lowbirthweight infants, who are at risk for longterm neurodevelopmental disabilities such as cerebral palsy and cognitive impairment. More recently, it has been postulated that even without these comorbidities, twinning in and of itself may incur a neurodevelopmental disadvantage even among term newborns. The purpose of this review is to report primarily on neuromotor outcomes of twins compared to singletons. In addition, we describe specific environmental risk factors among twins which are associated with poorer outcomes. Several putative neurodevelopmental modulators are explored, including death of a cotwin, chorionicity, birth weight discordance, and twintwin transfusion. By teasing out environmental influences that potentially influence neurocognitive outcomes, families can receive more specific counseling and developmental services can be provided to those twins at especially high risk. © 2009 WileyLiss, Inc.

Adults born preterm are at a higher risk of cardiopulmonary disease and premature death. Preterm birth is associated with abnormalities in right ventricular (RV) structure and function, but the impact of bronchopulmonary dysplasia (BPD), a common complication of extremely preterm birth, on these parameters remains unknown.

Preterm infants are at increased risk of osteopenia of prematurity due to insufficient bone mineral accretion. Data on long term effects of prematurity on bone health are conflicting. This study aimed to compare bone mineral density (BMD) in young adults born very preterm and full-term controls and to examine factors associated with long-term bone health.

ObjectivesIdentify determinants of neurodevelopmental outcome in preterm children.MethodsProspective national cohort study of children born between 2009 and 2011 at <29 weeks gestational age, admitted to one of 28 Canadian neonatal intensive care units and assessed at a Canadian Neonatal Follow-up Network site at 21 months corrected age for cerebral palsy (CP), visual, hearing and developmental status using the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III). Stepwise regression analyses evaluated the effect of (1) prenatal and neonatal characteristics, (2) admission severity of illness, (3) major neonatal morbidities, (4) neonatal neuroimaging abnormalities, and (5) site on neurodevelopmental impairment (NDI) (Bayley-III score < 85, any CP, visual or hearing impairment), significant neurodevelopmental impairment (sNDI) (Bayley-III < 70, severe CP, blind or hearing aided and sNDI or death.ResultsOf the 3700 admissions without severe congenital anomalies, 84% survived to discharge and of the 2340 admissions, 46% (IQR site variation 38%–51%) had a NDI, 17% (11%–23%) had a sNDI, 6.4% (3.1%–8.6%) had CP, 2.6% (2.5%–13.3%) had hearing aids or cochlear implants and 1.6% (0%–3.1%) had a bilateral visual impairment. Bayley-III composite scores of <70 for cognitive, language and motor domains were 3.3%, 10.9% and 6.7%, respectively. Gestational age, sex, outborn, illness severity, bronchopulmonary dysplasia, necrotising enterocolitis, late-onset sepsis, retinopathy of prematurity, abnormal neuroimaging and site were significantly associated with NDI or sNDI. Site variation ORs for NDI, sNDI and sNDI/death ranged from 0.3–4.3, 0.04–3.5 and 0.12–1.96, respectively.ConclusionMost preterm survivors are free of sNDI. The risk factors, including site, associated with neurodevelopmental status suggest opportunities for improving outcomes.