Impact of preterm birth on muscle mass and function: a systematic review and meta-analysis.

Individuals born preterm present lower exercise capacity. Along with the cardiopulmonary responses and activity level, muscle strength is a key determinant of exercise capacity. This systematic review aimed to summarize the current knowledge on the impact of preterm birth on skeletal muscle mass and function across the lifespan. The databases PubMed, MEDLINE, EBM, Embase, CINAHL Plus, Global Index Medicus, and Google Scholar were searched using keywords and MeSH terms related to skeletal muscle, preterm birth, and low birth weight. Two independent reviewers undertook study selection, data extraction, and quality appraisal using Covidence review management. Data were pooled to estimate the prematurity effect on muscle mass and function using the R software. From 4378 studies retrieved, 132 were full-text reviewed and 25 met the inclusion/exclusion criteria. Five studies presented a low risk of bias, and 5 had a higher risk of bias due to a lack of adjustment for confounding factors and presenting incomplete outcomes. Meta-analyses of pooled data from homogenous studies indicated a significant reduction in muscle thickness and jump test (muscle power) in individuals born preterm versus full-term with standardized mean difference and confidence interval of - 0.58 (0.27, 0.89) and - 0.45 (0.21, 0.69), respectively.    Conclusion: Overall, this systematic review summarizing the existing literature on the impact of preterm birth on skeletal muscle indicates emerging evidence that individuals born preterm, display alteration in the development of their skeletal muscle mass and function. This work also highlights a clear knowledge gap in understanding the effect of preterm birth on skeletal muscle development. What is Known: • Preterm birth, which occurs at a critical time of skeletal muscle development and maturation, impairs the development of different organs and tissues leading to a higher risk of comorbidities such as cardiovascular diseases. • Preterm birth is associated with reduced exercise capacity. What is New: • Individuals born preterm display alterations in muscle mass and function compared to individuals born at term from infancy to adulthood. • There is a need to develop preventive or curative interventions to improve skeletal muscle health in preterm-born individuals.

Cardiopulmonary response to exercise in adults born very preterm.

This study aims to compare cardiopulmonary response to aerobic exercise between young adults born very preterm, including a subgroup with bronchopulmonary dysplasia (BPD), and term controls.Seventy-one adults (18-29 years) born <30 weeks' gestational age (24 with BPD) and 73 term controls were recruited. Assessment included cardiopulmonary exercise testing with impedance cardiography. We compared group differences in peak O2 consumption (peak VO2) and in ventilatory and cardiovascular responses to exercise using linear regression analyses.Preterm participants had reduced peak VO2 (mean difference -2.7; 95% CI -5.3, -0.1 mL·kg-1 lean body mass·min-1) versus controls. Those with BPD achieved lower peak work-rate compared to term controls (-21; 95% CI -38, -5 watts). There was no difference across groups in breathing reserve, ventilatory efficiency, peak heart rate and cardiac output. VO2 to work-rate relationship (ΔVO2/ΔWR) was reduced in preterm versus term. Peak systolic blood pressure and circulatory power (systolic blood pressure*VO2) were also lower in BPD versus term controls. In the preterm group, longer NICU stay and lower peak cardiac output were associated with lower peak VO2Results suggest limitations with peripheral O2 uptake in the muscle with reduced ΔVO2/ΔWR and peak circulatory power, but normal cardiac output. Investigations into skeletal muscle perfusion and O2 use during exercise are warranted to better understand mechanisms of exercise limitation.

Sleep-disordered breathing symptoms and their association with structural and functional pulmonary changes in children born extremely preterm.

This study aimed to evaluate symptoms of sleep-disordered breathing (SDB) among children born extremely preterm, with and without a history of bronchopulmonary dysplasia (BPD), including associations between sleep and respiratory symptoms, physical activity, pulmonary function, and pulmonary magnetic resonance imaging (MRI). This multi-center cross-sectional study enrolled children aged 7-9 years born extremely preterm with and without BPD. Participants completed the Pediatric Sleep Questionnaire (PSQ), the modified Epworth sleepiness scale, a respiratory symptom questionnaire, pedometer measurements, pulmonary function testing, and pulmonary MRI. Spearman's correlations and univariate and multivariable linear regression modelling were performed. Twenty-eight of 45 children included had a history of moderate-to-severe BPD. The prevalence of sleep-related symptoms was low, with the exception of hyperactivity and inattention. There were no differences in mean (SD) scores on sleep questionnaires in children with and without BPD (PSQ: 0.21 (0.13) vs 0.16 (0.14), p = 0.3; modified Epworth: 2.4 (2.4) vs 1.8 (2.8), p = 0.4). Multiple regression analyses examining difference in sleep scores between groups, adjusting for gestational age and intraventricular hemorrhage, found no statistical difference (p > 0.05). Greater daytime sleepiness was moderately correlated with FEV1%-predicted (r = - 0.52); no other moderate-strong associations were identified.  Conclusions: There was no evidence of clinically important differences in sleep symptoms between children with and without BPD, suggesting that sleep symptoms may be related to prematurity-related factors other than a BPD diagnosis, including airflow limitation. Further research is necessary to explore the relationship between sleep symptoms, airway obstruction, and neurobehavioral symptoms among premature-born children.  Trial registration: NCT02921308. Date of registration: October 3, 2016. What is Known: • Presence of bronchopulmonary dysplasia (BPD) may further contribute to the development of SDB, though its impact is not well-studied. • Premature-born children have a greater risk of lung structural and functional differences, including sleep-disordered breathing (SDB). What is New: • There was no difference in sleep symptoms between children with and without BPD, suggesting that sleep symptoms are related to other prematurity-related factors, such as airflow limitation. • Greater daytime sleepiness was correlated with lower FEV1 in our population, which reflects greater airflow limitation.

Gratitude, fragility and strength: Perspectives of adults born preterm about prematurity.

AIM: The aim of the study was to explore how young adults thought that being born preterm had affected their lives. METHODS: Adult participants of a research cohort were questioned about their perspectives. Answers were analysed using mixed methods. RESULTS: Forty-five participants evaluated their health at median score of 8/10. When asked about the meaning of being born preterm, 65% had positive self-centred answers, invoking two main themes: being stronger/'a fighter'/more resilient and being a survivor/chosen; 42% also reported negative themes, such as having health problems and a difficult start. All heard about their prematurity from their parents, 55% with positive child-centred or healthcare system-centred themes, 19% with neutral themes; 35% also heard negative parent-centred themes (tragic experience, guilt, mother's health). When asked which words were associated with prematurity, participants mainly chose positive words for themselves and their family, but more negative words for how the media and society depicted prematurity. Answers were not correlated with adverse objective health measures. CONCLUSION: Participants evaluated their health in a balanced fashion. Preterm-born adults often feel that they have experienced positive transformations as a result of their traumatic start. They often have feelings of gratitude and strength, independent of health problems.

Small-for-gestational-age and predictors of HOMA indices, leptin and adiponectin in infancy.

AIM: To assess whether small-for-gestational-age (SGA) - an indicator of poor fetal growth, may affect metabolic health biomarkers in infancy and explore the predictors. METHODS: This was a nested matched (1:2) prospective observational study of 65 SGA (birth weight < 10th percentile) and 130 optimal-for-gestational-age (OGA, birth weight 25th-75th percentiles, control) infants in the 3D birth cohort with subjects recruited in Canada from 1 May 2010 to 31 August 2012. The outcomes included homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-ß), circulating leptin and adiponectin concentrations at age 2 years. RESULTS: HOMA-IR, HOMA-ß, leptin and adiponectin concentrations were similar in SGA versus OGA infants. Female sex and accelerated growth in length during mid-infancy (3-12 months) were associated with higher HOMA-IR. Caucasian ethnicity and decelerated growth in weight during late infancy (12-24 months) were associated with lower HOMA-IR. Current BMI was positively associated with circulating adiponectin in SGA infants only (+13.4% [4.0%-23.7%] per BMI z score increment). CONCLUSION: Insulin resistance and secretion, circulating leptin and adiponectin levels were normal in SGA subjects in infancy at age 2 years. The novel observation in SGA-specific positive association between current BMI and circulating adiponectin suggests dysfunctional adiposity-adiponectin negative feedback loop development during infancy in SGA subjects.

Cardiac-specific deficiency of 3-hydroxy-3-methylglutaryl coenzyme A lyase in mice causes cardiomyopathy and a distinct pattern of acyl-coenzyme A-related biomarkers.

Deficiency of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase (HL) is an autosomal recessive inborn error of acyl-CoA metabolism affecting the last step of leucine degradation. Patients with HL deficiency (HLD) can develop a potentially fatal cardiomyopathy. We created mice with cardiomyocyte-specific HLD (HLHKO mice), inducing Cre recombinase-mediated deletion of exon 2 at two months of age. HLHKO mice survive, but develop left ventricular hypertrophy by 9 months. Also, within minutes after intraperitoneal injection of the leucine metabolite 2-ketoisocaproate (KIC), they show transient left ventricular hypocontractility and dilation. Leucine-related acyl-CoAs were elevated in HLHKO heart (e.g., HMG-CoA, 34.0 ± 4.4 nmol/g versus 0.211 ± 0.041 in controls, p < 0.001; 3-methylcrotonyl-CoA, 5.84 ± 0.69 nmol/g versus 0.282 ± 0.043, p < 0.001; isovaleryl-CoA, 1.86 ± 0.30 nmol/g versus 0.024 ± 0.014, p < 0.01), a similar pattern to that in liver of mice with hepatic HL deficiency. After KIC loading, HMG-CoA levels in HLHKO heart were higher than under basal conditions, as were the ratios of HMG-CoA/acetyl-CoA and of HMG-CoA/succinyl-CoA. In contrast to the high levels of multiple leucine-related acyl-CoAs, biomarkers in urine and plasma of HLHKO mice show isolated hyper-3-methylglutaconic aciduria (700.8 ± 48.4 mmol/mol creatinine versus 37.6 ± 2.4 in controls, p < 0.001), and elevated C5-hydroxyacylcarnitine in plasma (0.248 ± 0.014 µmol/L versus 0.048 ± 0.005 in controls, p < 0.001). Mice with liver-specific HLD were compared, and showed normal echocardiographic findings and normal acyl-CoA profiles in heart. This study of nonhepatic tissue-specific HLD outside of liver reveals organ-specific origins of diagnostic biomarkers for HLD in blood and urine and shows that mouse cardiac HL is essential for myocardial function in a cell-autonomous, organ-autonomous fashion.

Perinatal adversity profiles and suicide attempt in adolescence and young adulthood: longitudinal analyses from two 20-year birth cohort studies.

BACKGROUND: We aimed to identify groups of children presenting distinct perinatal adversity profiles and test the association between profiles and later risk of suicide attempt. METHODS: Data were from the Québec Longitudinal Study of Child Development (QLSCD, N = 1623), and the Avon Longitudinal Study of Parents and Children (ALSPAC, N = 5734). Exposures to 32 perinatal adversities (e.g. fetal, obstetric, psychosocial, and parental psychopathology) were modeled using latent class analysis, and associations with a self-reported suicide attempt by age 20 were investigated with logistic regression. We investigated to what extent childhood emotional and behavioral problems, victimization, and cognition explained the associations. RESULTS: In both cohorts, we identified five profiles: No perinatal risk, Poor fetal growth, Socioeconomic adversity, Delivery complications, Parental mental health problems (ALSPAC only). Compared to children with No perinatal risk, children in the Poor fetal growth (pooled estimate QLSCD-ALSPAC, OR 1.89, 95% CI 1.04-3.44), Socioeconomic adversity (pooled-OR 1.42, 95% CI 1.08-1.85), and Parental mental health problems (OR 1.74, 95% CI 1.27-2.40), but not Delivery complications, profiles were more likely to attempt suicide. The proportion of this effect mediated by the putative mediators was larger for the Socioeconomic adversity profile compared to the others. CONCLUSIONS: Perinatal adversities associated with suicide attempt cluster in distinct profiles. Suicide prevention may begin early in life and requires a multidisciplinary approach targeting a constellation of factors from different domains (psychiatric, obstetric, socioeconomic), rather than a single factor, to effectively reduce suicide vulnerability. The way these factors cluster together also determined the pathways leading to a suicide attempt, which can guide decision-making on personalized suicide prevention strategies.

Neurodevelopmental consequences of early plasma sodium changes in very preterm infants.

BACKGROUND: Sodium fluctuations in very preterm neonates and their neurodevelopmental consequences are not well described. METHODS: We assessed the changes in plasma sodium and glucose in the first days of life in very preterm neonates and studied the association of glucose-corrected plasma sodium fluctuations on neurodevelopmental outcomes. We included 147 consecutive neonates born before 29 weeks of gestation in our center and retrospectively obtained plasma sodium, glucose, and glucose-corrected sodium levels. Neurodevelopmental assessment was obtained from the Canadian Neonatal Follow-Up Network. RESULTS: Mean ± standard deviation of plasma sodium changes within the first 10 days of life were 16.2 ± 6.0, 14.8 ± 5.3, and 11.1 ± 5.2 mmol/l in neonates born ≤25, 25-26, and 26-27 weeks of gestation, respectively (p < 0.001). Non-steroidal anti-inflammatory drug administration was associated with larger plasma sodium fluctuation. Eighty-six percent had a known neurological status at 18 months. Higher fluctuations in glucose-corrected plasma sodium were associated with death or neurodevelopmental impairment at 18 months corrected age (B = 3.19, 95% CI [1.24, 5.14]), and this association remained after adjustment for gestational age (B = 2.1, 95% CI [0.16, 4.04]). CONCLUSIONS: Neonates born very preterm show fluctuations in glucose-corrected plasma sodium during the first days of life, which may increase the risk of death or developmental impairment. IMPACT: Risk factors and neurodevelopmental consequences of plasma sodium changes in early neonatal life of preterm infants are not well characterized. This study shows for the first time that glucose-corrected plasma sodium fluctuations within the first days of life are more severe in preterm infants receiving non-steroidal anti-inflammatory drugs (NSAIDs) and are associated with death or neurodevelopmental impairment at 18 months corrected age. Large plasma sodium and glucose fluctuations should be expected more often in preterm infants receiving NSAIDs and should be avoided.

Exposure to high levels of oxygen in neonatal rats induce a decrease in hemoglobin levels.

BACKGROUND: Anemia of prematurity is common in extremely preterm neonates, and oxygen exposure may participate to anemia by inhibiting erythropoietin secretion. We aimed to determine whether hyperoxia exerts an independent role in the occurrence of the anemia of prematurity. METHODS: Sprague-Dawley pups were exposed to 80% oxygen or room air from days 3 to 10 of life. Main outcome was the difference in hemoglobin and circulating erythropoietin levels in animals exposed to hyperoxia at 10 days of life. We performed a complete blood count analysis using fluorescent laser flow cytometry and measured circulating erythropoietin levels using ELISA. RESULTS: We found lower hemoglobin in the hyperoxia group, compared to the normoxia group, both in males (70 ± 3 versus 78 ± 2 g/l) and in females (71 ± 2 versus 81 ± 3 g/l) at 10 days of life. Reticulocyte count was not increased in the hyperoxia group. Circulating erythropoietin levels were lower at 10 days of life in the animals exposed to hyperoxia, both in males (33 ± 7 versus 73 ± 6 pg/ml) and in females (37 ± 5 versus 66 ± 3 pg/ml), but were similar at 28 days of life. CONCLUSION: Neonatal exposure to hyperoxia decreases hematopoiesis in rats. IMPACT: Mechanisms leading to anemia of prematurity are not well known and their study in humans is complicated due to multiple confounders. This study shows for the first time that exposure to high concentrations of oxygen in the neonatal period decreases hematopoiesis in rats, providing insight on the pathophysiological mechanisms of the anemia of prematurity. This research paves the way for future therapeutic developments aiming to reduce the burden of anemia of prematurity and the necessity of red blood cell transfusions in extremely preterm neonates.

Cardiopulmonary Function Abnormalities in Cohort of Adults following Bronchopulmonary Dysplasia as Preterm Infants.

OBJECTIVE: This study was aimed to describe the cardiopulmonary profiles of adult patients with bronchopulmonary dysplasia (BPD), comparing them to normative adult values. STUDY DESIGN: This study presents a retrospective chart review of all BPD patients followed in the adult BPD clinic, identified from institutional and archive databases, born preterm at ≤33 weeks of estimated gestational age (EGA) between January 1980 and December 2000. RESULTS: Forty-four patients with BPD (26.4 ± 2.7 weeks of EGA) were included. Average age at follow-up was 19 years. Majority (61.4%) of the patients had a diagnosis of asthma. Mean spirometry values were: first second of forced expiration (FEV1) 74.1%, forced vital capacity (FVC) 80.7%, and FEV1/FVC 82.5%. Echocardiography (ECHO) images were reviewed, left ventricular (LV) structure and performance did not differ between obstructive and nonobstructive pulmonary function test (PFT) groups, but values of LV longitudinal strain were 4.8% lower than expected normal for adults. Patients with obstructive PFT had additional decreased right ventricular (RV) function by ECHO. CONCLUSION: BPD patients in this study were found to have a burden of cardiorespiratory alterations that persisted into adulthood, with RV performance abnormalities found among patients with obstructive PFT. KEY POINTS: · BPD patients born at extremes of prematurity have cardiorespiratory alterations in adulthood.. · Among patients with obstructive lung function, subtle cardiac performance abnormalities were found.. · Future directions should include systematic follow-up of premature newborns with BPD..

Contribution of birth weight to mental health, cognitive and socioeconomic outcomes: two-sample Mendelian randomisation.

BACKGROUND: Low birth weight is associated with adult mental health, cognitive and socioeconomic problems. However, the causal nature of these associations remains difficult to establish owing to confounding. AIMS: To estimate the contribution of birth weight to adult mental health, cognitive and socioeconomic outcomes using two-sample Mendelian randomisation, an instrumental variable approach strengthening causal inference. METHOD: We used 48 independent single-nucleotide polymorphisms as genetic instruments for birth weight (genome-wide association studies' total sample: n = 264 498) and considered mental health (attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder, bipolar disorder, major depressive disorder, obsessive-compulsive disorder, post-traumatic stress disorder (PTSD), schizophrenia, suicide attempt), cognitive (intelligence) and socioeconomic (educational attainment, income, social deprivation) outcomes. RESULTS: We found evidence for a contribution of birth weight to ADHD (OR for 1 s.d. unit decrease (~464 g) in birth weight, 1.29; 95% CI 1.03-1.62), PTSD (OR = 1.69; 95% CI 1.06-2.71) and suicide attempt (OR = 1.39; 95% CI 1.05-1.84), as well as for intelligence (ß = -0.07; 95% CI -0.13 to -0.02) and socioeconomic outcomes, i.e. educational attainment (ß = -0.05; 95% CI -0.09 to -0.01), income (ß = -0.08; 95% CI -0.15 to -0.02) and social deprivation (ß = 0.08; 95% CI 0.03-0.13). However, no evidence was found for a contribution of birth weight to the other examined mental health outcomes. Results were consistent across a wide range of sensitivity analyses. CONCLUSIONS: These findings support the hypothesis that birth weight could be an important element on the causal pathway to mental health, cognitive and socioeconomic outcomes.

Transient neonatal exposure to hyperoxia, an experimental model of preterm birth, leads to skeletal muscle atrophy and fiber type switching.

Individuals born preterm show reduced exercise capacity and increased risk for pulmonary and cardiovascular diseases, but the impact of preterm birth on skeletal muscle, an inherently critical part of cardiorespiratory fitness, remains unknown. We evaluated the impacts of preterm birth-related conditions on the development, growth, and function of skeletal muscle using a recognized preclinical rodent model in which newborn rats are exposed to 80% oxygen from days 3 to 10 of life. We analyzed different hindlimb muscles of male and female rats at 10 days (neonatal), 4 weeks (juvenile), and 16 weeks (young adults). Neonatal high oxygen exposure increased the generation of reactive oxygen species (ROS) and the signs of inflammation in skeletal muscles, which was associated with muscle fiber atrophy, fiber type shifting (reduced proportion of type I slow fibers and increased proportion of type IIb fast-fatigable fibers), and impairment in muscle function. These effects were maintained until adulthood. Fast-twitch muscles were more vulnerable to the effects of hyperoxia than slow-twitch muscles. Male rats, which expressed lower antioxidant defenses, were more susceptible than females to oxygen-induced myopathy. Overall, preterm birth-related conditions have long-lasting effects on the composition, morphology, and function of skeletal muscles; and these effects are sex-specific. Oxygen-induced changes in skeletal muscles could contribute to the reduced exercise capacity and to increased risk of diseases of preterm born individuals.

Arterial Structure and Stiffness Are Altered in Young Adults Born Preterm.

OBJECTIVE: Preterm birth has been associated with changes in arterial structure and function. Association with complications occurring during the neonatal period, including bronchopulmonary dysplasia, on vascular outcomes in adulthood is unknown. Approach and Results: We evaluated a cohort of 86 adults born preterm (below 30 weeks of gestation), compared to 85 adults born term, at a mean age of 23 years. We performed ultrasonographic assessment of the dimensions of the ascending aorta, carotid and brachial arteries, and estimated flow-mediated dilation, carotid-femoral pulse wave velocity, augmentation index corrected for heart rate, and carotid intima-media thickness. All analyses were performed with and without adjustment for potential confounding variables, including height, sex, and body mass index. Ascending aorta diameter in diastole was smaller in the preterm group, but carotid and brachial arteries were similar. Carotid and brachial strain, a marker of arterial distensibility, was smaller in the preterm group, while carotid-femoral pulse wave velocity, was similar between groups, indicating similar aortic stiffness. Carotid intima-media thickness, endothelial function flow-mediated dilation, blood nitrite, and nitrate levels were similar between groups. Individuals with bronchopulmonary dysplasia had lower brachial artery strain suggesting long-term association of this neonatal complication with vascular structure. Diastolic blood pressure was higher in the preterm group and was associated with decreased brachial and carotid distensibility. CONCLUSIONS: Young adults born preterm display alterations in arterial distensibility that are associated with a history of bronchopulmonary dysplasia.

Health perception by young adults born very preterm.

AIM: This study assessed the self-reported health perception and use of health care by adults born very preterm before 30 weeks of gestation. METHODS: The participants were part of a cross-sectional observational study that assessed the global health of young adults aged 18-29 years born very preterm in Quebec, Canada. Health perception was explored from 2011 to 2016 using the second Short-Form 36 Health Survey (SF-36v2), and objective health measures were obtained. Further in-depth open-ended questions were asked in 2018. RESULTS: The 101 preterm subjects had similar perceptions of their health to 105 term-born controls, according to the SF-36v2, despite significantly more adverse health conditions. Their healthcare use was similar. However, the later in-depth questionnaire showed that 23% of 45 preterm subjects and 3% of 34 term-born subjects perceived their health as poorer than the general population. Major factors that could improve their respective health were lifestyle habits (74% vs. 81%) and eliminating specific adverse symptoms (52% vs. 27%). Only 10% of preterm individuals had been asked about their perinatal history by physicians. CONCLUSION: Adults born very preterm said their health was poorer than the general population and identified specific factors that should be addressed during routine health monitoring.

Duration of neonatal oxygen supplementation, erythropoiesis and blood pressure in young adults born preterm.

BACKGROUND: Although erythropoiesis is impaired and anaemia frequent in neonates born preterm, haematopoiesis in adults born preterm has not been previously studied. OBJECTIVE: We, 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. METHODS: We 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. RESULTS: Compared 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. CONCLUSIONS: Haemoglobin 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.

Electrocardiographic features at rest and during exercise in young adults born preterm below 30 weeks of gestation.

BACKGROUND: Preterm birth has adverse consequences on the cardiovascular system. Whether premature birth is associated with conduction and repolarisation abnormalities past childhood and into adulthood still needs to be demonstrated. METHODS: We analyzed the ECG of young adults (23.9 ± 3.1 years) born term (≥37 weeks, n = 53) and preterm (<30 weeks, n = 49) at rest, peak exercise and 3 min into recovery during an exercise test on a cycle ergometer. We measured PR, QRS and QT intervals, calculated the corrected QT (QTc), and determined blood calcium, magnesium, potassium and fasting glucose. RESULTS: Mean gestational age was 39.7 ± 1.1 and 27.3 ± 1.3 weeks for the term and the preterm groups, respectively. Apart from an increased heart rate at rest in individuals born preterm, no significant difference was found between both groups for any other ECG parameters at rest. None of the participants had a severely prolonged QTc (>500 ms) at rest; exercise revealed severely prolonged QTc in two participants including one in the preterm group. The use of QT-prolonging medications did not influence ECG parameters in either groups. CONCLUSIONS: We observed no significant difference in electrocardiographic measurements between young adults born preterm and term. Current results do not support avoidance of QT-prolonging medications in individuals born preterm. IMPACT: Preterm birth is associated with adverse cardiovascular consequences in early adulthood, but controversial evidence exists regarding differences in electrocardiographic features between young individuals born term and preterm.This study aims to assess the differences in electrocardiographic features between young adults born term and preterm, at rest and during exercise training.In contrast with previously published data, we observed no significant difference in electrocardiographic measurements between young adults born preterm and term.Our study does not support that preterm birth itself exposes young adults to a higher risk of QT prolongation.Current results do not support avoidance of QT-prolonging medications in individuals born preterm.

Interaction of chorioamnionitis at term with maternal, fetal and obstetrical factors as predictors of neonatal mortality: a population-based cohort study.

BACKGROUND: Chorioamnionitis is a frequent complication of pregnancy and is known to be associated with serious adverse post-natal outcomes including death. However, the assessment of fetal well-being in labor in the context of chorioamnionitis is often challenging because of fetal tachycardia. Identifying specific risk factors for adverse neonatal outcomes in the context of chorioamnionitis could therefore be of paramount importance. This study aimed to determine if maternal and fetal risk factors for increased neonatal mortality and early neonatal mortality are modified in the context of chorioamnionitis in term pregnancies. METHODS: A retrospective population-based cohort study using the United States birth/infant death public file from 2011 to 2013 was performed, including all live births at 37 weeks gestation and beyond. Interaction between chorioamnionitis and maternal demographic variables as well as labor and delivery potential risk factors were analyzed for association with neonatal death (< 28 days) and early neonatal death (< 7 days) using multivariate logistic regressions. RESULTS: Among 9,034,428 live births, the prevalence of chorioamionitis was 1.29% (95% CI 1.28-1.30%). The incidence of neonatal death and early neonatal death were 0.09 and 0.06% in the chorioamnionitis group versus 0.06 and 0.04% in the no chorioamnionitis group (p = 0.0003 and < 0.0001), respectively. Smoking was significantly associated with neonatal death and early neonatal death in the context of chorioamnionitis (OR 2.44, CI:1.34-4.43/ 2.36 CI:1.11-5.01) but was either less strongly or not associated in the absence of chorioamnionitis (OR 1.24, CI:1.14-1.35/0.93, CI:0.82-1.05). The association between gestational age (37 weeks compared to 39 weeks) and neonatal death was more important in the context of chorioamnionitis (OR = 3.19, CI: 1.75-5.82 versus 1.63, CI: 1.49-1.79). Multivariate analysis identified the following risk factors for neonatal death and/or early neonatal death: low maternal education, extreme maternal age, obesity (BMI > 35 kg/m2), late or no prenatal care, diabetes, meconium-stained amniotic fluid, gestational ages other than 39 weeks, neonatal weight < 2500 g and delivery by vacuum or caesarian. CONCLUSIONS: Smoking as well as early term have a positive interaction with chorioamnionitis for the risk of neonatal mortality. This should be taken into account when counseling pregnant women and managing laboring pregnant women with suspected chorioamnionitis.

Effect of Maternal Docosahexaenoic Acid Supplementation on Bronchopulmonary Dysplasia-Free Survival in Breastfed Preterm Infants: A Randomized Clinical Trial.

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.

Acceptability to nurses of reducing NICU light and noise levels during skin-to-skin care: A pilot study.

INTRODUCTION: Light and noise levels may influence preterm infants and their mothers when they are experiencing skin-to-skin contact [SSC] in the Neonatal Intensive Care Unit [NICU]. METHODS: A pilot randomized controlled trial [RCT] of an intervention aiming at reducing light and noise levels during SSC was conducted. Twenty-one neonatal nurses from a level III NICU completed questionnaires assessing their acceptability of NICU light and noise levels reduction during SSC, whether it interfered with their care delivery, in addition to acceptability of specific interventions reducing these levels. FINDINGS: The majority of nurses considered that the reduction of NICU light and noise levels during SSC was acceptable in general, did not interfere with their care delivery, and that the nine selected interventions were also acceptable. CONCLUSION AND RESEARCH IMPLICATIONS: Nurses found it acceptable to reduce NICU light and noise levels during SSC. These findings support the conduct of a full-scale RCT to evaluate the effect of such an intervention on preterm infants and mothers' well-being.

The Canadian Partnership for Tomorrow Project: a pan-Canadian platform for research on chronic disease prevention.

BACKGROUND: Understanding the complex interaction of risk factors that increase the likelihood of developing common diseases is challenging. The Canadian Partnership for Tomorrow Project (CPTP) is a prospective cohort study created as a population-health research platform for assessing the effect of genetics, behaviour, family health history and environment (among other factors) on chronic diseases. METHODS: Volunteer participants were recruited from the general Canadian population for a confederation of 5 regional cohorts. Participants were enrolled in the study and core information obtained using 2 approaches: attendance at a study assessment centre for all study measures (questionnaire, venous blood sample and physical measurements) or completion of the core questionnaire (online or paper), with later collection of other study measures where possible. Physical measurements included height, weight, percentage body fat and blood pressure. Participants consented to passive follow-up through linkage with administrative health databases and active follow-up through recontact. All participant data across the 5 regional cohorts were harmonized. RESULTS: A total of 307 017 participants aged 30-74 from 8 provinces were recruited. More than half provided a venous blood sample and/or other biological sample, and 33% completed physical measurements. A total of 709 harmonized variables were created; almost 25% are available for all participants and 60% for at least 220 000 participants. INTERPRETATION: Primary recruitment for the CPTP is complete, and data and biosamples are available to Canadian and international researchers through a data-access process. The CPTP will support research into how modifiable risk factors, genetics and the environment interact to affect the development of cancer and other chronic diseases, ultimately contributing evidence to reduce the global burden of chronic disease.