A Novel Integrated Clinical-Biochemical-Radiological and Sonographic Classification of Necrotizing Enterocolitis.

OBJECTIVE: To evaluate the sensitivity and specificity of clinical, laboratory, and radiological markers and the neonatologist-performed intestinal ultrasound (NP-IUS) for treatment interventions in preterm neonates who developed necrotizing enterocolitis (NEC). STUDY DESIGN: This was a case-control study of preterm neonates < 35 weeks with a diagnostic workup for NEC. The diagnostic workup included NP-IUS performed by trained neonatologists using a standard protocol, abdominal roentgenogram (AXR), and laboratory investigations. Intestinal ultrasound (IUS) performed by two neonatologists was standardized to detect 11 injury markers. AXRs were read independently by experienced pediatric radiologists. The investigators who retrospectively interpreted the IUS were blinded to the clinical and treatment outcomes. RESULTS: A total of 111 neonates were assessed. Fifty-four did not require intervention and formed the control group. Twenty cases were treated medically, 21 cases were treated with late surgery for stricture or adhesions, and 16 were treated with early surgery. The integrated model of cumulative severity of ultrasound markers, respiratory and hemodynamic instability, abdominal wall cellulitis, and C- reactive protein > 16 mg/L had an area under the curve (AUC) of 0.89 (95% confidence interval [CI]: 0.83-0.94%, p < 0.0001) for diagnosing NEC requiring surgical intervention. We also investigated the utility of Bell's classification to diagnose either the need for surgery or death, and it had an AUC of 0.74 (95% CI: 0.65-0.83%, p < 0.0001). CONCLUSION: In this cohort, a combination of specific IUS markers and clinical signs of instability, abdominal wall cellulitis, plus laboratory markers were diagnostic of NEC requiring interventions. KEY POINTS: · The diagnosis of necrotizing enterocolitis requires a combination of markers.. · The combination of specific ultrasound markers, clinical signs, and laboratory markers were diagnostic of NEC requiring intervention.. · The intestinal ultrasound performed by a trained neonatologist was the most sensitive diagnostic marker of NEC requiring surgical intervention..

Hyperbilirubinemia Among Infants Born Preterm: Peak Levels and Association with Neurodevelopmental Outcomes.

OBJECTIVE: To describe the distribution of peak bilirubin levels among infants born before 29 weeks of gestation in the first 14 days of life and to study the association between quartiles of peak bilirubin levels at different gestational ages and neurodevelopmental outcomes. STUDY DESIGN: Multicenter, retrospective, nationwide cohort study of neonatal intensive care units in the Canadian Neonatal Network and Canadian Neonatal Follow-Up Network, including neonates born preterm at 220/7 to 286/7 weeks of gestation born between 2010 and 2018. Peak bilirubin levels were recorded during the first 14 days of age. Main outcome was significant neurodevelopmental impairment, defined as cerebral palsy with Gross Motor Function Classification System ≥3, or Bayley III-IV scores of <70 in any domain, or visual impairment, or bilateral hearing loss requiring hearing aids. RESULTS: Among 12 554 included newborns, median gestational age was 26 weeks (IQR 25-28) and birth weight was 920 g (IQR 750-1105 g). The median peak bilirubin values increased as gestational age increased (112 mmol/L [6.5 mg/dL] at 22 weeks and 156 mmol/L [9.1 mg/dL] at 28 weeks). Significant neurodevelopmental impairment was identified in 1116 of 6638 (16.8%) of children. Multivariable analyses identified an association between peak bilirubin in the highest quartile and neurodevelopmental impairment (aOR 1.27, 95% CI 1.01-1.60) and receipt of hearing aid/cochlear implant (aOR 3.97, 95%CI: 2.01-7.82) compared with the lowest quartile. CONCLUSION: In this multicenter cohort study, peak bilirubin levels in neonates of <29 weeks of gestation increased with gestational age. Peak bilirubin values in the highest gestational age-specific quartile were associated with significant neurodevelopmental and hearing impairments.

Mental Disorders Among Mothers of Children Born Preterm: A Population-Based Cohort Study in Canada.

BACKGROUND: Our aim was to examine the association between preterm delivery and incident maternal mental disorders using a population-based cohort of mothers in Canada. METHODS: Retrospective matched cohort study using Manitoba Centre for Health Policy (MCHP) administrative data in Manitoba. Mothers who delivered preterm babies (<37 weeks gestational age) between 1998 and 2013 were matched 1:5 to mothers of term babies using socio-demographic variables. Primary outcome was any incident mental disorder within 5 years of delivery defined as any of (a) mood and anxiety disorders, (b) psychotic disorders, (c) substance use disorders, and (d) suicide or suicide attempts. Multivariable Poisson regression model was used to estimate the 5-year adjusted incidence rate ratios (IRRs). RESULTS: Mothers of preterm children (N = 5,361) had similar incidence rates of any mental disorder (17.4% vs. 16.6%, IRR = 0.99, 95% CI, 0.91 to 1.07) compared to mothers of term children (N = 24,932). Mothers of term children had a higher rate of any mental disorder in the first year while mothers of preterm children had higher rates from 2 to 5 years. Being the mother of a child born <28 week (IRR = 1.5, 95% CI, 1.14 to 2.04), but not 28-33 weeks (IRR = 1.03, 95% CI, 0.86 to 1.19) or 34-36 weeks (IRR = 0.96, 95% CI, 0.88 to 1.05), was associated with any mental disorder. INTERPRETATION: Mothers of preterm and term children had similar rates of incident mental disorders within 5-years post-delivery. Extreme prematurity was a risk factor for any mental disorder. Targeted screening and support of this latter group may be beneficial.

Neonatal outcomes of twins <29 weeks gestation of mothers with hypertensive disorders of pregnancy.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with dysfunctional placentation and are a major cause of maternal and neonatal morbidity and mortality. Twin pregnancies have a larger placental mass and are a risk factor for HDP. The effect of HDP on neonatal outcomes in twin pregnancies is unknown. METHODS: Retrospective cohort study using the Canadian Neonatal Network database from 2010-2018 of twin infants <29 weeks gestation born to mothers with HDP and normotensive pregnancies. Using multivariable models, we determined adjusted odds ratios (AORs) and 95% confidence intervals (CI) for mortality, bronchopulmonary dysplasia, severe neurologic injury, severe retinopathy of prematurity (ROP), necrotizing enterocolitis, and nosocomial infection in twin infants of mothers with HDP compared to twin infants of normotensive mothers. RESULTS: Of the 2414 eligible twin infants <29 weeks gestational age, 164 (6.8%) were born to mothers with HDP and had higher odds of severe ROP (AOR 2.48, 95% CI 1.34-4.59). Preterm twin infants born to mothers with HDP also had higher odds of mortality (AOR 2.02, 95% CI 1.23-3.32). There was no difference in other outcomes. CONCLUSION: Preterm twin infants <29 weeks gestation of HDP mothers have higher odds of severe ROP and mortality. IMPACT: Hypertensive disorders of pregnancy, associated with placental dysfunction, are a major cause of maternal and neonatal morbidity and mortality. Twin pregnancy, associated with a larger placental mass, is a risk factor for hypertensive disorders of pregnancy. The effect of hypertensive disorders of pregnancy on outcomes of preterm twins is unknown. Preterm twins of mothers with hypertensive disorders of pregnancy are at higher risk of severe retinopathy of prematurity and mortality. Our data can be used to counsel parents and identify infants at higher risk of severe retinopathy of prematurity and mortality.

Clinical burden associated with therapies for cardio-pulmonary critical decompensation in preterm neonates across Canadian neonatal intensive care units.

The aim of this retrospective cohort study was to study the clinical burden associated with cardio-pulmonary critical decompensations (CPCDs) in preterm neonates and factors associated with mortality. Through the Canadian Neonatal Network (30 tertiary NICUs, 2010-2017), we identified infants < 32-week gestational age with CPCDs, defined by "significant exposure" to cardiotropes and/or inhaled nitric oxide (iNO): (1) either therapy for ≥ 3 consecutive days, (2) both for ≥ 2 consecutive days, or (3) any exposure within 2 days of death. Early CPCDs (≤ 3 days of age) and late CPCDs (> 3 days) were examined separately. Outcomes included CPCD-incidence, mortality, and inter-site variability using standardized ratios (observed/adjusted expected rate) and network funnel plots. Mixed-effects analysis was used to quantify unit-level variability in mortality. Overall, 10% of admissions experienced CPCDs (n = 2915). Late CPCDs decreased by ~ 5%/year, while early CPCDs were unchanged during the study period. Incidence and CPCD-associated mortality varied between sites, for both early (0.6-7.5% and 0-100%, respectively) and late CPCDs (2.5-15% and 14-83%, respectively), all p < 0.01. Units' late-CPCD incidence and mortality demonstrated an inverse relationship (slope = -2.5, p < 0.01). Mixed-effects analysis demonstrated clustering effect, with 6.4% and 8.6% of variability in mortality after early and late CPCDs respectively being site-related, unexplained by available patient-level characteristics or unit volume. Mortality was higher with combined exposure than with only-cardiotropes or only-iNO (41.3%, 24.8%, 21.5%, respectively; p < 0.01). CONCLUSIONS: Clustering effects exist in CPCD-associated mortality among Canadian NICUs, with higher incidence units showing lower mortality. These data may aid network-level benchmarking, patient-level risk stratification, parental counseling, and further research and quality improvement work. WHAT IS KNOWN: • Preterm neonates remain at high risk of acute and chronic complications; the most critically unwell require therapies such as cardiotropic drugs and inhaled nitric oxide. • Infants requiring these therapies are known to be at high risk for adverse neonatal outcomes and for mortality. WHAT IS NEW: • This study helps illuminate the national burden of acute cardio-pulmonary critical decompensation (CPCD), defined as the need for cardiotropic drugs or inhaled nitric oxide, and highlights the high risk of morbidity and mortality associated with this disease state. • Significant nationwide variability exists in both CPCD incidence and associated mortality; a clustering effect was observed with higher incidence sites showing lower CPCD-associated mortality.

Lung Ultrasound for Prediction of Bronchopulmonary Dysplasia in Extreme Preterm Neonates: A Prospective Diagnostic Cohort Study.

OBJECTIVES: To evaluate the diagnostic and predictive ability of lung ultrasound at 3 time points in the first 2 weeks after birth for predicting bronchopulmonary dysplasia (BPD) among infants <29 weeks of gestational age. STUDY DESIGN: This was a prospective, diagnostic cohort study. Lung ultrasound was performed on days 3, 7, and 14 after birth and lung ultrasound scores (LUS) were calculated in blinded fashion. Diagnostic test characteristics and area under receiver operating characteristic (AUROC) curves were calculated. RESULTS: A total of 152 infants were enrolled with mean (SD) gestational age of 25.8 (1.5) weeks gestation. Of them, 87 (57%) infants were diagnosed with BPD. The LUS were significantly higher in infants diagnosed with BPD compared with those without BPD at all scan time points (P < .01). The score of >10 at all 3 time points had higher sensitivity (0.89, 0.89, and 0.77), specificity (0.87, 0.90, and 0.92), and corresponding clinically important positive and negative likelihood ratios. The AUROC for LUS at the 3 time points were 0.96, 0.97, and 0.95 on day 3, 7, and 14, respectively. Compared with the model using clinical characteristics, LUS alone had higher AUROC (P < .05 for all 3 time points). CONCLUSIONS: In this cohort, LUS in the first 2 weeks after birth had a very high predictive value for the diagnosis of BPD among infants of <29 weeks of gestation. TRIAL REGISTRATION: ClinicalTrials.govNCT04756297.

Costs of Neonatal Intensive Care for Canadian Infants with Preterm Birth.

OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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 of <29 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. CONCLUSIONS: 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.

Association between changes in urine output and successful indomethacin treatment for patent ductus arteriosus in preterm neonates.

AIM: To investigate the relationship between changes in urine output during indomethacin treatment and ductal closure in preterm neonates. METHODS: It is a retrospective study in neonates ≤32 weeks who had received two courses of indomethacin for PDA treatment over a 5-year period. Indomethacin courses with pre- and post-echocardiography confirmation of PDA status were included. Various urine output indices were collected and compared between successful versus unsuccessful indomethacin courses. Indomethacin treatment success was defined as: (i) where PDA closed or became haemodynamically insignificant (hisPDA) after treatment and (ii) only including neonates where PDA had complete closure after treatment. ROC analysis was performed to examine predictive ability of urine output during indomethacin for treatment success. RESULTS: One hundred and eight indomethacin courses (first course: 52, second course: 56) in 80 neonates were included. The mean gestational age and birthweight were 25.4 ± 1.3 weeks and 762 ± 165 g, respectively. Irrespective of the definition used, there was no significant differences seen in any of urine output parameters between groups, except for a higher urine output during indomethacin associated with complete PDA closure (3.6 ± 1.3 vs. 3.0 ± 1.0 mL/kg/h, P = 0.02). The incidence of significant oliguria, hyponatraemia and need to withhold/delay indomethacin doses were also similar across groups. CONCLUSION: Urine output was not a useful predictor of ductal response to indomethacin treatment in preterm neonates.

Effect of Vasopressin on Systemic and Pulmonary Hemodynamics in Neonates.

OBJECTIVE: Despite its increasing use in neonates, the literature on the use of vasopressin (VP) in neonates is limited. The aim of this study is to evaluate the systemic and pulmonary effects of VP in neonates and to assess its safety among them. STUDY DESIGN: This retrospective study enrolled all neonates in two level III neonatal intensive care units in Winnipeg, Manitoba, who had received VP therapy between 2011 and 2016. Infants with congenital malformations/chromosomal disorders were excluded. The changes in cardiovascular and pulmonary parameters were collected from patient charts. The primary outcome was the mean blood pressure (MBP) post-VP initiation. Secondary outcomes included systolic blood pressure (SBP) and diastolic blood pressure (DBP), vasoactive inotropic score (VIS), pH, urine output, lactate, base deficit (BD), mean airway pressure (MAP), and oxygen requirement. RESULTS: A total of 33 episodes from 26 neonates were analyzed. The postnatal age at VP initiation was 14 days (interquartile range [IQR]: 4-25), and the median starting dose was 0.3 mU/kg/min (IQR: 0.2-0.5). MBP improved significantly after VP initiation from 28 to 39 mm Hg 24 hours after VP initiation (p < 0.001). Similar changes are observed with SBP and DBP. VIS declined from 15 to 6 at 24 hours, while pH, lactate, BD, and oxygen requirement improved significantly. While urine output marginally improved, there were no changes to MAP 24 hours post-VP initiation. Hyponatremia was observed in 21 episodes (64%) and severe hyponatremia in 7 episodes (33%). CONCLUSION: VP appears to be a promising rescue therapy in catecholamine resistant shock or refractory pulmonary hypertension in neonates.

Prone versus Supine Position for Lung Ultrasound in Neonates with Respiratory Distress.

OBJECTIVE: To study the feasibility of lung ultrasound (LUS) in prone position and to compare it with supine position in neonates with respiratory distress. STUDY DESIGN: Neonates ≥ 29 weeks of gestational age with respiratory distress requiring respiratory support within first 12 hours of life were enrolled prospectively. First LUS (fLUS) was done in the position infant was nursed (supine or prone), infant's position changed, a second LUS (sLUS) was performed immediately and a third LUS (tLUS) was done 1 to 2 hours later. Primary outcome was the comparison of LUS scores (LUSsc) between fLUS and sLUS. RESULTS: Sixty-four neonates were enrolled. Common respiratory diagnoses were transient tachypnea of newborn (TTN; 53%) and respiratory distress syndrome (RDS; 41%). LUSsc was different between fLUS and sLUS (fLUSsc 6 [interquatile range: 4, 7] vs. sLUSsc 7 [4, 10], p < 0.001), while there was no difference between the fLUS and tLUS (fLUSsc 6 [4, 7] vs. tLUSsc 5 [3, 7], p = 0.43). Subgroup analysis confirmed similar findings in neonates with TTN, while in babies with RDS, all the three LUSsc were similar. CONCLUSION: LUS is feasible in prone position in neonates. LUS scores were higher immediately after a change in position but were similar to baseline 1 hour after the change in position.

A call for a streamlined ethics review process for multijurisdictional, child health research studies.

To be time and resource efficient in neonatal research and to answer clinically relevant questions with validity and generalizability, large numbers of infants from multiple hospitals need to be included. Multijurisdictional research in Canada is currently fraught with research ethics review process hurdles that lead to delays, administrative costs, and possibly termination of projects. We describe our experience applying for ethics review to 13 sites in 7 provinces for a project comparing two standard of care therapies for preterm born infants with respiratory distress syndrome. We welcome the current opportunity created by the Institute of Human Development Child and Youth Health and the Institute for Genetics, to collaboratively identify practical solutions that would benefit Canadian researchers, Research Ethics Boards, and children and families.

Clinical and echocardiography predictors of response to inhaled nitric oxide in hypoxic preterm neonates.

AIM: To evaluate the clinical and echocardiography modulators of treatment response in hypoxemic preterm infants exposed to inhaled nitric oxide (iNO). METHODS: In this multicentre retrospective study, clinical parameters, including oxygenation, ventilation and haemodynamics, were collected for preterm infants <36 weeks gestation before and 2 h after initiation of iNO for acute hypoxemia. Comprehensive echocardiography, performed near the time iNO initiation, was analysed by experts blind to the clinical course. Multiple logistic regression analysis was used to identify factors associated with iNO response as defined by a reduction in the fraction of inspired oxygen by >0.20. RESULTS: A total of 213 infants met eligibility criteria, of which 73 had echocardiography data available and formed the study cohort. Response to iNO was demonstrated in 56% of patients. Younger post-natal age (odds ratio (OR) 0.94; 95% confidence interval (CI) 0.89, 0.99) and the presence of pulmonary hypertension (PH) (OR 4.47; 95% CI 1.23-11.9) were independently predictive of iNO response regardless of gestational age. Among neonates <72 h old with documented PH, iNO response was seen in 82%. The onset of a new diagnosis of severe (grade III/IV) intraventricular haemorrhage (IVH) after iNO treatment was seen in 6 of 40 patients <28 weeks' gestational age, with a greater frequency in responders (32 vs. 0%, P = 0.02). CONCLUSIONS: Positive response to iNO is greatest in the first 3 days of life and in patients with echo-confirmed PH, independent of gestational age. The association between critical illness, iNO administration and IVH in extremely premature infants may merit prospective delineation.

A Lung Ultrasound Severity Score Predicts Chronic Lung Disease in Preterm Infants.

OBJECTIVE: To test the hypothesis that a lung ultrasound severity score (LUSsc) can predict the development of chronic lung disease (CLD) in preterm neonates. STUDY DESIGN: Preterm infants <30 weeks' gestational age were enrolled in this study. Lung ultrasound (LUS) was performed between 1 and 9 postnatal weeks. All ultrasound studies were done assessing three lung zones on each lung. Each zone was given a score between 0 and 3. A receiver operating characteristic curve was constructed to assess the ability of LUSsc to predict CLD. RESULTS: We studied 27 infants at a median (interquartile range [IQR]) gestational age and birth weight of 26 weeks (25-29) and 780 g (530-1,045), respectively. Median (IQR) postnatal age at the time of LUS studies was 5 (2-8) weeks. Fourteen infants who developed CLD underwent 34 studies. Thirteen infants without CLD underwent 30 studies. Those who developed CLD had a higher LUSsc than those who did not (median [IQR] of scores: 9 [6-12] vs. 3 [1-4], p < 0.0001). An LUSsc cutoff of 6 has a sensitivity and specificity of 76 and 97% and positive and negative predictive values of 95 and 82%, respectively. Adding gestational age < 27 weeks improved sensitivity and specificity to 86 and 98% and positive and negative predictive values to 97 and 88%. CONCLUSION: LUSsc between 2 and 8 weeks can predict development of CLD in preterm neonates.

Cardiac Air Embolism in Neonates: A Hemodynamic Perspective.

Cardiac air embolism should be suspected in any neonate with acute unexplained cardiovascular collapse or worsening oxygenation. We present here five cases that presented with the above symptoms. A comprehensive evaluation including targeted neonatal echocardiography and near-infrared spectroscopy helped confirm the diagnosis and assess the hemodynamic state. Management was supportive including left lateral positioning, chest compressions, and cardiovascular medications to treat pulmonary hypertension and systemic hypotension.

Predictors of PDA Treatment in Preterm Neonates Who Had Received Prophylactic Indomethacin.

OBJECTIVE: To identify clinical factors those predict the need for patent ductus arteriosus (PDA) treatment in preterm neonates who had received prophylactic indomethacin. PATIENTS AND METHODS: Preterm neonates with <28 weeks' gestational age admitted to level III neonatal intensive care units (NICUs) in Canada between 2010 and 2015 and who had received prophylactic indomethacin were included. Primary outcome was surgical ligation of PDA, while secondary outcomes were any PDA treatment and common neonatal morbidities. RESULTS: Of the 7,024 eligible neonates, 843 (12%) neonates had received prophylactic indomethacin. Of them, 84 neonates (10%) required surgical ligation while 367 neonates (44%) received medical or surgical treatment for PDA. Logistic regression analyses identified gestational age (odds ratio [OR]: 0.71, 95% confidence interval [CI]: 0.58-0.87) and outborn status (OR: 2.07, 95% CI: 1.09-3.93) as predictors for surgical ligation. Maternal hypertension (OR: 0.57, 95% CI: 0.37-0.89), rupture of membranes (ROM) ≥24 hours (OR: 0.68, 95% CI: 0.48-0.96), and surfactant treatment (OR: 1.70, 95% CI: 1.09-2.66) were predictors for medical or surgical treatment of PDA. CONCLUSION: In extremely preterm neonates who had received prophylactic indomethacin, gestational age and outborn status were predictors for surgical ligation of PDA, while maternal hypertension, ROM ≥24 hours, and surfactant treatment were associated with the medical or surgical treatment of PDA.

Grade 7 school performance of children born preterm: a retrospective Canadian Cohort study.

IMPORTANCE: Data on the middle school outcomes of preterm children are limited and have methodologic issues. OBJECTIVE: To study the association between preterm birth and grade 7 school performance. METHODS: A retrospective population-based cohort study of children born in Manitoba, Canada between 1994 and 2006 using their grade 7 school performance data. A secondary sibling cohort was created comprising children born preterm and their full-term siblings. Primary exposure was preterm birth categorized as <28, 28-33 and 34-36 weeks gestation. The two co-primary grade 7 outcome measures were: not meeting the mathematics competencies, and not meeting the student engagement competencies. Multivariable logistic regression models tested the association between preterm birth and both co-primary outcomes; adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated. RESULTS: 7653 preterm (gestational age median [IQR]: 35 weeks [34,36]) and 110,313 term (40 [39,40]) were included. 43% of < 28 weeks, 18% of 28-33 weeks and 17% of 34-36 weeks had the mathematics co-primary outcome compared to 13% of term children. The corresponding % for the student engagement outcome were 42%, 24%, 24% and 24% respectively. Preterm birth was associated with the mathematics (<28 weeks: 5.48, 3.89-7.70; 28-33 weeks: 1.47, 1.27-1.70; 34-36 weeks: 1.26, 1.16-1.35) and student engagement outcomes (<28 weeks: 2.49, 1.76-3.51; 28-33 weeks: 1.21, 1.06-1.39; 34-36 weeks: 1.09, 1.01-1.16). However, there was no difference in outcomes among the sibling cohort. CONCLUSIONS AND RELEVANCE: Children born preterm had lower grade 7 performance compared to children born term in this population-based cohort. Screening and supports for them in their middle school years are warranted.

Mental Disorders Among Adolescents and Young Adults With Cancer: A Canadian Population-Based and Sibling Cohort Study.

PURPOSE: To compare the cumulative incidence of mental disorders among adolescents and young adults (AYAs) diagnosed with cancer with the general population and their unaffected siblings. METHODS: A retrospective, population-based, matched cohort design was used to investigate the impact of cancer diagnosis on mental disorders among individuals age 15-39 diagnosed between 1989 and 2019. Two cancer-free cohorts were identified: matched population-based and sibling cohorts. Outcomes included incidence of mood and anxiety disorders, substance use disorders, suicide outcomes, psychotic disorders, and any of the preceding four categories within 5 years of cancer diagnosis. Competing risk regression was used to estimate adjusted subhazard ratios (aSHR) and 95% CIs. RESULTS: Among 3,818 AYAs with cancer matched to the population-based cancer-free cohort, individuals with cancer were more likely to be diagnosed with incident mental disorders than those without cancer; the risk was highest immediately after a cancer diagnosis and decreased over time with aSHR [95% CI] for mood and anxiety disorders at 0-6 months (11.27 [95% CI, 6.69 to 18.97]), 6-12 months (2.35 [95% CI, 1.54 to 3.58]), and 12-24 months (2.06 [95% CI, 1.55 to 2.75]); for substance use disorders at 0-6 months (2.73 [95% CI, 1.90 to 3.92]); for psychotic disorders at 0-6 months (4.69 [95% CI, 2.07 to 10.65]); and for any mental disorder at 0-6 months (4.46 [95% CI, 3.41 to 5.85]), 6-12 months (1.56 [95% CI, 1.14 to 2.14]), and 12-24 months (1.7 [95% CI, 1.36 to 2.13]) postcancer diagnosis. In sibling comparison, cancer diagnosis was associated with a higher incidence of mood and anxiety and any mental disorder during first 6 months of cancer diagnosis. CONCLUSION: AYAs with cancer experience a greater incidence of mental disorders after cancer diagnosis relative to population-based and sibling cohorts without cancer, primarily within first 2 years, underscoring the need to address mental health concerns during this period.

CPAP Versus NIPPV Postextubation in Preterm Neonates: A Comparative-Effectiveness Study.

BACKGROUND AND OBJECTIVES: Nasal intermittent positive pressure ventilation (NIPPV) has been shown to be superior to nasal continuous positive airway pressure (CPAP) postextubation in preterm neonates. However, studies have not permitted high CPAP pressures or rescue with other modes. We hypothesized that if CPAP pressures >8 cmH2O and rescue with other modes were permitted, CPAP would be noninferior to NIPPV. METHODS: We conducted a pragmatic, comparative-effectiveness, noninferiority study utilizing network-based real-world data from 22 Canadian NICUs. Centers self-selected CPAP or NIPPV as their standard postextubation mode for preterm neonates <29 weeks' gestation. The primary outcome was failure of the initial mode ≤72 hours. Secondary outcomes included failure ≤7 days, and reintubation ≤72 hours and ≤7 days. Groups were compared using a noninferiority adjusted risk-difference (aRD) margin of 0.05, and margin of no difference. RESULTS: A total of 843 infants extubated to CPAP and 974 extubated to NIPPV were included. CPAP was not noninferior (and inferior) to NIPPV for failure of the initial mode ≤72 hours (33.0% vs 26.3%; aRD 0.07 [0.03 to 0.12], Pnoninferiority(NI) = .86), and ≤7 days (40.7% vs 35.8%; aRD 0.09 [0.05 to 0.13], PNI = 0.97). However, CPAP was noninferior (and equivalent) to NIPPV for reintubation ≤72 hours (13.2% vs 16.1%; aRD 0.01 [-0.05 to 0.02], PNI < .01), and noninferior (and superior) for reintubation ≤7 days (16.4% vs 22.8%; aRD -0.04 [-0.07 to -0.001], PNI < .01). CONCLUSIONS: CPAP was not noninferior to NIPPV for failure ≤72 hours postextubation; however, it was noninferior to NIPPV for reintubation ≤72 hours and ≤7 days. This suggests CPAP may be a reasonable initial postextubation mode if alternate rescue strategies are available.

Longitudinal growth of very low birth weight neonates during first year of life and risk factors for malnutrition in a developing country.

AIMS: To study growth of very low birth weight neonates (VLBW) during first year and identify risk factors for malnutrition. METHODS: Neonates ≤34 weeks and ≤1500 g enrolled in a human milk fortification trial were prospectively followed till 1 year corrected age (CA). Anthropometry was plotted on WHO charts. Risk factors were compared between well nourished and underweight infants. RESULTS: One hundred and thirty-two, 127, 110, 99 and 101 neonates were followed at CA of 40 weeks, 3, 6, 9 and 12 months. Weight (Mean Z score -2.3 ± 1.2 to -1.7 ± 1.4; p = 0.005) and length (-2.1 ± 1.5 to -1.5 ± 1.3; p = 0.004) improved significantly, from 40 weeks to one year while head circumference declined (-0.92 ± 1.1 to -1.2 ± 1.1; p < 0.001). Incidence of underweight, stunting, microcephaly and wasting changed from 63%, 53%, 13% and 52% neonates at 40 weeks to 41%, 32%, 21% and 27% at one year. Growth between fortified and unfortified or small for gestational age (SGA) and appropriate for gestational age (AGA) groups were similar, while extremely low birth weight (ELBW) neonates showed poorer growth. Z score of weight at 3 months emerged as an independent predictor of malnutrition at one year. CONCLUSION: VLBW neonates, especially the ELBW group remained growth retarded at CA of one year. Z score of weight at 3 months was a significant risk factor for malnutrition at one year.

Grade 3 school performance among children born preterm: a population-based cohort study.

OBJECTIVE: To study the association between prematurity and grade 3 school performance in a contemporary cohort of children. METHODS: Population-based retrospective cohort study in Manitoba, Canada. Children born between 1999 and 2011 who had their grade 3 school performance data available were eligible. Preterm birth (<37 weeks) was the exposure of interest assessed using multivariable logistic regression models. Our primary outcomes were 'needs ongoing help' or 'outside the range' in at least two of each of the (1) four numeracy and (2) three reading competencies. RESULTS: Of the 186 956 eligible children, 101 436 children (7187 preterm (gestational age, median (IQR) 35 weeks (34, 36)) and 94 249 term (40 weeks (39,40)) were included. Overall, 19% of preterm and 14% of term children had the numeracy outcome (adjusted OR (aOR) 1.38; 95% CI 1.29 to 1.47, p<0.001), while 19% and 13% had the reading outcome (aOR 1.38; 1.29 to 1.48, p<0.001). These differences showed a gestational age gradient. Gestational age (for numeracy, <28 weeks aOR 4.93 (3.45 to 7.03), 28-33 weeks 1.72 (1.50 to 1.98), 34-36 weeks 1.24 (1.15 to 1.34); for reading, <28 weeks 3.51 (2.40 to 5.14), 28-33 weeks 1.72 (1.49 to 1.98), 34-36 weeks 1.24 (1.17-1.37)), male sex, small for gestational age and maternal medical and sociodemographic factors were associated with the numeracy and reading outcomes in this cohort. CONCLUSIONS AND RELEVANCE: Children born preterm had poorer performance in grade 3 numeracy and reading proficiencies than children born full term. All children born preterm, not just those born extremely preterm, should be screened for reading and numeracy performance in school and strategies implemented to address any deficits.