Objective To determine the sensitivity and specificity of the 21-month neurodevelopmental outcome for predicting the presence of neurodevelopmental impairment at 36 months corrected age in a population of preterm infants under 29 weeks gestation. Study design This is a retrospective observational cohort study. Preterm infants born under 29 weeks gestation who were followed up at both 18–21 months and 36 months corrected age with outcome data available were enrolled. Results Overall, 713 preterm infants <29 weeks gestation and were included in the final analysis. The specificity of the 21-month assessment for predicting neurodevelopmental impairment at 36 months corrected age was 66% (95% confidence interval[CI] 62–71%) with a positive predictive value of 61% (95% CI 56–66%). Conclusion In preterm neonates born <29 weeks gestation, the 18–21 months corrected neurodevelopmental outcome had low specificity and positive predictive value for predicting the presence of neurodevelopmental impairment at 36 months corrected age.

Objective To determine the association of maternal pre-pregnancy body mass index (BMI) and neurodevelopmental impairment (NDI) at 18–24 months corrected age (CA) in infants born < 29 weeks gestation. Study design Infants born between 2005 and 2015 at < 29 weeks gestation were included. BMI was categorized into BMI 1 [18.5–24.9 kg/m 2 ], BMI 2 [25–29.9 kg/m 2 ], BMI 3 [ ≥ 30 kg/m 2 ]. Primary outcome was death or NDI (Bayley-III scores < 85, cerebral palsy, hearing or visual impairment). Univariate and multivariate analysis were used. Results There were 315 infants in BMI 1 , 235 in BMI 2, and 147 in BMI 3 groups. Adjusted odds ratio (aOR) of death or NDI in BMI 2 vs. BMI 1 and BMI 3 vs BMI 1 groups were 1.33 (95% CI 0.86–2.06) and 0.76 (95% CI 0.47–1.22). Adjusted odds ratio of Bayley-III language composite < 85 was 2.06 (95% CI 1.28–3.32). Conclusion Pre-pregnancy BMI was not associated with death or NDI in extremely preterm infants. Infants born to overweight mothers had higher odds of low language scores.

Abstract Background Increasing rates of obesity are of growing concern to maternal and child health as mothers with obesity are at risk of pregnancy complications. Infants of mothers with overweight/obese pre-pregnancy body mass index (BMI) may also be at risk of significant neurodevelopmental disorders. The relationship between maternal pre-pregnancy BMI and neurodevelopmental outcomes in preterm infants is not yet clearly defined. Objectives To determine the association of pre-pregnancy BMI of mothers of infants born <29 weeks gestational age (GA) and neurodevelopmental impairment (NDI) at 18-24 months corrected age (CA). Design/Methods Preterm infants born <29 weeks GA between January 2005 and December 2015 evaluated in the neonatal follow-up clinic at 18-24 months CA were included. Demographic characteristics as well as neurodevelopmental status including Bayley-III cognitive, language, and motor scores and sensory impairments were compared between three groups based on maternal pre-pregnancy BMI (BMI1 [18.5-24.9 kg/m2] vs. BMI2 [25-29.9 kg/m2] vs. BMI3 [≥30 kg/m2]) using univariate and multivariable regression models. The primary outcome was a composite of death or NDI. NDI was defined as the presence of Bayley-III <85 on one or more of the cognitive, motor, or language composite scores, any cerebral palsy (GMFCS ≥1), sensorineural or mixed hearing impairment, or unilateral or bilateral visual impairment. Results Of 771 eligible infants, 53 not seen in the follow-up clinic and 21 born to mothers with BMI <18.5 kg/m2 were excluded. Of the remaining 697 participants, 315 (45%) infants were in BMI1, 235 (34%) in BMI2, and 147 (21%) in BMI3 groups. Infants in BMI1, BMI2, and BMI3 groups had mean (SD) birth weight of 897 (231), 854 (208), and 867 (234) grams and median GA (IQR) of 27 (3), 26 (2), and 27 (3) weeks respectively. Rates of associated impairments are shown in Figure 1. The odds of a composite of death or NDI in BMI2 vs. BMI1 and BMI3 vs BMI1 groups were 1.33 (95%CI 0.86-2.06) and 0.76 (95%CI 0.47-1.22) respectively (Table 1). Infants born to mothers in the BMI2 group had twice the odds of scoring <85 on the Bayley-III language composite than those in BMI1 (adjusted odds ratio 2.06 [95% CI; 1.28-3.32]). Conclusion Pre-pregnancy body mass index was not associated with death or neurodevelopmental impairment in very preterm infants at 18-24 months corrected age. However, infants born to mothers who were overweight were more likely to have lower language scores.

Objectives To identify the prevalence and risk factors for childhood overweight and obesity (OWO) at 3-year corrected age in children born <1500 g <29 weeks gestation. Study design A multicentre retrospective cohort study for preterm infants admitted to neonatal intensive care units between 2001 and 2014. Results Data were available for 911 (89.4%) of the 1019 infants who met the inclusion criteria. Of them, 22 (2.4%) had OWO. There were no associations between OWO and being small for gestational age (RR = 1.3, 95% confidence interval (CI): 0.3–5.4) or weight <10th percentile at 36 weeks (RR = 1.1, 95% CI: 0.4–2.8). OWO was associated with low maternal education (RR = 7.4, 95% CI: 2.1–26), maternal diabetes (RR = 5.2, 95% CI: 1.9–15) and neonatal brain injury (RR = 4.9, 95% CI: 1.8–14). Adjusting for concurrent child weight at 3 years of age resulted in an overadjustment bias. Conclusion Small size at birth or at 36 weeks gestation in extremely preterm infants is not associated with increased risk of early childhood overgrowth or obesity. Clinical trial registration NCT03064022.

Introduction: Evidence is lacking regarding the benefit of caesarean section (CS) for long-term neurodevelopmental outcomes in singleton preterm neonates. Therefore, uncertainty remains regarding obstetrical best practice in the delivery of premature neonates. Objective: Our objective was to determine the association between the mode of delivery and neurodevelopmental outcomes in preterm singleton neonates who were delivered by vaginal route (VR), CS with labour (CS-L), or CS without labour (CS-NL). Methods: Singleton neonates of less than 29 weeks' gestation born January 1995 through December 2010 and admitted to our NICU and then assessed at neonatal follow-up clinic were studied. The primary outcome was neurodevelopmental impairment (NDI) defined as cerebral palsy, cognitive delay, major or minor visual impairment, or hearing impairment or deafness at 36 months' corrected age. Results: In this retrospective cohort study of 1,452 neonates, 1,000 were eligible for the study and 881 (88.1%) were available for follow-up. There was no significant difference in mortality between VR group, CS-L group, and CS-NL group. At 3 years, there was no significant difference between the three groups in terms of NDI. The odds of composite outcome of mortality or NDI for neonates born via CS-NL versus VR, and CS-L versus VR were 0.90 (95% confidence interval [CI]: 0.59 to 1.37) and 1.08 (95% CI: 0.72 to 1.61), respectively. Propensity score-based matched-pair analyses did not show a significant association between the composite outcome and CS with or without labour. Conclusions: CS was not associated with increased survival or decreased risk of NDI in premature singleton neonates born at less than 29 weeks' gestation.

Objective To assess diagnostic accuracy of 36-week anthropometric weight, length, and head circumference <10th and <3rd percentiles to predict preterm infant cognitive impairment. Study design Cohort study of 898 preterm <30-week very-low-birth weight (<1500 g) infants. Anthropometric measures’ accuracy to predict cognitive impairment (Bayley-III Cognitive Composite score) <80, 21-months corrected age (CA) and Wechsler Preschool and Primary Scale of Intelligence Quotient (intellectual outcomes) <70, 36-months CA, were determined using receiver operating characteristic (ROC) curves. Result Thirty-six-week weight, length or head circumference <10th or <3rd percentile did not predict cognitive impairment; areas under ROC curves were <0.6. Sensitivities and specificities for 10th and 3rd percentile cut points were all poor, with most not exceeding 70%, whether the Fenton 2013 or INTERGROWTH 2015 growth charts were used. Brain injury and low maternal education were better predictors of cognitive impairment. Conclusion Preterm infant 36-week anthropometric measurements are not accurate predictors of cognitive impairment.

Background: The ability to definitively diagnose cerebral palsy (CP) at 18-24 months is unknown. Aims: To describe very preterm children who, at 19 months, have suspected CP defined as neither having a definitive diagnosis of CP nor no CP and compare them with children with and without CP. Study design and methods: Longitudinal national cohort study of births < 29 weeks' gestation with linked Canadian Neonatal Network and Canadian Neonatal Follow-up Network data with 19 month assessments and 3 year questionnaires (Ages and Stages-3 and Health Status Classification System-Preschool). CP, no CP and suspected CP groups, classified at 19 months, were compared using chi square and ANOVA. Results: Of 3086 survivors, 2280 had complete 19-month corrected age (CA) and 1261 had 3-year CA data. Suspected CP (3.6%), CP (6.4%) and no CP (90%) groups differed (p < 0.05) in birth weight, gestational age, complications of prematurity and NICU length of stay. Children with suspected CP had Bayley-III motor, cognitive and language composite scores at 18 months midway between CP and no CP, had the lowest sensory impairment rates and highest hospital readmission rates. At 3 years, gross motor, fine motor, problem-solving, communication and social skill abilities differed: abnormal outcomes were intermediate for children with suspected CP (p < 0.01). Conclusions: CP incidence varied from 6.4% to 10% with exclusion or inclusion of children with suspected CP. Children with suspected CP have characteristics mostly midway between those with and without CP and developmental concerns persist to 3 years and require surveillance beyond 19 months.

Extremely preterm infants are at increased risk of motor impairment. The Canadian Neonatal Follow-Up Network (CNFUN) afforded an opportunity to study the outcomes of extremely preterm children. The purpose of this study was to compare 18-month corrected age (CA) motor outcomes of extremely preterm infants with parent-reported functional outcomes at 3 years CA. CNFUN data of 1376 infants were used to conduct chi-square analyses to compare Bayley-III motor scores (composite, gross, and fine motor) at 18 months CA with parent-reported Ages and Stages Questionnaire motor scores (gross and fine motor) at 3 years CA. The correlation of motor scores at 18-months CA with parent-reported gross and fine motor scores at 3 years CA was also examined. We found that 1 in 5 infants scoring within or above the average range on the Bayley-III had parent-reported functional fine and gross motor difficulties at 3 years CA. Bayley-III scores were only moderately correlated with functional motor outcomes. Results of the study suggest that the Bayley-III at 18 months CA was able to detect the majority of infants with motor problems, but not all; therefore, ongoing follow-up of extremely preterm infants is required. The Bayley-III motor composite score has greater clinical utility compared to sub-scale scores.

OBJECTIVE:To compare mortality and neurodevelopmental outcomes of extremely low gestational age neonates who received delivery room extensive cardiopulmonary resuscitation (DR-CPR) to those who did not require DR-CPR.METHODS:Preterm neonates born at <29 weeks' gestational age between January 2010 and September 2011 and assessed at Canadian Neonatal Follow-Up Network centers were studied. Neonates who received DR-CPR were compared to those who did not require DR-CPR using univariate and multivariable analyses. The primary outcome was a composite of mortality or any neurodevelopmental impairment at 18 to 24 months corrected age defined as the presence of any one or more of the following: cerebral palsy; Bayley-III cognitive, language, or motor composite scores <85 on any one of the components; sensorineural/mixed hearing loss or unilateral or bilateral visual impairment. Secondary outcomes were the individual components of the composite outcomes.RESULTS:Of the 2760 neonates born, 173 were excluded and remaining 2587 eligible neonates were included in our study. Of these 2068 had outcome data (80%) of whom 190 (9.2%) received DR-CPR. DR-CPR was independently associated with mortality or neurodevelopmental impairment (adjusted odds ratio [aOR] 1.76; 95% CI 1.21-2.55) and mortality alone (aOR1.94; 95% CI 1.33-2.83). DR-CPR was also associated with increased odds of motor impairment (aOR 2.03; 95% CI 1.28-3.23).CONCLUSION:In extremely low gestational age neonates, DR-CPR was associated with higher odds of the composite outcome of mortality or neurodevelopmental impairment, mortality alone, and lower motor scores at 18 to 24 months' corrected age.

OBJECTIVE:To compare neurodevelopmental outcomes of preterm infants at 18-21 months corrected age (CA) whose mothers smoked during pregnancy to those whose mothers did not smoke.STUDY DESIGN:Preterm infants born at <29 weeks of gestation and evaluated at 18-21 months CA were included. Primary outcome was a composite outcome of death or neurodevelopmental impairment (NDI).RESULTS:Of a total of 2760 infants, 699 met exclusion criteria. Of the remaining 2061 infants, 280 (13.6%) were exposed to maternal smoking and 1781 (86.4%) were not. The odds of the composite outcome of death or NDI (aOR 1.40; 95% CI: 1.03-1.91), NDI alone (aOR 1.43; 95% CI: 1.01-2.03), and Bayley-III motor score <85 (aOR 1.91; 95% CI: 1.31-2.81) were higher in exposed infants.CONCLUSIONS:Exposure to maternal smoking was associated with adverse composite outcome of death or NDI, NDI alone and lower motor scores at 18-21 months CA.

The association between poor growth and neurodevelopmental impairment (NDI) among preterm infants is well-established whether due to inadequate nutrition, adverse events or both. The present study assessed the diagnostic accuracy of 36-week anthropometric measures, including corresponding < 10th and < 3rd percentile cut points to predict NDI in preterm infants. This study included data from the PreM Growth Cohort Study for preterm infants < 30 weeks of gestational age (GA) and birth weights < 1500 grams. The accuracy with which measured weight, length and head circumference z-scores can predict cognitive impairment (Bayley-III Cognitive Composite score < 80) at 21 months corrected age (born in 2005–2014) and intellectual impairment (Wechsler Preschool and Primary Scale of Intelligence-3rd and 4th Edition (Intellectual test) score < 70) at 3-years corrected age (born in 2001–2014) was determined by the area under the receiver operating characteristic curve (AUROC). At 21 months 98/621 (15.8%) of infants had low Bayley scores and 57/613 (9.3%) had low Intellectual test scores at 3 years. None of the AUROCs exceeded 0.6 and none were significantly different from 0.5. Sensitivities and specificities for the 10th and 3rd percentile cut points were equally poor, with most not exceeding 70% (Figures). The findings were similar between the Fenton 2013 and INTERGROWTH 2015 growth charts. The addition of morbidities increased the accuracy of predicting cognitive impairments except for infants with cerebral palsy, other morbidities had relatively marginal associations with impairment. Preterm infant measures of weight, length, and head circumference z-scores at 36 weeks, including corresponding < 10th and < 3rd percentile cut points, are not accurate as predictors of NDI. This study confirms previous findings that preterm infants show some “catch up” in weight relative to growth references between 37–44 weeks GA. ClinicalTrials.gov Identifier: NCT03064022 Canadian Foundation for Dietetic Research.

BACKGROUND:Although caffeine use for apnea of prematurity is well studied, the long-term safety and benefit of routine early caffeine administration has not been explored. Our objective was to determine the association between early (within 2 days of birth) versus late caffeine exposure and neurodevelopmental outcomes in preterm infants. METHODS:Infants of <29 weeks' gestation born between April 2009 and September 2011 and admitted to Canadian Neonatal Network units and then assessed at Canadian Neonatal Follow-up Network centers were studied. Neonates who received caffeine were divided into early- (received within 2 days of birth) and late-caffeine (received after 2 days of birth) groups. The primary outcome was significant neurodevelopmental impairment, defined as cerebral palsy, or a Bayley Scales of Infant and Toddler Development, Third Edition composite score of <70 on any component, hearing aid or cochlear implant, or bilateral visual impairment at 18 to 24 months' corrected age. RESULTS:Of 2108 neonates who were eligible, 1545 were in the early-caffeine group and 563 were in the late-caffeine group. Rates of bronchopulmonary dysplasia, patent ductus arteriosus, and severe neurologic injury were lower in the early-caffeine group than in the late-caffeine group. Significant neurodevelopmental impairment (adjusted odds ratio 0.68 [95% confidence interval 0.50-0.94]) and odds of Bayley Scales of Infant and Toddler Development, Third Edition cognitive scores of <85 (adjusted odds ratio 0.67 [95% confidence interval 0.47-0.95]) were lower in the early-caffeine group than in the late-caffeine group. Propensity score-based matched-pair analyses revealed lower odds of cerebral palsy and hearing impairment only. CONCLUSIONS:Early caffeine therapy is associated with better neurodevelopmental outcomes compared with late caffeine therapy in preterm infants born at <29 weeks' gestation.

To assess the impact of variations in the definition of severe neurodevelopmental impairment (NDI) on the incidence of severe NDI and the association with risk factors using the Canadian Neonatal Follow-Up Network cohort. Literature review of severe NDI definitions and application of these definitions were performed in this database cohort study. Infants born at 23-28 completed weeks of gestation between 2009 and 2011 (n = 2187) admitted to a Canadian Neonatal Network neonatal intensive care unit and assessed at 21 months' corrected age were included. The incidence of severe NDI, aORs, and 95% CIs were calculated to express the relationship between risk factors and severe NDI using the definitions with the highest and the lowest incidence rates of severe NDI. The incidence of severe NDI ranged from 3.5% to 14.9% (highest vs lowest rate ratio 4.29; 95% Cl 3.375.47). The associations between risk factors and severe NDI varied depending on the definition used. Maternal ethnicity, employment status, antenatal corticosteroid treatment, and gestational age were not associated consistently with severe NDI. Although maternal substance use, sex, score of neonatal acute physiology >20, late-onset sepsis, bronchopulmonary dysplasia, and brain injury were consistently associated with severe NDI irrespective of definition, the strength of the associations varied. The definition of severe NDI significantly influences the incidence and the associations between risk factors and severe NDI. A standardized definition would facilitate site comparisons and scientific communication.

Objective Investigate neurodevelopmental outcomes at 3 years corrected age in infants with a birth weight ≤1250 g born to single parents. Study Design Infants born between 1995 and 2010 with a birth weight ≤1250 g were considered eligible. Primary outcome was neurodevelopmental impairment; considered present if a child had any of the following: cerebral palsy, cognitive delay, visual impairment, or deafness/neurosensory hearing impairment. Univariate and multivariate analyses were performed. Result A total of 1900 infants were eligible for inclusion. Follow-up data were available for 1395; 88 were born to a single parent. Infants in the single-parent group had higher mortality (18% vs. 11%, p = 0.009), IQ ≥1 SD below the mean (40% vs. 21%, p = 0.001) and any neurodevelopmental impairment (47% vs. 29%, p = 0.003). Single-parent family status, maternal education, bronchopulmonary dysplasia and severe neurological injury were significant predictors of intellectual impairment at 3 years corrected age. Conclusion Preterm infants with a birth weight ≤1250 g born to single parents at birth have poorer intellectual functioning at 3 years corrected age.

Objective To evaluate predictive validity and establish cut-off scores on the Bayley-III at age 21 months that best predict Intelligence Quotient (IQ) scores <70 or <80) at 3 years in a high-risk preterm cohort. Method Bayley-III evaluations at 21 months corrected age and intellectual assessments, primarily with the WPPSI-III, at 3 years corrected age were conducted with 520 infants born less than 29 weeks gestational age or less than 1250 g birth weight. Receiver Operator Characteristic (ROC) curves were used to establish Bayley-III Cognitive Composite cut-off scores that maximized Sensitivity and Specificity in predicting low IQ. Similar analyses were performed using the Language Composite, and a research derived mean Cognitive-Language Composite. Results A regression model for the association between 21-month Bayley-III Cognitive Composite and 3-year IQ scores was significant (P<0.0001, Adjusted R2=0.36). The ROC area under the Curve was 0.90 for the Cognitive Composite predicting IQ<70. The cut-off score that maximized Sensitivity and Specificity for predicting 3-year IQ<70 was a Cognitive Composite of <80. The ROC Area under the Curve was 0.80 for Cognitive Composites predicting IQ<80 and a Cognitive Composite cut-off score of <90 maximized Sensitivity and Specificity. Conclusion In this high-risk preterm cohort, there was a strong association between the Bayley-III Cognitive Composite at 21 months and IQ at 3 years. A Cognitive Composite cut-off score of <80 optimized classification of IQ<70 at 3 years, and a Cognitive Composite cut-off score of <90 optimized classification of IQ<80.

Developmental and language outcomes at 2 years of age of children who had arterial switch operation (ASO) for transposition of the great arteries 2004–2010 are described.

Background: Children with congenital heart disease are at increased risk of adverse long-term neurodevelopmental outcomes believed in part secondary to a prenatal insult. Altered fetal middle cerebral arterial (MCA) Dopplers suggestive of brain sparing (low Pulsatility Index, PI) as well as

BACKGROUND: Neurodevelopmental outcomes of preterm infants who receive extensive CPR (ECPR), defined as chest compression with or without epinephrine in the delivery room, remain unclear. OBJECTIVES: To compare the neurodevelopmental outcomes of preterm infants admitted to Canadian NICUs requiring ECPR versus those who did not require ECPR in the delivery room. DESIGN/METHODS: Preterm infants born at <29 weeks GA between January 1, 2010 and September 30, 2011 and evaluated at CNFUN centers were retrospectively evaluated. The primary outcome was a composite of death or neurodevelopmental impairment (NDI) at 18-21 months CA defined as presence of any one or more of the following: definitive cerebral palsy or Bayley- III cognitive, language, motor scores <85 on any one of the components or hearing impairment or visual impairment. Demographic factors, neurodevelopmental status including Bayley III cognitive, language and motor scores and sensory impairments were compared between the ECPR and the no ECPR group using univariate and multivariate analyses. RESULTS: Of 2488 eligible infants, 197 (7.9%) received ECPR. 83% of surviving infants had follow-up data. Demographic and outcomes data are summarized below in Table 1 and 2 respectively. CONCLUSION: In very preterm neonates, ECPR was associated with increased risk of death or neurodevelopmental impairment and lower motor scores at 18-21 months CA.

Objective To compare the new intraventricular hemorrhage (IVH) Abdi score to the Papile grading system of IVH for prediction of composite outcome of death or neurodevelopmental impairment (NDI).Methods In a cohort study, all preterm infants with IVH who were born <= 1,250 g and/or <= 28 weeks of gestation at birth were prospectively followed up in our neonatal follow-up clinic. All cranial ultrasounds of the included infants were reviewed by neuroradiologists who were blinded to the clinical data and neurodevelopmental outcomes. Cranial ultrasounds were graded according to the Papile scoring system and by calculation of the Abdi score.Results A total of 183 preterm infants met inclusion and exclusion criteria. Of these, 80 (44%) had the composite primary outcome of death or NDI (51 died, 29 survived with NDI). The area under receiver operating characteristic curve for predicting death or NDI was 0.87 (95% confidence interval [CI]: 0.81-0.93) for Abdi score and 0.85 (95% CI: 0.79-0.91) for Papile grading (p = 0.04). Abdi scores had higher specificity than Papile grade II at Abdi score 5 (63.9 vs. 39.2%; p < 0.001) and Abdi score 6 (73.2 vs. 39.2%; p < 0.001).Conclusion Abdi scores seem to be more specific than Papile grading system in predicting death or NDI by 3 years' corrected age.