Predictive value of Bayley-III Motor Index for later motor difficulties in children born extremely preterm.

AIM: To investigate the predictive ability of the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) Motor Index, in children born extremely preterm (<27 gestational weeks) without cerebral palsy. METHODS: Children from the EXPRESS study (all extremely preterm births in Sweden, 2004-2007) without neurosensory impairments assessed with Bayley-III at 2.5 years corrected age and Movement Assessment Battery for Children, Second Edition (MABC-2), at 6.5 years comprised the eligible study population (n = 282). Motor difficulty was defined as MABC-2 ≤5th percentile. RESULTS: Motor difficulties were found in 57 of 282 children (20.2%) at 6.5 years. The Bayley-III explained 18.0% of the variance in the MABC-2 (p < 0.001). The area under the receiver operating curve was 0.71 (95% confidence interval 0.64-0.79, p < 0.001). At a Bayley-III cut-off value of 85, sensitivity, specificity and positive and negative predictive values for motor difficulties were 26.3% (15.5-39.7), 92.9% (88.1-95.9), 48.4% (33.0-64.0) and 83.3% (80.9-85.4). Likelihood ratios were inconclusive. CONCLUSION: The Bayley-III at 2.5 years corrected age was a modest predictor of motor outcome in children born extremely preterm at 6.5 years, and underestimated the rate of motor difficulties. Children require follow-up beyond preschool age.

Neurobehavioral symptoms in children born extremely preterm: A Swedish National Study.

AIM: To determine the prevalence of neurobehavioral symptoms at 6.5 years in children born extremely preterm (EPT, <27 weeks' gestation). METHODS: Population-based cohort study of infants born EPT in Sweden from 2004 to 2007. Of 486 survivors 375 were assessed and compared with 369 matched term-born controls. EPT children free from neurosensory and intellectual disabilities (neurodevelopmental disabilities [NDD]-free, n = 236) were compared separately. Standardised questionnaires were used to assess parental ratings of hyperactivity and attention, emotional, peer-relation, conduct and social problems; and deficits in perception, language and memory. RESULTS: EPT children had more reported problems in all assessed neurobehavioral domains than controls, with more than three times greater odds for most outcomes. Except for conduct problems, increased problems were identified also in NDD-free children. The odds of having neurobehavioral problems in ≥3 co-occurring domains were five (whole EPT group) and three (NDD-free group) times higher than in controls. CONCLUSION: EPT children with or without NDD have more neurobehavioral problems in multiple domains than term peers. Ongoing assessments of behaviour until school age or beyond should recognise early symptoms of attention, everyday social problems, perceptual, emotional or language difficulties.

Perinatal risk factors for developmental coordination disorder in children born extremely preterm.

AIM: Children born extremely preterm frequently have developmental coordination disorder (DCD). We aimed to evaluate perinatal risk factors for DCD. METHODS: Swedish national cohort study including 226 children born before 27 gestational weeks without major neurodevelopmental disabilities at 6.5 years. Outcome was DCD, defined as ≤5th percentile on the Movement Assessment Battery for Children-Second Edition. Perinatal risk factors were evaluated using multivariable logistic regression. RESULTS: DCD was present in 84/226 (37.2%) children. Of the risk factors known at 40 weeks gestation, independent and significant risk factors for DCD were: mother's age at delivery (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.07-2.80); pre-eclampsia (2.79, 1.14-6.80); mother born in a non-Nordic country (2.23, 1.00-4.99); gestational age per week increase (0.70, 0.50-0.99) and retinopathy of prematurity (2.48, 1.26-4.87). Of factors known at discharge, postnatal steroids exposure (2.24, 1.13-4.46) and mechanical ventilation (1.76, 1.06-2.09) were independent risk factors when added to the model in separate analyses. CONCLUSION: The risk of DCD in children born extremely preterm was multifactorial and associated with gestational age largely mediated by ROP, maternal factors, pre-eclampsia, administration of postnatal steroids and mechanical ventilation. These risk factors are common among children born extremely preterm, contributing to their high risk of DCD.

Birth outcomes between 22 and 26 weeks' gestation in national population-based cohorts from Sweden, England and France.

AIM: We investigated the timing of survival differences and effects on morbidity for foetuses alive at maternal admission to hospital delivered at 22 to 26 weeks' gestational age (GA). METHODS: Data from the EXPRESS (Sweden, 2004-07), EPICure-2 (England, 2006) and EPIPAGE-2 (France, 2011) cohorts were harmonised. Survival, stratified by GA, was analysed to 112 days using Kaplan-Meier analyses and Cox regression adjusted for population and pregnancy characteristics; neonatal morbidities, survival to discharge and follow-up and outcomes at 2-3 years of age were compared. RESULTS: Among 769 EXPRESS, 2310 EPICure-2 and 1359 EPIPAGE-2 foetuses, 112-day survival was, respectively, 28.2%, 10.8% and 0.5% at 22-23 weeks' GA; 68.5%, 40.0% and 23.6% at 24 weeks; 80.5%, 64.8% and 56.9% at 25 weeks; and 86.6%, 77.1% and 74.4% at 26 weeks. Deaths were most marked in EPIPAGE-2 before 1 day at 22-23 and 24 weeks GA. At 25 weeks, survival varied before 28 days; differences at 26 weeks were minimal. Cox analyses were consistent with the Kaplan-Meier analyses. Variations in morbidities were not clearly associated with survival. CONCLUSION: Differences in survival and morbidity outcomes for extremely preterm births are evident despite adjustment for background characteristics. No clear relationship was identified between early mortality and later patterns of morbidity.

The ability of Bayley-III scores to predict later intelligence in children born extremely preterm.

AIM: To investigate the ability of the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III), scores to predict later Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV), performances in a cohort of children born extremely preterm. METHODS: 323 children, born <27 gestational weeks, were tested with the Bayley-III at corrected age 2.5 years and with the WISC-IV at 6.5 years. Regression analyses investigated the association between Bayley-III scores and WISC-IV full-scale intelligence quotient (IQ). The ability of Bayley-III Cognitive Index scores to predict low IQ was evaluated using receiver operating characteristic curves. RESULTS: Bayley-III Cognitive Index scores and IQ had a moderately positive correlation and accounted for 38% of the IQ variance. Using a Bayley-III cut-off score of 70, the sensitivity to detect children with IQ<70 was 18%, and false positive rate was 7%. A Bayley-III cut-off score of 85 corresponded to sensitivity and false positive rates of 44% and 7%, respectively. CONCLUSIONS: Results emphasise the relative importance of Bayley-III Cognitive Index scores as predictors of IQ. An 85 score cut-off for suspecting subnormal IQ is supported. A less conservative threshold would increase identification of true cases yet increase the risk of wrongly diagnosing children.

Cognitive profiles of extremely preterm children: Full-Scale IQ hides strengths and weaknesses.

AIM: To study whether a specific cognitive profile can be identified for children born extremely preterm (EPT) by investigating: 1) strengths and weaknesses not revealed by Full-Scale IQ, 2) overlap between different cognitive deficits and 3) proportion of EPT children with multiple deficits. METHODS: We analysed data from the 4th version of Wechsler Intelligence Scales for Children in EPT children (n = 359) and matched controls (n = 367), collected within the 6.5-year follow-up of a population-based prospective cohort study. RESULTS: Extremely preterm children performed worse than controls on all measures. Group differences were the largest in Perceptual Reasoning (PRI) and Working Memory (WMI), but differences between indices were small. However, when conducting categorical analyses, deficits in PRI and/or WMI were not more common than other combinations. Many EPT children had no or mild cognitive deficits, although often in multiple domains. CONCLUSION: Extremely preterm children had greater weaknesses in working memory and perceptual abilities. However, detailed analyses of cognitive subscales showed large heterogeneity and provided no support for a specific cognitive profile. In conclusion, Full-Scale IQ scores hide strengths and weaknesses and individual profiles for EPT children need to be considered in order to provide appropriate support.

The type and timing of patent ductus arteriosus treatment was associated with neurodevelopment when extremely preterm infants reached 6.5 years.

AIM: This study investigated patent ductus arteriosus (PDA) treatment and neurodevelopmental outcomes when extremely preterm born children reached 6.5 years. METHOD: Our cohort was 435 children with neonatal PDA treatment data and neurodevelopmental follow-up data, born in 2004-2007, who participated in the Extremely Preterm Infants in Sweden Study. Pharmacological or surgical PDA treatment and the age at PDA treatment, were investigated in relation to the risks of moderate to severe neurodevelopmental impairment (NDI) and full-scale intelligence quotient (FSIQ) at 6.5 years. RESULTS: The children who received PDA drug treatment, including those who also had surgery, had the same risk of moderate to severe NDI or lower FSIQ as untreated children. However, children who had primary PDA surgery faced increased risks of NDI, with an adjusted incidence rate ratio of 1.62 (95% confidence interval [CI] 1.28-2.06) and a lower adjusted mean difference FSIQ of -7.1 (95% CI -11 to -3.2). Surgery at less than 10 days of life was associated with a significantly increased risk of moderate to severe NDI and lower FSIQ than surgery after 20 days. CONCLUSION: Drug treatment followed by deferred surgery appeared to be a safer option for extremely preterm infants severely affected by PDA.

Validation of the diagnosis of necrotising enterocolitis in a Swedish population-based observational study.

AIM: The definition of necrotising enterocolitis (NEC) is based on clinical and radiological signs that can be difficult to interpret. The aim of the present study was to validate the incidence of NEC in the Extremely Preterm Infants in Sweden Study (EXPRESS) METHODS: The EXPRESS study consisted of all 707 infants born before 27 + 0 gestational weeks during the years 2004-2007 in Sweden. Of these infants, 38 were recorded as having NEC of Bell stage II or higher. Hospital records were obtained for these infants. Furthermore, to identify missed cases, all infants with a sudden reduction of enteral nutrition, in the EXPRESS study were identified (n = 71). Hospital records for these infants were obtained. Thus, 108 hospital records were obtained and scored independently by two neonatologists for NEC. RESULTS: Of 38 NEC cases in the EXPRESS study, 26 were classified as NEC after validation. Four cases not recorded in the EXPRESS study were found. The incidence of NEC decreased from 6.3% to 4.3%. CONCLUSION: Validation of the incidence of NEC revealed over- and underestimation of NEC in the EXPRESS study despite carefully collected data. Similar problems may occur in other national data sets or quality registers.

Association Between Year of Birth and 1-Year Survival Among Extremely Preterm Infants in Sweden During 2004-2007 and 2014-2016.

Importance: Since 2004-2007, national guidelines and recommendations have been developed for the management of extremely preterm births in Sweden. If and how more uniform management has affected infant survival is unknown. Objective: To compare survival of extremely preterm infants born during 2004-2007 with survival of infants born during 2014-2016. Design, Setting and Participants: All births at 22-26 weeks' gestational age (n = 2205) between April 1, 2004, and March 31, 2007, and between January 1, 2014, and December 31, 2016, in Sweden were studied. Prospective data collection was used during 2004-2007. Data were obtained from the Swedish pregnancy, medical birth, and neonatal quality registries during 2014-2016. Exposures: Delivery at 22-26 weeks' gestational age. Main Outcomes and Measures: The primary outcome was infant survival to the age of 1 year. The secondary outcome was 1-year survival among live-born infants who did not have any major neonatal morbidity (specifically, without intraventricular hemorrhage grade 3-4, cystic periventricular leukomalacia, necrotizing enterocolitis, retinopathy of prematurity stage 3-5, or severe bronchopulmonary dysplasia). Results: During 2004-2007, 1009 births (3.3/1000 of all births) occurred at 22-26 weeks' gestational age compared with 1196 births (3.4/1000 of all births) during 2014-2016 (P = .61). One-year survival among live-born infants at 22-26 weeks' gestational age was significantly lower during 2004-2007 (497 of 705 infants [70%]) than during 2014-2016 (711 of 923 infants [77%]) (difference, -7% [95% CI, -11% to -2.2%], P = .003). One-year survival among live-born infants at 22-26 weeks' gestational age and without any major neonatal morbidity was significantly lower during 2004-2007 (226 of 705 infants [32%]) than during 2014-2016 (355 of 923 infants [38%]) (difference, -6% [95% CI, -11% to -1.7%], P = .008). Conclusions and Relevance: Among live births at 22-26 weeks' gestational age in Sweden, 1-year survival improved between 2004-2007 and 2014-2016.

Infant abuse diagnosis associated with abusive head trauma criteria: incidence increase due to overdiagnosis?

Background: The hypothesis of this study is that the diagnosis of infant abuse is associated with criteria for shaken baby syndrome (SBS)/abusive head trauma (AHT), and that that changes in incidence of abuse diagnosis in infants may be due to increased awareness of SBS/AHT criteria. Methods: This was a population-based register study. Setting: Register study using the Swedish Patient Register, Medical Birth Register, and Cause of Death Register. The diagnosis of infant abuse was based on the International Classification of Diseases, 9th and 10th revision. Participants: All children born in Sweden during 1987-2014 with a follow-up until 1 year of age (N = 2 868 933). SBS/AHT criteria: subdural haemorrhage, cerebral contusion, skull fracture, convulsions, retinal haemorrhage, fractures rib and long bones. Outcomes: Incidence, rate ratios, aetiologic fractions and Probit regression analysis. Results: Diagnosis of infant abuse was strongly associated with SBS/AHT criteria, but not risk exposure as region, foreign-born mother, being born preterm, multiple birth and small for gestational age. The incidence of infant abuse has increased tenfold in Sweden since the 1990s and has doubled since 2008, from 12.0 per 100 000 infants during 1997-2007 to 26.5/100 000 during 2008-2014, with pronounced regional disparities. Conclusions: Diagnosis of infant abuse is related to SBS/AHT criteria. The increase in incidence coincides with increased medical preparedness to make a diagnosis of SBS/AHT. Hidden statistics and a real increase in abuse are less plausible. Whether the increase is due to overdiagnosis cannot be answered with certainty, but the possibility raises ethical and medico-legal concerns.

Impact of major neonatal morbidities on adolescents born at 23-25 weeks of gestation.

AIM: More infants born extremely preterm (EPT) are surviving, but major neonatal morbidities are consistently high. This study examined the impact of bronchopulmonary dysplasia (BPD), brain injuries and severe retinopathy of prematurity (ROP) on adolescents who were born EPT. METHODS: We focused on EPT infants born at 23-25 weeks at the Swedish university hospitals in Uppsala and Umeå from January 1992 to December 1998. The poor outcome data covered 140 of 142 who survived to 36 weeks, and the chronic conditions data reported by parents covered 132 of 134 still alive at 10-15 years. RESULTS: Of the 140 survivors at 36 weeks, 29 (21%) had poor outcomes: eight of 140 (6%) died, and 21 of 132 (16%) adolescent survivors had severe neurodevelopmental disabilities (NDD). BPD, severe ROP and/or brain injuries correlated independently with poor outcome. Of those adolescents who were free from BPD, brain injury and severe ROP, 6% had a severe NDD. The corresponding rates with any one, any two or all three neonatal morbidities were 21, 33 and 67%, respectively. BPD and brain injuries were associated with high rates of chronic conditions at 10-15 years of age resulting in functional limitations. CONCLUSION: In adolescent EPT survivors, BPD and brain injuries were associated with high rates of chronic conditions and special healthcare needs.

Extreme prematurity, treated retinopathy, bronchopulmonary dysplasia and cerebral palsy are significant risk factors for ophthalmological abnormalities at 6.5 years of age.

AIM: This study evaluated the contributions of various prenatal and postnatal predictive factors to a documented high prevalence of ophthalmological abnormalities in children aged 6.5 years who were born extremely preterm. METHODS: We carried out a prospective population-based study of all children born in Sweden at a gestational age of 22 + 0 to 26 + 6 weeks based on the Extremely Preterm Infants in Sweden Study. The main outcome measures were a combined score of visual impairment, refractive errors and strabismus at 6.5 years of age. Models of univariate and multivariable regression were used to analyse potential prenatal and postnatal predictive factors at different clinically relevant time-points from one minute after birth to 30 months. RESULTS: We focused on 399 known extremely preterm survivors and compared them to 300 full-term controls. Significant antecedents for ophthalmological abnormalities included prematurity per se, retinopathy of prematurity that required treatment, severe bronchopulmonary dysplasia and cerebral palsy. Severe intraventricular haemorrhage was no longer a significant risk factor when we adjusted it for the 30-month cognitive and neuromotor development outcomes. CONCLUSION: This time-course risk analysis model showed a changing panorama of significant risk factors for ophthalmological abnormalities in children aged 6.5 years who were born extremely preterm.

National population-based cohort study found that visual-motor integration was commonly affected in extremely preterm born children at six-and-a-half years.

AIM: This study aimed to explain the relationship between visual-motor integration (VMI) abilities and extremely preterm (EPT) birth, by exploring the influence of perinatal variables, cognition, manual dexterity and ophthalmological outcomes. METHODS: This was part of the population-based national Extremely Preterm Infant Study in Sweden (EXPRESS) study. We studied 355 children, born at a gestational age of <27 weeks from April 2004 to March 2007, and 364 term-born controls. At six-and-a-half years of age, we assessed VMI, cognitive function, motor skills and vision. VMI impairment was classified as <-1 standard deviation (SD). RESULTS: The mean (SD) VMI score was 87 (±12) in preterm children compared to 98 (±11) in controls (p < 0.001). VMI impairment was present in 55% of preterm infants and in 78% of children born at 22-23 weeks. Male sex and postnatal steroids showed a weak association with poorer visual-motor performance, whereas low manual dexterity and cognitive function showed a stronger association. CONCLUSION: Poor VMI performance was common in this EXPRESS cohort of children born EPT. Its strong association to cognition and manual dexterity confirms that all of these factors need to be taken into account when evaluating risks in preterm born children.

Impact of obstetric factors on outcome of extremely preterm births in Sweden: prospective population-based observational study (EXPRESS).

INTRODUCTION: A population-based observational study investigated the contribution of obstetric factors to the survival and postnatal development of extremely preterm infants. MATERIAL AND METHODS: Mortality up to 1 year and neurodevelopment at 2.5 years (Bayley-III test, cerebral palsy, vision, hearing) were evaluated in infants born before 27 weeks of gestation in Sweden 2004-2007 (n = 1011), using logistic regression analyses of risk factors. RESULTS: Of 844 fetuses alive at admission, 8.4% died in utero before labor, 7.8% died intrapartum. Of 707 live-born infants, 15% died within 24 h, 70% survived ≥365 days, 64% were assessed at 2.5 years. The risk of death within 24 h after birth decreased with gestational age [odds ratio (OR) 0.3; 95% CI 0.2-0.4], antenatal corticosteroids (OR 0.3; 95% CI 0.1-0.6), and cesarean section (OR 0.4; 95% CI 0.2-0.9); it increased with multiple birth (OR 3.0; 95% CI 1.5-6.0), vaginal breech delivery (OR 2.3; 95% CI 1.0-5.1), 5-min Apgar score <4 (OR 50.4; 95% CI 28.2-90.2), and birth at a level II hospital (OR 2.6; 95% CI 1.2-5.3). The risk of death between 1 and 365 days remained significantly decreased for gestational age and corticosteroids. The risk of mental developmental delay at 2.5 years decreased with gestational age, birthweight and fetal growth; it increased with vaginal breech delivery (OR 2.0; 95% CI 1.2-7.4), male gender, low Apgar score and high Clinical Risk Index for Babies score. CONCLUSION: Several obstetric factors, including abdominal delivery, influenced the risk of death within the first day of life, but not later. Antenatal corticosteroids and gestational age decreased the mortality up to 1 year. Mental developmental delay was related to vaginal breech delivery.

Sepsis as a risk factor for neonatal morbidity in extremely preterm infants.

AIM: This study evaluated sepsis as a risk factor for neonatal morbidities and investigated the association between specific pathogens and neonatal morbidities. METHODS: This was a nationwide Swedish prospective cohort study, consisting of the 497 extremely premature children, who were born before 27 weeks of gestation between 2004 and 2007 and survived their first year of life. Neonatal sepsis was evaluated as a risk factor for neonatal morbidity using multiple logistic linear regression analyses. RESULTS: We found that 326 (66%) of the infants had at least one sepsis episode and coagulase-negative staphylococci was the most common pathogen. Definite sepsis, with an odds ratio (OR) of 1.6, was associated with severe bronchopulmonary dysplasia, but not clinical sepsis (OR 1.1). Definite sepsis was also associated with a prolonged hospital stay (OR 1.6). Sepsis was not significantly associated with a higher risk of retinopathy of prematurity or intraventricular haemorrhage. CONCLUSION: Extremely preterm infants face a great risk of acquiring neonatal sepsis, with coagulase-negative staphylococci being the most common pathogen in this population. Definite sepsis seemed to be a risk factor for severe bronchopulmonary dysplasia and prolonged hospital stay, but the associations were weaker than in previous studies.

EXPRESS study shows significant regional differences in 1-year outcome of extremely preterm infants in Sweden.

AIM: The aim of this study was to investigate differences in mortality up to 1 year of age in extremely preterm infants (before 27 weeks) born in seven Swedish healthcare regions. METHODS: National prospective observational study of consecutively born, extremely preterm infants in Sweden 2004-2007. Mortality was compared between regions. Crude and adjusted odds ratios and 95% CI were calculated. RESULTS: Among 844 foetuses alive at mother's admission for delivery, regional differences were identified in perinatal mortality for the total group (22-26 weeks) and in the stillbirth and perinatal and 365-day mortality rates for the subgroup born at 22-24 weeks. Among 707 infants born alive, regional differences were found both in mortality before 12 h and in the 365-day mortality rate for the subgroup (22-24 weeks) and for the total group (22-26 weeks). The mortality rates were consistently lower in two healthcare regions. There were no differences in the 365-day mortality rate for infants alive at 12 h or for infants born at 25 weeks. Neonatal morbidity rates among survivors were not higher in regions with better survival rates. Perinatal practices varied between regions. CONCLUSION: Mortality rates in extremely preterm infants varied considerably between Swedish healthcare regions in the first year after birth, particularly between the most immature infants.

Behaviours related to executive functions and learning skills at 11 years of age after extremely preterm birth: a Swedish national prospective follow-up study.

AIM: We investigated a national cohort of children born extremely immature (<26 weeks gestation, EI) regarding the nature, frequency and severity of the behavioural problems related to the executive functions (EF) and concerning learning skills, from the perspectives of parents and teachers. METHODS: At 11 years of age 86 of 89 survivors of this cohort were studied and compared with an equal number of controls. Behaviours related to EF, and learning skills were assessed by a validated instrument, namely the Five to Fifteen questionnaire sent by mail to parents and teachers. RESULTS: Compared with controls, parents of EI children reported significantly more problems in behaviours related to EF in all areas assessed (Attention, Hyperactivity/Impulsivity, Hypoactivity, Planning/Organizing, and Working Memory). Teachers' ratings showed a similar pattern. EI children also displayed deficient skills in the 4 standard measures of learning skills. Multivariate analysis revealed that prematurity, gender and behavioural composite score was associated with learning skills. Only a relatively small proportion of EI children (10-30%) exhibited clinically significant impairments. CONCLUSION: Despite a favourable outcome in many school-age children born at the threshold of viability, these are at increased risk of developing behavioural problems related to EF.

Nutrient intakes independently affect growth in extremely preterm infants: results from a population-based study.

AIM: To explore associations between energy and macronutrient intakes and early growth in extremely low gestational age (ELGA) infants. METHODS: Retrospective population-based study of all ELGA infants (<27 weeks) born in Sweden during 2004-2007. Detailed data on nutrition and anthropometric measurements from birth to 70 days of postnatal age were retrieved from hospital records. RESULTS: Study infants (n = 531) had a mean ± SD gestational age of 25.3 ± 1.1 weeks and a birth weight of 765 ± 170 g. Between 0 and 70 days, average daily energy and protein intakes were 120 ± 11 kcal/kg and 3.2 ± 0.4 g/kg, respectively. During this period, standard deviation scores for weight, length and head circumference decreased by 1.4, 2.3 and 0.7, respectively. Taking gestational age, baseline anthropometrics and severity of illness into account, lower energy intake correlated with lower gain in weight (r = +0.315, p < 0.001), length (r = +0.215, p < 0.001) and head circumference (r = +0.218, p < 0.001). Protein intake predicted growth in all anthropometric outcomes, and fat intake was positively associated with head circumference growth. CONCLUSION: Extremely low gestational age infants received considerably less energy and protein than recommended and showed postnatal growth failure. Nutrient intakes were independent predictors of growth even after adjusting for severity of illness. These findings suggest that optimized energy and macronutrient intakes may prevent early growth failure in these infants.

Neurodevelopmental outcome in extremely preterm infants at 2.5 years after active perinatal care in Sweden.

IMPORTANCE: Active perinatal care increases survival of extremely preterm infants; however, improved survival might be associated with increased disability among survivors. OBJECTIVE: To determine neurodevelopmental outcome in extremely preterm children at 2.5 years (corrected age). DESIGN, SETTING, AND PARTICIPANTS: Population-based prospective cohort of consecutive extremely preterm infants born before 27 weeks of gestation in Sweden between 2004 and 2007. Of 707 live-born infants, 491 (69%) survived to 2.5 years. Survivors were assessed and compared with singleton control infants who were born at term and matched by sex, ethnicity, and municipality. Assessments ended in February 2010 and comparison estimates were adjusted for demographic differences. MAIN OUTCOMES AND MEASURES: Cognitive, language, and motor development was assessed with Bayley Scales of Infant and Toddler Development (3rd edition; Bayley-lll), which are standardized to mean (SD) scores of 100 (15). Clinical examination and parental questionnaires were used for diagnosis of cerebral palsy and visual and hearing impairments. Assessments were made by week of gestational age. RESULTS: At a median age of 30.5 months (corrected), 456 of 491 (94%) extremely preterm children were evaluated (41 by chart review only). For controls, 701 had information on health status and 366 had Bayley-lll assessments. Mean (SD) composite Bayley-III scores (cognition, 94 [12.3]; language, 98 [16.5]; motor, 94 [15.9]) were lower than the corresponding mean scores for controls (cognition, 104 [10.6]; P < .001; adjusted difference in mean scores, 9.2 [99% CI, 6.9-11.5]; language, 109 [12.3]; P < .001; adjusted difference in mean scores, 9.3 [99% Cl, 6.4-12.3]; and motor, 107 [13.7]; P < .001; adjusted difference in mean scores, 12.6 [99% Cl, 9.5-15.6]). Cognitive disability was moderate in 5% of the extremely preterm group vs 0.3% in controls (P < .001) and it was severe in 6.3% of the extremely preterm group vs 0.3% in controls (P < .001). Language disability was moderate in 9.4% of the extremely preterm group vs 2.5% in controls (P < .001) and severe in 6.6% of the extremely preterm group vs 0% in controls (P < .001). Other comparisons between the extremely preterm group vs controls were for cerebral palsy (7.0% vs 0.1%; P < .001), for blindness (0.9% vs 0%; P = .02), and for hearing impairment (moderate and severe, 0.9% vs 0%; P = .02, respectively). Overall, 42% (99% CI, 36%-48%) of extremely preterm children had no disability, 31% (99% CI, 25%-36%) had mild disability, 16% (99% CI, 12%-21%) had moderate disability, and 11% (99% CI, 7.2%-15%) had severe disability. Moderate or severe overall disability decreased with gestational age at birth (22 weeks, 60%; 23 weeks, 51%; 24 weeks, 34%; 25 weeks, 27%; and 26 weeks, 17%; P for trend < .001). CONCLUSIONS AND RELEVANCE: Of children born extremely preterm and receiving active perinatal care, 73% had mild or no disability and neurodevelopmental outcome improved with each week of gestational age. These results are relevant for clinicians counseling families facing extremely preterm birth.

Factors associated with the increased incidence of necrotising enterocolitis in extremely preterm infants in Sweden between two population-based national cohorts (2004-2007 vs 2014-2016).

OBJECTIVE: To investigate potential risk factors behind the increased incidence of necrotising enterocolitis (NEC) in Swedish extremely preterm infants. DESIGN: Registry data from two population-based national cohorts were studied. NEC diagnoses (Bell stage ≥II) were validated against hospital records. PATIENTS: All liveborn infants <27 weeks of gestation 2004-2007 (n=704) and 2014-2016 (n=895) in Sweden. MAIN OUTCOME MEASURES: NEC incidence. RESULTS: The validation process resulted in a 28% reduction of NEC cases but still confirmed a higher NEC incidence in the later epoch compared with the earlier (73/895 (8.2%) vs 27/704 (3.8%), p=0.001), while the composite of NEC or death was lower (244/895 (27.3%) vs 229/704 (32.5%), p=0.022). In a multivariable Cox regression model, censored for mortality, there was no significant difference in early NEC (0-7 days of life) between epochs (HR=0.9 (95% CI 0.5 to 1.9), p=0.9), but being born in the later epoch remained an independent risk factor for late NEC (>7 days) (HR=2.7 (95% CI 1.5 to 5.0), p=0.001). In propensity score analysis, a significant epoch difference in NEC incidence (12% vs 2.8%, p<0.001) was observed only in the tertile of infants at highest risk of NEC, where the 28-day mortality was lower in the later epoch (35% vs 50%, p=0.001). More NEC cases were diagnosed with intramural gas in the later epoch (33/73 (45.2%) vs 6/26 (23.1%), p=0.047). CONCLUSIONS: The increase in NEC incidence between epochs was limited to cases occurring after 7 days of life and was partly explained by increased survival in the most extremely preterm infants. Misclassification of NEC is common.