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Half of the infants surviving extremely preterm birth suffered from severe neonatal morbidities. Studies on how to reduce these morbidities and on the long-term health of survivors are warranted.

IMPORTANCE There are concerns that apparently healthy extremely preterm children face a risk of developing motor impairments, such as developmental coordination disorder. OBJECTIVE To evaluate the prevalence of developmental coordination disorder and associated comorbidities in a national cohort of apparently healthy children born at 22 to 26 gestational weeks, compared alongside term-born peers. DESIGN, SETTING, AND PARTICIPANTS This prospective, population-based cohort study included all children who were consecutively born at 22 to 26 gestational weeks in Sweden from April 1, 2004, through March 31, 2007. At 6.5 years, 441 preterm children were evaluated alongside 371 controls. A total of 275 preterm children (62.4%) and 359 term-born children (96.8%) did not have neurodevelopmental disabilities. Motor assessments were completed for 229 of 275 preterm children (83.3%) and 344 of 359 (95.8%) term-born children, who composed the final study sample. MAIN OUTCOMES AND MEASURES Developmental coordination disorder was defined as a score of the fifth percentile or lower on the Movement Assessment Battery for Children-Second Edition scale, using control group scores. Assessment tools included the Wechsler Intelligence Scale for Children-Fourth Edition, the Brown Attention-Deficit Disorder Scales, the Five to Fifteen questionnaire, and the Strengths and Difficulties questionnaire. RESULTS Of the 229 extremely preterm children and 344 term-born controls who underwent motor assessments, 115 (50.2%) and 194 (56.4%) were boys, respectively. Developmental coordination disorder was present in 85 of 229 (37.1%) preterm children and in 19 of 344 controls (5.5%) (adjusted odds ratio [OR], 7.92; 99% CI, 3.69-17.20). When preterm children with developmental coordination disorder were compared with term-born peers, the risk was increased for total behavioral problems, internalizing, externalizing, attentional problems, hyperactivity, perceptual problems, executive dysfunction, and poor social skills, with adjusted ORs varying from 2.66 (99% CI, 1.09-6.48) for time concepts to 9.06 (99% CI, 3.60-22.8) for attentional problems (all P < .01). When preterm children with and without developmental coordination disorder were compared, preterm children with developmental coordination disorder had more behavioral problems; the adjusted OR for total behavioral problems was 2.71 (99% CI, 1.15-6.37); for externalizing problems, 2.80 (99% CI, 1.10-7.12); for inattention, 3.38 (99% CI, 1.39-8.18); and for combined attention/hyperactivity problems, 3.68 (99% CI, 1.47-9.16) (all P < .01). Parents underestimated the children's motor problems and only a few of the children had received psychological care or physiotherapy. CONCLUSIONS AND RELEVANCE Children who were born extremely preterm faced a high risk for developmental coordination disorder with associated comorbidities. Our findings support the importance of a structured follow-up of motor function, behavior, and cognition. 

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.

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.

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.

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.

Aims To assess the cognitive and behavioral aspects of executive functioning (EF) and learning skills in extremely preterm (EPT) children compared with term control children aged 10 to 15 years. Methods A total of 132 of 134 (98% of all eligible survivors) EPT children born at the 2 Swedish regional tertiary care centers from 1992 to 1998 (mean age = 12 years, mean birth weight = 718 g, and mean gestational age = 24.4 weeks) and 103 matched term controls were assessed. General intelligence was assessed using the Wechsler Intelligence Scale for Children (WISC-III-R), and cognitive aspects of EF were analyzed using EF-sensitive sub-scales of the WISC-III-R and Tower test of the Delis-Kaplan Executive Function Scale (D-KEFS). Behaviors related to EF and learning skills were assessed using the Five to Fifteen questionnaire, which is a validated parent and teacher instrument. Academic performance in school was assessed by teachers' responses on Achenbach's Teachers Report Form. Analyses performed included multivariate analyses of covariance (ANCOVA and MANCOVA) and logistic regression analyses. Results The EPT children displayed significant deficits in cognitive aspects of EF compared with the controls, exhibiting decreases on the order of 0.9 SD to 1.2 SD for tasks of verbal conceptual reasoning, verbal and non-verbal working memory, processing speed and planning ability (P < 0.001 for all). After excluding the children with major neurosensory impairment (NSI) or a Full Scale intelligence quotient (FSIQ) of < 70, significant differences were observed on all tests. Compared with controls, parents and teachers of EPT children reported significantly more EF-related behavioral problems. MANCOVA of teacher-reported learning skills in children with FSIQ > 70 and without major NSI revealed no interactions, but significant main effects were observed for the behavioral composite executive function score, group status (EPT vs control) and FSIQ, for which all effect sizes were medium to large. The corresponding findings of MANCOVA of the parent-reported learning skills were very similar. According to the teachers' ratings, the EPT children were less well adjusted to the school environment. Conclusion EPT children born in the 1990s who received active perinatal care are at an increased risk of executive dysfunction, even after excluding children with significant neurodevelopmental disabilities. Even mild to moderate executive dysfunctions has a significant impact on learning skills. These findings suggest the need for timely interventions that address specific cognitive vulnerabilities and executive dysfunctions.

OBJECTIVE: To evaluate the perinatal and 2-year outcomes in pregnancies complicated by preterm premature rupture of membranes (PROM) during the second trimester.

METHODS: Fifty-three consecutive singleton pregnancies with PROM at 14 to 28 weeks of gestation were studied retrospectively. Management goals were to prolong the pregnancies to 32 weeks through expectant management and to avoid fetal compromise through closer monitoring and active intervention, when necessary, after 23 weeks. Outcome of the surviving infants was based on neurologic, audiometric, and ophthalmologic examinations at 2 years of corrected age.

RESULTS: Rupture of membranes occurred at 14-19 weeks (mean 17.4 weeks) in 10 women, at 20-25 weeks (mean 24.0 weeks) in 24, and at 26-28 weeks (mean 27.6 weeks) in 19. The median latency periods to delivery were 72 days, 12 days, and 10 days when rupture of membranes occurred at 14-19 weeks, 20-25 weeks, and 26-28 weeks, respectively. The overall incidence of chorioamnionitis was 28%. There were no fetal deaths and nine neonatal deaths. When rupture of membranes occurred at 14-19 weeks, 20-25 weeks, and 26-28 weeks, the perinatal survival rates were 40%, 92%, and, 100%, respectively. Pulmonary hypoplasia accounted for seven deaths. Of the live-born infants, 81% were alive at 2 years of corrected age. Survival without major impairment was observed in 75%, 80%, and 100% of the survivors when rupture of membranes occurred at 14-19 weeks, 20-25 weeks, and 26-28 weeks, respectively.

CONCLUSION: Expectant management of second-trimester PROM offers better perinatal and long-term survival than previously thought.

Abstract

OBJECTIVE: We investigated a national cohort of extremely immature children with respect to behavioral and emotional problems and social competencies, from the perspectives of parents, teachers, and children themselves.

METHODS: We examined 11-year-old children who were born before 26 completed weeks of gestation in Sweden between 1990 and 1992. All had been evaluated at a corrected age of 36 months. At 11 years of age, 86 of 89 survivors were studied and compared with an equal number of control subjects, matched with respect to age and gender. Behavioral and emotional problems, social competencies, and adaptive functioning at school were evaluated with standardized, well-validated instruments, including parent and teacher report questionnaires and a child self-report, administered by mail.

RESULTS: Compared with control subjects, parents of extremely immature children reported significantly more problems with internalizing behaviors (anxiety/depression, withdrawn, and somatic problems) and attention, thought, and social problems. Teachers reported a similar pattern. Reports from children showed a trend toward increased depression symptoms compared with control subjects. Multivariate analysis of covariance of parent-reported behavioral problems revealed no interactions, but significant main effects emerged for group status (extremely immature versus control), family function, social risk, and presence of a chronic medical condition, with all effect sizes being medium and accounting for 8% to 12% of the variance. Multivariate analysis of covariance of teacher-reported behavioral problems showed significant effects for group status and gender but not for the covariates mentioned above. According to the teachers' ratings, extremely immature children were less well adjusted to the school environment than were control subjects. However, a majority of extremely immature children (85%) were functioning in mainstream schools without major adjustment problems.

CONCLUSIONS: Despite favorable outcomes for many children born at the limit of viability, these children are at risk for mental health problems, with poorer school results.

Background: Uncertainty continues regarding the extent to which neonatal morbidities predict poor long-term outcome and functional abilities in extremely preterm infants.

Objective: The goal of this study was to determine the impact of bronchopulmonary dysplasia (BPD), ultrasonographic signs of brain injury, and severe retinopathy of prematurity (ROP) on 11-year outcomes in infants born at <26 weeks' gestation.

Methods: A total of 247 infants were born alive before 26 completed weeks of gestation from 1990 through 1992 in all of Sweden, and 98 (40%) survived to a postmenstrual age of 36 weeks. Main outcome measures were (1) poor outcome, defined as combined end point of death after 36 weeks' postmenstrual age or survival with at least 1 major disability at 11 years, and (2) consequences of chronic conditions in the survivors according to a validated instrument administered to parents.

Results: Brain injury and severe ROP but not BPD correlated independently with poor outcome at 11 years of age. Among children who were free from BPD, brain injury, and severe ROP, 10% had a poor outcome. Corresponding rates with any 1, any 2, and all 3 neonatal morbidities were 19%, 58%, and 80%, respectively. Multivariate analysis revealed that brain injury and severe ROP were associated with high rates of consequences of chronic conditions.

Conclusions: In infants born extremely preterm who survive to a postmenstrual age of 36 weeks, severe ROP and brain injury separately predict the risk of death or major disability at 11 years of age. Thus, continued research to determine how to prevent these complications of prematurity is critical.

Context Up-to-date information on infant survival after extremely preterm birth is needed for assessing perinatal care services, clinical guidelines, and parental counseling.

Objective To determine the 1-year survival in all infants born before 27 gestational weeks in Sweden during 2004-2007.

Design, Setting, and Patients Population-based prospective observational study of extremely preterm infants (707 live-born and 304 stillbirths) born to 887 mothers in 904 deliveries (102 multiple births) in all obstetric and neonatal units in Sweden from April 1, 2004, to March 31, 2007.

Main Outcome Measures Infant survival to 365 days and survival without major neonatal morbidity (intraventricular hemorrhage grade >2, retinopathy of prematurity stage >2, periventricular leukomalacia, necrotizing enterocolitis, severe bronchopulmonary dysplasia). Associations between perinatal interventions and survival.

Results The incidence of extreme prematurity was 3.3 per 1000 infants. Overall perinatal mortality was 45% (from 93% at 22 weeks to 24% at 26 weeks), with 30% stillbirths, including 6.5% intrapartum deaths. Of live-born infants, 91% were admitted to neonatal intensive care and 70% survived to 1 year of age (95% confidence interval [CI], 67%-73%). The Kaplan-Meier survival estimates for 22, 23, 24, 25, and 26 weeks were 9.8% (95% CI, 4%-23%), 53% (95% CI, 44%-63%), 67% (95% CI, 59%-75%), 82% (95% CI, 76%-87%), and 85% (95% CI, 81%-90%), respectively. Lower risk of infant death was associated with tocolytic treatment (adjusted for gestational age odds ratio [OR], 0.43; 95% CI, 0.36-0.52), antenatal corticosteroids (OR, 0.44; 95% CI, 0.24-0.81), surfactant treatment within 2 hours after birth (OR, 0.47; 95% CI, 0.32-0.71), and birth at a level III hospital (OR, 0.49; 95% CI, 0.32-0.75). Among 1-year survivors, 45% had no major neonatal morbidity.

Conclusion During 2004 to 2007, 1-year survival of infants born alive at 22 to 26 weeks of gestation in Sweden was 70% and ranged from 9.8% at 22 weeks to 85% at 26 weeks.

 Preterm AGA infants with higher SDS for weight, length and HC at birth are at higher risk of inadequate growth during their hospital stay.

To establish breastfeeding in preterm infants, test weighing before and after breastfeeding and gradual reduction of supplementation are both applicable regimens. Mothers can be encouraged to choose either of them, although test weighing may help infants attain exclusive breastfeeding at an earlier PMA.

BACKGROUND AND OBJECTIVES: The risk of cerebral palsy (CP) is high in preterm infants and is often accompanied by additional neurodevelopmental comorbidities. The present study describes lifetime prevalence of CP in a population-based prospective cohort of children born extremely preterm, including the type and severity of CP and other comorbidities (ie, developmental delay and/or cognitive impairment, neurobehavioral morbidity, epilepsy, vision and hearing impairments), and overall severity of disability. In this study, we also evaluate whether age at assessment, overall severity of disability, and available sources of information influence outcome results.

METHODS: All Swedish children born before 27 weeks’ gestation from 2004 to 2007 were included (the Extremely Preterm Infants in Sweden Study). The combination of neonatal information, information from clinical examinations and neuropsychological assessments at 2.5 and 6.5 years of age, original medical chart reviews, and extended chart reviews was used.

RESULTS: The outcome was identified in 467 (94.5%) of eligible children alive at 1 year of age. Forty-nine (10.5%) children had a lifetime diagnosis of CP, and 37 (76%) were ambulatory. Fourteen (29%) had CP diagnosed after 2.5 years of age, 37 (76%) had at least 1 additional comorbidity, and 27 (55%) had severe disability. The probability for an incomplete evaluation was higher in children with CP compared with children without CP.

CONCLUSIONS: Children born extremely preterm with CP have various comorbidities and often overall severe disability. The importance of long-term follow-up and of obtaining comprehensive outcome information from several sources in children with disabilities is shown.

IMPORTANCE Follow-up at 30 months' corrected age reveals eye and visual problems in one-third of children born extremely prematurely (<27 weeks' gestation).

OBJECTIVE To investigate the ophthalmologic outcome of extremely preterm children at 30 months' corrected age.

DESIGN, SETTING, AND PARTICIPANTS A prospective, population-based follow-up study (Extremely Preterm Infants in Sweden Study [EXPRESS]) was conducted in Sweden. The population included extremely preterm infants (<27 weeks' gestation) born in Sweden between 2004 and 2007, of whom 491 survived until age 2.5 years. Screening for retinopathy of prematurity (ROP) was performed in the neonatal period. At 30 months' corrected age, an ophthalmologic assessment was performed in 411 of 491 children (83.7%).

MAIN OUTCOMES AND MEASURES Visual acuity, manifest strabismus, and refractive errors were evaluated.

RESULTS Visual impairment was identified in 3.1% of the children, and 1.0% were blind. Refractive errors, defined as myopia less than -3 diopters (D), hypermetropia greater than +3 D, astigmatism 2 D or more, and/or anisometropia 2 D or more, were found in 25.6% of the children, and 14.1% had manifest strabismus. There were significant associations between visual impairment and treated ROP (P = .02), cognitive disability (P < .001), and birth weight (P = .02). Multiple regression analyses revealed significant associations between strabismus and treated ROP (P < .001), cognitive disability (P < .01), and cerebral palsy (P = .02). Refractive errors were significantly correlated with severity of ROP (right eye, P < .001; left eye, P < .01). Children who had been treated for ROP had the highest frequency (69.0%) of eye and visual abnormalities.

CONCLUSIONS AND RELEVANCE One-third of the extremely prematurely born children in this study had some kind of eye or visual problems, such as visual impairment, strabismus, or major refractive error. Despite being born extremely preterm, the present cohort has a similar prevalence of blindness and visual impairment as in previous Swedish cohorts of children born less prematurely.

OBJECTIVE: We examined chronic conditions, functional limitations, and special health care needs in extremely preterm children (EPT; 23-25 weeks' gestation) born between 1992 and 1998 at 2 Swedish tertiary care centers that offered regional and active perinatal care to all live-born EPT infants. METHODS: Of 134 surviving EPT children, 132 (98%) were assessed at 10 to 15 years of age alongside 103 term-born controls. Identification of children with functional limitations and special health care needs was based on a questionnaire administered to parents. Categorization of medical diagnoses and developmental disabilities was based on child examinations, medical record reviews, and parent questionnaires. RESULTS: In logistic regression analyses adjusting for social risk factors and sex, the EPT children had significantly more chronic conditions than the term-born controls, including functional limitations (64% vs 6%; odds ratio [OR], 15; 95% confidence interval [CI], 6.1-37.2; P < .001), compensatory dependency needs (60% vs 29%; OR, 3.8; 95% CI, 2.2-6.6; P < .001), and services above those routinely required by children (64% vs 25%; OR, 5.4; 95% CI, 3.0-9.6; P < .001). Specific diagnoses and disabilities for the EPT group versus controls included cerebral palsy (9.1% vs 0%; P < .001), asthma (21.2% vs 6.8%; P = 001), IQ < -2 SD (31.1% vs 4.9%; P < .001), poor motor skills without neurosensory impairment (21.9% vs 1.9%; P < .001), and psychiatric conditions (15.2% vs 1.9%; P < .001). CONCLUSIONS: Adolescents born EPT have considerable long-term health and educational needs. Few had severe impairments that curtailed major activities of daily life.

Aim: Active perinatal care (APC) increases the survival of extremely preterm (EPT) infants, but may increase the rate of disabilities. We examined neurodevelopmental outcomes in adolescents aged 10-15 years who were born EPT and received APC in two Swedish tertiary care centres.

Methods: Cognitive function was assessed using the Wechsler Intelligence Scale for Children, and neurosensory impairments were assessed by reviewing the case records and a standard parent health questionnaire. The outcomes were compared to term-born controls.

Results: We assessed 132 EPT adolescents and 103 controls. The rates of cerebral palsy, moderate to severe visual impairment and moderate to severe hearing impairment were 9%, 4% and 6%, respectively, for the EPT children and zero for the controls. Serious cognitive impairment was present in 31% of the EPT adolescents and 5% of the controls. Combining impairments across domains showed that 34% of EPT adolescents had moderate and severe disabilities compared with 5% of the controls. Impairments were more common at 23-24 weeks of gestational age (43%) than at 25 weeks (28.4%).

Conclusion: Two-thirds (66%) of adolescents born EPT who received APC had mild or no disabilities. Our results are relevant for healthcare providers and clinicians counselling families.

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 Umea 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.

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 27weeks 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 24h, 70% survived 365days, 64% were assessed at 2.5years. The risk of death within 24h 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.

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.

The study aim was to explore the relationship between a developmental assessment at preschool age and an intelligence quotient (IQ) assessment at school age. One hundred sixty-two children were assessed at 2.5 years with the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III) and then at 6.5 years with the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV). The Bayley-III Cognitive Index score was the Bayley entity that showed the highest correlation with WISC-IV Full-Scale IQ (FSIQ; r = .41). There was a significant difference between the individual WISC-IV FSIQ and the Bayley-III Cognitive Index scores. Analyses showed an average difference of -4 units and 95% limits of agreement of -18.5 to 26.4 units. A multivariate model identified the Bayley-III Cognitive Index score as the most important predictor for FSIQ and General Ability Index (GAI), respectively, in comparison with demographic factors. The model explained 24% of the total FSIQ variation and 26% of the GAI variation. It was concluded that the Bayley-III measurement was an insufficient predictor of later IQ.

AimThis study evaluated sepsis as a risk factor for neonatal morbidities and investigated the association between specific pathogens and neonatal morbidities. MethodsThis was a nationwide Swedish prospective cohort study, consisting of the 497 extremely premature children, who were born before 27weeks 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. ResultsWe 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. ConclusionExtremely 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.

BACKGROUND: This study examined mental health outcomes in extremely preterm children (EPT) born at 23 to 25 weeks of gestation between 1992 and 1998 at 2 Swedish tertiary care centers that offered regional and active perinatal care to all live-born EPT infants. METHODS; We assessed 132 (98%) of the 134 EPT survivors at 10 to 15 years of age alongside term-born controls. Behavioral and emotional problems were evaluated by using Achenbach's Child Behavior Checklist and Teacher Report Form and Conners' Parent and Teacher scales for attention-deficit/hyperactivity disorder. RESULTS: Parents and teachers reported significantly more problems with internalizing behaviors as well as attention, social, and thought problems in EPT children than in controls, even when those with major neurodevelopmental disabilities (NDDs) were excluded. Multivariate analysis of covariance of the behavioral problems reported by parents and teachers revealed no interactions, hut significant main effects emerged for group status (EPT versus control) and sex, with all effect sizes being medium to large and accounting for 8% to 14% of the variance. Compared with the controls, EPT children without NDDs had significantly increased rates of >= 90th percentile for total Conners' attention-deficit/hyperactivity disorder problem scores (parents: 40% vs 15%, odds ratio: 3.7, P <.001) (teachers: 24% vs 9%, odds ratio: 3.3, P =.005). The corresponding rates were higher in the total population. CONCLUSIONS: EPT children with or without NDDs had behavioral problems characterized by a higher risk for anxiety and attention, social, and thought problems. These findings further strengthen the proposition that a preterm behavioral phenotype is recognizable in adolescents born EPT.

AIMS: To provide descriptive data on women who delivered at 23-25 wk of gestation, and to relate foetal and neonatal outcomes to maternal factors, obstetric management and the principal reasons for preterm birth. METHODS: Medical records of all women who had delivered in two tertiary care centres in 1992-1998 were reviewed. At the two centres, policies of active perinatal and neonatal management were universally applied. Logistic regression models were used to identify prenatal factors associated with survival. RESULTS: Of 197 women who delivered at 23-25 wk, 65% had experienced a previous miscarriage, 15% a previous stillbirth and 12% a neonatal death. The current pregnancy was the result of artificial reproduction in 13% of the women. In 71%, the pregnancy was complicated either by pre-eclampsia, chorioamnionitis, placental abruption or premature rupture of membranes. Antenatal steroids were given in 63%. Delivery was by caesarean section in 47%. The reasons for preterm birth were idiopathic preterm labour in 36%, premature rupture of membranes in 41% and physician-indicated deliveries in 23% of the mothers. Demographic details, use of antenatal steroids, caesarean section delivery and birthweight differed between mothers depending on the reason for preterm delivery. Of 224 infants, 5% were stillbirths and 63% survived to discharge. On multivariate logistic regression analysis comprising prenatally known variables, reasons for preterm birth were not associated with survival. Advanced gestational duration (OR: 2.43 per wk; 95% CI: 1.59-3.74), administration of any antenatal steroids (OR: 2.21; 95% Cl: 1.14-4.28) and intrauterine referral from a peripheral hospital (OR: 2.93; 95% CI: 1.5-5.73) were associated with survival. CONCLUSIONS: Women who deliver at 23-25 wk comprise a risk group characterized by a high risk of reproductive failure and pregnancy complications. Survival rates were similar regardless of the reason for preterm birth. Policies of active perinatal management virtually eliminated intrapartum stillbirths.

AIM: To determine major neonatal morbidity in surviving infants born at 23-25 weeks, and to identify maternal and infant factors associated with major morbidity. METHODS: The medical records of 224 infants who were delivered at two tertiary care centres in 1992-1998 were reviewed retrospectively. At these centres, policies of active perinatal and neonatal management were universally applied. Of the 213 liveborn infants, 140 (66%) survived to discharge. Data were analysed by gestational age and considered in three time periods. Logistic regression models were used to identify factors associated with morbidity. RESULTS: Of the survivors, 6% had intraventricular haemorrhage grade > or = 3 (severe IVH) or periventricular leukomalacia (PVL), 15% retinopathy of prematurity > or = stage 3 (severe ROP) and 36% bronchopulmonary dysplasia (BPD). On logistic regression analysis, severe IVH or PVL was associated with duration of mechanical ventilation (odds ratio, OR: 1.53 per 1-wk increment in duration; 95% confidence interval, CI: 1.01-2.33). Severe ROP was associated with the presence of a patent ductus arteriosus (PDA) (OR: 3.31; 95% CI: 1.11-9.90) and birth in time period 3 versus time periods 1 and 2 combined (OR: 6.28; 95% CI: 2.10-18.74). BPD was associated with duration of mechanical ventilation (OR: 2.71 per 1-wk increment in duration; 95% CI: 1.76-4.18) and with the presence of any obstetric complication (OR: 2.67; 95% CI: 1.07-6.65). Gestational age and birthweight were not associated with major morbidity. Of all survivors, 81% were discharged home without severe IVH, PVL or severe ROP. CONCLUSIONS: Increased survival as a result of active perinatal and neonatal management was associated with favourable morbidity rates compared with those in recent studies. Among survivors born at 23-25 weeks, neither gestational age nor birthweight was a significant determinant of major morbidity.

AIM: To determine neonatal survival rates based on both foetal (stillborn) and neonatal deaths among infants delivered at 23-25 wk, and to identify maternal and neonatal factors associated with survival. METHODS: The medical records of 224 infants who were delivered in two tertiary care centres in 1992-1998 were reviewed retrospectively. At these centres, policies of active perinatal and neonatal management were universally applied. Data were analysed by gestational age groups and considered in three time periods. Logistic regression models were used to identify factors associated with survival. RESULTS: The rate of foetal death was 5%. Of infants born alive, 63% survived to discharge. Survival rates including foetal deaths in the denominator at 23, 24 and 25 wk were 37%, 61% and 74%, respectively, and survival rates excluding foetal deaths were 43%, 63% and 77%, respectively. Of infants born with 1-min Apgar scores of 0-1, 43% survived. In the total cohort, survival rates including foetal deaths in the denominator increased from 52% in time period 1 to 61% in time period 2 and 74% in time period 3 (p < 0.02). On multivariate logistic regression analysis, higher birthweight (OR: 1.91 per 100 g increment; 95% CI: 1.45-2.52), female gender (OR: 3.33; 95% CI: 1.65-6.75), administration of antenatal steroids (OR: 2.95; 95% CI: 1.46-5.98) and intrauterine referral from a peripheral hospital (OR: 2.35; 95% CI: 1.18-4.68) were associated with survival. Apgar score < or = 3 at 1 min (OR: 0.46; 95% CI: 0.22-0.95) was associated with decreased survival. The use of antenatal steroids was protective at 23-24 wk (OR: 5.2; 95% CI: 2.0-13.7), but not at 25 wk. CONCLUSIONS: Active perinatal management that included universal initiation of neonatal intensive care virtually eliminated intrapartum stillbirths and delivery room deaths, and resulted in survival rates that compare favourably with those of recent studies. However, the policies of active care postponed death in non-survivors. Individual variations in outcome in relation to the infant's condition at birth as reflected by the Apgar scores preclude the making of treatment decisions in the delivery room.

SBU:s bedömning av kunskapsläget

Förlossningsasfyxi innebär att barnet i samband med födelsen drabbas av en kombination av syrebrist och nedsatt blodförsörjning. Om asfyxin är allvarlig kan barnet kort efter födelsen utveckla symtom på hjärnskada, så kallad hypoxisk ischemisk encefalopati (HIE). Vid måttlig till svår asfyxi kan skadorna på hjärna och andra organ till följd av syrebrist bli mycket allvarliga, och en del av barnen avlider. Hos dem som överlever finns en ökad risk för måttliga eller svåra funktionshinder, t ex i form av cerebral pares (CP) eller syn- och hörselskador. Kylbehandling är en ny metod för behandling av HIE efter asfyxi i samband med födelsen och ges som ett komplement till sedvanlig symtomlindrande behandling.

• Kylbehandling av fullgångna nyfödda barn som har drabbats av måttliga eller svåra symtom på hjärnskada (HIE) till följd av allvarlig förlossningsasfyxi minskar risken för att barnen dör eller drabbas av svårt funktionshinder (Evidensstyrka 2)*. Det vetenskapliga underlaget är dock otillräckligt* för att bedöma metodens effekter på längre sikt än 18 månader.

• Det vetenskapliga underlaget är otillräckligt* för att dra säkra slutsatser om biverkningar och komplikationer relaterade till kylbehandling. Inga allvarliga biverkningar eller komplikationer har identifierats i de studier som granskats i denna rapport, men dessa studier har inte varit specifikt upplagda för att studera detta.

• Det vetenskapliga underlaget är otillräckligt* för att dra säkra slutsatser om metodens kostnadseffektivitet. Det faktum att metodens merkostnader är relativt måttliga och effekterna goda, talar dock för att metoden är kostnadseffektiv.

• Det är oklart hur behandlingen ska utföras på bästa sätt. Därför är det viktigt att erfarenheter och resultat av behandlingen följs upp, t ex med hjälp av ett centralt kvalitetsregister. Det är också angeläget med fortsatt forskning för att vinna kunskap om optimal praxis och eventuella komplikationer och biverkningar.

OBJECTIVE: To examine the association between intensity of perinatal care and outcome at 2.5 years' corrected age (CA) in extremely preterm (EPT) infants (<27 weeks) born in Sweden during 2004-2007. METHODS: A national prospective study in 844 fetuses who were alive at the mother's admission for delivery: 707 were live born, 137 were stillborn. Infants were assigned a perinatal activity score on the basis of the intensity of care (rates of key perinatal interventions) in the infant's region of birth. Scores were calculated separately for each gestational week (gestational age [GA]-specific scores) and for the aggregated cohort (aggregated activity scores). Primary outcomes were 1-year mortality and death or neurodevelopmental disability (NDI) at 2.5 years' CA in fetuses who were alive at the mother's admission. RESULTS: Each 5-point increment in GA-specific activity score reduced the stillbirth risk (adjusted odds ratio [aOR]: 0.90; 95% confidence interval [CI]: 0.83-0.97) and the 1-year mortality risk (aOR: 0.84; 95% CI: 0.78-0.91) in the primary population and the 1-year mortality risk in live-born infants (aOR: 0.86; 95% CI: 0.79-0.93). In health care regions with higher aggregated activity scores, the risk of death or NDI at 2.5 years' CA was reduced in the primary population (aOR: 0.69; 95% CI: 0.50-0.96) and in live-born infants (aOR: 0.68; 95% CI: 0.48-0.95). Risk reductions were confined to the 22- to 24-week group. There was no difference in NDI risk between survivors at 2.5 years' CA. CONCLUSIONS: Proactive perinatal care decreased mortality without increasing the risk of NDI at 2.5 years' CA in EPT infants. A proactive approach based on optimistic expectations of a favorable outcome is justified.

IMPORTANCE Active perinatal care increases the rate of survival of extremely preterm infants, but there are concerns that improved survival might increase the rate of disabled survivors. OBJECTIVE To determine the neurodevelopmental outcomes of a national cohort of children 6.5 years of age who had been born extremely preterm (<27 weeks' gestational age) in Sweden. DESIGN, SETTING, AND PARTICIPANTS Population-based prospective cohort study of consecutively born extremely preterm infants. All of these infants were born in Sweden during the period from April 1, 2004, to March 31, 2007. Of 707 live-born extremely preterm infants, 486 (68.7%) survived to 6.5 years of age. These children were assessed and compared with matched controls who had been born at term. Comparison estimates were adjusted for demographic differences. Assessments ended in February 2014, and analysis started thereafter. MAIN OUTCOMES AND MEASURES Cognitive ability was measured with the fourth edition of the Wechsler Intelligence Scale for Children (WISC-IV), and the mean (SD) scores of the children who had been born extremely preterm were compared with those of the controls. Clinical examinations and parental questionnaires were used for diagnosis of cerebral palsy, hearing and vision impairments, and cognition for the children who were not assessed with the WISC-IV. RESULTS Of 486 eligible infants who were born extremely preterm, 441 (90.7%) were assessed at 6.5 years of age (59 by medical record review only) alongside 371 controls. The adjusted mean (SD) full-scale WISC-IV score was 14.2 (95% CI, 12.1-16.3) points lower for children who had been born extremely preterm than for controls. Cognitive disability was moderate for 18.8% of extremely preterm children and 2.2% of controls (P < .001), and it was severe for 11.1% of extremely preterm children and 0.3% of controls (P < .001). Cerebral palsy was observed in 9.5% of extremely preterm children and 0.0% of controls (P < .001), blindness was observed in 2.0% of extremely preterm children and 0.0% of controls (P < .001), and hearing impairment was observed in 2.1% of extremely preterm children and 0.5% of controls (P = .07). Overall, 36.1%(95% CI, 31.7%-40.6%) of extremely preterm children had no disability, 30.4%(95% CI 26.3%-34.8%) had mild disability, 20.2%(95% CI, 16.6%-24.2%) had moderate disability, and 13.4%(95% CI, 10.5%-16.9%) had severe disability. For extremely preterm children, moderate or severe overall disability decreased with gestational age at birth (adjusted odds ratio per week, 0.65 [95% CI, 0.54-0.79]; P < .001) and increased from 26.6% to 33.5%(P = .01) for children assessed both at 2.5 and 6.5 years. CONCLUSIONS AND RELEVANCE Of the 441 extremely preterm infants who had received active perinatal care, 293 (66.4%) had no or mild disability at 6.5 years; of the 371 controls, 11 (3.0%) had moderate or severe disability. Disability rates at 6.5 years increased relative to the rates at 2.5 years. Results are relevant for health care professionals and planners, and for clinicians counseling families facing extremely preterm births.

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-III), 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-III 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.

Aim: The aim of this study was to investigate differences in mortality up to 1year of age in extremely preterm infants (before 27weeks) 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 (22-26weeks) and in the stillbirth and perinatal and 365-day mortality rates for the subgroup born at 22-24weeks. Among 707 infants born alive, regional differences were found both in mortality before 12h and in the 365-day mortality rate for the subgroup (22-24weeks) and for the total group (22-26weeks). The mortality rates were consistently lower in two healthcare regions. There were no differences in the 365-day mortality rate for infants alive at 12h or for infants born at 25weeks. 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.

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 (<27weeks) born in Sweden during 2004-2007. Detailed data on nutrition and anthropometric measurements from birth to 70days of postnatal age were retrieved from hospital records.

Results Study infants (n=531) had a meanSD gestational age of 25.3 +/- 1.1weeks and a birth weight of 765 +/- 170g. Between 0 and 70 days, average daily energy and protein intakes were 120 +/- 11kcal/kg and 3.2 +/- 0.4g/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.