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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.

This study assesses rates of extremely preterm births (22-26 weeks’ gestation) and their outcomes by hospital level of care among all births registered in Sweden from 2014 to 2019.

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.

Objective To compare length of stay (LOS) in neonatal care for babies born extremely preterm admitted to networks participating in the International Network for Evaluating Outcomes of Neonates (iNeo). Study design Data were extracted for babies admitted from 2014 to 2016 and born at 24 to 28 weeks of gestational age (n = 28 204). Median LOS was calculated for each network for babies who survived and those who died while in neonatal care. A linear regression model was used to investigate differences in LOS between networks after adjusting for gestational age, birth weight z score, sex, and multiplicity. A sensitivity analysis was conducted for babies who were discharged home directly. Results Observed median LOS for babies who survived was longest in Japan (107 days); this result persisted after adjustment (20.7 days more than reference, 95% CI 19.3-22.1). Finland had the shortest adjusted LOS (−4.8 days less than reference, 95% CI –7.3 to −2.3). For each week's increase in gestational age at birth, LOS decreased by 12.1 days (95% CI –12.3 to −11.9). Multiplicity and male sex predicted mean increases in LOS of 2.6 (95% CI 2.0-3.2) and 2.1 (95% CI 1.6-2.6) days, respectively. Conclusions We identified between-network differences in LOS of up to 3 weeks for babies born extremely preterm. Some of these may be partly explained by differences in mortality, but unexplained variations also may be related to differences in clinical care practices and healthcare systems between countries.

Background Very preterm infants are at high risk of death or severe morbidity. The objective was to determine the significance of severe congenital heart defects ( CHDs ) for these risks. Methods and Results This cohort study included infants from 10 countries born from 2007–2015 at 24 to 31 weeks’ gestation with birth weights CHDs were defined by International Classification of Diseases, Ninth Revision ( ICD‐9 ) and Tenth ( ICD‐10 ) codes and categorized as those compromising systemic output, causing sustained cyanosis, or resulting in congestive heart failure. The primary outcome was in‐hospital mortality. Secondary outcomes were neonatal brain injury, necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy of prematurity. Adjusted and propensity score–matched odds ratios ( ORs ) were calculated. Analyses were stratified by type of CHD , gestational age, and network. A total of 609 (0.77%) infants had severe CHD and 76 371 without any malformation served as controls. The mean gestational age and birth weight were 27.8 weeks and 1018 g, respectively. The mortality rate was 18.6% in infants with CHD and 8.9% in controls (propensity score–matched OR , 2.30; 95% CI , 1.61–3.27). Severe CHD was not associated with neonatal brain injury, necrotizing enterocolitis, or retinopathy of prematurity, whereas the OR for bronchopulmonary dysplasia increased. Mortality was higher in all types, with the highest propensity score–matched OR (4.96; 95% CI, 2.11–11.7) for CHD causing congestive heart failure. While mortality did not differ between groups at OR for mortality in infants with CHD increased to 10.9 (95% CI, 5.76–20.70) at 31 weeks’ gestational age. Rates of CHD and mortality differed significantly between networks. Conclusions Severe CHD is associated with significantly increased mortality in very preterm infants.

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 in ...

Background: At term-equivalent age, infants born prematurely are shorter, lighter and have more adipose tissue compared to term counterparts. Little is known on whether the differences in body composition persist in later age. Methods: We prospectively recruited 33 preterm infants (Results: At 4 months of age preterm infants were lighter and shorter than term controls (mean weight-for-age z-score: –0.73 vs. 0.06, p = 0.001; mean length-for-age z-score: –1.31 vs. 0.29, p < 0.0001). The significantly greater percentage of total body fat seen in preterm infants at term-equivalent age (20.2 vs. 11.7%, p < 0.0001) was no longer observed at 4 months. A deficit of fat-free mass persisted until 4 months of age (fat-free mass at term-equivalent age: 2.71 vs. 3.18 kg, p < 0.0001; at 4 months: 4.3 vs. 4.78 kg, p < 0.0001). The fat mass index and fat-free mass index (taking length into account) did not differ between the groups. Nutrition had little effect on body composition. Higher protein intake at week 2 was a negative predictor of fat-free mass at discharge. Conclusions: At 4 months corrected age, preterm infants were both lighter and shorter than term controls and the absolute fat-free mass deficit remained until this age. Little effect of nutrition on body composition was observed.

This study aimed to investigate cognitive and behavioral outcomes in relation to gestational age (GA) in school-aged children born preterm (PT). Results from the Wechsler Intelligence Scale for Children, 4th edition (WISC-IV), and the Child Behavior Checklist (CBCL) were analyzed in 51 children (mean age: 7.8 years [range: 7.0–8.7]) born PT (mean GA: 31 weeks [range: 23–35]; birth weight, mean: 1,637 g [range: 404–2,962]) with the majority (96%) having no diagnosed cognitive, sensory, or motor impairments. The control group included 57 age-matched typically developing children (mean age: 7.9 years [range: 6.2–8.7]) born full-term (FT). Children born PT, extremely PT (GA < 28) in particular, showed significantly lower cognitive performance and higher behavioral problem scores compared with children born FT. GA was found to predict aspects of both cognitive functioning and behavioral problems within the PT group, with lower GA being related to both poorer cognitive outcomes and elevated affective and attention-deficit/hyperactivity problems. Global cognitive functioning did not independently predict aspects of behavioral outcomes. Findings demonstrate that, even in children born PT without severe perinatal and/or postnatal complications and receiving active perinatal care, a short gestation is an evident risk factor for long-term negative effects on mental health independent of cognitive functioning. Additional findings suggest that both reduced growth and lower parental educational level may contribute to increased risk for poorer cognitive and behavioral functioning in children born PT.

Few studies have examined the parents of moderately preterm children. The aim of this study was to investigate the experiences of parents of both extremely and moderately preterm children.Qualitative telephone interviews were conducted in 2013-2014 with 13 mothers and 10 fathers of extremely preterm children and with 11 mothers and seven fathers of moderately preterm children. The children were born between 2000 and 2003. Data were analysed with a narrative approach.Parents of extremely preterm children recounted dramatic birth stories that, for most, ended positively. Parents of moderately preterm children presented more neutral birth stories, and most recounted that their children did not receive attention for prematurity from medical staff. Parents from both groups described staff members' treatment in terms of long-lasting impressions, and they were deeply affected by the hospital environment and the other parents and children admitted. Parents whose children died or were disabled recounted dramatic stories and endless fights for support.Parents from both groups reported long-lasting impressions of the medical staff and the hospital environment, which they found important to talk about, even a decade after the birth of their child/children.

ObjectiveTo evaluate the effectiveness of drugs used to constrict patent ductus arteriosus (PDA) in newborns

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.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.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%).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.

This article explores the ways in which mothers of extremely premature children make sense of their negative feelings towards their newborn child and their strategies for performing “proper motherhood”. The analysis was guided by discursive psychology and the feminist debate on attachment, mother–infant bonding, and “good motherhood”. The empirical material was created within a sub-study that set out to explore mothers’ and fathers’ experiences of having a premature child and was part of a project investigating the need for support for premature children and their families. Parents were interviewed about the pregnancy, their experiences of the birth and hospital period, the process of going home, the experiences of pre-school and school, and thoughts about the future. The stories of four mothers, which dealt with negative feelings towards their child and the guilt and distress related to this, were selected for analysis. The mothers handled their troubled positions as subjects unable to feel “motherly love” by referring to notions of attachment and bonding, and good motherhood as being loving and caring. Yet, the mothers also talked about motherhood as being socially constructed, as duties that can be performed without the “right motherly feelings”, and as something that men could also perform.

In the PDA-TOLERATE trial, persistent (even for several weeks) moderate to large patent ductus arteriosus (PDA) was not associated with an increased risk of BPD when the infant required

ObjectiveTo compare early routine pharmacologic treatment of moderate-to-large patent ductus arteriosus (PDA) at the end of week 1 with a conservative approach that requires prespecified respiratory and hemodynamic criteria before treatment can be given.Study designA total of 202 neonates of

To assess associations between neonatal intensive care unit (NICU)-level patent ductus arteriosus (PDA) treatment rates (pharmacologic or surgical) and neonatal outcomes.This cohort study included infants born at 24-28 weeks of gestation and birth weight1500 g in 2007-2015 in NICUs caring for ≥100 eligible infants in 6 countries. The ratio of observed/expected (O/E) PDA treatment rates was derived for each NICU by estimating the expected rate using a logistic regression model adjusted for potential confounders and network. The primary composite outcome was death or severe neurologic injury (grades III-IV intraventricular hemorrhage or periventricular leukomalacia). The associations between the NICU-level O/E PDA treatment ratio and neonatal outcomes were assessed using linear regression analyses including a quadratic effect (a square term) of the O/E PDA treatment ratio.From 139 NICUs, 39 096 infants were included. The overall PDA treatment rate was 45% in the cohort (13%-77% by NICU) and the O/E PDA treatment ratio ranged from 0.30 to 2.14. The relationship between the O/E PDA treatment ratio and primary composite outcome was U-shaped, with the nadir at a ratio of 1.13 and a significant quadratic effect (P.001). U-shaped relationships were also identified with death, severe neurologic injury, and necrotizing enterocolitis.Both low and high PDA treatment rates were associated with death or severe neurologic injury, whereas a moderate approach was associated with optimal outcomes.

To explore how parents of preterm infants express the constructive aspects of their experiences. Using the notion of post-traumatic growth as a back-drop, this study supplements the research on parents' difficulties by providing a more nuanced understanding of what it is like to have a preterm child.Researchers have reported that parents feel afraid, worried, helpless, powerless, guilty and stressed, as well as that preterm birth can be associated with physical and psychological ill health among parents; however, a few researchers have found indications of post-traumatic growth among parents.This study includes qualitative interviews and relates to COREQ guidelines for reporting qualitative research.A total of 13 mothers and 10 fathers of extremely preterm children, as well as 11 mothers and 7 fathers of moderately preterm children, were interviewed. The data analysis was based on thematic analysis.The analysis resulted in six themes that describe various constructive aspects of having a preterm child: acceptance of the fact that events do not always occur as planned; gratitude and reconsideration of the situation; reappraisal of close relationships; reliance on one's own ability to deal with events; thankfulness for what one has; and openness to being exposed to various kinds of people and their experiences.The parents recounted constructive aspects of their experiences such as an altered understanding of themselves, others and life itself. These themes provide a more nuanced way of understanding how parents can relate to having preterm children.This knowledge can help professionals to enable parents to activate their social network and to acknowledge their care for each other, as well as to help parents see beyond cultural ideals regarding childbirth and family life and to find their own solutions to everyday life.

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.To compare survival of extremely preterm infants born during 2004-2007 with survival of infants born during 2014-2016.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.Delivery at 22-26 weeks' gestational age.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).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).Among live births at 22-26 weeks' gestational age in Sweden, 1-year survival improved between 2004-2007 and 2014-2016.

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.

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, but 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.

To explore relations between aspects of upper-body spatiotemporal movement organization and intelligence in children born preterm at school age.Three-dimensional (3D) kinematic recordings of arm and head movements during a unimanual precision task were related to performance on the Wechsler Intelligence Scale for Children, 4th edition, in a sample of 32 children born preterm (gestational age, mean: 31.5 weeks [range: 22-35 weeks]; birth weight, mean: 1699 g [range: 404-2962 g]) at 6 years to 8 years with no diagnosed cognitive, sensory, or motor impairments compared with 40 age-matched control children born fullterm.In the children born preterm, upper-limb movement duration and segmentation of movement trajectories were significantly associated with full-scale intelligence quotient independent of gestational age (GA) and sex. These effects pertained to the preferred side, characterized by more effective movement organization being linked with increased intelligence scores. The same relations were not seen in the controls. Within the children born preterm, a significant effect of GA was also found for some aspects of upper-limb movement organization. Full-scale intelligence quotient was within normal limits for both groups but significantly lower in the preterm (mean: 94.5 [range: 72-120]) compared with the fullterm (mean: 101.7 [range: 76-119]) born children.The findings demonstrate that, independent of GA, the spatiotemporal organization of upper-limb movements is partly associated with cognitive performance in children born preterm.

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.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.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.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.

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.

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.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.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.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.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.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.

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 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.

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

OBJECTIVE To compare rates of a composite outcome of mortality or major morbidity in very-preterm/very low birth weight infants between 8 members of the International Network for Evaluating Outcomes. STUDY DESIGN We included 58 004 infants born weighing

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. Knowledge of long-term growth of extremely preterm infants in relation to gestational age is incomplete, and there are concerns regarding their poor growth in early childhood. As part of a longitudinal study of a national cohort of infants born at METHODS. Two hundred forty-seven extremely immature children were born alive from April 1990 through March 1992 in the whole of Sweden, and 89 (36%) survived. Growth and neurosensory outcomes of all extremely immature survivors were evaluated at 36 months of age. Eighty-six (97%) extremely immature children were identified and assessed at 11 years of age. In this growth study, 83 extremely immature infants (mean [SD]: birth weight, 772 g [110 g]; gestational age, 24.6 weeks [0.6 weeks]) without severe motor disability were followed up prospectively from birth to 11 years old and compared with a matched group of 83 children born at term. z scores for weight, height, head circumference, and BMI were computed for all children. We also examined gender-specific longitudinal growth measures. Predictors of 11-year growth were studied by multivariate analyses.RESULTS. Extremely immature children were significantly smaller in all 3 growth parameters than the controls at 11 years. Extremely immature children showed a sharp decline in weight and height z scores up to 3 months' corrected age, followed by catch-up growth in both weight and height up to 11 years. In contrast to weight and height, extremely immature children did not exhibit catch-up growth in head circumference after the first 6 months of life. The mean BMI z scores increased significantly from 1 to 11 years in both groups. The mean BMI change between 1 and 11 years of age was significantly larger in extremely immature than in control participants. Extremely immature girls showed a faster weight increase than extremely immature boys, whereas catch-up growth in height and head circumference was similar in these groups. Multiple-regression analyses revealed that preterm birth and parental height were significant predictors of 11-year height, and group status (prematurity) correlated strongly with head circumference.CONCLUSIONS. Children born at the limit of viability attain poor growth in early childhood, followed by catch-up growth to age 11 years, but remain smaller than their term-born peers. Strategies that improve early growth might improve the outcome.

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 ...

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 sur ...

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.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.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.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.

BACKGROUNDThere is a renewed interest in metabolism of sphingolipids because of their role in signal transduction. Sphingomyelin is the dominating phospholipid in human milk but its metabolism and possible function in the gastrointestinal tract of breast fed infants is unknown. We explored whether bile salt-stimulated milk lipase has a role in sphingolipid metabolism.METHODSIn vitro assays of sphingomyelinase and ceramidase activities, using radiolabeled substrates, human milk samples and purified native and recombinant variants of bile salt-stimulated milk lipase with or without known activators or inhibitors.RESULTSHuman whey and purified lipase catalysed hydrolysis of palmitoyl-labeled ceramide with the highest rate around pH 8.5-9.0. 1 mg of lipase hydrolysed 0.7 micromol ceramide in one hour at pH 8.5 in presence of 4 mM bile salt. The activity of whey was inhibited by antibodies towards human bile salt-stimulated milk lipase, indicating that this lipase accounted for virtually all ceramidase activity in the milk. In contrast, bile salt-stimulated milk lipase showed no activity against sphingomyelin. However we give evidence of a separate, hitherto unknown, acid sphingomyelinase in human milk. Under the used in vitro conditions this sphingomyelinase could account for hydrolysis of half of milk sphingomyelin in one hour.CONCLUSIONSHuman milk bile salt-stimulated milk lipase hydrolyses ceramide and may thus have a role in sphingomyelin digestion, but only after initial hydrolysis to ceramide and phosphorylcholine. Part of the latter could be carried out in the stomach by the acid milk sphingomyelinase now described. We speculate that these two milk enzymes may be of importance for optimal use of human milk sphingolipids. (Less)

AimsTo 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.MethodsA 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 subscales 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.ResultsThe 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 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.ConclusionEPT 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.

Pervasive behavioural problems are common in children born at less than 26 weeks of gestation.

Introduction:Although children born preterm (PT) are at known risk for impaired neuromotor development, longitudinal studies using detailed measurements of motor performance are rare. This study in ...

BACKGROUND. Children born extremely immature (gestational age METHODS. We studied 11-year-old children born before 26 completed weeks of gestation in all of Sweden from 1990 through 1992. All had been evaluated at 36 months' corrected age. Identification of children with chronic conditions lasting ≥12 months was based on a questionnaire administered to parents. Neurosensory impairments were identified by reviewing health records. Information regarding other specific medical diagnoses and developmental disabilities was obtained by standard parent and teacher questionnaires. RESULTS. Of 89 eligible children, 86 (97%) were studied at a mean age of 11 years. An equal number of children born at term served as controls. Logistic-regression analyses adjusting for social risk factors and gender showed that significantly more extremely immature children than controls had chronic conditions, including functional limitations (64% vs 11%, respectively), compensatory dependency needs (59% vs 25%), and services above those routinely required by children (67% vs 22%). Specific diagnoses or disabilities with higher rates in extremely immature children than in controls included neurosensory impairment (15% vs 2%), asthma (20% vs 6%), poor motor skills of >2 SDs above the mean (26% vs 3%), poor visual perception of >2 SDs above the mean (21% vs 4%), poor learning skills of >2 SDs above the mean (27% vs 3%), poor adaptive functioning with T scores of CONCLUSIONS. Children born extremely immature have significantly greater health problems and special health care needs at 11 years of age. However, few children have severe impairments that curtail major activities of daily living.

Objective To determine the nature of cognitive function, frequency and severity of cognitive deficit, in 10 to 15-year-old extremely preterm (EPT) children born at 2 tertiary care centers in Sweden adhering to a policy of universal resuscitation of all infants born alive. Methods The outcomes of 121 surviving EPT children, born 1992–1998, were compared to a control group of 100 term children. Children were assessed with WISC- III at 9–16 years of age. Relationship of perinatal risk factors (PNRF) with the outcomes was examined with multivariate regression analyses (MRA). Results The EPT group had a mean IQ of 80 (controls 103). 29% of the EPT children had an IQ below 70 (controls 3.4%), of which 9 % were under IQ 55 (controls 0). Another 30% of EPT children had IQ within the mildly delayed range, 70–84 (controls 12.6%). The preterm group has a greater variance between cognitive domains, with the language skills as relative strength and spatial thinking as pronounced weakness. MRA revealed that only gestaional age was inversely related to FSIQ (B 7.1, P 022) and Performance IQ (B 9.8, P Conclusion Cognitive dysfunctions remain high in EPT children. These numbers are similar to those from centres with less active perinatal care policies. Very few have severe cognitive impairment that curtail their activities in daily life.

Background Active perinatal care increases the survival of extremely preterm infants but there are concerns that improved survival might increase the rate of disabled survivors. Objective To determine neurodevelopmental outcome at 6.5 years of age in extremely preterm children (EPT, Design/methods Poulation-based prospective cohort of all EPT children born in Sweden from April 1, 2004, to March 31, 2007. Survivors were assessed and compared with a term-born control group. Of 707 live-born infants, 69% survived to 6.5 years. Intellectual ability was measured with WISC- lV and results were related to the mean and SD of the controls. Clinical examination and parental questionnaires were used for diagnosis of cerebral palsy, hearing and vision impairments. Results At a median age of 78 months, 445 of 494 eligible EPT children (90%) were assed (59 by chart review). The rates of cerebral palsy, moderate visual impairment, blindness and deafness were 9.2%, 5.2%, 2.0% and 0.7%, respectively vs 0.0%, 0.5%, 0% and 0%, respectively among 370 controls. 364 EPT children and 369 controls were formally tested with WISC-lV. Intellectual impairment -3SD, and Conclusion Disability rates are comparable to similar studies that report lower survival rates.

To evaluate the perinatal and 2-year outcomes in pregnancies complicated by preterm premature rupture of membranes (PROM) during the second trimester.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.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.Expectant management of second-trimester PROM offers better perinatal and long-term survival than previously thought.

The alkaline sphingomyelinase (SMase) was first found in rat intestinal brush border. The important roles of this enzyme in digestion of sphingomyelin and in mucosal cell proliferation have been suggested. In the present work, the distribution of the alkaline SMase in the tissues of human beings and animals have been studied. By assaying the enzyme activity in human biopsy samples, we found that the alkaline SMase activity was absent in the stomach, increased in the duodenum, present at high levels in the small intestine, and slightly declined in the colon and rectum. High activities were found similarly in the intestinal contents of the healthy adults and infants. The activities were also found in the intestinal mucosa of rats, normal and germ-free mice, and hamsters with the same distribution pattern as in humans, but not in the intestinal mucosa of guinea pigs. Apart from the intestinal tract, a SMase activity preferring alkaline pH was identified in human and guinea pig bile, but not in the bile of rat, pig, sheep, and cow. No activity was found in either pancreatic tissue or pancreatic juice in all species tested, and none was detected in human urine and milk. In conclusion, alkaline SMase exists predominantly in the digestive system with considerable tissue and species differences.

Background and Aims To examine neurosensory outcomes and special health care needs in 10 to 16-year-old extremely preterm (EPT) children born at 2 tertiary care centers in Sweden adhering to a policy of universal resuscitation of all infants born alive. Design and methods The outcomes of 122 surviving EPT children were compared to a matched control of children born at term. Neurosensory impairments (NSI) were assessed by review of pediatric case records, intelligence by WISC-III, and functional limitations and special health care needs by validated parental interviews (QUICCC). Results Of 213 consecutive EPT live births, 140 (66%) survived to discharge home and 6 infants died in the first year of life. Of survivors, 122 children (91%) were recruited for the study. Table 1 shows rates of disabilities. EPT children had significantly higher rates of functional limitations and special health care needs than controls but the vast majority was free from severe disability that curtail them from activities of daily life. Conclusions Disability rates and special health care needs remain high in EPT children, but have not increased since 1990s despite the marked increase in their survival.

Aim To determine the nature, frequency and severity of executive dysfunction (EDF) in 10 to 15-year-old extremely preterm (EPT) children born at 2 tertiary care centers in Sweden adhering to a policy of universal resuscitation of all infants born alive. Design/methods The outcomes of 121 surviving EPT (86% of all EPT survivors) children born 1992 through 1998 were compared to a matched control of children born at term. Cognitive function was assessed by WISC-III. Executive functions were assessed by D- KEFS Tower of London and ADHD-symptoms by Conners 10-item rating scale. Relationship of perinatal risk factors (PNRF) with the outcomes was examined with appropriate statistical analyses. Results The EPT children exhibited significant EDF compared with their controls in many EFs such as impulsivity, inattention and planning ability even after controlling for intelligence (IQ). Mean scores in EPT and controls were, respectively, 79 vs 101 in full scale IQ, P Conclusions School-aged children who were born EPT in the 1990s are at greater risk for developing EDF and these contribute excess morbidity over cognitive impairment in EPT children. Thus these children require ongoing neuropsychological review throughout their childhood and adolescence.