Extremely Preterm Children Research Articles

Development and predictors of childhood mental health problems in former extremely preterm infants

ObjectiveTo investigate development and predictors of mental health problems from five to eleven years of age in children born extremely preterm (EP). MethodIn a national Norwegian cohort of children born before a gestational age of 28 weeks or with a birthweight <1000 g mental health was assessed by parents at five and eleven years of age using The Strengths and Difficulties Questionnaire. A Total Difficulties Score ≥ 90th percentile (TDS90) for a reference group was used as a measure of a mental health problem. Of 338 eligible EP children, 162 (48%) attended at both ages. ResultsThe rate of TDS90 was 52 (32%) at five and 37 (23%) at eleven years of age (p = 0.025). Of the 52 children with TDS90 at five years, 25 had TDS90 at eleven years of age, and of 37 children with TDS90 at eleven, 25 had TDS90 at five years of age. Mental health problems and an IQ of 70–84 at five years were independent predictors of TDS90 at eleven years of age. ConclusionThe rate of mental health problems decreased from five to eleven years, but individual stability was moderate. Mental health problems and intellectual function in the lower normal range at preschool age were independent predictors of later mental health problems.

Child Motivation and Family Environment Influence Outcomes of Working Memory Training in Extremely Preterm Children

Cognitive training can improve working memory in children at risk of working memory difficulties; however, response to training can vary and doubt exists if working memory improvements can be sustained long- term. This study aimed to explore whether child motivation and family environment are associated with working memory trajectories in children born extremely preterm or extremely low birth weight. Forty-five 7-year-old children completed Cogmed Working Memory Training® at home over 5–7 weeks. Children and their families completed working memory tests and child motivation and family environment questionnaires at baseline, with working memory further tested 2 weeks, 12 months and 24 months post-training. Latent growth modelling was used to explore whether child motivation and family environment factors were associated with working memory trajectories. Children’s desire for challenge, training competence, and being from a single-parent household were associated with short-term improvements in verbal short-term memory. Children from poorer functioning families were associated with short-term improvements in working memory. There was little evidence that child motivation or family environment was associated with long-term working memory changes. Child motivation and the training environment may be important for understanding training effects in children born extremely preterm or extremely low birth weight, and warrant closer examination in working memory training studies.

Physical Activity Program Improves Functional Exercise Capacity and Flexibility in Extremely Preterm Children With Bronchopulmonary Dysplasia Aged 4–6 Years: A Randomized Controlled Trial

IntroductionBronchopulmonary dysplasia (BPD) is the most common complication of extreme preterm delivery, and is associated with reduced exercise tolerance and exercise capacity. The aim of this study was to assess the effects of a physical activity programme on exercise tolerance, exercise capacity, flexibility, and lung function in prematurely born children with BPD. MethodsThis was a randomized controlled trial. Preterm children with BPD (4–6 years) were randomized to intervention (IG) and control (CG) groups. The CG did not participate in any physical activity during the study period. The IG performed a 4-week exercise programme based on aerobic interval and resistance training. Outcomes were based on the 6-minute walk test (6MWT), incremental shuttle walk test (ISWT), modified sit and reach test (MSRT) and spirometry results. ResultsTwenty individuals were recruited. In the IG (n=10), statistical and clinical improvement was observed in the 6MWT (316.3±31.4m vs 376.2±39.5m; P=.002). Significant improvements were also seen in the IG in the ISWT (248.0±45.2m vs 465.3±58.2m; P=.013), MSRT (14.5±7.7cm vs 22.8±6.9cm; P=.003), and FEV1 (102%±16% pred vs 104%±17% pred; P=.004). No significant differences between pre- and post-intervention were observed in the CG for all outcomes (n=10). ConclusionThis 4-week programme resulted in statistical and clinical improvements in exercise tolerance, exercise capacity and flexibility in preterm children with BPD.

Behavioural dysfunctions of 10-year-old children born extremely preterm associated with corticotropin-releasing hormone expression in the placenta.

To evaluate the relationship between corticotropin-releasing hormone (CRH) expression in the placenta and the risk of school-related dysfunctions at the age of 10 years among children born extremely preterm (EP). Corticotropin-releasing hormone expression was measured in the placenta of 761 EP children, who had the following assessments at the age of 10 years: Differential Ability Scales, Oral and Written Language Scales, the Wechsler Individual Achievement Test-III, NEPSY-II and the Child Symptom Inventory-4. We evaluated whether lowest and highest quartiles of CRH mRNA were associated with undesirable scores on these assessments. With 272 evaluations, we would expect 14 to be significant at p < 0.05. Only 16 associations were statistically significant. On the other hand, seven of these were social limitations among girls whose placenta CRH mRNA was in the top quartile. Adjusting for delivery indication or restricting the sample to one delivery indication group resulted in few differences. Overall, placenta CRH mRNA concentrations in the top or bottom quartiles were not associated with increased risks of dysfunctions 10 years later. Girls whose placenta CRH expression was in the top quartile, however, were at increased risk of seven indicators/correlates of social limitations.

Physical Activity Program Improves Functional Exercise Capacity and Flexibility in Extremely Preterm Children With Bronchopulmonary Dysplasia Aged 4–6 Years: A Randomized Controlled Trial

IntroductionBronchopulmonary dysplasia (BPD) is the most common complication of extreme preterm delivery, and is associated with reduced exercise tolerance and exercise capacity. The aim of this study was to assess the effects of a physical activity programme on exercise tolerance, exercise capacity, flexibility, and lung function in prematurely born children with BPD. MethodsThis was a randomized controlled trial. Preterm children with BPD (4–6 years) were randomized to intervention (IG) and control (CG) groups. The CG did not participate in any physical activity during the study period. The IG performed a 4-week exercise programme based on aerobic interval and resistance training. Outcomes were based on the 6-minute walk test (6MWT), incremental shuttle walk test (ISWT), modified sit and reach test (MSRT) and spirometry results. ResultsTwenty individuals were recruited. In the IG (n=10), statistical and clinical improvement was observed in the 6MWT (316.3±31.4m vs 376.2±39.5m; P=.002). Significant improvements were also seen in the IG in the ISWT (248.0±45.2m vs 465.3±58.2m; P=.013), MSRT (14.5±7.7cm vs 22.8±6.9cm; P=.003), and FEV1 (102%±16% pred vs 104%±17% pred; P=.004). No significant differences between pre- and post-intervention were observed in the CG for all outcomes (n=10). ConclusionThis 4-week programme resulted in statistical and clinical improvements in exercise tolerance, exercise capacity and flexibility in preterm children with BPD.

Motor Impairment Trends in Extremely Preterm Children: 1991-2005.

There are increasing numbers of surviving children who were born extremely preterm (EP; gestational age <28 weeks) or extremely low birth weight (ELBW; birth weight <1000 g). Our objective in this study was to compare the rates of motor impairment at 8 years of age between 3 cohorts of EP and/or ELBW and term-born children to establish if motor impairment rates are changing over time. All children born EP and/or ELBW in the calendar years of 1991-1992, 1997, and 2005 in Victoria, Australia, were recruited at birth. Randomly selected normal birth weight (>2499 g) and term-born controls were matched for expected date of birth, sex, and sociodemographic status. At 8 years' corrected age, motor impairment was defined as cerebral palsy (CP) or a score less than the fifth centile on the Movement Assessment Battery for Children for the 1991-1992 and 1997 cohorts and less than or equal to the fifth centile on the Movement Assessment Battery for Children-Second Edition for the 2005 cohort. Motor impairment was more likely in children born EP and/or ELBW compared with children born at term for all epochs. There was a significant increase in motor impairment in EP and/or ELBW children over the 3 eras, from 23% in 1991-1992 and 26% in 1997 to 37% in 2005 (χ2trend = 10.2; P = .001). This was due to an increase in non-CP motor impairment (13% in 1991 to 1992; 15% in 1997; 26% in 2005; χ2trend = 12.5; P < .001), not CP (11% in 1991 to 1992; 11% in 1997; 12% in 2005). The rate of motor impairment in EP and/or ELBW children assessed at 8 years of age increased between eras, an increase caused by non-CP motor impairment.

Sensory-motor performance in seven-year-old children born extremely preterm

BackgroundChildren born preterm are prone to motor problems. Research on their motor performance has, however, rarely been integrated with sensory processing. AimTo examine sensory-motor performance in children born extremely preterm (EPT). MethodIn a longitudinal prospective cohort study, 49 EPT (born <28 gestational weeks; 32 boys and 17 girls) and 33 term-born (16 boys and 17 girls) children were assessed with six individual subtests from the Sensory Integration and Praxis Tests at the age of 7.0 to 7.3 years. ResultsThe rate of test z-scores indicating dysfunction [from −2 standard deviations (SD) to < −1 SD for mild and < −2 SD for moderate-to-severe] was significantly higher in EPT children than in term-born children in all the subtests. When comparing mean performance adjusted for gender and mother's education, EPT children performed worse than term-born children in Design Copying (z-score difference − 0.83; 95% confidence interval −1.32 to −0.34), Motor Accuracy (−0.82; −1.26 to −0.38), Postural Praxis (−0.95; −1.45 to −0.45), Manual Form Perception (−0.59; −1.12 to −0.06), and Finger Identification (−0.88; −1.45 to −0.31). Additional adjustment for Full-Scale Intelligence Quotient rendered difference in Manual Form Perception non-significant. ConclusionSeven-year-old EPT children perform worse than their term-born peers in tests for visual-motor, somatosensory, and motor planning performance.

Respiratory morbidity through the first decade of life in a national cohort of children born extremely preterm

BackgroundAdvances in perinatal care have markedly increased the prospects of survival for infants born extremely preterm (EP). The aim of this study was to investigate hospitalisation rates and respiratory morbidity from five to 11 years of age in a prospective national cohort of EP children born in the surfactant era.MethodsThis was a national prospective cohort study of all children born in Norway during 1999 and 2000 with gestational age (GA) < 28 weeks or birth weight < 1000 grams, and of individually matched term-born controls recruited for a regional subsample. Data on hospital admissions, respiratory symptoms, and use of asthma medication was obtained by parental questionnaires at 11 years of age.ResultsQuestionnaires were returned for 232/372 (62%) EP-born and 57/61 (93%) regional term-born controls. Throughout the study period, 67 (29%) EP-born and seven (13%) term-born controls were admitted to hospital (odds ratio (OR) 2.90, 95% confidence interval (CI): 1.25, 6.72). Admissions were mainly due to surgical procedures, with only 12% due to respiratory causes, and were not influenced by neonatal bronchopulmonary dysplasia (BPD) or low GA(≤ 25 weeks). Respiratory symptoms, asthma and use of asthma medication tended to be more common for EP-born, significantly so for medication use and wheeze on exercise. Neonatal BPD was a risk factor for medication use, but not for current wheeze. In multivariate regression models, home oxygen after discharge (OR 4.84, 95% CI: 1.38, 17.06) and parental asthma (OR 4.38, 95% CI: 1.69, 11.38) predicted current asthma, but neither BPD nor low GA were associated with respiratory symptoms at 11 years of age.ConclusionsHospitalisation rates five to 11 years after EP birth were low, but twice those of term-born controls, and unrelated to neonatal BPD and low GA. Respiratory causes were rare. Respiratory complaints were more common in children born EP, but the burden of symptoms had declined since early childhood.

Antenatal and Neonatal Antecedents of Executive Dysfunctions in Extremely Preterm Children.

To find out why children born extremely preterm are at heightened risk of executive dysfunctions, the authors assessed 716 children who were 10 years old born extremely preterm whose IQ was ≥ 70. A working memory dysfunction (n = 169), an inhibition dysfunction (n = 360), a switching dysfunction (355), and all 3 (executive dysfunction; n = 107) were defined on the basis of Z-scores ≤ -1 on the Differential Ability Scales-II Working Memory composite, and/or on the NEPSY-II Inhibition-Inhibition and Inhibition-Switching subtests. All risk profiles include an indicator of socioeconomic disadvantage. The risk profile of each of the 3 individual dysfunctions includes an indicator of the newborn's immaturity, and the risk profiles of the inhibition dysfunction and switching dysfunction also include an indicator of inflammation. Only the switching dysfunction was associated with fetal growth restriction. The risk factors for executive dysfunction can be subsumed under the 4 themes of socioeconomic disadvantage, immaturity/vulnerability, inflammation, and fetal growth restriction.

Maternal educational status at birth, maternal educational advancement, and neurocognitive outcomes at age 10 years among children born extremely preterm

BackgroundTo determine if a key marker of socioeconomic status, maternal education, is associated with later neurocognitive and academic outcomes among children born extremely preterm (EP).MethodEight hundred and seventy-three children born at 23 to 27 weeks of gestation were assessed for cognitive and academic ability at age 10 years. With adjustments for gestational age (GA) and potential confounders, outcomes of children whose mothers had fewer years of education at the time of delivery and children whose mother advanced in education between birth and 10 years were examined.ResultsChildren of mothers in the lowest education stratum at birth were significantly more likely to score ≥2 SDs below normative expectation on 17 of 18 tests administered. Children of mothers who advanced in education (n=199) were at reduced risk for scoring ≥2 SDs on 15 of 18 measures, but this reduction was statistically significant on only 2 of 18 measures.ConclusionAmong EP children, socioeconomic disadvantage at birth, indexed by maternal education, is associated with significantly poorer neurocognitive and academic outcomes at 10 years of age, independently of GA. Maternal educational advancement during the child's first 10 years of life is associated with modestly improved neurocognitive outcomes.

Early surgery and neurodevelopmental outcomes of children born extremely preterm

ObjectivesTo (1) compare the neurodevelopmental outcomes at 8 years of age of children born extremely preterm (EP) who underwent surgical procedures during the course of their initial hospital admission with...

Neurocognitive Correlates of Attention-Deficit Hyperactivity Disorder Symptoms in Children Born at Extremely Low Gestational Age.

Compared with children born near term, those born extremely preterm (EP) are at much higher risk for attention-deficit hyperactivity disorder (ADHD). Little information is available about differences in neuropsychological outcomes among EP children with and without ADHD. Our analyses aimed to evaluate the neuropsychological correlates of ADHD symptoms in extremely low gestational age newborns (ELGANs). We obtained Child Symptom Inventory-4 reports from parents (n = 871) and teachers (n = 634) of 10-year-old children born before the 28th week of gestation. Participants completed standardized assessments of neurocognitive and academic functioning. In the total sample, children who screened positive for ADHD symptoms were at increased risk for neurocognitive limitations. These associations were weaker when the sample was limited to those with intelligence quotient (IQ) ≥70 or ≥85. Even those with IQ ≥85 who screened positive for ADHD symptoms were more likely than their peers to have deficits on the DAS-II Working Memory Cluster and the NEPSY-II Auditory Response subtest. The risks for impaired academic performance (Z ≤ -1) on components of the WIAT-III were 2-to-3 times higher in this group than among ELGANs not classified as having ADHD symptoms. Among children born EP, those with ADHD symptoms are more likely to have global neurocognitive impairment. When IQ is within normal limits, ADHD symptoms are associated with deficits in executive functioning skills. These findings highlight a group at risk for executive functioning deficits and related academic difficulties, even in the absence of intellectual disability.

Long-term follow-up of cardiorespiratory outcomes in children born extremely preterm: Recommendations from a Canadian consensus workshop

Bronchopulmonary dysplasia, the most common pulmonary complication of extremely preterm (EPT) birth, has longstanding multiorgan repercussions, with increasing reports of emphysema and cardiac disease in early adulthood. There are currently no clear recommendations pertaining to best practices for optimal multidisciplinary cardiorespiratory follow-up of EPT children. We report the outcomes of a 2-day consensus workshop involving a Canadian panel of 31 multidisciplinary experts with the goal of improvement and standardization of the cardiopulmonary follow-up care of EPT infants (i.e., born at <28 weeks' gestation), from neonatal discharge to mid childhood. The most relevant and important clinical outcomes to evaluate were identified. Practical aspects of integrating cardiopulmonary follow-up into ambulatory care clinics were explored. This article summarizes the discussions from this workshop and provides the panel's recommendations for clinical follow-up and research priorities.

Exploring the “Preterm Behavioural Phenotype” in Extremely Preterm Children at School‐Age

Exploring the “Preterm Behavioural Phenotype” in Extremely Preterm Children at School‐Age

Lack of Cortical Correlates of Response Inhibition in 6-Year-Olds Born Extremely Preterm – Evidence from a Go/NoGo Task in Magnetoencephalographic Recordings

Children born extremely preterm (EPT) may have difficulties in response inhibition, but the neural basis of such problems is unknown. We recorded magnetoencephalography (MEG) during a somatosensory Go/NoGo task in 6-year-old children born EPT (n = 22) and in children born full term (FT; n = 21). The children received tactile stimuli randomly to their left little (target) and index (non-target) finger and were instructed to squeeze a soft toy with the opposite hand every time they felt a stimulus on the little finger. Behaviorally, the EPT children performed worse than the FT children, both in responding to the target finger stimulation and in refraining from responding to the non-target finger stimulation. In MEG, after the non-target finger stimulation (i.e., during the response inhibition), the sensorimotor alpha oscillation levels in the contralateral-to-squeeze hemisphere were elevated in the FT children when compared with a condition with corresponding stimulation but no task (instead the children were listening to a story and not attending to the fingers). This NoGo task effect was absent in the EPT children. Further, in the sensorimotor cortex contralateral to the tactile stimulation, the post-stimulus suppression was less pronounced in the EPT than FT children. We suggest that the missing NoGo task effect and lower suppression of sensorimotor oscillations are markers of deficient functioning of the sensorimotor networks in the EPT children.

Do Social Functioning Problems of Premature Children Persist Between 7 and 11 Years of Age?

A number of studies report that from the first years of life, preterm children have more difficulty self-regulating and communicating in their social group. If these children show signs of difficulty adjusting socially, the question then is whether or not these problems continue and persist over time. The objective is to observe the combined effects of birth status and the passage of time on the resolution/persistence of the social problems. At age 7, the social adjustment of 96 extremely preterm (EP) children was assessed in a school setting, and 82 (85%) were followed at 11 years, and matched with three healthy term peers of the same sex and socioeconomic status (SES) recruited in the same classroom. A total of 375 children have been “casted” by their classmates in social roles through a sociometric interview at 7 and 11 years. The findings indicate a customary stability in term children but persistent or even increasing problems of victimization in EP children and a decrease of aggressiveness over time in the EP boys subgroup. Moreover, we found persistent social isolation problems in the subgroup of EP girls at 7 and 11 years. It can be concluded that prematurity is associated with a process of social marginalization that results from both the children’s very limitations and the resultant reputation effects. At these ages, any discrepancy is quickly judged as a weakness that children do not want to be associated with. Furthermore, the passage of time confirms this and reinforces the marginalization process.

Predictive role of early milestones-related psychomotor profiles and long-term neurodevelopmental pitfalls in preterm infants

BackgroundDevelopmental milestones are useful signposts developed to assess the pace and the trajectory of maturation occurring during specific time-windows called critical periods. The predictive role of their clinical assessment in premature infants is challenging, however, it actually represents an easy and reliable tool at follow-up. Aim and study designRelying on a milestone-based neurological examination, we aimed to detect the interdependence between time of achievement of each milestone with long-term neuropsychological and neurodevelopmental outcomes. The influence of pre-perinatal events was also considered. Patients & methodsTwo-hundred-eighty patients (53.2% M) were serially assessed by classic neurological examination during the first 18months and subsequently evaluated by Griffiths Developmental Mental Scale. Children were sorted by ranges of gestational age and compared according to their different profiles. ResultsThe Extremely PreTerms appeared to have a globally delayed development with subsequent attentional and behavioral troubles. Differently, the older peers, from Moderately to Full Term ones, although did not show significant differences in achievement of gross motor skills, had a stable delay of visual and social skills across the age ranges. This gap was not evidenced at the long-term evaluation, except for the Extremely PreTerm children. Pre-perinatal factors played a significant role on short and long term neurodevelopmental outcome. ConclusionsEarly assessed classic neurological examination might address neurodevelopmental trajectories in PreTerm children in which visual and social skills appear to be the mostly affected. It remains the easiest and most reliable tool of evaluation throughout the follow-up programs.

Two-thirds of adolescents who received active perinatal care after extremely preterm birth had mild or no disabilities.

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.

Altered breathing mechanics and ventilatory response during exercise in children born extremely preterm

BackgroundExtreme preterm birth confers risk of long-term impairments in lung function and exercise capacity. There are limited data on the factors contributing to exercise limitation following extreme preterm birth. This...

Antecedents of Attention-Deficit/Hyperactivity Disorder Symptoms in Children Born Extremely Preterm.

To investigate antecedents of attention-deficit/hyperactivity disorder (ADHD) symptoms in children born extremely preterm (EP; <26-wk gestation). The EPICure study recruited all babies born EP in the United Kingdom and Ireland in March-December 1995. Neurodevelopmental outcomes were assessed at 2.5 (n = 283; 90%), 6 (n = 160; 78%), and 11 (n = 219; 71%) years of age. Parents and teachers completed the DuPaul Rating Scale IV to assess inattention and hyperactivity/impulsivity symptoms at 11 years. Regression analyses were used to explore the association of neonatal, neurodevelopmental, and behavioral outcomes to 6 years with ADHD symptoms at 11 years. Extremely preterm (EP) children had significantly more inattention (mean difference, 1.2 SD; 95% CI, 0.9-1.5) and hyperactivity/impulsivity (mean difference, 0.5 SD; 95% CI, 0.2-0.7) than controls, with a significantly greater effect size for inattention than hyperactivity/impulsivity. Significant independent predictors of inattention at 11 years included smaller head circumference, lower intelligence quotient (IQ), and pervasive peer relationship problems at 6 years, and motor development at 2.5 years. In contrast, significant independent predictors of hyperactivity/impulsivity included lower IQ, pervasive conduct problems and ADHD symptoms at 6 years, externalizing problems at 2.5 years, and non-white maternal ethnicity. Extremely preterm children are at increased risk for ADHD symptoms, predominantly inattention, for which the antecedents differ by symptom domain. Attention deficits after EP birth were associated with poor brain growth and neurological function. Cognitive and behavioral assessments in early and middle childhood to identify neurodevelopmental and peer relationship problems may be beneficial for identifying EP children at risk for inattention.