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Unlabelled: Obstetric analgesia in the form of pethidine (meperidine) to mothers during delivery has adverse effects on some aspects of the behaviour of their newborn infants. The non-nutritive sucking (NNS) pattern of nine healthy full-term infants exposed to pethidine in utero was compared to that of a control group of infants. The pattern was analysed and quantified using an automatic computer-based method. The results are discussed in the context of endogenous and exogenous opiates and their effect on brain-stem rhythm generators.Conclusions: The typical NNS pattern with alternating sucking activity (bursts) and pauses is preserved in the exposed infants. There is a significantly lower sucking frequency (md 1.74 vs 1.90 Hz, p = 0.030*) and a tendency to a less stable rhythm in pethidine-exposed infants. [ABSTRACT FROM AUTHOR]

Non-nutritive sucking (NNS) patterns in full-term newborn and preterm infants were studied at term conceptional age. The preterm group showed a distinct NNS pattern with a higher frequency and lower amplitude. In the preterm group, gender differences were observed, the girls having higher frequency and larger amplitude. The full-term infants' NNS patterns were also related to pacifier use during early childhood. Experience, gender, maturity and level of tension are suggested as explanatory factors for differences in NNS patterns. [ABSTRACT FROM AUTHOR]

Aim: To determine the prevalence of neurobehavioral symptoms at 6.5 years in children born extremely preterm (EPT, <27 weeks' gestation)., Methods: Population-based cohort study of infants born EPT in Sweden from 2004 to 2007. Of 486 survivors 375 were assessed and compared with 369 matched term-born controls. EPT children free from neurosensory and intellectual disabilities (neurodevelopmental disabilities [NDD]-free, n = 236) were compared separately. Standardised questionnaires were used to assess parental ratings of hyperactivity and attention, emotional, peer-relation, conduct and social problems; and deficits in perception, language and memory., Results: EPT children had more reported problems in all assessed neurobehavioral domains than controls, with more than three times greater odds for most outcomes. Except for conduct problems, increased problems were identified also in NDD-free children. The odds of having neurobehavioral problems in ≥3 co-occurring domains were five (whole EPT group) and three (NDD-free group) times higher than in controls., Conclusion: EPT children with or without NDD have more neurobehavioral problems in multiple domains than term peers. Ongoing assessments of behaviour until school age or beyond should recognise early symptoms of attention, everyday social problems, perceptual, emotional or language difficulties., (© 2023 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

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., (© 2023 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Aim: To identify the aetiology and outcome of seizure-like events leading to hospital referrals in infants and to identify early predictors of epilepsy and delayed neurodevelopment., Methods: This Norwegian population-based study focused on all children born in Sør-Trøndelag county, who were up to one year of age in 2014-2015. They were identified by diagnostic codes for seizure-like events and electroencephalography (EEG) examinations. Hospital records were examined up to 1.5 years of age., Results: The one-year prevalence of seizure-like events was 1.5% (114/7430). Epilepsy was diagnosed in 17%, 57% had non-epileptic paroxysmal events (NEPE), 16% had febrile seizures, and 10% had other acute symptomatic epileptic seizures. Neurodevelopmental delay occurred in 21%. The cumulative incidence was 0.22% for epilepsy and 0.79% for NEPE. Abnormal brain magnetic resonance imaging, abnormal first EEGs and neonatal care increased the likelihood of epilepsy and delayed development. Identifying situation-related factors decreased the epilepsy risk. Occurrence at a younger age increased the risk of delayed development. Absence of unambiguous motor symptoms was less common in epilepsy than in NEPE., Conclusion: Seizure-like events were common in infants and most were not caused by epilepsy. Specific anamnestic clues, and detailed descriptions of the entire event, helped to predict adverse outcomes., (© 2020 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Aim: To evaluate sex differences in infants born at term with metabolic acidosis with regard to perinatal health and symptomatology, and developmental outcome., Methods: From a population-based cohort of infants born at term (n = 14 687), 78 were prospectively identified as having metabolic acidosis at birth. Two matched controls per case were selected. Sex differences in perinatal characteristics and in neurodevelopmental outcome at 6.5 years of age were analysed. Subgroup analysis was made based on need of neonatal care and planned follow-up., Results: Acidotic boys who appeared healthy, that is with no need of specialised neonatal care respectively only followed at ordinary health care service, have worse perinatal symptoms and less favourable neurodevelopmental outcome compared to girls. The male disadvantage concerning neurodevelopmental outcome was also indicated in children without acidosis. Outcome at 6.5 years was associated with Apgar at 10 minutes (p = 0.03), need of neonatal care (p = 0.04) and sex (p = 0.02) but not acidosis per se (p = 0.54)., Conclusion: Sex affected immediate symptomatology in term acidotic infants and neurodevelopmental outcome at the age of 6.5 years. The findings were seen in those who appeared healthy in the neonatal period. The results suggest that sex should be considered in assessment of acidotic children., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

We identified individuals with variations in ACTL6B, a component of the chromatin remodeling machinery including the BAF complex. Ten individuals harbored bi-allelic mutations and presented with global developmental delay, epileptic encephalopathy, and spasticity, and ten individuals with de novo heterozygous mutations displayed intellectual disability, ambulation deficits, severe language impairment, hypotonia, Rett-like stereotypies, and minor facial dysmorphisms (wide mouth, diastema, bulbous nose). Nine of these ten unrelated individuals had the identical de novo c.1027G>A (p.Gly343Arg) mutation. Human-derived neurons were generated that recaptured ACTL6B expression patterns in development from progenitor cell to post-mitotic neuron, validating the use of this model. Engineered knock-out of ACTL6B in wild-type human neurons resulted in profound deficits in dendrite development, a result recapitulated in two individuals with different bi-allelic mutations, and reversed on clonal genetic repair or exogenous expression of ACTL6B. Whole-transcriptome analyses and whole-genomic profiling of the BAF complex in wild-type and bi-allelic mutant ACTL6B neural progenitor cells and neurons revealed increased genomic binding of the BAF complex in ACTL6B mutants, with corresponding transcriptional changes in several genes including TPPP and FSCN1, suggesting that altered regulation of some cytoskeletal genes contribute to altered dendrite development. Assessment of bi-alleic and heterozygous ACTL6B mutations on an ACTL6B knock-out human background demonstrated that bi-allelic mutations mimic engineered deletion deficits while heterozygous mutations do not, suggesting that the former are loss of function and the latter are gain of function. These results reveal a role for ACTL6B in neurodevelopment and implicate another component of chromatin remodeling machinery in brain disease., (Copyright © 2019 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

De novo germline mutations in GNB1 have been associated with a neurodevelopmental phenotype. To date, 28 patients with variants classified as pathogenic have been reported. We add 18 patients with de novo mutations to this cohort, including a patient with mosaicism for a GNB1 mutation who presented with a milder phenotype. Consistent with previous reports, developmental delay in these patients was moderate to severe, and more than half of the patients were non-ambulatory and nonverbal. The most observed substitution affects the p.Ile80 residue encoded in exon 6, with 28% of patients carrying a variant at this residue. Dystonia and growth delay were observed more frequently in patients carrying variants in this residue, suggesting a potential genotype-phenotype correlation. In the new cohort of 18 patients, 50% of males had genitourinary anomalies and 61% of patients had gastrointestinal anomalies, suggesting a possible association of these findings with variants in GNB1. In addition, cutaneous mastocytosis, reported once before in a patient with a GNB1 variant, was observed in three additional patients, providing further evidence for an association to GNB1. We will review clinical and molecular data of these new cases and all previously reported cases to further define the phenotype and establish possible genotype-phenotype correlations., (© 2018 Wiley Periodicals, Inc.)

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.

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., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

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.

Background: Deletions including chromosome 15q24 have been delineated in recent years as a separate syndrome with phenotypic variability. Here we report a familial 15q24 deletion and further contribute to the phenotypic description of this syndrome., Methods: Molecular karyotyping and description of the phenotype of three patients in the same family with a 15q24 deletion., Results: Parental transmission of the 15q24 deletion syndrome is described in the same family. The affected, the father and his twin offspring, all exhibit the typical facial features, signs and symptoms consistent with the syndromic phenotype. A distinct phenotypic variability is nevertheless noted although they all share the same deletion., Conclusions: These three patients are to our knowledge the first described cases of 15q24 syndrome in the same family. Urogenital malformations have previously been described as a part of this syndrome. Our adult male patient exhibits no such malformations but has a documented reduced fertility. This fact points to other factors such as haploinsufficiency of one and/or further genes on 15q24 as being responsible for the infertility. Array analysis could be considered as a first hand analysis in the investigation of cases of infertility and intellectual deficiency in adults in analogy to the existing consensus regarding cases of intellectual deficiency in children., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Objectives: Infants who develop encephalopathy after perinatal asphyxia have an increased risk of death and adverse neurologic outcome. Conflicting results exist concerning outcome in healthy infants with metabolic acidosis at birth. The aim of the current study was to evaluate whether metabolic acidosis at birth in term infants who appear healthy is associated with long-term developmental abnormalities., Methods: From a population-based cohort (14,687 deliveries), 78 infants were prospectively identified as having metabolic acidosis (umbilical artery pH < 7.05 and base deficit in the extracellular fluid >12.0 mmol/L). Two matched controls per case were selected. The child health and school health care records were scrutinized for developmental abnormalities., Results: Outcome measures at 6.5 years of age for 227 of 234 children (97%) were obtained. No differences were found concerning neurologic or behavioral problems in need of referral action or neurodevelopmental diagnosis in comparison of control children with acidotic children who had appeared healthy at birth, ie, had not required special neonatal care or had no signs of encephalopathy., Conclusions: Infants born with cord metabolic acidosis and who appear well do not have an increased risk for neurologic or behavioral problems in need of referral actions or special teaching approaches at the age of 6.5 years.

Background: Gavage feeding is required in preterm infants who cannot feed by themselves. Insertion of the feeding tube is painful, and reducing the discomfort in these patients is desirable., Objective: The aim of this study was to assess pain and discomfort during nasal insertion of a feeding tube, and to evaluate different measures for pain relief., Methods: We included 24 preterm infants with postmenstrual age 28 to 32 weeks' who were in stable condition. Each infant acted as his or her own control over a 3-week period during which the tube was changed 6 times. On these occasions, 6 different treatment combinations were given in randomized order: pacifier or no pacifier, combined with no fluid, sterile water, or 30% sucrose. Pain and discomfort were assessed by at least 2 independent and experienced observers using a pain assessment tool, the Premature Infant Pain Profile; score range: 0 to 21. In general, scores of 4 to 6 are interpreted as normal or no discomfort; ≥ 12 usually signals significant pain and distress., Results: The median Premature Infant Pain Profile score during the procedure was 9 and decreased gradually toward 4 after 5 minutes. The lowest pain score was achieved by combining a pacifier with oral sucrose. Sterile water without a pacifier gave the highest score., Conclusions: Insertion of a feeding tube in preterm infants leads to a measurable degree of pain and discomfort, according to the Premature Infant Pain Profile assessment tool. Pain relief was best achieved by combining a pacifier with 30% sucrose.

Background: Non-nutritive sucking (NNS) by the newborn infant is a fundamental behaviour and is one of the first coordinated muscular activities in the fetus., Aims: Our objective is to study the NNS pattern in prematurely born infants, who had various conditions commonly associated with immaturity., Method: A specially designed computer-based method that analyses and quantifies components of the NNS pattern was used., Subjects: The pattern of 51 clinically stable prematurely born infants (gestational ages 26-35 weeks) making a total of 206 observations were analysed and findings were compared with those obtained from 58, healthy preterm infants., Results: The rhythmic NNS pattern of alternating sucking and pauses was elicited in all examined infants, the earliest at post-menstrual age (PMA) 26 weeks. The role of PMA, the dominant predictor for several sucking variables seen in the control group, became diminished for the infants with risk factors but changes were otherwise similar. The infants' sucking activity and sucking frequency increased and the variability of the pattern declined with increased PMA and weight. Follow-up of a subgroup of infants revealed fewer sucking bursts per minute, slower sucking frequency and a greater variability of the frequency and amplitudes in those infants who developed sequelae., Conclusions: It would, thus, appear that the NNS pre-programmed rhythm generator, primarily modulated by maturation in healthy preterm infants, becomes affected by known risk associated events and in infants who later develop sequelae. Quantification of the NNS pattern in preterm infants may be a valuable future component of their evaluation.

In the infant, sucking behaviour is one of the first coordinated muscular activities. It is under the control of the brainstem. In utero sucking is observed from 13 weeks' gestation. The healthy full-term newborn infant has a very stable rhythm of alternating bursts of sucking with pauses in between. The non-nutritive sucking (NNS) patterns of 58 low-risk prematurely born infants (gestational ages between 26 and 35 weeks) were studied using a specially designed computer-based method that analyses and quantifies NNS. A total of 183 observations were analysed. The typical NNS pattern with bursts of sucking activity separated by quiescent periods was recorded in all infants studied and was already present before 30 weeks of gestation. A gradual change over time of their NNS was seen. With increased maturation the sucking activity, sucking frequency, amplitude and burst duration all increased, while the variability of the sucking frequency and the duration of the intervals between bursts declined. Post-menstrual age (PMA) was the dominant predictor of this result but gender, state of activity and weight also influenced it to some extent. Girls had more sucking activity and a higher sucking frequency than boys. State of activity affected the stability of the rhythm. The weight of the infant influenced both sucking activity and duration of separate bursts.