Associations between the aetiology of preterm birth and mortality and neurodevelopment up to 11 years.

AIM: To investigate how the aetiology of very preterm birth/very low birth weight is associated with mortality and later neurodevelopmental outcomes. METHODS: Very preterm/very low-birth weight singletons were categorised based on the aetiology of preterm birth: spontaneous preterm birth (n = 47, 28.1%), preterm premature rupture of membranes (n = 56, 33.5%) or placental vascular pathology (n = 64, 38.3%). Mortality, cerebral palsy, severe cognitive impairment by 11 years of age (<2SD) and mean full-scale intelligence quotient at 11 years were studied in association with birth aetiology. RESULTS: There was no difference in mortality or rate of cerebral palsy according to birth aetiologies. The rate of severe cognitive impairment was lower (4.9% vs. 15.3%) in the preterm premature rupture of the membrane group in comparison to the placental vascular pathology group (OR 0.2, 95% CI 0.03-0.9, adjusted for gestational age). At 11 years, there was no statistically significant difference in the mean full-scale intelligence quotient. CONCLUSION: Placental vascular pathology, as the aetiology of very preterm birth/very low birth weight, is associated with a higher rate of severe cognitive impairments in comparison to preterm premature rupture of membranes, although there was no difference in the mean full-scale intelligence quotient at 11 years. The aetiology of very preterm birth/very low birth weight was not associated with mortality or the rate of cerebral palsy.

Mathematical skills of 11-year-old children born very preterm and full-term.

Preterm birth affects the academic development of children, especially in mathematics. Remarkably, only a few studies have measured specific effects of preterm birth on mathematical skills in primary school. The aim of this study was to compare 11-year-old children, with an IQ above 70, born very preterm (N = 64) and full-term (N = 72) on a variety of 5th grade mathematical skills and cognitive abilities important for mathematical learning. The measures were spontaneous focusing on numerosity (SFON), spontaneous focusing on quantitative relations (SFOR), arithmetic fluency, mathematics achievement, number line estimation, rational number magnitude knowledge, mathematics motivation, reading skills, visuospatial processing, executive functions, and naming speed. The children born very preterm and full-term differed in arithmetic fluency, SFON and SFOR. Domain general cognitive abilities did not fully explain the group differences in SFON and SFOR. Retrospective comparisons of the samples at the age of five years showed large group differences in early mathematical skills and cognitive abilities. Despite lower early mathematical skills, the children born very preterm reached peer equivalent performance in many mathematical skills by the age of 11 years. Nevertheless, they appear less likely to focus on implicit mathematical features in their everyday life.

Hammersmith Infant Neurological Examination and long-term cognitive outcome in children born very preterm.

AIM: To study the association between the Hammersmith Infant Neurological Examination (HINE) at age 2 years and neurocognition at age 11 years in children born very preterm. We hypothesized that the HINE at 2 years would be associated with neurocognition, that is, neurological, motor, and cognitive outcomes at 11 years. METHOD: A total of 174 children (mean gestational age 29.0wks, SD 2.7; minimum 23.0, maximum 35.9; 95 [55%] males, 79 [45%] females) born very preterm (birthweight ≤1500g/gestational age <32wks), were included in a prospective cohort recruited from 2001 to 2006 in Turku, Finland. The HINE was performed at 2 years' corrected age. Neurocognition at 11 years was assessed with the Touwen neurological examination, Movement Assessment Battery for Children, Second Edition (MABC-2), and full-scale IQ (Wechsler Intelligence Scale for Children, Fourth Edition). RESULTS: The HINE global score was associated with the results of the Touwen neurological examination (odds ratio [OR]=0.9, 95% confidence interval [CI] 0.8-0.9, p=0.001), MABC-2 (ß=1.4, 95% CI 0.7-2.2, p<0.001), and full-scale IQ (ß=1.2, 95% CI 0.8-1.7, p<0.001), even when adjusted. When children with cerebral palsy (CP) were excluded, the HINE was still associated with full-scale IQ (unadjusted ß=1.2, 95% CI 0.3-2.1, p=0.01). INTERPRETATION: A higher HINE global score at 2 years was associated with better general intelligence at 11 years even in children without CP. The HINE may be a useful tool to detect children at risk for later cognitive impairment. What this paper adds A Hammersmith Infant Neurological Examination (HINE) global score at 2 years was associated with long-term neurocognitive function. Severe cognitive impairment was significantly more common in 11-year-old children with complex minor neurological dysfunction compared to typically developing children. The HINE performed at 2 years detects risks of cognitive impairment at 11 years in children born very preterm. A higher HINE score at 2 years was associated with better general intelligence at 11 years.

Social functioning questionnaires of adolescents born preterm show average profiles and attenuated sex differences.

AIM: Prematurity has been shown to affect social competence in children and adults. Our aim was to evaluate profiles of self-reported social behaviours and loneliness in preterm- and term-born adolescents. METHODS: Preterm (≤1500 g and, or, <32 gestational weeks)- and term-born infants were recruited in Turku University Hospital from 2001 to 2006. The Multisource Assessment of Children's Social Competence Scale and the Peer Network and Dyadic Loneliness Scale were completed at the age of 11. Profiles of social competence and loneliness were labelled as low, average or high. RESULTS: A total of 172 preterm-born and 134 term-born adolescents returned the questionnaires. Most frequently, preterm adolescents reported a profile of average social competence and average levels of loneliness. Preterm-born boys reported a profile of low social functioning less often (preterm-born 36% vs. term-born 54%), and preterm-born girls reported a profile of high social functioning less frequently (preterm-born 26% vs. term-born 37%) than same-sex controls. Sex differences in social functioning profiles were smaller in preterm than term-born adolescents. CONCLUSION: The majority of young adolescents born preterm reported a high or average social functioning profile irrespective of sex. Prematurity seems to level out differences between the sexes.

School performance is age appropriate with support services in very preterm children at 11 years of age.

AIM: This Finnish regional birth-cohort study compared the school performance of very preterm and full-term children when they reached 11 years of age. METHODS: Teachers rated the educational abilities of 123 preterm children and 133 full-term controls at the age of 11 years as well as the support services they received. The children were all born in the Turku University Hospital between 2001 and 2005. In the preterm group, neurosensory impairments were confirmed at two years of corrected age, and full-scale intelligence quotient (IQ) was assessed at 11 years of age using the Wechsler Intelligence Scale, Fourth Edition. RESULTS: Educational abilities, including academic skills and classroom functioning, did not differ between the two groups after excluding the children with a full-scale IQ < 70. However, 40% of the preterm group and 26% of the controls had received at least one support service (p <0.02). The 13 preterm children with a full-scale IQ <70 and the 10 with neurosensory impairment received more support services. Boys in both groups displayed more classroom-functioning problems than girls. CONCLUSION: A full-scale IQ ≥ 70 and age-appropriate educational abilities do not exclude a significant need for support services in very preterm children at the age of 11 years.

Babbling in children with neurodevelopmental disability and validity of a simplified way of measuring canonical babbling ratio.

Babbling is an important precursor to speech, but has not yet been thoroughly investigated in children with neurodevelopmental disabilities. Canonical babbling ratio (CBR) is a commonly used but time-consuming measure for quantifying babbling. The aim of this study was twofold: to validate a simplified version of the CBR (CBRUTTER), and to use this measure to determine if early precursors to speech and language development could be detected in children with different neurodevelopmental disabilities. Two different data sets were used. In Part I, CBRUTTER was compared to two other CBR measures using previously obtained phonetic transcriptions of 3571 utterances from 38 audio recordings of 12-18 month old children with and without cleft palate. In CBRUTTER, number of canonical utterances was divided by total number of utterances. In CBRsyl, number of canonical syllables was divided by total number of syllables. In CBRutt, number of canonical syllables was divided by total number of utterances. High agreement was seen between CBRUTTER and CBRsyl, suggesting CBRUTTER as an alternative. In Part II, babbling in children with neurodevelopmental disability was examined. Eighteen children aged 12-22 months with Down syndrome, cerebral palsy or developmental delay were audio-video recorded during interaction with a parent. Recordings were analysed by observation of babbling, consonant production, calculation of CBRUTTER, and compared to data from controls. The study group showed significantly lower occurrence of all variables, except for of plosives. The long-term relevance of the findings for the speech and language development of the children needs to be investigated.

Factors affecting the cognitive profile of 11-year-old children born very preterm.

BackgroundPreterm birth is a risk for cognitive development. This study assessed the cognitive profile of children born very preterm at the age of 11 years as well as the associated risk factors.MethodsA total of 128 children born very preterm were included. Magnetic resonance imaging was performed at term age. Cognitive development was assessed using the full-scale intelligence quotient (IQ) and four domains of the Wechsler Intelligence Scale for Children, fourth edition (WISC-IV), Finnish translation. The results were compared with test norms.ResultsMost study children performed at average (51%) or low average (21%) levels in the full-scale IQ assessment. The correlation between 5- and 11-year full-scale IQ was 0.73 (P<0.001). Compared with the normative data, children born very preterm performed poorer in all domains of the cognitive profile. The only significant risk factor for poor general cognition was major brain pathology. When considering all four domains of WISC-IV, low paternal education, male gender, and low birth weight z score were also found to be significant risk factors.ConclusionsLess than one-third of the children born very preterm performed below the low average cognitive level at 11 years of age. Specific neonatal and sociodemographic risk factors were identified as affecting the cognitive profile.

Importance of toxicokinetics for interspecies variation in sensitivity to chemicals.

Interspecies variation in sensitivity to synthetic chemicals can be orders of magnitude large. Species traits causing the variation can be related to toxicokinetics (uptake, distribution, biotransformation, elimination) or toxicodynamics (interaction with biological target sites). We present an approach to systematically measure and model the contribution of uptake, biotransformation, internal distribution, and elimination kinetics toward species sensitivity differences. The aim is to express sensitivity as target tissue specific, internal lethal concentrations. A case study with the pesticides diazinon, imidacloprid, and propiconazole and the aquatic invertebrates Gammarus pulex, Gammarus fossarum, and Lymnaea stagnalis illustrates the approach. L. stagnalis accumulates more pesticides than Gammaridae when measured in whole organisms but less in target tissues such as the nervous system. Toxicokinetics, i.e. biotransformation and distribution, explain the higher tolerance of L. stagnalis to the insecticide diazinon when compared to Gammaridae. L. stagnalis was again more tolerant to the other neurotoxicant imidacloprid; however, the difference in sensitivity could not be explained by toxicokinetics alone, indicating the importance of toxicodynamic differences. Sensitivity to propiconazole was comparable among all species and, when expressed as internal lethal concentrations, falls in the range of baseline toxicity.

Expressive vocabulary intervention for four 2- to 3-year-old children with cerebral palsy and speech/language difficulties: A single-case A-B study.

PURPOSE: To evaluate a parent-delivered expressive vocabulary intervention using focused stimulation for young children with cerebral palsy (CP). METHOD: A single case A-B design was used. Use of expressive target words was evaluated during the baseline (A) and intervention (B) phases. Untrained expressive words were used as control behaviour. Four 2- to 3-year-old boys with CP and their parents participated. All participants had an expressive vocabulary of less than 50 words at study intake. Following training, parents delivered the intervention daily at home for 5 weeks. Generalisation of the intervention was measured with a parent-rated vocabulary checklist. RESULT: Two participants showed clear gains and one participant showed a smaller gain in target words. Two of these three participants did not improve on control words, but one participant increased his use of both target and control words. One participant did not increase his use of either control or target words. All participants improved on parent-reported expressive vocabulary, and for two children, improvements were large. CONCLUSION: Parent-delivered focused stimulation may lead to gains in expressive vocabulary in children with CP and speech and language difficulties. The intervention would be suitable for larger single-case studies with more experimental control.

Altered temporal connectivity and reduced meta-state dynamism in adolescents born very preterm.

Adolescents born very preterm have an increased risk for anxiety, social difficulties and inattentiveness, i.e. the 'preterm behavioural phenotype'. The extreme end of these traits comprises the core diagnostic features of attention and hyperactivity disorders and autism spectrum disorder, which have been reported to show aberrant dynamic resting-state functional network connectivity. This study aimed to compare this dynamism between adolescents born very preterm and controls. A resting-state functional magnetic resonance imaging was performed on 24 adolescents born very preterm (gestational age <32 weeks and/or birth weight ≤1500 g) and 32 controls born full term (≥37 weeks of gestation) at 13 years of age. Group-wise comparisons of dynamic connectivity between the resting-state networks were performed using both hard clustering and meta-state analysis of functional network connectivity. The very preterm group yielded a higher fraction of time spent in the least active connectivity state in hard clustering state functional network connectivity, even though no group differences in pairwise connectivity patterns were discovered. The meta-state analysis showed a decreased fluidity and dynamic range in the very preterm group compared with controls. Our results suggest that the 13-year-old adolescents born very preterm differ from controls in the temporal characteristics of functional connectivity. The findings may reflect the long-lasting effects of prematurity and the clinically acknowledged 'preterm behavioural phenotype'.

Peripapillary retinal nerve fibre layer thickness and macular ganglion cell layer volume in association with motor and cognitive outcomes in 11-year-old children born very preterm.

PURPOSE: The purpose of the study was to study the association between retinal parameters and motor and cognitive outcomes in children born very preterm. METHODS: This study is part of a prospective cohort study of very preterm infants (birth weight ≤ 1500 grams/gestational age < 32 weeks). At 11 years of age, the ophthalmological assessment included a retinal optical coherence tomography (OCT) examination of the peripapillary retinal nerve fibre layer (PRNFL) and the macular ganglion cell layer (GCL). The motor performance was assessed with the Movement Assessment Battery for Children-Second Edition (Movement ABC-2), and the cognitive outcome with the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV). RESULTS: A total of 141 children were included. The mean (SD) average PRNFL was 95 µm (10.2 µm). The mean (SD) macular GCL volume was 0.34 mm3 (0.03 mm3 ). Higher PRNFL thickness associated with higher percentiles for total scores in the motor assessment (b = 0.5, 95% CI 0.1-0.8, p = 0.01) and higher macular GCL volume with higher scores in the cognitive assessment (b = 1.4, 95% CI 0.5-2.3, p = 0.002), also when adjusted for gender, birth weight z-score (birth weight in relation to gestational age) and major brain pathology at term. CONCLUSION: The associations between higher average PRNFL thickness and better motor performance as well as higher macular GCL volume and better cognitive performance refer to more generalized changes in the brain of 11-year-old children born very preterm. Retinal OCT examinations might provide a deeper insight than mere eyesight in long-term neurodevelopmental follow-up of children born very preterm.

Metformin Versus Insulin for Gestational Diabetes: Cognitive and Neuropsychological Profiles of Children Aged 9 years.

OBJECTIVE: We compared cognitive profile and neuropsychological performance in 9-year-old offspring of mothers who were treated with metformin or insulin for gestational diabetes mellitus (GDM). METHODS: A total of 172 children whose mothers were randomly assigned to receive either metformin or insulin for GDM were studied at the age of 9 years. Of these children, 127 were from Turku, Finland (63 metformin and 64 insulin), and 45 from Oulu, Finland (19 metformin and 26 insulin). Clinical and demographic background characteristics were obtained at enrolment, birth, and 9-year follow-up. Cognitive profiles were examined at age 9 years with the Wechsler Intelligence Scale for Children. Neuropsychological functions were examined with 2 subtests of the Developmental Neuropsychological Assessment test battery assessing comprehension of instructions and narrative memory, Trail Making Test assessing attention and with Behavioral Rating Inventory of Executive Functioning, including parent-rated and teacher-rated evaluations. Academic functioning was studied with reading fluency subtest of the Screening test for reading, writing, and calculus for first to sixth grades and information about educational support received at school reported by parents. RESULTS: The cognitive profiles, including indexes of verbal comprehension, perceptual reasoning, working memory, and processing speed, did not differ significantly between metformin-treated and insulin-treated groups. Significant differences were not found between the treatment groups in assessed neuropsychological functions, reading fluency, or received level of support at school. CONCLUSION: Cognitive and neuropsychological outcomes were similar in 9-year-old children whose mothers had either metformin or insulin treatment of GDM.

Toxicokinetic-toxicodynamic modelling of survival of Gammarus pulex in multiple pulse exposures to propiconazole: model assumptions, calibration data requirements and predictive power.

Toxicokinetic-toxicodynamic (TKTD) models quantify the time-course of internal concentration, which is defined by uptake, elimination and biotransformation (TK), and the processes which lead to the toxic effects (TD). TKTD models show potential in predicting pesticide effects in fluctuating concentrations, but the data requirements and validity of underlying model assumptions are not known. We calibrated TKTD models to predict survival of Gammarus pulex in propiconazole exposure and investigated the data requirements. In order to assess the need of TK in survival models, we included or excluded simulated internal concentrations based on pre-calibrated TK. Adding TK did not improve goodness of fits. Moreover, different types of calibration data could be used to model survival, which might affect model parameterization. We used two types of data for calibration: acute toxicity (standard LC50, 4 d) or pulsed toxicity data (total length 10 d). The calibration data set influenced how well the survival in the other exposure scenario was predicted (acute to pulsed scenario or vice versa). We also tested two contrasting assumptions in ecotoxicology: stochastic death and individual tolerance distribution. Neither assumption fitted to data better than the other. We observed in 10-d toxicity experiments that pulsed treatments killed more organisms than treatments with constant concentration. All treatments received the same dose, i.e. the time-weighted average concentration was equal. We studied mode of toxic action of propiconazole and it likely acts as a baseline toxicant in G. pulex during 10-days of exposure for the endpoint survival.

Optimal peripheral nerve stimulation intensity for paired associative stimulation with high-frequency peripheral component in healthy subjects.

Paired associative stimulation (PAS) with high-frequency peripheral nerve stimulation (PNS), called "high-PAS", induces motor-evoked potential (MEP) potentiation in healthy subjects and improves muscle activity and independence in incomplete spinal cord injury patients. Data on optimal PNS intensity in PAS are scarce. In a high-PAS protocol, PNS intensity is defined as "minimal intensity required to produce F-responses". We sought to further refine this definition and to investigate how PNS intensity affects PAS outcome. Two experiments were performed on 10 healthy subjects where MEP amplitude change was measured 0, 30, and 60 min after PAS. In the first experiment, the intensity required to achieve 7/10 persistence of F-responses was used to define PNS intensity level. In the second experiment, we used the intensity required to achieve 1/10 persistence ("baseline"). In addition, we applied this intensity at + 25%, - 25%, and - 50% levels. In the first experiment, PAS did not produce significant MEP potentiation. In the second experiment, PAS produced statistically significant MEP potentiation, with PNS intensity of "baseline" and "baseline - 25%" levels but not at + 25% or - 50% levels. In conclusion, for PAS utilizing high-frequency PNS, the intensity required to achieve 1/10 F-response persistence or the intensity 25% lower produces significant MEP potentiation in healthy subjects.

Augmentative and alternative communication with children with severe/profound intellectual and multiple disabilities: speech language pathologists' clinical practices and reasoning.

PURPOSE: Augmentative and alternative communication (AAC) is recommended to be included in communication interventions directed at children/youth with severe/profound intellectual and multiple disabilities (S/PIMD). Even so, the evidence base for AAC practices with children with S/PIMD is limited. Also, little is known about how frequently AAC is implemented with this target group, which AAC tools and methods are applied, and the related clinical reasoning of speech-language pathologists (SLPs). This study aimed to explore SLPs' beliefs, clinical reasoning and practices in relation to AAC implementation with children/youth with S/PIMD. MATERIALS AND METHODS: In this sequential, mixed-methods study, 90 SLPs working with children with disabilities within habilitation services in Sweden participated in an online survey. The survey answers were statistically analysed. Subsequently, focus group data were collected from seven SLPs and analysed using thematic analysis. RESULTS AND CONCLUSIONS: Despite AAC being highly prioritized, SLPs found it challenging and complex to implement with this target group. A wide variety of AAC methods and tools were considered and implemented. Clinical decision-making was a balancing act between competing considerations and was mainly guided by the SLPs' individual, clinical experiences. The resources, engagement and wishes of the social network surrounding the child were considered crucial for clinical decision-making on AAC. Implications for research and practice are discussed.Implications for rehabilitationSpeech-language pathologists (SLPs) seemingly find a wide variety of Augmentative and Alternative Communication (AAC), ranging from unaided methods to assistive technology of various complexity, to be potentially suitable for children/youth with severe/profound intellectual and multiple disabilities (S/PIMD).The motivation and preferences of the social network surrounding the child with S/PIMD seem to influence SLPs' clinical decision-making on AAC to a high degree. Sometimes this may be considered an even more important factor than the abilities of the child.SLPs' clinical decision-making on AAC for children/youth is guided by their individual, clinical experience to a high degree.An increase in family oriented AAC intervention research targeting individuals with S/PIMD could potentially strengthen the association between research and the current, experience-based clinical practice.

Canonical babbling ratio - Concurrent and predictive evaluation of the 0.15 criterion.

INTRODUCTION: Canonical babbling ratio (CBR) is a commonly used measure to quantify canonical babbling (CB), and 0.15 is the commonly accepted criterion for the canonical babbling stage. However, this has not been thoroughly investigated. The aim of this study was to evaluate the validity of this criterion using concurrent and predictive comparisons. METHODS: Longitudinal data from 50 children recruited in different clinical projects were used. At 10 months of age, CBR was calculated based on counted utterances from audio-video recorded parent-child interactions. The videos were also assessed by CB observation, where an observer made an overall judgement on whether the child was in the canonical babbling stage or not. For the concurrent evaluation, CBR was compared to CB observation as a reference test, using area under the curve (AUC). The criterion resulting in the best combination of sensitivity and specificity was identified using positive likelihood ratios. In the predictive comparisons CBR was analyzed as a predictor of speech/language difficulties at 30-36 months. Participants presenting with difficulties in consonant production and/or parent-reported vocabulary were considered to have speech/language difficulties. Sensitivity and specificity were compared for CBR using the 0.15 criterion and the new criterion identified in this study. RESULTS: An AUC of 0.87 indicated that CBR is a valid measure of canonical babbling in 10-month-old children. The best combination of sensitivity and specificity was found at a criterion of 0.14 (sensitivity 0.96, specificity 0.70). In the predictive comparison, CBR with a 0.14 or 0.15 criterion revealed the same sensitivity (0.71) but 0.14 showed a slightly better specificity (0.52 versus 0.42). CONCLUSIONS: CBR is a valid measure of CB (at 10 months). However, when using CBR to classify children's babbling as canonical or non-canonical, researchers need to carefully consider the implications of the chosen criterion.

Analgesic effect of paired associative stimulation in a tetraplegic patient with severe drug-resistant neuropathic pain: a case report.

OBJECTIVES: There is no effective evidence-based non-pharmacological treatment for severe neuropathic pain after spinal cord injury (SCI). Paired associative stimulation (PAS) has been used in motor rehabilitation of patients after SCI. In the SCI-PAS protocol for tetraplegic patients, peripheral and central nerve tracts are activated with subject-specific timing, such that ascending and descending signals appear simultaneously at the cervical level. The effect on motor rehabilitation is thought to arise via strengthening of cervical upper and lower motoneuron synapses. We have observed an analgesic effect of PAS on mild-to-moderate neuropathic pain in tetraplegic patients receiving PAS for motor rehabilitation. Here, we applied PAS to a patient with severe drug-resistant neuropathic pain. METHODS: The patient is a 50-year-old man who had a traumatic cervical SCI three years earlier. He has partial paresis in the upper limbs and completely plegic lower limbs. The most severe pain is located in the right upper limb and shoulder region. The pain has not responded to either pharmacological therapy or repetitive-TMS therapy targeted to either primary motor cortex or secondary somatosensory cortex. PAS was targeted to relieve pain in the right upper arm. Peripheral nerve stimulation targeted the median, ulnar, and radial nerves and was accompanied by TMS pulses to the motor representation area of abductor pollicis brevis, abductor digiti minimi, and extensor digitorum communis muscles, respectively. RESULTS: Hand motor function, especially finger abduction and extension, was already enhanced during the first therapy week. Pain decreased at the end of the second therapy week. Pain was milder especially in the evenings. Numerical rating scale scores (evening) decreased 44% and patient estimation of global impression of change was 1, subjectively indicating great benefit when compared to before therapy. Quality of sleep also improved. CONCLUSIONS: The SCI-PAS protocol reduced neuropathic pain in our subject. The mechanism behind the analgesic effect may involve the modulation of nociceptive and sensory neuronal circuits at the spinal cord level. The possibility to use PAS as an adjunct treatment in drug-resistant post-SCI neuropathic pain warrants further investigation and sham-controlled studies. Patients with neuropathic pain due to SCI may benefit from PAS therapy in addition to PAS therapy-induced improvement in motor function.

Speech and Language in 5-year-olds with Different Neurological Disabilities and the Association between Early and Later Consonant Production.

The primary aim was to describe speech and language abilities in a clinical group of verbal 5-year-old children diagnosed with neurological disability (ND) in infancy, and the secondary aim was to trace precursors to consonant production at age 5 years (T2) in data from 12 to 22 months (T1). The participants (n = 11, with Down syndrome (DS), cerebral palsy, and chromosomal deletion syndromes) were tested with a battery of speech and language tests. Consonant production at T2 was compared to data on consonant use at T1. At T2, two participants had age appropriate speech and language and another three had age-appropriate speech, but low results on language tests. The remaining six participants had severe speech and language difficulties. Participants with DS had significantly lower results on consonant production measures. An association between consonant production at T1 and T2 for participants with DS indicates that number of different true consonants might be a predictive measure when evaluating young children with DS.

Neurological and Cognitive Performance After Childhood Encephalitis.

Background: Children with encephalitis have increased risk for long-term neurological sequelae. We investigated minor neurological dysfunction (MND) and cognitive performance as a measurement for long-term outcome of encephalitis in childhood. Materials and Methods: Children with encephalitis (n = 98) treated in Turku University Hospital during the years 1995-2016 were retrospectively identified. We included the patients without severe developmental delay before the encephalitis and without recorded neurological disability caused by encephalitis. MND was assessed using the Touwen examination. Age-appropriate Wechsler Intelligence Scale was used to determine the full-scale intelligence quotient (IQ). Residual symptoms in everyday life were evaluated using a questionnaire. Results: Forty-two subjects participated in the study and returned the questionnaire regarding residual symptoms. The median age was 4.3 years at the time of encephalitis, and 11.3 years at the time of the Touwen examination (n = 41) and the cognitive assessment (n = 38). The Touwen examination indicated MND in 29 of 41 participants (71%; simple MND in 16 and complex MND in 13 patients). The median full-scale IQ was lower in participants with MND compared with participants without MND (98 vs. 110, p = 0.02). Participants with IQ < 85 (n = 5) had lower median age at acute encephalitis compared to participants with IQ ≥ 85 (n = 33) (1.8 vs. 5.3 years, p = 0.03). Problems in daily performance were reported in participant with MND (p = 0.2) and low full-scale IQ (p = 0.008). Conclusions: The prevalence of MND was high and it was related to lower cognitive performance after childhood encephalitis. Younger age at acute encephalitis was a risk factor for lower cognitive performance.

A longitudinal study of plasma BAFF levels in mothers and their infants in Uganda, and correlations with subsets of B cells.

Malaria is a potentially life-threatening disease with approximately half of the world's population at risk. Young children and pregnant women are hit hardest by the disease. B cells and antibodies are part of an adaptive immune response protecting individuals continuously exposed to the parasite. An infection with Plasmodium falciparum can cause dysregulation of B cell homeostasis, while antibodies are known to be key in controlling symptoms and parasitemia. BAFF is an instrumental cytokine for the development and maintenance of B cells. Pregnancy alters the immune status and renders previously clinically immune women at risk of severe malaria, potentially due to altered B cell responses associated with changes in BAFF levels. In this prospective study, we investigated the levels of BAFF in a malaria-endemic area in mothers and their infants from birth up to 9 months. We found that BAFF-levels are significantly higher in infants than in mothers. BAFF is highest in cord blood and then drops rapidly, but remains significantly higher in infants compared to mothers even at 9 months of age. We further correlated BAFF levels to P. falciparum-specific antibody levels and B cell frequencies and found a negative correlation between BAFF and both P. falciparum-specific and total proportions of IgG+ memory B cells, as well as CD27- memory B cells, indicating that exposure to both malaria and other diseases affect the development of B-cell memory and that BAFF plays a part in this. In conclusion, we have provided new information on how natural immunity against malaria is formed.