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Background: Early detection of developmental problems is important as it allows for early intervention. Previous studies, in high-risk infants, found high predictive values of atypical scores on the Standardized Infant NeuroDevelopmental Assessment (SINDA) for later neurodevelopmental disorders (i.e., cerebral palsy, intellectual disability)., Aims: The present study explored SINDA's predictive values to identify risk of developmental delay at 4-5 years., Study Design: Cohort study., Subjects: 786 low-risk Dutch children (367 boys; median gestational age: 40 (27-42) weeks; mean birth weight: 3455 (SD 577) grams)., Outcome Measures: The SINDA was assessed at 2-12 months and risk of developmental delay was assessed using the Ages and Stages Questionnaire (ASQ) at 4-5 years. SINDA's predictive values were determined for five ASQ domains and the total ASQ score for children at risk of marked (all ASQ domains deviant) and any (one or more ASQ domains deviant) developmental delay., Results: Presence of one atypical SINDA scale score showed low to moderate sensitivities (12-88 %, depending on the SINDA scale and ASQ domain involved), moderate to high specificities (66-94 %), low positive predictive values (PPVs; 3-16 %), and high negative predictive values (NPVs; 95-100 %) for children at risk of marked and any developmental. Presence of multiple atypical SINDA scale scores predicted deviant ASQ domains slightly better (sensitivities = 11-62 %, specificities = 90-98 %, PPVs = 6-30 %, and NPVs = 95-100 %)., Conclusions: In low-risk infants, SINDA's predictive value is low for detecting children at risk of marked and any developmental delay at 4-5 years, as reflected by the low sensitivities. One of the explanations is the relatively low prevalence of developmental delay in low-risk populations. This might have consequences for the application of the SINDA in general healthcare settings (e.g. child health clinics), but further studies are needed to draw this conclusion., Competing Interests: Declaration of competing interest Mijna Hadders-Algra is one of the authors of the SINDA manual., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Infants with complex congenital heart disease are at increased risk of impaired fetal brain growth, brain injury, and developmental impairments. The General Movement Assessment (GMA) is a valid and reliable tool to predict cerebral palsy (CP), especially in preterm infants. Predictive properties of the GMA in infants with complex congenital heart disease (CCHD) are unknown., Aim: To evaluate predictive properties of the GMA to predict developmental outcomes, including cerebral palsy (CP), at 18-months corrected age (CA) in children with CCHD undergoing heart surgery in the first month of life., Methods: A prospective cohort of 56 infants with CCHD (35 males, 21 females) was assessed with GMA at writhing age (0-6 weeks CA) and fidgety age (7-17 weeks CA) and the Bayley Scales of Infant Development at 18 months. GMA focused on markedly reduced GM-variation and complexity (definitely abnormal (DA) GM-complexity) and fidgety movements. Predictive values of GMA for specific cognitive, language and motor delay (composite scores <85th percentile) and general developmental delay (delay in all domains) were calculated at 18 months., Results: At fidgety age, all infants had fidgety movements and no child was diagnosed with CP. DA GM-complexity at fidgety age predicted general developmental delay at 18 months (71 % sensitivity, 90 % specificity), but predicted specific developmental delay less robustly. DA GM-complexity at writhing age did not predict developmental delay, nor did it improve prediction based on DA GM-complexity at fidgety age., Conclusions: In infants with CCHD and fidgety movements, DA GM-complexity at fidgety age predicted general developmental delay., Competing Interests: Declaration of competing interest Mijna Hadders-Algra has provided courses on the GMA since 1993. She did not get an honorarium, grant, or other form of payment to produce this manuscript. The other authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Longer gestation at term and post-term age is associated with increased perinatal mortality. Nonetheless, recent neuroimaging studies indicated that longer gestation is also associated with better functioning of the child's brain., Aims: to assess whether longer gestation in term and post-term (in short: term) singletons is associated with better infant neurodevelopment., Study Design: cross-sectional observational study., Subjects: Participants were all singleton term infants (n = 1563) aged 2-18 months of the IMP-SINDA project that collected normative data for the Infant Motor Profile (IMP) and Standardized Infant NeuroDevelopmental Assessment (SINDA). The group was representative of the Dutch population., Outcome Measures: Total IMP score was the primary outcome. Secondary outcomes were atypical total IMP scores (scores <15th percentile) and SINDA's neurological and developmental scores., Results: Duration of gestation had a quadratic relationship with IMP and SINDA developmental scores. IMP scores were lowest at a gestation of 38·5 weeks, SINDA developmental scores at 38·7 weeks. Next, both scores increased with increasing duration of gestation. Infants born at 41-42 weeks had significantly less often atypical IMP scores (adjusted OR [95 % CI]: 0·571 [0·341-0·957] and atypical SINDA developmental scores (adjusted OR: 0·366 [0·195-0·688]) than infants born at 39-40 weeks. Duration of gestation was not associated with SINDA's neurological score., Conclusions: In term singleton infants representative of the Dutch population longer gestation is associated with better infant neurodevelopment scores suggesting better neural network efficiency. Longer gestation in term infants is not associated with atypical neurological scores., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The Infant Motor Profile (IMP) is an appropriate tool to assess and monitor infant motor behaviour over time. Infants at very high risk (VHR) due to a lesion of the brain generally show impaired motor development. They may grow into or out of their neurodevelopmental deficit., Aims: Evaluate associations between IMP-trajectories, summarised by IMP-scores in early infancy and rates of change, and functional and cognitive outcome at school-age in VHR-children., Study Design: Longitudinal study., Subjects: 31 VHR-children, mainly due to a brain lesion, who had multiple IMP-assessments during infancy, were re-assessed at 7-10 years (school-age)., Outcome Measures: Functional outcome was assessed with the Vineland-II, cognition with RAKIT 2. Associations between IMP-trajectories and outcome were tested by multivariable linear regression analyses., Results: When corrected for sex, maternal education and follow-up age, initial scores of total IMP, variation and performance domains, as well as their rates of change were associated with better functional outcome (unstandardised coefficients [95% CI]): 36.44 [19.60-53.28], 33.46 [17.43-49.49], 16.52 [7.58-25.46], and 513.15 [262.51-763.79], 356.70 [148.24-565.15], and 269 [130.57-407.43], respectively. Positive rates of change in variation scores were associated with better cognition at school-age: 34.81 [16.58-53.03]., Conclusion: Our study indicated that in VHR-children IMP-trajectories were associated with functional outcome at school-age, and to a minor extent also with cognition. Initial IMP-scores presumably reflect the effect of an early brain lesion on brain functioning, whereas IMP rate of change reflects whether infants are able to grow into or out of their initial neurodevelopmental deficit., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Previously it had been had reported that active head lifting from supine (AHLS) in high-risk infants was associated with lower cognitive scores in the second year. AHLS was generally accompanied by stereotyped leg movements., Aims: To examine in a standardized way whether AHLS with or without stereotyped leg movements in the general population is associated with prenatal, perinatal, neonatal and socio-economic risk factors or with lower scores on concurrent infant tests., Study Design: Cross-sectional study SUBJECTS: 1700 infants aged 2-18 months representative of the Dutch population., Outcome Measures: Infant Motor Profile (IMP) and Standardized Infant NeuroDevelopmental Assessment (SINDA). Assessments were video-recorded and included at the youngest ages 3min of behaviour in supine. AHLS and the presence of stereotyped leg movements were recorded. Standardized information on early risk factors was available., Results: AHLS occurred at 4-9 months (prevalence per months: 1-14%; highest prevalence at 6 months). It was not associated with early risk factors or scores on infant tests. When AHLS was accompanied by stereotyped leg movements it was associated with a higher prevalence of an IMP-variation score < P15 (Odds Ratio (OR) 2.472 [95%CI 1.017; 6.006]). Stereotyped leg movements irrespective of AHLS were associated with more unfavourable total IMP scores and IMP performance scores (B coefficients -3.212 [-4.065; -2.360], -2.521 [-3.783; -1.259]) and IMP variation and SINDA neurological scores (ORs 5.432 [3.409; 8.655], 3.098 [1.548; 6.202])., Conclusions: The data suggest that AHLS is not a red flag. Rather its co-occurring stereotyped leg movements may signal less favourable neurodevelopment., (Copyright © 2021. Published by Elsevier B.V.)

Background: Muscle tone is an indispensable element in motor development. Its assessment forms an integral part of the infant neurological examination. Knowledge on the prevalence of atypical tone in infancy is lacking., Aim: To assess the prevalence of atypical muscle tone in infancy and of the most common atypical muscle tone patterns, and associations between atypical tone and perinatal risk and neurodevelopmental status., Study Design: Cross-sectional study., Subjects: 1100 infants (585 boys; gestational age 39.4 weeks (27.3-42.4)), 6 weeks-12 months corrected age, representative of the Dutch population., Outcome Measures: Muscle tone and neurodevelopmental status were assessed with the Standardized Infant NeuroDevelopmental Assessment (SINDA). Perinatal information was obtained by questionnaire and medical records. Univariable and multivariable statistics were applied., Results: Ninety-two infants (8%) had atypical muscle tone in 3-4 body parts (impaired pattern), while atypical muscle tone in 1-2 body parts was observed in 50%. Isolated leg hypotonia and isolated arm hypertonia were most common. Isolated arm hypertonia and the impaired pattern were most clearly but only moderately associated with perinatal risk. These patterns were also most clearly associated with lower neurological scores. Only the impaired pattern was associated with lower developmental scores., Conclusion: Atypical muscle tone in one or two body parts is common in infancy and has in general little clinical significance. This finding corresponds to the well-known high prevalence of a typical but non-optimal neurological condition. Eight percent of infants show atypical muscle tone in 3-4 body parts. This clinically relevant pattern is associated with perinatal risk and less favourable neurodevelopmental status., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Advances in diagnostic technologies, surgical management, and perioperative care have increased survival for neonates with complex congenital heart disease (CCHD). The success of these advances exposed a heightened risk of brain injury and developmental disabilities. The General Movements Assessment, a non-invasive method, may detect early neurodevelopmental impairments in high-risk infants., Aims: To examine whether infants with CCHD undergoing neonatal surgery have higher prevalence of atypical general movements (GMs) than a reference group, and whether single ventricle physiology with systemic oxygen saturations <90% increases risk for atypical GMs., Methods: Serial General Movements Assessment (GMA) in a cohort of infants with CCHD (n = 74) at writhing (term-6 weeks) and fidgety (7-17 weeks) GM-age. GMA focused on the presence of definitely abnormal GM-complexity and absent fidgety movements. Single GMAs at 3 months were available from a reference sample of Dutch infants (n = 300). Regression analyses examined relationships between cardiac characteristics and definitely abnormal GM-complexity., Results: Higher prevalence of definitely abnormal GM-complexity in infants with CCHD compared to reference infants (adjusted OR 5.938, 95% CI 2.423-14.355), single ventricle CCHD increased the risk. Occurrence of absent fidgety movements was similar in infants with CCHD and reference infants (adjusted OR 0.475, 95% CI 0.058-3.876). Systemic postoperative oxygen saturations <90% was associated with higher risk of definitely abnormal GM-complexity at fidgety (adjusted OR 16.445 95% CI 1.149-235.281), not at writhing age., Conclusions: Infants with CCHD, especially those with single ventricle CCHD, are at increased risk of definitely abnormal GM-complexity. GMA at fidgety age is recommended., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The Alberta Infant Motor Scale (AIMS) has been developed in Canada in the 90ies. The AIMS and its Canadian norms are frequently used across the world to monitor infants' gross motor development. Currently, it is disputed whether the Canadian norms are valid for non-Canadian infants., Aims: To compare scores on the AIMS of Dutch infants with that of the Canadian norms, to compare the sequence of motor milestones in Dutch and Canadian infants, and to establish Dutch AIMS norms., Study Design: Cross-sectional study., Subjects: 1697 infants, aged 2-18 months, representative of the Dutch population (gestational age 39.7 weeks (27-42))., Outcome Measure: AIMS assessments, based on standardized video. Perinatal and social information was obtained by questionnaire and medical records. To create Dutch reference values quantile regression with polynomial splines was used., Results: 1236 Dutch infants (73%) scored below the 50th (P50) percentile of the Canadian norms, 653 (38%) below the P10 and 469 (28%) below the P5. In infants aged 6 to 12 months these values were: 567 infants (81%) < P50, 288 infants (41%) < P10, 201 infants (29%) < P5. The sequence of achievement of motor milestones of Dutch and Canadian infants was similar. Dutch norm-reference values of the AIMS were calculated., Conclusions and Implications: Gross motor development of Dutch infants is considerably slower than that of the Canadian AIMS norms sample. To prevent overdiagnosis of developmental delay and overreferral to paediatric physiotherapy Dutch AIMS norms are required. The paper introduces these norms, including percentile ranks., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Movement complexity and the presence of fidgety movements (FMs) during general movements (GMs) both reflect aspects of neurological integrity in early infancy., Aim: To assess interrelations between the degree of movement complexity and characteristics of FMs during typical GMs and to investigate associations between mildly impaired GMs and risk factors and neurodevelopmental condition., Study Design: Observational cohort study., Subjects: 283 infants (25 born preterm) at 2-4 months corrected age, representative of the general Dutch population., Outcome Measures: GMs were classified in terms of GM-complexity (normal or mildly abnormal (MA)) and FMs (clearly present, sporadic, or exaggerated). Concurrent neurological, developmental and socio-emotional status were measured with the Standardized Infant NeuroDevelopmental Assessment (SINDA)., Results: Infants with MA GM-complexity had a higher risk of having sporadic FMs and exaggerated FMs. Perinatal complications were not associated with mildly impaired GMs. MA GM-complexity was associated with advanced maternal age (adjusted OR = 2.29 [1.11, 4.76]) and having a non-native Dutch mother (adjusted OR = 2.93 [1.29, 6.64]). It was also associated with atypical neurological (OR = 7.62 [3.51, 16.54]) and developmental scores (OR = 2.38 [1.16, 4.88]). Sporadic and exaggerated FMs were associated with low-to-middle maternal education (adjusted OR = 2.88, [1.45, 5.72]) and having a non-native Dutch father (adjusted OR = 7.16 [1.41, 36.32]), respectively. However, neither sporadic nor exaggerated FMs were associated with the SINDA outcomes., Conclusions: GM-complexity and FMs are two interrelated but different aspects of GMs. Mild impairments in GM-complexity and FMs share a non-optimal socio-economic background as risk factor, but only MA GM-complexity is associated with a concurrent non-optimal neurodevelopmental condition., Competing Interests: Declaration of competing interest None., (Copyright © 2020. Published by Elsevier B.V.)

Background: General Movement Assessment (GMA) is a powerful tool to predict Cerebral Palsy (CP). Yet, GMA requires substantial training challenging its broad implementation in clinical routine. This inspired a world-wide quest for automated GMA., Aims: To test whether a low-cost, marker-less system for three-dimensional motion capture from RGB depth sequences using a whole body infant model may serve as the basis for automated GMA., Study Design: Clinical case study at an academic neurodevelopmental outpatient clinic., Subjects: Twenty-nine high risk infants were assessed at their clinical follow-up at 2-4 month corrected age (CA). Their neurodevelopmental outcome was assessed regularly up to 12-31 months CA., Outcome Measures: GMA according to Hadders-Algra by a masked GMA-expert of conventional and computed 3D body model ("SMIL motion") videos of the same GMs. Agreement between both GMAs was tested using dichotomous and graded scaling with Kappa and intraclass correlations, respectively. Sensitivity and specificity to predict CP at ≥12 months CA were assessed., Results: Agreement of the two GMA ratings was moderate-good for GM-complexity (κ = 0.58; ICC = 0.874 [95%CI 0.730; 0.941]) and substantial-good for fidgety movements (FMs; Kappa = 0.78, ICC = 0.926 [95%CI 0.843; 0.965]). Five children were diagnosed with CP (four bilateral, one unilateral CP). The GMs of the child with unilateral CP were twice rated as mildly abnormal with FMs. GM-complexity and somewhat less FMs, of both conventional and SMIL motion videos predicted bilateral CP comparably to published literature., Conclusions: Our computed infant 3D full body model is an attractive starting point for automated GMA in infants at risk of CP., Competing Interests: Declaration of competing interest MJB is a co-founder and investor in Meshcapade GmbH, which is commercializing infant shape and motion technology., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In vitro fertilization (IVF) is not associated with neurological abnormalities in offspring's early childhood. Yet, it is unclear whether this is also true for school age. Neither do we know the role of parental subfertility in offspring's neurological development. The present study examined neurological condition at 9 years of 57 singletons born after controlled ovarian hyperstimulation IVF (COH-IVF), 46 singletons born after modified natural cycle IVF (MNC-IVF) and 66 singletons born to subfertile parents after natural conception (Sub-NC). To assess the effect of subfertility, the groups were pooled to form a subfertile group, and compared with a prospectively followed fertile reference group (n = 282). The sensitive Minor Neurological Dysfunction (MND) examination was used, resulting in the detailed Neurological Optimality Score (NOS) and the prevalence of the clinically relevant complex MND. Neurological condition of the three subfertile groups did not differ significantly: median NOS was 53 in each subfertile group and the prevalence of complex MND in the three subfertile groups was 30%, 37% and 36%, respectively. However, the NOS was lower and the prevalence of complex MND higher in children born to subfertile couples than in children of fertile couples (adjusted mean difference [95% CI]: -4.48 [-5.53 to -3.42]) and adjusted OR [95% CI]: 5.13 [2.60-10.16], respectively). We conclude that ovarian hyperstimulation, in vitro procedures, and the combination of both were not associated with a less favourable neurological outcome of 9-year-old singletons. However, the presence of parental subfertility was associated with less favourable neurological outcome of offspring at 9 years follow up., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Early identification of infants at risk of cerebral palsy (CP) is desirable in order to provide early intervention. We previously demonstrated differences in knee jerk responses between 3-month-old high risk and typically developing infants., Aims: To improve early identification by investigating whether the presence of tonic responses (continuous muscle activity occurring after the typical phasic response), clonus or contralateral responses to the knee jerk during infancy is associated with CP., Study Design: Longitudinal EMG-study., Subjects: We included 34 high-risk infants (median gestational age 31.9 weeks) who participated in the LEARN2MOVE 0-2 years trial., Outcome Measures: Video-recorded knee jerk EMG-assessments were performed during infancy (1-4 times). Developmental outcome was assessed at 21 months corrected age (CA). Binomial generalized estimating equations models with repeated measurements were fitted using predictor variables., Results: Infants who later were diagnosed with CP (n = 18) showed more often than infants who were not diagnosed with CP i) tonic responses - from 4 months CA onwards, ii) clonus - from 13 months CA onwards, and iii) contralateral responses - from 15 months CA onwards., Limitations: The main limitation is the relatively small sample size., Conclusions: The assessment of tonic responses to the knee jerk using EMG may be a valuable add-on tool to appraise a high risk of CP., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aim: To investigate associations between neurological condition, assessed with the Hempel examination, in terms of minor neurological dysfunction (MND) and neurological optimality, and cognition and behaviour at 4years., Study Design: Cross-sectional analyses within a prospective, assessor-blinded follow-up study., Subjects: Four-year-old singletons born to subfertile parents (n=235; 120 boys)., Outcome Measures: Outcome parameters were complex minor neurological dysfunction (complex MND) and the neurological optimality score (NOS). Cognitive outcome was evaluated with the Kaufman Assessment Battery for Children, resulting in a total intelligence quotient (IQ). Behavioural outcome was evaluated with the Child Behavior Checklist, resulting in a total problem T-score., Results: Fifty-seven (24.3%) children had complex MND. None of the children showed fine motor dysfunction, suggesting a ceiling effect of the Hempel assessment. Complex MND was not correlated with IQ or total problem T-score. Nevertheless, a higher NOS was correlated with a higher IQ and a lower total problem T-score (adjusted mean estimate [95% confidence interval]: cognition: 0.445 [0.026; 0.865], p=0.038; behaviour: -0.458 [-0.830; -0.087], p=0.016)., Interpretation: At age 4, complex MND assessed with the Hempel assessment was not associated with cognition and behaviour, presumably due to a ceiling effect in the Hempel domain of fine motor function. A more optimal neurological condition was associated with higher IQ and better behaviour., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This prospective cohort study evaluated whether the cognitive development, neurological condition, anthropometrics and blood pressure of 4-year-old IVF twins differed from those of 4-year-old IVF singletons; 103 IVF singletons and 48 IVF twins born after conventional IVF treatment were included. Primary outcome was total intelligence quotient (IQ). Secondary outcomes were minor neurological dysfunction, anthropometrics and blood pressure. Unadjusted analyses found that the total IQ score of twins was lower than that of singletons, with a mean difference of -5.4 (-9.7 to -1.0). Weight (singletons: 18.6 [18.1 to 19.1] kg; twins: 16.9 [16.0 to 17.9] kg) and height (singletons: 108.8 [107.9 to 109.8] cm; twins: 105.9 [104.0 to 107.7] cm) of twins were lower than those of singletons (mean values [95% CI]). All differences disappeared after adjusting for mediators and confounders. Neurological outcome, systolic and diastolic blood pressure of twins and singletons were similar. Four-year-old IVF twins had a lower total IQ (-5.4 points), lowerbodyweight (-1.7 kg) and were shorter (-2.9 cm) than 4-year-old IVF singletons. After adjustment, the adverse twin effect disappeared, implying that increased risk for impaired health and development in twins also holds true for IVF twins, and is not altered by IVF., (Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: The long-term effect of early intervention in infants at risk for developmental disorders is unclear. The VIP project (n=46, originally) evaluated by means of a randomised controlled trial the effect of the family centred early intervention programme COPCA (Coping with and Caring for infants with special needs) in comparison to that of traditional infant physiotherapy (TIP)., Aims: To evaluate the effect of early intervention on functional outcome at school age., Methods and Procedures: Parents of 40 children (median age 8.3years) participated in this follow-up study. Outcome was assessed with a standardised parental interview (Vineland Adaptive Behaviour Scale) and questionnaires (Developmental Coordination Disorder Questionnaire, Child Behaviour Checklist, Utrechtse Coping List, and questions on educational approach). Quantified video information on physiotherapeutic actions during infancy was available., Outcomes and Results: Child functional outcome in the two randomised groups was similar. Process evaluation revealed that some physiotherapeutic actions were associated with child mobility and parental educational approach at follow-up: e.g., training and instructing were associated with worse mobility., Conclusions and Implications: Functional outcome at school age after early intervention with COPCA is similar to that after TIP. However, some specific physiotherapeutic actions, in particular the physiotherapist's approach, are associated with outcome., What This Paper Adds: Early intervention is generally applied in infants at risk for developing disorders, with the aim of improving overall functional outcome. However, little is known on the long-term effect. The VIP project evaluated by means of a randomised controlled trial the effect of the family centred early intervention programme COPCA (Coping with and Caring for infants with special needs) in comparison to that of traditional infant physical therapy (TIP). Outcome at 18months corrected age was virtually similar. Process evaluation of the physiotherapy actions revealed that some characteristics of COPCA were associated with improved developmental outcome at 18months. This paper presents data on functional outcome at school age (median 8.3years) in 87% of the original participants. Outcome of infants who received three months of COPCA and that of infants who received three months of TIP was similar. Yet, parents of families who had received the COPCA intervention still more often used a trial and error approach when the child learned a new skill than parents of children who had received TIP. Process evaluation showed that more time spent on caregiver training and strict instructions during early intervention was associated with worse mobility. Four other physiotherapeutic actions were associated with parental educational approach. None of the neuromotor actions were associated with child outcome at school age. We conclude that long-term outcome after three months of COPCA or TIP is similar. However, our study does suggest that the professional approach of the physiotherapist can make a difference., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Research on cognitive and behavioural development of children born after assisted conception is inconsistent. This prospective study aimed to explore underlying causal relationships between ovarian stimulation, in-vitro procedures, subfertility components and child cognition and behaviour. Participants were singletons born to subfertile couples after ovarian stimulation IVF (n = 63), modified natural cycle IVF (n = 53), natural conception (n = 79) and singletons born to fertile couples (reference group) (n = 98). At 4 years, cognition (Kaufmann-ABC-II; total IQ) and behaviour (Child Behavior Checklist; total problem T-score) were assessed. Causal inference search algorithms and structural equation modelling was applied to unravel causal mechanisms. Most children had typical cognitive and behavioural scores. No underlying causal effect was found between ovarian stimulation and the in-vitro procedure and outcome. Direct negative causal effects were found between severity of subfertility (time to pregnancy) and cognition and presence of subfertility and behaviour. Maternal age and maternal education acted as confounders. The study concludes that no causal effects were found between ovarian stimulation or in-vitro procedures and cognition and behaviour in childrenaged 4 years born to subfertile couples. Subfertility, especially severe subfertility, however, was associated with worse cognition and behaviour., (Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Long chain polyunsaturated fatty acid (LCPUFA) status is associated with risk of cardiovascular diseases in adulthood. We previously demonstrated no effect of LCPUFA supplementation after birth on BP and anthropometrics. Little is known about the association between fatty acid status at birth and cardiometabolic health at older ages., Aim: To evaluate associations between docosahexaenoic acid (DHA) and arachidonic acid (AA) levels in the umbilical cord and blood pressure (BP) and anthropometrics at 9years., Study Design: Observational follow-up study. Multivariable analyses were carried out to adjust for potential confounders., Subjects: 229 children who took part in a randomized controlled trial (RCT) on the effects of LCPUFA formula supplementation., Outcome Measures: BP was chosen as primary outcome; heart rate and anthropometrics as secondary outcomes., Results: AA levels in the wall of the umbilical vein and artery were negatively associated with diastolic BP (B: vein -0.831, 95% CI: -1.578; -0.083, p=0.030; artery: -0.605, 95% CI: -1.200; -0.010, p=0.046). AA was not associated with systolic BP; DHA not with diastolic nor systolic BP. The AA:DHA ratio in the umbilical vein was negatively associated with diastolic BP (B: -1.738, 95% CI: -3.141; -0.335, p=0.015). Heart rate and anthropometrics were not associated with neonatal LCPUFA status., Conclusions: Higher AA levels and a higher AA:DHA ratio at birth are associated with lower diastolic BP at age 9. This suggests that the effect of LCPUFAs at early age is different from that in adults, where DHA is regarded anti-adipogenic and AA as adipogenic., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Assessing the quality of general movements (GMs) is a non-invasive tool to identify at early age infants at risk for developmental disorders., Aim: To investigate whether specific characteristics of definitely abnormal GMs are associated with developmental outcome at school age., Study Design: Observational cohort study (long-term follow-up)., Subjects: Parents of 40 children (median age 8.3 years, 20 girls) participated in this follow-up study. In infancy (median corrected age 10 weeks), the children (median gestational age 30.3 weeks; birth weight 1243 g) had shown definitely abnormal GMs according to Hadders-Algra (2004). Information on specific GM characteristics such as the presence of fidgety movements, degree of complexity and variation, and stiff movements, was available (see Hamer et al. 2011)., Outcome Measures: A standardised parental interview (presence of CP, attendance of school for special education, Vineland Adaptive Behavior Scale to determine functional performance) and questionnaires (Developmental Coordination Disorder Questionnaire [DCD-Q] to evaluate mobility and Child Behavior Checklist to assess behaviour) were used as outcome measures., Results: Six children had cerebral palsy (CP), ten children attended a school for special education, and eight children had behavioural problems. Both the absence of fidgety movements and the presence of stiff movements were associated with CP (p=0.001; p=0.003, respectively). Stiff movements were also related to the need of special education (p=0.009). A lack of movement complexity and variation was associated with behavioural problems (p=0.007). None of the GM characteristics were related to DCD-Q scores., Conclusions: The evaluation of fidgety movements and movement stiffness may increase the predictive power of definitely abnormal GMs for motor outcome--in particular CP. This study endorses the notion that the quality of GMs reflects the integrity of the infant's brain, assisting prediction of long-term outcome., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: General movement (GM) assessment is a well-established tool to predict cerebral palsy in high-risk infants. Little is known on the predictive value of GM assessment in low-risk populations., Aims: To assess the predictive value of GM quality in early infancy for the development of the clinically relevant form of minor neurological dysfunction (complex MND) and behavioral problems at preschool age., Study Design: Prospective cohort study., Subjects: A total of 216 members of the prospective Groningen Assisted Reproductive Techniques (ART) cohort study were included in this study. ART did not affect neurodevelopmental outcome of these relatively low-risk infants born to subfertile parents., Outcome Measures: GM quality was determined at 2 weeks and 3 months. At 18 months and 4 years, the Hempel neurological examination was used to assess MND. At 4 years, parents completed the Child Behavior Checklist; this resulted in the total problem score (TPS), internalizing problem score (IPS), and externalizing problem score (EPS). Predictive values of definitely (DA) and mildly (MA) abnormal GMs were calculated., Results: DA GMs at 2 weeks were associated with complex MND at 18 months and atypical TPS and IPS at 4 years (all p<0.05). Sensitivity and positive predictive value of DA GMs at 2 weeks were rather low (13%-60%); specificity and negative predictive value were excellent (92%-99%). DA GMs at 3 months occurred too infrequently to calculate prediction. MA GMs were not associated with outcome., Conclusions: GM quality as a single predictor for complex MND and behavioral problems at preschool age has limited clinical value in children at low risk for developmental disorders., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

This study evaluated the prevalence of asthma and asthma medication use in 213 4-year-old singletons followed from birth onwards, including three groups of children born following: (i) controlled ovarian hyperstimulation IVF/intracytoplasmic sperm injection (ICSI); (ii) modified natural cycle IVF/ICSI; and (iii) natural conception in subfertile couples. The rate of asthma medication was higher in the ovarian hyperstimulation-IVF/ICSI than in the subfertile group (adjusted odds ratios [aOR]: 1.96 [1.00-3.84]). Time to pregnancy, a proxy for the severity of subfertility, was not associated with asthma and asthma medication. In conclusion, controlled ovarian hyperstimulation-IVF/ICSI is associated with the use of asthma medication in 4-year-old offspring of subfertile couples., (Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Long-chain polyunsaturated fatty acids (LCPUFA) are important for prenatal brain development. Previous studies of others assessed outcome until 7 years. The associations between neonatal LCPUFA status and long-term developmental outcome are debated., Aim: To investigate the relationship between fatty acid status at birth and neurodevelopment at 9 years. Age 9 is a unique age after a significant neurodevelopmental transition., Study Design: Correlation study. Multivariable analyses were carried out to adjust for potential confounders., Subjects: 317 children who participated in a trial on effects of postnatal LCPUFA supplementation were eligible. 235 children (74%) were reassessed at age 9., Outcome Measures: At birth, docosahexaenoic acid (DHA) and arachidonic acid (AA) were determined in the wall of the umbilical vein. We primarily studied the correlation between DHA and AA with the complex form of minor neurological dysfunction (cMND). Secondary correlations that were studied were DHA and AA levels with cognitive development in terms of full IQ, and with behavioural development in terms of a total problem score., Results: Boys with cMND showed lower DHA values in the umbilical vein than children with better neurological condition (p=0.033). A similar association was absent in girls. Neonatal AA values were not associated with neurological outcome. Neither neonatal DHA nor AA values were associated with cognition and behaviour at 9., Conclusions: Higher umbilical DHA levels in boys are associated with better neurological development at 9 years. AA status at birth was not associated with neurodevelopment at 9 years., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Some evidence suggests that children with specific behavioral problems are at risk for motor problems. It is unclear whether neurological condition plays a role in the propensity of children with behavioral problems to develop motor problems., Aims: To examine the relation between behavioral problems, motor performance and neurological condition in school-aged children., Study Design: Cross-sectional study., Subjects: 174 children (95 boys) receiving mainstream education and 106 children (82 boys) receiving special education aged 6 to 13 years (mean 9 y 7 m, SD 1 y 10 m)., Outcome Measures: Behavior was assessed with questionnaires: the parental Child Behavior Checklist (CBCL) and Teacher's Report Form (TRF). Motor performance was assessed with the Movement Assessment Battery for Children (MABC). MABC-scores ≥5th percentile were considered as age-adequate and scores <5th percentile indicated definite motor problems. Neurological condition was assessed in terms of Minor Neurological Dysfunction (MND)., Results: The majority of specific behavioral problems were associated with definite motor problems, except somatic complaints and rule breaking behavior. Children with externalizing problems, according to the CBCL or TRF, and motor problems had more often MND than children with externalizing problems only. The same holds true for internalizing problems according to the CBCL., Conclusions: The present study demonstrated that various forms of behavioral problems were associated with motor problems. Especially children with motor and behavioral problems showed MND., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Children with cerebral palsy (CP) have impaired postural control. Posture is controlled in two levels: direction-specificity, and fine-tuning of direction-specific adjustments, including recruitment order. Literature suggests that direction-specificity might be a prerequisite for independent sitting., Aim: To study development of postural adjustments in infants at very high risk for CP (VHR-infants) during developing the ability to sit independently., Method: In a longitudinal study surface electromyograms of the neck-, trunk- and arm muscles of 11 VHR-infants and 11 typically developing (TD) infants were recorded during reaching in sitting before and after developing the ability to sit unsupported (median ages: VHR 8.0 and 14.9months; TD 5.7 and 10.4months). Sessions were video-recorded., Results: In VHR- and TD-infants the prevalence of direction-specific adjustments and recruitment order did not change when the infant learned to sit independently. In VHR-infants able to sit independently more successful reaching was associated with a higher frequency of bottom-up recruitment (Spearman's rho=0.828, p=0.006) and a lower frequency of simultaneous recruitment (Spearman's rho=-0.701, p=0.035), but not with more direction-specificity. In TD-infants not able to sit independently, more successful reaching was associated with higher rates of direction-specific adjustments at the neck level (Spearman's rho=0.778, p=0.014), but not with recruitment order., Conclusions: In VHR- and TD-infants postural adjustments during reaching in terms of direction-specificity and recruitment order are not related to development of independent sitting. Postural adjustments are associated with success of reaching, be it in a different way for VHR- and TD-infants., Clinical Trial Registration Number: NTR1428., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: The effect of in vitro fertilisation (IVF) on neurodevelopment is not fully understood. Probably, IVF does not affect traditional measures of neurodevelopment in infancy. Recently, an instrument, the Infant Motor Profile (IMP), was developed that evaluates the quality of motor behaviour. It includes the evaluation of movement variation (i.e. movement repertoire size), a parameter reflecting the integrity of cortical connectivity., Aim: To evaluate the effect of ovarian hyperstimulation and the in vitro procedure on movement variation during infancy., Study Design: Prospective cohort study., Subjects: Singletons born following IVF or intracytoplasmic sperm injection (ICSI) with conventional controlled ovarian hyperstimulation (COH-IVF/ICSI, n=68), in a modified natural cycle (MNC-IVF/ICSI, n=57) and natural conception born to subfertile couples (Sub-NC, n=90)., Outcome Measures: Children were assessed with the IMP at 4, 10 and 18 months, resulting in a total IMP score and five domain scores: variation, variability, symmetry, fluency and performance. Primary outcome was the domain score variation., Results: A significant effect of study group was observed for the variation score up until 18 months of age (p=0.039). COH-IVF/ICSI children had a significantly lower mean variation score than MNC-IVF/ICSI children (mean difference [95% confidence interval] -1.010 [-1.766; -0.254]). Mean variation scores of COH-IVF/ICSI and Sub-NC children were similar; the same held true for the comparison between MNC-IVF/ICSI and Sub-NC. Total IMP scores and other domain scores of the three groups were similar., Conclusion: The present study did not demonstrate a clear effect of ovarian hyperstimulation and the in vitro procedure on movement variation throughout infancy., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: In children with developmental disorders, motor problems often co-occur with cognitive difficulties. Associations between specific cognitive deficits underlying learning problems and minor neurological dysfunction (MND) are still unknown., Aims: To assess associations between specific types of MND as clinical markers of non-optimal brain function and performance in specific cognitive domains., Study Design: Part of a randomized controlled trial., Subjects: Three hundred and forty one 9-year-old children born at term (177 boys, 164 girls)., Outcome Measures: Children were neurologically assessed to detect eight types of MND: mild dysfunction in posture and muscle tone, reflexes, coordination, fine manipulative ability, sensory function, cranial nerve function, choreiform dyskinesia and excessive associated movements. Cognitive function in the domains of attention, memory and language was evaluated using the Test of Everyday Attention for Children (TEA-Ch), a developmental neuropsychological assessment (NEPSY) and the Children's Memory Scale., Results: Fine manipulative disability and coordination problems were associated with lower scores on attention, memory and learning and language, other types of MND were not. Girls with coordination problems performed significantly worse on attention/executive function than those without this dysfunction; however, in boys, such association was absent., Conclusion: Particularly, fine manipulative disability and coordination problems were associated with worse cognitive function in the domains of attention, learning and memory and language. Previous and present data suggest a minor sex difference in neurocognitive associations: in girls dysfunction of the cerebello-thalamo-cortical pathways may be associated with cognitive deficits, while in boys cognitive impairment may be associated with dysfunction of cortico-striato-thalamo-cortical pathways., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Children with unilateral congenital below elbow deficiency (UCBED) lack a part of an arm, thereby lacking a part of the typical hand function. Little is known on the performance of daily activities in very young children with UCBED, usage of their affected arm with or without prosthesis during play, and neurological condition., Aim: To explore daily activities, the use of the affected limb with or without prosthesis and neurological condition over time in young children with UCBED., Design: A longitudinal observational multiple case study., Methods: Four children with UCBED were assessed (first assessment at 3-16months) every 6-8months (follow-up 13-49months) with a video-recorded, standardized play session and a neurological examination. Yearly, functioning in daily activities was evaluated using the Pediatric Evaluation of Disability Inventory - Dutch Version (PEDI-NL). Play behaviour was assessed with and without prosthesis, where applicable (n=2). Video-analysis focused on achievement, exploration, variation and adaptability of the affected limb. Behavioural changes over time were plotted and analysed visually., Results: Over time, children with UCBED showed efficient usage of their affected arm during spontaneous play. Prosthesis use seemed to be associated with reduced manipulation, exploration, variation and adaptation. Three children showed minor neurological dysfunction. Functioning in daily activities was comparable to a norm population., Conclusion: The short limb of children with UCBED is used as an exploratory, manipulatory and fixating tool from the beginning of infancy. Its value seems to be reflected in these children's normal functioning in daily life. Prosthetic use may lead to less effective performance., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: An increased risk of major congenital abnormalities after IVF and ICSI has been described, but underlying mechanisms are unclear. This study evaluates the effects of ovarian hyperstimulation, the in vitro procedure and time to pregnancy (TTP) - as proxy for the severity of subfertility - on the prevalence of dysmorphic features., Design/methods: Participants were singletons born following controlled ovarian hyperstimulation-IVF/ICSI (COH-IVF/ICSI; n=66), or modified natural cycle-IVF/ICSI (MNC-IVF/ICSI; n=56), or to subfertile couples who conceived naturally (Sub-NC; n=86). Dysmorphic features were assessed according to the method of Merks et al., and are classified into 'minor variants' (minor anomalies or common variants) and 'abnormalities' (clinically relevant or irrelevant abnormalities). We focussed on minor anomalies as they indicate altered embryonic development and because they have the advantage of a higher prevalence., Results: The prevalences of any of the outcome measures were similar in the three groups. One or more minor anomalies, our primary outcome measure, occurred in 50% of COH-IVF/ICSI, 54% of MNC-IVF/ICSI and 53% of Sub-NC children. TTP in years was significantly associated with abnormalities (adjustedOR=1.20; 95%CI=1.02-1.40), especially with clinically relevant abnormalities (adjustedOR=1.22; 95%CI=1.01-1.48)., Conclusions: The study indicates that ovarian hyperstimulation and the in vitro procedure are not associated with an increase in dysmorphic features. The positive association between TTP and clinically relevant abnormalities suggests a role of the underlying subfertility and its determinants in the genesis of dysmorphic features., (Copyright © 2012. Published by Elsevier Ireland Ltd.)

It takes >20 y before the human brain obtains its complex adult configuration. Most dramatic neurodevelopmental changes occur prenatally and early postnatally, including a major transformation in cortical organization 3-4 mo after term. The long-lasting changes have practical implications for studies evaluating the effect of prenatal and early postnatal supplementation with long-chain polyunsaturated fatty acids (LC-PUFAs). Whether studies of the effect of supplementation will reveal an effect not only depends on the dosage and duration of supplementation but also on 1) the timing of supplementation, 2) the age at which the outcome is assessed, 3) the application of age-specific sensitive neurodevelopmental tools, and 4) the functional domain evaluated. Studies of the effects of prenatal supplementation with docosahexaenoic acid (DHA) or fish oil have provided inconsistent results. However, maternal and neonatal concentrations of DHA and arachidonic acid are associated with improved outcomes in early infancy, and concentrations of DHA are associated with favorable neurodevelopmental outcome beyond early infancy. Studies of LC-PUFA supplementation in preterm infants have not shown evidence of a positive effect on neurodevelopmental outcome. Similar studies in full-term infants have indicated that supplementation with 0.30% DHA (by wt) promotes neurodevelopmental outcome in early infancy, but positive effects on later outcome have not been shown. However, information on the effects on outcomes at school age or later is virtually absent. This article stresses the need for long-term longitudinal studies that apply age-specific, sensitive neurodevelopmental tools, which also take into account lifestyle habits, maternal prepregnancy nutritional status, and genetic variation in metabolism.

Beneficial effects of perinatal DHA supply on later neurological development have been reported. We assessed the effects of maternal DHA supplementation on the neurological development of their children. Healthy pregnant women from Spain, Germany, and Hungary were randomly assigned to a dietary supplement consisting of either fish oil (FO) (500 mg/d DHA + 150 mg/d EPA), 400 μg/d 5-methyltetrahydrofolate, both, or placebo from wk 20 of gestation until delivery. Fatty acids in plasma and erythrocyte phospholipids (PL) were determined in maternal blood at gestational wk 20 and 30 and in cord and maternal blood at delivery. Neurological development was assessed with the Hempel examination at the age of 4 y and the Touwen examination at 5.5 y. Minor neurological dysfunction, neurological optimality score (NOS), and fluency score did not differ between groups at either age, but the odds of children with the maximal NOS score increased with every unit increment in cord blood DHA level at delivery in plasma PL (95% CI: 1.094-2.262), erythrocyte phosphatidylethanolamine (95% CI: 1.091-2.417), and erythrocyte phosphatidylcholine (95% CI: 1.003-2.643). We conclude that higher DHA levels in cord blood may be related to a better neurological outcome at 5.5 y of age.

Background: There is an association between rapid growth in early life and overweight in childhood. This adverse association needs to be balanced against potential beneficial effects on cognitive functioning observed in children who are born small for gestational age (SGA)., Objective: We examined potential beneficial effects of rapid growth on cognitive functions in non-SGA children., Design: We performed a systematic literature search of 3 databases. In addition, we analyzed data from the Avon Longitudinal Study on Parents and Children (ALSPAC). The association of rapid weight or length gain (defined as an increase of gt 0.67 in the SD score of weight or length between birth and the age of 25 mo) on intelligence quotient (IQ) measurements at 49 mo and 8 y (n = 836 and n = 701, respectively) was assessed in linear models adjusted for potential confounders., Results: We identified 14 studies that assessed associations between any kind of early weight gain and cognitive outcome and that included non-SGA children. No study explicitly examined the effect of rapid weight gain. In the ALSPAC data, there was no positive association between rapid weight gain and IQ scores at either 49 mo [effect estimate (95% CI): minus 1.4 ( minus 3.6, 0.7)] or 8 y [ minus 0.8 ( minus 3.4, 1.9)] in non-SGA children. Subgroup analyses with stratification by sex of the children yielded similar results, as did analyses with rapid length gain. Supplementary analyses showed no linear association between weight gain and IQ., Conclusion: We showed no evidence that proposed adverse effects of rapid growth regarding later overweight will be counterbalanced by beneficial effects on cognitive functions in non-SGA children.

Background: Children born preterm are known to be at risk for neurodevelopmental disorders. The role of perinatal asphyxia in this increased risk is still a matter of debate., Aim: To analyze the contribution of perinatal asphyxia in a population of preterm infants admitted to a secondary paediatric setting to neurological dysfunction in the first months after birth and to the development of cerebral palsy., Methods: 17 preterm infants with perinatal asphyxia born before 35 weeks postmenstrual age (PMA) and 34 carefully matched preterm controls without asphyxia were studied. Neuromotor outcome was examined by means of three assessments of the quality of general movements (GM) at "preterm" (around 34 weeks PMA), "writhing" (around term age) and "fidgety" GM age (around 3 months post term). Follow-up until at least 18 months corrected age focused on the presence of cerebral palsy (CP)., Results: GM-quality of infants with asphyxia and of those without did not differ. Multivariate analysis revealed that abnormal GMs at "preterm" age were associated with respiratory problems, those at "writhing" age with none of the assessed risk factors, and those at "fidgety" age with the severity of periventricular leukomalacia (PVL) on neonatal ultrasound scan. Perinatal asphyxia was not associated with the development of CP. CP was associated with PVL and the presence of abnormal GMs at "fidgety" age., Conclusion: Perinatal asphyxia in preterm infants is not associated with an increased risk for neurodevelopmental problems including CP. Respiratory problems during the neonatal period are associated with PVL and adverse neurological outcome., (2010 Elsevier Ltd. All rights reserved.)

Background: Parental anxiety and stress may have consequences for infant neurological development., Aims: To study relationships between parental anxiety or well-being and infant neurological development approximately one year after birth., Study Design: Longitudinal study of a birth cohort of infants born to subfertile couples., Subjects: 206 parent-child dyads., Outcome Measures: Infant neurology was assessed with the Touwen Infant Neurological Examination (TINE) at 10 months and a developmental questionnaire at 12 months. Parental measures included trait anxiety measured by the State-Trait Anxiety Inventory (STAI) and well-being measured by the General Health Questionnaire (GHQ)., Results: Maternal trait anxiety was associated with a less optimal neurological condition (r(s)= -0.19, p<0.01) of the infant. This association persisted after adjusting for confounders and results were confirmed by the outcome of the developmental questionnaire. Paternal trait anxiety and parental well-being were not related to the infant's neurodevelopmental outcome., Conclusions: Infants of mothers with high trait anxiety have an increased vulnerability to develop a non-optimal nervous system. The association may be mediated in part by early programming of monoaminergic systems. Future research should include an exploration of specific windows of vulnerability to maternal anxiety., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Background: The quality of general movements (GMs) is a sensitive tool to measure neurodevelopmental condition in early infancy. No information is available on prevalence rates of abnormal GMs in the general population., Objective: To assess the prevalence of abnormal GMs in the general population of three-month-old infants and to evaluate the association of abnormal GM quality with medical and social risk factors., Method: We recruited 535 infants in six well baby clinics in The Netherlands. GMs were video-taped at the corrected age of 2 to 4 months. GM-quality was assessed by two persons unaware of the infant's history. GM-quality was classified as normal optimal (NO), normal suboptimal (SO), mildly abnormal (MA) and definitely abnormal (DA). Only the last category implies clinically relevant dysfunction. Social, perinatal and postnatal characteristics were collected and their association with DA and abnormal (DA+MA) GMs were evaluated by means of univariate and logistic regression analyses., Results: GM-quality could be assessed reliably in 455 infants (85%). Seventeen infants (3.7%) showed DA GMs and 113 (25%) MA GMs. DA GMs were associated with preterm birth and smoking during pregnancy; abnormal (DA+MA) GMs with preterm birth, a relatively low level of paternal profession and urban living conditions. These factors explained between 3% and 7% of variance., Conclusion: The study indicates that the prevalence of definitely abnormal GMs in the general population is 3.7% and that of mildly abnormal GMs 25%. The clinically relevant definitely abnormal GMs were associated with preterm birth and smoking during pregnancy.

Background: Perinatal asphyxia may result in a developmental disorder. A recently developed non-invasive tool to investigate brain function at an early age is the assessment of general movements (GMs)., Aim: To evaluate relationships between perinatal risk factors and the quality of GMs in the neonatal period and at 3 months in term newborns with asphyxia in a secondary paediatric setting., Methods: 64 term (>36 weeks postmenstrual age (PMA)) infants with perinatal asphyxia were studied. GMs were assessed at 'writhing' GM age (38-47 weeks PMA) and at 'fidgety' GM age (48-56 weeks PMA). Pre- and perinatal factors were collected in a standardized way., Results: Multivariate analysis revealed that DA GMs at 'writhing' age mainly correlated with asphyxia related illness. DA GMs at 'fidgety' age correlated in particular with abnormalities on the neonatal ultrasound scan of the brain., Conclusion: In secondary paediatric settings GM-assessment especially around 3 months is a valuable tool for the assessment of the integrity of the nervous system in term infants with asphyxia.

Background: General movements (GMs) form the basic motility of young infants. The quality of GMs may predict neurological outcome, but little is known about relationships between GM-quality and behavioral problems, including those resulting in overt psychiatric morbidity., Aim: To explore relationships between abnormal GMs and behavioral problems, in particular relationships between abnormal GMs and Attention Deficit Hyperactivity Disorder (ADHD) with or without psychiatric co-morbidity at school-age., Methods: Twenty-five low-risk full term infants and 16 infants at high risk for neurodevelopmental disorder but without cerebral palsy were studied prospectively. GM-quality was assessed during 'writhing' age (around term till 2 months post-term) and 'fidgety' age (2-4 months post-term). GMs were classified into normal and abnormal movements. When the children were 9-12 years, parents completed the Child Behavior Checklist (CBCL) and provided information on the presence of psychiatric diagnoses; teachers completed the Teachers Report Form (TRF). Both parents and teachers completed a questionnaire on ADHD-like behavior., Results: Abnormal GMs at 'writhing' and 'fidgety' age were related to the presence of ADHD with psychiatric co-morbidity (p<0.05), but not to isolated ADHD. Abnormal GMs at 'fidgety' age were weakly related to problematic behavior at school (TRF-scores) and hyperactive behavior at home (ADHD-questionnaire)., Conclusions: This explorative study suggests that abnormal GMs in early infancy may be associated with an increased risk for behavioral problems, in particular for ADHD with psychiatric co-morbidity at school-age.

Evidence is accumulating that abundance in cerebral connectivity is the neural basis of human behavioural variability, i.e., the ability to select adaptive solutions from a large repertoire of behavioural options. Recently it was demonstrated that variability in motor behaviour- the hallmark of typical development--emerges coincident with the onset of synaptic activity in the embryonic cortex. This inspired the hypothesis that variability results from cortical activity and that its expression depends on integrity of cortical connectivity. Recent findings in preterm infants with cerebral white matter injury and in children with autism spectrum disorder (ASD) allow the elaboration of this hypothesis: diffuse damage of the cerebral white matter is associated with an overall reduction in variability, i.e., in a reduction of movement complexity and variation, whereas reduction in long-distance cortical connectivity, as described in children with ASD, is associated with reduced variability, in which movement complexity may be conserved.

Background: Few studies have examined the overall effect of maternal fish intake during pregnancy on child development or examined whether the developmental benefits of maternal fish intake are greater in infants breastfed for a shorter duration., Objective: We aimed to study associations of maternal prenatal fish intake and breastfeeding duration with child developmental milestones., Design: We studied 25 446 children born to mothers participating in the Danish National Birth Cohort, a prospective population-based cohort study including pregnant women enrolled between 1997 and 2002. Mothers reported child development by a standardized interview, which we used to generate developmental scores at ages 6 and 18 mo. We used multivariate cumulative ordinal logistic regression to evaluate the odds of higher developmental scores associated with maternal fish intake and breastfeeding, after adjustment for child age, sex, and growth; maternal size and pregnancy characteristics; and parental education and social status., Results: Higher maternal fish intake and greater duration of breastfeeding were associated with higher child developmental scores at 18 mo [odds ratio: 1.29 (95% CI: 1.20, 1.38) for the highest versus the lowest quintile of fish intake, and 1.28 (1.18, 1.38) for breastfeeding for > or =10 mo compared with breastfeeding for < or =1 mo]. Associations were similar for development at 6 mo. Associations of fish intake with child development did not differ by breastfeeding duration., Conclusions: Maternal fish intake during pregnancy and the duration of breastfeeding are independently associated with better early child development. Future research and consumption guidelines, incorporating nutritional benefits as well as contaminant risks, should consider the overall effect of prenatal fish consumption on child development.

The present paper reviews current data on the structural development of the human nervous system. Focus is on the timing of ontogenetic events in the telencephalon. Neuronal proliferation and migration especially occur during the first half of gestation; the second half of gestation is the period of the existence of the functionally important transient structure 'subplate' and the major period of glial cell proliferation and programmed cell death. Axon and dendrite sprouting and synapse formation bloom during the last trimester of gestation and the first postnatal year. Major part of telencephalic myelination occurs during the first year after birth. Many developmental processes, such as myelination, synapse formation and synapse elimination continue throughout childhood and adolescence. Evidence is emerging that the peak of synapse elimination occurs between puberty and the onset of adulthood. Neurotransmitter systems are present from early foetal life onwards and their pre- and perinatal development is characterized by periods of transient overexpression. The latter is for instance true for the acetylcholinergic, catecholaminergic and glutamate systems. Thus, the development of the human brain is characterized by a protracted, neatly orchestrated chain of specific ontogenetic events. The continuous changes of the nervous system have consequences for vulnerability to adverse conditions, for diagnostics and for physiotherapeutical intervention.

Objective: The aim of the study was to assess the relationship between acid-base status and quality and quantity of General Movements (GMs) at birth and quality of GMs at age 3 months and motor, cognitive and behavioural functioning at the age of 4 years., Methods: From a cohort of 84 term children with different umbilical artery pH without severe neonatal neurological abnormalities, GMs were assessed at term and at 3 months. At the age of 4 years, 44 children were assessed by means of the Movement Assessment Battery for Children (Movement-ABC), Neurological Examination for Toddlers of Hempel, Kaufman Assessment Battery for Children information processing (Kaufman ABC), Visuomotor Integration (VMI), the Child Behaviour Checklist (CBCL) and Precursors ADHD Questionnaire (PAQ)., Results: We found no relationship between pH or GM-quality and quantity at term or GM-quality at 3 months and scores on most of the items of the Movement-ABC, cognitive and behavioural outcome. However, neonatal pH value and GM-quality at 3 months were related to some extent to the presence of subtle signs of neuromotor dysfunction as measured by the Hempel test., Conclusions: In a sample of infants with a large variation in umbilical artery pH and without severe neonatal neurological abnormalities, acid-base status at birth and quality of GMs at 3 months of age is not predictive for motor milestone achievement, cognitive and behavioural functioning at 4 years, but these parameters are related to a less optimal condition of the nervous system. The latter finding has, however, limited clinical significance.

Background: Whether long-chain polyunsaturated fatty acids (LCPs) play a role in the development of the young nervous system in term infants is debated., Objective: We investigated whether supplementation of formula with LCPs for 2 mo improves the quality of general movements (GMs) in healthy term infants at 3 mo of age., Design: A prospective, double-blind, randomized controlled study was conducted with 2 groups of healthy term infants: a control-formula (CF) group (n = 131) and an LCP-supplemented-formula (LF) group (n = 119). A breastfed (BF) group (n = 147) served as a reference. Information on potential confounders was collected at enrollment. Videotapes were made of the infants' spontaneous motor behavior at 3 mo of age to assess the quality of their GMs. On the basis of quality, normal GMs were classified as normal-optimal or normal-suboptimal, and abnormal GMs were classified as mildly or definitely abnormal. Attrition at 3 mo of age was 15% and nonselective. Multivariate regression analyses with adjustment for confounders were carried out to evaluate the effect of the type of feeding., Results: None of the infants had definitely abnormal GMs. Infants in the CF group had mildly abnormal GMs significantly more often than did infants in the LF and BF groups (31% compared with 19% and 20%, respectively). Infants in the BF group had normal-optimal GMs more frequently than did infants in the LF and CF groups (34% compared with 18% and 21%, respectively). Logistic regression analyses confirmed these findings., Conclusion: Supplementation of healthy term infants with LCPs during the first 2 mo of life reduces the occurrence of mildly abnormal GMs.