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Over de functionele gevolgen op latere leeftijd van de matige start bij de geboorte is nog weinig bekend. In het Gelre Ziekenhuis te Apeldoorn werden 64 op tijd geborenen met een matige start en 81 controlekinderen gevolgd, bij wie in de jonge babyperiode hun general movements(GMs) werden beoordeeld. Hoe meer variatie deze bewegingen vertonen, hoe gezonder het zenuwstelsel is. GM-kwaliteit is een goede voorspeller voor de verdere ontwikkeling. De kinderen werden op zesjarige leeftijd opnieuw uitgebreid onderzocht, met speciale aandacht voor motorische activiteiten. Bij een matige start na de geboorte die leidt tot neonatale neurologische symptomen, blijken kinderen op zesjarige leeftijd een verhoogde kans te hebben op ontwikkelingsproblemen, vooral in de fijne motoriek. Verder voorspelt de GM-kwaliteit bij op tijd geboren kinderen zonder ernstige problemen bij de geboorte wel in zekere mate de ontwikkeling van latere problemen, maar minder goed dan bij te vroeg geboren kinderen. Geadviseerd wordt om de ontwikkeling van op tijd geboren kinderen met een matige start, die neonatale neurologische symptomen vertonen, zorgvuldig te monitoren, te beginnen met het monitoren van de GMs in de eerste levensmaanden van het kind.

UNICEF and other international bodies must produce a clear plan that prioritizes development and education for children with disabilities, especially in low- and middle-income settings, as required for achieving the United Nations Sustainable Development Goals.

IMPORTANCE: Cerebral palsy (CP) is the most common childhood physical disability. Early intervention for children younger than 2 years with or at risk of CP is critical. Now that an evidence-based guideline for early accurate diagnosis of CP exists, there is a need to summarize effective, CP-specific early intervention and conduct new trials that harness plasticity to improve function and increase participation. Our recommendations apply primarily to children at high risk of CP or with a diagnosis of CP, aged 0 to 2 years. OBJECTIVE: To systematically review the best available evidence about CP-specific early interventions across 9 domains promoting motor function, cognitive skills, communication, eating and drinking, vision, sleep, managing muscle tone, musculoskeletal health, and parental support. EVIDENCE REVIEW: The literature was systematically searched for the best available evidence for intervention for children aged 0 to 2 years at high risk of or with CP. Databases included CINAHL, Cochrane, Embase, MEDLINE, PsycInfo, and Scopus. Systematic reviews and randomized clinical trials (RCTs) were appraised by A Measurement Tool to Assess Systematic Reviews (AMSTAR) or Cochrane Risk of Bias tools. Recommendations were formed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and reported according to the Appraisal of Guidelines, Research, and Evaluation (AGREE) II instrument. FINDINGS: Sixteen systematic reviews and 27 RCTs met inclusion criteria. Quality varied. Three best-practice principles were supported for the 9 domains: (1) immediate referral for intervention after a diagnosis of high risk of CP, (2) building parental capacity for attachment, and (3) parental goal-setting at the commencement of intervention. Twenty-eight recommendations (24 for and 4 against) specific to the 9 domains are supported with key evidence: motor function (4 recommendations), cognitive skills (2), communication (7), eating and drinking (2), vision (4), sleep (7), tone (1), musculoskeletal health (2), and parent support (5). CONCLUSIONS AND RELEVANCE: When a child meets the criteria of high risk of CP, intervention should start as soon as possible. Parents want an early diagnosis and treatment and support implementation as soon as possible. Early intervention builds on a critical developmental time for plasticity of developing systems. Referrals for intervention across the 9 domains should be specific as per recommendations in this guideline.

Supplemental Digital Content is Available in the Text.This study investigates the postural effects of a family-centered program applied at 3-6 months corrected age in infants at high risk of cerebral palsy.

Supplemental Digital Content is Available in the Text.This study monitored changes in time spent on pediatric physical therapy actions during a ‘COPing with and CAring for Infants with special Needs’ course.

IMPORTANCE: Cerebral palsy describes the most common physical disability in childhood and occurs in 1 in 500 live births. Historically, the diagnosis has been made between age 12 and 24 months but now can be made before 6 months’ corrected age. OBJECTIVES: To systematically review best available evidence for early, accurate diagnosis of cerebral palsy and to summarize best available evidence about cerebral palsy–specific early intervention that should follow early diagnosis to optimize neuroplasticity and function. EVIDENCE REVIEW: This study systematically searched the literature about early diagnosis of cerebral palsy in MEDLINE (1956-2016), EMBASE (1980-2016), CINAHL (1983-2016), and the Cochrane Library (1988-2016) and by hand searching. Search terms included cerebral palsy, diagnosis, detection, prediction, identification, predictive validity, accuracy, sensitivity, and specificity. The study included systematic reviews with or without meta-analyses, criteria of diagnostic accuracy, and evidence-based clinical guidelines. Findings are reported according to the PRISMA statement, and recommendations are reported according to the Appraisal of Guidelines, Research and Evaluation (AGREE) II instrument. FINDINGS: Six systematic reviews and 2 evidence-based clinical guidelines met inclusion criteria. All included articles had high methodological Quality Assessment of Diagnostic Accuracy Studies (QUADAS) ratings. In infants, clinical signs and symptoms of cerebral palsy emerge and evolve before age 2 years; therefore, a combination of standardized tools should be used to predict risk in conjunction with clinical history. Before 5 months’ corrected age, the most predictive tools for detecting risk are term-age magnetic resonance imaging (86%-89% sensitivity), the Prechtl Qualitative Assessment of General Movements (98% sensitivity), and the Hammersmith Infant Neurological Examination (90% sensitivity). After 5 months’ corrected age, the most predictive tools for detecting risk are magnetic resonance imaging (86%-89% sensitivity) (where safe and feasible), the Hammersmith Infant Neurological Examination (90% sensitivity), and the Developmental Assessment of Young Children (83% C index). Topography and severity of cerebral palsy are more difficult to ascertain in infancy, and magnetic resonance imaging and the Hammersmith Infant Neurological Examination may be helpful in assisting clinical decisions. In high-income countries, 2 in 3 individuals with cerebral palsy will walk, 3 in 4 will talk, and 1 in 2 will have normal intelligence. CONCLUSIONS AND RELEVANCE: Early diagnosis begins with a medical history and involves using neuroimaging, standardized neurological, and standardized motor assessments that indicate congruent abnormal findings indicative of cerebral palsy. Clinicians should understand the importance of prompt referral to diagnostic-specific early intervention to optimize infant motor and cognitive plasticity, prevent secondary complications, and enhance caregiver well-being.

Supplemental Digital Content is Available in the Text.This study assesses the reliability and completeness of the Groningen Observation Protocol to quantify contents of pediatric physical therapy.

Background:Following our clinical observation of tonic responses in response to the knee jerk in infants at very high risk for cerebral palsy (VHR infants), we systematically studied tonic responses, clonus, and reflex irradiation. We questioned (i) whether these responses occurred more often in VHR infants than in typically developing (TD) infants, and (ii) whether they were associated with abnormal general movement quality.Methods:Twenty-four VHR and 26 TD infants were assessed around 3 mo corrected age. Surface electromyograms of leg, trunk, neck, and arm muscles were recorded while eliciting the knee jerk. All assessments were video-recorded.Results:VHR infants more often than TD infants showed tonic responses in the ipsilateral quadriceps and hamstring (Mann-Whitney U; P = 0.0005 and P = 0.0009), clonus (Chi-square; P = 0.0005) and phasic responses in the contralateral quadriceps and hamstring (Mann-Whitney U; P = 0.002 and P = 0.0003, respectively). Widespread reflex irradiation occurred in VHR and TD infants. Definitely abnormal general movements and stiff movements were associated with tonic responses (Mann-Whitney U; P = 0.0005, P = 0.007, respectively) and clonus (Mann-Whitney U; P = 0.003 and P = 0.0005) in the ipsilateral quadriceps.Conclusion:Similar to clonus, tonic responses may be regarded as a marker of a loss of supraspinal control. Reflex irradiation primarily is a neurodevelopmental phenomenon of early ontogeny.

Reliability scoring the Infant Motor Profile demonstrated good intra and inter-rater reliability (after 2 days of training) for most domains with the exception of symmetry.

Since publication of DSM-IV in 1994, the prevalence of parent-reported diagnosed attentiondeficithyperactivity disorder (ADHD) has tripled to more than 10 of children. Although it is hard to know for sure whether ADHD is overdiagnosed, underdiagnosed, or misdiagnosed, it is argued that ADHD is especially prone to diagnostic inflation and overdiagnosis. Therefore, we propose a model of stepped diagnosis for childhood ADHD, which may reduce overdiagnosis without risking undertreatment. Calling attention to stepped diagnosis and formalizing the steps may improve its application in clinical practice. (Journal of Psychiatric Practice2014;20:169–177)

Background:Recent studies suggest that in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are associated with suboptimal cardiometabolic outcome in offspring. It is unknown whether preimplantation genetic screening (PGS), which involves embryo biopsy, affects blood pressure (BP), anthropometrics, and the frequency of received medical care.Methods:In this prospective multicenter follow-up study, we assessed BP, anthropometrics, and received medical care of 4-y-old children born to women who were randomly assigned to IVF/ICSI with PGS (n = 49) or without PGS (controls; n = 64). We applied linear and generalized linear mixed-effects models to investigate possible effects of PGS.Results:BP in the PGS and control groups was similar: 102/64 and 100/64 mm Hg, respectively. Main anthropometric outcomes in the PGS vs. control group were: BMI: 16.1 vs. 15.8; triceps skinfold: 108 vs. 98?mm; and subscapular skinfold: 54 vs. 53?mm (all P values > 0.05). More PGS children than controls had received paramedical care (speech, physical, or occupational therapy: 14 (29%) vs. 9 (14%); P = 0.03 in multivariable analysis). The frequency of medicial treatment was comparable.Conclusion:PGS does not seem to affect BP or anthropometrics in 4-y-old children. The higher frequency of received paramedical care after PGS may suggest an effect of PGS on subtle developmental parameters.

Background:The aim of this work was to investigate in a prospective study whether moderate hyperbilirubinemia in healthy term neonates is associated with an increase of minor neurological dysfunction (MND) and behavioral problems up to 18 mo.Method:We enrolled 43 healthy term infants with a bilirubin level =220 µmol/l (BILI group) at 72–96?h postnatally at the University Medical Center Groningen (UMCG), including eight referrals for hyperbilirubinemia. Seventy healthy term infants born at the UMCG with bilirubin level <220 µmol/l served as comparisons (COMP group). We evaluated the neurologic condition neonatally and at 3 and 18 mo; behavior was evaluated at birth and 18 mo.Results:Rates of MND in BILI and COMP groups were similar at all ages. However, bilirubin levels of =300 µmol/l (n = 10) were associated with an increased risk of complex MND (odds ratio: 4.21; 95% confidence interval: 1.02–17.37). Neonatally, BILI infants were more often lethargic than COMP infants (odds ratio: 3.54; 95% confidence interval: 1.32–9.51); at 18 mo, they had higher hyperactivity scores (effect: 0.32; 95% confidence interval: 0.08–0.56).Conclusion:Occurrence of complex MND at 18 mo in infants with moderate hyperbilirubinemia was not different from that in comparison infants, but bilirubin level =300 was associated with an increased risk of complex MND. This study also suggests that minor behavioral effects of moderate hyperbilirubinemia cannot be excluded.

To evaluate longitudinal applicability of the Gross Motor Function Measure (GMFM) in infants younger than 2 years.

Conflicting evidence exists on the effect of long-chain polyunsaturated fatty acid (LCPUFA) formula supplementation on cardiovascular health in term infants. It is known that LCPUFA supplementation does not affect infant growth, but long term outcome data are not available. The current study investigates whether 2 mo LCPUFA formula supplementation affects cardiovascular and anthropometric development at 9 y. A prospective, double-blind, randomized trial was performed in healthy term infants: a standard formula control group (CF, n = 169) and a LCPUFA-supplemented group [LF, n = 145; 0.45% (by wt) AA and 0.30% (by wt) docosahexaenoic acid (DHA)]. A breastfed group (BF; n = 159) served as reference. At the age of 9 y, systolic and diastolic blood pressure, heart rate, head circumference, weight, and height were measured. Univariate and multivariate analyses were performed; 63 to 79% of children were assessed. None of the cardiovascular or anthropometric measurements differed between the formula groups. Breastfed children had a marginally lower heart rate than formula-fed children, in particular compared with children fed control formula. Blood pressure and parameters of growth including BMI of breast and formula-fed children did not differ. In conclusion, the study suggests that short-term LCPUFA supplementation does not influence cardiovascular and anthropometric development at 9 y.

Conflicting evidence exists on the effect of long-chain polyunsaturated fatty acid (LCPUFA) formula supplementation on cardiovascular health in term infants. It is known that LCPUFA supplementation does not affect infant growth, but long term outcome data are not available. The current study investigates whether 2 mo LCPUFA formula supplementation affects cardiovascular and anthropometric development at 9 y. A prospective, double-blind, randomized trial was performed in healthy term infants: a standard formula control group (CF, n169) and a LCPUFA-supplemented group LF, n145; 0.45% (by wt) AA and 0.30% (by wt) docosahexaenoic acid (DHA). A breastfed group (BF; n159) served as reference. At the age of 9 y, systolic and diastolic blood pressure, heart rate, head circumference, weight, and height were measured. Univariate and multivariate analyses were performed; 63 to 79% of children were assessed. None of the cardiovascular or anthropometric measurements differed between the formula groups. Breastfed children had a marginally lower heart rate than formula-fed children, in particular compared with children fed control formula. Blood pressure and parameters of growth including BMI of breast and formula-fed children did not differ. In conclusion, the study suggests that short-term LCPUFA supplementation does not influence cardiovascular and anthropometric development at 9 y.

This article reviews developmental processes in the human brain and basic principles underlying typical and atypical motor development. The Neuronal Group Selection Theory is used as theoretical frame of reference. Evidence is accumulating that abundance in cerebral connectivity is the neural basis of human behavioral variability (ie, the ability to select, from a large repertoire of behavioral solutions, the one most appropriate for a specific situation). Indeed, typical human motor development is characterized by variation and the development of adaptive variability. Atypical motor development is characterized by a limited variation (a limited repertoire of motor strategies) and a limited ability to vary motor behavior according to the specifics of the situation (ie, limited variability). Limitations in variationare related to structural anomalies in which disturbances of cortical connectivity may play a prominent role, whereas limitations in variabilityare present in virtually all children with atypical motor development. The possible applications of variation and variability in diagnostics in children with or at risk for a developmental motor disorder are discussed.

Aim of this study was to evaluate the effect of preimplantation genetic screening (PGS) on neurodevelopmental outcome in children. We conducted a prospective follow-up study of children born to women randomly assigned to in vitro fertilization with or without PGS. Primary outcome was adverse neurologic outcome at 18 mo; secondary outcomes were types of minor neurologic dysfunction (MND), neurologic outcome before 18 mo, neonatal intensive care admission, and congenital malformations. Twenty women in the PGS group participated with 25 children and 26 women in the control group participated with 31 children. Five PGS pregnancies (25%) and four control pregnancies (15%) resulted in birth of at least one child with an adverse neurologic outcome (adjusted odds ratio: 2.3 [0.4–12.0]). Dysfunction in fine motor abilities and posture and muscle tone dysregulation tended to be present more frequently after PGS. Neurologic outcome before 18 mo, neonatal intensive care admission, and prevalence of congenital malformations were similar in study and control pregnancies. Nevertheless, at child level, rates of adverse outcome were higher after PGS. In conclusion, outcome in pregnancies after in vitro fertilization (IVF) with and without PGS was similar. The small sample size precludes the conclusion that PGS is not associated with less favorable neurologic outcome. Safety of new assisted reproductive techniques should be evaluated before large-scale implementation.

Aim of this study was to evaluate the effect of preimplantation genetic screening (PGS) on neurodevelopmental outcome in children. We conducted a prospective follow-up study of children born to women randomly assigned to in vitrofertilization with or without PGS. Primary outcome was adverse neurologic outcome at 18 mo; secondary outcomes were types of minor neurologic dysfunction (MND), neurologic outcome before 18 mo, neonatal intensive care admission, and congenital malformations. Twenty women in the PGS group participated with 25 children and 26 women in the control group participated with 31 children. Five PGS pregnancies (25%) and four control pregnancies (15%) resulted in birth of at least one child with an adverse neurologic outcome (adjusted odds ratio: 2.3 0.4–12.0). Dysfunction in fine motor abilities and posture and muscle tone dysregulation tended to be present more frequently after PGS. Neurologic outcome before 18 mo, neonatal intensive care admission, and prevalence of congenital malformations were similar in study and control pregnancies. Nevertheless, at child level, rates of adverse outcome were higher after PGS. In conclusion, outcome in pregnancies after in vitrofertilization (IVF) with and without PGS was similar. The small sample size precludes the conclusion that PGS is not associated with less favorable neurologic outcome. Safety of new assisted reproductive techniques should be evaluated before large-scale implementation.

The study aim was to describe and quantify physical therapy interventions for infants at high risk for developmental disorders.

To find out whether supplementation of formula milk by long-chain polyunsaturated fatty acids (LCPUFA) affects neurodevelopment at 18 months of age in term or preterm infants by an individual patient data (IPD) meta-analysis.

To find out whether supplementation of formula milk by long-chain polyunsaturated fatty acids (LCPUFA) affects neurodevelopment at 18 months of age in term or preterm infants by an individual patient data (IPD) meta-analysis. Data of 870 children from 4 large randomised clinical trials for formula milk with and without LCPUFAs allowed for assessing the effect of LCPUFA with adjustment for potential confounders and extensive subgroup analysis on prematurity, LCPUFA source, and dosage. Any additional clinical trials examining the effect of LCPUFA supplementation on Bayley Scales of Infant Development at 18 months were regarded as relevant. Two relevant studies were identified by MEDLINE, but were not available to us. An IPD meta-analysis was performed with subgroup analyses by preterm delivery, very low birth weight (<1500 g), trials with higher amounts of docosahexaenoic acid (DHA) and arachidonic acid (AA), and specific sources of LCPUFA. The sample size of 870 children was sufficient to detect clinically relevant differences in Bayley Scales even in subgroups. There were no significant differences in mental or psychomotor developmental indexes between LCPUFA-supplemented and control groups for all children or in subgroups. This was confirmed with adjustment for the possible confounders: sex, gestational age, birth weight, maternal age, and maternal smoking. The adjusted mean differences in mental developmental index and psychomotor developmental index for all of the children were -0.8 (95% confidence interval -2.8 to 1.2) and -1.0 (-2.7 to 0.7), respectively. These data based on considerable sample size provide substantial evidence that LCPUFA supplementation of infant formula does not have a clinically meaningful effect on the neurodevelopment as assessed by Bayley scores at 18 months. Inclusion of all relevant data should not have led to differing conclusions except, possibly, for very-low-birth-weight infants.

Perinatal qualitative assessment of general movements (GMs) is a tool to evaluate the integrity of the young nervous system. The aim of this investigation was to study the emergence of GMs. Fetal onset of GMs was studied sonographically in 18 fetuses during the first trimester of uncomplicated in vitro fertilization (IVF) pregnancies in weekly assessments. The earliest motility consisting of small and simple sideways bending (SB) of head and/or rump starts at 7 wk, lasting about 1 s. Between 7 and 8.5 wk, motility differentiates further into movements in which also one or two arms or legs become active; movements are still slow, small, and in one direction, but the duration increases to a few seconds. The transition into GMs at 9–10 wk is characterized by variation in participating body parts and amplitude, speed, and direction during longer periods of time. Between 9 and 13 wk, simple and stereotyped SBs and GMs may coexist. At 9 wk, the incidence of SBs decreases (p = 0.01) and that of GMs increases (p = 0.006). The data suggest that initial simple fetal motility is generated by spinal and brainstem circuitries, and the emergence of complex and variable GMs denotes the onset of supraspinal modulation of this spinal and brainstem activity.

Perinatal qualitative assessment of general movements (GMs) is a tool to evaluate the integrity of the young nervous system. The aim of this investigation was to study the emergence of GMs. Fetal onset of GMs was studied sonographically in 18 fetuses during the first trimester of uncomplicated in vitrofertilization (IVF) pregnancies in weekly assessments. The earliest motility consisting of small and simple sideways bending (SB) of head and/or rump starts at 7 wk, lasting about 1 s. Between 7 and 8.5 wk, motility differentiates further into movements in which also one or two arms or legs become active; movements are still slow, small, and in one direction, but the duration increases to a few seconds. The transition into GMs at 9–10 wk is characterized by variation in participating body parts and amplitude, speed, and direction during longer periods of time. Between 9 and 13 wk, simple and stereotyped SBs and GMs may coexist. At 9 wk, the incidence of SBs decreases (p0.01) and that of GMs increases (p0.006). The data suggest that initial simple fetal motility is generated by spinal and brainstem circuitries, and the emergence of complex and variable GMs denotes the onset of supraspinal modulation of this spinal and brainstem activity.

Prenatal long-chain polyunsaturated fatty acids (LCPUFAs) and trans-fatty acids may affect neurodevelopment. In healthy term children, we determined relationships between relative fatty acid contents of umbilical arteries and veins and neurodevelopment at 18 mo. The study comprised a mixed group of 317 breast-fed, formula-fed, and LCPUFA formula-fed children. Study endpoints were the Hempel neurologic examination resulting in a neurologic classification and neurologic optimality score (NOS), and the Bayley Psychomotor Developmental Index (PDI) and Mental Developmental Index (MDI). Fifteen children showed minor neurologic dysfunction (MND). The umbilical vein trans, trans-18:2n-6 content was higher in children with MND than in the normal group. The NOS was significantly reduced in infants with an umbilical vein docosahexaenoic acid (DHA) content within the lowest quartile. Umbilical vein arachidonic acid (AA) was related to NOS in univariate statistics but not in multivariate analyses. The sum of trans-fatty acids and that of C18 trans-fatty acids showed a negative association with NOS in both univariate and multivariate analyses. No associations were found between AA, DHA and total trans-fatty acids with PDI or MDI. In conclusion, neonates with a relatively low DHA status and those with high trans-fatty acid levels have a less favorable neurologic condition at 18 mo.