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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.

Background. A difficult birth at term (DBAT) may manifest as fetal acidosis and low Apgar scores and is often referred to as 'perinatal asphyxia,' especially when infants show signs of neonatal encephalopathy (NE). In contrast to DBAT resulting in moderate-to-severe NE, which is associated with neurodevelopmental disorders, little is known about the prognosis of less severe forms of DBAT, with or without NE. Objective. The purpose of this study was to evaluate the International Classification of Functioning, Disability and Health, Children & Youth Version activity 'mobility' and other neurodevelopmental sequelae in infants with DBAT at age 6 years. Methods. The index cohort (n=62; 35 boys, 27 girls) consisted of consecutive term infants with DBAT based on clinical criteria in a Dutch nonacademic hospital from 1999 to 2005. Neonatal encephalopathy was assessed according to the Samat grading system and excluded infants with severe NE. The matched reference cohort (n=81; 49 boys, 32 girls) consisted of healthy term infants. The primary outcome at 6 years was limited mobility (Movement Assessment Battery for Children score < 15th percentile). Secondary outcomes included learning and behavioral problems and the presence of minor neurological dysfunction. Results. Three children developed cerebral palsy and were excluded from analyses. Children with DBAT more often had limited mobility than children without DBAT (risk ratio [RR]=2.44; 95% confidence interval [95% CI] = 1.16, 5.14). The risk of limited mobility rose with increasing severity of NE (mild NE: RR=3-38; 95% CI=1.40, 8.16; moderate NE: RR=4.00; 95% 0=1.54, 10.40), and manual abilities especially were affected (RR=4.12; 95% 0=1.40, 12.14). Learning problems, need for physical therapy, and complex minor neurological dysfunction were more common in children with DBAT than in children without DBAT. Conclusions. Term infants who develop mild or moderate NE following DBAT are at increased risk for limited mobility at age 6 years. Routine monitoring of neuromotor development in these children is warranted., In industrialized countries, 1 in 1,000 infants has a difficult birth at term (DBAT), (1) which may manifest as an abnormal fetal cardiotocogram, fetal acidosis, and low Apgar scores. (2,3) [...]

Background. It is debatable whether adaptive riding (AR) in children with cerebral palsy (CP) improves postural control and gross motor development. Objective. The study aim was to explore the feasibility of an extensive assessment protocol for a randomized controlled trial of therapist-designed adaptive riding (TDAR) in children with CP, with the goals of assessing the effect on child outcomes and evaluating working mechanisms of sitting postural control. Design. A pretest-posttest group design with 2 baseline measurements was used. Methods. Six children (1 girl, 5 boys; age range = 6-12 years, median age = 8 years 9 months) with bilateral spastic CP (Gross Motor Function Classification System level III) participated. Outcomes were evaluated 3 times (T0, T1, and T2) at 6-week intervals. T0 and T1 were baseline measurements; between T1 and T2, a TDAR intervention including an integrated program of postural challenge exercises (2 times per week for 1 hour) was applied. The complex protocol included the 88-item Gross Motor Function Measure (GMFM-88) and electromyographic (EMG) recording of postural muscle activity during reaching while sitting (EMG recording at T1 and T2 only). Results. The protocol was feasible. Median GMFM-88 scores changed from 64.4 at T0 to 66.7 at T1 and from 66.7 at T1 to 73-2 at T2. The change scores for all children exceeded the minimal clinically important difference of the GMFM-88. Five of 6 children showed a decrease in stereotyped top-down recruitment between T1 and T2. Limitations. Study limitations included the lack of a control group, small sample size, and potential assessor bias for all but the EMG parameters. Conclusions. The feasibility of the complex protocol was established. The data suggested that a 6-week TDAR intervention may improve gross motor function and may reduce stereotyped postural adjustments in children with CP. The limited results warrant replication in a well-powered randomized controlled trial., Equine-assisted activities and therapies are frequently used in children with cerebral palsy (CP). (1,2) However, it is debatable whether equine-assisted activities and therapies are effective in reducing bodily impairments, such [...]

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.

Background. Evidence for effectiveness of pediatric physical therapy in infants at high risk for developmental motor disorders is limited. Therefore, 'Coping With and Caring for Infants With Special Needs' (COPCA), a family-centered, early intervention program, was developed. The COPCA program is based on 2 components: (1) family involvement and educational parenting and (2) the neuromotor principles of the neuronal group selection theory. The COPCA coach uses principles of coaching to encourage the family's own capacities for solving problems of daily care and incorporating variation, along with trial and error in daily activities. Objective. The purpose of this study was to evaluate whether the content of sessions of the home-based, early intervention COPCA program differs from that of traditional infant physical therapy (TIP) sessions, which in the Netherlands are largely based on neurodevelopmental treatment. Setting. The study was conducted at the University Medical Center Groningen in the Netherlands. Design. A quantitative video analysis of therapy sessions was conducted with infants participating in a 2-arm randomized trial. Patients and Intervention. Forty-six infants at high risk for developmental motor disorders were randomly assigned to receive COPCA (n = 21) or TIP (n = 25) between 3 and 6 months corrected age. Intervention sessions were videotaped at 4 and 6 months corrected age and analyzed with a standardized observation protocol for the classification of physical therapy actions. Outcome parameters were relative amounts of time spent on specific physical therapy actions. Results. The content of COPCA and TIP differed substantially. For instance, in TIP sessions, more time was spent on facilitation techniques, including handling, than in COPCA sessions (29% versus 3%, respectively). During COPCA, more time was spent on family coaching and education than during TIP (16% versus 4%, respectively). Limitations. The major limitation of the study was its restriction to the Netherlands, implying that findings cannot be generalized automatically to other countries. Conclusion. The COPCA program differs broadly from TIP as applied in the Netherlands. Studies on the effectiveness of this family-centered program are needed., The evidence of the effectiveness of traditional physical therapy, based on neurodevelopmental treatment, in infants with special needs is inconclusive. This study describes the family-centered program 'Coping With and Caring [...]

Background. Systematic reviews have suggested that early intervention by means of specific motor training programs and general developmental programs in which parents learn how to promote infant development may be the most promising ways to promote infant motor and cognitive development of infants with or at high risk for developmental motor disorders. Objective. The purpose of this study was to investigate the effects of a recently developed pediatric physical therapy intervention program ('Coping With and Caring for Infants With Special Needs' [COPCA]) on the development of infants at high risk for developmental disorders using a combined approach of a 2-arm randomized trial and process evaluation. Setting. The study was conducted at the University Medical Center Groningen in the Netherlands. Participants and Intervention. Forty-six infants at high risk for developmental disorders were randomly assigned to receive COPCA (a family-centered program) (n=21) or traditional infant physical therapy (TIP) (n=25) between 3 to 6 months corrected age (CA). Developmental outcome was assessed by blinded assessors at 3, 6, and 18 months CA with a neurological examination, the Alberta Infant Motor Scales, the Pediatric Evaluation of Disability Inventory, and the Mental Developmental Index (MDI) of the Bayley Scales of Infant Development. Contents of the intervention were analyzed by a quantitative video analysis of therapy sessions. Quantified physical therapy actions were correlated to evaluate associations between intervention and developmental outcome components. Results. The trial revealed that developmental outcome in both groups was largely identical. Process evaluation showed that typical COPCA actions--(1) family involvement and educational actions, (2) application of a wide variation in challenging the infant to produce motor behavior by himself or herself and allowing the infant to continue this activity, and (3) stimulation of motor behavior at the limit of the infant's capabilities--had positive correlations with developmental outcome at 18 months CA. The use of handling techniques was negatively associated with the Pediatric Evaluation of Disability Inventory outcome at 18 months CA. Limitations. Major limitations were the limited size of the groups studied and the differences between the groups in frequency and duration of physical therapy sessions. Conclusion. Extending the randomized trial with process evaluation was needed to obtain insight into associations between the components of intervention and developmental outcome. Specific therapist behaviors of parent coaching are associated with improved developmental outcome measures. Further studies are needed to examine whether these associations are caused by therapist behavior or whether therapist behavior is modified by children's motor skills., The evidence for the effectiveness of pediatric physical therapy for infants with developmental disorders is inconclusive. Specific motor-training programs and general developmental programs seem to offer the most promise in [...]

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 variation are related to structural anomalies in which disturbances of cortical connectivity may play a prominent role, whereas limitations in variability are 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., Human behavior is characterized by variation: each human individual has a large repertoire of motor, cognitive, and social actions that can be arranged in virtually endless combinations. This repertoire allows [...]

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 >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): -1.4 (-3.6, 0.7)] or 8 y [-0.8 (-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. doi: 10.3945/ajcn.2009.29116

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 develop mental 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 too. 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 [greater than or equal to] 10 mo compared with breastfeeding for [less than or equal to]1 mo]. Associations were similar for development at 6 too. Associations offish 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. Am J Clin Nutr 2008;88:789-96.

Background and Purpose Because it is debatable whether seat surface inclination improves motor function in children with cerebral palsy (CP), the effect of seat surface tilting on postural control and quality of reaching was studied. Subjects The subjects were 58 children with CP aged 2 to 11 years (34 with unilateral spastic CP, 24 with bilateral spastic CP). Methods During the task of reaching movements, surface electromyographic and kinematic data were recorded for posture and reaching with the dominant arm in 3 sitting conditions: horizontal seat surface, seat surface tilted forward 15 degrees, and seat surface tilted backward 15 degrees. Results In the children with unilateral spastic CP, forward tilting improved postural efficiency and quality of reaching. In the children with bilateral spastic CP, both forward and backward tilting of the seat surface was associated with more postural instability and did not affect the quality of reaching. Discussion and Conclusion The results suggest that, in terms of postural control and quality of reaching, children with unilateral spastic CP benefit from a forward-tilted position and children with bilateral spastic CP benefit from a horizontal sitting position., Children with cerebral palsy (CP) often are hampered by dysfunctional postural control. (1,2) It is debatable whether postural control of sitting in children with CP can be enhanced by inclination [...]

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. KEY WORDS General movements, long-chain polyunsaturated fatty acids, infants, nutrition, nervous system, motor development, breastfeeding, term infants, n-3 fatty acids, docosahexaenoic acid

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.

Although research results suggest that antiepileptic medication is teratogenic (causes birth defects), in practice it is difficult to separate drug effects from effects due to maternal seizures themselves or to social and economic risk factors, also elevated among epileptic women. A study was carried out to disentangle these effects, using 61 children selected from a larger sample born to 132 epileptic mothers. None of these women had seizures during the pregnancy. The mothers had taken phenobarbital only (13 subjects); carbamazepine only (12); both drugs (12); or no antiepileptic drugs at all (24) during pregnancy; a matched control group was also selected. The study was long-term; the current report concerns 57 children between the ages of 6 and 13. The children underwent neurologic examination (and were scored as either normal, presence of minor neurologic dysfunctions, or abnormal); testing for reading, spelling, and arithmetic; and behavioral evaluation. Results showed no differences between the children of epileptic mothers and controls in the rate of minor neurologic dysfunction. However, the group born to mothers from the phenobarbital-only group had a higher proportion of poor performers on the arithmetic and spelling tests. No differences were found for other measures of cognitive development or behavior. Physical measurements revealed normal weight and height for all children, but skull circumferences for phenobarbital-only children were smaller (this may be linked to an adverse effect on cognitive development). A greater proportion of the children of epileptic mothers (including those whose mothers had not taken an antiepileptic drug) than controls had minor physical abnormalities (abnormality of posture, muscle tone, or coordination). Thus both major and minor birth defects seem to be associated more closely with the maternal epilepsy than the medication taken during pregnancy. But the results also suggest that phenobarbital may be a potential teratogen; the issue deserves further investigation. (Consumer Summary produced by Reliance Medical Information, Inc.)

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.

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.

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.

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.

Prenatal essential fatty acid (EFA) status might be an important factor in the development of the central nervous system (CNS). The aim of the present study was to evaluate the relationship between the fatty acid compositions of the umbilical blood vessels at birth, used as a proxy of prenatal EFA status, and quality of general movements (GMs) at 3 mo. Umbilical artery and vein fatty acid compositions were investigated in a mixed group of breastfed infants and infants fed with formula with or without long-chain polyunsaturated fatty acid (LCPUFA) supplementation. At the age of 3 mo, video assessment of the quality of GMs was performed to evaluate neurologic condition. The quality of GMs was scored by assessing the degree of variation, complexity, and fluency. Outcomes were classified as normal-optimal, normal suboptimal, mildly abnormal, and definitely abnormal movements. Information on potential confounders, including the type of postnatal feeding, was collected prospectively. Associations between fatty acid status at birth and quality of GMs were investigated, and multinomial logistic regression analyses were carried out. None of the infants showed definitely abnormal movements. Infants with mildly abnormal GMs had a lower EFA index, lower arachidonic acid (AA) content, higher total n-9 fatty acid, and higher total monounsaturated fatty acid (MUFA) content in the umbilical artery compared with infants with normal GMs. Multivariate analyses confirmed these findings. We conclude that mildly abnormal GMs are associated with a less favorable EFA status in the umbilical artery.

The relationships between kinematic characteristics of sitting posture during reaching movements of the dominant arm and 1) the kinematics of the reaching movement itself and 2) functional performance during daily life activities (PEDI) were assessed in 51 sitting preterm children with cerebral palsy (CP). The children were 2–11 y, 33 had spastic hemiplegia (SH) and 18 bilateral CP (Bi-CP). The data were compared with those of 26 typically developing children (TD). Sitting posture before the onset of reaching of children with CP differed from that of TD children: they sat with a more reclined pelvis and a more collapsed trunk. The more reclined pelvic position was associated with a better quality of reaching movements. The different sitting postures of pelvis and trunk were not related to functional performance during daily life activities. Displacement of the head, trunk, and pelvis of the children with CP did not differ from that of the TD children. Nevertheless, in the children with CP a more stable head, a more mobile trunk, and a more stable pelvis were related to better functional performance and/or a better quality of reaching. This suggests that physiotherapeutic guidance of children with CP should focus rather on the latter postural parameters than on the different sitting posture of pelvis and trunk.

A substantial proportion of the “apparently normal” preterm infants exhibit minor and moderate dysfunctions in neuromotor outcome as they grow older. Birth characteristics, minor abnormalities on the neonatal ultrasound scan of the brain, and motor milestones have only limited value in the early detection of these children. The aim of the present study was to investigate whether nonoptimal reaching and relatively immobile postural behavior at an early age are associated with dysfunctional neuromotor and behavioural development at school age. The preterm children and full-term children of the present follow-up study participated in a previous study on the characteristics of reaching kinematics and the kinetics of posture at 4 and 6 mo corrected age. At the age of 6 y, the children were re-assessed by means of the Touwen neurologic assessment, the Movement ABC, and the Child Behavior Check List. The results demonstrated that in preterm children without cerebral palsy, a lack of successful reaching at 4 mo and a nonoptimal quality of reaching at 6 mo are related to the development of a complex form of minor neurologic dysfunction (MND) and fine manipulative disability at 6 y. Thus, these early signs indicate the presence of clinically significant brain dysfunction. A relatively immobile postural behavior at 4 mo was associated with simple MND, coordination problems, and at 6 mo with a worse score on the Movement ABC and internalizing behavior. This suggests that a relatively immobile postural behavior points to a mild form of brain dysfunction.

Kinematic characteristics of reaching movements of the dominant arm were assessed in 51 sitting preterm children who were aged 2–11 y and had cerebral palsy (CP), including 33 with spastic hemiplegia and 18 with bilateral CP (Bi-CP). Reference data of 29 typically developing children were present. The results indicated that the quality of reaching movements from the dominant arm of children with CP was significantly worse than that of typically developing children. This held true in particular for the children with Bi-CP. For example, reaching movements of children with CP took more time and consisted less often of one movement unit. The quality of reaching was related to the severity of lesion present on the neonatal ultrasound scan of the brain, the severity of motor disorder, the degree of spasticity, and the ability to perform activities of daily life. The last indicates that movements of the dominant arm in children with spastic hemiplegia and Bi-CP deserve clinical attention.

Kinematic characteristics of reaching movements of the dominant arm were assessed in 51 sitting preterm children who were aged 2–11 y and had cerebral palsy (CP), including 33 with spastic hemiplegia and 18 with bilateral CP (Bi-CP). Reference data of 29 typically developing children were present. The results indicated that the quality of reaching movements from the dominant arm of children with CP was significantly worse than that of typically developing children. This held true in particular for the children with Bi-CP. For example, reaching movements of children with CP took more time and consisted less often of one movement unit. The quality of reaching was related to the severity of lesion present on the neonatal ultrasound scan of the brain, the severity of motor disorder, the degree of spasticity, and the ability to perform activities of daily life. The last indicates that movements of the dominant arm in children with spastic hemiplegia and Bi-CP deserve clinical attention.

The present review evaluates the effect of pre- and postnatal supplementation of nutrition with long-chain polyunsaturated fatty acids (LCPUFA) on neurodevelopmental outcome of term infants. The few studies which have been performed on the role of prenatal LCPUFA status or prenatal LCPUFA supplementation in neurodevelopmental outcome suggest that a better prenatal arachidonic acid (AA) and doxosahexaenoic acid (DHA) status might be related to a better neurodevelopmental outcome in early infancy. A review of the randomised controlled trials on postnatal formula supplementation with LCPUFA in term infants revealed that supplementation with LCPUFA, in particularly supplementation with ≥0.30% DHA, has a beneficial effect on neurodevelopmental outcome till 4 months of age. The studies could not demonstrate a consistent positive effect beyond that age. However, in the majority of studies neurodevelopmental outcome was assessed at 6 to 24 months, i.e. at an age where there is a latency in the expression of minor neurological dysfunction. This may mean that it is possible that LCPUFA may have a long lasting beneficial effect on neurodevelopmental outcome at school-age and beyond. This hypothesis urgently needs testing in nutritional intervention studies in which children are followed till at least school-age.

Detection of children with a developmental disorder, such as cerebral palsy, at an early age is notoriously difficult. Recently, a new form of neuromotor assessment of young infants was developed, based on the assessment of the quality of general movements (GMs). GMs are movements of the fetus and young infant in which all parts of the body participate. The technique of GM assessment is presented and the features of normal, mildly abnormal, and definitely abnormal GMs discussed. Essential to GM assessment is the Gestalt evaluation of movement complexity and variation. The quality of GMs at 2 to 4 months postterm (so-called fidgety GM age) has been found to have the highest predictive value. The presence of definitely abnormal GMs at this age—that is, GMs devoid of complexity and variation—puts a child at very high risk for cerebral palsy. This implies that definitely abnormal GMs at fidgety age are an indication for early physiotherapeutic intervention.

Gradually it is getting clear that motor development – in particular balance control – in so-called “low-risk” preterm infants often differs from that in full-term infants. However, little is known on the etiology and pathophysiology of these problems. The aim of this study was to evaluate postural behavior during reaching by means of kinetic and kinematic measurements. Preterm infants (n = 32) without cerebral palsy were investigated longitudinally at the corrected ages of 4 and 6 mo. Thirteen age-matched full-term infants served as controls. Cognitive and motor development were assessed by means of the quality of General Movements (GMs) at 4 mo and Bayley scales at 6 and 12 mo. The infants were lying supine on a forceplate reaching for a toy and the kinetics of the total body's Center of Pressure (COP) was measured in cranial-caudal and medial-lateral direction. The analysis focused on COP displacement, Vmaxand oscillatory changes of the COP displacement during reaching. The kinematic analysis of reaching focused on movement units, Vmaxand a compound kinematic variable reflecting the quality of reaching. The results showed that preterm infants showed a remarkable “still” postural behavior, which differed significantly from the mobile COP behavior of the full-term infants. More “still” postural behavior at 6 mo was associated with a better quality of reaching movements and with normal GMs at 4 mo. We concluded that “still” postural behavior is an adequate postural strategy of preterm infants. But it might be that this postural behavior is an indicator of later dysfunction.

Many preterm infants may experience so-called minor developmental disorders; however, in general, the problems in motor behavior are not detected until school age. To introduce therapies aimed at the prevention of these problems, we need to increase our knowledge of motor function and dysfunction at early age. The present study focused on the organization of reaching movements in full-term and preterm infants without cerebral palsy. The reaching behavior of premature infants (n63) was assessed longitudinally at the corrected ages of 4 and 6 mo. Clinical assessments were made at 6 and 12 mo of age. On the basis of the infant’s morbidity during the early stay in the neonatal intensive care unit, the preterm infants were allocated into a high-risk and a low-risk group. Results from a previous study in full-term infants (n13) were included. Kinematics of reaching movements in supine position were measured, and the analysis focused on movement velocity and movement units. A compound parameter of kinematic variables was created, reflecting the quality of reaching movements. The present study showed that at the age of 4 mo, low-risk preterm infants showed more often optimal reaching behavior than full-term and preterm high-risk infants. This better reaching performance was related to a better general motor and behavioral development during the first year of life. At the age of 6 mo, the advantage of the low-risk group in reaching behavior had disappeared and a disadvantage in the form of nonoptimal reaching behavior of the high-risk group emerged.

In 1994 the American Academy of Pediatrics recommended more liberal rules for the treatment of hyperbilirubinemia in healthy term newborns. Yet, the safety of moderate degrees of hyperbilirubinemia in healthy term newborns is debated. To evaluate the safety of moderate degrees of hyperbilirubinemia, we assessed neurologic condition of 20 healthy nonhemolytic term newborns with peak total serum bilirubin levels of 233-444 µmol/L and 20 control infants matched for sex and gestational age at birth. Neurologic condition was evaluated with techniques focusing on the presence of minor neurologic dysfunction: in the newborn period according to Prechtl, at 3 mo on the basis of the quality of general movements, and at 12 mo according to Touwen. Moderate hyperbilirubinemia turned out to be associated with a significant increase in minor neurologic dysfunction throughout the first year of life. At 12 mo a strong dose-response relationship between the degree of hyperbilirubinemia and the severity of minor neurologic dysfunction was present. Our results indicate that total serum bilirubin levels 335 µmol/L should be avoided.