Achievement Of Gross Motor Milestones Research Articles

Patient selection considerations for AADC deficiency gene therapy

AbstractBackgroundAromatic ʟ‐amino acid decarboxylase (AADC) deficiency is a rare, severe neurological disorder caused by pathogenic variants in the dopa decarboxylase (DDC) gene, resulting in a combined deficiency of monoamine neurotransmitters. Clinically, patients present with a range of dysfunctions that impact motor, autonomic, and cognitive development. The constellation of symptoms of AADC deficiency varies among patients, and clinical presentation falls across a wide spectrum. However, most patients with AADC deficiency experience significant impairments when compared with children with normal development, irrespective of genotype, phenotype, or disease severity. Further, AADC deficiency is associated with increased mortality.MethodsIn response to the recent approval of a disease‐modifying gene therapy for AADC deficiency, this review presents considerations for the selection of patients for treatment.ConclusionSuggested clinical criteria to determine whether a patient is a candidate for gene therapy are: (1) genetically and biochemically confirmed AADC deficiency; (2) lack of achievement of gross motor milestones and/or persistence of clinically significant movement disorders; (3) persistent neurocognitive or systemic symptoms secondary to AADC deficiency despite standard medical therapy; and (4) informed parental/guardian decision and consent to treatment.

The double burden of malnutrition and gross motor development in infants: A cross-sectional study

The objective of the present work was to study the relationship between the double burden of malnutrition and gross motor development in infants. ology: Sample included 5900 infants under 24 months of age, participants of the ENSANUT-ECU study. To evaluate nutritional status, we calculated z-scores for body mass index/age (BAZ) and height/age (HAZ). Six gross motor milestones were considered: sitting without-support, crawling, standing and walking with-support, standing and walking without-support. Data was analysed using logistic regression models in R. Independently form age, sex and other socio-economic factors, the probability of achieving three gross motor milestones was significantly lower among chronically undernourished infants compared to their peers: sitting without-support, crawling, and walking without-support. Compared to no malnourished infants the probability of sitting without-support at six months was 10% lower for chronically undernourished infants (0.70, 95%CI [0.64-0.75]; 0.60, 95%CI [0.52-0.67]; respectively). The probability of crawling at eight months and walking without-support at 12 months were also significantly lower among chronically undernourished infants (0.62, 95%CI [0.58-0.67]); 0.25, 95%CI [0.20-0.30]; respectively) in comparison to no malnourished infants (0.67, 95%CI [0.63-0.72]); 0.29, 95%CI [0.25-0.34]; respectively). Obesity/overweight was not associated with the achievement of gross motor milestones, except for sitting without-support. Chronically undernourished infants with low or high BMI/age were generally delayed in the achievement of gross motor milestones than their peers. Chronic undernutrition is related to delayed gross motor development. Public health measures are needed to be implemented to prevent the double burden of malnutrition and its detrimental effects on infant development.

Middle ear effusion, ventilation tubes and neurological development in childhood.

Otitis media with middle ear effusion (MEE) can be treated with ventilation tubes (VT) insertion, and it has been speculated that prolonged MEE in childhood can affect neurological development, which in turn may be important for later academic achievements. To investigate the association between middle ear effusion (MEE), treatment with ventilation tubes (VT) and childhood neurological development. We examined 663 children from the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) unselected mother-child cohort study. Children were followed by study pediatricians with regular visits from pregnancy until 3 years of age. MEE was diagnosed using tympanometry at age 1, 2 and 3 years. Information regarding VT from age 0-3 years was obtained from national registries. We assessed age at achievement of gross motor milestones from birth, language scores at 1 and 2 years, cognitive score at 2.5 years and general development score at age 3 years using standardized quantitative tests. Children with MEE had a lower 1-year word production vs. children with no disease: (median 2, IQR [0-6] vs. 4, IQR [1-7]; p = 0.017), and a lower 1-year word comprehension (median 36; IQR [21-63] vs. 47, IQR [27-84]; p = 0.03). Children with VT had a lower 2-5-year cognitive score vs. children with no disease; estimate -2.34; 95% CI [-4.56;-0.12]; p = 0.039. No differences were found between children with vs. without middle ear disease regarding age at achievement of gross motor milestones, word production at 2 years or the general developmental score at 3 years. Our study supports the previous findings of an association between MEE and concurrent early language development, but not later neurological endpoints up to the age of 3. As VT can be a treatment of those with symptoms of delayed development, we cannot conclude whether treatment with VT had positive or negative effects on neurodevelopment.

Achievement of Developmental Milestones Recorded in Real Time: A Mobile App-Based Study

To clarify the characteristics of milestone achievement of Japanese infants using data assessed and recorded in real time via a Web-based app by caregivers. Between 2014 and 2019, the achievement of developmental milestones of 16 627 Japanese infants were recorded via the mobile app Papatto Ikuji along with pertinent information including sex, birth date, anthropometric measurements, and information on feeding. The milestones consisted of 20 items belonging to 4 domains: personal-social, fine motor-adaptative, language, and gross motor. The distribution of age at milestone achievement was compared with 4 conventional normative data. Subgroup analyses according to sex, season of birth, and feeding methods were performed with restricted mean survival time analysis. Age distributions of milestone achievement were generally similar in the app-based and conventional data. The exception was "Smile responsively," for which the age at achievement seemed higher in the app-based data. Subgroup analyses showed female-dominant sex differences in the achievement of person-social and language milestones. The results also showed seasonality in achievement of gross motor milestones, with earlier achievement in infants born in winter compared with those born in summer. We describe mobile app-based data on developmental milestone achievements that were recordedin real time. The app-based data were generally comparable with conventional normative data, suggesting that its potential to assess the development of children in real time. This could be used complementarily with the current well-child visits at scheduled time points.

Association Between Age of Achieving Gross Motor Development Milestones During Infancy and Body Fat Percentage at 6 to 7 Years of Age

ObjectivesThe later achievement of gross motor milestones during infancy is associated with adiposity in early childhood. However, the associations between gross motor development and adiposity after entering primary school are unclear. This study examined the associations between the ages at which six gross motor milestones were achieved and adiposity during early school years.MethodsThis retrospective study was conducted in 2012 and 2013. Data were collected from 225 first-grade primary school children (mean age, 6.9 years; 39% girls). Adiposity was assessed using dual-energy X-ray absorptiometry and expressed as body fat percentage. Data describing the ages of achieving six gross motor milestones (holding head up, sitting, crawling, standing supported, walking supported, and independent walking) were obtained from the Maternal and Child Health Handbooks.ResultsMean body fat percentage was 21.7%. Multiple linear regression analyses revealed that later ages of achieving crawling (p < .001 [95% confidence interval: 0.33–1.16]), standing supported (p < .001 [95% confidence interval: 0.64–1.65]), and walking supported [p = .013 (95% confidence interval: 0.13–1.07)] were associated with increased fat. However, the ages of achieving holding head up (p = .053), sitting (p = .175), and independent walking (p = .736) were not statistically significant.ConclusionsAchieving crawling, standing supported, and walking supported later predict increased body fat when aged 6–7 years. The practice of observing gross motor milestone achievements may allow early targeted interventions to optimize body composition before beginning school and thereby, potentially prevent childhood obesity.

Fish Oil Supplementation in Pregnancy and Neurodevelopment in Childhood-A Randomized Clinical Trial.

A double-blind randomized controlled trial of n-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation or matching placebo during third trimester of pregnancy was conducted within the COPSAC2010 mother-child cohort consisting of 736 women and their children. The objective was to determine if maternal n-3 LCPUFA pregnancy supplementation affects offspring neurodevelopment until 6years. Neurodevelopment was evaluated in 654 children assessing age of motor milestone achievement, language development, cognitive development, general neurodevelopment, and emotional and behavioral problems. Maternal n-3 LCPUFA supplementation during pregnancy improved early language development and reduced the impact of emotional and behavioral problems. The n-3 LCPUFA supplementation was in boys associated with the earlier achievement of gross motor milestones, improved cognitive development, and a reduced impact of emotional and behavioral problems.

Early-onset of symptoms and clinical course of Pompe disease associated with the c.-32–13 T > G variant

BackgroundIndividuals with late-onset Pompe disease (LOPD) and the common c.-32–13 T > G variant are widely thought to have milder, adult-onset disease. This belief, and the consequent low suspicion of clinical involvement in children, has led to delays in diagnosis and treatment initiation in patients with early onset of symptoms. Previous reports of LOPD in children do not include description of the early-onset phenotype. This description of signs and symptoms, some of which are subtle and less known, is important to facilitate prompt identification and appropriate treatment in symptomatic children. MethodsRetrospective chart review of a cohort of 84 LOPD patients with the c.-32–13 T > G variant was conducted to identify patients diagnosed clinically (as opposed to through newborn screening) who had clinically documented symptom-onset within the first two years of life. ResultsFour patients had early onset of symptoms, with age at onset ranging from 10 days to 20 months. Initial symptoms included delay in achievement of gross motor milestones, signs of proximal muscle weakness, swallow and feeding difficulties, and sleep apnea. Early and characteristic alterations in posture and movement were identified in all patients. Age at diagnosis ranged from 10 months to 26 months. Median age at enzyme replacement therapy (ERT) initiation was 23.5 months. Despite ERT, progression of musculoskeletal involvement and residual muscle weakness was evident in all patients, as evidenced by ptosis, myopathic facies, scoliosis, lumbar lordosis, scapular winging, and trunk and lower extremity weakness. Standardized functional assessments showed gross motor function below age level as measured by the Alberta Infant Motor Scales, the Peabody Developmental Motor Scales-2, the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition, and the six-minute walk test. ConclusionsOnset of symptoms including delay in achievement of gross motor milestones, signs of proximal muscle weakness, swallow and feeding difficulties, and sleep apnea in the first two years of life is not uncommon in individuals with LOPD and the c.-32–13 T > G variant. Patients with early-onset disease appear to have a more, rapid and severe progression of disease with persistent residual muscle deficits which partially improve with higher doses of ERT. Careful evaluation for specific and characteristic patterns of posture and movement in patients with this variant is necessary to identify those who have early onset of disease. Increased awareness of the early-onset signs and symptoms may also enable early identification of disease onset in children who are diagnosed through newborn screening.

Timing of motor milestones achievement and development of overweight in childhood: a study within the Danish National Birth Cohort

Overweight may hinder achievement of gross motor milestones and delayed achievement of milestones may increase the risk of later overweight for reasons involving physical activity and the building of lean body mass. To investigate whether increased birth weight and body mass index (BMI) at 5 months is associated with the achievement of the ability to sit up and walk and whether delayed achievement of these milestones is associated with overweight at age 7 years. We used data from the Danish National Birth Cohort on 25,148 children born between 1998 and 2003. Follow-up took place from 2003 to 2010. Mean age at follow-up was 7.04 years. We used logistic and linear regression analyses. Birth weight and BMI at 5 months were marginally associated with earlier achievement of the ability to sit up and walk (regression coefficients between -0.027 months; [CI -0.042; -0.013] and -0.092 months [CI -0.118; -0.066]). Age in months of sitting and walking were not associated with overweight at age 7 years (ORs between 0.97 [CI 0.95-1.00] and 1.00 [CI 0.96-1.04]). Later achievement of sitting and walking predicted lower BMI at age 7 years (ln-BMI -z-scores between -0.023 [CI -0.029; -0.017] and -0.005 [CI -0.015; 0.005)). All observed associations were of negligible magnitude and we conclude that birth weight or BMI at age 5 months and motor milestones appear largely independent of each other and that timing of achievement of motor milestones seems not to be associated with later overweight or increased BMI.

Achievement of Gross Motor Milestones in Children With Idiopathic Clubfoot Treated With the Ponseti Method

The Ponseti method of idiopathic clubfoot treatment involves a series of weekly casts, a percutaneous Achilles tenotomy if needed, followed by wearing a foot abduction orthosis (FAO). Gross motor development of children with idiopathic clubfoot has not been examined. The purposes of this study were to determine the ages of achievement of gross motor milestones in children with clubfoot treated with Ponseti method and to compare those ages with historical normative developmental data. In this prospective study, 51 children with idiopathic clubfoot who had their first cast applied when ≤90 days old, were full-term with no other orthopaedic conditions or previous clubfoot treatment, and were compliant with wearing FAO were enrolled. Parents were interviewed repeatedly to acquire the ages of achievement of 8 gross motor milestones. Fifteen children were excluded for reasons such as noncompliance with FAO, and not returning for follow-up. Thirty-six children, mean age of 15.2 days at first casting, achieved rolling prone to supine at a mean age of 5.1 months, rolling supine to prone at 5.1 months, sitting without support at 6.6 months, crawling on stomach at 7.1 months, crawling on hands and knees at 8.6 months, pull-to-stand at 9.0 months, cruising at 10.2 months, and ambulating independently at 13.9 months. When compared with previously published values for unaffected children, the mean ages of achievement for 6 of 8 milestones were significantly greater (P<0.05) for the children with clubfoot. The preambulatory milestones were achieved from 0.7 to 1.5 months later and independent ambulation up to 2.2 months later. Fifty percent of children with clubfoot were ambulating at 13.8 months; 90% at 17.7 months. Minimal delays in gross motor milestone achievement were found in children with idiopathic clubfoot treated with the Ponseti method. Delays were, at most, 1.5 months, except for independent ambulation, which was approximately 2 months. These findings should enable pediatric clinicians to alleviate the concerns of parents of children with idiopathic clubfoot regarding gross motor milestone achievement. Therapeutic Level II.

Variations in early gross motor milestones and in the age of walking in Japanese children

Gross motor development is usually assessed in terms of age of achievement of motor milestones. Although there is generally an impression of faster development if the milestones are achieved at younger ages, no longitudinal studies have been done on the associations between the milestones, especially in Japan. As a part of the Japan Children's Study, the purpose of the present study was to determine whether the achievement of gross motor milestones in infancy is related with the age of walking. This was a prospective cohort study of 290 healthy and term infants born in a district of Osaka City, Japan. Three milestones (rolling over, sitting, and crawling) were observed in the laboratory for infants aged at 4 and 9 months by a pediatrician and a developmental psychologist, and the age of walking was confirmed in questionnaires filled in by the parents at 18 and 27 months. Children who could roll over at 4 months, and sit and crawl at 9 months, walked earlier than children who could not roll over, sit and crawl, respectively. With regard to crawling, children who were creeping had a 1 month delay in walking, and those who could not move forward had a 2 month delay compared to typical crawlers. On multiple regression analysis these three milestones were positively associated with walking: rolling over (β= 0.567), sitting (β= 1.973) and crawling (β= 1.473). The age and the patterns of sitting, crawling and rolling over were all related to the age of independent walking among Japanese infants. Consideration of milestone definition and variations is essential in medical check-up.

P1-514 Timing of motor milestones achievement and development of overweight in childhood

BackgroundLate achievement of motor milestones may increase the risk of overweight since early achievers have increased possibility to build lean body mass and expend energy. Further overweight infants may have...

Age of Achievement of Gross Motor Milestones in Infancy and Adiposity at Age 3 Years

Early life physical activity may help prevent obesity but is difficult to measure. The purpose of this study was to examine associations of age of achievement of gross motor milestones in infancy with adiposity at age 3 years. Seven forty one mother/infant dyads participated in a longitudinal study in Massachusetts. Exposures were age of attainment of 4 gross motor milestones-rolling over, sitting up, crawling, and walking. Outcomes were 3-year sum of subscapular and triceps skinfold thickness (SS + TR) for overall adiposity, their ratio (SS:TR) for central adiposity, and body mass index (BMI) z-score. We used linear regression models adjusted for confounders to examine motor milestone achievement and later adiposity. Rolling over (0.04, 95% CI: 0.008, 0.07) and sitting up (0.02, 95% CI: 0.001, 0.05) at ≥ 6 months were associated with increased SS:TR compared with attainment before 6 months. Walking at ≥ 15 months was associated with 0.98 mm higher SS + TR (95% CI: 0.05, 1.91) compared with walking before 12 months. Age at crawling was not associated with the outcomes. None of the milestones were associated with BMI z-score. Age of motor milestone achievement was only a modest predictor of adiposity. Later rolling over and sitting up were associated with greater central adiposity, and later age at walking was associated with greater overall adiposity at age 3 years. Although we controlled for birth weight and 6-month weight-for-length in our models, more detailed assessment of early adiposity prior to achievement of motor milestones is needed to help determine causality.

Docosahexaenoic acid supplementation and time at achievement of gross motor milestones in healthy infants: a randomized, prospective, double-blind, placebo-controlled trial

BackgroundDocosahexaenoic acid (DHA) intake throughout the first year of life is associated with neurodevelopmental and neuropsychological benefits. Few studies have evaluated the role of DHA intakes on age at achievement of gross motor milestones. ObjectiveThe objective was to assess the effects of DHA supplementation throughout the first year of life on the achievement of four gross motor milestones in healthy infants. DesignIn this multicenter prospective, randomized, double-blind, placebo-controlled trial, 1160 healthy neonates were assigned to receive supplementation with either 20 mg liquid DHA (n = 580) or placebo (n = 580) orally once daily throughout the first year of life. The primary endpoint was the time at achievement of 4 gross motor milestones (sitting without support, hands-and-knees crawling, standing alone, and walking alone). All analyses were performed on an intention-to-treat basis. ResultsThe time to achievement of sitting without support was shorter (P < 0.001) in infants who received DHA [median: 26 wk; interquartile range (IQR): 24–29 wk] than in those who received placebo (27 wk; 26–31 wk). No significant difference between infants who received DHA or placebo was found for hands-and-knees crawling [39 wk (34–44 wk) compared with 40 wk (35–44 wk), respectively], standing alone [49 wk (43–55 wk) compared with 49 wk (44–57 wk), respectively], and walking alone [55 wk (50–60 wk) compared with 56 wk (52–61 wk), respectively]. ConclusionsDespite the 1-wk advance in sitting without support associated with DHA supplementation, no demonstrable persistent effects of DHA supplementation on later motor development milestones were found. Thus, the long-term clinical significance of the 1-wk change in sitting without support, if any, remains unknown. This trial is registered at clinicaltrials.gov as NCT00610922.