Do fidgety general movements predict cerebral palsy and cognitive outcome in clinical follow-up of very preterm infants?

MANUSCRIPT CITATION

Datta AN, Furrer MA, Bernhardt I, Huppi PS, Borradori-Tolsa C, Bucher HU, et al. Fidgety Movements in Infants Born Very Preterm: Predictive Value for Cerebral Palsy in a Clinical Multicentre Setting. Dev Med Child Neurol 2017; 59:618-624. PMID 28102574.

REVIEWED BY

Joy Olsen, Dr
Murdoch Children’s Research Institute and the Royal Women’s Hospital, Melbourne, Australia

Peter Marschik, Associate Professor
interdisciplinary Developmental Neuroscience, Department of Phoniatrics, Medical University of Graz, Austria, and Center of Neurodevelopmental Disorders, Karolinska Institutet, Stockholm, Sweden

Alicia Spittle, Associate Professor
The University of Melbourne, Murdoch Children’s Research Institute and the Royal Women’s Hospital, Melbourne, Australia

TYPE OF INVESTIGATION

Prognosis

QUESTION

In very preterm infants born <32 weeks’ gestation does the Prechtl General Movement Assessment at 3 months’ corrected age in a clinical setting predict cerebral palsy and other neurodevelopmental impairment at 2 years’ corrected age?

METHODS

  • Design: Multicentre longitudinal cohort study
  • Allocation: Not applicable.
  • Blinding: The authors do not specify whether assessors were blind to infant clinical history when scoring.
  • Follow-up period: Follow-up assessment was conducted at 2 years’ corrected age (CA).
  • Setting: Three centres in Zurich, Bern and Geneva, as part of the Swiss Neonatal Network and Follow-Up Group.
  • Patients: Infants born preterm at <32 weeks’ gestation from the participating centres and who were part of the national follow-up program were included. Infants with malformations (not specified) were excluded.
  • Intervention: Infants born very preterm were assessed using the Prechtl General Movement Assessment (GMA) at 3 months’ CA as part of a clinical follow-up program. GMA was classified as normal fidgety, abnormal fidgety and absent fidgety.
  • Outcomes: At 2 years’ CA, neurodevelopment was assessed using the Bayley Scales of Infant Development, 2nd edition (BSID-II) and a structured neurological assessment was conducted by a paediatrician.
  • Primary outcome: The primary outcome was cerebral palsy (CP) at 2 years’ CA. Cerebral palsy was diagnosed and classified according to the guidelines of the Surveillance Group of CP in Europe and the Gross Motor Function Classification System.
  • Secondary outcomes: Cognitive and motor development was assessed using the BSID-II, and the Mental Development Index (MDI) and Psychomotor Development Index (PDI) were reported.
  • Analysis and Sample Size: Perinatal and demographic characteristics were compared between infants with normal and abnormal GMA using chi squared, t-test and Mann-Whitney U tests as appropriate. The authors used regression models to examine associations between abnormal GMA and neurodevelopmental outcomes of CP, and MDI and PDI scores on the BSID-II at 2 years’ CA. They also examined the associations between abnormal GMA at 3 months combined with neonatal cranial ultrasound findings (major brain injury, defined as intraventricular haemmorhage grade III/IV or cystic periventricular leukomalacia) with CP at 2 years using regression models. Regression was conducted unadjusted and then adjusted for socioeconomic status and perinatal variables known to affect neurodevelopmental outcome (e.g. bronchopulmonary dysplasia, gestational age <28 weeks). Predictive values of abnormal GMA for CP outcome at 2 years were calculated, including sensitivity, specificity, positive predictive and negative predictive values. The sample size was based on convenience sampling.
  • Patient follow-up: There were 535 infants with data available for the 3 month GMA and 2 year neurodevelopmental assessment. This represents a relatively low proportion of infants born very preterm at the participating centres. Of the infants born <32 weeks’ gestation during the study period (2004-2011, n=2435), 446 died and 114 had malformations who were not included. The reasons for eligible infants not being included in the study and their sample characteristics were not provided and therefore the representativeness of the included cohort could not be ascertained. Outcome assessment was conducted at average CA of 23 months (range 18-38 months).

MAIN RESULTS

Of the 535 participants included: 55% were female, mean gestational age was 28.2 weeks (range 23.9-31.9) and mean birthweight was 1023 grams (range 380-1600). There were 37 (7%) infants with major brain lesion and 21(4%) with cystic periventricular leukomalacia.

The mean age at GMA was 12.7 (range 12.0-20.0) weeks’ corrected age. The majority of GMA were classified as normal, n=432 (81%), with 82 (15%) and 21 (4%) classified as absent and abnormal fidgety respectively.

At 2 years’ corrected age, 39 (7%) of infants were diagnosed with cerebral palsy (CP) with the following subtypes: bilateral spastic (n=22), unilateral spastic (n=11), ataxic (n=5) and dyskinetic (n=1). There were 20 infants with absent fidgety and 3 with abnormal fidgety GMA who were diagnosed with CP at 2 years, while the majority of infants with absent fidgety GMA (n=62) did not have CP. There were 16/39 infants who had normal fidgety GMA who were later diagnosed with CP resulting in lowered sensitivity. Predictive values for absent fidgety for CP at 2 years: sensitivity 56% (95% confidence interval [CI] 38-72), specificity 87% (95% CI 84-90), positive predictive value 24% (95% CI 16-32) and negative predictive value 96% (95% CI 94-98).

Absent fidgety GMA was associated with increased odds of CP at 2 years’ CA on the unadjusted (odd ratio [OR] 8.9; 95% CI 4.1,17.1; p=<0.001) and the adjusted analysis (OR 10.9; 95% CI 4.2,28.0; p=<0.001).  A stronger association was evident when abnormal GMA (absent and abnormal fidgety GMA) was combined with major brain lesion on neonatal cranial ultrasound on both the unadjusted and adjusted analysis (OR 17.8; 95% CI 5.2, 61.6; p=<0.001 and OR 31.1; 95% CI 4.4, 222.0; p=<0.001 respectively).

Absent fidgety GMA was associated with lower mean MDI scores on the BSID-II (coeff: -5.4; 95% CI -9.6, -1.2; p=<0.05) but not with PDI scores (coeff: -2.2; -6.5, 2.2; p=>0.05) at 2 years. The association with MDI scores was weaker when infants with CP were excluded (coeff: -3.1; 95% CI -8.2, 1.9; p value not reported). Further, the predictive values of abnormal/absent fidgety GMA were not reported for cognitive outcome.

CONCLUSION

The authors conclude that the GMA conducted at 3 months’ corrected age is useful in a clinical setting for predicting CP at 2 years’ corrected age for children born <32 weeks’ gestation. Accuracy to predict CP increased when combined with neonatal cranial ultrasound findings. The authors also found that abnormal GMA at 3 months was associated with poorer cognitive outcome at 2 years, although further research is required to determine the predictive value of GMA for cognitive outcome separate to CP diagnosis.

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COMMENTARY

Infants born very preterm (<32 weeks’ gestation) have increased risk for cerebral palsy (CP) compared with their term-born peers, and are often included in developmental follow-up programs to allow early detection of CP and identify as soon as possible, those infants who will require specific intervention. The Prechtl General Movement Assessment (GMA) evaluates the quality of infants’ spontaneous movements and has excellent predictive validity for CP (1), with the highest sensitivity and specificity between 9-16 weeks when “fidgety” general movements (small amplitude movements in all directions of variable acceleration and moderate speed throughout the whole body) are present.  The GMA also offers considerable utility as it is observational, and is increasingly used by clinicians in preterm follow-up programs (2). The recent study by Datta et al. examined the predictive validity of GMA at three months’ corrected age for CP and other neurodevelopmental impairment for 535 infants born very preterm seen as part of developmental follow-up across three centres.

The study has two key findings. Firstly, that within a clinical context, the GMA at three months is a useful tool for predicting CP for very preterm infants, in agreement with previous research (1, 2). Absent fidgety GMA was associated with CP at two years’ corrected age, and predictive accuracy for CP increased when combined with brain injury on neonatal cranial ultrasound. The GMA therefore provides valuable information as part of the clinical assessment comprising neuroimaging, clinical history, and other neurodevelopmental assessment (1). A second finding was the association between absent fidgety GMA and poorer cognitive outcome, similar to previous studies (3). However, it should be noted that the association was weaker when children with CP were excluded, given the high incidence of cognitive impairment in children with CP (1). Rather than predicting cognitive outcomes, abnormal GMA findings may help clinicians identify infants who warrant closer follow-up of their cognitive development (4).

As a qualitative, observational assessment, there are important methodological considerations to ensure the reliability and subsequent predictive validity of the GMA in clinical follow-up. This was not a prospective cohort study with clear eligibility criteria and it should be noted that the follow-up rate was low at 28.5%. Previous clinical follow-up studies have used double-scorers and reviewed ambiguous cases (2). While Datta et al. reported specificity of the GMA that was similarly high to other studies, sensitivity was lower. There were also differences in the sensitivity and specificity between centres, which the authors attributed to rater differences (although inter-rater reliability was not reported). The GMA is usually scored from video, necessitating additional time to the standard clinic visit. Guzzetta, et al. (5) compared the predictive validity of GMA through direct observation and GMA scored from video. The predictive validity of both methods was high, as was the correlation between the two methods, however, 6% of cases could not be definitively scored from direct observation. They concluded that direct observation was similarly sensitive as GMA scored from video, however, recommended videoed assessment for cases that were not clear.

In clinical practice, there is scope to use technology, such as smartphone applications (6), for parents to upload a video for GMA prior to their clinic visit. Clinicians can then determine whether further GMA is required, and organise additional measures such as brain magnetic resonance imaging for infants with abnormal GMA, to increase the predictive accuracy for neurodevelopmental outcome, such as CP, and thereby target early intervention.

REFERENCES

  1. Novak I, Morgan C, Adde L, Blackman J, Boyd RN, Brunstrom-Hernandez J, et al. Early, accurate diagnosis and early intervention in cerebral palsy: advances in diagnosis and treatment. Jama Pediatr 2017; 171: 897-907
  2. Øberg GK, Jacobsen BK, Jørgensen L. Predictive value of general movement assessment for cerebral palsy in routine clinical practice. Phys Ther 2015; 95: 1489-95
  3. Spittle AJ, Spencer-Smith MM, Cheong JLY, Eeles AL, Lee KJ, Anderson PJ, et al. General Movements in Very Preterm Children and Neurodevelopment at 2 and 4 Years. Pediatr 2013; 132: e452-8
  4. Einspieler C, Bos AF, Libertus ME, Marschik PB. The General Movement Assessment Helps Us to Identify Preterm Infants at Risk for Cognitive Dysfunction. Front Psychol 2016; 7: 406
  5. Guzzetta A, Belmonti V, Battini R, Boldrini A, Paolicelli PB, Cioni G. Does the assessment of general movements without video observation reliably predict neurological outcome? Eur J Paediatr Neurol 2007; 11: 362-7
  6. Spittle AJ, Olsen J, Kwong A, Doyle LW, Marschik PB, Einspieler C, et al. The Baby Moves prospective cohort study protocol: using a smartphone application with the General Movements Assessment to predict neurodevelopmental outcomes at age 2 years for extremely preterm or extremely low birthweight infants. BMJ Open 2016; 6: e013446

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