Alison Loughran-Fowlds

Early, Accurate Diagnosis and Early Intervention in Cerebral Palsy: Advances in Diagnosis and Treatment

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.

Distraction osteogenesis and glossopexy for Robin sequence with airway obstruction

Background:  We present six cases of infants with Robin sequence and severe obstructive sleep apnoea who failed treatment with nasal mask continuous positive airway pressure (CPAP). Surgical intervention with mandibular distraction osteoneogenesis with glossopexy meant tracheostomy was avoided. Polysomnography (PSG) was used to document the severity of the obstructive sleep apnoea. The aim of this report was to assess the value of mandibular distraction osteogenesis with glossopexy in children with Robin sequence using PSG preoperatively and post‐operatively.

Neurodevelopmental Outcomes of Premature Infants Treated for Patent Ductus Arteriosus: A Population-Based Cohort Study.

OBJECTIVE To compare neurodevelopmental outcomes of extremely preterm infants diagnosed with patent ductus arteriosus (PDA) who were treated medically or surgically and those who were not diagnosed with PDA or who did not undergo treatment for PDA. STUDY DESIGN This retrospective population-based cohort study used data from a geographically defined area in New South Wales and the Australian Capital Territory served by a network of 10 neonatal intensive care units. Patients included all preterm infants born at <29 completed weeks of gestation between 1998 and 2004. Moderate/severe functional disability at 2-3 years corrected age was defined as developmental delay, cerebral palsy requiring aids, sensorineural or conductive deafness (requiring bilateral hearing aids or cochlear implant), or bilateral blindness (best visual acuity of <6/60). RESULTS Follow-up information at age 2-3 years was available for 1473 infants (74.8%). Compared with infants not diagnosed with a PDA or who did not receive PDA treatment for PDA, those with medically treated PDA (aOR, 1.622; 95% CI, 1.199-2.196) and those with surgically treated PDA (aOR, 2.001; 95% CI, 1.126-3.556) were at significantly greater risk for adverse neurodevelopmental outcomes at age 2-3 years. CONCLUSION Our results demonstrate that treatment for PDA may be associated with a greater risk of adverse neurodevelopmental outcome at age 2-3 years. This was particularly so among infants born at <25 weeks gestation. These results may support permissive tolerance of PDAs; however, reasons for this association remain to be elucidated through carefully designed prospective trials.

Neonatal pain: A comparison of the beliefs and practices of junior doctors and current best evidence

Aim:  To obtain information on the practices and beliefs of junior doctors regarding neonatal pain and to compare this with best evidence.

A comparison of the performance of healthy Australian 3-year-olds with the standardised norms of the Bayley Scales of Infant and Toddler Development (version-III)

Background Standardised developmental tests are now widely used in neurodevelopmental assessments of infants and children. In 2006, the revised and updated version of the Bayley Scales of Infant and Toddler Development (version III) replaced the previous version and is now widely used in neonatal developmental follow-up clinics. Several papers from Australia have highlighted underestimation of developmental impairment up to age 2 using this revised version. We aimed to ascertain how a cohort of healthy 3-year-old children performed compared to the standardised norms of the Bayley Scales of Infant and Toddler Development (version-III). Method Term healthy newborn control infants from the prospective Development after Infant Surgery (DAISy) study were included. At 3 years of age, the mean scores on each of the five subscales for 156 children were compared with the standardised norms. Results At 3 years of age, the mean scores were higher than the standardised norms on four of the subscales, cognition (<0.05), receptive and expressive language and fine motor (p<0.001). There was no significant difference in the gross motor scale (p=0.435). Conclusions Healthy term Australian children have a statistically significantly higher mean score on the Bayley Scales of Infant and Toddler Development (version-III) compared with the standardised means in four of the subtests, with the greatest difference in receptive language. This has implications for the assessment of children as the test may miss those with a minor delay and not reflect the severity of delay of infants that it does identify. We recommend that consideration ought to be given to re-standardising this assessment on Australian children.

Developmental outcomes at 3 years of age following major non-cardiac and cardiac surgery in term infants: A population-based study.

The objective of this study was to determine whether there remain developmental differences between term infants at 3 years of age following major non‐cardiac surgery (NCS) and cardiac surgery (CS) compared with healthy control infants in New South Wales (NSW), Australia.

Developmental outcomes at three years of age of infants with esophageal atresia

BACKGROUND/AIMS Previous work assessing early developmental outcomes of infants at one year of age following surgery for esophageal atresia (OA) and/or tracheoesophageal fistula (TOF) found a significantly lower score in expressive language compared with control infants. The purpose of this study was to determine whether these differences were still evident at three years of age. METHODS Between August 2006 and July 2008, infants who required surgical correction of OA/TOF were prospectively enrolled as part of a large study which examined developmental outcomes following surgery. Patients were reassessed using the Bayley Scales of Infant and Toddler Development Version III. Cognition, expressive and receptive language, fine motor and gross motor skills scores were compared with both the standardized norms and also with contemporaneous control infants. RESULTS 24 of the 31 infants (77%) assessed at one year were reassessed at three years of age. There was no significant difference between the Bayley scores of the infants with OA/TOF and the standardized norms of the tests in four of the subsets: cognition, expressive language, fine and gross motor skills. Infants with OA scored higher than normative values for the receptive language subscale (P=0.001). When compared with the controls, there were no significant differences in any of the subscales. CONCLUSION Compared with the outcomes at one year, infants with OA/TOF have improved and were scoring within the normal range for the assessment at three years. This may in part be because of the early intervention services which many of these children were provided.

Contemporary incidence of stroke (focal infarct and/or haemorrhage) determined by neuroimaging and neurodevelopmental disability at 12 months of age in neonates undergoing cardiac surgery utilizing cardiopulmonary bypass

OBJECTIVES When evaluated prospectively, acute brain injury is reported in up to 75% of neonates undergoing cardiopulmonary bypass (CPB), predominantly white matter injury rather than stroke. This study investigates the incidence of stroke (focal infarct and/or haemorrhage) detected by neuroimaging in contemporary clinical practice, whereby magnetic resonance imaging/computed tomography routinely occurs in response to clinical events, comparing those undergoing the Norwood procedure with those undergoing other neonatal procedures involving CPB, and defines the relationship between stroke and neurodevelopmental disability (NDD) at 12 months of age. METHODS One hundred and twenty neonates underwent CPB between July 2011 and December 2014: 25 Norwood procedures and 95 non-Norwood procedures. Data were retrospectively collected including clinical data and 12-month neurodevelopmental assessment using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). RESULTS Stroke was detected in 12% of neonates in current clinical practice: 24% of the Norwood group vs 8% of the non-Norwood group (P = 0.03). Significant predictors of stroke in the univariate analysis included the Norwood procedure, lowest operative temperature and use of extracorporeal membrane oxygenation (P < 0.05). The lowest operative temperature and use of extracorporeal membrane oxygenation remained significant in the multivariate analysis (P < 0.05). Fifty-seven percent were assessed using the BSID-III assessment, and 68% demonstrated NDD in at least 1 subscale. In neonates who suffered stroke, the incidence of NDD was significantly greater in 4/5 subscales compared with those with no injury (P < 0.05). The Norwood group had a significantly greater incidence of NDD in 2/5 subscales when compared with the non-Norwood group (P < 0.05). CONCLUSIONS Stroke, established by neuroimaging in contemporary clinical practice, was detected in 12% of neonates having CPB, and those undergoing the Norwood procedure have a 3-fold risk of injury. Stroke was associated with NDD at 12 months of age.

Methicillin-resistant Staphylococcus aureus bacteraemia and epidural abscess in a neonate.

A 24‐day‐old boy presented with fever, irritability and poor feeding. Blood culture grew methicillin‐resistant Staphylococcus aureus. Cerebrospinal fluid analysis showed pleocytosis, and methicillin‐resistant Staphylococcus aureus grew from enrichment broth. Magnetic resonance imaging revealed an epidural abscess extending from C2–3 to T8–9. Staphylococcal infections of the central nervous system are uncommon in neonates. This case demonstrates the importance of performing a lumbar puncture in isolated staphylococcal bacteraemia. The case also highlights that cerebrospinal fluid pleocytosis may indicate a parameningeal focus of infection.

Prediction of three year outcomes using the Bayley-III for surgical, cardiac and healthy Australian infants at one year of age

BACKGROUND Previous predictive research has predominantly focussed on infants who are preterm, low birth weight, who have a specific condition or who have undergone a specific procedure. AIM This study investigated the ability of outcomes at one year of age to predict outcomes at three years using the Bayley-III for infants who have undergone early major cardiac surgery (CS) or non-cardiac (NC) surgery and their healthy peers. STUDY DESIGN Participants who were part of the Development After Infant Surgery (DAISy) study who had complete Bayley-III assessments at one and three years of age were included in the analyses. This included 103 infants who had undergone CS, 158 who had NC surgery and 160 controls. RESULTS Bayley-III outcomes at one, although statistically significantly associated with three year outcomes in all domains were weak predictors of those outcomes for CS, NC surgical and healthy infants. Specificity for three year outcomes was good for cognitive, receptive language and fine motor domains for infants who had undergone CS and NC surgery. Sensitivity for <-1 SD at three years was poor for cognitive, expressive and receptive language, and fine motor outcomes for CS and NC surgical participants. CONCLUSION It remains difficult to predict how performance at one year on the Bayley-IIII predicts performance at three on the Bayley-III for infants who have undergone early major CS or NC surgery and for healthy Australian infants.