Angela Huertas-Ceballos

Evaluation of early childhood social-communication difficulties in children born preterm using the Quantitative Checklist for Autism in Toddlers.

OBJECTIVES To characterize early childhood social-communication skills and autistic traits in children born very preterm using the Quantitative Checklist for Autism in Toddlers (Q-CHAT) and explore neonatal and sociodemographic factors associated with Q-CHAT scores. STUDY DESIGN Parents of children born before 30 weeks gestation and enrolled in a study evaluating routinely collected neurodevelopmental data between the post-menstrual ages of 20 and 28 months were invited to complete the Q-CHAT questionnaire. Children with severe neurosensory disabilities and cerebral palsy were excluded. Participants received neurodevelopmental assessments using the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III). Q-CHAT scores of this preterm cohort were compared with published general population scores. The association between Bayley-III cognitive and language scores and neonatal and sociodemographic factors with Q-CHAT scores were examined. RESULTS Q-CHAT questionnaires were completed from 141 participants. At a mean post-menstrual age of 24 months, the Q-CHAT scores of the preterm cohort (mean 33.7, SD 8.3) were significantly higher than published general population scores (mean 26.7; SD 7.8), indicating greater social-communication difficulty and autistic behavior. Preterm children received higher scores, particularly in the categories of restricted, repetitive, stereotyped behavior, communication, and sensory abnormalities. Lower Bayley-III language scores and non-white ethnicity were associated with higher Q-CHAT scores. CONCLUSIONS Preterm children display greater social-communication difficulty and autistic behavior than the general population in early childhood as assessed by the Q-CHAT. The implications for longer-term outcome will be important to assess.

Impact of ethnicity and extreme prematurity on infant pulmonary function

The impact of birth before 27 completed weeks of gestation on infant pulmonary function (PF) was explored in a multi‐ethnic population in comparison to more mature preterm controls (PTC) and healthy fullterm infants. Plethysmographic lung volume (FRCpleth) and forced expired volume (FEV0.5) were obtained at ∼12 months post‐term age in 52 extremely preterm (EP) infants (median [range] gestational age [GA]: 26 [23–27] weeks; 40% White mothers; 79% with BPD), 41 PTC (GA:35 [30–36] weeks; 37% White mothers) and 95 fullterm infants (GA:40 [37–42] weeks; 86% White mothers). Using reference equations based on identical equipment and techniques, results were expressed as z‐scores to adjust for age, sex and body size. FEV0.5 was significantly lower in EP infants when compared with PTC (mean difference [95% CI]: −1.02[−1.60; −0.44] z‐scores, P < 0.001), as was forced vital capacity (FVC) but there were no significant differences in FRCpleth or FEV0.5/FVC ratio. FEV0.5, FVC, and FEV0.5/FVC were significantly lower in both preterm groups when compared with fullterm controls. On multivariable analyses of the combined preterm dataset: FEV0.5 at ∼1 year was 0.11 [0.05; 0.17] z‐scores higher/week GA, and 1.28 (0.49; 2.08) z‐scores lower in EP infants with prior BPD. Among non‐white preterm infants, FEV0.5 was 0.70 (0.17; 1.24) z‐scores lower, with similar reductions in FVC, such that there were no ethnic differences in FEV0.5/FVC. Similar ethnic differences were observed among fullterm infants. These results confirm the negative impact of preterm birth on subsequent lung development, especially following a diagnosis of BPD, and emphasize the importance of taking ethnic background into account when interpreting results during infancy as in older subjects. Pediatr Pulmonol. 2014; 49:679–687.

Review of NICE guidelines on routine postnatal infant care

The National Institute for Health and Clinical Excellence (NICE) has recently published guidelines on the management of women and their newborn infants during the first 6–8 weeks after delivery.1 NICE guidelines aim at describing the “best practice advice on the core care of women and their babies during the postnatal period”. The present scheme of postnatal care was developed many years ago and NICE has reviewed it based on existing evidence. Unsurprisingly, the scientific evidence for best practice is incomplete. The money and time spent on postnatal care in Britain alone justify a systematic evaluation, but the clinical efficacy of existing practice has also raised concerns. The high proportion of women who intend but fail to breast feed successfully, the number of women who complain of additional health problems in the weeks following delivery and the number of infants with significant anomalies that are unrecognised when examined postnatally2–5 are some of the reasons for questioning whether we are offering families optimal care. In addition, the NICE guidelines point out that various recent surveys have found significant levels of dissatisfaction with the postnatal care among the women who have received it.1 We have confined our review to advice on infant care, although the wellbeing of mothers is inextricably linked to that of their infant and vice versa. The potential hazards of the postnatal period are demonstrated by the global annual neonatal death rate of around 4 million infants; the overwhelming majority of these deaths occur in low-income countries.6 In Britain we are spared much of this tragedy; our relatively healthy adult population and routine high-quality antenatal screening has led to serious, unexpected illness or death in the neonatal period being uncommon. There is a danger that we become blase about the risks of the newborn …

Magnetic Resonance Biomarkers in Neonatal Encephalopathy (MARBLE): a prospective multicountry study.

Introduction Despite cooling, adverse outcomes are seen in up to half of the surviving infants after neonatal encephalopathy. A number of novel adjunct drug therapies with cooling have been shown to be highly neuroprotective in animal studies, and are currently awaiting clinical translation. Rigorous evaluation of these therapies in phase II trials using surrogate MR biomarkers may speed up their bench to bedside translation. A recent systematic review of single-centre studies has suggested that MR spectroscopy biomarkers offer the best promise; however, the prognostic accuracy of these biomarkers in cooled encephalopathic babies in a multicentre setting using different MR scan makers is not known. Methods and analysis The MR scanners (3 T; Philips, Siemens, GE) in all the participating sites will be harmonised using phantom experiments and healthy adult volunteers before the start of the study. We will then recruit 180 encephalopathic infants treated with whole body cooling from the participating centres. MRI and spectroscopy will be performed within 2 weeks of birth. Neurodevelopmental outcomes will be assessed at 18–24 months of age. Agreement between MR cerebral biomarkers and neurodevelopmental outcome will be reported. The sample size is calculated using the ‘rule of 10’, generally used to calculate the sample size requirements for developing prognostic models. Considering 9 parameters, we require 9×10 adverse events, which suggest that a total sample size of 180 is required. Ethics and dissemination Human Research Ethics Committee approvals have been received from Brent Research Ethics Committee (London), and from Imperial College London (Sponsor). We will submit the results of the study to relevant journals and offer national and international presentations. Trial registration number Clinical Trials.gov Number: NCT01309711.

Pressure passivity of cerebral mitochondrial metabolism is associated with poor outcome following perinatal hypoxic ischemic brain injury

Hypoxic ischemic encephalopathy (HIE) leads to significant morbidity and mortality. Impaired autoregulation after hypoxia-ischaemia has been suggested to contribute further to injury. Thalamic lactate/N-Acetylasperate (Lac/NAA) peak area ratio of > 0.3 on proton (1H) magnetic resonance spectroscopy (MRS) is associated with poor neurodevelopment outcome following HIE. Cytochrome-c-oxidase (CCO) plays a central role in mitochondrial oxidative metabolism and ATP synthesis. Using a novel broadband NIRS system, we investigated the impact of pressure passivity of cerebral metabolism (CCO), oxygenation (haemoglobin difference (HbD)) and cerebral blood volume (total haemoglobin (HbT)) in 23 term infants following HIE during therapeutic hypothermia (HT). Sixty-minute epochs of data from each infant were studied using wavelet analysis at a mean age of 48 h. Wavelet semblance (a measure of phase difference) was calculated to compare reactivity between mean arterial blood pressure (MABP) with oxCCO, HbD and HbT. OxCCO-MABP semblance correlated with thalamic Lac/NAA (r = 0.48, p = 0.02). OxCCO-MABP semblance also differed between groups of infants with mild to moderate and severe injury measured using brain MRI score (p = 0.04), thalamic Lac/NAA (p = 0.04) and neurodevelopmental outcome at one year (p = 0.04). Pressure passive changes in cerebral metabolism were associated with injury severity indicated by thalamic Lac/NAA, MRI scores and neurodevelopmental assessment at one year of age.

Developmental follow-up of children and young people born preterm, NICE guideline 2017

In August 2017, the National Institute for Health and Care Excellence (NICE) published a guideline entitled ‘Developmental follow-up of children and young people born preterm’.1 The 668-page guideline, with similar length in appendices, describes the risks of developmental problems, and the assessments and support recommended for children and young people born before 37+0 weeks’ gestation. The Guideline Committee included paediatric and neonatal clinicians, therapists, psychologists, researchers in neonatology and two lay members. Extensive research has been conducted in the UK on outcomes of prematurity through the EPICure studies,2 and several individual units, regions and networks have developed local guidelines.3 However, there has been no previous standardised guideline on developmental follow-up for these babies. In 2009, the 2-year assessment for those born before 30+0 weeks’ gestation was added to the toolkit in neonatology from the Department of Health,4 and is now in the National Neonatal Audit Programme as a standard of care for the management of children, as well as a measure of perinatal and neonatal outcomes.5 However, there is still wide variation in the provision of the 2-year assessment for premature babies throughout the UK,6 with partial data available for just 60% of these babies.5 This NICE guideline on developmental follow-up of the premature baby is welcome, as there is an urgent need for an adequately funded, equipped, staffed and effective surveillance service for this vulnerable population.

PO-0751 Use Of Postnatal Steroids In Ventilator Dependant Preterm Infants

Background and aim Bronchopulmonary Dysplasia (BPD), results in prolonged hospitalisation, poor growth and adverseneurodevelopment outcome. Postnatal steroids may decrease prolonged ventilation, one of the risk factors for BPD. However, there are concerns about adverse effects of steroids. The aim of the study was to assess the safety and efficacy of hydrocortisonein ventilator dependant preterm infants, thus ensuring safe practice and improve the quality of care given. Methods The study was a retrospective analysis over 17 months (Jan 2012–May 2013) in preterm infants less than 32 weeks gestation. Demographic data along with data on adverse effects related to hydrocortisone was collected. Results Fifteen percent (42/281) of preterm infants received hydrocortisone starting at dose of 5 mg/kg/d to aid extubation. The mean gestation was 25.17 weeks with a mean birth weight of 696 g. Forty-six percent had more than one failed extubation, 54% required >90% oxygen pre-treatment and 70% had either medical or surgical intervention for PDA. Only 24% had a documented discussion with parents regarding steroid treatment. The dose was reduced by 0.5–1 mg/kg, the time frequency of reduction varied between 1–7 days. Adverse events related to hydrocortisone treatment included hypertension, oesophageal perforation, hyponatremic, hyperglycaemic requiring insulin, left ventricular hypertrophy, fractures and poor weight gain. Conclusions The incidence of steroid use reflected that of other centres. Awareness of adverse events related to use of steroids along with improved parental communication is required.

PC.70 Signs of feed intolerance in the premature infant: is it functional dysmotility or necrotizing enterocolitis (NEC)?

Aim To observe signs of gastrointestinal dysmotility [gastric residual volume (GRV*), bile stained aspirates (BSA), abdominal distension (AD^), first passage of meconium (FPOM), and time to regular bowel habit (RBH)] whilst establishing enteral feeds. To examine how these signs were used to suggest diagnosis of NEC. Methods From April–October 2013, intestinal motility data on all preterm infants ≤32 weeks was prospectively observed from birth-14 days old or until tolerating full enteral feeds (150 ml/kg/day) if sooner. Results GRV, BSA and AD were common: (39/65 (60%), 37/65 (57%) and 17/65 (26%) respectively) and significantly prolonged time to full feeds: (median [IQR] (days) 13 [11–18] P = 0.0003, 13 [11–21] P = 0.0002 and 21 [12–28] P = 0.0001 respectively). Cox regression, adjusting for birth weight, showed each sign was a significant independent predictor of time to full feeds. Moreover, the number of signs in the first week following feed introduction predicted time to full feeds (Figure). Neither GRV nor BSA occurred more frequently in the NEC treatment group, but AD did (p = 0.002). Morphine had a stronger effect than gestational age on FPOM (P < 0.005) and RBH (P < 0.0005). Surprisingly, infants with functional dysmotility had significant earlier FPOM (day) than those who didn’t (2.0 vs. 3.3, P = 0.03). Conclusion Functional intestinal dysmotility of the preterm infant is readily observed through GRV, BSA and AD soon after birth and should be considered, in the first two weeks of life, as possibly physiological before stopping enteral feeds or commencing NEC treatment. Abstract PC.70 Figure * Defined as (≥ 2ml/kg+33% of feed volume) ^ Tense none-soft abdomen

1224 Sociodemographic and Neonatal Factors Associated with Early Childhood Social-Communication Difficulties in Children Born Preterm

Background The Quantitative Checklist for Autism in Toddlers (Q-CHAT) is a parent-completed questionnaire providing a quantitative measure of early childhood social-communication difficulty (Allison et al, J Autism Dev Disord, 2008). The Q-CHAT scores of children born preterm are higher than the general population, indicating greater autistic traits (Wong et al, Neonatal Society Proceedings 2012 Spring Meeting). Aim To examine sociodemographic and neonatal factors associated with social-communication abilities in preterm infants at 24 months corrected age. Methods The parents of children born at < 30 weeks gestation and enrolled in a study evaluating routinely collected neurodevelopmental data were asked to complete the Q-CHAT. Children with severe neurosensory disabilities and cerebral palsy were excluded. The effect of factors identified a priori (maternal age, gestation, birthweight z-score, gender, multiple pregnancy, length of mechanical ventilation, supplemental oxygen requirement at 36 weeks post-menstrual age (BPD) and index of multiple deprivation (IMD)) on Q-CHAT scores were examined using univariable and multivariable linear regressions. Results The Q-CHAT was completed by the parents of 104 children (mean[SD] gestation 27.0[1.7] weeks, when the children were at a mean corrected age of 24.7[2.7] months). On univariable analysis, gestation, multiple pregnancy, BPD and IMD were positively associated with Q-CHAT scores. Low gestation (p=0.02) and higher IMD (p<0.01) were independently associated with higher Q-CHAT scores on multivariable analysis. Conclusion Preterm birth is a recognised risk factor for autism spectrum disorder. We report a novel finding of high deprivation as an independent predictor of early childhood social-communication difficulty in the preterm population.

Motor repertoire and neurological outcome in preterm infants.

Neurological assessment is important in high-risk populations, and improved survival of infants who would otherwise have died has led to the development of several methods to assess health status and neurodevelopment. These neurological examinations have included assessments of tone and reactions (Amiel-Tison and Stewart), behaviour (Brazelton), movements (Prechtl), and others integrating the different approaches into one (Dubowitz). Prechtl’s technique of studying ‘general movements’ – a specific type of spontaneous movement – is a particularly fascinating neurological assessment and over the last 20 years it has been repeatedly documented that standardized observation of general movements is highly predictive of neurological outcome, particularly of cerebral palsy (CP). The value of the general movement assessment in screening at-risk populations is already well established and the study by de Vries and Bos is an important step in evaluating the clinical significance of abnormal movements in extremely low-birthweight infants (ELBW) at term age in relation to their neurological outcome at 21⁄2 years. The authors found that abnormal general movements at term age are very common in ELBW infants, as 10 out of 13 infants in their study demonstrated. This figure may seem surprisingly high but many clinicians will have observed that the general movements of ELBW infants are not optimum when compared with term born infants. By 3 months corrected age, however, the majority of the infants in the study had normalized with only three showing abnormal movements. Between 2 and 5 months postterm age generals movements are referred to as ‘fidgety movements’ which are considered to be highly predictive of outcome and have been used in many studies either to complement imaging or in isolation to predict CP. It is absent fidgety movements in particular which have been correlated to CP. None of the three infants classified as abnormal at 3 months in the de Vries and Bos’ study showed absent fidgety movements and none had developed CP at 21⁄2 years. The study by de Vries et al., reminds us that clinicians have to be very cautious interpreting the clinical significance of a single assessment in ELBW infants at term age. Other studies involving serial assessments of general movements around term age and up to fidgety age (2–5mo postterm) have demonstrated a strong predictive value. For example, Ferrari et al. showed in a study of preterm infants with abnormal head scans that when a particular pattern of abnormal general movements called cramped synchronized, was persistent and predominant in serial assessments over time there was 92.5 to 100% specificity in predicting CP. Consistency of results through serial assessments is essential. Nakajima et al. and Einspieler et al. also describe a study where a consistent and specific pattern of a poor repertoire of general movements is predictive of dyskinetic CP. Therefore, as recommended by Einspieler, and illustrated in Ferrari et al.’s study, it is very important to evaluate general movements in terms of their trajectory and consider a classification once a consistent pattern has been established. Faced with clinical findings of uncertain significance we stress the importance of using serial recordings for accurate classification, as well as knowledge of medical histories and patterns of brain damage. Clinicians may then be in a better position to identify those with pathology and in need of early intervention. The authors mention recording the infants for at least 5 minutes and in reality it can be a challenge to maintain the infant any longer than this in an awake and non-fussing state whilst lying supine. However, recordings should be for as long as possible, particularly when an abnormal pattern is observed. Any change in the character of the general movements during the recording should also be closely observed. Parents, when shown how, are often very willing to provide additional helpful recordings. de Vries and Bos document important details regarding the concurrent motor repertoire of ELBW infants. The pattern of extended leg lifting accompanied by cramped and stiff movements, flat postures, and a monotonous repertoire sounds sadly familiar. Whilst the authors found that this movement pattern did not have prognostic value for CP it may well be prognostic for, or contribute to, a whole array of other difficulties ELBW infants present with at school age. Infants showing an abnormal pattern at any age should have serial reassessments and appropriate developmental interventions. Parents need to be advised regarding therapeutic activities which may be beneficial, including postural support to increase flexor activity. The study by de Vries and Bos reminds us of the importance of clearly differentiating physiological from pathological movements in ELBW infants. Extended legs at term age and