Nadia Badawi

Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy

Neonatal encephalopathy (NE) is the clinical manifestation of disordered neonatal brain function. Lack of universal agreed definitions of NE and the sub-group with hypoxic-ischaemia (HIE) makes the estimation of incidence and the identification of risk factors problematic. NE incidence is estimated as 3.0 per 1000 live births (95%CI 2.7 to 3.3) and for HIE is 1.5 (95%CI 1.3 to 1.7). The risk factors for NE vary between developed and developing countries with growth restriction the strongest in the former and twin pregnancy in the latter. Potentially modifiable risk factors include maternal thyroid disease, receipt of antenatal care, infection and aspects of the management of labour and delivery, although indications for some interventions were not reported and may represent a response to fetal compromise rather than the cause. It is estimated that 30% of cases of NE in developed populations and 60% in developing populations have some evidence of intrapartum hypoxic-ischaemia.

What constitutes cerebral palsy

Cerebral palsy (CP) is a term of convenience applied to a group of motor disorders of central origin defined by clinical description. It is not a diagnosis in that its application infers nothing about pathology, aetiology, or prognosis. It is an umbrella term covering a wide range of cerebral disorders which result in childhood motor impairment. The precise inclusion criteria vary with the objectives for using the term. For meaningful comparison of rates of CP, as performed by and between CP registers, it is important that the rates should be generated using the same criteria. As generally understood there must be motor impairment, and this impairment must stem from a malfunction of the brain (rather than spinal cord or muscles). Furthermore, the brain malfunction must be non‐progressive and it must be manifest early in life. For the purposes of comparisons of rates across time even when the condition meets all the above criteria, it must not historically have been excluded from the category of CP. This paper addresses the problem of standardizing the inclusion criteria for selecting people included on CP registers with particular reference to this last criterion.

Predictors of neonatal encephalopathy in full term infants

Abstract Objective: Preliminary investigation of the contribution of adverse antepartum and intrapartum factors to neonatal encephalopathy in singleton neonates born full term. Design: Matched case-control study based on incidence density sampling of controls. Setting: Two major teaching hospitals (one paediatric and one obstetric) and three peripheral maternity hospitals in Perth, Western Australia (population 1.2 million). Subjects: 89 cases, all the full term singleton neonates born during an eight month period in 1992 who fulfilled one or more of six criteria during the first week of life (seizures, abnormal conscious state, persistent hypertonia or hypotonia, and feeding or respiratory difficulties of central origin). One full term control infant without neonatal encephalopathy was matched to each case by sex, hospital of delivery, time of day and day of the week of birth, and maternal health insurance status. Main outcome measures: Odds ratio estimates of relative risk of neonatal encephalopathy associated with antepartum and intrapartum factors. Results: Estimated incidence of moderate or severe encephalopathy in first week of life was 3.75 per 1000 full term live births. Thirteen cases and no controls had evidence suggestive of important intrapartum hypoxia, and in only five of these cases was the neurological condition at birth attributed to events during the intrapartum period. Univariate conditional logistic regression analysis identified significant differences between cases and controls for maternal vaginal bleeding in pregnancy, maternal thyroxine treatment, congenital abnormalities, induction of labour, interval from membrane rupture to delivery, maternal pyrexia in labour, augmentation of labour, abnormal intrapartum cardiotocograms, and meconium in labour. Family history of convulsions also approached significance. Conclusions: Our preliminary results suggest that intrapartum hypoxia, according to currently used criteria, was not the cause of neonatal encephalopathy in most cases in this population. Our findings suggest that many aetiologies of neonatal encephalopathy originate in the antepartum period.

A systematic review of risk factors for cerebral palsy in children born at term in developed countries

Aim  The aim of this study was to conduct a systematic review in order to identify the risk factors for cerebral palsy (CP) in children born at term. The secondary aim was to ascertain if the potential for prevention of these risk factors has been adequately explored.

The origins of cerebral palsy.

Purpose of reviewCerebral palsy is the most common and visible motor disability of childhood. Its aetiology remains a topic of hot debate between those who see it as a reflection of medical mismanagement of an avoidable complication and those who see its origins in the development of the fetal brain affected at many points along a causal pathway to damage. This review outlines the themes of research publications over the year 2004/2005. Recent findingsThe review looks at recent findings relating to epidemiology, infection and inflammation, prematurity, multiple pregnancy, thrombophilias, genetics, placenta, neuroimaging and rescue therapies in cerebral palsy. SummaryPapers this year have helped clarify risk groups and identify some areas (e.g. the management of thrombophilias and the potential of induced hypothermia) with the potential to be rapidly introduced into clinical practice. In this enigmatic and multifactorial condition, however, progress remains slow. New tools such as magnetic resonance imaging are providing valuable insights into the lesions that result in cerebral palsy but the pathways to injury remain unclear. The future of cerebral palsy research lies in understanding the complex interactions of multiple factors on the road to cerebral palsy or in looking for final common pathways such as inflammation which may be amenable to manipulation.

Cerebral palsy following term newborn encephalopathy : a population-based study

Cerebral palsy (CP) can occur in term infants with or without preceding newborn encephalopathy. We compared the type and severity of CP and associated disability in these two groups. Participants from a population-based case-control study of term newborn encephalopathy were followed up for 6 years and linked to the Western Australian Cerebral Palsy Register. The remaining term infants with CP for the same period were also identified from the Cerebral Palsy Register. 13% of neonatal survivors of term newborn encephalopathy had CP, a rate of 116 per 1000 term live births. Overall, 24% of term infants with CP followed newborn encephalopathy. CP following newborn encephalopathy was more likely to: affect males (72% vs 56%); be severe (47% vs 25%); and be of spastic quadriplegia or dyskinetic types. Cognitive impairment was more common (75% vs 43%) and severe (41% vs 16%), as was epilepsy (53% vs 29%) in survivors of encephalopathy. These children were also more likely to: be non-verbal (47% vs 22%); have a severe composite disability score (47% vs 26%); and die between time of diagnosis of CP and age 6 years (5-year cumulative mortality 19% vs 5%). Children born at term who develop CP following newborn encephalopathy have a poorer prognosis than those with CP who were not encephalopathic in the first week of life.

Gastroschisis: an update

Gastroschisis (GS) continues to increase in frequency, with several studies now reported an incidence of between 4 and 5 per 10,000 live births. The main risk factor would seem to be young maternal age, and it is in this group that the greatest increase has occurred. Whilst various geographical regions confer a higher risk, the impact of several other putative risk factors, including smoking and illicit drug use, may be less important than when first identified in early epidemiological studies. Over 90% of cases of GS will now be diagnosed on antenatal ultrasound, but its value in determining the need for early delivery remains unclear. There would appear no clear evidence for either routine early delivery or elective caesarean section for infants with antenatally diagnosed GS. Delivery at a centre with paediatric surgical facilities reduces the risk of subsequent morbidity and should represent the standard of care. The relative roles of primary closure, staged closure and ward reduction, with or without general anaesthesia, appear less clear with considerable variation between centres in both the use of these techniques and subsequent surgical outcomes. Survival rates continue to improve, with rates well in excess of 90% now routine. The limited long-term developmental data available would suggest that normal or near-normal outcomes may be expected although there remains a need for further studies.

Enriched Environments and Motor Outcomes in Cerebral Palsy: Systematic Review and Meta-analysis

BACKGROUND AND OBJECTIVES: Neuroplasticity evidence from animals favors an early enriched environment for promoting optimal brain injury recovery. In infants, systematic reviews show environmental enrichment (EE) improves cognitive outcomes but the effect on motor skills is less understood. The objective of this review was to appraise the effectiveness evidence about EE for improving the motor outcomes of infants at high risk of cerebral palsy (CP). METHODS: A systematic review was conducted. Cochrane Central Register of Controlled Trials (PubMed), Cumulative Index to Nursing and Allied Health Literature, Education Resource Information Center, SocINDEX, and PsycINFO databases were searched for literature meeting inclusion criteria: randomized controlled trials; high risk of /diagnosis of CP; >25% participants ≤2 years; parent or infant interventions postdischarge; and motor outcomes reported. Data were extracted using the Cochrane protocol regarding participants, intervention characteristics, and outcomes. Methodological quality was assessed using risk of bias assessment and GRADE. RESULTS: A total of 226 studies were identified. After removing duplicates and unrelated studies, 16 full-text articles were reviewed, of which 7 studies met inclusion criteria. The risk of bias varied between studies with the more recent studies demonstrating the lowest risk. Enrichment interventions varied in type and focus, making comparisons difficult. A meta-analysis was conducted of studies that compared enrichment to standard care (n = 5), and totaled 150 infants. A small positive effect for enrichment was found; standardized mean difference 0.39 (95% confidence interval 0.05–0.72; I2 = 3%; P = .02) CONCLUSIONS: EE looks promising for CP, and therefore high-quality studies with well-defined EE strategies are urgently required.

Gastroschisis: determinants of neonatal outcome

Abstract. This retrospective study elicits information regarding the dependence of neonatal outcome in gastroschisis upon: (1) the mode of delivery, (2) place of birth, (3) time for birth to surgery, (4) method of closure, (5) time from operation to commencement of first enteral feeds. The neonatal intensive care database from five major tertiary centres was used to identify 181 neonates with gastroschisis from 1990 to 2000. There were 8 deaths. There were no significant differences in outcome for infants delivered vaginally (102) versus Caesarean section (79), those born near the tertiary centre (133) as compared to infants born away (48), ones operated within 7 hours (125) compared with those operated after 7 hours (56), with delayed closure (30) versus primary closure (151). Neonates fed within 10 days of operation (85) had significantly lower incidence of sepsis, duration of TPN and hospital stay when compared to those fed after 10 days (96). Early commencement of feeds decreases the incidence of sepsis, duration of total parenteral nutrition (TPN) and hospital stay. Place of delivery, mode of delivery, time to surgery and type of closure do not influence neonatal outcome.

Antecedents of cerebral palsy and perinatal death in term and late preterm singletons.

OBJECTIVE: To examine the antecedents of cerebral palsy and of perinatal death in singletons born at or after 35 weeks of gestation. METHODS: From a total population of singletons born at or after 35 weeks of gestation, we identified 494 with cerebral palsy and 508 neonates in a matched control group, 100 neonatal deaths, and 73 intrapartum stillbirths (all deaths in selected birth years). Neonatal death and cerebral palsy were categorized as without encephalopathy, after neonatal encephalopathy, or after neonatal encephalopathy considered hypoxic–ischemic. We examined the contribution of potentially asphyxial birth events, inflammation, fetal growth restriction, and birth defects recognized by age 6 years to each of these outcomes and to intrapartum stillbirths. RESULTS: The odds of total cerebral palsy after potentially asphyxial birth events or inflammation were modestly increased (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.1–3.2 and OR 2.2, 95% CI 1.0–4.2, respectively). However, potentially asphyxial birth events occurred in 34% of intrapartum stillbirths and 21.6% of cerebral palsy after hypoxic–ischemic encephalopathy. Inflammatory markers occurred in 13.9% and 11.9% of these outcomes, respectively. Growth restriction contributed significantly to all poor outcome groups. Birth defects were recognized in 5.5% of neonates in the control group compared with 60% of neonatal deaths and more than half of cases of cerebral palsy without hypoxic–ischemic encephalopathy. In children with cerebral palsy, a potentially asphyxial birth event, inflammation, or both were experienced by 12.6%, whereas growth restriction, a birth defect, or both were experienced by 48.6% (P<.001). CONCLUSION: Fetal growth restriction and birth defects recognized by age 6 years were more substantial contributors to cerebral palsy and neonatal death than potentially asphyxial birth events and inflammation. LEVEL OF EVIDENCE: II