Early Human Development

Editorial Board

2010-06-01

Hypoxic ischaemic encephalopathy in newborn infants

Denis Azzopardi — 2010-06-01

Neonatal encephalopathy remains a major challenge in perinatal care. Hypoxic ischaemic encephalopathy, which refers to neonatal encephalopathy resulting from intrapartum hypoxia ischaemia is especially concerning because of the perception that in many cases avoidable factors are contributory. Despite intensive research, several surveys show that hypoxic ischaemic encephalopathy continues to occur relatively frequently in resource rich countries. Neonatal encephalopathy has high societal and opportunity costs that potentially have major adverse effects on the health economy even of industrialised countries – these costs are even enormous in the developing countries where a lack of basic maternity care contributes to the high incidence of intrapartum deaths and neonatal hypoxic ischaemic encephalopathy.

Epidemiology of neonatal encephalopathy and hypoxic–ischaemic encephalopathy

Jennifer J. Kurinczuk, Melanie White-Koning, Nadia Badawi — 2010-06-01

Abstract: 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.

Obstetric aspects of hypoxic ischemic encephalopathy

Sailesh Kumar, Sara Paterson-Brown — 2010-06-01

Abstract: Hypoxic ischemic encephalopathy (HIE) describes neonatal encephalopathy that is caused by intrapartum asphyxia and it can result in the long term sequelae of cerebral palsy which is a major cause of disability. The incidence of cerebral palsy has not changed over the last few decades and the challenge to obstetricians remains how best to recognise those babies at risk of this intrapartum insult both before and during labour. Many associations and risk factors are unavoidable or unrecognisable, and others are fairly common and associated with poor predictive value. Intrapartum fetal heart monitoring remains the main focus of attention but how this is best achieved is still the subject of research. Computerised decision support systems built into fetal heart rate monitoring and non-invasive fetal ECG signal pick-up are currently being explored.

Clinical management of the baby with hypoxic ischaemic encephalopathy

Denis Azzopardi — 2010-06-01

Abstract: The results of randomized clinical trials indicate that the optimal management for infants with hypoxic ischaemic encephalopathy is therapeutic hypothermia combined with high quality standard neonatal intensive care. In addition to therapeutic hypothermia clinical management of the infant with hypoxic ischaemic encephalopathy should include the management of multiorgan dysfunction, obtaining and documenting detailed clinical information and performing appropriate investigations and assessment to confirm the diagnosis and to help direct care, and providing counseling and support to the family. This article is a summary of the in hospital clinical management of infants with hypoxic ischaemic encephalopathy.

Magnetic resonance imaging in hypoxic-ischaemic encephalopathy

2010-06-01

Abstract: Magnetic resonance imaging of the brain is invaluable in assessing the neonate who presents with encephalopathy. Successful imaging requires adaptations to both the hardware and sequences used for adults. Knowledge of the perinatal and postnatal details are essential for the correct interpretation of the imaging findings. Perinatal lesions are at their most obvious on conventional imaging between 1 and 2weeks from delivery. Very early imaging is useful to guide management in ventilated neonates but abnormalities may be subtle on conventional sequences. Diffusion-weighted imaging (DWI) is clinically useful for the early identification of ischaemic tissue in the neonatal brain, the pattern of which can predict outcome. DWI may underestimate the final extent of injury, particularly basal ganglia and thalamic lesions. Serial imaging with quantification of both tissue damage and structure size provides invaluable insights into the effects of perinatal injury on the developing brain.

Therapeutic hypothermia for neonatal hypoxic ischaemic encephalopathy

Aniko Roka, Denis Azzopardi — 2010-06-01

Abstract: There is now a strong evidence base supporting therapeutic hypothermia for infants with moderate or severe neonatal hypoxic ischaemic encephalopathy. Experimental and clinical data indicate that induced hypothermia reduces cerebral hypoxic ischaemic injury and randomized clinical trials in newborns with hypoxic ischaemic encephalopathy confirm improved neurological outcomes and survival at 18months of age with therapeutic hypothermia. Studies are on-going to confirm whether these benefits are maintained in later childhood. Efforts are now focused on optimal implementation of therapeutic hypothermia in clinical practice: training in the assessment of severity of encephalopathy; initiation and maintenance of hypothermia before admission to a cooling facility; care of the infant during cooling; and appropriate investigation and follow-up are crucial for optimizing neurological outcomes. The establishment of registries of infants with hypoxic ischaemic encephalopathy and audit are important for guiding clinical practice.

Experimental treatments for hypoxic ischaemic encephalopathy

Dorottya Kelen, Nicola J. Robertson — 2010-06-01

Abstract: Hypoxic ischaemic encephalopathy continues to be a significant cause of death and disability worldwide. In the last 1–2years, therapeutic hypothermia has entered clinical practice in industrialized countries and neuroprotection of the newborn has become a reality. The benefits and safety of cooling under intensive care settings have been shown consistently in trials; therapeutic hypothermia reduces death and neurological impairment at 18months with a number needed to treat of approximately nine. Unfortunately, around half the infants who receive therapeutic hypothermia still have abnormal outcomes. Recent experimental data suggest that the addition of another agent to cooling may enhance overall protection either additively or synergistically. This review discusses agents such as inhaled xenon, N-acetylcysteine, melatonin, erythropoietin and anticonvulsants. The role of biomarkers to speed up clinical translation is discussed, in particular, the use of the cerebral magnetic resonance spectroscopy lactate/N-acetyl aspartate peak area ratios to provide early prognostic information. Finally, potential future therapies such as regeneration/repair and postconditioning are discussed.

Behavioural problems at the age of eleven years in preterm-born children with or without fetal brain sparing: A prospective cohort study

Antonia J.M. van den Broek, Joke H. Kok, Bregje A. Houtzager, Sicco A. Scherjon — 2010-06-01

Abstract: Background: In severe intrauterine growth restriction (IUGR) due to placental insufficiency a haemodynamic adaptation occurs, resulting in preferential blood flow to the fetal brain (brain sparing). With Doppler ultrasound an increased ratio between the umbilical and the cerebral artery pulsatility index (U/C ratio) can be demonstrated. IUGR is associated with impaired neurodevelopmental outcome.Objective: Evaluation of the effect of fetal brain sparing on behavioural problems at eleven years in premature born children.Methods: Prospective cohort study in premature children born in 1989, with a gestational age of 26 0/7 to 33 0/7weeks. An U/C ratio>0.72 was defined as brain sparing. Behavioural problems were assessed with the parent-reported Child Behaviour Check List (CBCL) and the Teacher's Report Form (TRF). T scores >60 for total problem score and subscales of internalizing and externalizing behaviour, were considered abnormal.Results: Ninety-eight of the 116 survivors were assessed, of which 31 with antenatally established fetal brain sparing. According to the CBCL-total problem score 23.3% of the premature born babies in the brain sparing group had behavioural problems compared with 22.8% of those without brain sparing. According to the TRF-total problem score the percentages were 21.4% and 20.0%, respectively. Logistic regression analysis failed to show a significant association of U/C ratio with behavioural problems. In this model oxygen dependency at 28days, IQ<85 at five years, cranial ultrasound abnormalities, fetal growth ratio<0.80, Apgar scores<7 after 5min and birth weight

Conductive hearing loss in children with bronchopulmonary dysplasia: A longitudinal follow-up study in children aged between 6 and 24months

2010-06-01

Abstract: Aims: To determine the occurrence of isolated and recurrent episodes of conductive hearing loss (CHL) during the first two years of life in very low birth weight (VLBW) infants with and without bronchopulmonary dysplasia (BPD).Study design, subjects and outcome measures: In a longitudinal clinical study, 187 children were evaluated at 6, 9, 12, 15 18 and 24months of age by visual reinforcement audiometry, tympanometry and auditory brain response system.Results: Of the children with BPD, 54.5% presented with episodes of CHL, as opposed to 34.7% of the children without BPD. This difference was found to be statistically significant. The recurrent or persistent episodes were more frequent among children with BPD (25.7%) than among those without BPD (8.3%). The independent variables that contributed to this finding were small for gestational age and a 5min Apgar score.Conclusions: Recurrent CHL episodes are more frequent among VLBW infants with BPD than among VLBW infants without BPD.

The influence of early postnatal nutrition on retinopathy of prematurity in extremely low birth weight infants

Peter J. Porcelli, R. Grey Weaver — 2010-06-01

Abstract: Background: Retinopathy of prematurity(ROP) is the most common serious ophthalmic disease in preterm infants. Human milk may provide a protective effect for ROP; however, beneficial effects of human milk preclude randomized trials. Therefore, we conducted a retrospective analysis comparing early postnatal nutrition with ROP development.Objective: Evaluate relationship between early postnatal nutriture and ROP surgery.Design/methods: Nutrition data was collected for inborn AGA infants, BW 700–1000g. ROP surgery was the primary outcome variable. A single pediatric ophthalmologist supervised examinations. All infants received triweekly IM vitamin A as chronic lung disease prophylaxis (Tyson: NEJM, 1999).Results: BW and gestational age were 867±85g and 26.3±1.2weeks (n=77, mean±1SD). ROP surgery infants(n=11) received more parenteral nutrition, 1648mL, and less human milk, 13.8mL/kg-day, and vitamin E, 1.4mg/kg-day, during the second postnatal week. Human milk was a negative predictor for ROP surgery, odds ratio=0.94. Both groups met vitamin A recommendations; however, 74% was administered via IM injections. Neither group met vitamin E recommendations.Conclusions: Human milk feeding, parenteral nutrition volume and vitamin E intake were predictors for ROP surgery. IM vitamin A injections provided the majority of vitamin A; vitamin E administration was insufficient. Improving human milk feeding rates and vitamin dosing options may affect ROP surgery rates.