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Biomedical subjects

Richard W I Cooke

Publications and source records attributed to Richard W I Cooke.

6 recordsLinked to original sources

Conventional birth weight standards obscure fetal growth restriction in preterm infants.

BACKGROUND AND OBJECTIVE: It has been suggested that fetal growth restriction (FGR) is associated with fetal maturation so that, compared with appropriately grown preterm infants, mortality and some neonatal morbidities may be reduced. The evidence for this is conflicting, and severe FGR has been shown to be harmful. In addition excessive growth has also been shown to be associated with poorer outcomes. As preterm infants are often also growth restricted, centiles for birth weights are distorted and may conceal the degree of growth restriction in a given infant. This study investigated whether using estimated fetal weights (EFW) might reveal the effects of hidden FGR. POPULATION AND METHODS: Using a 25-year database of preterm admissions to a single neonatal unit the ORs for mortality and neonatal morbidities for z scores for birth weight above and below the mean were computed and compared with those computed for z scores for EFW. RESULTS: In 7898 infants born at less than 35 weeks' gestation, the OR for mortality was lowest for birth weights between 1 SD and 3 SD above the mean, but was lowest for EFW between -2 SD and 0 SD below the mean. For periventricular haemorrhage, increasing FGR below the mean reduced the OR with both birth weight and EFW. Apparent reductions in OR for septicaemia, chronic lung disease, persistent ductus arteriosus and necrotising enterocolitis with birth weights of >1 SD above the mean were not seen with EFW. FGR of >-3 SD was associated with increased OR for necrotising enterocolitis with both birth weight and EFW. CONCLUSION: Using fetal growth rather than birth weight standards gives a better indication of the incidence and role of FGR in neonatal disease.

Birth Weight↗

Good practice in consent.

Informed parental consent reminds the health professional to respect parent autonomy with respect to their infant's health care. It involves at least four elements: information, assessment of understanding, assessment of capacity, and freedom to choose. Critical issues are training of staff, timing of approach, and quality and presentation of information. In the newborn period, additional problems include parental distress and competence, consent for research into emergency treatments (exceptions to this are proposed below); screening for future disease, circumcision and withdrawing intensive care are considered as special cases. Variation in practice and policies in European neonatal units is described.

Female↗

Reduction of oxidative stress marker in lung fluid of preterm infants after administration of intra-tracheal liposomal glutathione.

BACKGROUND: Low levels of glutathione are associated with subsequent chronic lung disease in preterm infants. Incorporation of glutathione into liposomes offers a method of increasing levels with a prolonged half-life compared with direct inhalation. OBJECTIVES: The aim of this study was to examine the clinical feasibility of administering a single dose of liposomal glutathione and its effectiveness at raising glutathione at 12 and 24 h after treatment. METHODS: Fourteen ventilated preterm infants from the Regional Neonatal Intensive Care Unit at Liverpool Women's Hospital received 1 mg/kg or 10 mg/kg liposomal glutathione intra-tracheally and bronchoalveolar lavage fluid was collected prior to treatment, 12 and 24 h after dosing for glutathione and malondialdehyde estimation. RESULTS: Mean glutathione was initially 12.2 micromol/l, increasing to 52.8 micromol/l at 12 h (p = 0.006). Mean malondialdehyde was initially 265.6 nmol/l decreasing to 11.2 nmol/l at 12 h (p = 0.018). CONCLUSIONS: Intra-tracheal liposomal glutathione instillation offers a feasible method of raising pulmonary glutathione in preterm infants and shows biochemical antioxidant effects.

Biomarkers↗

Caudate and hippocampal volumes, intelligence, and motor impairment in 7-year-old children who were born preterm.

Children who survive very preterm birth without major disability have a high prevalence of learning difficulty, attention deficit, and minor motor impairment (MMI). To determine whether these difficulties are associated with structural brain abnormalities, we studied 105 preterm children (<32 wk) at 7 y with tests of IQ and MMI (Movement ABC) and detailed magnetic resonance brain scans. Scans were assessed qualitatively for visible cerebral lesions. Volume measurements of the caudate nuclei and hippocampal formations were made. Total brain volume (TBV) was estimated from the head circumference. Qualitative assessment of the scans showed evidence of cerebral lesions in 20 (19%), which were associated with lower IQ and more frequent MMI. IQ correlated with right and left caudate volume (Spearman's rho 0.304 and 0.349; p < 0.01). This association persisted (except for verbal IQ) when caudate volume was expressed as a percentage of estimated TBV to allow for overall brain size. No significant correlations with hippocampal volumes were observed. These differences persisted when only scans from children without visible lesions on scan were considered. MMI was significantly associated only with TBV and was more common in children with evidence of thinning of the posterior corpus callosum, although most children with MMI have a normal corpus callosum. Lower IQs in children who were born preterm are related to poorer development of the caudate relative to the rest of the brain, independent of other lesions. These findings suggest abnormal brain development after perinatal injury or postnatal nutritional deficits is responsible for cognitive deficits in preterm children.

Brain↗

Genetic polymorphisms and retinopathy of prematurity.

PURPOSE: Retinopathy of prematurity (ROP) is a major problem among very preterm survivors of neonatal intensive care. Neovascularization of the retina is prominent in the proliferative stages of ROP and is under the control of several factors such as vascular endothelial growth factor (VEGF). This study was undertaken on the hypothesis that genetic polymorphisms of VEGF, transforming growth factor (TGF)-beta1, and tumor necrosis factor (TNF)-alpha would occur more frequently in preterm infants with progressive ROP than in those with mild or no disease. METHODS: The frequencies of VEGF -634 G-->C, VEGF *936 C-->T, TNF-alpha -308 G-->A, and TGF-beta -509 C-->T were determined in DNA from 91 infants who had received treatment for threshold ROP and 97 comparison infants. RESULTS: The frequencies of the VEGF *936 C-->T, TNF-alpha -308 G-->A and TGF-beta -509 C-->T polymorphisms were similar in both groups. The distribution of alleles at VEGF -634 was significantly different between the two groups (P = 0.03). Homozygotes for the G allele, associated with higher VEGF production were twice as likely to have threshold ROP. CONCLUSIONS: The progression of ROP to threshold ROP in very preterm infants may be influenced by genetic differences in VEGF production. Future efforts at prevention of threshold ROP may be directed toward blocking excess production of VEGF.

Genotype↗

Magnetic resonance imaging and T2 relaxometry of cerebral white matter and hippocampus in children born preterm.

The objective of this study was to determine whether intelligence and minor motor impairments in children who are born preterm without major disability are associated with cerebral white matter (CWM) and hippocampal abnormalities on magnetic resonance imaging (MRI). A total of 103 preterm children were studied at age 7 y with detailed magnetic resonance brain scans, including a T2-mapping sequence from which T2 relaxation times of the CWM and hippocampal formations were calculated. All of the children had no major motor disability, attended normal school, and had undergone assessment of IQ and a test for minor motor impairment (MMI). Twenty children had visible lesions on MRI, which were associated with lower IQ and more frequent MMI. Mean (SD) IQ was 90 (14.1). Twenty-five children were shown to have MMI (Movement ABC at below the fifth centile). This group was shown to have significantly longer T2 relaxation times for CWM (mean difference 2.1 ms right, 3.1 ms left) but not the hippocampus than the children without MMI. These differences persisted when only children without visible lesions on scans were considered (mean difference 1.5 ms bilaterally). There was no significant correlation between IQ and T2 relaxation times. Children who are born preterm without subsequent major neurodisability may, in addition to visible lesions on MRI scans, have a diffuse abnormality of CWM, manifest as an increase in T2 relaxation time. This abnormality shows a close correlation with minor motor impairment but not with full-scale IQ.

Brain Mapping↗