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Biomedical subjects

Neil Marlow

Publications and source records attributed to Neil Marlow.

At least 19 recordsLinked to original sources
PubMed2007

Protocol for the smoking, nicotine and pregnancy (SNAP) trial: double-blind, placebo-randomised, controlled trial of nicotine replacement therapy in pregnancy.

BACKGROUND: Smoking in pregnancy remains a public health challenge. Nicotine replacement therapy (NRT) is effective for smoking cessation in non-pregnant people, but because women metabolise nicotine and cotinine much faster in pregnancy, it is unclear whether this will be effective for smoking cessation in pregnancy. The NHS Health Technology Assessment Programme (HTA)-funded smoking, nicotine and pregnancy (SNAP) trial will investigate whether or not nicotine replacement therapy (NRT) is effective, cost-effective and safe when used for smoking cessation by pregnant women. METHODS/DESIGN: Over two years, in 5 trial centres, 1050 pregnant women who are between 12 and 24 weeks pregnant will be randomised as they attend hospital for ante-natal ultrasound scans. Women will receive either nicotine or placebo transdermal patches with behavioural support. The primary outcome measure is biochemically-validated, self-reported, prolonged and total abstinence from smoking between a quit date (defined before randomisation and set within two weeks of this) and delivery. At six months after childbirth self-reported maternal smoking status will be ascertained and two years after childbirth, self-reported maternal smoking status and the behaviour, cognitive development and respiratory symptoms of children born in the trial will be compared in both groups. DISCUSSION: This trial is designed to ascertain whether or not standard doses of NRT (as transdermal patches) are effective and safe when used for smoking cessation during pregnancy.

Adolescent↗
PubMed2006

Establishing neonatal networks: the reality.

Managed clinical networks for neonatal care were established in England from 2004. Their structure and effectiveness varies widely over the country. Changes in medical manpower and the scarcity of neonatal nurses make the move towards networks urgent, but there is little evidence of a coordinated approach to improving capacity in the tertiary centres, who will have to absorb the activity that follows reconfiguration. Changes in the governance of hospitals, NHS authority boundaries and in commissioning specialist services, with the drive towards reducing health costs, places the process at some considerable risk. Despite these challenges, the development of coordinated clinical networks will be an important force in improving outcome for very preterm babies in the UK. The development of some form of national coordination of network activities and greater sharing of good practice would enhance the value of the managed clinical neonatal networks.

Community Networks↗
PubMed2006

Non-pharmacological pain relief.

The delivery of humane neonatal care demands that attention is given to interventions that reduce pain effectively. Painful procedures are common for neonatal patients and a growing body of research suggests that simple non-pharmacological methods are effective in reducing the signs of pain. Both oral sucrose and pacifiers reduce pain scores during procedures, and other simple measures, including facilitated tucking and skin-to-skin contact, might also be effective. Organising care to reduce exposure to painful procedures and also optimising the devices used for procedures might reduce the experience of pain. There is some evidence of long-term improvement in pain sensitivity following pain reduction programmes. Further research is needed to understand the detail of how and when to best apply these interventions; the long-term outcomes of policies that give routine prominence to pain reduction on the neonatal intensive care unit also need to be investigated. The absence of long-term effect should not impede the introduction of these simple, low-cost humane measures.

Analgesia↗
PubMed2006

Outcome after neonatal continuous negative-pressure ventilation: follow-up assessment.

BACKGROUND: A previous randomised trial of continuous negative extrathoracic pressure (CNEP) versus standard treatment for newborn infants with respiratory distress syndrome raised public concerns about mortality and neonatal morbidity. We studied the outcome in late childhood of children entered into the trial to establish whether there were long-term sequelae attributable to either mode of ventilation. METHODS: Outpatient assessment of neurological outcome, cognitive function, and disability was done by a paediatrician and a psychologist using standardised tests. 133 of 205 survivors from the original trial were assessed at 9-15 years of age. Of the original pairs randomly assigned to each ventilation mode, the results from 65 complete pairs were available. The primary outcome was death or severe disability. FINDINGS: Primary outcome was equally distributed between groups (odds ratio for the CNEP group 1.0; 95% CI 0.41-2.41). In unpaired analysis there was no significant difference between treatment modalities (1.05; 0.54-2.06). Full IQ did not differ significantly between the groups, but mean performance IQ was 6.8 points higher in the CNEP group than in the conventional-treatment group (95% CI 1.5-12.1). Results of neuropsychological testing were consistent with this finding, with scores on language production and visuospatial skills being significantly higher in the CNEP group. INTERPRETATION: We saw no evidence of poorer long-term outcome after neonatal CNEP whether analysis was by original pairing or by unpaired comparisons, despite small differences in adverse neonatal outcomes. The experience of our study indicates that future studies of neonatal interventions with the potential to influence later morbidity should be designed with longer-term outcomes in mind.

Adolescent↗
PubMed2006

Staff views on the management of the extremely preterm infant.

OBJECTIVE: To explore the opinions of different healthcare professionals about the use of interventions and outcome in extremely preterm labour. STUDY DESIGN: This was a prospective questionnaire survey. A structured questionnaire was mailed to 142 obstetricians, neonatologists, midwives and neonatal nurses working at City Hospital and Queen's Medical Centre, Nottingham, UK. The current opinions of practice of the healthcare professionals in their antenatal and intrapartum management of a woman with an extremely preterm infant were sought. RESULTS: The overall response was 49% (n=69) after two mailings. Most respondents overestimated infant survival and underestimated intact infant survival rates. Neonatal staff were most likely to wish to use electronic fetal monitoring and administer corticosteroids at the lower extreme gestations. There was no consensus on when to use corticosteroids. Consultant obstetricians were expected to be responsible for counselling parents before delivery, when time allows, but their presence at delivery was not thought to be essential. Neonatal nurses would recommend in utero transfer for women more readily at lower gestations whereas midwives were more reluctant to accept these women as in utero transfers. There were no significant differences in the attitudes to resuscitation of the extremely preterm infant among the different professionals. The median birthweights at which active resuscitation should be commenced ranged from 400 g for neonatal nurses to 500 g for midwives. CONCLUSIONS: Different professional groups perceive outcome differently and this may affect willingness to use interventions at borderline viability. Generally, neonatal staff wished to be more interventional at 21-23 weeks of gestation.

Adrenal Cortex Hormones↗
PubMed2006

Developmental screen or developmental testing?

Given the high risk for residual disability in preterm infants, outcome monitoring is a crucial function of neonatal care. Provision of neurodevelopmental follow-up to at least 2 years of age corrected for prematurity forms part of national recommendations for neonatal services. This should include a developmental assessment at 2 years to identify disability. Although screening tools are cost and time efficient measures, they are not diagnostic and have less utility in high-risk populations. In contrast, standardised developmental tests are ideally suited for follow-up purposes and have become widely accepted as outcome measures. We highlight the properties of standardised tests and review the most commonly used tools for assessment in infancy. We also outline a number of practical issues in the use of standardised tests with preterm infants in identifying morbidity and predicting later impairment. Parental reports are also discussed and key guidelines for developmental testing at 2 years are provided.

Developmental Disabilities↗
PubMed2006

Pushing the boundaries of viability: the economic impact of extreme preterm birth.

BACKGROUND: Previous assessments of the economic impact of preterm birth focussed on short term health service costs across the broad spectrum of prematurity. OBJECTIVE: To estimate the societal costs of extreme preterm birth during the sixth year after birth. METHODS: Unit costs were applied to estimates of health, social and broader resource use made by 241 children born at 20 through 25 completed weeks of gestation in the United Kingdom and Republic of Ireland and a comparison group of 160 children born at full term. Societal costs per child during the sixth year after birth were estimated and subjected to a rigorous sensitivity analysis. The effects of gestational age at birth on annual societal costs were analysed, first in a simple linear regression and then in a multiple linear regression. RESULTS: Mean societal costs over the 12 month period were 9541 pounds sterling (standard deviation 11,678 pounds sterling) for the extreme preterm group and 3883 pounds sterling (1098 pounds sterling) for the term group, generating a mean cost difference of 5658 pounds sterling (bootstrap 95% confidence interval: 4203 pounds sterling, 7256 pounds sterling) that was statistically significant (P<0.001). After adjustment for clinical and sociodemographic covariates, sex-specific extreme preterm birth was a strong predictor of high societal costs. CONCLUSION: The results of this study should facilitate the effective planning of services and may be used to inform the development of future economic evaluations of interventions aimed at preventing extreme preterm birth or alleviating its effects.

Cohort Studies↗
PubMed2006

The costs to the NHS of multiple births after IVF treatment in the UK.

OBJECTIVES: To determine the cost to the NHS resulting from multiple pregnancies arising from IVF treatment in the UK, and to compare those costs with the cost to the NHS due to singleton pregnancies resulting from IVF treatment. DESIGN: A modelling study using data from published literature and cost data from national sources in the public domain, calculating direct costs from the diagnosis of a clinical pregnancy until the end of the first year after birth. SETTING: Academic Unit of Reproductive and Developmental Medicine. POPULATION: Theoretic core modelling study using data from published literature. METHODS: The analysis was based on the total annual number of births resulting from an IVF treatment in the UK. Main outcome measures total direct costs to the NHS per IVF singleton, twin or triplet family. MAIN OUTCOME MEASURES: Cost of singleton, twin and triplet IVF pregnancies in the UK. RESULTS: Total direct costs to the NHS per IVF twin or triplet family (maternal + infant costs) are substantially higher than per IVF singleton family (singleton: pounds 3313; twin: pounds 9122; and triplet: pounds 32,354). Multiple pregnancies after IVF are associated with 56% of the direct cost of IVF pregnancies, although they represent less than 1/3 of the total annual number of maternities in the UK. CONCLUSIONS: Multiple pregnancies after IVF are associated with high direct costs to the NHS. Redirection of money saved by implementation of a mandatory 'two embryo transfer' policy into increased provision of IVF treatment could double the number of NHS-funded IVF treatment cycles at no extra cost. Further savings could be made if a selective 'single embryo transfer' policy were to be adopted.

Decision Trees↗
PubMed2006

Neurodevelopmental and respiratory follow-up results at 7 years for children from the United Kingdom and Ireland enrolled in a randomized trial of early and late postnatal corticosteroid treatment, systemic and inhaled (the Open Study of Early Corticosteroid Treatment).

OBJECTIVES: The goals were to compare early school-age neurodevelopmental and respiratory outcomes for children who were treated with either early (<3 days) or delayed selective (>15 days) postnatal corticosteroid therapy and to compare systemic dexamethasone treatment with inhaled budesonide treatment. METHODS: One hundred twenty-seven (84%) of 152 survivors from the United Kingdom and Ireland who were recruited to the Open Study of Early Corticosteroid Treatment, a randomized trial of inhaled and systemic corticosteroid therapy to prevent chronic lung disease, were traced and assessed at a median age of 7 years. Outcome measures were level of disability, presence of cerebral palsy, cognitive ability, behavioral difficulties and competencies, growth, and respiratory symptoms. Results were adjusted for potential confounding variables (gestational age, birth weight, gender, prenatal steroid therapy, method of delivery, Apgar score at 5 minutes, and Clinical Risk Index for Babies score). RESULTS: There were no significant differences among the treatment groups in cognitive ability, behavioral competencies or difficulties, overall disability rates, cerebral palsy, combined outcomes of death or cerebral palsy and death or moderate/severe disability, growth, respiratory morbidity, or diastolic blood pressure. Those assigned to dexamethasone were more likely to have high systolic blood pressure and to have a diagnosis of asthma than were those assigned to budesonide. CONCLUSIONS: Although postnatal steroid therapy has been associated with poor long-term outcomes, this study failed to show significant differences in cognitive function between dexamethasone- and budesonide-allocated groups. There may be increased systolic blood pressure and a greater likelihood of developing asthma in childhood after postnatal dexamethasone treatment.

Administration, Inhalation↗
PubMed2005

The effect of a monetary incentive on return of a postal health and development questionnaire: a randomised trial [ISRCTN53994660].

BACKGROUND: Postal questionnaires are widely used to collect data in healthcare research but a poor response rate may reduce the validity and reliability of results. There was a lack of evidence available relating to use of a monetary incentive to improve the response rate in the healthcare setting. METHODS: The MRC ORACLE Children Study is assessing the health and development of nearly 9000 seven year old children whose mothers' joined the MRC ORACLE Trial. We carried out a randomised controlled trial of inclusion of monetary incentive (five pound voucher redeemable at many high street stores) with the reminder questionnaire to parents. This trial took place between April 2002 and November 2003. When the parents were sent the reminder questionnaire about their child's health and development they were randomly assigned by concealed computer-generated allocation stratified by week of birthday to receive a five pound voucher or no incentive. The population were 722 non-responders to the initial mailing of a 12-page questionnaire. MAIN OUTCOME MEASURES: Difference in response rate between the two groups. RESULTS: Inclusion of the voucher with the reminder questionnaire resulted in a 11.7%(95% CI 4.7% to 18.6%) improvement in the response rate between the two groups. CONCLUSION: This improvement in response rate and hence the validity and reliability of results obtained appears to be justified ethically and financially.

Adult↗
PubMed2005

Does angiotensin-1 converting enzyme genotype influence motor or cognitive development after pre-term birth?

ABSTRACT : BACKGROUND : Raised activity of the renin-angiotensin system (RAS) may both amplify inflammatory and free radical responses and decrease tissue metabolic efficiency and thus enhance cerebral injury in the preterm infant. The angiotensin-converting enzyme (ACE) DD genotype is associated with raised ACE and RAS activity as well as potentially adverse stimuli such as inflammation. The DD genotype has been associated with neurological impairments in the elderly, and thus may be also associated with poorer motor or cognitive development amongst children born preterm prematurely. METHODS : The association of DD genotype with developmental progress amongst 176 Caucasian children born at less than 33 weeks gestation (median birthweight 1475 g, range 645-2480 g; gestation 30 weeks, range 22-32; 108 male) was examined at 2 and 5 1/2 years of age. Measured neuro-cognitive outcomes were cranial ultrasound abnormalities, cerebral palsy, disability, Griffiths Developmental Quotient [DQ] at 2 yrs, and General Cognitive Ability [British Ability Scales-11] and motor performance [ABC Movement], both performed at 5 1/2 yrs. All outcomes were correlated with ACE genotype. RESULTS : The DD genotype was not associated with lower developmental quotients even after accounting for important social variables. CONCLUSION : These data do not support either a role for ACE in the development of cognitive or motor function in surviving infants born preterm or inhibition of ACE as a neuroprotective therapy.

Journal Article↗
PubMed2005

Neurologic and developmental disability at six years of age after extremely preterm birth.

BACKGROUND: Birth before 26 weeks of gestation is associated with a high prevalence of neurologic and developmental disabilities in the infant during the first two years of life. METHODS: We studied at the time of early school age children who had been born at 25 or fewer completed weeks of gestation in the United Kingdom and Ireland in 1995. Each child had been evaluated at 30 months of age. The children underwent standardized cognitive and neurologic assessments at six years of age. Disability was defined as severe (indicating dependence on caregivers), moderate, or mild according to predetermined criteria. RESULTS: Of 308 surviving children, 241 (78 percent) were assessed at a median age of six years and four months; 160 classmates delivered at full term served as a comparison group. Although the use of test reference norms showed that cognitive impairment (defined as results more than 2 SD below the mean) was present in 21 percent of the children born extremely preterm (as compared with 1 percent in the standardized data), this value rose to 41 percent when the results were compared with those for their classmates. The rates of severe, moderate, and mild disability were 22 percent, 24 percent, and 34 percent, respectively; disabling cerebral palsy was present in 30 children (12 percent). Among children with severe disability at 30 months of age, 86 percent still had moderate-to-severe disability at 6 years of age. In contrast, other disabilities at the age of 30 months were poorly predictive of developmental problems at 6 years of age. CONCLUSIONS: Among extremely preterm children, cognitive and neurologic impairment is common at school age. A comparison with their classroom peers indicates a level of impairment that is greater than is recognized with the use of standardized norms.

Case-Control Studies↗
PubMed2005

Variation in the interleukin-6 gene is associated with impaired cognitive development in children born prematurely: a preliminary study.

The pro-inflammatory cytokine IL-6 may be neurocytopathogenic, and elevated levels are associated with impaired neurological outcome among children born prematurely. However, the precise mechanisms underlying this association remain unclear. The rare C (rather than G) variant at position -572 in the IL-6 gene is associated with an increased IL-6 synthetic response. If IL-6 mediates cerebral injury, we would anticipate the -572 C allele to be associated with impaired childhood development. We have examined this hypothesis, studying 113 Caucasian children born at < or =32 wk gestation. Cognitive and motor functions were assessed using the Griffiths Developmental Scales at 2 y and British Ability Scales (2nd Ed.) and the ABC Movement Score at 51/2 y. Performance (median, interquartile range) in all three scales was worse in the 10 carriers of the C allele than for those with GG genotype: Griffiths Developmental Quotient: C allele, 92.4 (89.9-96.6) versus CG 100.9 (96.7-104.8), p = 0.002; General Cognitive Ability: C allele, 88.0 (80.3-102.8) versus GG 103.0 (92.0-112.0), p = 0.037; Movement ABC score: C allele 8.3 (6.6-20.3) versus GG 4.0 (1.0-9.5), p = 0.081. The presence of the rare (> or =1) IL-6 -572 C-allele (CC+GC genotypes) is associated with impaired cognitive development among children born before 32 wk gestation. These data support a role for IL-6 in the genesis of neurologic impairment in such children.

Alleles↗
PubMed2004

Radiological outcome of very prematurely born infants randomised to high frequency oscillatory or conventional ventilation.

UNLABELLED: The appearance of the chest radiograph (CXR) at 28 days after birth or 36 weeks post-menstrual age (PMA) has been shown to be predictive of respiratory symptoms at follow-up. The aim of this study was to determine whether the CXR appearance at 28 days or 36 weeks PMA differed according to the ventilatory mode used in the perinatal period. CXRs were routinely obtained at 28 days and 36 weeks PMA from infants entered into a multicentre randomised trial (UKOS) comparing high frequency oscillatory ventilation (HFOV) and conventional mechanical ventilation (CMV); the ventilation allocation mode had been instituted within 60 min of birth. The CXRs were assessed using a scoring system (maximum score 8) for the presence of fibrosis/interstitial shadows, cystic elements and hyperinflation. A total of 487 infants, median gestational age 26+5 weeks (range 23-28+6 weeks) and birth weight 865 g (range 428-1459 g) who had had a CXR taken at 28 days and/or 36 weeks PMA. No significant differences were found between the total CXR scores of the two groups either at 28 days or 36 weeks PMA (mean scores 3.2 HFOV versus 3.5 CMV, 95%CI for difference -0.66 to 0.06, P=0.11 at 28 days and mean scores 3.5 HFOV versus 3.6 CMV, 95% for difference -0.49 to 0.29, P=0.61 at 36 weeks PMA). CONCLUSION: These results are consistent with high frequency oscillatory ventilation and conventional mechanical ventilation having similar effects on pulmonary function in very prematurely born infants.

Chronic Disease↗
PubMed2004

Paediatric consequences of fetal growth restriction.

The evidence for outcome following fetal growth restriction (FGR) has previously been inferred from studies, based on babies who were born small for gestational age (SGA). Great care is required when evaluating studies in this area due to a number of potential confounders. It does appear, however, that FGR is associated with an increased risk of poor neurological outcome. This includes an increased risk of cerebral palsy in babies greater than 32 weeks' gestation. Below 32 weeks, the effects of prematurity appear to negate the effects of FGR. FGR is also associated with cognitive deficit and behaviour problems. Babies with poor prenatal head growth appear to have a worse cognitive outcome. However, the role of 'fetal brain sparing' remains unclear, as impaired cognitive outcome is still evident in babies with appropriate head growth. Recent studies, which have identified FGR more accurately using fetal growth standards, have found an increased incidence of major intracranial injury and other adverse neonatal outcomes, which had previously been thought to occur less frequently in FGR babies. FGR is also associated with poor postnatal growth. The majority of children with FGR demonstrate catch-up growth in the first 2 years of life. Children who fail to demonstrate catch-up growth have a high risk of long-term growth problems. There is evidence of impaired growth hormone activity in some children with FGR who have persistent poor growth in the postnatal period.

Cerebral Palsy↗
PubMed2004

Validation of a parent report measure of cognitive development in very preterm infants.

Parental report may provide an inexpensive alternative to standardized assessments of children's development. We have adapted and validated a parental questionnaire on cognitive development for use with very preterm infants. Sixty-four 2-year-olds (28 males, 36 females) born less than 30 weeks' gestation (median 28.5 weeks, range 23 to 31 weeks), median birthweight 980g (range 500 to 1905g) were assessed using the Mental Development Index (MDI) of the Bayley Scales of Infant Development-II and the parental questionnaire. Significant correlations between parent report and MDI scores (r=0.54-0.68, p<0.001) indicated good concurrent validity. Diagnostic use of the parent report for predicting an MDI score of less than 70 was assessed by using receiver operating characteristic (ROC) curves. The optimal cut off produced equal sensitivity and specificity (81%), indicating good discriminatory power in diagnosing developmental delay. Test-retest reliability was demonstrated and accuracy of parent reporting was not affected by sociodemographic factors. Our questionnaire provides a valid outcome measure for use in randomized trials or large population surveys.

Child Development↗
PubMed2004

Does interleukin-6 genotype influence cerebral injury or developmental progress after preterm birth?

OBJECTIVE: The severity of the proinflammatory response may determine outcome in the critically ill. Genetic variation in the promoter region of the gene encoding the proinflammatory cytokine interleukin-6 (IL-6; -174 CC genotype) may encode enhanced production of IL-6. Our objective was to determine whether the CC genotype is associated with worse early illness severity, neurologic injury, and lower developmental scores among surviving preterm children. METHODS: Genotype was determined from dried blood spots that were taken for neonatal screening tests 7 days or more after birth; outcome was independently assessed as part of a longitudinal study of children of < or =32 weeks' gestational age. RESULTS: CC genotype was associated with worse intensive care indices. Significant hemorrhagic brain injuries occurred in 5 (19%) of 27 children with CC genotype compared with 7 (6%) of 121 children with GC or GG genotype, and images consistent with white matter damage (ventriculomegaly or cystic periventricular leukomalacia) occurred in 9 (26%) of CC patients compared with 9 (7%) in GC/GG children. Disability occurred significantly more often in CC children: 8 (31%) compared with 16 (13%). A similar trend was also noted in children with cerebral palsy (15% compared with 7%, respectively). Developmental, cognitive, and motor scores at 2 years and 5.5 years were independent of genotype among children with or without disability. CONCLUSIONS: In a population of surviving children who were born at < or =32 weeks' gestational age, variation of the gene that may increase IL-6 synthesis is associated with disabling brain injury but not cognitive development despite association with worse early critical care indices.

Cerebral Hemorrhage↗