Regional differences in the frequency of the c.985A>G ACADM mutation: findings from a meta-regression of genotyping and screening studies.

Several countries include medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, a rare autosomal recessive disease, in their newborn screening programmes despite prevalence uncertainty. We estimated the frequency of its most common mutation, c.985A>G, tested for regional differences and compared screening and genotype frequencies. We identified 43 studies reporting the frequency of c.985A>G over 10 million individuals, and pooled frequency data using a novel Bayesian approach. We found significant variation in the frequency of the mutation across regions supporting a reported founder effect. The proportion of c.985A>G homozygotes was highest in Western Europe with 4.1 (95%CI: 2.8-5.6) per 100,000 individuals, then the New World (3.2, 95%CI: 2.0-4.7), Southern (1.2, 95%CI: 0.6-2.0) and Eastern European regions (0.9, 95%CI: 0.5-1.7). No cases with the mutation were identified in Asian and Middle Eastern regions. Significant differences were found in some countries between the genotype and screening allele frequency of c.985A>G. Our predictions could inform the frequency of the mutation by region and our approach could apply to other genetic conditions.

Using cohort studies in lifecourse epidemiology.

The UK Medical Research Council (MRC) Population Health Sciences Research Network is a network of MRC research units and centres that aims to bring together and add value to existing MRC investment in public health, health services and epidemiological research. This symposium held in August 2011 at the World Congress of Epidemiology, Edinburgh, discussed a range of topics including methodology and analytical issues based on a number of examples of cohort studies within the context of lifecourse epidemiology.

Risk factors for rapid weight gain in preschool children: findings from a UK-wide prospective study.

OBJECTIVE: To examine risk factors for rapid weight gain between 3 and 5 years of age. DESIGN: Nationally representative prospective cohort study. PARTICIPANTS: A total of 11 653 preschool children participating in the UK Millennium Cohort Study, with anthropometry at 3 and 5 years. MEASUREMENTS: Weight gain z-scores were calculated from 3 to 5 years. Children in the top quarter of this distribution were classified as gaining weight rapidly. A total of 26 biological and early life, social, psychological, behavioural and environmental risk factors were examined. RESULTS: Among the participants, 13% of normal weight, 63% of overweight and 88% of obese 5-year olds had experienced rapid weight gain since 3 years of age. Six biological and early life factors and two social factors were found to be significantly associated with this growth pattern. In a mutually adjusted model, children were more likely to gain weight rapidly if they had a higher body mass index at age 3 (adjusted odds ratio: 1.27, 95% confidence interval: 1.23-1.32), if they were of Bangladeshi (adjusted odds ratio: 1.88, 95% confidence interval: 1.27-2.79) or black (adjusted odds ratio: 1.47, 95% confidence interval: 1.07-2.02) ethnicity, if their mother was overweight (adjusted odds ratio: 1.32, 95% confidence interval: 1.15-1.51) or had been overweight before pregnancy (adjusted odds ratio: 1.56, 95% confidence interval: 1.36-1.79), if their father was overweight (adjusted odds ratio: 1.56, 95% confidence interval: 1.34-1.81) or if their mother smoked during pregnancy (adjusted odds ratio:1.23, 95% confidence interval: 1.09-1.38). Children were also more likely to gain weight rapidly if others smoked in the same room (adjusted odds ratio: 1.31, 95% confidence interval: 1.16-1.49) or if they were a lone child in the household (adjusted odds ratio: 1.14, 95% confidence interval: 1.01-1.30). CONCLUSIONS: Factors operating during pregnancy and early life increase the risk of rapid weight gain in young children; thus, signalling the importance of obesity prevention programmes before and during pregnancy and for children at an early age. In particular, these programmes should address parental weight status and smoking habits, both modifiable risk factors.

Rubella seroprevalence in pregnant women in North Thames: estimates based on newborn screening samples.

OBJECTIVES: Routine screening for rubella susceptibility is recommended in the UK so that women found to be susceptible can be offered immunization in the post partum period. We demonstrate the use of newborn dried blood spot samples linked to routine vital statistics datasets to monitor rubella susceptibility in pregnant women and to investigate maternal characteristics as determinants of rubella seronegativity. SETTING: North Thames region of England (including large parts of inner London). METHODS: Maternally acquired rubella IgG antibody levels were measured in 18882 newborn screening blood spot samples. Latent class regression finite mixture models were used to classify samples as seronegative to rubella. Data on maternal country of birth were available through linkage to birth registration data. RESULTS: An estimated 2.7% (95% CI 2.4%-3.0%) of newly delivered women in North Thames were found to be seronegative. Mothers born abroad, particularly in Sub-Saharan Africa and South Asia, were more likely to be seronegative than UK-born mothers, with adjusted odds ratios of 4.2 (95% CI 3.1-5.6) and 5.0 (3.8-6.5), respectively. Mothers under 20 years were more likely to be seronegative than those aged 30 to 34. CONCLUSION: Our findings highlight the need for vaccination to be targeted specifically at migrant women and their families to ensure that they are protected from rubella in pregnancy and its serious consequences.

Ethnicity of children with homozygous c.985A>G medium-chain acyl-CoA dehydrogenase deficiency: findings from screening approximately 1.1 million newborn infants.

OBJECTIVES: It has been suggested that homozygous c.985A>G medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a disease of White ethnic origin but little is known regarding its ethnic distribution. We estimated ethnic-specific homozygous c.985A>G MCADD birth prevalence from a large-scale UK newborn screening study. METHODS: Homozygous c.985A>G MCADD cases were ascertained in six English newborn screening centres between 1 March 2004 and 28 February 2007 by screening approximately 1.1 million newborns using tandem mass spectrometry analysis of underivatised blood spot samples to quantitate octanoylcarnitine (C8). Follow-up biochemistry and mutation analyses for cases (mean triplicate C8 value >/=0.5 micromol/L) were reviewed to confirm diagnosis. Ethnicity was ascertained from clinician report and denominators from 2001 UK Census estimates of ethnic group of children less than one year. RESULTS: Sixty-four infants were c.985A>G MCADD homozygotes (overall prevalence 5.8 per 100,000 live births; 95% CI 4.4-7.2). Sixty (93%) were White, two (3%) were mixed/other and two were of unknown ethnic origin. No Asian or Black homozygotes were identified. Proportions of White, mixed/other, Asian and Black births in screening regions were estimated, yielding homozygous c.985A>G MCADD birth prevalence of 6.9 per 100,000 (95% CI 5.2-8.8) in White, and 95% CI estimates of 0-2.7 per 100,000 in Asian and 0-5.8 in Black populations. The c.985A>G carrier frequency in the White group was estimated at one in 65 (95% CI 1/74, 1/61) under Hardy-Weinberg conditions. CONCLUSION: c.985A>G homozygous MCADD is not found in Black and Asian ethnic groups that have been screened at birth in England. This is consistent with the earlier published observations suggesting that MCADD due to the c.985A>G mutation is a disease of White ethnic origin.

The hip trial: psychosocial consequences for mothers of using ultrasound to manage infants with developmental hip dysplasia.

BACKGROUND: The hip trial aimed to assess clinical effectiveness, economic and psychosocial costs, and benefits of ultrasound imaging (US) compared with conventional clinical assessment alone to guide the management of infants with neonatal hip instability. OBJECTIVE: To report on psychosocial consequences for mothers and the developing mother-child relationship of US, and associations between abduction splinting and maternal psychosocial distress. DESIGN: Multicentre randomised controlled trial. SETTING: Thirty three hospitals in the United Kingdom and Ireland. PARTICIPANTS, INTERVENTIONS: A total of 629 infants with neonatal hip instability randomised to US examination or clinical assessment alone before treatment decision. Questionnaires were completed by 561 (89%) mothers at 8 weeks and 494 (79%) at 1 year. MAIN OUTCOME MEASURES: Anxiety, postnatal depression, parenting stress assessed by standardised questionnaires. Maternal concerns about hip problems were assessed using the Infant hip worries inventory. RESULTS: At 8 weeks, there were no differences between US and non-US groups of the trial in maternal anxiety (mean difference (MD) -1.2, 95% confidence interval (CI) -3.2 to 0.8), depression (MD 0.0, 95% CI -0.7 to 0.8), parenting stress (MD -1.2, 95% CI -2.8 to 0.4), or other measures. The same pattern was evident at 1 year. In an explanatory analysis, early splinting was associated with increased anxiety at 8 weeks (MD 3.8, 95% CI 1.7 to 5.9) and increased level of hip worries at 8 weeks (MD 6.8, 95% CI 5.6 to 7.9) and 1 year (MD 1.3, 95% CI 0.3 to 2.4). CONCLUSIONS: Although early splinting is associated with maternal anxieties, US is not associated with any increase or reduction in psychosocial effects on mothers. Together with the clinical findings, this suggests that the use of US allows reduction in splinting rates without increased risk of adverse clinical or psychosocial outcomes.

Congenital and infantile cataract in the United Kingdom: underlying or associated factors. British Congenital Cataract Interest Group.

PURPOSE: Prevention of visual impairment and blindness in childhood due to congenital and infantile cataract is an important international goal. Preventive strategies require information about etiology that is currently unavailable for many regions of the world. From a national epidemiologic study, the underlying or associated factors in newly diagnosed cases of congenital or infantile cataract in the United Kingdom are reported, and the implications for future etiological research are discussed. METHODS: All children with congenital or infantile cataract newly diagnosed during 1 year in the United Kingdom were ascertained independently through two national active surveillance schemes comprising ophthalmologists and pediatricians, respectively. Detailed information about cases, including disease causes, was collected from reporting clinicians using standard questionnaires. RESULTS: Of 243 children with newly diagnosed congenital or infantile cataract, 160 (66%) had bilateral disease. Isolated cataract was more common in bilateral than unilateral cases (61% versus 47%, P = 0.05) as was cataract associated with a systemic disorder (25% versus 6%, P < 0.001). Conversely, cataract with associated ocular anomalies was more common in unilateral than bilateral cases (47% versus 14%, P < 0.001). No underlying or associated risk factors for cataract could be identified in 92% of unilateral and 38% of bilateral cases, although putative prenatal and perinatal risk factors were reported in a proportion of these idiopathic cases. Hereditary disease was associated with 56% of bilateral but only 6% of unilateral cases. Prenatal infections and other systemic factors were reported in only 6% of bilateral and 2% of unilateral cases. CONCLUSIONS: Given the high proportion of idiopathic congenital and infantile cataract, the scope for primary prevention in the United Kingdom is currently limited. There is a need for further etiological research, to examine the roles of environmental and genetic risk factors for idiopathic cataract.

Capture-recapture analysis of ascertainment by active surveillance in the British Congenital Cataract Study.

PURPOSE: Active surveillance has not been widely used in ophthalmologic research. The use of capture-recapture analysis to determine completeness of case ascertainment by active surveillance in a national study of congenital cataract is reported. METHODS: In 1 year in the United Kingdom, all incident diagnoses of congenital and infantile cataract were notified through independent ophthalmic and pediatric active surveillance schemes. Two-source capture-recapture analysis was applied to assess the level of ascertainment of infants (age < or = 12 months) by these two schemes. RESULTS: In a 12-month period, 161 infants with newly diagnosed congenital or infantile cataract were notified. Overall ascertainment was estimated to be 92% complete and was higher in the ophthalmic (85%) than in the pediatric (45%) scheme. Comparison with the number of cases expected, from disease frequency reported in existing national congenital anomaly notification systems, suggests previous underascertainment of congenital cataract in such passive reporting systems. CONCLUSIONS: This study shows the effectiveness of two-source active surveillance in identifying a nationally representative cohort that will provide better information about this disorder than has been available from sources of routinely collected data.

Measuring and interpreting the incidence of congenital ocular anomalies: lessons from a national study of congenital cataract in the UK.

PURPOSE: Prevention of visual impairment due to congenital cataract is an international priority. Estimates of incidence are required for implementation and assessment of preventive strategies, but are not widely available, despite routine monitoring of birth defects at a national level in many industrialized countries. The purpose of this study was to determine the incidence of new diagnosis of congenital and infantile cataract in the United Kingdom. METHODS: All children with newly diagnosed congenital and infantile cataract in the United Kingdom in 1 year from October 1995 through September 1996 were identified using independent ophthalmic and pediatric national active surveillance schemes. Capture-recapture analysis was used to estimate completeness of ascertainment. Annual age-specific and cumulative incidence were estimated and adjusted for ascertainment. RESULTS: Two hundred forty-eight children with newly diagnosed congenital or infantile cataract were identified-an estimated 92% of eligible cases. The adjusted annual age-specific incidence of new diagnosis of congenital and infantile cataract was highest in the first year of life, being 2.49 per 10,000 children (95% confidence interval [CI], 2.10-2.87). Adjusted cumulative incidence at 5 years was 3.18 per 10,000 (95% CI, 2.76-3.59), increasing to 3.46 per 10,000 by 15 years (95% CI, 3.02-3.90). Incidence of bilateral cataract was higher than that of unilateral, but incidence did not vary by sex or country of residence. CONCLUSIONS: These estimates of congenital and infantile cataract incidence were higher than reported previously from routine sources relying on passive notification around the time of birth. Studies of congenital ocular anomalies that are not always readily diagnosed at birth should consider the potential influence on disease frequency of diagnostic practices as well as of underlying disease risk.

Hering-Breuer reflex and respiratory system compliance in the first year of life: a longitudinal study.

The airway occlusion technique for measuring passive respiratory mechanics in infants relies on an ability to evoke the Hering-Breuer lung inflation reflex (HBR). However, there is conflicting evidence regarding the persistence of the HBR beyond the early newborn period. This study was designed to assess maturational changes in HBR activity and passive total respiratory system compliance (Crs) in healthy infants during the 1st yr of life. The strength of the HBR was assessed from the relative change in expiratory time (TE) after brief end-inspiratory airway occlusions compared with resting TE during spontaneous breathing. Crs was measured using the multiple-occlusion technique. Paired measurements of HBR activity and Crs were obtained during sedated sleep in 30 infants at 4-8 wk and at 1 yr of age. Significant HBR activity during tidal breathing persisted throughout the 1st yr of life, with TE increasing during occlusion by at least 26% in every infant. However, the relative strength of the reflex response decreased from a mean of 88.3% (range, 34-160%) at approximately 6 wk to 50.3% (range, 26-125%) by 1 yr of age (P < 0.001). All infants showed an increase in Crs with age, with mean Crs increasing from 60.1 +/- 8.9 (SD) to 149.0 +/- 20.6 ml/kPa between 6 wk and 1 yr. However, there was no apparent relationship between the magnitude of decline in HBR response and the age-related changes in Crs.(ABSTRACT TRUNCATED AT 250 WORDS)

Respiratory compliance in infants--a preliminary evaluation of the multiple interrupter technique.

Measurements of total respiratory system compliance (Crs) using the multiple occlusion technique (MOT) in spontaneously breathing infants can be difficult to interpret in the presence of an unstable end-expiratory level. Similarly, measurements using the passive flow volume technique (PFV) are invalidated if there is alinearity of the expiratory time constant (Trs), irrespective of respiratory effort. For possibly overcoming these problems, we assessed the feasibility of a technique using multiple interruptions of of a single expiration (MIT), obtaining several pairs of volume-pressure data, from one expiration, which relate to a single end-expiratory level. Crs was measured in 16 infants aged 0.5 to 20 months using the MOT, MIT, and PFV technique. The MOT and the MIT each failed in one (different) infant, both succeeding where the other failed. The PFV technique failed in five infants in whom no acceptable plateau of airway pressure during occlusion and no Trs could be obtained from a single breath. Failure to obtain a linear Trs was accompanied by failure of the MIT in only one infant. Individual differences between the MIT and the MOT were less than 9%. However, the PFV measurements varied from -16.3% and +25.7% of the values from MIT or MOT. The greatest differences between Crs values coincided with the greatest differences between volume intercepts of the extrapolated volume-pressure (MOT, MIT) and flow-volume (PFV) data. From this preliminary study, the MIT proved as successful as the MOT, requiring fewer occluded breaths to measure Crs. In infants with a rapid respiratory rate, the data from several expirations can be merged and analyzed as for the MOT.

A critical assessment of uncalibrated respiratory inductance plethysmography (Respitrace) for the measurement of tidal breathing parameters in newborns and infants.

We have compared results obtained with an uncalibrated respiratory inductance plethysmograph (RIP) with those of a face mask and pneumotachograph (PNT) for the computerized measurement of the time to reach peak tidal expiratory flow as a ratio of total expiratory time (tPTEF:tE). Simultaneous measurements were made in 32 healthy neonates aged 0-3 weeks, 35 healthy infants aged 5-82 weeks, and 28 infants aged 15-94 weeks with physician diagnosed recurrent wheeze. The group mean (+/- SD) values of tPTEF:TE determined using a PNT were 0.455 (+/- 0.129), 0.263 (+/- 0.077), and 0.232 (+/- 0.089) for the neonates, healthy infants and infants with recurrent wheeze respectively. RIP gave mean (+/- SD) values that were 0.055 (+/- 0.044) and 0.025 (+/- 0.104) lower than the PNT in healthy neonates and infants with recurrent wheeze respectively; RIP values were 0.002 (+/- 0.073) higher in the healthy infants over 4 weeks of age than measurements by PNT. Although the difference between the two measurements was not related to the thoracoabdominal phase angle, as measured from Lissajous figures, examination of the RIP ribcage and abdominal signals revealed that many healthy subjects, while appearing clinically in phase, had ribcage and abdominal signals that differed markedly from each other in terms of convexity/concavity during early expiration. This may explain the lack of agreement between the two methods. We conclude that uncalibrated RIP should be used with caution for the determination of tPTEF:tE, even in subjects whose ribcage and abdomen appear to move synchronously. The measurement of tPTEF:tE did not differentiate between the healthy infants and infants with recurrent wheezing.

Influence of jacket placement on respiratory compliance during raised lung volume measurements in infants.

SUMMARY. Recent introduction of the raised lung volume rapid thoraco-abdominal compression (RVRTC) technique for measuring forced expiratory maneuvers in infants provides the potential opportunity to assess respiratory mechanics simultaneously by using multiple linear regression (MLR) of the relaxed breaths preceding jacket inflation to force expiration. This study was undertaken to investigate whether data obtained from raised lung volume are influenced by placement of the rapid thoraco-abdominal compression (RTC) squeeze jacket. Paired measurements of tidal volume (V(T)) and respiratory rate (RR) during tidal breathing, and of inflation volume (V(inf)), respiratory system compliance (C(rs)), and resistance (R(rs)) during passive lung inflations were made in 60 (30 male) healthy term infants with and without a fastened, but uninflated RTC jacket in place. Jacket placement was associated with a significant reduction (P < 0.0001) in weight-corrected V(inf) [-1.86 (95% confidence interval, -2.46, -1.27) mL.kg(-1)] and C(rs) [-0.77 (-1.04, -0.49) mL.kPa(-1).kg(-1)]. This represented a reduction in weight-corrected C(rs) from 9.00 to 8.24 mL.kPa(-1).kg(-1), with the fall being >10% in 42% of infants studied. There was no significant change in R(rs) or weight-corrected V(T). If passive respiratory mechanics are to be measured during raised lung volume maneuvers, they should be performed prior to the jacket being fastened, unless considerable care is taken with each infant to ensure that the jacket does not restrict chest wall movement during maximum inflation.

The effect of triclofos sodium sedation on respiratory rate, oxygen saturation, and heart rate in infants and young children.

Chloral hydrate is frequently used to sedate infants for lung function testing. While no effect on respiratory function has been demonstrated, a recent study has reported a fall in oxygen saturation (SaO2) following sedation in wheezy infants. This study was designed to assess the effects of the closely related but less gastrically irritant drug triclofos sodium on respiratory rate (RR), heart rate (HR), and SaO2 in infants without cardiopulmonary disease. Paired measurements using respiratory inductance plethysmography and pulse oximetry were obtained in 10 infants (4-19 months of age) during natural and sedated sleep. Following sedation with triclofos, mean RR rose by 1.9 breaths min-1 (95% confidence intervals [Cl] of the mean difference: 0.13-3.7 min-1). Mean heart rate rose by 5.5 beats min-1 (95% Cl: -0.9-11.9 min-1). Mean SaO2 fell by 0.68% (95% Cl -1.8-0.45%). None of these changes are considered to be of clinical importance, and only the change in RR reached statistical significance at the 5% level.

Influence of sedation on the Hering-Breuer inflation reflex in healthy infants.

The airway occlusion technique for measuring passive respiratory mechanics in infants relies on an ability to evoke the Hering-Breuer inflation reflex (HBR). However, the persistence of this reflex beyond the early newborn period remains controversial. We have recently demonstrated that there is no change in the strength of this reflex during the first two months of life in healthy infants during natural sleep. Measurements beyond this immediate newborn period are difficult without sedation, but it is unclear whether sedation itself may influence this reflex. To investigate the influence of sedation, the HBR was measured in 66 healthy, full-term infants aged 4-8 weeks. Thirty-three infants were measured during natural sleep, and 33 after triclofos sodium sedation (75 mg.kg-1). The strength of the HBR was assessed from the change in expiratory time (TE) following brief end-inspiratory airway occlusion, as compared to TE during spontaneous breathing. The mean increase in TE following occlusion was 89.45% (SD, 29.8; range, 44-175) in infants sleeping naturally, and 92.42% (SD, 31.2; range, 34-179) in sedated infants. Using unpaired t tests, no statistically significant difference was found between groups (P = 0.7516). We conclude that the strength of the HBR in healthy infants is not influenced by sedation with triclofos sodium, in doses normally used for lung function testing.

The relationship between tPTEF:tE and specific airway conductance in infancy.

This study examines the association between the time taken to achieve peak tidal expiratory flow as a proportion of total expiratory time (tPTEF:tE) and specific airways conductance (SGaw) in healthy infants and those with prior physician diagnosed, associated, lower respiratory illness with wheezing (prior LRI) during the first year of life. We compared tPTEF:tE and SGaw, the latter estimated during both initial inspiration (ll) and end-expiration (EE), in 168 infants (94 males), measured on 220 occasions. Mean (range) tPTEF:tE was 0.321 (0.150-0.522) in 73 healthy infants aged less than 3 months (mean, 7.8 weeks), in whom mean (range) EE SGaw and plethysmographic thoracic gas volume at functional residual capacity (FRCpleth) were 2.47 s-1 kPa-1 (0.6-5.8) and 141 mL (87-204), respectively. Both tPTEF:tE and EE SGaw were significantly lower in older infants with prior LRI (n = 79; mean age, 50.0 weeks) compared to a similarly aged group of healthy infants (n = 68; mean age, 48.5 weeks), the mean difference [95% confidence intervals (CI)] being -0.039 (-0.013, -0.064) and -0.48 s-1 kPa-1 (-0.24, -0.72), respectively. A significant but weak association between tPTEF:tE and EE SGaw was found among infants above 3 months of age, irrespective of prior wheezing status. However, this relationship was not significant in healthy younger infants, in whom a significant but weak association with FRCpleth was found. Further work is needed to elucidate the factors influencing tidal expiratory flow patterns in infancy.

Evaluating the national screening programme for congenital dislocation of the hip.

In 1969 universal clinical screening for neonatal hip instability was formally adopted in the United Kingdom with the aim of detecting and treating children considered to be at high risk of congenital dislocation of the hip (CDH). However, clinical screening is associated with both false positive and false negative diagnoses and has never been evaluated in a randomised trial. The emergence of hip ultrasound provides renewed impetus to reconsider and formally evaluate screening for CDH. Ultrasound imaging of the newborn hip may be used as a screening test and to assess and manage infants with clinically detected hip instability. Universal primary ultrasound screening has been adopted in some European countries, but enthusiasm for this new technology has been tempered by the subsequent large increases in treatment and follow up. This paper reviews the existing evidence to support the different approaches to screening and describes the research agenda of the MRC working party on congenital dislocation of the hip. A randomised trial of screening is required to evaluate the policy options before ultrasound screening becomes widely adopted within the United Kingdom. The feasibility and acceptability of a trial need to be explored and key issues relating to trial design addressed.

Prevalence of breastfeeding at four months in general practices in south London.

BACKGROUND: Successive quinquennial National Infant Feeding Surveys have provided a valuable picture of national and regional variations in infant feeding practices within the United Kingdom. Social variation in breastfeeding has been recognised to be an important source of health inequalities in childhood by the Independent Inquiry into Inequalities in Health Report. AIM: To determine the prevalence of breastfeeding at birth and at four months in a sample of women from urban general practices, its variation between practices, and relation to practice population deprivation scores. To report the timing of introduction of solid feeds. DESIGN OF STUDY: Cross-sectional questionnaire survey based on a random cluster sample. SETTING: Women with infants aged four months in general practices in South London. METHOD: Mode of infant feeding at birth and four months, and time of introduction of solids. Jarman score as a measure of practice population deprivation. Housing tenure, maternal ethnic group, and maternal age at leaving full-time education. RESULTS: Twenty-five general practices were sampled. Median practice Jarman score was 15.0 (interquartile range [IQR] = 12.6-21.9). Responses were received from 1053 out of 1532 mothers approached (69%). Of these, 87% (897) had breastfed at birth, while 59% (609) were still breastfeeding their babies at four months. Mothers in rented accommodation were less likely to breastfeed than owner-occupiers (odds ratio [95% CI] = 0.52 [0.37-0.74]), as were women of white, compared with those of black, ethnic origin (odds ratio [95% CI] = 0.55 [0.36-0.82]). Those who completed up to two years and more than two years education after the age of 16 were 2.94 (95% CI = 1.85-4.66) and 9.25 (95% CI = 6.02-14.21) more likely to breastfeed at four months, respectively, than mothers whose formal education was completed at or before 16 years. Practice-specific rates of breastfeeding ranged from 71% to 100% at birth (median 87%; IQR = 79-93%) and 22% to 83% at four months (median 61%; interquartile range = 47-66%). The intra-practice correlation coefficient for breastfeeding at four months was 0.052 (within-cluster variance = 0.23, between-cluster variance = 0.013). There was no association between breastfeeding at four months and practice-specific Jarman score. Median age of starting solids was 16 weeks (IQR = 15-17 weeks). CONCLUSIONS: Housing tenure, maternal education, and ethnic group are significantly associated with breastfeeding prevalence at four months. Between-practice variation in breastfeeding prevalence is not associated with measures of practice population deprivation, as assessed by Jarman scores. Consideration should be given to including information on maternal ethnic group and housing tenure in future National Infant Feeding Surveys. Current weaning practices fall short of the recommendation of the World Health Assembly.

Oral non-steroidal anti-inflammatory drug therapy for cystic fibrosis.

BACKGROUND: Maintenance of optimal lung function is an important therapeutic goal in cystic fibrosis as it is lung damage that, in the long term, is responsible for most premature death among affected people. It has been hypothesised that lung damage results from inflammation and that prolonged use of non-steroidal anti-inflammatory drugs may prevent progressive pulmonary deterioration and respiratory morbidity in cystic fibrosis. It is thus important to establish the current level of evidence about the potential benefits and harms of treatment with non-steroidal anti-inflammatory drugs. OBJECTIVES: The aim of this systematic review is to assess the effectiveness of treatment with non-steroidal anti-inflammatory agents in cystic fibrosis. SEARCH STRATEGY: Trials were ascertained from the Cochrane Cystic Fibrosis and Genetic Disorders Specialised Register of Controlled Trials which includes published and unpublished trials identified through electronic databases such as Medline and Embase as well as those identified from handsearching of journals and conference proceedings. Pharmaceutical companies manufacturing non-steroidal anti-inflammatory drugs were also contacted to identify any trials of non-steroidal anti-inflammatory drugs in cystic fibrosis. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: All randomised or pseudorandomised controlled trials, published and unpublished, comparing non-steroidal anti-inflammatory drugs, administered orally at any dose for a period of at least two months, to placebo in patients with cystic fibrosis. DATA COLLECTION AND ANALYSIS: The following outcomes were assessed: objective measures of lung function, nutritional status, radiological assessment of pulmonary involvement, use of intravenous antibiotics, hospital admissions, survival, frequency of major and minor adverse effects and compliance with therapy. MAIN RESULTS: Three trials involving 145 patients aged from five to 39 years with a maximum follow up of four years met the inclusion criteria. Methodological quality was deemed good or adequate in two. Two trials, both reporting effectiveness of ibuprofen in subjects with mild lung disease, were from the same centre and included some patients in common, while the third assessed piroxicam in subjects with more severe impairment of respiratory function. Variation in outcomes reported and their summary measures precluded calculation of pooled treatment estimates. Only one trial reported within-subject changes in pulmonary function and the findings of this trial suggested that there was a greater absolute annual decline in percentage predicted forced expiratory volume in one second among controls than among those treated with ibuprofen. In a post-hoc sub-group analysis this effect was confined to children aged five to 13 years. In addition, in this one trial long term use of high dose ibuprofen was associated with reduced intravenous antibiotic usage, improved nutritional and radiological pulmonary status. No major adverse effects were reported but the power of the trials to identify clinically important differences in the incidence of adverse effects was low. REVIEWER'S CONCLUSIONS: While there is preliminary evidence to suggest that non-steroidal anti-inflammatory drugs may prevent pulmonary deterioration in subjects with mild lung disease due to cystic fibrosis, currently their routine use cannot be recommended. Further trials are required to confirm that their use prevents pulmonary deterioration and is associated with improved nutritional status. Such trials should also address the age group of subjects most likely to benefit, the prevalence of important adverse effects and the optimal dosage schedule as well as any reduction in concomitant therapy. Multi-centre trials will add to the validity of findings by enhancing their generalisability. The question of whether anti-inflammatory treatment prevents lung damage in pre-symptomatic

Neonatal screening for sickle cell disease.

BACKGROUND: Sickle cell disease is an inherited disorder that occurs throughout the world with its highest incidence in areas of Africa where malaria is endemic. It affects up to one in 60 infants born in some areas of Africa. There are a number of potentially serious complications associated with the condition, and it is suggested that early treatment (before symptoms develop) can improve both morbidity and mortality. Screening for the condition in the neonatal period would enable early diagnosis and therefore early treatment. OBJECTIVES: To assess whether there is evidence that neonatal screening for sickle cell disease rather than symptomatic diagnosis reduces adverse short and long term outcomes for those in whom the disease is detected, without adverse outcomes in the population screened. SEARCH STRATEGY: We searched the Controlled Trials Register of the Cochrane Cystic Fibrosis and Genetic Disorders Group (See Group search strategy). Contact was made with experts in the field for any work as yet unpublished and reference lists of published studies were also searched. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: Any randomised or pseudorandomised trial, published or unpublished comparing diagnosis by screening to clinical diagnosis would have been considered eligible for inclusion. DATA COLLECTION AND ANALYSIS: No trials of neonatal screening for sickle cell disease were found. MAIN RESULTS: No trials of neonatal screening for sickle cell disease were found. REVIEWER'S CONCLUSIONS: There is a lack of evidence from trials of neonatal screening for sickle cell disease. There is evidence of benefit from early treatment which is made possible by screening and there are a number of reviews and economic analyses of non-trial literature suggesting that screening is appropriate. Health care providers must therefore assess whether the information provided by these documents is relevant to their practice and situation when making decisions regarding neonatal screening for sickle cell disease. Systematic reviews of early treatments/interventions, including penicillin prophylaxis, pneumococcal vaccine and parental education should be considered.