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1.  Impact of congenital colour vision defects on occupation 
Archives of Disease in Childhood  2005;90(9):906-908.
Aims: To investigate whether there is an association between congenital colour vision defects (CVD) and occupational choice and employment history, in order to inform the debate about the value of universal childhood screening for these disorders.
Methods: Participants were 6422 males and 6112 females from the 1958 British birth cohort, followed from birth to 33 years, whose colour vision was assessed (Ishihara test) at 11 years.
Results: A total of 431 males (6.7%) had CVD. Men with CVD had pursued some careers for which normal colour vision is currently regarded as essential; for example, eight men (3.1%) with CVD were in the police, armed forces, or fire-fighting service at 33 years compared to 141 men (3.8%) with normal colour vision. They were, however, under-represented compared to those with normal colour vision, in other occupations; for example, no men with CVD were employed in electrical and electronic engineering at 33 years compared to 15 men (0.4%) with normal colour vision.
Conclusions: The findings of this study suggest there is little to be gained by continuing with existing school screening programmes for CVD, whose primary purpose is to advise affected children against certain careers. Other ways of informing young people about potential occupational difficulties and pathways for referral for specialist assessment are likely to be more useful.
doi:10.1136/adc.2004.062067
PMCID: PMC1720587  PMID: 15914497
2.  Does amblyopia affect educational, health, and social outcomes? Findings from 1958 British birth cohort 
BMJ : British Medical Journal  2006;332(7545):820-825.
Objective To determine any association of amblyopia with diverse educational, health, and social outcomes in order to inform current debate about population screening for this condition.
Design, setting, and participants Comparison of 8432 people with normal vision in each eye with 429 (4.8%) people with amblyopia (childhood unilateral reduced acuity when tested with correction and unaccounted for by eye disease) from the 1958 British birth cohort, with respect to subsequent health and social functioning.
Results No functionally or clinically significant differences existed between people with and without amblyopia in educational outcomes, behavioural difficulties or social maladjustment, participation in social activities, unintended injuries (school, workplace, or road traffic accidents as driver), general or mental health and mortality, paid employment, or occupation based social class trajectories.
Conclusions It may be difficult to distinguish, at population level, between the lives of people with amblyopia and those without, in terms of several important outcomes. A pressing need exists for further concerted research on what it means to have amblyopia and, specifically, how this varies with severity and how it changes with treatment, so that screening programmes can best serve those who have the most to gain from early identification.
doi:10.1136/bmj.38751.597963.AE
PMCID: PMC1432137  PMID: 16520328
4.  Decline in mortality, AIDS, and hospital admissions in perinatally HIV-1 infected children in the United Kingdom and Ireland 
BMJ : British Medical Journal  2003;327(7422):1019.
Objective To describe changes in demographic factors, disease progression, hospital admissions, and use of antiretroviral therapy in children with HIV.
Design Active surveillance through the national study of HIV in pregnancy and childhood (NSHPC) and additional data from a subset of children in the collaborative HIV paediatric study (CHIPS).
Setting United Kingdom and Ireland.
Participants 944 children with perinatally acquired HIV-1 under clinical care.
Main outcome measures Changes over time in progression to AIDS and death, hospital admission rates, and use of antiretroviral therapy.
Results 944 children with perinatally acquired HIV were reported in the United Kingdom and Ireland by October 2002; 628 (67%) were black African, 205 (22%) were aged ≥ 10 years at last follow up, 193 (20%) are known to have died. The proportion of children presenting who were born abroad increased from 20% in 1994-5 to 60% during 2000-2. Mortality was stable before 1997 at 9.3 per 100 child years at risk but fell to 2.0 in 2001-2 (trend P < 0.001). Progression to AIDS also declined (P < 0.001). From 1997 onwards the proportion of children on three or four drug antiretroviral therapy increased. Hospital admission rates declined by 80%, but with more children in follow up the absolute number of admissions fell by only 26%.
Conclusion In children with HIV infection, mortality, AIDS, and hospital admission rates have declined substantially since the introduction of three or four drug antiretroviral therapy in 1997. As infected children in the United Kingdom and Ireland are living longer, there is an increasing need to address their medical, social, and psychological needs as they enter adolescence and adult life.
PMCID: PMC261655  PMID: 14593035
5.  Use of dried blood spots for the detection and confirmation of HTLV-I specific antibodies for epidemiological purposes. 
Journal of Clinical Pathology  1995;48(10):904-907.
AIMS--To modify and evaluate a gelatin particle agglutination test that could provide a sensitive, specific and inexpensive method for the detection of HTLV-I antibody in dried blood spot samples (DBS) collected on filter paper. METHODS--A set of 26 reference samples confirmed as HTLV-I antibody positive were assembled from patients with tropical spastic paraparesis or adult T cell leukaemia and blood donors. Serum samples and simulated antibody positive dried blood spot eluates were tested using the Serodia assay together with two confirmatory tests: HTLV BLOT 2.3, a western blot, and Select-HTLV, an enzyme immunoassay (EIA). Both confirmatory tests use synthetic peptides to differentiate between antibodies to HTLV-I and -II. The modified Serodia assay was then used to test anonymously 10,135 DBS collected from neonates from London. Samples reactive in the modified Serodia test producing a positive result were titrated to an end point and confirmed as before. RESULTS--All 26 eluates made from simulated DBS derived from positive reference samples were identified as positive by the modified Serodia HTLV-I test and were confirmed as anti-HTLV-I positive by EIA. Two eluates derived from relatively low titre reference samples gave indeterminate results on western blotting. Screening of the 10,135 neonatal DBS resulted in six repeat reactives, five of which were confirmed. The remaining reactive sample gave an indeterminate result on western blotting and there was insufficient eluate for testing by EIA. The overall seroprevalence of HTLV-I in this population was 0.05% (five of 10,135). CONCLUSION--The modified Serodia HTLV-I assay provides a sensitive, specific and inexpensive (10 pence/test) method for screening large numbers of DBS. The format of the assay makes it ideally suited for simultaneous screening of antibodies to HIV-1, HIV-2 and HTLV-I using semi-automated equipment.
PMCID: PMC502943  PMID: 8537486
6.  Epidemiology and detection of HIV-1 among pregnant women in the United Kingdom: results from national surveillance 1988-96. 
BMJ : British Medical Journal  1998;316(7127):253-258.
OBJECTIVE: To describe the epidemiology of HIV-1 infection in pregnant women in the United Kingdom. DESIGN: Serial unlinked serosurveillance for HIV-1 in neonatal specimens and surveillance through registers of diagnosed maternal and paediatric infections from reporting by obstetricians, paediatricians, and microbiologists. SETTING: United Kingdom, 1988-96. SUBJECTS: Pregnant women proceeding to live births and their children. MAIN OUTCOME MEASURES: Time trends in prevalence of HIV-1 seropositivity in newborn infants (as a proxy for infection in mothers); the proportions of mothers with diagnosed HIV-1 infections, and their characteristics. RESULTS: HIV-1 prevalence among mothers in London rose sixfold between 1988 and 1996 (0.19% of women tested; 1 in 520 in 1996). Apart from in Edinburgh and Dundee, levels remained low in Scotland (0.025%; 1 in 3970) and elsewhere in the United Kingdom (0.016%; 1 in 1930). Over a third of births to infected mothers in 1996 occurred outside London. In London the reported infections were predominantly among black African women, whereas in Scotland most were associated with drug injecting. The contribution of reported infection among African women increased over time as that of drug injecting declined. In Scotland 51% of mothers' infections were diagnosed before the birth. In England, despite a national policy initiative in 1992 to increase the antenatal detection rate of HIV, no improvement in detection was observed, and in 1996 only 15% of previously unrecognised HIV infections were diagnosed during pregnancy. CONCLUSIONS: HIV-1 infection affects mothers throughout the United Kingdom but is most common in London. Levels of diagnosis in pregnant women have not improved. Surveillance data can monitor effectively the impact of initiatives to reduce preventable HIV-1 infections in children.
PMCID: PMC2665507  PMID: 9472504
7.  Factors affecting uptake of antenatal HIV testing in London: results of a multicentre study. 
BMJ : British Medical Journal  1998;316(7127):259-261.
OBJECTIVES: To measure the uptake of antenatal HIV testing and determine its relation to risk of HIV and to screening practices. DESIGN: Multicentre prospective questionnaire study. SUBJECTS: Pregnant women attending six maternity units. SETTING: Inner London, 1995-6. MAIN OUTCOME MEASURES: Uptake of testing by risk factors for HIV, ethnicity, and factors about the antenatal interview. RESULTS: All units had a "universal offer" policy for HIV testing. In five units forms were completed for 18,791 (88%) of 21,247 pregnant women. The sixth unit, where the response rate was too low to assess uptake, was excluded from the analysis. Uptake ranged from 3.4% to 51.2% (overall 22.9%), in parallel with detection of previously undiagnosed infection in pregnant women (4.9-60%). Controlling for unit, uptake was higher among the 7% who disclosed risk factors. Among those at low risk, uptake varied by ethnic group (South Asian women 9%; Latin American and Mediterranean women 33%). The relation between uptake and HIV risk category varied greatly across units. Despite increased HIV seroprevalence in black African women, uptake was similar in this group to that among women at low risk (24%). Uptake increased 2.1-fold if HIV transmission was discussed. Midwives reported spending 7 (2-15) minutes discussing HIV issues. CONCLUSIONS: Uptake of HIV testing was unacceptably low in all units, with maternity unit the strongest predictor. New approaches to antenatal HIV testing are urgently required and uptake should be audited routinely.
PMCID: PMC2665481  PMID: 9472505
8.  Evaluation of five commercial assays for screening antenatal sera for antibodies to Toxoplasma gondii. 
Journal of Clinical Pathology  1992;45(5):435-438.
AIMS: To evaluate the suitability of five commercial assays (Toxoreagent, DA, Captia Toxo IgG, Toxenz-G, Toxonostika-G) for screening large numbers of sera for antibodies to Toxoplasma gondii. METHODS: Sera from 1000 pregnant women booking for antenatal care at a London hospital were screened in parallel by each test. Sera giving discordant results were retested. RESULTS: The Captia Toxo IgG enzyme immune assay gave the best specificity on initial screening, with 0/773 false positives and only 2/218 false negatives. The Toxoreagent latex agglutination test performed well provided sera were tested at several dilutions to prevent prozone effects; 0/218 false negatives (greater than 12 IU/ml). Only one evidently false positive result was seen in the 1000 samples tested. The DA test gave no false negative results but produced 23/773 false positives. After repeat testing there were 9/1000 sera which gave equivocal results which were negative by the Captia Toxo IgG test (less than 12 IU/ml) but with low titres of 16 in the Toxoreagent test or 4 IU/ml in the DA test. In this situation women would have been asked for a follow up sample for repeat testing. Only 300 sera were tested by Toxenz-G; initial screening produced 4/58 false negative results and 4/242 false positives. CONCLUSIONS: The Captia Toxo IgG test gave the fewest discordant results on initial screening. Results could be readily expressed in international units using a programmable plate reader, and this may be useful for epidemiological studies. The Toxoreagent test is considerably cheaper, and is a simple and reliable method for screening provided that at least two dilutions are used.
PMCID: PMC495309  PMID: 1597524
9.  Adult outcome of normal children who are short or underweight at age 7 years. 
BMJ : British Medical Journal  1995;310(6981):696-700.
OBJECTIVES--To evaluate the adult growth outcome (at age 23) of children who are short or underweight at age 7 years in whom no identifiable pathological cause exists for their poor growth. DESIGN--Longitudinal follow up of a birth cohort. SETTING--The national child development study (1958 birth cohort) of Great Britain. SUBJECTS--523 children with a height or a weight below the fifth centile at age 7. Of these, 70 (13.4%) were excluded because they had a longstanding illness that could account for their poor growth. The remaining 453 subjects, who were followed to age 23, provided the base group from which those with additional data, such as parental height, were obtained. RESULTS--55/174 (31.6%) boys who were short at age 7 became short men; 60/211 (28.4%) girls who were short at age 7 became short women. Among boys who were underweight at age 7, 46/160 (28.7%) were still underweight at age 23, while 61/200 (30.5%) girls underweight at age 7 became underweight women. Having short parents did not increase the probability of being small as an adult. Children with delayed puberty were as likely to remain small as those in whom puberty was not delayed. CONCLUSIONS--One in three normal children who was short or underweight at age 7 became a short or underweight adult. This informs the management of short children and may be valuable when prolonged growth hormone treatment for short stature is being considered.
PMCID: PMC2549095  PMID: 7711536
10.  Maternal prevalence of Toxoplasma antibody based on anonymous neonatal serosurvey: a geographical analysis. 
Epidemiology and Infection  1993;110(1):127-133.
A total of 12,902 neonatal samples collected on absorbent paper for routine metabolic screening were tested anonymously for antibodies to toxoplasma. Seroprevalence varied from 19.5% in inner London, to 11.6% in suburban London, and 7.6% in non-metropolitan districts. Much of this variation appeared to be associated with the proportions of livebirths in each district to women born outside the UK. However, additional geographical variation remained and seroprevalence in UK-born women was estimated to be 12.7% in inner London, 7.5% in suburban London, and 5.5% in non-metropolitan areas. These estimates are considerably lower than any previously reported in antenatal sera in the UK. The wide geographical variation highlights a need for further research to determine the relative importance of different routes of transmission.
PMCID: PMC2271970  PMID: 8432316
12.  Birth weight and body mass index in childhood, adolescence, and adulthood as predictors of blood pressure at age 36. 
STUDY OBJECTIVE--The purpose of this study was to investigate the relation between blood pressure at age 36, and birth weight and body mass index (BMI) in childhood, adolescence and adulthood. DESIGN--Prospective longitudinal survey over a period of 36 years in England, Scotland, and Wales. PARTICIPANTS--A nationally representative sample consisting of 3332 men and women born in one week in March 1946. Altogether 82% of these subjects had complete data for the present analysis. MAIN RESULTS--There was an inverse linear relation between birth weight and blood pressure at age 36. The relation between BMI and blood pressure at age 36 was initially inverse and became increasingly positive throughout life. Weight gain in childhood was positively associated with adult blood pressure, although less important than weight change in later life. The associations between blood pressure and birth weight, and blood pressure and adult BMI were independent, and together they accounted for no more than 4% of the variation in adult blood pressure. Both low birth weight (birth weight < or = 2.5kg) and high BMI at age 36 (BMI > 30kg/m2) were associated with hypertension (> 140/90mmHg), but the per cent population risk of hypertension attributable to low birth weight was less than 5%, and to high BMI less than 12%. CONCLUSIONS--Low birth weight and high BMI at age 36 were independently related to high blood pressure. A reduction in the percentage of low birthweight babies born in the fourth decade of this century would only have a negligible effect on the incidence of adult hypertension 30-40 years later.
PMCID: PMC1059853  PMID: 8120494
13.  Vertically transmitted HIV infection in the British Isles. 
BMJ : British Medical Journal  1993;306(6888):1296-1299.
OBJECTIVE--To describe the epidemiology of vertically acquired HIV infection in the British Isles, the level of underreporting, the vertical transmission rate, and clinical spectrum of paediatric AIDS. DESIGN--Confidential, linked registers based on reporting from obstetricians and paediatricians; anonymous unlinked neonatal HIV serosurveys. SETTING--British Isles. SUBJECTS--Children born to mothers with HIV infection. MAIN OUTCOME MEASURES--Trends in HIV infection and vertical transmission rate. RESULTS--In Scotland and the Irish Republic, where most maternal HIV infection is related to drug misuse, the annual number of reports of children born to infected mothers has fallen since 1989. In England and Wales nearly half of maternal infections have been acquired overseas, and the number of children born to these women, and to women who became infected in Britain, is increasing. In south east England the proportion of live births to women whose infection was identified before delivery was only 17% (50/287), compared with 68% (26/38) in Scotland. The vertical transmission rate was 13.7% (23/168), and 23% of infected children developed AIDS in the first year of life. 41% (38/92) of children born to infected mothers who were ascertained after delivery were breast fed, compared with 5% (12/236) of those ascertained before delivery. CONCLUSIONS--The incidence of vertically transmitted HIV infection is increasing in England and Wales. More extensive antenatal testing would enable infected women to be counselled against breast feeding, which could prevent a substantial proportion of vertical transmission in some areas, and would increase opportunities for early diagnosis and treatment of infected children.
PMCID: PMC1677747  PMID: 8518568
15.  Screening for toxoplasmosis during pregnancy. 
Archives of Disease in Childhood  1993;68(1 Spec No):3-5.
PMCID: PMC1029156  PMID: 8439194
16.  Cytomegalovirus prevalence in pregnant women: the influence of parity. 
Archives of Disease in Childhood  1992;67(7 Spec No):779-783.
Over 20,000 women attending for antenatal care at three London hospitals were prospectively studied to determine the prevalence of cytomegalovirus (CMV) antibodies; 54.4% of these women were CMV seropositive. Ethnic group was strongly associated with CMV status: 45.9% of white women were seropositive, 88.2% of Asian, and 77.2% of black women (African/Caribbean ethnic origin). Among 12,159 white women born in the British Isles, seropositivity was independently associated with increasing parity, older age, lower social class, and being single at antenatal booking. The findings are consistent with the hypothesis that, in the UK, child to mother transmission of infection plays a significant part in the acquisition of CMV infection in adult life.
PMCID: PMC1590405  PMID: 1325757
18.  Outcome of confirmed symptomatic congenital cytomegalovirus infection. 
Archives of Disease in Childhood  1991;66(9):1068-1069.
Sixty five neonates with confirmed symptomatic congenital cytomegalovirus infection were followed up prospectively until they were 3 to 4 year of age. Twenty nine children (45%) had neurological impairment of whom 22 had gross motor or psychomotor abnormalities; in the remaining seven sensorineural deafness was the main abnormality. Infants who had had neurological signs during the neonatal period had a worse prognosis than those who had not, with 16/22 (73%) and 13/43 (30%) having neurological deficit at follow up, respectively. Our results indicate that the prognosis for infants with symptomatic congenital cytomegalovirus infection is better than previously reported.
PMCID: PMC1793063  PMID: 1656894
19.  Too many ethical committees. 
BMJ : British Medical Journal  1990;301(6763):1274.
PMCID: PMC1664373  PMID: 2271833
21.  Childhood morbidity and adulthood ill health. 
STUDY OBJECTIVE--The aim of the study was to investigate the relationship between the state of health in childhood and ill health in early adult life. DESIGN--The study used data collected as part of the National Child Development Study and related health at 7 years of age to that at 23. A wide range of information on child health in the cohort was available, which was used to construct a broader measure of health status than selected diagnostic categories. SETTING--The survey population was nationwide. PARTICIPANTS--The study population included all children born in the week 3-9 March 1958. They were followed up at 7, 11, 16, and 23 years. Of the target population of 17,733 births, 12,537 (76%) were retraced and interviewed at 23. MEASUREMENTS AND MAIN RESULTS--Children at age 7 were allocated to 13 morbidity groups; 20% of children had reported no ill-health apart from the common infectious diseases, but 10% were included in four or more of the morbidity groups. Children with no reported morbidity retained their health advantage into early adulthood: ratios of observed to expected ill health for four of the five indices examined at age 23 were all significantly below one (self rated health 0.81, asthma and/or wheezy bronchitis 0.63, allergies 0.79, emotional health 0.75). Children with more morbidity at age 7 had higher ratios of ill health in adulthood. A chronic condition in childhood was associated not only with excess morbidity in the short term but also with a poor health rating in early adult life (ratio = 1.38). Morbidity was significantly increased for most of the adulthood indices among children with asthma and/or wheezy bronchitis. However most ill health in young adulthood occurred in study members with a relatively healthy childhood. CONCLUSIONS--Although the state of health in childhood has long term implications, it does not form a substantial contribution to ill health in early adult life.
PMCID: PMC1060601  PMID: 2348153
22.  Computer matching of oligonucleotide patterns on electrophoretic gels: an application to the epidemiology of cytomegalovirus. 
Epidemiology and Infection  1988;100(3):467-479.
A computer program was written to analyse oligonucleotide patterns displayed by gel electrophoresis following restriction endonuclease digestion of human cytomegaloviral DNA, and was applied to an epidemiological study of the transmission of infection in a hospital special care baby unit, with regard to infant-to-infant and mother-to-infant transmission. The program calculates the molecular weight of oligonucleotides from their mobilities, using a cubic spline curve based on the mobilities of oligonucleotides from the AD169 strain. A matching algorithm then calculates the number of unmatched fragments for each pair of viral isolates. This was used as a similarity measure which successfully distinguished mother and infant isolate pairs from epidemiologically unrelated pairs. The program is not intended to provide fully automatic matching, but could be recommended as a screening device to pick out pairs of strains which are sufficiently similar to suggest a common source of infection, and which may warrant closer comparison. Other applications are discussed, and the possible use of densitometers to automate data entry is considered.
Images
PMCID: PMC2249347  PMID: 2837406
23.  Cerebral palsy in two national cohort studies. 
Archives of Disease in Childhood  1989;64(6):848-852.
The prevalence of cerebral palsy in the 1958 British Perinatal Mortality Survey and the 1970 British Births Survey remained constant at 2.5/1000 births (40 and 41 cases, respectively). The prevalence at 10 years was higher in the 1970 cohort in which all children with cerebral palsy survived, whereas 22% of the cases in the 1958 cohort died during the first 10 years of life. A case-control study matched three controls for social class, maternal age, parity and marital state, and a further three controls for the infant's sex, gestation, and birth weight. Comparison of cases and controls showed no consistent differences in social and environmental factors, history of pregnancy, labour, or delivery. Important differences were found in the incidence of respiratory and neurological symptoms in the neonatal period. These prospective data derived form two whole populations of births support the hypothesis that most cases of cerebral palsy are not associated with adverse obstetric factors, and confirm that neonatal neurological symptoms are associated with subsequent cerebral palsy.
PMCID: PMC1792585  PMID: 2774617
24.  Weight and age at menarche. 
Archives of Disease in Childhood  1989;64(3):383-387.
In the National Child Development Study (1958 cohort) information on their age at menarche and their weights and heights measured at 7, 11, and 16 years was available for 4427 girls. The distribution of age at menarche was not influenced by social class. Weight adjusted for height did not play an important part in the timing of sexual maturation of the girls in the study. Relative weight (weight expressed as a percentage of standard weight) at the ages of 7 and 11 years explained only 3.2%, and 4.9%, respectively of the variation in age at menarche, and changes in relative weight between these two ages accounted for 2%. Girls with early menarche were more likely to be overweight at ages 7, 11, and 16 years than those with late menarche, although early menarche was also reported by girls who were underweight or of average weight. These findings support the hypothesis that in well nourished populations the relation between menarche and body size is largely regulated by genetic factors and that nutrition is less important.
PMCID: PMC1791908  PMID: 2705803
25.  Prevalence of antibodies to herpes simplex virus types 1 and 2 in pregnant women, and estimated rates of infection. 
There has been a recent increase in notifications of genital herpes but it is not known whether this has been reflected in the pregnant population. We have therefore carried out a study to determine the prevalence of herpes simplex antibodies in pregnant women and to estimate the incidence of primary infection. Sera were collected from 3533 women at antenatal clinics and tested for total antibodies to herpes simples virus (HSV), and if positive, for specific antibodies to HSV-2. Estimates of HSV-1 seroprevalence were derived from the HSV-2 seronegative population. HSV-1 seroprevalence was nearly 100% in black women born in Africa or the Caribbean and 60-80% in white, Asian and UK born black women. It was lower in women in non-manual employment. HSV-2 seroprevalence was related to age, rising from 0 at age 16 to 40% at age 35 in black women, and to about 10% in Asian and white women. The estimated incidence of primary HSV-2 infection during pregnancy, per 1000 pregnancies, was about 2.4 in Asian women, 5 in white women, and 20 in black women. Estimates of the incidence of neonatal infection were derived from these figures and compared to the nationally reported rates.
PMCID: PMC1052791  PMID: 2556492

Results 1-25 (54)