Syphilis screening in pregnancy in the United Kingdom, 2010-2011: a national surveillance study.

OBJECTIVE: To evaluate the national antenatal syphilis screening programme and provide evidence for improving screening and management strategies. DESIGN: National population-based surveillance. SETTING: United Kingdom (UK). POPULATION: All pregnant women screening positive for syphilis, 2010-2011. METHODS: Demographic, laboratory and treatment details for each pregnancy were collected from UK antenatal units (~210), along with follow-up information on all infants born to women requiring syphilis treatment in pregnancy. MAIN OUTCOME MEASURES: Proportion of women with newly or previously diagnosed syphilis among those with positive screening tests in pregnancy; proportion requiring treatment. RESULTS: Overall, 77% (1425/1840) of reported pregnancies were confirmed syphilis screen-positive. Of these, 71% (1010/1425) were in women with previously diagnosed syphilis (155 requiring treatment), 26% (374/1425) with newly diagnosed syphilis (all requiring treatment) and 3% (41/1425) required treatment but the reason for treatment was unclear. Thus 40% (570/1425) required treatment overall; of these, 96% (516/537) were treated (missing data: 33/570), although for 18% (83/456), this was not until the third trimester (missing data: 60/537). Follow up of infants born to treated women was poor, with at least a third not followed. Six infants were diagnosed with congenital syphilis; two mothers were untreated, three had delayed treatment and one had incomplete treatment (first trimester). CONCLUSION: Over 2 years, among pregnant women with confirmed positive syphilis screening results in the UK, a quarter had newly diagnosed infections and 40% required treatment. Despite high uptake of treatment, antenatal syphilis management could be improved by earlier detection, earlier treatment, and stronger links between healthcare teams. TWEETABLE ABSTRACT: 25% of pregnant women screening positive for syphilis in the UK were newly diagnosed and 40% needed treatment.

Hepatitis C virus seroprevalence in pregnant women delivering live-born infants in North Thames, England in 2012.

To estimate HCV seroprevalence in subpopulations of women delivering live-born infants in the North Thames region in England in 2012, an unlinked anonymous (UA) cross-sectional survey of neonatal dried blood spot samples was conducted. Data were available from 31467 samples from live-born infants received by the North Thames screening laboratory. Thirty neonatal samples had HCV antibodies, corresponding to a maternal seroprevalence of 0·095% (95% confidence interval 0·067-0·136). Estimated HCV seroprevalences in women born in Eastern Europe, Southern Asia and the UK were 0·366%, 0·162% and 0·019%, respectively. For women born in Eastern Europe seroprevalence was highest in those aged around 27 years, while in women born in the UK and Asia-Pacific region, seroprevalence increased significantly with age. HCV seroprevalence in UK-born women whose infant's father was also UK-born was 0·016%. One of the 30 HCV-seropositive women was HIV-1 seropositive. Estimated HCV seroprevalence for women delivering live-born infants in North Thames in 2012 (0·095%) was significantly lower than that reported in an earlier UA survey in 1997-1998 (0·191%). Data indicate that the cohort of UK-born HCV-seropositive women is ageing and that, in this area of England, most perinatally HCV-exposed infants were born to women themselves born in Southern Asia or Eastern Europe.

Antiretroviral therapy and preterm delivery-a pooled analysis of data from the United States and Europe.

OBJECTIVE: To investigate reported differences in the association between highly active antiretroviral therapy (HAART) in pregnancy and the risk of preterm delivery among HIV-infected women. DESIGN: Combined analysis of data from three observational studies. SETTING: USA and Europe. POPULATION: A total of 19, 585 singleton infants born to HIV-infected women, 1990-2006. METHODS: Data from the Pediatric Spectrum of HIV Disease project (PSD), a US monitoring study, the European Collaborative Study (ECS), a consented cohort study, and the National Study of HIV in Pregnancy and Childhood (NSHPC), the United Kingdom and Ireland surveillance study. MAIN OUTCOME MEASURE: Preterm delivery rate (<37 weeks of gestation). RESULTS: Compared with monotherapy, HAART was associated with increased preterm delivery risk in the ECS (adjusted odds ratio [AOR] 2.40, 95% CI 1.49-3.86) and NSHPC (AOR 1.43, 95% CI 1.10-1.86), but not in the PSD (AOR 0.92, 95% CI 0.67-1.26), after adjusting for relevant covariates. Because of heterogeneity, data were not pooled for this comparison, but heterogeneity disappeared when HAART was compared with dual therapy (P = 0.26). In a pooled analysis, HAART was associated with 1.5-fold increased odds of preterm delivery compared with dual therapy (95% CI 1.19-1.87, P=0.001), after adjusting for covariates. CONCLUSIONS: Heterogeneity in the association between HAART and preterm delivery was not explained by study design, adjustment for confounders or a standard analytical approach, but may have been the result of substantial differences in populations and data collected. The pooled analysis comparing HAART with dual therapy showed an increased risk of preterm delivery associated with HAART.

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.

Feasibility of collecting oral fluid samples in the home setting to determine seroprevalence of infections in a large-scale cohort of preschool-aged children.

Oral fluid is a non-invasive biological sample, which can be returned by post, making it suitable for large-scale epidemiological studies in children. We report our experience of oral fluid collection from 14 373 preschool-aged children in the UK Millennium Cohort Study. Samples were collected by mothers in the home setting following the guidance of trained interviewers, and posted to the laboratory. Samples were received from 11 698 children (81.4%). Children whose mothers were of Black Caribbean ethnicity and who lived in non-English-speaking households were less likely to provide a sample, and those with a maternal history of asthma more likely to provide a sample [adjusted risk ratio (95% CI) 0.85 (0.73-0.98), 0.87 (0.77-0.98) and 1.03 (1.00-1.05) respectively]. Collection of oral fluid samples is feasible and acceptable in large-scale child cohort studies. Formal interpreter support may be required to increase participation rates in surveys that collect biological samples from ethnic minorities.

Visual impairment due to undiagnosed refractive error in working age adults in Britain.

BACKGROUND: Detection and treatment of undiagnosed refractive error (RE), with its attendant functional consequences, is a priority of VISION 2020, the global initiative against avoidable visual disability. The authors investigated the frequency of visual impairment due to undiagnosed RE and its associations with vision-related quality of life (VRQOL), general health and social circumstances in a contemporary and nationally representative population of British working-age adults. METHODS: 9271 members of the 1958 British birth cohort had visual acuity and VRQOL assessed at 44/45 years. The authors compared those with undiagnosed RE with those with diagnosed RE, defining undiagnosed RE as >or=0.2 logMAR units/2 lines acuity improvement in both eyes with pinhole in individuals without current or prior optical treatment or ophthalmic history. RESULTS: 144/9271 (1.6%) individuals had undiagnosed and 3513/9271 (37.9%) diagnosed RE. 18% (24/144) of those with undiagnosed RE were classifiable as visually impaired. Individuals with undiagnosed RE were more likely to have a manual (vs non-manual) occupation and to be separated, divorced or widowed, and less likely to be in social or professional organisations. There is also some evidence that they are more likely to express concern, embarrassment and frustration about their eyesight and worry about coping with life. CONCLUSION: A significant proportion of working age adults in Britain appear to have undiagnosed but visually significant RE. Improvements in existing opportunities for detecting RE in adults could benefit these individuals during their working lives and avoid the serious adverse consequences associated with vision impairment in later life.

Trends in management and outcome of pregnancies in HIV-infected women in the UK and Ireland, 1990-2006.

OBJECTIVE: To describe the changing demographic profile of diagnosed HIV-infected pregnant women over time and trends in pregnancy outcome, uptake of interventions and mother-to-child transmission. DESIGN: National surveillance study. SETTING: UK and Ireland. POPULATION: Diagnosed HIV-infected pregnant women, 1990-2006. METHODS: Active surveillance of obstetric and paediatric HIV conducted through the National Study of HIV in Pregnancy and Childhood. MAIN OUTCOME MEASURES: Maternal characteristics, pregnancy outcome, use of antiretroviral therapy, mode of delivery and mother-to-child transmission. RESULTS: A total of 8327 pregnancies were reported, increasing from 82 in 1990 to 1394 in 2006, with an increasing proportion from areas outside London. Injecting drug use as the reported risk factor for maternal HIV acquisition declined from 49.2% (185/376) in 1990-1993 to 3.1% (125/4009) in 2004-2006 (P < 0.001), while the proportion of women born in sub-Saharan Africa increased from 43.5% (93/214) in 1990-1993 to 78.6% (3076/3912) in 2004-2006 (P < 0.004). Reported pregnancy terminations decreased from 29.6% (111/376) in 1990-1993 to 3.4% (135/4009) in 2004-2006 (P < 0.001). Most (56.4%, 3717/6593) deliveries were by elective caesarean section, with rates highest in 1999 (66.4%, 144/217). Vaginal deliveries increased from 16.6% (36/217) in 1999 to 28.3% (321/1136) in 2006 (P < 0.001). Use of antiretroviral therapy in pregnancy increased over time, reaching 98.4% (1092/1110) in 2006, and the overall mother-to-child transmission rate declined from 18.5% (35/189) in 1990-1993 to 1.0% (29/2832) in 2004-2006. CONCLUSIONS: The annual number of reported pregnancies increased dramatically between 1990 and 2006, with changing demographic and geographic profiles and substantial changes in pregnancy management and outcome.

Analysis of rubella antibody distribution from newborn dried blood spots using finite mixture models.

Eluted dried blood spot specimens from newborn screening, collected in 2004 in North Thames and anonymously linked to birth registration data, were tested for maternally acquired rubella IgG antibody as a proxy for maternal antibody concentration using an enzyme-linked immunosorbent assay. Finite mixture regression models were fitted to the antibody concentrations from 1964 specimens. The Bayesian Information Criterion (BIC) was used as a model selection criterion to avoid over-fitting the number of mixture model components. This allowed investigation of the independent effect of maternal age and maternal country of birth on rubella antibody concentration without dichotomizing the outcome variable using cut-off values set a priori. Mixture models are a highly useful method of analysis in seroprevalence studies of vaccine-preventable infections in which preset cut-off values may overestimate the size of the seronegative population.

Agreement of rubella IgG antibody measured in serum and dried blood spots using two commercial enzyme-linked immunosorbent assays.

Cases of congenital rubella are now rare in the United Kingdom. However, in certain areas such as London, where a significant proportion of pregnant women has been born abroad and uptake of trivalent measles-mumps-rubella (MMR) vaccination is low, the risk of a rubella outbreak remains. Prior to carrying out a seroprevalence study using rubella IgG antibody in newborn dried blood spots as an indirect marker of maternal immunity, rubella IgG antibody concentrations in serum and dried blood spot samples were investigated. Anonymous paired serum-dried blood spot samples left over from occupational health screening were tested for rubella IgG antibody by two commercially available enzyme-linked immunosorbent assays (ELISAs) (Dade Behring, Marburg, Germany, and Diesse, Siena, Italy). Agreement between serum samples and dried blood spot samples was high for both assays. There were no significant differences in antibody concentrations in paired samples, as 67 of 73 samples tested with the Diesse ELISA (91.8%), and 76 out of 79 samples tested with the Dade Behring ELISA (96.2%) were within two standard deviations of the mean difference. Commercial ELISAs are an appropriate test for seroprevalence surveys based on rubella IgG in dried blood spot samples.

Capturing myopia and hypermetropia 'phenotypes' without formal refraction.

PURPOSE: Understanding genetic and environmental factors that together contribute to the development of myopia is an international research priority. We have investigated the feasibility and accuracy of identifying and classifying refractive error, without formal refraction, as a means of easily identifying affected individuals in a large-scale, non-ophthalmological, and population-based survey. METHODS: At age 44/45 years, members of the 1958 British birth cohort underwent a biomedical, community survey. Refractive error (autorefraction) was measured and categorised by spherical equivalent (SE) measurement; myopia (SE of -1.00 or more extreme), hypermetropia (+1.00 or more extreme), or emmetropia (-0.99 to +0.99). Lenses of prescribed distance glasses, if worn, were assessed as minifying, magnifying, or making no difference to a standard viewed image and cohort members reported on 'short' or 'long' sightedness. RESULTS: A total of 2499 cohort members, randomly selected, had formal refraction (autorefraction) and 917 (36.7%) of these individuals had their prescribed distance glasses examined. Sensitivities for myopia and hypermetropia using examination of glasses were over 80% and positive predictive values were 95 and 65% respectively whereas self-report of 'short-sightedness' or 'long-sightedness' had poor accuracy. CONCLUSION: We suggest examination of prescribed distance glasses can be an effective method of 'screening' for refractive error in the field, especially where prevalence is high.

HIV-1 subtypes in pregnant women in the UK.

We analyse the distribution of HIV-1 subtypes in HIV-1-seropositive samples from 333,270 residual neonatal dried blood spot samples tested for routine newborn screening tests in the UK between July 1999 and December 2002. Of the 813 antibody-positive samples shown to contain passively acquired, maternal HIV-1 for which subtyping was attempted, 333 (41%) could not be subtyped due to cross-reactivity or low values of the assay results, and 480 (59%) were classified as B (35, 7.3%) or non-B (445, 92.7%). The proportions of subtyped B samples differed significantly (P=0.004) between those from neonates whose mothers were born in the UK (21.4%) and those from neonates whose mothers were known to be born abroad (7%). Using a serological approach to establish viral serotype, we document the distribution of HIV-1 subtypes in infected pregnant women in the UK.

Does amblyopia affect educational, health, and social outcomes? Findings from 1958 British birth cohort.

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.

Impact of congenital colour vision defects on occupation.

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.

The health and social environment of uninfected infants born to HIV-infected women.

Against a background of increasing numbers of uninfected children born to HIV-infected women in Europe, we describe the social environment and occurrence of infectious disease in 1,667 infants enrolled in the European Collaborative Study (ECS) and followed prospectively. In the ECS, the proportion of children born to black women from Sub-Saharan Africa who acquired their HIV infection heterosexually has increased since the mid-1980s, while the proportion of those born to white women with a history of illicit drug use has decreased, in both northern and southern Europe. The percentage of children who had been in alternative (non-parental) care decreased from 17% (82/469) in 1985-1989 to 5% (23/436) in 1999-2002. A total of 135 infants (with 1,475 child-years of follow-up) experienced at least one moderate/severe infective or febrile episode requiring medical attention in the first year of life; there was little correlation with recorded sociodemographic and child characteristics. The rate of hospitalization remained relatively stable over the study period at between 243-299 admissions per 1,000 child-years. Description of disease burden and social circumstances of uninfected children is needed, not only because of their increasing numbers but also because they are often used as controls in studies addressing vertically-acquired HIV infection.

Decline in mortality, AIDS, and hospital admissions in perinatally HIV-1 infected children in the United Kingdom and Ireland.

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 > or = 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.

Congenital toxoplasmosis in the United Kingdom: to screen or not to screen?

The United Kingdom National Screening Committee recently reviewed the evidence for prenatal and neonatal screening for toxoplasma infection and concluded that there was insufficient evidence to recommend screening in the United Kingdom. This issue will need to be revisited as new information or treatments become available. In this paper, the extent to which the research evidence on toxoplasma infection meets the criteria that need to be fulfilled for the introduction of screening in the United Kingdom is reviewed.