Seasonal patterns of malaria, genital infection, nutritional and iron status in non-pregnant and pregnant adolescents in Burkina Faso: a secondary analysis of trial data.

BACKGROUND: Adolescents are considered at high risk of developing iron deficiency. Studies in children indicate that the prevalence of iron deficiency increased with malaria transmission, suggesting malaria seasonally may drive iron deficiency. This paper examines monthly seasonal infection patterns of malaria, abnormal vaginal flora, chorioamnionitis, antibiotic and antimalarial prescriptions, in relation to changes in iron biomarkers and nutritional indices in adolescents living in a rural area of Burkina Faso, in order to assess the requirement for seasonal infection control and nutrition interventions. METHODS: Data collected between April 2011 and January 2014 were available for an observational seasonal analysis, comprising scheduled visits for 1949 non-pregnant adolescents (≤19 years), (315 of whom subsequently became pregnant), enrolled in a randomised trial of periconceptional iron supplementation. Data from trial arms were combined. Body Iron Stores (BIS) were calculated using an internal regression for ferritin to allow for inflammation. At recruitment 11% had low BIS (< 0 mg/kg). Continuous outcomes were fitted to a mixed-effects linear model with month, age and pregnancy status as fixed effect covariates and woman as a random effect. Dichotomous infection outcomes were fitted with analogous logistic regression models. RESULTS: Seasonal variation in malaria parasitaemia prevalence ranged between 18 and 70% in non-pregnant adolescents (P < 0.001), peaking at 81% in those who became pregnant. Seasonal variation occurred in antibiotic prescription rates (0.7-1.8 prescriptions/100 weekly visits, P < 0.001) and chorioamnionitis prevalence (range 15-68%, P = 0.026). Mucosal vaginal lactoferrin concentration was lower at the end of the wet season (range 2-22 µg/ml, P < 0.016), when chorioamnionitis was least frequent. BIS fluctuated annually by up to 53.2% per year around the mean BIS (5.1 mg/kg2, range 4.1-6.8 mg/kg), with low BIS (< 0 mg/kg) of 8.7% in the dry and 9.8% in the wet seasons (P = 0.36). Median serum transferrin receptor increased during the wet season (P < 0.001). Higher hepcidin concentration in the wet season corresponded with rising malaria prevalence and use of prescriptions, but with no change in BIS. Mean Body Mass Index and Mid-Upper-Arm-Circumference values peaked mid-dry season (both P < 0.001). CONCLUSIONS: Our analysis supports preventive treatment of malaria among adolescents 15-19 years to decrease their disease burden, especially asymptomatic malaria. As BIS were adequate in most adolescents despite seasonal malaria, a requirement for programmatic iron supplementation was not substantiated.

Excess risk of preterm birth with periconceptional iron supplementation in a malaria endemic area: analysis of secondary data on birth outcomes in a double blind randomized controlled safety trial in Burkina Faso.

BACKGROUND: Iron supplementation before a first pregnancy may improve the future health of mother and baby by reducing maternal anaemia. Iron supplementation could, however, increase malaria infections, notably in primigravidae who are most susceptible. The pathogenicity of other iron-utilizing pathogens could also increase, causing inflammation leading to increased risk of adverse birth outcomes. This paper reports pre-specified secondary birth outcomes from a safety trial in Burkina Faso in an area of high malaria endemicity. Primary outcomes from that trial had investigated effects of long-term weekly iron supplementation on malaria and genital tract infections in non-pregnant and pregnant women. METHODS: A double-blind, randomized controlled trial. Nulliparous, mainly adolescent women, were individually randomized periconceptionally to receive weekly either 60 mg elemental iron and 2.8 mg folic acid, or 2.8 mg folic acid alone, continuing up to the first antenatal visit for those becoming pregnant. Secondary outcomes were ultrasound-dated gestational age, fetal growth, placental malaria, chorioamnionitis and iron biomarkers. Seasonal effects were assessed. Analysis was by intention to treat. RESULTS: 478 pregnancies occurred to 1959 women: 258/980 women assigned iron and folic acid and 220/979 women assigned folic acid alone. Malaria prevalence at the first antenatal visit was 53% (iron) and 55% (controls). Mean birthweight was 111 g lower in the iron group (95% CI 9:213 g, P = 0.033). Mean gestational ages were 264 days (iron) and 269 days (controls) (P = 0.012), with 27.5% under 37 weeks compared to 13.9% in controls (adjRR = 2.22; 95% CI 1.39-3.61) P < 0.001). One-third of babies were growth restricted, but incidence did not differ by trial arm. Half of placentae had evidence of past malaria infection. C-reactive protein > 5 mg/l was more common prior to births < 37 weeks (adjRR = 2.06, 95% CI 1.04-4.10, P = 0.034). Preterm birth incidence during the rainy season was ~ 50% in the iron arm and < 20% in controls (P = 0.001). Chorioamnionitis prevalence peaked in the dry season (P = 0.046), with no difference by trial arm (P = 0.14). CONCLUSION: Long-term weekly iron supplementation given to nulliparous women in a malaria endemic area was associated with higher risk of preterm birth in their first pregnancy. Trial Registration NCT01210040. Registered with Clinicaltrials.gov on 27th September 2010.

Effects of Weekly Iron and Folic Acid Supplements on Malaria Risk in Nulliparous Women in Burkina Faso: A Periconceptional, Double-Blind, Randomized Controlled Noninferiority Trial.

Background: The safety of iron supplementation for young women is uncertain in malaria-endemic settings. Methods: This was a double-blind, randomized controlled noninferiority trial in rural Burkina Faso. Results: A total of 1959 nulliparae were assigned to weekly supplementation (60 mg iron and 2.8 mg folic acid) (n = 980) or 2.8 mg folic acid (n = 979) until first antenatal visit (ANC1), or 18 months if remaining nonpregnant. Three hundred fifteen women attended ANC1, and 916 remained nonpregnant. There was no difference at ANC1 in parasitemia prevalence (iron, 53.4% [95% confidence interval {CI}, 45.7%-61.0%]; control, 55.3% [95% CI, 47.3%-62.9%]; prevalence ratio, 0.97 [95% CI, .79-1.18]; P = .82), anemia (adjusted effect, 0.96 [95% CI, .83-1.10]; P = .52), iron deficiency (adjusted risk ratio [aRR], 0.84 [95% CI, .46-1.54]; P = .58), or plasma iron biomarkers. Outcomes in nonpregnant women were parasitemia (iron, 42.9% [95% CI, 38.3%-47.5%]; control, 39.2% [95% CI, 34.9%-43.7%]; prevalence ratio, 1.09 [95% CI, .93-1.28]; P = .282); anemia (aRR, 0.90 [95% CI, .78-1.05]; P = .17), and iron deficiency (aRR, 0.99 [95% CI, .77-1.28]; P = .96), with no iron biomarker differences. Conclusions: Weekly iron supplementation did not increase malaria risk, improve iron status, or reduce anemia in young, mostly adolescent menstruating women, nor in early pregnancy. World Health Organization Guidelines for universal supplementation for young nulliparous women may need reassessment. Clinical Trials Registration: NCT01210040.

Community approval required for periconceptional adolescent adherence to weekly iron and/or folic acid supplementation: a qualitative study in rural Burkina Faso.

BACKGROUND: Iron deficiency remains a prevalent adolescent health problem in low income countries. Iron supplementation is recommended but improvement of iron status requires good adherence. OBJECTIVES: We explored factors affecting adolescent adherence to weekly iron and/or folic acid supplements in a setting of low secondary school attendance. METHODS: Taped in-depth interviews were conducted with participants in a randomised, controlled, periconceptional iron supplementation trial for young nulliparous women living in a rural, malaria endemic region of Burkina Faso. Participants with good, medium or poor adherence were selected. Interviews were transcribed and analysed thematically. RESULTS: Thirty-nine interviews were conducted. The community initially thought supplements were contraceptives. The potential benefits of giving iron supplementation to unmarried "girls" ahead of pregnancy were not recognised. Trial participation, which required parental consent, remained high but was not openly admitted because iron supplements were thought to be contraceptives. Unmarried non-school attenders, being mobile, were often sent to provide domestic labour in varied locations. This interrupted adherence - as did movement of school girls during vacations and at marriage. Field workers tracked participants and trial provision of free treatment encouraged adherence. Most interviewees did not identify health benefits from taking supplements. CONCLUSIONS: For success, communities must be convinced of the value of an adolescent intervention. During this safety trial, benefits not routinely available in iron supplementation programmes were important to this low income community, ensuring adolescent participation. Nevertheless, adolescents were obliged to fulfil cultural duties and roles that interfered with regular adherence to the iron supplementation regime. TRIAL REGISTRATION: Trial Registration at clinicaltrials.gov : NCT01210040.

Effects of long-term weekly iron and folic acid supplementation on lower genital tract infection - a double blind, randomised controlled trial in Burkina Faso.

BACKGROUND: Provision of routine iron supplements to prevent anaemia could increase the risk for lower genital tract infections as virulence of some pathogens depends on iron availability. This trial in Burkina Faso assessed whether weekly periconceptional iron supplementation increased the risk of lower genital tract infection in young non-pregnant and pregnant women. METHODS: Genital tract infections were assessed within a double blind, controlled, non-inferiority trial of malaria risk among nulliparous women, randomised to receive either iron and folic acid or folic acid alone, weekly, under direct observation for 18 months. Women conceiving during this period entered the pregnancy cohort. End assessment (FIN) for women remaining non-pregnant was at 18 months. For the pregnancy cohort, end assessment was at the first scheduled antenatal visit (ANC1). Infection markers included Nugent scores for abnormal flora and bacterial vaginosis (BV), T. vaginalis PCR, vaginal microbiota, reported signs and symptoms, and antibiotic and anti-fungal prescriptions. Iron biomarkers were assessed at baseline, FIN and ANC1. Analysis compared outcomes by intention to treat and in iron replete/deficient categories. RESULTS: A total of 1954 women (mean 16.8 years) were followed and 478 (24.5%) became pregnant. Median supplement adherence was 79% (IQR 59-90%). Baseline BV prevalence was 12.3%. At FIN and ANC1 prevalence was 12.8% and 7.0%, respectively (P < 0.011). T. vaginalis prevalence was 4.9% at FIN and 12.9% at ANC1 (P < 0.001). BV and T. vaginalis prevalence and microbiota profiles did not differ at trial end-points. Iron-supplemented non-pregnant women received more antibiotic treatments for non-genital infections (P = 0.014; mainly gastrointestinal infections (P = 0.005), anti-fungal treatments for genital infections (P = 0.014) and analgesics (P = 0.008). Weekly iron did not significantly reduce iron deficiency prevalence. At baseline, iron-deficient women were more likely to have normal vaginal flora (P = 0.016). CONCLUSIONS: Periconceptional weekly iron supplementation of young women did not increase the risk of lower genital tract infections but did increase general morbidity in the non-pregnant cohort. Unabsorbed gut iron due to malaria could induce enteric infections, accounting for the increased administration of antibiotics and antifungals in the iron-supplemented arm. This finding reinforces concerns about routine iron supplementation in highly malarious areas. TRIAL REGISTRATION: Trial registration number NCT01210040 . Registered with Clinicaltrials.gov on 27 September 2010.

Effect of Human Papillomavirus vaccination of daughters on the cervical screening uptake of their non-vaccinated mothers.

AIM: This study investigated return to cervical screening rates for 112,451 under-screened mothers of daughters offered Human Papillomavirus (HPV) vaccination over two school academic years and a comparator group of women with no vaccine-eligible daughter. RESULTS: Mothers returned to screening more often than the comparator group: odds ratio (OR) 1.04 (95% confidence intervals 1.02-1.07) for lapsed and 1.57 (1.48-1.67) for never screened. Screening return was significantly higher in the year prior to HPV vaccination for lapsed mothers (OR = 1.06) and in the current vaccination year for lapsed and never screened mothers (OR = 1.05 and 1.16 respectively). CONCLUSION: The modest increase in screening attendance indicates a potential for the HPV vaccine programme to increase screening uptake of mothers.

Interventions to improve cervical cancer screening uptake amongst young women: a systematic review.

OBJECTIVES: In view of declining screening uptake in young women, this review aims to summarise the available evidence relating to interventions designed to increase cervical screening uptake amongst women aged ≤ 35 years. METHODS: Electronic databases were searched and further articles located by manual searches. Study designs employing a valid comparison group and including women aged ≤ 35 years published through 2012 were considered. Data was extracted on the uptake from either screening programme statistics or as reported by the study subjects. A narrative synthesis was undertaken for each category of interventions identified. RESULTS: Ninety-two records were screened with 36 articles retrieved for further assessment. Four studies met the inclusion criteria, two of which evaluated more than one intervention. One of the studies evaluated the use of a modified invitation letter and reported no significant increase in uptake compared to a standard invitation. Three studies investigated the use of a reminder letter, with two reporting a positive effect on screening uptake in women aged 24-34. Three studies were included which supported the use of physician and telephone reminders. One study on HPV self-sampling reported a positive effect when compared with a reminder letter. CONCLUSIONS: There is a lack of randomised controlled trials designed to specifically address falling cervical screening uptake in amongst young women. Cervical screening programmes need to look beyond the use of invitation/reminders letters in this group of women to develop interventions which attempt to overcome as many barriers to uptake as possible.

Development of a pre-notification leaflet to encourage uptake of cervical screening at first invitation: a qualitative study.

Cervical screening attendance among women aged 25-29 years in England is lower than at older ages. There is some evidence that pre-notification leaflets motivate women who have not yet considered their response to a health intervention. We aimed to identify key information to motivate young women at their first cervical screening invitation. Six focus groups were conducted, five with young women aged 17-25 registered with a General Practice in Manchester, UK, and one with Practice nurses. Some women took part in two further groups to discuss leaflet design. There was low awareness of the purpose or procedures of cervical screening, and most women were de-motivated by reports of bad experiences. Some intended to be screened, but not immediately after invitation. Screening was viewed as a test for a cancer that affected older women. Since none of the participants believed that they had cervical cancer, screening seemed unnecessary. We conclude that the perception that screening is unimportant when you are young needs to be challenged. Women also need to be better informed of screening procedures. A pre-notification leaflet incorporating key information was designed and will be tested in a randomized trial of complex interventions within the routine cervical screening programme.

Parental smoking and increased likelihood of female births.

BACKGROUND: A recent decline in the male:female (M:F) sex ratio may relate to pregnancy cigarette smoke exposure. AIM: To assess trends and cigarette exposure dose-response effects on the sex ratio. SUBJECTS AND METHODS: A retrospective analysis was carried out of deliveries at the Liverpool Women's Hospital between 1998 and 2003, and of deliveries reported in community surveys from the same area in 1998 and 2006. RESULTS: For the hospital sample, the M:F sex ratio was 1.14 if no parent smoked, and 0.77 when both parents smoked during the mother's pregnancy (p < 0.001). Heavy maternal smokers (>10 cigarettes per day) were more likely to deliver a female baby than light smokers (p < 0.001). Smoking was associated with increased likelihood of female birth controlling for birth year, socio-economic status, alcohol exposure, maternal haemoglobin and body mass index (adjusted OR: 1.41, 95% CI 1.12-1.92, p < 0.001). In the community sample controlling for socio-economic status the ratios were 1.13 (95% CI 1.03-1.24, p = 0.015) in 1998 and 1.31 (95% CI 1.16-1.48, p < 0.001) in 2006. Secular trends showed decreasing ratios in hospital and community samples for both smokers and non-smokers. CONCLUSION: Pregnancy cigarette smoking increased the proportion of female births with evidence for a dose-response association.

Iron Status of Burkinabé Adolescent Girls Predicts Malaria Risk in the Following Rainy Season.

High levels of storage iron may increase malaria susceptibility. This risk has not been investigated in semi-immune adolescents. We investigated whether baseline iron status of non-pregnant adolescent girls living in a high malaria transmission area in Burkina Faso affected malaria risk during the following rainy season. For this prospective study, we analysed data from an interim safety survey, conducted six months into a randomised iron supplementation trial. We used logistic regression to model the risk of P. falciparum infection prevalence by microscopy, the pre-specified interim safety outcome, in relation to iron status, nutritional indicators and menarche assessed at recruitment. The interim survey was attended by 1223 (82%) of 1486 eligible participants, 1084 (89%) of whom were <20 years at baseline and 242 (22%) were pre-menarcheal. At baseline, prevalence of low body iron stores was 10%. At follow-up, 38% of adolescents had predominantly asymptomatic malaria parasitaemias, with no difference by menarcheal status. Higher body iron stores at baseline predicted an increased malaria risk in the following rainy season (OR 1.18 (95% CI 1.05, 1.34, p = 0.007) after adjusting for bed net use, age, menarche, and body mass index. We conclude that routine iron supplementation should not be recommended without prior effective malaria control.

Rural Gambian women's reliance on health workers to deliver sulphadoxine-pyrimethamine as recommended intermittent preventive treatment for malaria in pregnancy.

BACKGROUND: The use of most anti-malarial medications is restricted during pregnancy, but two doses of sulphadoxine-pyrimethamine are recommended after the first trimester as intermittent preventive treatment in pregnancy (IPTp). In The Gambia, only 32% of women receive two doses and very little research has been conducted on women's awareness of drug safety during pregnancy. The objective of this paper was to assess whether rural Gambian women were aware of the importance of the timing of the two-dose IPT dose schedule and its relevance to drug safety. METHODS: This was a qualitative study in which 41 interviews and 16 focus group discussions with women, adolescents, men and traditional birth attendants were conducted. A generic qualitative approach was used to generate a theory as to why women might not participate in IPTp as recommended. RESULTS: Although most women used calendar months to count their stage of pregnancy, these months did not correlate with their concept of foetal development. Foetal growth was described following Islamic tradition as water, clot, piece of meat and human being, although there was little consensus about the order or timing in which these stages occurred. Common signs and conditions of malaria were known. Women were anxious about miscarriage and recognized that some medicines should not be taken in the first trimester, but were urged by men and traditional birth attendants to attend for antenatal care in the first trimester to "start treatment." General knowledge about the purpose of pregnancy medications and when they should be taken was poor among both men and women. One important result was that women relied entirely on health workers to provide safe drugs, at the correct time. CONCLUSION: Women did not have relevant information to judge the safety and appropriate timing of pregnancy drugs, which made them over-reliant on health workers. They should be encouraged to date their own pregnancies in culturally relevant terms and to anticipate when and which medications they should receive.

Delivery of chlamydia screening to young women requesting emergency hormonal contraception at pharmacies in Manchester, UK: a prospective study.

BACKGROUND: More women are requesting Emergency Hormonal Contraception (EHC) at pharmacies where screening for Chlamydia trachomatis is not routinely offered. The objective of this study was to assess the uptake of free postal chlamydia screening by women under 25 years who requested EHC at pharmacies in Manchester, UK. METHODS: Six Primary Care Trusts (PCTs) that had contracted with pharmacies to provide free EHC, requested the largest EHC providers (> or = 40 doses annually) to also offer these clients a coded chlamydia home testing kit. Pharmacies kept records of the ages and numbers of women who accepted or refused chlamydia kits. Women sent urine samples directly to the laboratory for testing and positive cases were notified. Audit data on EHC coverage was obtained from PCTs to assess the proportion of clients eligible for screening and to verify the uptake rate. RESULTS: 33 pharmacies participated. Audit data for 131 pharmacy months indicated that only 24.8% (675/2718) of women provided EHC were also offered chlamydia screening. Based on tracking forms provided by pharmacies for the whole of the study, 1348/2904 EHC clients (46.4%) who had been offered screening accepted a screening kit. 264 (17.6%) of those who accepted a kit returned a sample, of whom 24 (9.1%) were chlamydia-positive. There was an increase in chlamydia positivity with age (OR: 1.2 per year; 1.04 to 1.44; p = 0.015). CONCLUSION: Chlamydia screening for EHC pharmacy clients is warranted but failure of pharmacists to target all EHC clients represented a missed opportunity for treating a well defined high-risk group.

A qualitative study to assess school nurses' views on vaccinating 12-13 year old school girls against human papillomavirus without parental consent.

BACKGROUND: In the UK, parental consent for the routine vaccination of 12-13 year olds schoolgirls against human papillomavirus (HPV) is recommended, although legally girls may be able to consent themselves. As part of a vaccine study conducted ahead of the National HPV Vaccine Programme we sought the views of school nurses on vaccinating girls who did not have parental consent. METHODS: HPV vaccination was offered to all 12 year old girls attending schools in two Primary Care Trusts in Greater Manchester. At the end of the study semi-structured, tape-recorded interviews were conducted with school nurses who had delivered the vaccine (Cervarix). The interview template was based on concepts derived from the Theory of Planned Behaviour. Transcripts were analysed thematically in order to understand school nurses' intentions to implement vaccination based on an assessment of Gillick competency. RESULTS: School nurses knew how to assess the competency of under-16s but were still unwilling to vaccinate if parents had refused permission. If parents had not returned the consent form, school nurses were willing to contact parents, and also to negotiate with parents who had refused consent. They seemed unaware that parental involvement required the child's consent to avoid breaking confidentiality. Nurses' attitudes were influenced by the young appearance and age of the school year group rather than an individual's level of maturity. They were also confused about the legal guidelines governing consent. School nurses acknowledged the child's right to vaccination and strongly supported prevention of HPV infection but ultimately believed that it was the parents' right to give consent. Most were themselves parents and shared other parents' concerns about the vaccine's novelty and unknown long-term side effects. Rather than vaccinate without parental consent, school nurses would defer vaccination. CONCLUSION: Health providers have a duty of care to girls for whom no parental consent for HPV vaccination has been given, and in the UK, this includes conducting, and acting upon, an assessment of the maturity and competence of an adolescent minor. To facilitate this, policies, training and support structures for health providers should be implemented.

The second to fourth digit ratio (2D:4D) in women with and without human papillomavirus and cervical dysplasia.

UNLABELLED: Persistent infection with human papillomavirus (HPV) is associated with a high risk of cervical intraepithelial neoplasia (CIN) and disease progression is influenced by host hormonal factors. The role of fetal exposure to sex steroids has not been explored. The study compared the second to fourth digit ratio (2D:4D), a marker of exposure to fetal androgens, among women with and without HPV and CIN. Data were available from two studies in which HPV, 2D:4D and descriptive variables were assessed cross-sectionally at sexual health clinics. One study (case-control) also assessed cervical smears or biopsies, and some women were retested for persistent HPV. Using these data, 2D:4D was compared among groups defined by cervical smear and HPV result. The cross-sectional data included 90 adolescents and 240 nonadolescents. White women had a significantly higher 2D:4D than other ethnic groups. In the case-control analysis (n = 263), after controlling for ethnicity, women who developed CIN were significantly more likely to have a higher 2D:4D compared with HPV-negative women. A similar, nonsignificant trend was observed among women with a persistent HPV infection. CONCLUSION: Lower fetal androgen exposure may predispose to persistent HPV and increased risk of CIN.

Prenatal smoking exposure and asymmetric fetal growth restriction.

BACKGROUND: Prenatal smoking exposure causes intrauterine fetal growth restriction (IUGR), although its effects on fetal proportionality are less clearly defined. AIM: The present study assessed fetal proportionality in babies with IUGR using maternal salivary cotinine to indicate maternal smoking exposure. SUBJECTS AND METHODS: A case-control study at the Liverpool Women's Hospital, UK of babies with asymmetric and symmetric IUGR and non-growth restricted babies was carried out. RESULTS: 270 white women including 90 IUGR cases and 180 controls were enrolled. Asymmetry presented in 52.2% of IUGR cases. Geometric mean maternal cotinine concentration was higher with asymmetric (p=0.002) than symmetric IUGR (p=0.07), when compared to controls. Maternal smoking exposure was independently associated with asymmetric IUGR (OR 2.4, 95% CI, 1.5-4.4, p

A semi-qualitative study of attitudes to vaccinating adolescents against human papillomavirus without parental consent.

BACKGROUND: The first vaccine to prevent human papillomavirus (HPV) and cervical cancer has been licensed, and in future, vaccination may be routinely offered to 10-14 year old girls. HPV is a sexually transmitted virus and some parents may refuse consent for vaccination. Under-16s in the UK have a right to confidential sexual health care without parental consent. We investigated parents' views on making available HPV vaccination to adolescent minors at sexual health clinics without parental consent. METHODS: This was a semi-qualitative analysis of views of parents of 11-12 year old school children collected as part of a population-based survey of parental attitudes to HPV vaccination in Manchester. Parents were firstly asked if they agreed that a well-informed child should be able to request vaccination at a sexual health clinic without parental consent, and secondly, to provide a reason for this answer. Ethical perspectives on adolescent autonomy provided the framework for descriptive analysis. RESULTS: 307 parents answered the question, and of these, 244 (80%) explained their views. Parents with views consistent with support for adolescent autonomy (n = 99) wanted to encourage responsible behaviour, protect children from ill-informed or bigoted parents, and respected confidentiality and individual rights. In contrast, 97 parents insisted on being involved in decision-making. They emphasised adult responsibility for a child's health and guidance, erosion of parental rights, and respect for cultural and moral values. Other parents (n = 48) wanted clearer legal definitions governing parental rights and responsibilities or hoped for joint decision-making. Parents resistant to adolescent autonomy would be less likely to consent to future HPV vaccination, (67%) than parents supporting this principle (89%; p < 0.001). CONCLUSION: In the UK, the principle of adolescent autonomy is recognised and logically should include the right to HPV vaccination, but this may concern parents who would otherwise approve vaccination.

Review of the evidence for interventions to increase young people's use of health services in developing countries.

OBJECTIVE: This chapter reviews the evidence base for interventions that aim to increase young people's use of health services in developing countries. METHODS: We identified published and unpublished studies and reports from developing countries that provided information about interventions designed to increase young people's use of health services. The studies were classified into six different types based on whether they included some or all of the following characteristics: training for service providers and clinic staff; making efforts to improve the quality of the facilities; implementing community activities to generate demand and support for the services; and involving other sectors, notably schools and the media. The levels of evidence required to make decisions about policies and programmes were defined for each of these types. FINDINGS: Despite the lack of detailed descriptions of interventions in the studies and difficulties interpreting the data reported in the evaluations, the studies provided evidence of increased use of health services by young people for those types of interventions that included training for service providers, making improvements to clinic facilities and implementing activities in the community, with or without the involvement of other sectors. CONCLUSION: The evidence for the effectiveness of interventions to increase young people's use of health services was sufficient to recommend that interventions that include training for service providers, making improvements to clinics and using activities in the community should be widely implemented with careful monitoring of quality and coverage and that those that additionally involve other sectors should also be widely but cautiously implemented, provided they include a strong evaluation component. Operations research is also required to better understand the content of the interventions and their mechanisms of action.

A qualitative study to assess the potential of the human papillomavirus vaccination programme to encourage under-screened mothers to attend for cervical screening.

BACKGROUND: Coverage of the UK National Health Service Cervical Screening Programme is declining. Under-screened women whose daughters participate in the human papillomavirus (HPV) vaccination programme could be stimulated to attend. We investigated whether factors associated with the vaccination programme changed mothers' intentions for future screening. METHODS: Questionnaires were sent to mothers of girls aged 12-13 years across two North West primary care trusts (n=2387) to assess the effect of the HPV vaccination programme on screening intentions. This identified mothers whose intentions had changed. Consent was sought to contact them for a semi-structured interview to discuss their screening intentions. Key themes were identified using framework analysis. RESULTS: 97/606 women responding to the questionnaire had changed their views about cervical screening. 23 women were interviewed, 10 of whom expressed a positive change and 13 no change. Most had discussed the vaccine information, including cervical screening, with their daughters. Mothers who made a positive change decision recognised their daughters' risk of cervical cancer, the need for future screening, and the importance of their own example. In this way daughters became 'significant others' in reinforcing their mothers' cervical screening motivation. CONCLUSIONS: A daughter's invitation for HPV vaccination instigates a reassessment of cervical screening intention in some under-screened mothers.

Perspectives on the design and methodology of periconceptional nutrient supplementation trials.

Periconceptional supplementation could extend the period over which maternal and fetal nutrition is improved, but there are many challenges facing early-life intervention studies. Periconceptional trials differ from pregnancy supplementation trials, not only because of the very early or pre-gestational timing of nutrient exposure but also because they generate subsidiary information on participants who remain non-pregnant. The methodological challenges are more complex although, if well designed, they provide opportunities to evaluate concurrent hypotheses related to the health of non-pregnant women, especially nulliparous adolescents. This review examines the framework of published and ongoing randomised trial designs. Four cohorts typically arise from the periconceptional trial design--two of which are non-pregnant and two are pregnant--and this structure provides assessment options related to pre-pregnant, maternal, pregnancy and fetal outcomes. Conceptually the initial decision for single or micronutrient intervention is central--as is the choice of dosage and content--in order to establish a comparative framework across trials, improve standardisation, and facilitate interpretation of mechanistic hypotheses. Other trial features considered in the review include: measurement options for baseline and outcome assessments; adherence to long-term supplementation; sample size considerations in relation to duration of nutrient supplementation; cohort size for non-pregnant and pregnant cohorts as the latter is influenced by parity selection; integrating qualitative studies and data management issues. Emphasis is given to low resource settings where high infection rates and the possibility of nutrient-infection interactions may require appropriate safety monitoring. The focus is on pragmatic issues that may help investigators planning a periconceptional trial.

A cluster randomised trial of strategies to increase cervical screening uptake at first invitation (STRATEGIC).

BACKGROUND: Falling participation by young women in cervical screening has been observed at a time that has seen an increase in the incidence of cervical cancer in the UK in women aged < 35 years. Various barriers to screening have been documented, including fear, embarrassment and inconvenience. OBJECTIVES: To measure the feasibility, clinical effectiveness and cost-effectiveness of a range of interventions to increase the uptake of cervical screening among young women. DESIGN: A cluster randomised trial based on general practices performed in two phases. SETTING: Primary care in Greater Manchester and the Grampian region in Scotland. PARTICIPANTS: Phase 1: 20,879 women receiving their first invitation for cervical screening. Phase 2: 10,126 women who had not attended by 6 months. INTERVENTIONS: Phase 1: pre-invitation leaflet or not, and access to online booking (Manchester only). Phase 2: (1) vaginal self-sampling kits (SSKs) sent unrequested (n = 1141); or (2) offered on request (n = 1290); (3) provided with a timed appointment (n = 1629); (4) offered access to a nurse navigator (NN) (n = 1007); or (5) offered a choice between a NN or a SSK (n = 1277); and 3782 women in control practices. MAIN OUTCOME MEASURES: Uplift in screening compared with control practices, cost-effectiveness of interventions, and the women's preferences explored in a discrete choice experiment. RESULTS: The pre-invitation leaflet and offer of online booking were ineffective when compared with control practices at 3 months, 18.8% versus 19.2% [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.88 to 1.06; p = 0.485] and 17.8% versus 17.2% (OR 1.02, 95% CI 0.87 to 1.20; p = 0.802), respectively. The uptake of screening at 3 months was higher among previously human papillomavirus (HPV)-vaccinated women than unvaccinated women, 23.7% versus 11% (OR 2.07, 95% CI 1.69 to 2.53; p < 0.001). Among non-attenders, the SSK sent intervention showed a statistically significant increase in uptake at 12 months post invitation, 21.3% versus 16.2% (OR 1.51, 95% CI 1.20 to 1.91; p = 0.001), as did timed appointments, 19.8% versus 16.2% (OR 1.41, 95% CI 1.14 to 1.74; p = 0.001). The offer of a NN, a SSK on request, and a choice between timed appointments and NN were ineffective. Overall, there was a gradual rather than prompt response, as demonstrated by uptake among control practices. A discrete choice experiment indicated that women invited who had not yet attended valued the attributes inherent in self-sampling. The health economic analysis showed that both timed appointments and unsolicited SSK sent were likely to be cost-effective at a cost per quality-adjusted life-year (QALY) gained of £7593 and £8434, respectively, if extended across the national 25-year-old cohort throughout the duration of screening. The certainty of these being cost-effective at a ceiling ratio of £20,000 per QALY gained was > 90%. CONCLUSION: Women receiving their initial screening invitation frequently delay taking up the offer and the net impact of interventions was small. Timed appointments and SSKs sent to non-attenders at 6 months are likely to be a cost-effective means of increasing uptake and should be considered further. HPV vaccination in the catch-up programme was associated with an increased uptake of cervical screening. Future work should focus on optimising self-sampling in terms of age range, timing of offer for non-attenders and use of urine testing instead of vaginal samples. TRIAL REGISTRATION: Current Controlled Trials ISRCTN52303479. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 68. See the NIHR Journals Library website for further project information.