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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 ( Results Seasonal variation in malaria parasitaemia prevalence ranged between 18 and 70% in non-pregnant adolescents (P P P = 0.026). Mucosal vaginal lactoferrin concentration was lower at the end of the wet season (range 2–22 μg/ml, P 2, range 4.1–6.8 mg/kg), with low BIS (P = 0.36). Median serum transferrin receptor increased during the wet season (P P 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.

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 &lt, 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.

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. Electronic supplementary material The online version of this article (10.1186/s12978-018-0490-y) contains supplementary material, which is available to authorized users.

Objectives To measure the feasibility and effectiveness of interventions to increase cervical screening uptake amongst young women. Methods A two-phase cluster randomized trial conducted in general practices in the NHS Cervical Screening Programme. In Phase 1, women in practices randomized to intervention due for their first invitation to cervical screening received a pre-invitation leaflet and, separately, access to online booking. In Phase 2, non-attenders at six months were randomized to one of: vaginal self-sample kits sent unrequested or offered; timed appointments; nurse navigator; or the choice between nurse navigator or self-sample kits. Primary outcome was uplift in intervention vs. control practices, at 3 and 12 months post invitation. Results Phase 1 randomized 20,879 women. Neither pre-invitation leaflet nor online booking increased screening uptake by three months (18.8% pre-invitation leaflet vs. 19.2% control and 17.8% online booking vs. 17.2% control). Uptake was higher amongst human papillomavirus vaccinees at three months (OR 2.07, 95% CI 1.69–2.53, p Conclusions Amongst non-attenders, self-sample kits sent and timed appointments achieved an uplift in screening over the short term; longer term impact is less certain. Prior human papillomavirus vaccination was associated with increased screening uptake.

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 5 mg/l was more common prior to births 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

Weekly iron supplementation, given to young nulliparous women living in a malaria-endemic area, neither improved iron status nor increased malaria risk, suggesting that current iron recommendations may need revisiting for these women., 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.

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 daughter9s invitation for HPV vaccination instigates a reassessment of cervical screening intention in some under-screened mothers.

Background/Aim: Medication use by women of childbearing age is common and cannot be totally avoided because some pregnant women may have chronic pathological conditions that require continuous or uninterrupted treatment. Women may hold different beliefs about the use of medication during pregnancy, which affects their use. This study explores women's beliefs, views and practices concerning medication use during pregnancy. Methods: In this qualitative study, semi-structured interviews were held with 21 pregnant women (age range: 20–39 years) during their first visit to an antenatal clinic at Mitundu Community Hospital in Malawi. Data were collected using an interview guide between February and July 2010. Results: This is the first study in Malawi to interview women about their beliefs and views on medication use in early pregnancy. Notably, most women interviewed in this study did not rely wholly on western or traditional medicine, but used both. This was irrespective of age, parity and educational level. Three overarching themes emerged from the analytical process, namely: i) beliefs about modern and traditional medicines; ii) choice of medication during pregnancy; iii) protection from witchcraft. Conclusions: In general, the beliefs, views and practices of women concerning medication use during pregnancy demonstrate a reliance on superstitious or cultural beliefs to explain the causes of complications during pregnancy. Most of the women interviewed in this study had limited exposure to information, resulting in ignorance of medication use during pregnancy. Women need to be much better educated and encouraged to ask questions so that they are less accepting of superstitious beliefs.

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.

Background Since September 2008, a national vaccine programme in the UK has offered routine human papillomavirus (HPV) vaccination to young women aged 12–13 years. A catch-up programme also offered HPV vaccination to women born after 1 September 1990. Aim To compare indicators of risk and preventive behaviours among young women attending genitourinary medicine (GUM) clinics who had, and had not, received at least one dose of HPV vaccine. Methods Clinical histories and HPV vaccination status were obtained from 363 participants eligible for HPV vaccination (Cervarix ® ) in the UK vaccination programme (born after 1 September 1990) attending GUM clinics in the North West of England. Using logistic regression, markers of sexual and non-sexual risk behaviours were compared between vaccinated and unvaccinated women. Results At least one dose of HPV vaccine had been received by 63.6% ( n =231) of participants. Unvaccinated women demonstrated higher levels of risky behaviour than those who had undergone HPV vaccination. Unvaccinated women were significantly more likely to have had three or more partners in the last 6 months, attended the clinic with symptoms, not used a condom at first sexual intercourse, had anal intercourse with their last sexual contact, to have tested positive for Chlamydia trachomatis diagnosis at the clinic visit and to be a current smoker. Conclusions In the UK, where vaccine coverage is high, failure to initiate HPV vaccination amongst GUM attendees is a marker of high-risk behaviours. As a result, HPV vaccination status should be ascertained as part of an individual9s clinical history by sexual health services to ensure advice and counselling is provided to those at greatest risk of HPV-associated disease.

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.

To estimate the proportion of women in early pregnancy prescribed potentially feto-toxic medications at an out-patient clinic in Malawi.Over six-months the number of women of child-bearing age attending out-patient clinics and prescribed medicines at Mitundu Community Hospital was derived from the hospital's registry and pharmacy records. Women prescribed potentially feto-toxic medicines (using Food and Drug Administration classifications) by medical assessments were subsequently interviewed and pregnancy tested. Exposure to potentially feto-toxic medications was estimated and differences between pregnant and non-pregnant women were described.Of 8970 female outpatients, 1012 (11.3%; 95% CI: 10.6% to 12%) were prescribed potentially feto-toxic medicines. After excluding 740 as unlikely to be pregnant, 209 women had negative pregnancy tests and 63 were confirmed as pregnant, representing one in 16 of women prescribed contraindicated medicines or between 2.8% and 3.5% of all women attending in early pregnancy. Most medicines were FDA rated C or D. Only 152 (55.9%) of these women had been asked about pregnancy and prescribing practices did not discriminate between pregnant and non-pregnant patients.Assessment and prescribing practices for women attending out-patient clinics who might be in early pregnancy were inadequate, increasing the risk of exposure to potentially feto-toxic medicines.

Infection is a major cause of neonatal death in developing countries. This review investigates whether host iron status affects the risk of maternal and/or neonatal infection, potentially contributing to neonatal death, and summarizes the iron acquisition mechanisms described for pathogens causing stillbirth, preterm birth, and congenital infection. In vitro evidence shows that iron availability influences the severity and chronicity of infections that cause these negative outcomes of pregnancy. In vivo evidence is lacking, as relevant studies of maternal iron supplementation have not assessed the effect of iron status on the risk of maternal and/or neonatal infection. Reducing iron-deficiency anemia among women is beneficial and should improve the iron stores of babies; moreover, there is evidence that iron status in young children predicts the risk of malaria and, possibly, the risk of invasive bacterial diseases. Caution with maternal iron supplementation is indicated in iron-replete women who may be at high risk of exposure to infection, although distinguishing between iron-replete and iron-deficient women is currently difficult in developing countries, where a point-of-care test is needed. Further research is indicated to investigate the risk of infection relative to iron status in mothers and babies in order to avoid iron intervention strategies that may result in detrimental birth outcomes in some groups of women.

BackgroundFalling 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 ObjectivesTo measure the feasibility, clinical effectiveness and cost-effectiveness of a range of interventions to increase the uptake of cervical screening among young women.DesignA cluster randomised trial based on general practices performed in two phases.SettingPrimary care in Greater Manchester and the Grampian region in Scotland.ParticipantsPhase 1: 20,879 women receiving their first invitation for cervical screening. Phase 2: 10,126 women who had not attended by 6 months.InterventionsPhase 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 measuresUplift in screening compared with control practices, cost-effectiveness of interventions, and the women’s preferences explored in a discrete choice experiment.ResultsThe 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 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%.ConclusionWomen 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 registrationCurrent Controlled Trials ISRCTN52303479.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 68. See the NIHR Journals Library website for further project information.

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

Background: In England, cervical cancer is the second most common cancer in women aged under 35 years. Overall incidence of cervical cancer has decreased since the introduction of the national screening programme in 1988 but recent trends of incidence in young women have not been studied in detail. Methods: Information on 71 511 incident cases of cervical cancer in England, 1982–2006, in 20–79-year-olds was extracted from a national cancer registration database. Changes in incidence were analysed by age group, time period and birth cohort. Poisson regression was used to estimate annual percentage change (APC). Results: Overall incidence, during 1982–2006, fell significantly from 213 to 112 per million person years. However, in 20–29-year-olds, after an initial fall, incidence increased significantly during 1992–2006, (APC 2.16). In 30–39-year-olds incidence stabilised during the latter part of the study period. The pattern was most marked in the North East, Yorkshire and the Humber and East Midlands regions. Birth cohorts that were initially called for screening between 60–64 and 35–39 years of age show an incidence peak soon after the age of presumed first screen, whereas younger birth cohorts show a peak at about 35 years of age. Incidence in the 1977–1981 birth cohort has increased relative to that among women born between 1962 and 1976. Conclusion: These results have implications for cervical screening, human papilloma virus vaccination and other public health interventions targeting young people.

Two licensed vaccines designed to prevent certain human papillomavirus (HPV) infections are currently available. Their use to prevent cervical cancer has depended on data from clinical trials of safety, immunogenicity and efficacy in preventing surrogate end points of cancer. Following these pivotal studies, HPV vaccines are being introduced into national vaccination programs, mostly in developed countries, and are largely targeting girls 10–14 years of age, with a one-time catch-up opportunity for older teens. Some countries have achieved a level of coverage that is consistent with economic models predicting their cost–effectiveness. At the same time, clinical trials among males and older women have led to pressure to expand the population groups offered HPV vaccination. Over the next 5 years, health authorities will need to make clear decisions about how best to deploy HPV vaccines, as well as to increase or maintain high coverage among young adolescent girls.

This is the final paper in a four-part series which addresses the methodology of research studies under ethical review. The focus is on study conduct, governance and peer review. The nature and adequacy of peer review as a mechanism for assessing the study design and analysis are discussed. The paper argues that a properly constituted and functioning research team is crucial to the ethical conduct of a study and that an ethical review of methodology should extend beyond study design and analysis to a concern with data collection, storage and availability, and publication. While ethical review committees cannot monitor study conduct, they can ensure that the protocol pays sufficient attention to appropriate monitoring structures and personnel.

This was a qualitative study to understand why pharmacists, asked to offer free chlamydia postal screening to Emergency Hormonal Contraception clients, had not offered screening to all eligible women. Twenty-six pharmacists completed exit interviews and 12 agreed to semi-structured in-depth interviews. Although pharmacists were keen to expand their services, they were reluctant to offer chlamydia screening to women who were married or in a long term relationship. To avoid offence they selected women based on age, education and ethnicity. The rationale for chlamydia screening in pharmacy-based EHC schemes is compromised if pharmacists do not offer screening comprehensively.

This is the third of four papers to be published in Research Ethics Review in 2009, that address methodological issues of relevance to research ethics committees. It focuses on three issues: the representativeness of study participants, the size of the study and data analysis. Differences between best practices in qualitative and quantitative research are highlighted. The paper argues that, while lack of representativeness may not be unethical, the ethical implications of unnecessary restrictions on eligibility should be considered by committees. Studies that are either too small or too big can pose problems. Research teams need to have the necessary competence to enable an appropriate analysis focused on the main objectives and interpreted in the context of the limitations of the study design.

This is the second of four papers to be published in Research Ethics Review in 2009 that address methodological issues of relevance to research ethics committees. It focuses on three issues: the appropriateness of the research question, the different types of study design available, including both qualitative and quantitative, and the need for, and choice of, a control group. The paper argues that these issues are key to ethical consideration since inappropriate design may not be salvageable and can lead to unusable data, in which case the risks and burdens to participants would be unjustified.

Objectives: To determine the role of maternal CYP1A1, GSTT1, and GSTM1 metabolic gene polymorphisms in modulating the association between pregnancy smoking exposure and fetal growth restriction. Study design: A case-control study was conducted to investigate if the association of pregnancy smoking and birth outcome was modulated by maternal gene polymorphisms. A total of 90 mothers with an IUGR baby (cases) and 180 mothers without IUGR (controls) were enrolled. Results: Almost half of smokers who carried a CYP1A1 variant (51.3%), GSTT1 null (43.6%), or GSTM1 null genotypes (64.1%) delivered a baby with IUGR. Smokers with the variant CYP1A1 "aa" genotype had babies with lower mean birthweight than non-smokers with the same genotype (p = 0.004). An interaction test showed increased prevalence of IUGR in smokers with the CYP1A1 (Aa/aa) variant (adjusted OR, 1.9; 95% CI, 1.4-5.5, p = 0.01), or with the GSTT1 null (AOR, 1.5; 1.1-3.1, p = 0.001), or GSTM1 null genotypes (AOR, 1.5; 1.2-3.7, p = 0.001). Conclusions: Risk of fetal growth restriction in mothers who smoked during pregnancy was modulated by maternal metabolic gene polymorphisms. The genetic control of the conversion of toxic metabolites of tobacco smoke to less damaging substances is important for maternal and fetal health. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Objectives Control of infectious diseases in developing countries often requires using drugs that are contraindicated during pregnancy. Avoiding inadvertent exposure to drugs involves women (a) recognising pregnancy early, (b) disclosing the pregnancy to health workers and (c) using medicines in an informed manner. We explored these factors to inform and improve the process by which health workers provide care and treatment to pregnant women. Design Qualitative study. Setting The Gambia. Population Rural women and men. Methods We conducted 41 interviews and 16 focus group discussions with women, adolescents, men and traditional birth attendants (TBAs). Main outcome measure Pregnancy disclosure. Results Most women recognised early signs and symptoms of pregnancy and believed other people could easily do so. To avoid gossip, women hid their pregnancies and delayed antenatal care, even though husbands and TBAs insisted on attendance. Women acutely ill in early pregnancy hoped health workers would recognise pregnancy without explicit disclosure. Women said that they knew, and sought to avoid, some contraindicated drugs, but their knowledge was rudimentary. Health workers stressed the benefits, not the risks of prescribed drugs. Conclusions Despite public health and clinical benefits of preventing and treating pregnancy infections, women were ill informed and pressurised into taking drugs. These ethical issues should be more widely addressed.

With the introduction of human papillomavirus (HPV) vaccination an evidence base on effective adolescent educational interventions is urgently required. We undertook formative research to develop and evaluate a film on HPV and cervical cancer prevention for school children who will be offered HPV vaccination in the UK. The main outcome measures were the number of children allowed by parents to view the film and children's knowledge. Our results indicated that the film's four key messages were acceptable to parents and largely understood by adolescents but these messages will need reinforcing if the full potential of a prophylactic vaccine is to be realised.

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.

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

This review summarizes the epidemiology and consequences of maternal smoking in pregnancy, with emphasis on the adverse effects on birth outcomes. In developed countries, approximately 15%, and in developing countries, approximately 8% of women smoke cigarettes, and adolescents and women from lower socioeconomic groups are more likely than other women to smoke while pregnant. Maternal smoking during pregnancy is the largest modifiable risk factor for intrauterine growth restriction. A meta-analysis of recent studies showed that the pooled estimate for reduction of mean birthweight was 174 g (95% confidence limits 132–220 g). Other studies confirm a weaker association between maternal smoking and preterm birth. The population attributable risk of low birthweight due to maternal smoking in the UK is estimated to be 29–39%. Tobacco smoke toxins damage the placenta and may lead to placental abruption, abortion or placenta praevia. Infants of mothers who smoke in pregnancy are at an increased risk of respiratory complications including asthma, obesity and, possibly, behavioral disorders. These effects may be dose-related, as there is good evidence that mean birthweight decrements are greater with increased numbers of cigarettes smoked during pregnancy. Cotinine is a useful indicator of tobacco smoke exposure in pregnant women and higher levels in body fluids have been related to lower birthweights. Maternal genetic polymorphisms of the cytochrome P ( CYP)450 and glutathione- S-transferase ( GST) subfamilies of metabolic genes influence the magnitude of the effect of nicotine exposure on birth outcomes through their influence on nicotine metabolism. Greatly increased risk of cigarette smoke-induced diseases, including low birthweight, has been found in individuals with susceptible genotypes. Interventions to control maternal smoking are also considered.

The main target group for vaccination against human papillomavirus (HPV), the sexually transmitted virus that causes cervical cancer, will be young adolescents. We undertook a population-based survey to assess parental consent and potential HPV vaccine uptake in eight secondary schools using stratified randomisation according to school type and ethnicity. Our results suggest that in socially and ethnically mixed populations such as Manchester, an HPV vaccine uptake rate of 80% may be achievable if the vaccine is perceived to be safe and effective. However, most parents lack knowledge about HPV and some are concerned about sexual health issues that would arise as part of a HPV vaccine programme. It will be important to raise general awareness of the role of HPV in cervical cancer without stigmatizing the vaccine.

ObjectiveMenstrual disorders are common in young women, and heavy menstrual blood losses (MBL) are an important cause of anaemia. Menstrual morbidity normally goes untreated in developing countries where cultural barriers also serve to make the problems. We investigated the prevelance of menstrual morbidity, and measured MBL and its relationship to iron deficiency in a rural adolescent population. The rationale was to assess whether or not reducing heavy MBL could be part of a strategy to reduce iron deficiency anaemia.SettingRural village in south-east Nigeria.DesignCross-sectional survey.SubjectsThe studdy included all non-pregnant, unmarried nulliparous girls (< 20 years) who had menstruated, and who lived in K'Dere village.MethodsA field worker allocated to each girl completed a questionnaire, and supervised recovery and collection of soiled pads and ensured blood sampling. MBL was measured using the standard alkaline haematin method. Haemoglobin (HB), serum iron, transferin saturation and protoporphyrin levels (ZPP) were also measured.Results307 girls completed MBL measurements; 11.9% refused to participate. 12.1% had menorrhagia (> 80 ml);. median MBL was 33.1 ml. Menorrhagia was more frequent in girls who had menstruated for > 2 years (p = 0.048), and had longer duration of meneses (p < 0.001). Iron status as measured by haematocrit, serum iron, transferrin saturation and ZPP values was inversely related to MBL. Neither height nor body mass index for age was associated with current iron status.ConclusionsThe level of menorrhagia detected (12%) may be an ‘expected’ level for a condition which often has no underlying pathology. Heavy MBL is one of the most important factors contributing to iron deficiency anaemia. Measures are needed to alleviate menstrual disorders and improve iron status. Oral contraceptives can be part of a strategy to reduce anaemia, particularly for adolescents at high risk of unwanted pregnancies.

Non-formal education often represents a last chance for adolescent girls who do not attend school to receive some education to improve their health before they become mothers. This paper describes the development of a literacy and health education curriculum for adolescent girls in southern Malawi who will never enter formal schooling. The curriculum was redefined in the light of participants' feedback and providers' observations. The health messages could effect change but would have had limited impact on girls' health practices without the participation of the wider community. The curriculum's innate visibility ‘under the trees’ was a key factor in facilitating villagers' involvement and exponential learning.

Background. Cephalo pelvic disproportion (CPD) has been attributed to short stature. It has been suggested that nutritional supplementation to promote linear growth would increase birthweight and the risk of CPD. The objective of this study was to examine the factors associated with CPD, with particular reference to birthweight, stature, parity and maternal age. Design. Factors associated with CPD were analyzed using data abstracted from a detailed early hospital report from Ibadan, Nigeria and from a recent rural pregnancy study conducted in the Shire Valley Malawi. Results. In Nigeria, of 107 CPD cases admitted to hospital in Ibadan during 1953-54, 79% were women >20 years. Birthweight values increased significantly with age and parity. In 19.6% of cases, the baby had a low birthweight (< 2500 g). In Malawi, among the 1523 women delivering, the incidence of CPD was 2.3%. Of the 35 cases of CPD, only four were adolescents. Birthweights increased with increasing parity, age and height (p < 0.001). In 6.4% of CPD cases, the baby had a low birthweight. Nulliparity (OR 4.0; CI 1.7-9.3; p=0.0001), birthweight ? 3400 g (OR 4.6; CI 2.1-10.0; p = 0.0001) and height < 154 cm (OR 3.8; CI 1.8-7.9; p = 0.0003) were associated with an increased risk of CPD. Adolescent mothers were less likely to experience CPD (OR 0.3; C.I. 0.8-0.9; p = 0.03). Conclusions. Adolescents are not at high risk of CPD. Nutritional supplementation of girls and adolescents should not be discouraged for fear of increasing the risk of CPD by improving birthweight. When CPD is present, it may result from childhood rickets and calcium deficiency.

Sex hormones influence susceptibility and disease predisposition for many genital tract infections. This review describes the mechanisms by which sex steroids affect mucosal immunity, with particular reference to human immunodeficiency virus (HIV) and genital herpes, and the stage-specific effects of hormonal contraception on human papillomavirus (HPV) infection. Estrogen's role is important in the early stages of several infections as it stimulates antibody- and cell-mediated immune responses. There is increased expression of some cytokines in peripheral blood and vaginal fluids during the follicular phase of the menstrual cycle and with use of hormonal contraception. Whether estrogen exerts a protective or deleterious influence depends on the infecting organism and stage of infection or disease. Estrogen apparently reduces susceptibility to primary HPV infection but in the event of persistent HPV infection, sex steroid hormones (estrogen and/or progesterone) are associated with progression to cervical cancer. It is important that these stage-specific effects are better described because most vaccines will try to prevent either infection or disease. Clinicians with patients at high risk of sexually transmitted infections, especially HIV, require better information on the risks associated with different hormonal contraceptive regimes.

Most pregnant women in Burkina Faso are iron deficient and many are anemic. This study assessed women's understanding of anemia and the role of iron in preventing and treating this condition. A qualitative study was conducted within a randomized controlled trial of weekly iron supplementation in a rural malaria endemic area. Focus groups with women of similar age, parity, and marital status took place in 12 of 24 study villages. Two additional focus groups were conducted with female field workers. Tape-recorded transcripts were translated into French and analyzed using Framework analysis. Anemia, for which no Moore term or traditional treatment for anemia was evident, was described in terms of blood volume. Moderate blood loss (diminished blood) could be easily replaced by eating well and was not considered serious. Massive blood loss (finished blood) was a rare, life-threatening illness. Iron tablets could increase blood volume and help women withstand massive blood loss at delivery, but for the latter, transfusion was indicated. Women had no knowledge of iron's role and did not readily concede that iron supplements contained elemental iron. Neither adolescents nor field workers were convinced of the benefits of supplementing non-pregnant adolescents, who were incorrectly considered to be at low risk of anemia. Young women's knowledge of anemia did not provide an adequate explanatory framework to motivate anemia prevention. Improving information on the role of iron is especially important for adolescent girls who may be incorrectly considered at low risk of anemia as they have not yet experienced pregnancy.

Background Achieving high human papillomavirus (HPV) vaccine coverage may reduce inequalities in cervical cancer prevention by mitigating the inequalities seen in the cervical screening programme. This paper assesses whether the same sociodemographic factors are associated with both cervical screening and HPV vaccination. Methods Girls’ HPV vaccination records were linked by address to cervical screening records for their mothers in the North West of England. Index of Multiple Deprivation scores (2010) and census ethnicity data (2001) were used to investigate the association between deprivation and ethnic composition of area of residence with HPV vaccination and cervical screening uptake, along with potential differences between Primary Care Trusts (PCTs), which were responsible for vaccine delivery. Results Deprivation was not associated with routine (12–13-year-olds) vaccination initiation, but girls living in the most deprived quintile were significantly less likely to complete the three vaccine doses (OR 0.75; 95% CI 0.63 to 0.88). Mother–daughter pairs failing to engage in either screening or vaccination were also more likely to live in deprived areas (routine vaccination OR for most deprived quintile: 2.35; 95% CI 2.00 to 2.77). There were differences between PCTs after controlling for demographic effects (OR 1.35; 95% CI 1.23 to 1.52). Conclusions Ensuring completion of the vaccine schedule is critical for organisations responsible for vaccine delivery in order to reduce cancer risk among girls living in deprived areas. There remains a small minority of mothers and daughters from disadvantaged backgrounds who do not participate in either cervical screening or HPV vaccination.

Since September 2008, a national vaccine programme in the UK has offered routine human papillomavirus (HPV) vaccination to young women aged 12-13 years. A catch-up programme also offered HPV vaccination to women born after 1 September 1990.To compare indicators of risk and preventive behaviours among young women attending genitourinary medicine (GUM) clinics who had, and had not, received at least one dose of HPV vaccine.Clinical histories and HPV vaccination status were obtained from 363 participants eligible for HPV vaccination (Cervarix(®)) in the UK vaccination programme (born after 1 September 1990) attending GUM clinics in the North West of England. Using logistic regression, markers of sexual and non-sexual risk behaviours were compared between vaccinated and unvaccinated women.At least one dose of HPV vaccine had been received by 63.6% (n=231) of participants. Unvaccinated women demonstrated higher levels of risky behaviour than those who had undergone HPV vaccination. Unvaccinated women were significantly more likely to have had three or more partners in the last 6 months, attended the clinic with symptoms, not used a condom at first sexual intercourse, had anal intercourse with their last sexual contact, to have tested positive for Chlamydia trachomatis diagnosis at the clinic visit and to be a current smoker.In the UK, where vaccine coverage is high, failure to initiate HPV vaccination amongst GUM attendees is a marker of high-risk behaviours. As a result, HPV vaccination status should be ascertained as part of an individual's clinical history by sexual health services to ensure advice and counselling is provided to those at greatest risk of HPV-associated disease.

Sexually transmitted infections are a major health risk to all sexually active adolescents and improving clinical management for this age group is of major importance. Currently, adolescents are managed in the same way as adults. This paper summarizes recommendations by the World Health Organization that services be more responsive to adolescent concerns about confidentiality, risk assessment be more attuned to their sexual behavioral patterns, and services be tailored to give more time for counseling, assessment of stage of maturity and continuity of reproductive health care.

Neonatal and maternal tetanus infections remain an important cause of death in many countries. Few studies have reported tetanus toxoid antibody levels of adolescent girls. As part of the Expanded Programme on Immunization most girls receive up to 3 injections in early childhood, and many subsequently do not receive booster vaccinations until pregnant. We determined (by ELISA) tetanus antibody seropositivity in adolescent girls from Malawi (in 1996), Nigeria (in 1993) and Pakistan (in 1996), and response to tetanus vaccination in adolescent girls from Pakistan. Geometric mean titres (GMT, IU/mL) were 0.94 in 117 Malawian, 0.32 in 154 Nigerian and 1.08 in 162 Pakistani girls. In Nigeria, 54.7% of adolescents were seronegative, of whom 26.8% had a history of unsafe abortion. In Malawi and Pakistan all girls were seropositive and in Pakistan, following a booster vaccination, titres increased 3-fold, with a lower response in older girls. The results indicated that adequate childhood immunization is likely to provide protective levels through adolescence. Booster vaccination in late childhood/early adolescence should protect the majority of women throughout their reproductive lives. This practice would reduce the risks of girls exposed to infection through unsafe abortions, and may be the best option for countries seeking to improve their vaccination schedule, especially where tetanus vaccine coverage in pregnant women is unacceptably low.

This review highlights some of the difficulties inherent in controlling sexually transmitted diseases (STDs) in developing countries – especially amongst women. Considerable efforts have been made to improve the syndromic approach to STD management but the poor performance of the algorithm for managing vaginal discharge limits the effectiveness of this strategy. The facilitating role of the human immunodeficiency virus (HIV) has been the main impetus to STD control rather than reduction of morbidity in women, especially pregnant women and their children. There are no easy solutions — but action on several fronts, with more attention to core groups, men and adolescents is indicated.

Background: There is little information on girls' experiences of human papillomavirus (HPV) vaccination in the prevention of cervical cancer. We investigated the views of adolescent girls who had been offered the vaccine as part of a feasibility study conducted in Manchester. Methods: All 12 to 13-year-old girls in two primary care trusts were offered three doses of Cervarix (manufactured by GlaxoSmithKline). A letter was sent to 1084 parents who had consented to research follow-up. It requested parents to pass a questionnaire regarding HPV vaccination to their daughters to complete and post back in a prepaid envelope. Results: A total of 553 girls completed the questionnaire. Altogether, 77% (422) had shared with their parents in the vaccine decision. In all, 42% (n=13) of girls, whose parents refused vaccination, stated that they wanted the vaccine, whereas 10% (50) of those who were vaccinated did not want the vaccine. Although 54% (277) said the vaccine was very important to them, 39% (153) of vaccinated girls thought they might not recommend it to others. The vaccine was perceived to be painful and there were exaggerated rumours of serious adverse events and needle scares. A total of 79% (420) of girls agreed with a statement that vaccination reminded them of the risks of sexual contact, but 14% (73) agreed they might take more sexual risks because they had been vaccinated. Conclusion: Girls of this age form their own views on HPV vaccination but parental support for vaccination remains important, especially for completing the three doses. By discussing the vaccine, parents can encourage their daughters to determine the importance and implications of HPV vaccination.

This is the first of four papers to be published in Research Ethics Review in 2009 that address methodological issues of relevance to research ethics committees. These will be practical papers, intended to assist ethics committee members to determine whether a research method is both ethically justified and likely to lead to high quality research. This paper prepares the way for the series through a consideration of the relationship between research ethics and methodology.

Objective To assess the feasibility and acceptability of delivering a human papillomavirus (HPV) vaccine to adolescent girls. Design Prospective cohort study. Setting 36 secondary schools in two primary care trusts in Greater Manchester, United Kingdom. Participants 2817 schoolgirls in year 8 (12 and 13 year olds). Intervention Delivery of the bivalent vaccine at 0, 1, and 6 months over one school year. Main outcome measures Vaccine uptake for doses 1 and 2 of a three dose schedule. Results Vaccine uptake was 70.6% (1989/2817) for the first dose and 68.5% (1930/2817) for the second dose. Uptake was significantly lower in schools with a higher proportion of ethnic minority girls (P Conclusion Delivery of the first two doses of HPV vaccine to adolescent schoolgirls is encouraging, but the success of the vaccination programme depends on high coverage for the third dose.

To assess vitamin A and E status and anaemia in non-pregnant Malawian adolescent girls.A cross-sectional study in rural village communities in the Shire Valley, Southern Malawi.Adolescent girls, n = 118, aged between 10 and 19 y, 112 of whom were unmarried.Socio-demographic information was collected by questionnaire, heights and weights were measured. Vitamin A was assessed by the Modified Relative Dose Response (MRDR) test, in addition to serum retinol values. Blood samples were collected 4-5 h after administration of 3,4-didehydroretinyl acetate. Retinol and alpha-tocopherol levels were measured by HPLC. Serum retinol results for non-pregnant girls were compared with values for 43 adolescent pregnant girls which were available from a previous study.26.6% of non-pregnant girls had serum retinol values0.70 micromol/L; 40.2% had an MRDR ratio0.060. In 59.3%, serum tocopherol levels were11.5 micromol/L and the tocopherol/cholesterol ratio was2.2 in 23.9%. 11.3% had a haemoglobinor = 12 g/dl. Vitamin A levels were significantly related to age, and younger girls were more likely to be deficient. Significant correlations were found between serum retinol, MRDR values and serum tocopherol. Girls with a low body mass index for age had tocopherol cholesterol ratios2.2. Low serum retinol values occurred significantly more often in stunted girls (P=0.01). Serum retinol values of adolescent pregnant girls were significantly lower than those of non-pregnant adolescents (P=0.002).Vitamin A and E deficiency and anaemia were common in adolescent non-pregnant girls, and thought to partly result from increased growth requirements. Girls who become pregnant at an early age are at risk of depletion of their nutritional reserves. Measures to reduce nutritional deficiencies before the first pregnancy are needed.