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1.  Pregnancy-associated outcomes in women who spent some of their childhood looked after by local authorities: findings from the UK Millennium Cohort Study 
BMJ Open  2014;4(12):e005468.
There has been very little description of the health and social outcomes at pregnancy and early motherhood of girls who were previously looked after by local authorities. The objectives of this study were to compare the sociodemographic and health profiles of mothers who had spent time in a children's home or with foster parents as a child to mothers who had not. In particular, to examine associations between being looked after and the likelihood of smoking during pregnancy, birth weight, the presence of symptoms of maternal depression and the initiation of breastfeeding.
A retrospective cross-sectional study using the baseline questionnaire of the Millennium Cohort Study.
The UK.
A nationally representative study of 18 492 mothers of babies born in the UK during 2000–2002.
A history of spending time in a children's home or with foster parents.
Outcome measures
(1) Smoking during pregnancy; (2) low birth weight; (3) symptoms of maternal depression and (4) initiation of breastfeeding.
In univariable analyses, women who had been looked after by local authorities were significantly less likely to be of a higher social class, live in a high-income household or have achieved a high level of education. They were more likely to have a low-birthweight baby and be a single parent. In multivariable analyses, women who had been looked after by local authorities were more likely to smoke during pregnancy (adjusted OR 3.0 95% CI 2.14 to 4.3) and were more likely to have symptoms of depression (adjusted OR 1.98 95% CI 1.4 to 2.7) compared with women who had not been looked after.
Our results suggest that these women carry social disadvantage into motherhood, with the potential of continuing the cycle of deprivation. There is a case for increasing our attention on this group, which can be readily accessed by maternity and early years’ services.
PMCID: PMC4267074  PMID: 25510884
2.  Evaluation of Health in Pregnancy grants in Scotland: a protocol for a natural experiment 
BMJ Open  2014;4(10):e006547.
A substantial proportion of low birth weight is attributable to the mother's cultural and socioeconomic circumstances. Early childhood programmes have been widely developed to improve child outcomes. In the UK, the Health in Pregnancy (HiP) grant, a universal conditional cash transfer of £190, was introduced for women reaching the 25th week of pregnancy with a due date on/or after 6 April 2009 and subsequently withdrawn for women reaching the 25th week of pregnancy on/or after 1 January 2011. The current study focuses on the evaluation of the effectiveness and cost-effectiveness of the HiP grant.
Methods and analysis
The population under study will be all singleton births in Scotland over the periods of January 2004 to March 2009 (preintervention), April 2009 to April 2011 (intervention) and May 2011 to December 2013 (postintervention). Data will be extracted from the Scottish maternity and neonatal database. The analysis period 2004–2013 should yield over 585 000 births. The primary outcome will be birth weight among singleton births. Other secondary outcomes will include gestation at booking, booking before 25 weeks; measures of size and stage; gestational age at delivery; weight-for-dates, term at birth; birth outcomes and maternal smoking. The main statistical method we will use is interrupted time series. Outcomes will be measured on individual births nested within mothers, with mothers themselves clustered within data zones. Multilevel regression models will be used to determine whether the outcomes changed during the period in which the HiP grants was in effect. Subgroup analyses will be conducted for those groups most likely to benefit from the payments.
Ethics and dissemination
Approval for data collection, storage and release for research purpose has been given (6 May 2014, PAC38A/13) by the Privacy Advisory Committee. The results of this study will be disseminated through peer-reviewed publications in journals, national and international conferences.
PMCID: PMC4202003  PMID: 25324327
4.  Prenatal exposure to binge pattern of alcohol consumption: mental health and learning outcomes at age 11 
The objective of the study is to investigate whether episodic binge pattern of alcohol consumption during pregnancy is independently associated with child mental health and academic outcomes. Using data from the prospective, population-based Avon Longitudinal Study of Parents and Children (ALSPAC), we investigated the associations between binge patterns of alcohol consumption during pregnancy (≥4 drinks per day) and child mental health [as rated by both parent (n = 4,610) and teacher (n = 4,274)] and academic outcomes [based on examination results (n = 6,939)] at age 11 years. After adjusting for prenatal and postnatal risk factors, binge pattern of alcohol consumption (≥4 drinks in a day on at least one occasion) during pregnancy was associated with higher levels of mental health problems (especially hyperactivity/inattention) in girls at age 11 years, according to parental report. After disentangling binge-pattern and daily drinking, binge-pattern drinking was independently associated with teacher-rated hyperactivity/inattention and lower academic scores in both genders. Episodic drinking involving ≥4 drinks per day during pregnancy may increase risk for child mental health problems and lower academic attainment even if daily average levels of alcohol consumption are low. Episodic binge pattern of drinking appears to be a risk factor for these outcomes, especially hyperactivity and inattention problems, in the absence of daily drinking.
Electronic supplementary material
The online version of this article (doi:10.1007/s00787-014-0599-7) contains supplementary material, which is available to authorized users.
PMCID: PMC4186965  PMID: 25209690
Prenatal alcohol exposure; Fetal alcohol spectrum disorder; Academic achievement; Mental health problems; Hyperactivity
5.  Behavioral, Biological, and Demographic Risk and Protective Factors for New HIV Infections among Youth, Rakai, Uganda 
Prevalence of HIV infection is considerable among youth, although data on risk factors for new (incident) infections is limited. We examined incidence of HIV infection and risk and protective factors among youth in rural Uganda, including the role of gender and social transitions.
Participants were sexually experienced youth (15–24 years-old) enrolled in the Rakai Community Cohort Study,1999–2008 (n=6741). Poisson regression with robust standard errors was used to estimate incident rate ratios (IRR) and 95% confidence intervals (CI) of incident HIV infection.
HIV incidence was greater among young women than young men (14.1 vs. 8.3 per 1000 person-years, respectively); this gender disparity was greater among teens (14.9 vs. 3.6). Beyond behavioral (multiple partners and concurrency) and biological factors (sexually transmitted infection (STI) symptoms), social transitions such as marriage and staying in school influenced HIV risk. In multivariate analyses among women, HIV incidence was associated with living in a trading village [adjusted IRR (aIRR) = 1.48; 95% CI: 1.04 to 2.11], being a student (aIRR = 0.22; 95% CI: 0.07 to 0.72), current marriage (aIRR = 0.55; 95% CI: 0.37 to 0.81), former marriage (aIRR = 1.73; 95% CI: 1.01 to 2.96), having multiple partners, and sexually transmitted infection symptoms. Among men, new infections were associated with former marriage (aIRR = 5.57; 95% CI: 2.51 to 12.36), genital ulceration (aIRR = 3.56; 95% CI: 1.97 to 6.41), and alcohol use (aIRR = 2.08; 95% CI: 1.15 to 3.77).
During the third decade of the HIV epidemic in Uganda, HIV incidence remains considerable among youth, with young women particularly at risk. The risk for new infections was strongly shaped by social transitions such as leaving school, entrance into marriage, and marital dissolution; the impact of marriage was different for young men than women.
PMCID: PMC4131841  PMID: 23535293
Youth; Uganda; HIV; Incidence; Risk Factors; Education
6.  Violence as a public health problem: An ecological study of 169 countries☆ 
Social Science & Medicine (1982)  2014;104(100):220-227.
Individual level risk factors for violence have been widely studied, but little is known about country-level determinants, particularly in low and middle-income countries. We hypothesized that income inequality, through its detrimental effects on social cohesion, would be related to an increase in violence worldwide, and in low and middle-income countries in particular. We examined country-level associations of violence with socio-economic and health-related factors, using crime statistics from the United Nations Office on Drugs and Crime, and indicators from the Human Development Report published by the United Nations Development Programme. Using regression models, we measured relationships between country-level factors (age, education, measures of income, health expenditure, and alcohol consumption) and four violent outcomes (including measures of violence-related mortality and morbidity) in up to 169 countries. We stratified our analyses comparing high with low and middle-income countries, and analysed longitudinal data on homicide and income inequality in high-income countries. In low and middle-income countries, income inequality was related to homicide, robbery, and self-reported assault (all p's < 0.05). In high-income countries, urbanicity was significantly associated with official assault (p = 0.002, β = 0.716) and robbery (p = 0.011, β = 0.587) rates; income inequality was related to homicide (p = 0.006, β = 0.670) and self-reported assault (p = 0.020, β = 0.563), and longitudinally with homicide (p = 0.021). Worldwide, alcohol consumption was associated with self-reported assault rates (p < 0.001, β = 0.369) suggesting public policy interventions reducing alcohol consumption may contribute to reducing violence rates. Our main finding was that income inequality was related to violence in low and middle-income countries. Public health should advocate for global action to moderate income inequality to reduce the global health burden of violence.
•In low and middle-income countries, income inequality is related to rates of homicide and assault.•In high-income countries, urbanicity is associated with assault and robbery rates.•In high-income countries, income inequality is related to homicide and self-reported assault rates.•Worldwide, alcohol consumption is associated with self-reported assault rates.
PMCID: PMC3969091  PMID: 24581081
Crime; Violence; Public health; Income inequality; Alcohol
7.  Systematic review of heath care interventions to improve outcomes for women with disability and their family during pregnancy, birth and postnatal period 
Health care providers are often unfamiliar with the needs of women with disability. Moreover maternity and postnatal services may not be specifically tailored to the needs of women with disability and their families. We conducted a systematic review to determine the effectiveness of healthcare interventions to improve outcomes for pregnant and postnatal women with disability and for their families.
Studies on pregnant and postnatal women with disability and their families which evaluated the effectiveness of an intervention using a design that met the criteria used by the Cochrane Effective Practice and Organization of Care group were eligible for inclusion in this review. A comprehensive search strategy was carried using eleven electronic databases. No restriction on date or language was applied. Included studies were assessed for quality and their results summarized and tabulated.
Only three studies fully met the inclusion criteria. All were published after 1990, and conducted as small single-centre randomized controlled trials. The studies were heterogeneous and not comparable. Therefore the main finding of this review was the lack of published research on the effectiveness of healthcare interventions to improve outcomes for pregnant women with disability and their families.
More research is required to evaluate healthcare interventions to improve outcomes for pregnant women with disability and their families.
PMCID: PMC3922586  PMID: 24499308
Disability; Pregnancy; Postnatal; Maternity; Systematic review
8.  Association between limiting longstanding illness in mothers and their children: findings from the UK Millennium Cohort Study 
BMJ Open  2013;3(12):e004190.
To explore the association between maternal disability as measured by the presence of a limiting longstanding illness (LLI) 9 months postpartum and subsequent child health at the age of 7 years.
Nationally representative prospective longitudinal study.
England, Scotland, Wales and Northern Ireland.
Secondary analysis of data on 11 807 mother–child pairs recruited to the UK Millennium Cohort Study. Baseline interviews with mothers were carried out in 2001–2002. When the children were 7 years old, the follow-up survey included questions about limiting longstanding health conditions in the child.
Primary outcome measure
Any longstanding condition that was reported to limit the children's activities in any way.
Nearly 7% of all children were reported to have an LLI at the age of 7 years. The majority (88.1%, 95% CI 85.6% to 90.2%) of children whose mother was disabled did not have an LLI themselves. The children of disabled mothers, however, had higher odds of LLI (OR=1.9, 95% CI 1.5 to 2.5) independently of different maternal, pregnancy and birth characteristics and breast feeding duration. Inclusion of poverty measures in the model did not significantly affect the odds (OR=1.8, 95% CI 1.4 to 2.4), suggesting that maternal LLI around the time of birth increases the odds of child LLI at the age of 7 years independently of starting life in poverty.
There is a strong positive association between maternal and child LLI. Health professionals should work together with social care and other relevant service providers to identify the individual needs of disabled parents and provide adequate support throughout the pregnancy and after the child is born. Further research is important to clarify the exact nature of the associations for different types of maternal and child disability.
PMCID: PMC3856615  PMID: 24319277
Epidemiology; Public Health; Paediatrics
9.  Effect of Prenatal Alcohol Exposure on Childhood Academic Outcomes: Contrasting Maternal and Paternal Associations in the ALSPAC Study 
PLoS ONE  2013;8(10):e74844.
The impact of low-to-moderate levels of alcohol consumption during pregnancy on child cognitive outcomes has been of recent concern. This study has tested the hypothesis that low-to-moderate maternal alcohol use in pregnancy is associated with lower school test scores at age 11 in the offspring via intrauterine mechanisms.
We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a birth cohort study based in the South West of England. Analyses were conducted on 7062 participants who had complete data on: maternal and paternal patterns of alcohol use in the first trimester and at 18 weeks' gestation, child's academic outcomes measured at age 11, gender, maternal age, parity, marital status, ethnicity, household crowding, home ownership status and parental education. We contrasted the association of mother's alcohol consumption during pregnancy with child's National Curriculum Key Stage 2 (KS2) test scores with the association for father's alcohol consumption (during the time the mother was pregnant) with child's National Curriculum Key Stage 2 (KS2) test scores. We used multivariate linear regression to estimate mean differences and 95% confidence intervals [CI] in KS2 scores across the exposure categories and computed f statistics to compare maternal and paternal associations.
Findings and conclusions
Drinking up to 1 unit of alcohol a day during pregnancy was not associated with lower test scores. However, frequent prenatal consumption of 4 units (equivalent to 32 grams of alcohol) on each single drinking occasion was associated with reduced educational attainment [Mean change in offspring KS2 score was −0.68 (−1.03, −0.33) for maternal alcohol categories compared to 0.27 (0.07, 0.46) for paternal alcohol categories]. Frequent consumption of 4 units of alcohol during pregnancy may adversely affect childhood academic outcomes via intrauterine mechanisms.
PMCID: PMC3794033  PMID: 24130672
10.  Effect of the Mahatma Gandhi National Rural Employment Guarantee Act (MGNREGA) on Malnutrition of Infants in Rajasthan, India: A Mixed Methods Study 
PLoS ONE  2013;8(9):e75089.
Analyse the effect of the Mahatma Gandhi National Rural Employment Guarantee Act (MGNREGA), a wage-for-employment policy of the Indian Government, on infant malnutrition and delineate the pathways through which MGNREGA affects infant malnutrition. Hypothesis: MGNREGA could reduce infant malnutrition through positive effects on household food security and infant feeding.
Mixed methods using cross-sectional study and focus group discussions conducted in Dungarpur district, Rajasthan, India. Participants: Infants aged 1 to <12 months and their mothers/caregivers. Final sample 528 households with 1056 participants, response rate 89.6%. Selected households were divided into MGNREGA-households and non-MGNREGA-households based on participation in MGNREGA between August-2010 and September-2011. Outcomes: Infant malnutrition measured using anthropometric indicators - underweight, stunting, and wasting (WHO criteria).
We included 528 households with 1,056 participants. Out of 528, 281 households took part in MGNREGA between August’10, and September’11. Prevalence of wasting was 39%, stunting 24%, and underweight 50%. Households participating in MGNREGA were less likely to have wasted infants (OR 0·57, 95% CI 0·37–0·89, p = 0·014) and less likely to have underweight infants (OR 0·48, 95% CI 0·30–0·76, p = 0·002) than non-participating households. Stunting did not differ significantly between groups. We did 11 focus group discussions with 62 mothers. Although MGNREGA reduced starvation, it did not provide the desired benefits because of lower than standard wages and delayed payments. Results from path analysis did not support existence of an effect through household food security and infant feeding, but suggested a pathway of effect through low birth-weight.
Participation in MGNREGA was associated with reduced infant malnutrition possibly mediated indirectly via improved birth-weight rather than by improved infant feeding. Addressing factors such as lack of mothers’ knowledge and inappropriate feeding practices, over and above the social and economic policies, is key in efforts to reduce infant malnutrition.
PMCID: PMC3783470  PMID: 24086447
11.  Prenatal alcohol exposure and offspring cognition and school performance. A ‘Mendelian randomization’ natural experiment 
Background There is substantial debate as to whether moderate alcohol use during pregnancy could have subtle but important effects on offspring, by impairing later cognitive function and thus school performance. The authors aimed to investigate the unconfounded effect of moderately increased prenatal alcohol exposure on cognitive/educational performance.
Methods We used mother-offspring pairs participating in the Avon Longitudinal Study of Parents and Children (ALSPAC) and performed both conventional observational analyses and Mendelian randomization using an ADH1B variant (rs1229984) associated with reduced alcohol consumption. Women of White European origin with genotype and self-reported prenatal alcohol consumption, whose offspring’s IQ score had been assessed in clinic (N = 4061 pairs) or Key Stage 2 (KS2) academic achievement score was available through linkage to the National Pupil Database (N = 6268), contributed to the analyses.
Results Women reporting moderate drinking before and during early pregnancy were relatively affluent compared with women reporting lighter drinking, and their children had higher KS2 and IQ scores. In contrast, children whose mothers’ genotype predisposes to lower consumption or abstinence during early pregnancy had higher KS2 scores (mean difference +1.7, 95% confidence interval +0.4, +3.0) than children of mothers whose genotype predisposed to heavier drinking, after adjustment for population stratification.
Conclusions Better offspring cognitive/educational outcomes observed in association with prenatal alcohol exposure presumably reflected residual confounding by factors associated with social position and maternal education. The unconfounded Mendelian randomization estimates suggest a small but potentially important detrimental effect of small increases in prenatal alcohol exposure, at least on educational outcomes.
PMCID: PMC3807618  PMID: 24065783
Alcohol dehydrogenase; causality; cognition; confounding factors; educational measurement; ethanol; Mendelian randomization analysis; pregnancy
12.  Women with disability: the experience of maternity care during pregnancy, labour and birth and the postnatal period 
It has been estimated that 9.4% of women giving birth in the United Kingdom have one or more limiting longstanding illness which may cause disability, affecting pregnancy, birth and early parenting. No large scale studies on a nationally representative population have been carried out on the maternity experiences of disabled women to our knowledge.
Secondary analysis of data from a survey of women in 2010 by English National Health Service Trusts on behalf of the Care Quality Commission was undertaken. 144 trusts in England took part in the postal survey.
Women self-identified with disability and were excluded if less than 16 years of age or if their baby had died. The 12 page structured questionnaire with sections on antenatal, labour and birth and postnatal care covered access, information, communication and choice. Descriptive and adjusted analyses compared disabled and non-disabled groups. Comparisons were made separately for five disability subgroups: physical disability, sensory impairment, mental health conditions, learning disability and women with more than one type of disability.
Disabled women comprised 6.14% (1,482) of the total sample (24,155) and appeared to use maternity services more than non-disabled women. Most were positive about their care and reported sufficient access and involvement, but were less likely to breastfeed. The experience of women with different types of disability varied: physically disabled women used antenatal and postnatal services more, but had less choice about labour and birth; the experience of those with a sensory impairment differed little from the non-disabled women, but they were more likely to have met staff before labour; women with mental health disabilities also used services more, but were more critical of communication and support; women with a learning disability and those with multiple disabilities were least likely to report a positive experience of maternity care.
This national study describes disabled women’s experiences of pregnancy, child birth and postnatal care in comparison with non-disabled women. While in many areas there were no differences, there was evidence of specific groups appropriately receiving more care. Areas for improvement included infant feeding and better communication in the context of individualised care.
PMCID: PMC3848505  PMID: 24034425
Disability; Maternity care; Pregnancy; Birth; Maternity survey
13.  Non-enrollment for free community HIV care: findings from a population-based study in Rakai, Uganda 
AIDS care  2011;23(6):764-770.
Improved understanding of HIV-related health-seeking behavior at a population level is important in informing the design of more effective HIV prevention and care strategies. We assessed the frequency and determinants of failure to seek free HIV care in Rakai, Uganda. HIV-positive participants in a community cohort who accepted VCT were referred for free HIV care (cotrimoxazole prophylaxis, CD4 monitoring, treatment of opportunistic infections, and, when indicated, antiretroviral therapy). We estimated proportion and adjusted Prevalence Risk Ratios (adj. PRR) of non-enrollment into care six months after receipt of VCT using log-binomial regression. About 1145 HIV-positive participants in the Rakai Community Cohort Study accepted VCT and were referred for care. However, 31.5% (361/1145) did not enroll into HIV care six months after referral. Non-enrollment was significantly higher among men (38%) compared to women (29%, p=0.005). Other factors associated with non-enrollment included: younger age (15–24 years, adj. PRR=2.22; 95% CI: 1.64, 3.00), living alone (adj. PRR=2.22; 95% CI: 1.57, 3.15); or in households with 1–2 co-residents (adj. PRR=1.63; 95% CI: 1.31, 2.03) compared to three or more co-residents, or a CD4 count >250 cells/ul (adj. PRR=1.81; 95% CI: 1.38, 2.46). Median (IQR) CD4 count was lower among enrolled 388 cells/ul (IQR: 211,589) compared to those not enrolled 509 cells/ul (IQR: 321,754).
About one-third of HIV-positive persons failed to utilize community-based free services. Non-use of services was greatest among men, the young, persons with higher CD4 counts and the more socially isolated, suggesting a need for targeted strategies to enhance service uptake.
PMCID: PMC3722430  PMID: 21293989
HIV; HIV care; enrollment
14.  Traditional Herbal Medicine Use Associated with Liver Fibrosis in Rural Rakai, Uganda 
PLoS ONE  2012;7(11):e41737.
Traditional herbal medicines are commonly used in sub-Saharan Africa and some herbs are known to be hepatotoxic. However little is known about the effect of herbal medicines on liver disease in sub-Saharan Africa.
500 HIV-infected participants in a rural HIV care program in Rakai, Uganda, were frequency matched to 500 HIV-uninfected participants. Participants were asked about traditional herbal medicine use and assessed for other potential risk factors for liver disease. All participants underwent transient elastography (FibroScan®) to quantify liver fibrosis. The association between herb use and significant liver fibrosis was measured with adjusted prevalence risk ratios (adjPRR) and 95% confidence intervals (CI) using modified Poisson multivariable logistic regression.
19 unique herbs from 13 plant families were used by 42/1000 of all participants, including 9/500 HIV-infected participants. The three most-used plant families were Asteraceae, Fabaceae, and Lamiaceae. Among all participants, use of any herb (adjPRR = 2.2, 95% CI 1.3–3.5, p = 0.002), herbs from the Asteraceae family (adjPRR = 5.0, 95% CI 2.9–8.7, p<0.001), and herbs from the Lamiaceae family (adjPRR = 3.4, 95% CI 1.2–9.2, p = 0.017) were associated with significant liver fibrosis. Among HIV infected participants, use of any herb (adjPRR = 2.3, 95% CI 1.0–5.0, p = 0.044) and use of herbs from the Asteraceae family (adjPRR = 5.0, 95% CI 1.7–14.7, p = 0.004) were associated with increased liver fibrosis.
Traditional herbal medicine use was independently associated with a substantial increase in significant liver fibrosis in both HIV-infected and HIV-uninfected study participants. Pharmacokinetic and prospective clinical studies are needed to inform herb safety recommendations in sub-Saharan Africa. Counseling about herb use should be part of routine health counseling and counseling of HIV-infected persons in Uganda.
PMCID: PMC3507824  PMID: 23209545
15.  Fetal Alcohol Exposure and IQ at Age 8: Evidence from a Population-Based Birth-Cohort Study 
PLoS ONE  2012;7(11):e49407.
Observational studies have generated conflicting evidence on the effects of moderate maternal alcohol consumption during pregnancy on offspring cognition mainly reflecting problems of confounding. Among mothers who drink during pregnancy fetal alcohol exposure is influenced not only by mother’s intake but also by genetic variants carried by both the mother and the fetus. Associations between children’s cognitive function and both maternal and child genotype at these loci can shed light on the effects of maternal alcohol consumption on offspring cognitive development.
We used a large population based study of women recruited during pregnancy to determine whether genetic variants in alcohol metabolising genes in this cohort of women and their children were related to the child’s cognitive score (measured by the Weschler Intelligence Scale) at age 8.
We found that four genetic variants in alcohol metabolising genes in 4167 children were strongly related to lower IQ at age 8, as was a risk allele score based on these 4 variants. This effect was only seen amongst the offspring of mothers who were moderate drinkers (1–6 units alcohol per week during pregnancy (per allele effect estimates were −1.80 (95% CI = −2.63 to −0.97) p = 0.00002, with no effect among children whose mothers abstained during pregnancy (0.16 (95%CI = −1.05 to 1.36) p = 0.80), p-value for interaction  = 0.009). A further genetic variant associated with alcohol metabolism in mothers was associated with their child’s IQ, but again only among mothers who drank during pregnancy.
PMCID: PMC3498109  PMID: 23166662
16.  Hepatitis B virus and sexual behavior in Rakai, Uganda 
Journal of Medical Virology  2011;83(5):796-800.
HIV and hepatitis B virus (HBV) co-infection poses important public health considerations in resource-limited settings. Demographic data and sera from adult participants of the Rakai Health Sciences Program Cohort in Southwestern Uganda were examined to determine HBV seroprevalence patterns in this area of high HIV endemicity prior to the introduction of antiretroviral therapy. Commercially available EIAs were used to detect prevalent HBV infection (positive for HBV core antibody [anti-HBc] and/or positive HBV surface antigen [HBsAg]), and chronic infection (positive for HBsAg). Of 438 participants, 181 (41%) had prevalent HBV infection while 21 (5%) were infected chronically. Fourteen percent of participants were infected with HIV. Fifty three percent showed evidence of prevalent HBV infection compared to 40% among participants infected with HIV (p=0.067). Seven percent of participants infected with HIV were HBsAg positive compared to 4% among participants not infected with HIV (p=0.403). The prevalence of prevalent HBV infection was 55% in adults aged >50 years old, and 11% in persons under 20 years. In multivariable analysis, older age, HIV status and serologic syphilis were significantly associated with prevalent HBV infection. Transfusion status and receipt of injections were not significantly associated with HBV infection. Contrary to expectations that HBV exposure in Uganda occurred chiefly during childhood, prevalent HBV infection was found to increase with age and was associated sexually transmitted diseases (HIV and syphilis.) Therefore vaccination against HBV, particularly susceptible adults with HIV or at risk of HIV/STDs should be a priority.
PMCID: PMC3262046  PMID: 21412787
Hepatitis B virus HBV; HIV; Sexual transmission; Uganda; Africa
17.  Determinants of incidence and clearance of high-risk HPV infections in rural Rakai, Uganda 
We used self-administered vaginal swabs to assess the incidence and clearance of carcinogenic HPV infections in rural Rakai, Uganda.
Women provided self-administered vaginal swab at annual, home-based visits. Type-specific carcinogenic HPV incidence and clearance, and risk-factors were assessed.
Carcinogenic HPV incidence was 17.3/100 person-years (PY) among HIV-positive, compared with 7.0/100 PY among HIV-negative women (p<0.001). HPV-51 had the highest incidence followed by HPV-16 (1.8/100 PY, and 1.5/100 PY, respectively). In multivariate model, HIV-positive women were twice as likely to have incident infection compared to HIV-negatives. Younger women were at higher risk for incident infection, as were women with higher lifetime and recent sexual partners, and high perception of AIDS. Married women were less likely to have incident infection. Approximately half of all carcinogenic HPV infections cleared over the study follow-up of three years. HPV-31, 35, and 16 had the lowest clearance (16.7%, 27.9%, and 38.3%, respectively). In multivariate model, HIV-positives, women over 30, higher HPV viral burden, and more lifetime sex partners were less likely to clear infections.
Self-collected vaginal swabs provide accurate HPV exposure assessment for studying the HPV exposure and epidemiology, and can be an important tool for research in populations unwilling to undergo pelvic exam.
PMCID: PMC3158656  PMID: 18559545
HIV; incident; clearance; risk factors; carcinogenic HPV
18.  High Prevalence of Liver Fibrosis Associated with HIV Infection: A Cross-Sectional Study in Rural Rakai, Uganda 
Antiviral therapy  2011;16(3):405-411.
Liver disease is a leading cause of mortality among HIV-infected persons in the US and Europe; however, data regarding effects of HIV and anti-retroviral therapy (ART) on liver disease in Africa remains sparse.
500 HIV-infected participants in an HIV care program in Rakai, Uganda were frequency-matched by age, gender and site to 500 HIV-uninfected participants in a population cohort. All participants underwent transient elastography (FibroScan®) to quantify liver stiffness measurements (LSM) and identify participants with significant liver fibrosis, defined as LSM ≥9.3 kPa (≈ Metavir F ≥2). 962 (96 %) of participants had valid LSM data. Risk factors for liver fibrosis were identified by estimating adjusted prevalence risk ratios (adjPRR) and 95% confidence intervals (CI) using modified Poisson multivariate regression.
The prevalence of significant fibrosis was 17% among HIV-infected and 11% in HIV-uninfected participants (p =0.008). In multivariate analysis, HIV infection was associated with a 50% increase in liver fibrosis (adjPRR 1.5, 95%CI 1.1–2.1; p=0.010). Fibrosis was also associated with male gender (adjPRR 1.4, 95% CI 1.0–1.9; p=0.045), herbal medicine use (adjPRR 2.0, 95%CI 1.2–3.3; p=0.005), heavy alcohol consumption (adjPRR 2.3, 95% CI 1.3–3.9; 0.005), occupational fishing (adjPRR 2.5, 1.2–5.3; p=0.019), and chronic HBV infection (adjPRR 1.7, 95% CI 1.0–3.1; p=0.058). Among HIV-infected participants, ART appeared to reduce fibrosis risk (adjPRR 0.6, 95% CI 0.4–1.0; p=0.030).
The burden of liver fibrosis among rural Ugandans is high, particularly among persons with HIV infection. These data suggest that liver disease may represent a significant cause of HIV-related morbidity and mortality in Africa; clarifying the etiology of liver disease in this population is a research priority.
PMCID: PMC3142695  PMID: 21555823
HIV; fibrosis; hepatitis co-infection; liver; Uganda
19.  The effectiveness of antenatal care programmes to reduce infant mortality and preterm birth in socially disadvantaged and vulnerable women in high-income countries: a systematic review 
Infant mortality has shown a steady decline in recent years but a marked socioeconomic gradient persists. Antenatal care is generally thought to be an effective method of improving pregnancy outcomes, but the effectiveness of specific antenatal care programmes as a means of reducing infant mortality in socioeconomically disadvantaged and vulnerable groups of women has not been rigorously evaluated.
We conducted a systematic review, focusing on evidence from high income countries, to evaluate the effectiveness of alternative models of organising or delivering antenatal care to disadvantaged and vulnerable groups of women vs. standard antenatal care. We searched Medline, Embase, Cinahl, PsychINFO, HMIC, CENTRAL, DARE, MIDIRS and a number of online resources to identify relevant randomised and observational studies. We assessed effects on infant mortality and its major medical causes (preterm birth, congenital anomalies and sudden infant death syndrome (SIDS))
We identified 36 distinct eligible studies covering a wide range of interventions, including group antenatal care, clinic-based augmented care, teenage clinics, prenatal substance abuse programmes, home visiting programmes, maternal care coordination and nutritional programmes. Fifteen studies had adequate internal validity: of these, only one was considered to demonstrate a beneficial effect on an outcome of interest. Six interventions were considered 'promising'.
There was insufficient evidence of adequate quality to recommend routine implementation of any of the programmes as a means of reducing infant mortality in disadvantaged/vulnerable women. Several interventions merit further more rigorous evaluation.
PMCID: PMC3050773  PMID: 21314944
20.  Associations between HIV Antiretroviral Therapy and the Prevalence and Incidence of Pregnancy in Rakai, Uganda 
AIDS Research and Treatment  2011;2011:519492.
Background. Use of antiretroviral therapy (ART) may be associated with higher pregnancy rates. Methods. The prevalence and incidence of pregnancy was assessed in 712 HIV+ pre-ART women of reproductive age (WRA) (15–45) and 244 HIV+ WRA initiating ART. Prevalence rate ratios (PRR), incidence rate ratios (IRR), and 95% confidence interval (CI) were assessed. Results. The incidence of pregnancy was 13.1/100 py among women in pre-ART care compared to 24.6/100 py among women on ART (IRR = 0.54; 95% CI 0.37, 0.81, p < 0.0017). The prevalence of pregnancy at ART initiation was 12.0% with CD4 counts 100–250 compared with 3.2% with CD4 <100 (PRR = 3.24, CI 1.51–6.93), and the incidence of pregnancy while on ART was highest in women with a good immunologic response. Desire for more children was a very important factor in fertility. Conclusion. ART was associated with increased pregnancy rates in HIV+ women, particularly those with higher CD4 counts and good immunologic response to therapy, suggesting a need to strengthen reproductive health services for both women and their partners that could address their fertility decisions/intentions particularly after ART initiation.
PMCID: PMC3066572  PMID: 21490780
21.  Systematic review of the fetal effects of prenatal binge‐drinking 
The effects of binge‐drinking during pregnancy on the fetus and child have been an increasing concern for clinicians and policy‐makers. This study reviews the available evidence from human observational studies.
Systematic review of observational studies.
Pregnant women or women who are trying to become pregnant.
A computerised search strategy was run in Medline, Embase, Cinahl and PsychInfo for the years 1970–2005. Titles and abstracts were read by two researchers for eligibility. Eligible papers were then obtained and read in full by two researchers to decide on inclusion. The papers were assessed for quality using the Newcastle–Ottawa Quality Assessment Scales and data were extracted.
Main outcome measures
Adverse outcomes considered in this study included miscarriage; stillbirth; intrauterine growth restriction; prematurity; birth‐weight; small for gestational age at birth; and birth defects, including fetal alcohol syndrome and neurodevelopmental effects.
The search resulted in 3630 titles and abstracts, which were narrowed down to 14 relevant papers. There were no consistently significant effects of alcohol on any of the outcomes considered. There was a possible effect on neurodevelopment. Many of the reported studies had methodological weaknesses despite being assessed as having reasonable quality.
This systematic review found no convincing evidence of adverse effects of prenatal binge‐drinking, except possibly on neurodevelopmental outcomes.
PMCID: PMC2465662  PMID: 18000129
fetus; pregnancy; binge‐drinking
22.  Will circumcision provide even more protection from HIV to women and men? New estimates of the population impact of circumcision interventions 
Mathematical modelling has indicated that expansion of male circumcision services in high HIV prevalence settings can substantially reduce population-level HIV transmission. However, these projections need revision to incorporate new data on the effect of male circumcision on the risk of acquiring and transmitting HIV.
Recent data on the effect of male circumcision during wound healing and the risk of HIV transmission to women were synthesised based on four trials of circumcision among adults and new observational data of HIV transmission rates in stable partnerships from men circumcised at younger ages. New estimates were generated for the impact of circumcision interventions in two mathematical models, representing the HIV epidemics in Zimbabwe and Kisumu, Kenya. The models did not capture the interaction between circumcision, HIV and other sexually transmitted infections.
An increase in the risk of HIV acquisition and transmission during wound healing is unlikely to have a major impact of circumcision interventions. However, it was estimated that circumcision confers a 46% reduction in the rate of male-to-female HIV transmission. If this reduction begins 2 years after the procedure, the impact of circumcision is substantially enhanced and accelerated compared with previous projections with no such effect—increasing by 40% the infections averted by the intervention overall and doubling the number of infections averted among women.
Communities, and especially women, may benefit much more from circumcision interventions than had previously been predicted, and these results provide an even greater imperative to increase scale-up of safe male circumcision services.
PMCID: PMC3272710  PMID: 20966458
HIV; mathematical model; circumcision; Epidemiology; Africa
23.  Failure of immunologic criteria to appropriately identify antiretroviral treatment failure in Uganda 
AIDS (London, England)  2009;23(6):697-700.
Most antiretroviral treatment program in resource-limited settings use immunologic or clinical monitoring to measure response to therapy and to decide when to change to a second line regimen. Our objective was to evaluate immunologic failure criteria against gold standard virologic monitoring.
Observation cohort
Participants enrolled in an antiretroviral treatment program in rural Uganda who had at least 6 months of follow-up were included in this analysis. Immunologic monitoring was performed by CD4 cell counts every 3 months during the first year, and every 6 months thereafter. HIV-1 viral loads were performed every 6 months.
1133 participants enrolled in the Rakai Health Sciences Program antiretroviral treatment program between June 2004 and September 2007 were followed for up to 44.4 months (median follow-up 20.2 months; IQR 12.4–29.5 months). WHO immunologic failure criteria were reached by 125 (11.0%) participants. A virologic failure endpoint defined as HIV-1 viral load (VL) >400 copies/ml on two measurements was reached by 112 participants (9.9%). Only 26 participants (2.3%) experienced both an immunologic and virologic failure endpoint (2 VL>400 copies/ml) during follow-up.
Immunologic failure criteria performed poorly in our setting and would have resulted in a substantial proportion of participants with suppressed HIV-1 VL being switched unnecessarily. These criteria also lacked sensitivity to identify participants failing virologically. Periodic viral load measurements may be a better marker for treatment failure in our setting.
PMCID: PMC2720562  PMID: 19209067
HIV/AIDS; antiretroviral therapy; immunologic monitoring
24.  Contribution of smoking during pregnancy to inequalities in stillbirth and infant death in Scotland 1994-2003: retrospective population based study using hospital maternity records 
Objective To quantify the contribution of smoking during pregnancy to social inequalities in stillbirth and infant death.
Design Population based retrospective cohort study.
Setting Scottish hospitals between 1994 and 2003.
Participants Records of 529 317 singleton live births and 2699 stillbirths delivered at 24-44 weeks’ gestation in Scotland from 1994 to 2003.
Main outcome measures Rates of stillbirth and infant, neonatal, and post-neonatal death for each deprivation category (fifths of postcode sector Carstairs-Morris scores); contribution of smoking during pregnancy (“no,” “yes,” or “not known”) in explaining social inequalities in these outcomes.
Results The stillbirth rate increased from 3.8 per 1000 in the least deprived group to 5.9 per 1000 in the most deprived group. For infant deaths, the rate increased from 3.2 per 1000 in the least deprived group to 5.4 per 1000 in the most deprived group. Stillbirths were 56% more likely (odds ratio 1.56, 95% confidence interval 1.38 to 1.77) and infant deaths were 72% more likely (1.72, 1.50 to 1.97) in the most deprived compared with the least deprived category. Smoking during pregnancy accounted for 38% of the inequality in stillbirths and 31% of the inequality in infant deaths.
Conclusions Both tackling smoking during pregnancy and reducing infants’ exposure to tobacco smoke in the postnatal environment may help to reduce stillbirths and infant deaths overall and to reduce the socioeconomic inequalities in stillbirths and infant deaths perhaps by as much as 30-40%. However, action on smoking on its own is unlikely to be sufficient and other measures to improve the social circumstances, social support, and health of mothers and infants are needed.
PMCID: PMC2755727  PMID: 19797343
25.  A non-synonymous variant in ADH1B is strongly associated with prenatal alcohol use in a European sample of pregnant women 
Human Molecular Genetics  2009;18(22):4457-4466.
Pregnant women are advised to abstain from alcohol despite insufficient evidence on the fetal consequences of moderate prenatal alcohol use. Mendelian randomization could help distinguish causal effects from artifacts due to residual confounding and measurement errors; however, polymorphisms reliably associated with alcohol phenotypes are needed. We aimed to test whether alcohol dehydrogenase (ADH) gene variants were associated with alcohol use before and during pregnancy. Ten variants in four ADH genes were genotyped in women from South-West England. Phenotypes of interest were quantity and patterns of alcohol consumption before and during pregnancy, including quitting alcohol following pregnancy recognition. We tested single-locus associations between genotypes and phenotypes with regression models. We used Bayesian models (multi-locus) to take account of linkage disequilibrium and reanalyzed the data with further exclusions following two conservative definitions of ‘white ethnicity’ based on the woman's reported parental ethnicity or a set of ancestry-informative genetic markers. Single-locus analyses on 7410 women of white/European background showed strong associations for rs1229984 (ADH1B). Rare allele carriers consumed less alcohol before pregnancy [odds ratio (OR) = 0.69; 95% confidence interval (CI): 0.56–0.86, P = 0.001], were less likely to have ‘binged’ during pregnancy (OR = 0.55, 95% CI: 0.38–0.78, P = 0.0009), and more likely to have abstained in the first trimester of gestation (adjusted OR = 1.42, 95% CI: 1.12–1.80, P = 0.004). Multi-locus models confirmed these results. Sensitivity analyses did not suggest the presence of residual population stratification. We confirmed the established association of rs1229984 with reduced alcohol consumption over the life-course, contributing new evidence of an effect before and during pregnancy.
PMCID: PMC2766294  PMID: 19687126

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