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1.  Relative acidic compartment volume as a lysosomal storage disorder–associated biomarker 
The Journal of Clinical Investigation  2014;124(3):1320-1328.
Lysosomal storage disorders (LSDs) occur at a frequency of 1 in every 5,000 live births and are a common cause of pediatric neurodegenerative disease. The relatively small number of patients with LSDs and lack of validated biomarkers are substantial challenges for clinical trial design. Here, we evaluated the use of a commercially available fluorescent probe, Lysotracker, that can be used to measure the relative acidic compartment volume of circulating B cells as a potentially universal biomarker for LSDs. We validated this metric in a mouse model of the LSD Niemann-Pick type C1 disease (NPC1) and in a prospective 5-year international study of NPC patients. Pediatric NPC subjects had elevated acidic compartment volume that correlated with age-adjusted clinical severity and was reduced in response to therapy with miglustat, a European Medicines Agency–approved drug that has been shown to reduce NPC1-associated neuropathology. Measurement of relative acidic compartment volume was also useful for monitoring therapeutic responses of an NPC2 patient after bone marrow transplantation. Furthermore, this metric identified a potential adverse event in NPC1 patients receiving i.v. cyclodextrin therapy. Our data indicate that relative acidic compartment volume may be a useful biomarker to aid diagnosis, clinical monitoring, and evaluation of therapeutic responses in patients with lysosomal disorders.
doi:10.1172/JCI72835
PMCID: PMC3934186  PMID: 24487591
2.  Quality Control Methods in Accelerometer Data Processing: Identifying Extreme Counts 
PLoS ONE  2014;9(1):e85134.
Background
Accelerometers are designed to measure plausible human activity, however extremely high count values (EHCV) have been recorded in large-scale studies. Using population data, we develop methodological principles for establishing an EHCV threshold, propose a threshold to define EHCV in the ActiGraph GT1M, determine occurrences of EHCV in a large-scale study, identify device-specific error values, and investigate the influence of varying EHCV thresholds on daily vigorous PA (VPA).
Methods
We estimated quantiles to analyse the distribution of all accelerometer positive count values obtained from 9005 seven-year old children participating in the UK Millennium Cohort Study. A threshold to identify EHCV was derived by differentiating the quantile function. Data were screened for device-specific error count values and EHCV, and a sensitivity analysis conducted to compare daily VPA estimates using three approaches to accounting for EHCV.
Results
Using our proposed threshold of ≥ 11,715 counts/minute to identify EHCV, we found that only 0.7% of all non-zero counts measured in MCS children were EHCV; in 99.7% of these children, EHCV comprised < 1% of total non-zero counts. Only 11 MCS children (0.12% of sample) returned accelerometers that contained negative counts; out of 237 such values, 211 counts were equal to −32,768 in one child. The medians of daily minutes spent in VPA obtained without excluding EHCV, and when using a higher threshold (≥19,442 counts/minute) were, respectively, 6.2% and 4.6% higher than when using our threshold (6.5 minutes; p<0.0001).
Conclusions
Quality control processes should be undertaken during accelerometer fieldwork and prior to analysing data to identify monitors recording error values and EHCV. The proposed threshold will improve the validity of VPA estimates in children’s studies using the ActiGraph GT1M by ensuring only plausible data are analysed. These methods can be applied to define appropriate EHCV thresholds for different accelerometer models.
doi:10.1371/journal.pone.0085134
PMCID: PMC3890298  PMID: 24454804
3.  How active are our children? Findings from the Millennium Cohort Study 
BMJ Open  2013;3(8):e002893.
Objective
To describe levels of physical activity, sedentary time and adherence to Chief Medical Officers (CMO) physical activity guidelines among primary school-aged children across the UK using objective accelerometer-based measurements.
Design
Nationally representative prospective cohort study.
Setting
Children born across the UK, between 2000 and 2002.
Participants
6497 7-year-old to 8-year-old singleton children for whom reliable accelerometer data were available for at least 10 h a day for at least 2 days.
Main outcome measures
Physical activity in counts per minute (cpm); time spent in sedentary and moderate-to-vigorous intensity physical activity (MVPA); proportion of children meeting CMO guidelines (≥60 min/day MVPA); average daily steps.
Explanatory measures
Gender, ethnicity, maternal current/most recent occupation, lone parenthood status, number of children in the household and country/region of residence.
Results
The median daily physical activity level was 595 cpm (IQR 507, 697). Children spent a median of 60 min (IQR 47–76) in MVPA/day and were sedentary for a median of 6.4 h/day (IQR 6–7). Only 51% met CMO guidelines, with girls (38%) less active than boys (63%). Children took an average of 10 229 (95% CI (8777 to 11 775)) steps each day. Children of Indian ethnicity were significantly less active overall than all other ethnic groups. Children of Bangladeshi origin and those living in Northern Ireland were least likely to meet CMO guidelines.
Conclusions
Only half of 7-year-old children in the UK achieve recommended levels of physical activity, with significant gender, ethnic and geographic variations. Longitudinal studies are needed to better understand the relevance of these (in)activity patterns for long-term health and well-being. In the meantime population-wide efforts to boost physical activity among young people are needed which are likely to require a broad range of policy interventions.
doi:10.1136/bmjopen-2013-002893
PMCID: PMC3752053  PMID: 23965931
Public Health; Sports Medicine; Paediatrics
4.  Characteristics of 5-year-olds who catch-up with MMR: findings from the UK Millennium Cohort Study 
BMJ Open  2013;3(7):e003152.
Objectives
To examine predictors of partial and full measles, mumps and rubella (MMR) vaccination catch-up between 3 and 5 years.
Design
Secondary data analysis of the nationally representative Millennium Cohort Study (MCS).
Setting
Children born in the UK, 2000–2002.
Participants
751 MCS children who were unimmunised against MMR at age 3, with immunisation information at age 5.
Main outcome measures
Catch-up status: unimmunised (received no MMR), partial catch-up (received one MMR) or full catch-up (received two MMRs).
Results
At age 5, 60.3% (n=440) children remained unvaccinated, 16.1% (n=127) had partially and 23.6% (n=184) had fully caught-up. Children from families who did not speak English at home were five times as likely to partially catch-up than children living in homes where only English was spoken (risk ratio 4.68 (95% CI 3.63 to 6.03)). Full catch-up was also significantly more likely in those did not speak English at home (adjusted risk ratio 1.90 (1.08 to 3.32)). In addition, those from Pakistan/Bangladesh (2.40 (1.38 to 4.18)) or ‘other’ ethnicities (such as Chinese) (1.88 (1.08 to 3.29)) were more likely to fully catch-up than White British. Those living in socially rented (1.86 (1.34 to 2.56)) or ‘Other’ (2.52 (1.23 to 5.18)) accommodations were more likely to fully catch-up than home owners, and families were more likely to catch-up if they lived outside London (1.95 (1.32 to 2.89)). Full catch-up was less likely if parents reported medical reasons (0.43 (0.25 to 0.74)), a conscious decision (0.33 (0.23 to 0.48)), or ‘other’ reasons (0.46 (0.29 to 0.73)) for not immunising at age 3 (compared with ‘practical’ reasons).
Conclusions
Parents who partially or fully catch-up with MMR experience practical barriers and tend to come from disadvantaged or ethnic minority groups. Families who continue to reject MMR tend to have more advantaged backgrounds and make a conscious decision to not immunise early on. Health professionals should consider these findings in light of the characteristics of their local populations.
doi:10.1136/bmjopen-2013-003152
PMCID: PMC3717465  PMID: 23864213
Socio-economic factors; immunisation; measles-mumps-rubella vaccine; measles; child health services
5.  Quality Control Methods in Accelerometer Data Processing: Defining Minimum Wear Time 
PLoS ONE  2013;8(6):e67206.
Background
When using accelerometers to measure physical activity, researchers need to determine whether subjects have worn their device for a sufficient period to be included in analyses. We propose a minimum wear criterion using population-based accelerometer data, and explore the influence of gender and the purposeful inclusion of children with weekend data on reliability.
Methods
Accelerometer data obtained during the age seven sweep of the UK Millennium Cohort Study were analysed. Children were asked to wear an ActiGraph GT1M accelerometer for seven days. Reliability coefficients(r) of mean daily counts/minute were calculated using the Spearman-Brown formula based on the intraclass correlation coefficient. An r of 1.0 indicates that all the variation is between- rather than within-children and that measurement is 100% reliable. An r of 0.8 is often regarded as acceptable reliability. Analyses were repeated on data from children who met different minimum daily wear times (one to 10 hours) and wear days (one to seven days). Analyses were conducted for all children, separately for boys and girls, and separately for children with and without weekend data.
Results
At least one hour of wear time data was obtained from 7,704 singletons. Reliability increased as the minimum number of days and the daily wear time increased. A high reliability (r = 0.86) and sample size (n = 6,528) was achieved when children with ≥ two days lasting ≥10 hours/day were included in analyses. Reliability coefficients were similar for both genders. Purposeful sampling of children with weekend data resulted in comparable reliabilities to those calculated independent of weekend wear.
Conclusion
Quality control procedures should be undertaken before analysing accelerometer data in large-scale studies. Using data from children with ≥ two days lasting ≥10 hours/day should provide reliable estimates of physical activity. It’s unnecessary to include only children with accelerometer data collected during weekends in analyses.
doi:10.1371/journal.pone.0067206
PMCID: PMC3691227  PMID: 23826236
6.  Childhood Psychological Problems in School Settings in Rural Southern Africa 
PLoS ONE  2013;8(6):e65041.
Background
Many children can be exposed to multiple adversities in low and middle-income countries (LMICs) placing them at potential risk of psychological problems. However, there is a paucity of research using large representative cohorts examining the psychological adjustment of children in school settings in these countries. Children’s psychological adjustment has been shown to affect educational progress which is critical for their future. This study, based in a rural, socio-economically disadvantaged area of South Africa, aimed to examine the prevalence of children’s psychological problems as well as possible risk and protective factors.
Methods
Rates of psychological problems in 10–12 year olds were examined using teacher- and child-report questionnaires. Data on children from 10 rural primary schools, selected by stratified random sampling, were linked to individual and household data from the Agincourt health and socio-demographic surveillance system collected from households over 15 years.
Results
A total of 1,025 children were assessed. Teachers identified high levels of behavioural and emotional problems (41%). Children reported lower, but substantial rates of anxiety/depression (14%), and significant post-traumatic stress symptoms (24%); almost a quarter felt unsafe in school. Risk factors included being a second-generation former refugee and being from a large household. Protective factors highlight the importance of maternal factors, such as being more educated and in a stable partnership.
Conclusion
The high levels of psychological problems identified by teachers are a serious public health concern, as they are likely to impact negatively on children’s education, particularly given the large class sizes and limited resources in rural LMIC settings. Despite the high levels of risk, a proportion of children were managing well and research to understand resilience could inform interventions.
doi:10.1371/journal.pone.0065041
PMCID: PMC3680478  PMID: 23776443
7.  Predictors of non-response in a UK-wide cohort study of children's accelerometer-determined physical activity using postal methods 
BMJ Open  2013;3(3):e002290.
Objectives
To investigate the biological, social, behavioural and environmental factors associated with non-consent, and non-return of reliable accelerometer data (≥2 days lasting ≥10 h/day), in a UK-wide postal study of children's activity.
Design
Nationally representative prospective cohort study.
Setting
Children born across the UK, between 2000 and 2002.
Participants
13 681 7 to 8-year-old singleton children who were invited to wear an accelerometer on their right hip for 7 consecutive days. Consenting families were posted an Actigraph GT1M accelerometer and asked to return it by post.
Primary outcome measures
Study consent and reliable accelerometer data acquisition.
Results
Consent was obtained for 12 872 (94.5%) interviewed singletons, of whom 6497 (50.5%) returned reliable accelerometer data. Consent was less likely for children with a limiting illness or disability, children who did not have people smoking near them, children who had access to a garden, and those who lived in Northern Ireland. From those who consented, reliable accelerometer data were less likely to be acquired from children who: were boys; overweight/obese; of white, mixed or ‘other’ ethnicity; had an illness or disability limiting daily activity; whose mothers did not have a degree; who lived in rented accommodation; who exercised once a week or less; who had been breastfed; were from disadvantaged wards; had younger mothers or lone mothers; or were from households with just one, or more than three children.
Conclusions
Studies need to encourage consent and reliable data return in the wide range of groups we have identified to improve response and reduce non-response bias. Additional efforts targeted at such children should increase study consent and data acquisition while also reducing non-response bias. Adjustment must be made for missing data that account for missing data as a non-random event.
doi:10.1136/bmjopen-2012-002290
PMCID: PMC3612744  PMID: 23457328
Paediatrics
8.  The Double Burden of Obesity and Malnutrition in a Protracted Emergency Setting: A Cross-Sectional Study of Western Sahara Refugees 
PLoS Medicine  2012;9(10):e1001320.
Surveying women and children from refugee camps in Algeria, Carlos Grijalva-Eternod and colleagues find high rates of obesity among women as well as many undernourished children, and that almost a quarter of households are affected by both undernutrition and obesity.
Background
Households from vulnerable groups experiencing epidemiological transitions are known to be affected concomitantly by under-nutrition and obesity. Yet, it is unknown to what extent this double burden affects refugee populations dependent on food assistance. We assessed the double burden of malnutrition among Western Sahara refugees living in a protracted emergency.
Methods and Findings
We implemented a stratified nutrition survey in October–November 2010 in the four Western Sahara refugee camps in Algeria. We sampled 2,005 households, collecting anthropometric measurements (weight, height, and waist circumference) in 1,608 children (6–59 mo) and 1,781 women (15–49 y). We estimated the prevalence of global acute malnutrition (GAM), stunting, underweight, and overweight in children; and stunting, underweight, overweight, and central obesity in women. To assess the burden of malnutrition within households, households were first classified according to the presence of each type of malnutrition. Households were then classified as undernourished, overweight, or affected by the double burden if they presented members with under-nutrition, overweight, or both, respectively.
The prevalence of GAM in children was 9.1%, 29.1% were stunted, 18.6% were underweight, and 2.4% were overweight; among the women, 14.8% were stunted, 53.7% were overweight or obese, and 71.4% had central obesity. Central obesity (47.2%) and overweight (38.8%) in women affected a higher proportion of households than did GAM (7.0%), stunting (19.5%), or underweight (13.3%) in children. Overall, households classified as overweight (31.5%) were most common, followed by undernourished (25.8%), and then double burden–affected (24.7%).
Conclusions
The double burden of obesity and under-nutrition is highly prevalent in households among Western Sahara refugees. The results highlight the need to focus more attention on non-communicable diseases in this population and balance obesity prevention and management with interventions to tackle under-nutrition.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Good nutrition is essential for human health and survival. Insufficient food intake causes under-nutrition, which increases susceptibility to infections; intake of too much or inappropriate food, in particular in interaction with sedentary behaviour, can lead to obesity, which increases the risk of non-communicable diseases such as diabetes. During the past 30 years, the prevalence (the proportion of a population affected by a condition) of obesity has greatly increased, initially among adults in industrialized countries, but more recently among children and in less-affluent populations. Now, worldwide, overweight people outnumber under-nourished people. Furthermore, some populations are affected by both under-nutrition and obesity, forms of malnutrition that occur when the diet is suboptimal for health. So, for example, a child can be both stunted (short for his or her age, an indicator of long-term under-nutrition) and overweight (too heavy for his or her age). The emergence of this double burden of malnutrition has been attributed to the nutrition transition—the rapid move because of migration or urbanization to a lifestyle characterized by low levels of physical activity and high consumption of refined, energy-dense foods—without complete elimination of under-nutrition.
Why Was This Study Done?
Refugees are one group of people in whom under-nutrition and obesity sometimes coexist. Worldwide, in 2010, 15.4 million refugees were dependent on host governments and international humanitarian agencies for their food security and well-being. It is essential that these governments and organizations provide appropriate food assistance programs to refugees—policies that are appropriate during acute emergencies may not be appropriate in protracted emergencies and may contribute to the emergence of the double burden of malnutrition among refugees. Unfortunately, the extent to which the double burden of malnutrition affects refugees in protracted emergencies is unknown. In this cross-sectional study (an investigation that looks at the characteristics of a population at a single time), the researchers assessed the double burden of malnutrition among people from Western Sahara who have been living in four refugee camps near Tindouf city, Algeria, since 1975.
What Did the Researchers Do and Find?
The researchers used data from a 2010 survey that measured the height and weight of children and the height, weight, and waist circumference of women living in 2,005 households in the Algerian refugee camps. For the children, they estimated the prevalence of global acute malnutrition (which includes thin, “wasted” children, as indicated by a low weight for height based on the World Health Organization growth standards, and those with nutritional oedema), stunting, and underweight and overweight (low and high weight for age and gender, respectively). For the women, they estimated the prevalence of stunting, underweight (body mass index less than 18.5 kg/m2), overweight (body mass index greater than 25 kg/m2), and central obesity (a waist circumference of more than 80 cm). Among the children, 9.1% had global acute malnutrition, 29.1% were stunted, 8.6% were underweight, and 2.4% were overweight. Among the women, 14.8% were stunted, 53.7% were overweight, and 71.4% had central obesity. Notably, central obesity and overweight in women affected more households than global acute malnutrition, stunting, and underweight in children. Finally, based on whether a household included members with under-nutrition or overweight, alone or in combination, the researchers classified a third of households as overweight, a quarter as undernourished, and a quarter as affected by the double burden of malnutrition.
What Do These Findings Mean?
These findings indicate that there is a high prevalence of the double burden of malnutrition among households in Western Saharan refugee camps in Algeria. Although this study provides no information on men and does not investigate whether the obesity seen in these camps leads to an increased risk of diabetes and other non-communicable diseases, these findings have several important implications for the provision of food assistance and care for protracted humanitarian emergencies. For example, they highlight the need to promote long-term food security and to improve nutrition adequacy and food diversity in protracted emergencies. In addition, they suggest that current food assistance programs that are suitable for acute emergencies may not be suitable for extended emergencies. They also highlight the need to focus more attention on non-communicable diseases in refugee camps and to develop innovative ways to provide obesity prevention and management in these settings. However, as the researchers stress, careful policy and advocacy work is essential to ensure that efforts to deal with the threat of obesity among refugees do not jeopardize support for life-saving food assistance programs for refugees.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001320.
Wikipedia provides background information about the Western Sahara refugee camps near Tindouf, Algeria (note that Wikipedia is a free online encyclopedia that anyone can edit)
The World Health Organization provides information on all aspects of nutrition and obesity (in several languages)
The United Nations World Food Programme is the world's largest humanitarian agency fighting hunger worldwide; its website provides detailed information about hunger and information about its work in the Western Sahara refugee camps in Algeria, including personal stories and photographs of food distribution
The United Nations High Commissioner for Refugees is the United Nations body mandated to lead and coordinate international action to protect refugees and resolve refugee problems worldwide; its website provides detailed information about its work in the Western Sahara refugee camps in Algeria
Oxfam also provides detailed information about its work in the Algerian refugee camps, a description of the camps, and personal stories from people living in the camps
An article published by the Food and Agriculture Organization of the United Nations explains the double burden of malnutrition
doi:10.1371/journal.pmed.1001320
PMCID: PMC3462761  PMID: 23055833
9.  Body fat abnormality in HIV-infected children and adolescents living in Europe: prevalence and risk factors 
Objectives
To estimate the prevalence of, and identify risk factors for Lipodystrophy Syndrome (LS) and body fat abnormality in a population of HIV-infected children and adolescents.
Design
Cross-sectional observational study.
Methods
HIV-infected subjects aged 2-18 years were recruited from 15 HIV centres in Belgium, Italy and Poland between January 2007 and December 2008. Standardized assessments by the patient’s long-term clinician were performed to establish presence of abnormality. Risk factors were explored in logistic regression models for fat abnormality outcomes and LS (abnormality plus dyslipidemia).
Results
Among 426 subjects (70% white), median age was 12.2 (Inter quartile range, IQR: 9.0, 15.0) years and median duration of antiretroviral therapy (ART) was 5.2 (IQR: 2.2, 8.8) years. Prevalence was 57% (n=235) for LS and 42% (n=176) for fat abnormality; 90 subjects with abnormality were affected in ≥3 locations. Lipoatrophy occurred in 28% (n=117) subjects, and lipohypertrophy in 27% (n=115), most commonly in the face and trunk respectively. In multivariable analysis, white ethnicity, BMI, ritonavir/lopinavir and NNRTIs were each associated with increased risk of LS (p<0.05). White ethnicity, history of CDC-defined disease and stavudine were associated with risk of lipoatrophy (p<0.05). Increased risk of lipohypertrophy was associated with BMI and prior HIV disease.
Conclusions
Fat abnormality was prevalent in close to half of children and adolescents, who had accumulated long treatment durations. Risk of fat redistribution was associated with specific drugs, including stavudine and ritonavir, and other variables. Our results underline the importance of continued surveillance of children treated with ART.
doi:10.1097/QAI.0b013e31824330cb
PMCID: PMC3433033  PMID: 22205436
Children; adolescents; lipodystrophy syndrome; fat redistribution; ART
10.  Incidence, patterns, and predictors of repeat pregnancies among HIV-infected women in the United Kingdom and Ireland, 1990-2009 
Objective
To explore the pattern of repeat pregnancies among diagnosed HIV-infected women in the UK and Ireland, estimate the rate of these sequential pregnancies, and investigate the demographic and clinical characteristics of women experiencing them.
Design
Diagnosed HIV-infected pregnant women are reported through an active confidential reporting scheme to the National Study of HIV in Pregnancy and Childhood.
Methods
Pregnancies occurring during 1990-2009 were included. Multivariable analyses were conducted fitting Cox proportional hazards models.
Results
There were 14,096 pregnancies in 10,568 women; 2737 (25.9%) had two or more pregnancies reported. The rate of repeat pregnancies was 6.7 (95% CI: 6.5-7.0) per 100 woman-years. The proportion of pregnancies in women who already had at least one pregnancy reported increased from 20.3% (32/158) in 1997 to 38.6% (565/1465) in 2009 (p<0.001).
In multivariable analysis the probability of repeat pregnancy significantly declined with increasing age at first pregnancy. Parity was also inversely associated with repeat pregnancy. Compared with women born in the UK or Ireland, those from Europe, Eastern Africa, and Southern Africa were less likely to have a repeat pregnancy, while women from Middle Africa and Western Africa were more likely to. Maternal health at first pregnancy was not associated with repeat pregnancy.
Conclusions
The number of diagnosed HIV-infected women in the UK and Ireland experiencing repeat pregnancies is increasing. Variations in the probability of repeat pregnancies, according to demographic and clinical characteristics, are an important consideration when planning reproductive health services and HIV care for people living with HIV.
doi:10.1097/QAI.0b013e31823dbeac
PMCID: PMC3378493  PMID: 22227490
HIV; Women; Pregnancy; Surveillance; Epidemiology; United Kingdom and Ireland
11.  Insufficient antiretroviral therapy in pregnancy: missed opportunities for prevention of mother-to-child transmission of HIV in Europe 
Antiviral therapy  2011;16(6):895-903.
Background
Although mother-to-child transmission (MTCT) rates are at an all-time low in Western Europe, potentially preventable transmissions continue to occur. Duration of antenatal combination antiretroviral therapy (ART) is strongly associated with MTCT risk.
Methods
Data on pregnant HIV-infected women enrolled in the Western and Central European sites of the European Collaborative Study between January 2000 and July 2009 were analysed. The proportion of women receiving no antenatal ART or 1-13 days of treatment was investigated, and associated factors explored using logistic regression models.
Results
Of 2148 women, 142 (7%) received no antenatal ART, decreasing from 8% in 2000-03 to 5% in 2004-09 (χ2 =8.73, p<0.01). A further 41 (2%) received 1-13 days of ART. A third (64/171) of women with “insufficient” (no or 1-13 days) antenatal ART had a late HIV diagnosis (in the third trimester or intrapartum), but half (85/171) were diagnosed pre-conception. Preterm delivery <34 weeks was associated with receipt of no and 1-13 days antenatal ART (AOR 2.9 p<0.01 and AOR 4.5 p<0.01 respectively). Injecting drug use history was associated with an increased risk of no ART (AOR 2.9 p<0.01) and severe symptomatic HIV disease with a decreased risk (AOR 0.2, p<0.01). MTCT rates were 1.1% (15/1318) among women with ≥14 days antenatal ART and 7.4% (10/136) among those with insufficient ART.
Conclusions
Over the last 10 years, around 1 in 11 women in this study received insufficient antenatal ART, accounting for 40% of mother-to-child transmissions. Half of these women were diagnosed pre-conception, suggesting disengagement from care.
doi:10.3851/IMP1849
PMCID: PMC3428867  PMID: 21900722
12.  Cervical Screening within HIV Care: Findings from an HIV-Positive Cohort in Ukraine 
PLoS ONE  2012;7(4):e34706.
Introduction
HIV-positive women have an increased risk of invasive cervical cancer but cytologic screening is effective in reducing incidence. Little is known about cervical screening coverage or the prevalence of abnormal cytology among HIV-positive women in Ukraine, which has the most severe HIV epidemic in Europe.
Methods
Poisson regression models were fitted to data from 1120 women enrolled at three sites of the Ukraine Cohort Study of HIV-infected Childbearing Women to investigate factors associated with receiving cervical screening as part of HIV care. All women had been diagnosed as HIV-positive before or during their most recent pregnancy. Prevalence of cervical abnormalities (high/low grade squamous intraepithelial lesions) among women who had been screened was estimated, and associated factors explored.
Results
Overall, 30% (337/1120) of women had received a cervical screening test as part of HIV care at study enrolment (median 10 months postpartum), a third (115/334) of whom had been tested >12 months previously. In adjusted analyses, women diagnosed as HIV-positive during (vs before) their most recent pregnancy were significantly less likely to have a screening test reported, on adjusting for other potential risk factors (adjusted prevalence ratio (APR) 0.62, 95% CI 0.51–0.75 p<0.01 for 1st/2nd trimester diagnosis and APR 0.42, 95% CI 0.28–0.63 p<0.01 for 3rd trimester/intrapartum diagnosis). Among those with a cervical screening result reported at any time (including follow-up), 21% (68/325) had a finding of cervical abnormality. In adjusted analyses, Herpes simplex virus 2 seropositivity and a recent diagnosis of bacterial vaginosis were associated with an increased risk of abnormal cervical cytology (APR 1.83 95% CI 1.07–3.11 and APR 3.49 95% CI 2.11–5.76 respectively).
Conclusions
In this high risk population, cervical screening coverage as part of HIV care was low and could be improved by an organised cervical screening programme for HIV-positive women. Bacterial vaginosis testing and treatment may reduce vulnerability to cervical abnormalities.
doi:10.1371/journal.pone.0034706
PMCID: PMC3335834  PMID: 22545087
13.  Use of Zidovudine-Sparing HAART in Pregnant HIV-Infected Women in Europe: 2000–2009 
Background
Increasing numbers of women in resource-rich settings are prescribed zidovudine (ZDV)-sparing highly active antiretroviral therapy (HAART) in pregnancy. We compare ZDV-sparing with ZDV-containing HAART in relation to maternal viral load at delivery, mother-to-child transmission (MTCT) of HIV, and congenital abnormality.
Methods
This is an analysis of data from the National Study of HIV in Pregnancy and Childhood and the European Collaborative Study. Data on 7573 singleton births to diagnosed HIV-infected women between January 2000 and June 2009 were analyzed. Logistic regression models were fitted to estimate adjusted odds ratios (AORs).
Results
Overall, 15.8% (1199 of 7573) of women received ZDV-sparing HAART, with increasing use between 2000 and 2009 (P < 0.001). Nearly a fifth (18.4%) of women receiving ZDV-sparing HAART in pregnancy had a detectable viral load at delivery compared with 28.6% of women on ZDV-containing HAART [AOR 0.90; 95% confidence interval (CI): 0.72 to 1.14, P = 0.4]. MTCT rates were 0.8% and 0.9% in the ZDV-sparing and ZDV-containing groups, respectively (AOR 1.81; 95% CI: 0.77 to 4.26, P = 0.2). The congenital abnormality rate was the same in both groups (2.7%, AOR 0.98; 95% CI: 0.66 to 1.45, P = 0.9), with no significant difference between the groups in a subanalysis of pregnancies with first trimester HAART exposure (AOR 0.79; 95% CI: 0.48 to 1.30, P = 0.4).
Conclusions
We found no difference in risk of detectable viral load at delivery, MTCT, or congenital abnormality when comparing ZDV-sparing with ZDV-containing HAART. With increasing use of ZDV-sparing HAART, continued monitoring of pregnancy outcomes and long-term consequences of in utero exposure to these drugs is required.
doi:10.1097/QAI.0b013e31821d34d0
PMCID: PMC3319104  PMID: 21499113
antiretroviral agents; highly active antiretroviral therapy; HIV; pregnancy outcome; viral load; congenital abnormalities
14.  Interactions between PPAR-α and inflammation-related cytokine genes on the development of Alzheimer’s disease, observed by the Epistasis Project 
Objective
Neuroinflammation contributes to the pathogenesis of sporadic Alzheimer’s disease (AD). Variations in genes relevant to inflammation may be candidate genes for AD risk. Whole-genome association studies have identified relevant new and known genes. Their combined effects do not explain 100% of the risk, genetic interactions may contribute. We investigated whether genes involved in inflammation, i.e. PPAR-α, interleukins (IL) IL- 1α, IL-1β, IL-6, and IL-10 may interact to increase AD risk.
Methods
The Epistasis Project identifies interactions that affect the risk of AD. Genotyping of single nucleotide polymorphisms (SNPs) in PPARA, IL1A, IL1B, IL6 and IL10 was performed. Possible associations were analyzed by fitting logistic regression models with AD as outcome, controlling for centre, age, sex and presence of apolipoprotein ε4 allele (APOEε4). Adjusted synergy factors were derived from interaction terms (p<0.05 two-sided).
Results
We observed four significant interactions between different SNPs in PPARA and in interleukins IL1A, IL1B, IL10 that may affect AD risk. There were no significant interactions between PPARA and IL6.
Conclusions
In addition to an association of the PPARA L162V polymorphism with the AD risk, we observed four significant interactions between SNPs in PPARA and SNPs in IL1A, IL1B and IL10 affecting AD risk. We prove that gene-gene interactions explain part of the heritability of AD and are to be considered when assessing the genetic risk. Necessary replications will require between 1450 and 2950 of both cases and controls, depending on the prevalence of the SNP, to have 80% power to detect the observed synergy factors.
PMCID: PMC3316448  PMID: 22493750
AD; genetics; epistasis; inflammation; interleukin; steroid receptors; PPAR-alpha; sporadic; genetic interaction
15.  Actigraph Accelerometer-Defined Boundaries for Sedentary Behaviour and Physical Activity Intensities in 7 Year Old Children 
PLoS ONE  2011;6(8):e21822.
Background
Accurate objective assessment of sedentary and physical activity behaviours during childhood is integral to the understanding of their relation to later health outcomes, as well as to documenting the frequency and distribution of physical activity within a population.
Purpose
To calibrate the Actigraph GT1M accelerometer, using energy expenditure (EE) as the criterion measure, to define thresholds for sedentary behaviour and physical activity categories suitable for use in a large scale epidemiological study in young children.
Methods
Accelerometer-based assessments of physical activity (counts per minute) were calibrated against EE measures (kcal.kg−1.hr−1) obtained over a range of exercise intensities using a COSMED K4b2 portable metabolic unit in 53 seven-year-old children. Children performed seven activities: lying down viewing television, sitting upright playing a computer game, slow walking, brisk walking, jogging, hopscotch and basketball. Threshold count values were established to identify sedentary behaviour and light, moderate and vigorous physical activity using linear discriminant analysis (LDA) and evaluated using receiver operating characteristic (ROC) curve analysis.
Results
EE was significantly associated with counts for all non-sedentary activities with the exception of jogging. Threshold values for accelerometer counts (counts.minute−1) were <100 for sedentary behaviour and ≤2240, ≤3840 and ≥3841 for light, moderate and vigorous physical activity respectively. The area under the ROC curves for discrimination of sedentary behaviour and vigorous activity were 0.98. Boundaries for light and moderate physical activity were less well defined (0.61 and 0.60 respectively). Sensitivity and specificity were higher for sedentary (99% and 97%) and vigorous (95% and 91%) than for light (60% and 83%) and moderate (61% and 76%) thresholds.
Conclusion
The accelerometer cut points established in this study can be used to classify sedentary behaviour and to distinguish between light, moderate and vigorous physical activity in children of this age.
doi:10.1371/journal.pone.0021822
PMCID: PMC3154898  PMID: 21853021
16.  The dopamine β-hydroxylase -1021C/T polymorphism is associated with the risk of Alzheimer's disease in the Epistasis Project 
BMC Medical Genetics  2010;11:162.
Background
The loss of noradrenergic neurones of the locus coeruleus is a major feature of Alzheimer's disease (AD). Dopamine β-hydroxylase (DBH) catalyses the conversion of dopamine to noradrenaline. Interactions have been reported between the low-activity -1021T allele (rs1611115) of DBH and polymorphisms of the pro-inflammatory cytokine genes, IL1A and IL6, contributing to the risk of AD. We therefore examined the associations with AD of the DBH -1021T allele and of the above interactions in the Epistasis Project, with 1757 cases of AD and 6294 elderly controls.
Methods
We genotyped eight single nucleotide polymorphisms (SNPs) in the three genes, DBH, IL1A and IL6. We used logistic regression models and synergy factor analysis to examine potential interactions and associations with AD.
Results
We found that the presence of the -1021T allele was associated with AD: odds ratio = 1.2 (95% confidence interval: 1.06-1.4, p = 0.005). This association was nearly restricted to men < 75 years old: odds ratio = 2.2 (1.4-3.3, 0.0004). We also found an interaction between the presence of DBH -1021T and the -889TT genotype (rs1800587) of IL1A: synergy factor = 1.9 (1.2-3.1, 0.005). All these results were consistent between North Europe and North Spain.
Conclusions
Extensive, previous evidence (reviewed here) indicates an important role for noradrenaline in the control of inflammation in the brain. Thus, the -1021T allele with presumed low activity may be associated with misregulation of inflammation, which could contribute to the onset of AD. We suggest that such misregulation is the predominant mechanism of the association we report here.
doi:10.1186/1471-2350-11-162
PMCID: PMC2994840  PMID: 21070631
17.  Prenatal Treatment for Serious Neurological Sequelae of Congenital Toxoplasmosis: An Observational Prospective Cohort Study 
PLoS Medicine  2010;7(10):e1000351.
An observational study by Ruth Gilbert and colleagues finds that prenatal treatment of congenital toxoplasmosis could substantially reduce the proportion of infected fetuses that develop serious neurological sequelae.
Background
The effectiveness of prenatal treatment to prevent serious neurological sequelae (SNSD) of congenital toxoplasmosis is not known.
Methods and Findings
Congenital toxoplasmosis was prospectively identified by universal prenatal or neonatal screening in 14 European centres and children were followed for a median of 4 years. We evaluated determinants of postnatal death or SNSD defined by one or more of functional neurological abnormalities, severe bilateral visual impairment, or pregnancy termination for confirmed congenital toxoplasmosis. Two-thirds of the cohort received prenatal treatment (189/293; 65%). 23/293 (8%) fetuses developed SNSD of which nine were pregnancy terminations. Prenatal treatment reduced the risk of SNSD. The odds ratio for prenatal treatment, adjusted for gestational age at maternal seroconversion, was 0.24 (95% Bayesian credible intervals 0.07–0.71). This effect was robust to most sensitivity analyses. The number of infected fetuses needed to be treated to prevent one case of SNSD was three (95% Bayesian credible intervals 2–15) after maternal seroconversion at 10 weeks, and 18 (9–75) at 30 weeks of gestation. Pyrimethamine-sulphonamide treatment did not reduce SNSD compared with spiramycin alone (adjusted odds ratio 0.78, 0.21–2.95). The proportion of live-born infants with intracranial lesions detected postnatally who developed SNSD was 31.0% (17.0%–38.1%).
Conclusion
The finding that prenatal treatment reduced the risk of SNSD in infected fetuses should be interpreted with caution because of the low number of SNSD cases and uncertainty about the timing of maternal seroconversion. As these are observational data, policy decisions about screening require further evidence from a randomized trial of prenatal screening and from cost-effectiveness analyses that take into account the incidence and prevalence of maternal infection.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Toxoplasmosis is a very common parasitic infection. People usually become infected with Toxoplasma gondii, the parasite that causes toxoplasmosis, by eating raw or undercooked meat that contains the parasite, but it can also be contracted by drinking unfiltered water or by handling cat litter. Most people with toxoplasmosis never know they have the disease. However, if a pregnant woman becomes infected with T. gondii, she can transmit the parasite to her unborn baby (fetus). Overall, about a quarter of women who catch toxoplasmosis during pregnancy transmit the parasite to their fetus. If transmission occurs early during pregnancy, the resultant “congenital toxoplasmosis” increases the risk of miscarriage and the risk of the baby being born with brain damage, epilepsy, deafness, blindness, or developmental problems (“serious neurological sequelae”). In the worst cases, babies may be born dead or die soon after birth. Congenital toxoplasmosis caught during the final third of pregnancy may not initially cause any health problems but eyesight problems often develop later in life.
Why Was This Study Done?
Clinicians can find out if a woman has been infected with T. gondii during pregnancy by looking for parasite-specific antibodies (proteins made by the immune system that fight infections) in her blood. If the pattern of antibodies suggests a recent infection, the woman can be given spiramycin or pyrimethamine-sulfonamide, antibiotics that are thought to reduce the risk of transmission to the fetus and the severity of toxoplasmosis in infected fetuses. In some countries where toxoplasmosis is particularly common (for example, France), pregnant women are routinely screened for toxoplasmosis and treated with antibiotics if there are signs of recent infection. But is prenatal treatment an effective way to prevent the serious neurological sequelae or postnatal death (SNSD) associated with congenital toxoplasmosis? In this observational study, the researchers examine this question by studying a group of children identified as having congenital toxoplasmosis by prenatal or neonatal screening in six European countries. An observational study measures outcomes in a group of patients without trying to influence those outcomes by providing a specific treatment.
What Did the Researchers Do and Find?
The researchers followed 293 children in whom congenital toxoplasmosis had been identified by prenatal screening (in France, Austria, and Italy) or by neonatal screening (in Denmark, Sweden, and Poland) for an average 4 years. Two-thirds of the children received prenatal treatment for toxoplasmosis and 23 fetuses (8% of the fetuses) developed SNSD; nine of these cases of SNSD were terminated during pregnancy. By comparing the number of cases of SNSD among children who received prenatal treatment with the number among children who did not receive prenatal treatment, the researchers estimate that prenatal treatment reduced the risk of SNSD by three-quarters. They also estimate that to prevent one case of SNSD after maternal infection at 10 weeks of pregnancy, it would be necessary to treat three fetuses with confirmed infection. To prevent one case of SNSD after maternal infection at 30 weeks of pregnancy, 18 fetuses would need to be treated. Finally, the researchers report that the effectiveness of pyrimethamine-sulfonamide and spiramycin (which is less toxic) was similar, and that a third of live-born infants with brain damage that was detected after birth subsequently developed SNSD.
What Do These Findings Mean?
These findings suggest that prenatal treatment of congenital toxoplasmosis could substantially reduce the proportion of infected fetuses that develop SNDS and would be particularly effective in fetuses whose mothers acquired T. gondii during the first third of pregnancy. These findings should be interpreted with caution, however, because of the small number of affected fetuses in the study and because of uncertainty about the timing of maternal infection. Furthermore, these findings only relate to the relatively benign strain of T. gondii that predominates in Europe and North America; further studies are needed to test whether prenatal treatment is effective against the more virulent strains of the parasite that occur in South America. Finally, because this study is an observational study, its findings might reflect differences between the study participants other than whether or not they received prenatal treatment. These findings need to be confirmed in randomized controlled trials of prenatal screening, therefore, before any policy decisions are made about routine prenatal screening and treatment for congenital toxoplasmosis.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000351.
The US Centers for Disease Control and Prevention provides detailed information about all aspects of toxoplasmosis, including toxoplasmosis in pregnant women (in English and Spanish)
The UK National Health Services Choices website has information for patients about toxoplasmosis and about the risks of toxoplasmosis during pregnancy
KidsHealth, a resource maintained by the Nemours Foundation (a not-for-profit organization for children's health), provides information for parents about toxoplasmosis (in English and Spanish)
Tommy's, a nonprofit organization that funds research on the health of babies, also has information on toxoplasmosis
MedlinePlus provides links to other information on toxoplasmosis (in English and Spanish)
EUROTOXO contains reports generated by a European consensus development project
Uptodate provides information about toxoplasmosis and pregnancy
doi:10.1371/journal.pmed.1000351
PMCID: PMC2953528  PMID: 20967235
18.  25-Hydroxyvitamin D and Pre-Clinical Alterations in Inflammatory and Hemostatic Markers: A Cross Sectional Analysis in the 1958 British Birth Cohort 
PLoS ONE  2010;5(5):e10801.
Background
Vitamin D deficiency has been suggested as a cardiovascular risk factor, but little is known about underlying mechanisms or associations with inflammatory or hemostatic markers. Our aim was to investigate the association between 25-hydroxyvitamin D [25(OH)D, a measure for vitamin D status] concentrations with pre-clinical variations in markers of inflammation and hemostasis.
Methodology/Principal Findings
Serum concentrations of 25(OH)D, C-reactive protein (CRP), fibrinogen, D-dimer, tissue plasminogen activator (tPA) antigen, and von Willebrand factor (vWF) were measured in a large population based study of British whites (aged 45y). Participants for the current investigation were restricted to individuals free of drug treated cardiovascular disease (n = 6538). Adjusted for sex and month, 25(OH)D was inversely associated with all outcomes (p≤0.015 for all), but associations with CRP, fibrinogen, and vWF were explained by adiposity. Association with tPA persisted after full adjustment (body mass index, waist circumference, physical activity, TV watching, smoking, alcohol consumption, social class, sex, and month), and average concentrations were 18.44% (95% CI 8.13, 28.75) lower for 25(OH)D ≥75 nmol/l compared to <25 nmol/l. D-dimer concentrations were lower for participants with 25(OH)D 50–90nmol/l compared to others (quadratic term p = 0.01). We also examined seasonal variation in hemostatic and inflammatory markers, and evaluated 25(OH)D contribution to the observed patterns using mediation models. TPA concentrations varied by season (p = 0.02), and much of this pattern was related to fluctuations in 25(OH)D concentrations (p≤0.001). Some evidence of a seasonal variation was observed also for fibrinogen, D-dimer and vWF (p<0.05 for all), with 25(OH)D mediating some of the pattern for fibrinogen and D-dimer, but not vWF.
Conclusions
Current vitamin D status was associated with tPA concentrations, and to a lesser degree with fibrinogen and D-dimer, suggesting that vitamin D status/intake may be important for maintaining antithrombotic homeostasis.
doi:10.1371/journal.pone.0010801
PMCID: PMC2875406  PMID: 20520739
19.  Replication by the Epistasis Project of the interaction between the genes for IL-6 and IL-10 in the risk of Alzheimer's disease 
Background
Chronic inflammation is a characteristic of Alzheimer's disease (AD). An interaction associated with the risk of AD has been reported between polymorphisms in the regulatory regions of the genes for the pro-inflammatory cytokine, interleukin-6 (IL-6, gene: IL6), and the anti-inflammatory cytokine, interleukin-10 (IL-10, gene: IL10).
Methods
We examined this interaction in the Epistasis Project, a collaboration of 7 AD research groups, contributing DNA samples from 1,757 cases of AD and 6,295 controls.
Results
We replicated the interaction. For IL6 rs2069837 AA × IL10 rs1800871 CC, the synergy factor (SF) was 1.63 (95% confidence interval: 1.10–2.41, p = 0.01), controlling for centre, age, gender and apolipoprotein E ε4 (APOEε4) genotype. Our results are consistent between North Europe (SF = 1.7, p = 0.03) and North Spain (SF = 2.0, p = 0.09). Further replication may require a meta-analysis. However, association due to linkage disequilibrium with other polymorphisms in the regulatory regions of these genes cannot be excluded.
Conclusion
We suggest that dysregulation of both IL-6 and IL-10 in some elderly people, due in part to genetic variations in the two genes, contributes to the development of AD. Thus, inflammation facilitates the onset of sporadic AD.
doi:10.1186/1742-2094-6-22
PMCID: PMC2744667  PMID: 19698145
20.  The synergy factor: a statistic to measure interactions in complex diseases 
BMC Research Notes  2009;2:105.
Background
One challenge in understanding complex diseases lies in revealing the interactions between susceptibility factors, such as genetic polymorphisms and environmental exposures. There is thus a need to examine such interactions explicitly. A corollary is the need for an accessible method of measuring both the size and the significance of interactions, which can be used by non-statisticians and with summarised, e.g. published data. The lack of such a readily available method has contributed to confusion in the field.
Findings
The synergy factor (SF) allows assessment of binary interactions in case-control studies. In this paper we describe its properties and its novel characteristics, e.g. in calculating the power to detect a synergistic effect and in its application to meta-analyses. We illustrate these functions with real examples in Alzheimer's disease, e.g. a meta-analysis of the potential interaction between a BACE1 polymorphism and APOE4: SF = 2.5, 95% confidence interval: 1.5–4.2; p = 0.0001.
Conclusion
Synergy factors are easy to use and clear to interpret. Calculations may be performed through the Excel programmes provided within this article. Unlike logistic regression analysis, the method can be applied to datasets of any size, however small. It can be applied to primary or summarised data, e.g. published data. It can be used with any type of susceptibility factor, provided the data are dichotomised. Novel features include power estimation and meta-analysis.
doi:10.1186/1756-0500-2-105
PMCID: PMC2706251  PMID: 19527493
21.  Genetic and Epigenetic Factors at COL2A1 and ABCA4 Influence Clinical Outcome in Congenital Toxoplasmosis 
PLoS ONE  2008;3(6):e2285.
Background
Primary Toxoplasma gondii infection during pregnancy can be transmitted to the fetus. At birth, infected infants may have intracranial calcification, hydrocephalus, and retinochoroiditis, and new ocular lesions can occur at any age after birth. Not all children who acquire infection in utero develop these clinical signs of disease. Whilst severity of disease is influenced by trimester in which infection is acquired by the mother, other factors including genetic predisposition may contribute.
Methods and Findings
In 457 mother-child pairs from Europe, and 149 child/parent trios from North America, we show that ocular and brain disease in congenital toxoplasmosis associate with polymorphisms in ABCA4 encoding ATP-binding cassette transporter, subfamily A, member 4. Polymorphisms at COL2A1 encoding type II collagen associate only with ocular disease. Both loci showed unusual inheritance patterns for the disease allele when comparing outcomes in heterozygous affected children with outcomes in affected children of heterozygous mothers. Modeling suggested either an effect of mother's genotype, or parent-of-origin effects. Experimental studies showed that both ABCA4 and COL2A1 show isoform-specific epigenetic modifications consistent with imprinting.
Conclusions
These associations between clinical outcomes of congenital toxoplasmosis and polymorphisms at ABCA4 and COL2A1 provide novel insight into the molecular pathways that can be affected by congenital infection with this parasite.
doi:10.1371/journal.pone.0002285
PMCID: PMC2390765  PMID: 18523590
22.  Eating habits and attitudes among 10-year-old children of mothers with eating disorders 
Background
Children of mothers with eating disorders are at increased risk of developmental disturbance, but there has been little research in middle childhood, when disturbed eating habits tend to emerge.
Aims
To examine whether maternal eating disorders identified in the postnatal year are associated with the development of disturbed eating habits and attitudes in children at 10 years of age.
Method
Follow-up comparative study of 56 families (33 mothers with eating disorders and 23 controls).
Psychopathology of children, mothers and fathers was assessed by interview, and mother-child interaction observed.
Results
The index group of children scored higher than controls on three of four domains of eating disorder psychopathology and on a global score. Children’s eating disturbance was associated with length of exposure to mothers’ eating disorder and mother-child mealtime conflict at 5 years. There was some evidence of increased emotional problems in index children.
Conclusions
The children of mothers with eating disorders manifested disturbed eating habits and attitudes compared with controls, and may be at heightened risk of developing frank eating disorder psychopathology.
doi:10.1192/bjp.bp.105.014316
PMCID: PMC1888733  PMID: 17012655
23.  Maternal Cognitions and Mother–Infant Interaction in Postnatal Depression and Generalized Anxiety Disorder 
Journal of Abnormal Psychology  2012;121(4):795-809.
Postnatal depression and anxiety have been shown to increase the risk of disturbances in mother–child interaction and child development. Research into mechanisms has focused on genetics and maternal behavior; maternal cognitions have received little attention. Our aim was to experimentally determine if worry and rumination in mothers with generalized anxiety disorder (GAD) and major depressive disorder (MDD), diagnosed in the postnatal 6 months, interfered with maternal responsiveness to their 10-month old infants. Mothers (N = 253: GAD n = 90; MDD n = 57; control n = 106) and their infants were randomized to either a worry/rumination prime (WRP) or a neutral prime (NP); mother–infant interactions were assessed before and after priming. Type of priming was a significant predictor of maternal cognitions, with WRP resulting in more negative thoughts, higher thought recurrence and more self-focus relative to NP across the entire sample. Interaction effects between group and priming were significant for two parenting variables: Compared with controls, WRP had a more negative impact on maternal responsiveness to infant vocalization for GAD, and to a lesser extent for MDD; WRP led to decreased maternal vocalization for GAD. Also, mothers with GAD used stronger control after the NP than WRP, as well as compared with other groups, and overall post-priming, their children exhibited lower emotional tone and more withdrawal. Across the entire sample, WRP was associated with increased child vocalization relative to NP. This study demonstrated that disturbances in maternal cognitions, in the context of postnatal anxiety and to a lesser degree depression, play a significant role in mother–child interaction.
doi:10.1037/a0026847
PMCID: PMC3506203  PMID: 22288906
mother–child interaction; worry; rumination; attention; infancy

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