Learning from facial expressions in individuals with Williams syndrome.

BACKGROUND: Despite high levels of social engagement, the social competence of individuals with Williams syndrome (WS) is frequently compromised. This descriptive study explores the ability of young people with WS to learn from facial expressions when provided as a source of feedback for their actions. METHOD: Using a novel task, the ability to interpret facial expressions and adapt behaviour after receiving feedback in the form of happy or angry faces was assessed in 12 participants with WS aged between 10 and 28 years and with a mean nonverbal mental age of 6.5 years, and in typically developing (TD) children aged between 4 and 7 years. RESULTS: Individuals with WS were able to use facial expressions as feedback in a manner commensurate with their mental age, only when other cognitive demands were low. Their performance profile differed from that of the TD children matched for mental age and from the performance profile of 4 year olds. CONCLUSIONS: Possible explanations for the unique performance profile observed in the participants with WS are discussed. The results highlight the need to examine social competencies in the context of the cognitive demands characteristic of social environments.

Does type of disability make a difference in affiliate stigma among family caregivers of individuals with autism, intellectual disability or physical disability?

BACKGROUND: Studies have shown that beyond public and self stigma, stigma can also impact family members. Only scant research has examined the internalised aspects of stigma, known as affiliate stigma, among family caregivers of individuals with disabilities. This study examined affiliate stigma among family caregivers of individuals with developmental disabilities via a comparison between caregivers of individuals with intellectual disabilities (ID), autism spectrum disorders (ASD) and physical disabilities (PD) in Israel. METHODS: Family caregivers (n = 171) of individuals with developmental disabilities, mainly ID (22.4%), ASD (32.9%) and PD (27.1%), completed a self-report structured questionnaire including the Affiliate Stigma Scale and background variables. RESULTS: Results supported a one-factor structure for the Affiliate Stigma Scale. Overall, affiliate stigma was relatively low in this sample, but was found to be higher among caregivers of individuals with ASD when compared with caregivers of individuals with ID or PD. CONCLUSION: Findings from this study point to the importance of supporting caregivers of individuals with ASD to decrease their feelings of stigma. It is also important to further develop scales measuring affiliate stigma in order to capture the multi-dimensional nature of the concept.

Elevated plasma urokinase receptor predicts low birth weight in maternal malaria.

The blood level of soluble urokinase receptor (suPAR) is increased and associated with a poor clinical or fatal outcome in children with acute malaria. This study hypothesized that the suPAR level would be associated with foetal outcome in maternal malaria. suPAR was measured by ELISA in maternal and cord plasma samples taken during delivery in 253 pregnant Kenyan women stratified according to placental histology: no malaria infection (non-infected), active or active-chronic infection (actively infected) or past-chronic infection (past-infected). Maternal-suPAR was higher in actively infected women (median 3.93 (IQR 2.92-5.29) ng/mL) compared with non-infected (median 2.78 (IQR 1.86-3.87) ng/mL, P = 0.001) and past-infected (median 2.67 (IQR 1.94-3.7) ng/mL, P = 0.012) women. Cord-suPAR was comparable across the groups (median 2.98 (IQR 2.38-3.77) ng/mL). In actively infected women, maternal-suPAR and gestational age were the only independent predictors of birth weight in multivariate linear regression adjusted for maternal-suPAR, HIV-1 infection, age, BMI, haemoglobin, peripheral parasitaemia, parity and gestational age; 1 ng/mL higher maternal-suPAR predicted -56 g (95% CI -100 to -12, P = 0.016) reduced birth weight. Cord-suPAR could not predict birth weight after adjusting for gestational age. Future studies are warranted to investigate whether the maternal suPAR level is increased earlier in pregnancy in women with active placental malaria infection and whether early maternal suPAR measurements can predict birth weight. If so, measurements of maternal suPAR early in pregnancy might then potentially identify women with increased needs for antenatal care and intervention.

A randomized, placebo-controlled trial of intermittent preventive treatment with sulphadoxine-pyrimethamine in Gambian multigravidae.

We investigated the ability of intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine/pyrimethamine to prevent anaemia and low birthweight in Gambian multigravidae. Between July 2002 and February 2004, 2688 multigravidae living in a rural area of The Gambia received SP (1346 women) or placebo (1342 women) up to four times during pregnancy and were followed until 6-weeks post-partum. Shortly after delivery, 10.7% of women in the intervention group and 8.8% in the control group were severely anaemic [Hb < 7 g/dl, risk difference = 0.02 (95% CI -0.01, 0.04), P = 0.17]. The overall mean birthweight of infants born to women who had received SP (3103 g) was very similar to that observed in infants born to women in the control group [3075 g; difference = 28 g (95% CI -11 g, 67 g), P = 0.16]. However, among women who did not use a bednet (either insecticide treated or untreated), infants born to women who had received SP weighed more than infants born to women in the control group [3147 g vs. 3044 g; difference 143 g (95% CI 53 g, 232 g), interaction test P < 0.001]. This study did not show that IPTp with SP benefited Gambian multigravidae overall but that it may benefit a sub-group of women who do not use a bednet. In areas such as The Gambia, provision of insecticide-treated bednets to multigravidae may provide an adequate means of protection against malaria in pregnancy without the need for additional IPTp.

Association between the arginine vasopressin 1a receptor (AVPR1a) gene and autism in a family-based study: mediation by socialization skills.

We examined three microsatellites in the arginine vasopressin 1a receptor gene (AVPR1a), two in the promoter region (RS1 and RS3) and an intronic microsatellite (AVR), for association with autism as well as scores on the Vineland Adaptive Behavior Scale (VABS), the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Scale-Generic (ADOS-G), measures that are widely used to diagnose autism spectrum disorders. We tested for association between the AVPR1a microsatellites and autism in 116 families (128 probands diagnosed with the ADI-R and ADOS-G using a family-based association test (UNPHASED)). Testing each individual microsatellite showed significant transmission disequilibrium in these families with the AVR intronic microsatellite (UNPHASED: LRS=11.46, global P-value=0.009, df=3). Haplotype analysis of three microsatellites also showed significant association (LRS=144.94, df=103, global P=0.004). Additionally, significant association is observed between these three microsatellite haplotypes and the VABS scores (P=0.009), with the ADI-R (P=0.009) and the ADOS-G (P=0.0000765) diagnoses of autistic disorder versus pervasive developmental disorder-not otherwise specified (PDD-NOS) that were available for 47 of these probands. This is the third consecutive report of an association between the AVPR1a gene and autism spectrum disorders and in the current study a third microsatellite is shown to be associated with autism spectrum disorders as well as haplotypes consisting of all three markers. Importantly, the association appears to be mainly mediated by the role of the AVPR1a gene in shaping socialization skills, similar to its role in lower vertebrates.Molecular Psychiatry (2006) 11, 488-494. doi:10.1038/sj.mp.4001812; published online 7 March 2006.

Impaired uteroplacental blood flow in pregnancies complicated by falciparum malaria.

OBJECTIVE: In endemic areas, maternal malaria infection is usually asymptomatic. However, it is known that infected maternal erythrocytes sequester in the intervillous space of the placenta. There is a strong association between placental malaria infection and both low birth weight (LBW) and severe maternal anemia. We aimed to determine whether impaired uteroplacental blood flow might account for the low infant birth weight associated with maternal falciparum malaria infection. METHODS: This observational study was carried out during a large double-blind, randomized, controlled trial of an antimalarial drug intervention for primigravidae. Nine hundred and ninety-five women were recruited from the antenatal clinic at a district hospital on the Kenya coast and had at least one Doppler ultrasound scan. Uterine artery resistance index and the presence or absence of a diastolic notch were recorded. In the third trimester, blood was taken for hemoglobin and malaria film. RESULTS: Malaria infection at 32-35 weeks of gestation was associated with abnormal uterine artery flow velocity waveforms on the day of blood testing (relative risk (RR) 2.11, 95% confidence interval (CI) 1.24-3.59, P = 0.006). This association persisted after controlling for pre-eclampsia. Impaired uteroplacental blood flow in the women studied was also predictive of poor perinatal outcome, including low birth weight, preterm delivery and perinatal death. The risk of preterm delivery in women with histological evidence of past placental malaria infection was more than twice that of women without infection (RR 2.33, 95% CI 1.31-4.13, P = 0.004). CONCLUSIONS: Uteroplacental hemodynamics are altered in the presence of maternal falciparum malaria infection. This may account for some of the excess of LBW babies observed in malaria endemic areas. Strategies that prevent or clear placental malaria may confer perinatal benefit through preservation of placental function.

Malaria in pregnancy: adverse effects on haemoglobin levels and birthweight in primigravidae and multigravidae.

BACKGROUND: In areas of endemic transmission, malaria in pregnancy is associated with severe maternal anaemia and low birthweight babies. The prevalence of infection is highest in primigravidae (PG), and hence control efforts are usually geared towards this high risk group. Using a sensitive measure of placental infection, we investigated the relationship between active-acute, active-chronic and past placental infection with maternal anaemia and low birthweight in women of all gravidities. METHODS: Between January 1996 and July 1997, 912 women delivering in Kilifi District Hospital, Kenya, were recruited. Haemoglobin and peripheral malaria slides were taken prior to delivery, placental biopsies and smears were taken at the time of delivery and birthweight and maternal height and weight were measured soon after birth. Information was obtained on socio-economic and educational status. The association between placental malaria, severe anaemia and low birthweight was investigated for women of different gravidities. FINDINGS: By placental histology, the prevalence of active or past malaria in all gravidities was high, ranging from 64% in PG to 30% in gravidities 5 and above. In gravidities 1-4, active malaria infection was associated with severe maternal anaemia, adjusted OR 2.21 (95% CI 1.36, 3.61). There was a significant interaction between chronic or past malaria and severe anaemia in their effects on birthweight, whereby the risk of low birthweight was very high in women with both chronic or past placental malaria and severe anaemia: OR 4.53 (1.19, 17.2) in PG; 13.5 (4.57, 40) in gravidities 2-4. INTERPRETATION: In this area of moderate malaria transmission, women of all parities have substantially increased risk of low birthweight and severe anaemia as a result of malaria infection in pregnancy. The risk of low birthweight is likely to be particularly high in areas with a high prevalence of severe anaemia.

Screening for severe anaemia in pregnancy in Kenya, using pallor examination and self-reported morbidity.

Severe anaemia in pregnancy is an important preventable cause of maternal and perinatal morbidity and mortality. Different methods of screening for severe anaemia in pregnancy were evaluated in a 2-phased study conducted in Kilifi, Kenya. In phase 1 (in 1994/95), pallor testing was evaluated alone and in addition to raised respiratory/pulse rates: 1787 pregnant women were examined by one of 2 midwives. Sensitivities for detecting severe anaemia (haemoglobin < 7 g/dL) were 62% and 69% and specificities 87% and 77%, respectively for each of the midwives. Addition of high pulse rate increased sensitivity to 77% and 81%, but specificity reduced to 60% and 51%, respectively. In phase 2, following qualitative in-depth work, a screening questionnaire was developed. An algorithm based on screening questions had 80% sensitivity and 40% specificity. Midwife pallor-assessment was conducted following the screening questionnaire. In this phase (conducted in 1997), the midwife performed very highly in detecting severe anaemia, achieving sensitivity of 84% and specificity of 92%. Spending a few minutes asking women questions may have improved the ability to interpret pallor findings. This study demonstrates the value of pallor testing and raises alternative approaches to improving it.

Perceptions of soil-eating and anaemia among pregnant women on the Kenyan coast.

After a clinical study at Kilifi District hospital had shown a high prevalence of geophagy among pregnant women, and a strong association of geophagy, anaemia and iron depletion, 52 pregnant women from the same hospital, and 4 traditional healers from the surroundings of Kilifi in Kenya were interviewed on the topic of soil-eating and its perceived causes and consequences. The findings were substantiated by results from an earlier anthropological study on maternal health and anaemia in the same study area. Most of the pregnant women (73%) ate soil regularly. They mainly ate the soil from walls of houses, and their estimated median daily ingestion was 41.5 g. They described soil-eating as a predominantly female practice with strong relations to fertility and reproduction. They made associations between soil-eating, the condition of the blood and certain bodily states: pregnancy, lack of blood (upungufu wa damu), an illness called safura involving "weak" blood, and worms (minyolo). The relationships the women described between soil-eating and illness resemble to some extent the causalities explored in biomedical research on soil-eating, anaemia and intestinal worm infections. However the women did not conceptualise the issue in terms of the single causal links characteristic of most scientific thought. Instead, they acknowledged the existence of multiple links between phenomena which they observed in their own and other women's bodies. The women's ideas about soil-eating and their bodies shows the significance of both social and cultural context on the ways in which women derive knowledge from, and make sense of their bodily states. The cultural associations of soil-eating with blood, fertility and femininity exist alongside knowledge of its links to illness. Our findings show that soil-eating is more than just a physiologically induced behaviour; it is a rich cultural practice.

Intermittent sulphadoxine-pyrimethamine to prevent severe anaemia secondary to malaria in pregnancy: a randomised placebo-controlled trial.

BACKGROUND: In areas of endemic transmission, malaria in pregnancy is associated with severe maternal anaemia and low-birthweight babies. We studied the efficacy of intermittent treatment doses of sulphadoxine-pyrimethamine in preventing malaria and severe anaemia in pregnancy in a double-blind placebo-controlled trial among primigravid women living in Kilifi District, Kenya. METHODS: Between January, 1996, and April, 1997, 1264 primigravid women were recruited when they attended for antenatal care, and randomly assigned sulphadoxine-pyrimethamine (640) or placebo (624). Women received one, two, or three doses of study medication depending on the duration of gestation at enrolment. Primary outcome measures were severe anaemia (haemoglobin <8 g/dL) and malaria parasitaemia, assessed at 34 weeks of gestation. Analyses were based on intention to treat among women who had study blood tests at 34 weeks. FINDINGS: 30 (5.3%) of 567 women in the sulphadoxine-pyrimethamine group and 199 (35.3%) of 564 in the placebo group had peripheral parasitaemia (protective efficacy 85% [95% CI 78-90], p<0.0001). 82 (14.5%) and 134 (23.7%) had severe anaemia (protective efficacy 39% [22-52], p<0.0001). Even women who booked late and received only one dose of sulphadoxine-pyrimethamine benefited significantly from the intervention. The effects were seen both in women who owned insecticide-treated bednets and in women who did not. INTERPRETATION: Intermittent presumptive treatment with sulphadoxine-pyrimethamine is an effective, practicable strategy to decrease the risk of severe anaemia in primigravidae living in malarious areas.

Malaria in pregnancy: its relevance to safe-motherhood programmes.

Severe anaemia in pregnancy is an important contributor to maternal and perinatal morbidity and mortality. In sub-Saharan Africa severe anaemia in pregnancy is very common, the main causes being iron and folate deficiency, malaria, hookworm infestation and advanced HIV infection. Though most of these causes are preventable, the overall prevalence of anaemia has not changed over many years. This is probably due to a mixture of reasons, including operational problems and inadequate interventions. In addition, a true effect on severe anaemia may have been missed if the only measure taken is of the overall prevalence of anaemia. One cause of anaemia that has been neglected by safe-motherhood programmes has been malaria in pregnancy. In endemic areas, malaria in pregnancy is usually asymptomatic and often associated with a negative peripheral-blood film. Hence the condition needs to be treated and prevented as a matter of routine in all women at risk of infection. A trial conducted in Kenya demonstrated that intermittent treatment with the antimalarial sulfadoxine-pyrimethamine (SP), given a couple of times during pregnancy when women attend for antenatal care, can reduce severe anaemia in primigravidae by 39%. The results of this study demonstrate the important contribution of malaria to severe anaemia in pregnancy in areas of endemic transmission. Intermittent treatment with SP in pregnancy has also been shown to be effective in improving birthweight. Though questions remain about the optimal way to deliver this intervention to different groups of women, we cannot afford to wait for all of the answers. The degree to which malaria contributes to severe anaemia in pregnancy is now clear. In Kenya intermittent SP is now policy for pregnant women from malarious areas. The challenge now is for this regimen to be successfully implemented as part of an integrated programme of anaemia control in pregnancy.

Geophagy, iron status and anaemia among pregnant women on the coast of Kenya.

In a cross sectional survey based in an antenatal clinic at Kilifi District Hospital, Coast Province, Kenya, 154 of 275 pregnant women (56%) reported eating soil regularly. Geophagous women had lower haemoglobin and serum ferritin concentrations than non-geophagous women (mean haemoglobin level 9.1 vs. 10.0 g/dL, P < 0.001; median ferritin level 4.5 vs. 9.0 micrograms/L, P < 0.001). In multiple linear regression analyses, geophagy was a significant predictor of haemoglobin (beta = -6.4, P = 0.01) and serum ferritin concentrations (beta = -6.6, P = 0.002), while controlling for gestational age and malaria and hookworm infection. Another 38 pregnant women, who reported eating soil regularly, participated in focus group discussions and were interviewed on geophagy. The most commonly eaten soil was from the walls of houses. The median estimated daily intake was 41.5 g (range 2.5-219.0 g). Twenty-seven of these women assisted in the collection of soil samples which were then analysed for their content of iron, zinc and aluminium after extraction with 0.1 M HC1. The average daily soil intake supplied the geophagous women with 4.3 mg of iron, corresponding to 14% of the recommended dietary allowance of iron for pregnant women. The study revealed a strong negative association between geophagy and both haemoglobin and ferritin status. At the same time it demonstrated the potential of soil as a source of dietary iron for geophagous women. These seemingly contradictory results might be due to other components in the soil interfering with iron uptake or metabolism. Alternatively, it may be that the geophagous women had extremely depleted iron stores before starting to eat soil. From these cross-sectional data, no inference about causality could be made.

A community randomized controlled trial of insecticide-treated bednets for the prevention of malaria and anaemia among primigravid women on the Kenyan coast.

The effectiveness of insecticide-treated bednets (ITBN) in preventing malaria and anaemia among primigravidae living in Kilifi District, Kenya, was assessed by a randomized controlled trial between September 1994 and November 1995. All residents within 28 community clusters received ITBN in July 1993, whilst residents of another 28 clusters served as contemporaneous controls. All resident primigravid women with singleton pregnancies attending antenatal care at Kilifi District Hospital were eligible for recruitment. 503 primigravidae were recruited. 91.4% were anaemic antenatally (Hb < 11 g/dl): 91.0% from the intervention arm and 92.0% from the control arm. Severe anaemia (Hb < 7 g/dl) was found among 15.1% of intervention women and 20.1% of control women (P = 0.28). No significant differences were observed in reports of febrile illness or the presence of chloroquine in the serum or peripheral parasitaemia during the third trimester between the two groups. In the women delivering in hospital (n = 130), there was no association between placental malaria infection and the intervention: 77.4% of placentas from control women had evidence of past or active infection, compared with 72.0% of placentas from intervention women (P = 0.76). Similarly, in the women delivering in hospital, ITBN did not improve birth weight, and there were no differences in perinatal mortality between the two study groups. Despite ITBN having a great impact on paediatric severe malaria and mortality in this transmission setting, there was very little impact of ITBN on the morbidity associated with malaria infection in primigravidae. Alternative strategies are required to tackle this continued public health problem for pregnant women living in endemic areas similar to the Kenyan Coast.

The Autism Diagnostic Interview-Revised and the Childhood Autism Rating Scale: differences between diagnostic systems and comparison between genders.

Diagnoses for autism based on the Autism Diagnostic Interview-Revised (ADI-R) and the Childhood Autism Rating Scale (CARS) were examined for 83 individuals with suspected autism. Agreement between systems reached 85.7%. Participants receiving diagnosis of autism based on only one system were significantly younger in age than individuals receiving diagnoses according to both systems. Individuals who did not receive diagnosis of autism on the ADI-R had lower chronological and mental ages and lower CARS scores compared to individuals who received diagnosis of autism based on the ADI-R. Eighteen females and 18 males were matched to examine possible gender differences. No significant findings were revealed, suggesting that the symptoms of autism according to the ADI-R and CARS do not differ between males and females when matched for chronological and mental ages.

Autism or atypical autism in maternally but not paternally derived proximal 15q duplication.

Duplications of proximal 15q have been found in individuals with autistic disorder (AD) and varying degrees of mental retardation. Often these abnormalities take the form of a supernumerary inverted duplicated chromosome 15, more properly described as an isodicentric chromosome 15, or idic(15). However, intrachromosomal duplications also have been reported. In a few cases, unaffected mothers, as well as their affected children, carry the same duplications. During the course of the genotyping of trios of affected probands with AD and their parents, at the positional candidate locus D15S122, an intrachromosomal duplication of proximal 15q was detected by microsatellite analysis in a phenotypically normal mother. Microsatellite and methylation analyses of the pedigree in the following report show that, among three children, the two with autism or atypical autism have maternal inheritance of a 15q11-q13 duplication whereas the third child, who is unaffected, did not inherit this duplication. Their mother's 15q11-q13 duplication arose de novo from her father's chromosomes 15. This finding documents, for the first time, the significance of parental origin for duplications of 15q11-q13. In this family, paternal inheritance leads to a normal phenotype, and maternal inheritance leads to autism or atypical autism.