Chronic malaria exposure is associated with inhibitory markers on T cells that correlate with atypical memory and marginal zone-like B cells.

Chronic immune activation from persistent malaria infections can induce immunophenotypic changes associated with T-cell exhaustion. However, associations between T and B cells during chronic exposure remain undefined. We analyzed peripheral blood mononuclear cells from malaria-exposed pregnant women from Papua New Guinea and Spanish malaria-naïve individuals using flow cytometry to profile T-cell exhaustion markers phenotypically. T-cell lineage (CD3, CD4, and CD8), inhibitory (PD1, TIM3, LAG3, CTLA4, and 2B4), and senescence (CD28-) markers were assessed. Dimensionality reduction methods revealed increased PD1, TIM3, and LAG3 expression in malaria-exposed individuals. Manual gating confirmed significantly higher frequencies of PD1+CD4+ and CD4+, CD8+, and double-negative (DN) T cells expressing TIM3 in malaria-exposed individuals. Increased frequencies of T cells co-expressing multiple markers were also found in malaria-exposed individuals. T-cell data were analyzed with B-cell populations from a previous study where we reported an alteration of B-cell subsets, including increased frequencies of atypical memory B cells (aMBC) and reduction in marginal zone (MZ-like) B cells during malaria exposure. Frequencies of aMBC subsets and MZ-like B cells expressing CD95+ had significant positive correlations with CD28+PD1+TIM3+CD4+ and DN T cells and CD28+TIM3+2B4+CD8+ T cells. Frequencies of aMBC, known to associate with malaria anemia, were inversely correlated with hemoglobin levels in malaria-exposed women. Similarly, inverse correlations with hemoglobin levels were found for TIM3+CD8+ and CD28+PD1+TIM3+CD4+ T cells. Our findings provide further insights into the effects of chronic malaria exposure on circulating B- and T-cell populations, which could impact immunity and responses to vaccination.

The role of fingernail selenium in the association between arsenic, lead and mercury and child development in rural Vietnam: a cross-sectional analysis.

As, Pb and Hg are common environmental contaminants in low- and middle-income countries. We investigated the association between child toxicant exposure and growth and development and determined if this association was mitigated by Se concentration. Toxicant concentrations in fingernail samples, anthropometry and Bayley's Scales of Infant Development, 3rd edition domains were assessed in 36-month-old children whose mothers had been part of a randomised controlled trial in rural Vietnam. Multivariable regression analyses were performed to estimate the effect of toxicant exposure on clinical outcomes with adjustments for potential confounders and interaction with fingernail Se concentration. We analysed 658 children who had data for at least one physical or developmental outcome, and at least one toxicant measurement, and each of the covariates. Fingernail As concentration was negatively associated with language (estimate per 10 % increase in As: -0·19, 95 % CI: (-0·32, -0·05)). Pb was negatively associated with cognition (estimate per 10 % increase in Pb: -0·08 (-0·15, -0·02)), language (estimate per 10 % increase in Pb: -0·18 (-0·28, -0·10)) and motor skills (estimate per 10 % increase in Pb: -0·12 (-0·24, 0·00)). Hg was negatively associated with cognition (estimate per 10 % increase in Hg: -0·48, (-0·72, -0·23)) and language (estimate per 10 % increase in Hg -0·51, (-0·88, -0·13)) when Se concentration was set at zero in the model. As Se concentration increased, the negative associations between Hg and both cognition and language scores were attenuated. There was no association between toxicant concentration and growth. As, Pb and Hg concentrations in fingernails of 3-year-old children were associated with lower child development scores. The negative association between Hg and neurological development was reduced in magnitude with increasing Se concentration. Se status should be considered when assessing heavy metal toxicants in children and their impact on neurodevelopmental outcomes.

Enteric pathogen infection and consequences for child growth in young Aboriginal Australian children: a cross-sectional study.

BACKGROUND: To determine the prevalence of enteric infections in Aboriginal children aged 0-2 years using conventional and molecular diagnostic techniques and to explore associations between the presence of pathogens and child growth. METHODS: Cross-sectional analysis of Aboriginal children (n = 62) residing in a remote community in Northern Australia, conducted from July 24th - October 30th 2017. Stool samples were analysed for organisms by microscopy (directly in the field and following fixation and storage in sodium-acetate formalin), and by qualitative PCR for viruses, bacteria and parasites and serology for Strongyloides-specific IgG. Child growth (height and weight) was measured and z scores calculated according to WHO growth standards. RESULTS: Nearly 60% of children had evidence for at least one enteric pathogen in their stool (37/62). The highest burden of infection was with adenovirus/sapovirus (22.9%), followed by astrovirus (9.8%) and Cryptosporidium hominis/parvum (8.2%). Non-pathogenic organisms were detected in 22.5% of children. Ten percent of children had diarrhea at the time of stool collection. Infection with two or more pathogens was negatively associated with height for age z scores (- 1.34, 95% CI - 2.61 to - 0.07), as was carriage of the non-pathogen Blastocystis hominis (- 2.05, 95% CI - 3.55 to - 0.54). CONCLUSIONS: Infants and toddlers living in this remote Northern Australian Aboriginal community had a high burden of enteric pathogens and non-pathogens. The association between carriage of pathogens/non-pathogens with impaired child growth in the critical first 1000 days of life has implications for healthy child growth and development and warrants further investigation. These findings have relevance for many other First Nations Communities that face many of the same challenges with regard to poverty, infections, and malnutrition.

Dietary intake of Aboriginal Australian children aged 6-36 months in a remote community: a cross-sectional study.

BACKGROUND: Scarce literature comprehensively captures the transition to solid foods for children in remote Aboriginal Australian communities, a population expected to be especially vulnerable to nutritional inadequacy for largely socio-economic reasons. This study describes the dietary intake of children aged 6-36 months in a remote Aboriginal community during the years of solids introduction and establishment. Specifically, we aimed to explore milk feeding practices, major sources of nutrition and traditional food consumption, dietary patterns and nutrient and food group intakes, and compare these to national and international recommendations. METHODS: This dietary assessment was conducted as part of an observational, cross-sectional Child Health and Nutrition study. Three 24-h dietary recalls were completed with the parent/care-giver of each participant over 2-4 weeks, capturing a pay-week, non-pay-week and weekend day from October 2017-February 2018. Additional information collected included sociodemographic data, food security status, usual cooking practices, and attendance at playgroup. RESULTS: Diet histories for 40 children were included in the analysis (~ 40% of the population). Breast feeding rates were high (85%), with mothers exclusively feeding on demand. Very few participants met recommended intakes for wholegrains (n = 4, 10%), vegetables (n = 7, 18%), dairy (n = 5, 18%) and fruit (n = 13, 33%), while more children met the guidelines for meat (n = 19, 48%) and discretionary food intake (n = 28, 70%). Traditional foods were always nutritionally dense and consumed frequently (n = 22, 55% of children). Statistically significant pay-cycle differences in intakes of all macro-, and numerous micro-nutrients were observed. CONCLUSIONS: Many positive early feeding practices are currently enacted in remote Aboriginal communities including responsive and long duration breastfeeding, and nutrient-dense traditional food consumption from earliest solids introduction. However, the non-pay-week/pay-week cycle is impacting the quality and quantity of children's diets at a time of rapid growth and development.

Social and economic development and pregnancy mental health: secondary analyses of data from rural Vietnam.

BACKGROUND: This study aimed to establish whether changes in the socioeconomic context were associated with changes in population-level antenatal mental health indicators in Vietnam. METHODS: Social, economic and public policies introduced in Vietnam (1986-2010) were mapped. Secondary analyses of data from two cross-sectional community-based studies conducted in 2006 (n = 134) and 2010 (n = 419), involving women who were ≥ 28 weeks pregnant were completed. Data for these two studies had been collected in structured individual face-to-face interviews, and included indicators of antenatal mental health (mean Edinburgh Postnatal Depression Scale Vietnam-validation (EPDS-V) score), intimate partner relationships (Intimate Bonds Measure Vietnam-validation) and sociodemographic characteristics. Socioeconomic characteristics and mean EPDS-V scores in the two study years were compared and mediation analyses were used to establish whether indicators of social and economic development mediated differences in EPDS-V scores. RESULTS: Major policy initiatives for poverty reduction, hunger eradication and making domestic violence a crime were implemented between 2006 and 2010. Characteristics and circumstances of pregnant women in Ha Nam improved significantly. Mean EPDS-V score was lower in 2010, indicating better population-level antenatal mental health. Household wealth and intimate partner controlling behaviours mediated the difference in EPDS-V scores between 2006 and 2010. CONCLUSIONS: Changes in the socioeconomic and political context, particularly through policies to improve household wealth and reduce domestic violence, appear to influence women's lives and population-level antenatal mental health. Cross-sectoral policies that reduce social risk factors may be a powerful mechanism to improve antenatal mental health at a population level.

Co-morbid anaemia and stunting among children of pre-school age in low- and middle-income countries: a syndemic.

OBJECTIVE: To determine the prevalence of co-morbidity of two important global health challenges, anaemia and stunting, among children aged 6-59 months in low- and middle-income countries. DESIGN: Secondary analysis of data from Demographic and Health Surveys (DHS) conducted 2005-2015. Child stunting and anaemia were defined using current WHO classifications. Sociodemographic characteristics of children with anaemia, stunting and co-morbidity of these conditions were compared with those of 'healthy' children in the sample (children who were not stunted and not anaemic) using multiple logistic models. SETTING: Low- and middle-income countries. SUBJECTS: Children aged 6-59 months. RESULTS: Data from 193 065 children from forty-three countries were included. The pooled proportion of co-morbid anaemia and stunting was 21·5 (95 % CI 21·2, 21·9) %, ranging from the lowest in Albania (2·6 %; 95 % CI 1·8, 3·7 %) to the highest in Yemen (43·3; 95 % CI 40·6, 46·1 %). Compared with the healthy group, children with co-morbidity were more likely to be living in rural areas, have mothers or main carers with lower educational levels and to live in poorer households. Inequality in children who had both anaemia and stunting was apparent in all countries. CONCLUSIONS: Co-morbid anaemia and stunting among young children is highly prevalent in low- and middle-income countries, especially among more disadvantaged children. It is suggested that they be considered under a syndemic framework, the Childhood Anaemia and Stunting (CHAS) Syndemic, which acknowledges the interacting nature of these diseases and the social and environmental factors that promote their negative interaction.

Protocol for a process evaluation of a cluster randomized controlled trial of the Learning Club intervention for women's health, and infant's health and development in rural Vietnam.

BACKGROUND: Learning Clubs is a multi-component intervention to address the eight common risk factors for women's health, and infant's health and development in resource-constrained settings. We are testing in a cluster randomized controlled trial in rural Vietnam whether this intervention improves cognitive development in children when they are aged two. There are few comprehensive process evaluations of complex interventions to optimise early childhood development. The aim is to conduct a planned process evaluation of the Learning Clubs intervention in Vietnam. METHODS: The evaluation will be conducted alongside the Learning Clubs trial using both qualitative and quantitative methods. Four domains will be included in the evaluation: [1] Context - how contextual factors affect the implementation and outcomes; [2] Implementation - what aspects of the Learning Clubs intervention are actually delivered and how well the intervention is delivered; [3] Mechanism of impact - how the intervention produces changes in the primary and secondary outcomes; and [4] National integration - how the intervention can be scaled up for application nationally. Purposive sampling will be used to recruit project stakeholders from commune, provincial and national levels. Results of the process evaluation will be integrated with those of the outcome and economic evaluations to provide a comprehensive picture of the effectiveness of the Learning Clubs intervention for early childhood development in rural Vietnam. DISCUSSION: Results of the evaluation will provide evidence about the implementation of the intervention and explanations for any differences in the outcomes between participants in intervention and control conditions. The evaluation will be integrated into each stage of the outcome assessments, but will be implemented by a bilingual team independent of the team implementing the intervention. It will therefore provide evidence which will not be influenced by or influence the intervention and will inform both generalisation to other settings and scalability in Vietnam. TRIAL REGISTRATION: Trial registration number ACTRN12617000442303 on the Australian New Zealand Clinical Trials Registry. Registered 27/03/2017. Prospectively registered.

Sulphadoxine-pyrimethamine plus azithromycin for the prevention of low birthweight in Papua New Guinea: a randomised controlled trial.

BACKGROUND: Intermittent preventive treatment in pregnancy has not been evaluated outside of Africa. Low birthweight (LBW, <2,500 g) is common in Papua New Guinea (PNG) and contributing factors include malaria and reproductive tract infections. METHODS: From November 2009 to February 2013, we conducted a parallel group, randomised controlled trial in pregnant women (≤ 26 gestational weeks) in PNG. Sulphadoxine-pyrimethamine (1,500/75 mg) plus azithromycin (1 g twice daily for 2 days) (SPAZ) monthly from second trimester (intervention) was compared against sulphadoxine-pyrimethamine and chloroquine (450 to 600 mg, daily for three days) (SPCQ) given once, followed by SPCQ placebo (control). Women were assigned to treatment (1:1) using a randomisation sequence with block sizes of 32. Participants were blinded to assignments. The primary outcome was LBW. Analysis was by intention-to-treat. RESULTS: Of 2,793 women randomised, 2,021 (72.4%) were included in the primary outcome analysis (SPCQ: 1,008; SPAZ: 1,013). The prevalence of LBW was 15.1% (305/2,021). SPAZ reduced LBW (risk ratio [RR]: 0.74, 95% CI: 0.60-0.91, P = 0.005; absolute risk reduction (ARR): 4.5%, 95% CI: 1.4-7.6; number needed to treat: 22), and preterm delivery (0.62, 95% CI: 0.43-0.89, P = 0.010), and increased mean birthweight (41.9 g, 95% CI: 0.2-83.6, P = 0.049). SPAZ reduced maternal parasitaemia (RR: 0.57, 95% CI: 0.35-0.95, P = 0.029) and active placental malaria (0.68, 95% CI: 0.47-0.98, P = 0.037), and reduced carriage of gonorrhoea (0.66, 95% CI: 0.44-0.99, P = 0.041) at second visit. There were no treatment-related serious adverse events (SAEs), and the number of SAEs (intervention 13.1% [181/1,378], control 12.7% [174/1,374], P = 0.712) and AEs (intervention 10.5% [144/1,378], control 10.8% [149/1,374], P = 0.737) was similar. A major limitation of the study was the high loss to follow-up for birthweight. CONCLUSIONS: SPAZ was efficacious and safe in reducing LBW, possibly acting through multiple mechanisms including the effect on malaria and on sexually transmitted infections. The efficacy of SPAZ in the presence of resistant parasites and the contribution of AZ to bacterial antibiotic resistance require further study. The ability of SPAZ to improve pregnancy outcomes warrants further evaluation. TRIAL REGISTRATION: ClinicalTrials.gov NCT01136850 (06 April 2010).

Impact of intermittent preventive treatment in pregnancy with azithromycin-containing regimens on maternal nasopharyngeal carriage and antibiotic sensitivity of Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus: a cross-sectional survey at delivery.

Sulfadoxine-pyrimethamine (SP) plus azithromycin (AZ) (SPAZ) has the potential for intermittent preventive treatment of malaria in pregnancy (IPTp), but its use could increase circulation of antibiotic-resistant bacteria associated with severe pediatric infections. We evaluated the effect of monthly SPAZ-IPTp compared to a single course of SP plus chloroquine (SPCQ) on maternal nasopharyngeal carriage and antibiotic susceptibility of Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus at delivery among 854 women participating in a randomized controlled trial in Papua New Guinea. Serotyping was performed, and antibiotic susceptibility was evaluated by disk diffusion and Etest. Potential risk factors for carriage were examined. Nasopharyngeal carriage at delivery of S. pneumoniae (SPAZ, 7.2% [30/418], versus SPCQ, 19.3% [84/436]; P<0.001) and H. influenzae (2.9% [12/418] versus 6.0% [26/436], P=0.028), but not S. aureus, was significantly reduced among women who had received SPAZ-IPTp. The number of macrolide-resistant pneumococcal isolates was small but increased in the SPAZ group (13.3% [4/30], versus SPCQ, 2.2% [2/91]; P=0.033). The proportions of isolates with serotypes covered by the 13-valent pneumococcal conjugate vaccine were similar (SPAZ, 10.3% [3/29], versus SPCQ, 17.6% [16/91]; P=0.352). Although macrolide-resistant isolates were rare, they were more commonly detected in women who had received SPAZ-IPTp, despite the significant reduction of maternal carriage of S. pneumoniae and H. influenzae observed in this group. Future studies on SPAZ-IPTp should evaluate carriage and persistence of macrolide-resistant S. pneumoniae and other pathogenic bacteria in both mothers and infants and assess the clinical significance of their circulation.

Determining effects of areca (betel) nut chewing in a prospective cohort of pregnant women in Madang Province, Papua New Guinea.

BACKGROUND: Chewing areca nut (AN), also known as betel nut, is common in Asia and the South Pacific and the habit has been linked to a number of serious health problems including oral cancer. Use of AN in pregnancy has been associated with a reduction in mean birthweight in some studies, but this association and the relationship between AN chewing and other adverse pregnancy outcomes remain poorly understood. METHODS: We assessed the impact of AN chewing on adverse outcomes including stillbirth, low birthweight (LBW, <2,500 g) and anaemia at delivery (haemoglobin <11.0 g/dL) in a longitudinal cohort of 2,700 pregnant women residing in rural lowland Papua New Guinea (PNG) from November 2009 until February 2013. Chewing habits and participant characteristics were evaluated at first antenatal visit and women were followed until delivery. RESULTS: 83.3% [2249/2700] of pregnant women used AN, and most chewed on a daily basis (86.2% [1939/2249]. Smoking and alcohol use was reported by 18.9% (511/2700) and 5.0% (135/2688) of women, respectively. AN use was not associated with pregnancy loss or congenital abnormalities amongst women with a known pregnancy outcome (n = 2215). Analysis of 1769 birthweights did not demonstrate an association between AN and LBW (chewers: 13.7% [200/1459] vs. non-chewers: 14.5% [45/310], P = 0.87) or reduced mean birthweight (2957 g vs. 2966 g; P = 0.76). Women using AN were more likely to be anaemic (haemoglobin <11 g/dL) at delivery (75.2% [998/1314] vs. 63.9% [182/285], adjusted odds ratio [95% CI]: 1.67 [1.27, 2.20], P < 0.001). Chewers more commonly had male babies than non-chewers (46.1% [670/1455] vs. 39.8% [123/309], P = 0.045). CONCLUSIONS: AN chewing may contribute to anaemia. Although not associated with other adverse pregnancy outcome in this cohort gestational AN use should be discouraged, given the potential adverse effects on haemoglobin and well-established long-term health risk including oral cancer. Future research evaluating the potential association of AN use and anaemia may be warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT01136850 (06 April 2010).

Exclusive breast feeding in early infancy reduces the risk of inpatient admission for diarrhea and suspected pneumonia in rural Vietnam: a prospective cohort study.

BACKGROUND: Acute respiratory infections and diarrhea remain the leading causes of infant morbidity and mortality, with a high burden of both pneumonia and diarrhea in South-East Asia. The aim of the study was to determine antenatal and early infant predictive factors for severe morbidity episodes during the first 6 months of life in Ha Nam province, Vietnam. METHODS: A prospective cohort study of 1049 infants, born to women who had previously participated in a cluster randomized controlled trial of antenatal micronutrient supplementation in rural Vietnam, was undertaken between 28th September 2010 and 8th Jan 2012. Infants were followed until 6 months of age, and the outcome measure was inpatient admission for suspected pneumonia or diarrheal illness during the first 6 months of life. Risk factors were assessed using univariable logistic regression and multiple logistic regression. RESULTS: Of the 1049 infants seen at 6 months of age, 8.8 % required inpatient admission for suspected pneumonia and 4 % of infants required inpatient admission for diarrheal illness. One third of infants (32.8 %) were exclusively breast fed at 6 weeks of age. Exclusive breast feeding at 6 weeks of age significantly reduced the odds of inpatient admission for suspected pneumonia (Odds Ratio (OR) 0.39, 95 % Confidence Interval (CI) 0.20 to 0.75) and diarrheal illness (OR 0.37, 95 % CI 0.15 to 0.88). CONCLUSIONS: Exclusive breast feeding in early infancy reduces the risk of severe illness from diarrhea and suspected pneumonia. Public health programs to reduce the burden of inpatient admission from diarrheal and respiratory illness in rural Vietnam should address barriers to exclusive breast feeding.

Infant motor development in rural Vietnam and intrauterine exposures to anaemia, iron deficiency and common mental disorders: a prospective community-based study.

BACKGROUND: Antenatal anaemia, iron deficiency and common mental disorders (CMD) are prevalent in low- and middle-income countries. The aim of this study was to examine the direct and indirect effects of antenatal exposures to these risks and infant motor development. METHODS: A cohort of women who were pregnant with a single foetus and between 12 and 20 weeks pregnant in 50 randomly-selected rural communes in Ha Nam province was recruited. Participants provided data twice during pregnancy (early and late gestation) and twice after giving birth (8 weeks and 6 months postpartum). The Edinburgh Postnatal Depression Scale was used at all four data collection waves to detect CMD (score ≥ 4). Maternal anaemia (Hb < 11 g/dL) and iron deficiency (ferritin < 15 ng/mL) were evaluated at early and late gestation. Infants' motor development was assessed by the Bayley of Infant and Toddler Development Motor Scales (BSID-M) at the age of six months. Direct and indirect effects of the exposures on the outcome were examined with Path analysis. RESULTS: In total, 497 of 523 (97%) eligible pregnant women were recruited and 418 mother-infant pairs provided complete data and were included in the analyses. The prevalence of anaemia was 21.5% in early pregnancy and 24.4% in late pregnancy. There was 4.1% iron deficiency at early pregnancy and 48.2% at late pregnancy. Clinically significant symptoms of CMD were apparent among 40% women in early pregnancy and 28% in late pregnancy. There were direct adverse effects on infant BSID-M scores at 6 months of age due to antenatal anaemia in late pregnancy (an estimated mean reduction of 2.61 points, 95% Confidence Interval, CI, 0.57 to 4.65) and CMD in early pregnancy (7.13 points, 95% CI 3.13 to 11.13). Iron deficiency and anaemia in early pregnancy were indirectly related to the outcome via anaemia during late pregnancy. CONCLUSIONS: Antenatal anaemia, iron deficiency, and CMD have a negative impact on subsequent infant motor development. These findings highlight the need to improve the quality of antenatal care when developing interventions for pregnant women that aim to optimise early childhood development in low- and middle-income countries.

Postnatal growth outcomes and influence of maternal gestational weight gain: a prospective cohort study in rural Vietnam.

BACKGROUND: Suboptimal weight gain during pregnancy may result in adverse outcomes for both the mother and child, including increased risk of pre-eclampsia and gestational diabetes, delivery of low birth weight and small-for-gestational age (SGA) infants, and preterm delivery. The objectives of this study were to identify maternal predictors of rate of weight gain in pregnancy, and to evaluate the association of gestational weight gain with infant postnatal growth outcomes. METHODS: We conducted a prospective cohort study of infants born to women who had previously participated in a double-blind cluster randomized controlled trial of antenatal micronutrient supplementation, in Ha Nam province, Vietnam. Pregnant women (n = 1258) were seen at enrolment and 32 weeks gestation, and infants (n = 965) were followed until 6 months of age. Primary outcome was infant anthropometric indicators at 6 months of age (weight for age, length for age, weight for height z scores), and infant weight gain velocity during the first 6 months of life. RESULTS: Low body mass index (<18.5 kg/m2) was present in 26% of women, and rate of gestational weight gain was 0.4 kg per week [SD 0.12]. Rate of weight gain during pregnancy was significantly associated with infant weight-for-age (MD 1.13, 95% CI 0.58 to 1.68), length-for-age (MD 1.11, 95% CI 0.66 to 1.55), weight-for-length z scores (MD 0.63, 95% CI 0.07 to 1.19), and infant weight gain velocity during the first 6 months of life (MD 93.6 g per month, 95% CI 8.2 to 179.0). CONCLUSIONS: Rate of gestational weight gain is predictive of postnatal growth at six months of age in this setting. Public health programs should be targeted towards improving body mass index and weight gain in pregnant women in rural Vietnam.

Prevalence of dyslipidaemia and micronutrient deficiencies among newly arrived Afghan refugees in rural Australia: a cross-sectional study.

BACKGROUND: Afghanistan is the 15th least developed country in the world, with poor sanitation and high rates of infectious diseases and malnutrition. However, little is known about the health of young Afghan refugees resettling in Western countries. METHODS: We used a cross-sectional study design to examine the health profile of newly arrived Afghan refugees presenting to a General Practice between 20th April 2010 and 22nd March 2013 in rural Australia. Data collected included information on nutritional status and prevalence of infectious diseases. Challenges associated with health screening in a General Practice setting in this population were also documented. RESULTS: Data were available on 92 patients. Mean age of presentation was 22.6 years [SD 11.9], and the majority of patients were male (88%). Mean total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride concentrations were 4.4 mmol/L (95% CI, 2.9-7.3), 2.6 mmol/L (95% CI, 1.3-4.4), 1.24 mmol/L (95% CI, 0.7-2.0) and 1.19 mmol/L (95% CI, 0.4-4.7) respectively, and dyslipidaemia (defined as elevated total or low-density lipoprotein (LDL) cholesterol levels, or low levels of high-density lipoprotein (HDL) cholesterol) was seen in 27.5% of patients. There was also a high prevalence of vitamin D and B12 deficiency (50% and 18%, respectively) in this cohort. Issues that impacted on provision and access to health care for refugees included cost, language barriers, patient mobility and mental health issues. CONCLUSIONS: Dyslipidaemia and micronutrient deficiencies are significant health issues in young recently settled Afghan refugees, and routine screening should be considered for this population.

The effect of intermittent antenatal iron supplementation on maternal and infant outcomes in rural Viet Nam: a cluster randomised trial.

BACKGROUND: Anemia affects over 500 million women, and in pregnancy is associated with impaired maternal and infant outcomes. Intermittent antenatal iron supplementation is an attractive alternative to daily dosing; however, the impact of this strategy on infant outcomes remains unclear. We compared the effect of intermittent antenatal iron supplementation with daily iron supplementation on maternal and infant outcomes in rural Viet Nam. METHODS AND FINDINGS: This cluster randomised trial was conducted in Ha Nam province, Viet Nam. 1,258 pregnant women (< 16 wk gestation) in 104 communes were assigned to daily iron-folic acid (IFA), twice weekly IFA, or twice weekly multiple micronutrient (MMN) supplementation. Primary outcome was birth weight. Mean birth weight was 3,148 g (standard deviation 416). There was no difference in the birth weights of infants of women receiving twice weekly IFA compared to daily IFA (mean difference [MD] 28 g; 95% CI -22 to 78), or twice weekly MMN compared to daily IFA (MD -36.8 g; 95% CI -82 to 8.2). At 32 wk gestation, maternal ferritin was lower in women receiving twice weekly IFA compared to daily IFA (geometric mean ratio 0.73; 95% CI 0.67 to 0.80), and in women receiving twice weekly MMN compared to daily IFA (geometric mean ratio 0.62; 95% CI 0.57 to 0.68), but there was no difference in hemoglobin levels. Infants of mothers who received twice weekly IFA had higher cognitive scores at 6 mo of age compared to those who received daily IFA (MD 1.89; 95% CI 0.23 to 3.56). CONCLUSIONS: Twice weekly antenatal IFA or MMN did not produce a clinically important difference in birth weight, when compared to daily IFA supplementation. The significant improvement in infant cognitive outcomes at 6 mo of age following twice weekly antenatal IFA requires further exploration, and provides additional support for the use of intermittent, rather than daily, antenatal IFA in populations with low rates of iron deficiency. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry 12610000944033.

Promoting early childhood development in Viet Nam: cost-effectiveness analysis alongside a cluster-randomised trial.

BACKGROUND: Economic evaluations are critical to ensure effective resource use to implement and scale up child development interventions. This study aimed to estimate the cost-effectiveness of a multicomponent early childhood development intervention in rural Viet Nam. METHODS: We did a cost-effectiveness study alongside a cluster-randomised trial with a 30-month time horizon. The study included 669 mothers from 42 communes in the intervention group, and 576 mothers from 42 communes in the control group. Mothers in the intervention group attended Learning Clubs sessions from mid-pregnancy to 12 months after delivery. The primary outcomes were child cognitive, language, motor, and social-emotional development at age 2 years. In this analysis, we estimated the incremental cost-effectiveness ratios (ICERs) of the intervention compared with the usual standard of care from the service provider and household perspectives. We used non-parametric bootstrapping to examine uncertainty, and applied a 3% discount rate. FINDINGS: The total intervention cost was US$169 898 (start-up cost $133 692 and recurrent cost $36 206). The recurrent cost per child was $58 (1 341 741 Vietnamese dong). Considering the recurrent cost alone, the base-case ICER was $14 and mean ICER of 1000 bootstrap samples was $14 (95% CI -0·48 to 30) per cognitive development score gained with a 3% discount rate to costs. The ICER per language and motor development score gained was $22 and $20, respectively, with a 3% discount rate to costs. INTERPRETATION: The intervention was cost-effective: the ICER per child cognitive development score gained was 0·5% of Viet Nam's gross domestic product per capita, alongside other benefits in language and motor development. This finding supports the scaling up of this intervention in similar socioeconomic settings. FUNDING: Australian National Health and Medical Research Council and Grand Challenges Canada. TRANSLATION: For the Vietnamese translation of the abstract see Supplementary Materials section.

Structured, multicomponent, community-based programme for women's health and infant health and development in rural Vietnam: a parallel-group cluster randomised controlled trial.

BACKGROUND: Interventions to improve early childhood development have previously addressed only one or a few risk factors. Learning Clubs is a structured, facilitated, multicomponent programme designed to address eight potentially modifiable risk factors, and offered from mid-pregnancy to 12 months post partum; we aimed to establish whether this programme could improve the cognitive development of children at 2 years of age. METHODS: For this parallel-group cluster-randomised controlled trial, 84 of 116 communes (the clustering unit) in HaNam Province in rural Vietnam were randomly selected and randomly assigned to receive the Learning Clubs intervention (n=42) or usual care (n=42). Women aged at least 18 years who were pregnant (gestational age <20 weeks) were eligible for inclusion. Data sources were standardised, and study-specific questionnaires assessing risks and outcomes were completed in interviews in mid-pregnancy (baseline), late pregnancy (after 32 weeks of gestation), at 6-12 months post partum, and at the end of the study period when children were 2 years of age. Mixed-effects models were used to estimate trial effects, adjusting for clustering. The primary outcome was the cognitive development of children at 2 years of age, assessed by the Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III) cognitive score. This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000442303). FINDINGS: Between April 28, 2018, and May 30, 2018, 1380 women were screened and 1245 were randomly assigned (669 to the intervention group and 576 to the control group). Data collection was completed on Jan 17, 2021. Data at the end of the study period were contributed by 616 (92%) of 669 women and their children in the intervention group, and by 544 (94%) of 576 women and their children in the control group. Children aged 2 years in the intervention group had significantly higher mean Bayley-III cognitive scores than those in the control group (99·6 [SD 9·7] vs 95·6 [9·4]; mean difference 4·00 [95% CI 2·56-5·43]; p<0·0001). At 2 years of age, 19 (3%) children in the intervention group had Bayley-III scores less than 1 SD, compared with 32 (6%) children in the control group, but this difference was not significant (odds ratio 0·55 [95% CI 0·26-1·17]; p=0·12). There were no significant differences between groups in maternal, fetal, newborn, or child deaths. INTERPRETATION: A facilitated, structured, community-based, multicomponent group programme improved early childhood development to the standardised mean in rural Vietnam and could be implemented in other similarly resource-constrained settings. FUNDING: Australian National Health and Medical Research Council and Grand Challenges Canada Saving Brains Initiative. TRANSLATION: For the Vietnamese translation of the abstract see Supplementary Materials section.

Considering equity and cost-effectiveness in assessing a parenting intervention to promote early childhood development in rural Vietnam.

Considering equity in early childhood development (ECD) is important to ensure healthy development for every child. Equity-informative cost-effectiveness analysis can further guide decision makers to maximize outcomes with limited resources while promoting equity. This cost-effectiveness study aimed to examine the equity impacts of a multicomponent ECD intervention in rural Vietnam. We estimated the cost-effectiveness of the intervention with a 30-month time horizon from the service provider and household perspectives with equity considerations. Data were from a cluster-randomized controlled trial comparing the intervention with the local standard of care. The incremental cost-effectiveness ratios (ICERs) per child cognitive development score gained were estimated by household wealth quintile and maternal education level, adjusted for cluster effects and baseline characteristics such as maternal parity and age. A 3% discount rate was applied to costs, and non-parametric cluster bootstrapping was used to examine uncertainty around ICERs. Children in the intervention had higher cognitive development scores than those in the control arm across all subgroups. Based on intervention recurrent cost, the ICER per cognitive development score gained was lower in children from the poorest quintile (-US$6) compared to those from the richest quintile (US$16). Similarly, the ICER per cognitive development score gained was lower in children whose mothers had the lowest education level (-US$0.02) than those with mothers who had the highest education level (US$7). Even though our findings should be interpreted with caution due to the insufficient study power, the findings suggest that the intervention could promote equity while improving child cognitive development with greater cost-effectiveness in disadvantaged groups.

Child linear growth trajectories during the first three years of life in relation to infant iron status: a prospective cohort study in rural Vietnam.

BACKGROUND: Early childhood growth patterns have long-term consequences for health and disease. Little is known about the interplay between growth and iron status during childhood. We explored the interplay between linear growth and iron status during early childhood, by assessing child growth trajectories between 6 and 36 months (m) of age in relation to infant iron status at 6 months of age. METHODS: A cohort study of infants born to women who had previously participated in a cluster randomized controlled trial of antenatal micronutrient supplementation, conducted in rural Vietnam. The relationship between child linear growth trajectories and infant iron status (ferritin concentration) was examined using latent growth curve modeling. Primary outcomes were height for age z scores (HAZ) and growth trajectory between 6 and 36 m of age. RESULTS: A total of 1112 infants were included in the study. Mean [SD] HAZ scores decreased over time from -0·58 [0·94] at 6 m, to -0·97 [0·99] at 18 m, to -1·14 [0·89] at 36 m of age. There was a steep linear decline in the HAZ scores between 6 and 18 m of age, followed by a slower linear decline from 18 to 36 m of age. Ferritin concentration at 6 m of age was inversely associated with HAZ score at 6 m of age (-0·145, 95% CI [-0.189, -0.101]). There was no association between infant ferritin at 6 m of age and child growth trajectory between 6 and 36 m of age. CONCLUSIONS: Iron status at six months of age did not influence a child's later linear growth trajectory in this cohort of rural Vietnamese children. Longitudinal studies with repeated ferritin and height measurements are required to better delineate this relationship and inform public health interventions.

Continuing breastfeeding for at least two years after birth in rural Vietnam: prevalence and psychosocial characteristics.

BACKGROUND: The World Health Organization recommends breastfeeding for at least two years (24 months or more) after birth. In Vietnam, 22% of women continue breastfeeding for at least two years. The aim of this study was to determine the sociodemographic and psychosocial characteristics of mother-baby dyads associated with breastfeeding for 24 months or more in a rural setting in Vietnam. METHODS: A secondary analysis was conducted on existing data obtained from a prospective study in Ha Nam, Vietnam. Women were recruited when they were pregnant and were followed up until 36 months after giving birth. The data were collected between 2009 and 2011. The associations between sociodemographic and psychosocial characteristics and continued breastfeeding for 24 months or more were examined using a multivariable logistic regression model. RESULTS: Overall, 363 women provided complete data which were included in the analyses. Among those, 20.9% breastfed for 24 months or more. Women who were 31 years old or older were more likely to breastfeed for 24 months or more than women who were 20 years old or younger (adjusted odds ratio, AOR, 9.54 [95% CI 2.25, 40.47]). Women who gave birth to girls were less likely to breastfeed for 24 or more months than women who had boys (AOR 0.44; 95% CI 0.25, 0.80). CONCLUSIONS: This study provides evidence that may be useful for policy-makers to help improve breastfeeding practices for all children in Vietnam by targeting policy towards younger women and women with girls to promote continued breastfeeding for at least 24 months.