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Preterm birth is a major cause of neonatal mortality and morbidity worldwide. Bacterial infection and the subsequent inflammatory response are recognised as an important cause of preterm birth. It is hypothesised that these organisms ascend the cervical canal, colonise placental tissues, cause chorioamnionitis and in severe cases infect amniotic fluid and the foetus. However, the presence of bacteria within the intrauterine cavity does not always precede chorioamnionitis or preterm birth. Whereas previous studies observing the types of bacteria present have been limited in size and the specificity of a few predetermined organisms, in this study we characterised bacteria found in placental tissues from a cohort of 1391 women in rural Malawi using 16S ribosomal RNA gene sequencing. We found that specific bacteria found concurrently on placental tissues associate with chorioamnionitis and delivery of a smaller newborn. Severe chorioamnionitis was associated with a distinct difference in community members, a higher bacterial load and lower species richness. Furthermore, Sneathia sanguinengens and Peptostreptococcus anaerobius found in both matched participant vaginal and placental samples were associated with a lower newborn length-for-age Z-score. This is the largest study to date to examine the placental microbiome and its impact of birth outcomes. Our results provide data on the role of the vaginal microbiome as a source of placental infection as well as the possibility of therapeutic interventions against targeted organisms during pregnancy.

In Bangladesh, utilization of government health facility-based growth monitoring and promotion (GMP) services is notably low, prompting non-governmental organizations (NGOs) to collaborate with the government to enhance GMP service utilization through home-based delivery. Despite this, there is limited information available on home-based GMP service utilization. This study aimed to investigate the utilization of GMP services between home-based and facility-based programs and identifying key factors and barriers to caregiver engagement with GMP services in rural Bangladesh. A descriptive mixed-method study was conducted across six sub-districts from August to December 2019. Three sub-districts with home-based GMP services provided by NGOs were compared with three neighboring sub-districts offering government facility-based GMP services. A total of 3038 randomly selected mothers and children under one year old were included in the quantitative part of the study. Quantitative surveys include information on household socio-demographic information, GMP service components, knowledge, utilization, barriers, and qualitative approaches were used for data collection on caregivers and service providers perspectives on GMP services. Descriptive statistics were conducted for sociodemographic characteristics, caregivers' knowledge, perception and barriers to utilization of GMP services. Student's t-tests and chi-square tests were used to compare quantitative and qualitative variables between both GMP arms. Risk ratios (RR) with 95% confidence intervals were calculated to compare GMP knowledge. Simple logistic regression identified GMP service use levels and related barriers. Multiple logistic regression was employed to determine statistically significant associations between GMP utilization and independent variables such as caregivers who heard about GMP or GMP cards, were members of an NGO, and lacked interest in GMP services at p-value <0.05 and adjusted risk ratio (ARR) values. Thematic analysis of qualitative data was performed. Results were triangulated across sources. Children's average age was 9.8 months, with a 1:1 male-to-female ratio in both groups (home-based vs. facility-based: 51.9% vs. 50.0%). Home-based GMP services exhibited higher utilization rates, with more children receiving weight and length measurements and caregivers receiving counseling than facility-based services (40% vs. 0% utilization, respectively). Caregivers' utilization of GMP services in home-based areas was positively influenced by their knowledge of GMP or GMP cards (Adjusted risk ratio, ARR: 37.4) and their involvement with an NGO, association, or health program (ARR: 1.3). Caregivers in home-based GMP areas relied on NGO staff for service delivery, while those in facility-based areas reported no outreach from government health workers and lacked access to GMP cards due to supply issues. Across both areas, low awareness of GMP services and the absence of incentives contributed to limited utilization. GMP service utilization remains low in rural Mymensingh district of Bangladesh. Home-based GMP service utilization was 40% but none of the caregivers utilized facility-based GMP services. Higher utilization in home-based areas was linked to caregiver awareness, access to GMP cards, and NGO involvement, while key barriers included lack of government outreach, supply gaps, and absence of incentives. To improve GMP coverage, government programs should enhance community level outreach, ensure consistent supply of growth cards, and consider integrating small incentives to motivate caregivers.

BackgroundEarly development of neurocognitive functions in infants can be compromised by poverty, malnutrition and lack of adequate stimulation. Optimal management of neurodevelopmental problems in infants requires assessment tools that can be used early in life, and are objective and applicable across economic, cultural and educational settings.Objective and designThe present study examined the feasibility of infrared eye tracking as a novel and highly automated technique for assessing visual-orienting and sequence-learning abilities as well as attention to facial expressions in young (9-month-old) infants. Techniques piloted in a high-resource laboratory setting in Finland (N=39) were subsequently field-tested in a community health centre in rural Malawi (N=40).ResultsParents' perception of the acceptability of the method (Finland 95%, Malawi 92%) and percentages of infants completing the whole eye-tracking test (Finland 95%, Malawi 90%) were high, and percentages of valid test trials (Finland 69–85%, Malawi 68–73%) satisfactory at both sites. Test completion rates were slightly higher for eye tracking (90%) than traditional observational tests (87%) in Malawi. The predicted response pattern indicative of specific cognitive function was replicated in Malawi, but Malawian infants exhibited lower response rates and slower processing speed across tasks.ConclusionsHigh test completion rates and the replication of the predicted test patterns in a novel environment in Malawi support the feasibility of eye tracking as a technique for assessing infant development in low-resource setting. Further research is needed to the test–retest stability and predictive validity of the eye-tracking scores in low-income settings.

Body composition can be measured by several methods, each with specific benefits and disadvantages. Bioelectric impedance offers a favorable balance between accuracy, cost and ease of measurement in a range of settings. In this method, bioelectric measurements are converted to body composition measurements by prediction equations specific to age, population and bioimpedance device. Few prediction equations exist for populations in low-resource settings. We formed a prediction equation for total body water in Malawian adolescents using deuterium dilution as reference. We studied 86 boys and 92 girls participating in the 11-14-year follow-up of the Lungwena Antenatal Intervention Study, a randomized trial of presumptive infection treatment among pregnant women. We measured body composition by Seca m515 bioimpedance analyser. Participants ingested a weight-standardized dose of deuterium oxide, after which we collected saliva at baseline, at 3 and 4 h post-ingestion, measured deuterium concentration using Fourier-transform infrared spectroscopy and calculated total body water. We formed predictive equations for total body water using anthropometrics plus resistance and reactance at a range of frequencies, applying multiple regression and repeated cross-validation in model building and in prediction error estimation. The best predictive model for percentage total body water (TBW %) was 100*(1.11373 + 0.0037049*height (cm)2/resistance(Ω) at 50 kHz- 0.25778*height(m)- 0.01812*BMI(kg/m2)- 0.02614*female sex). Calculation of absolute TBW (kg) by multiplying TBW (%) with body weight had better predictive power than a model directly constructed to predict absolute total body water (kg). This model explained 96.4% of variance in TBW (kg) and had a mean prediction error of 0.691 kg. Mean bias was 0.01 kg (95% limits of agreement -1.34, 1.36) for boys and -0.01 kg (1.41, 1.38) for girls. Our equation provides an accurate, cost-effective and participant-friendly body composition prediction method among adolescents in clinic-based field studies in rural Africa, where electricity is available.

Asymptomatic malaria infections are common in endemic regions, yet their impact on children’s growth remains inadequately understood. This study investigates the association between asymptomatic malaria and 6-18-month-old children’s growth indices in rural Malawi. Dried blood spots from 840 participants in Lungwena Child Nutrition Intervention 5 (LCNI-5) clinical trial were analysed at the baseline ( N  = 697) and every 3 months for a year. The associations between asymptomatic Plasmodium falciparum (determined by real-time PCR), and growth indices (length-for-age Z score (LAZ), weight-for-age Z score (WAZ), and weight-for-length Z score (WLZ)) were examined. Across all ages (6 to 18 months), malaria-positive children had lower mean WAZ (-1.03 vs. -0.87, 95% CI -0.17 − -0.04) and WLZ (-0.03 vs. -0.13, 95% CI -0.22 − -0.06) compared to those uninfected peers, whereas LAZ showed no significant association. However, no significant impact was observed at individual time points, except at 12 months of age. After adjusting for confounders, malaria infection remained associated with poorer children growth outcome. Asymptomatic malaria is linked to impaired growth outcomes among young children in rural Malawi. Targeted interventions aimed at managing asymptomatic malaria could mitigate growth faltering and improve child health in malaria-endemic settings.

Whereas poor maternal nutritional status before and during pregnancy is widely associated with adverse birth outcomes, studies quantifying this association in low income countries are scarce. We examined whether maternal pre-pregnancy body mass index (BMI) and weight gain during pregnancy are associated with birth outcomes in rural Malawi. We analyzed the associations between pre-pregnancy BMI and average weekly gestational weight gain (WWG) and birth outcomes [duration of gestation, birth weight, length-for-age z-score (LAZ), and head circumference-for-age z-score (HCZ)]. We also determined whether women with low or high pre-pregnancy BMI or women with inadequate or excessive WWG were at increased risk of adverse birth outcomes. The analyses included 1287 women with a mean BMI of 21.8 kg/m2, of whom 5.9% were underweight (< 18.5 kg/m2), 10.9% were overweight (≥ 25 kg/m2), 71.8% had low WWG [below the lower limit of the Institute of Medicine (IOM) recommendation], and 5.2% had high WWG (above IOM recommendation). In adjusted models, pre-pregnancy BMI was not associated with duration of pregnancy (p = 0.926), but was positively associated with birth weight and HCZ (<0.001 and p = 0.003, respectively). WWG was positively associated with duration of gestation (p = 0.031), birth weight (p<0.001), LAZ (p<0.001), and HCZ (p<0.001). Compared to normal weight women, underweight women were at increased risk of having stunted infants (p = 0.029). Women with low WWG were at increased risk of having infants with low birth weight (p = 0.006) and small head circumference (p = 0.024) compared to those with normal weight gain. Those with high BMI or high WWG were not at increased risk of adverse birth outcomes. WWG is an important predictor of birth outcomes in rural Malawi. The high prevalence of inadequate WWG compared to low pre-pregnancy BMI highlights the need to investigate causes of inadequate weight gain in this region.

Theoretical and empirical considerations suggest that individual differences in infant visual attention correlate with variations in cognitive skills later in childhood. Here we tested this hypothesis in infants from rural Malawi (n = 198-377, depending on analysis), who were assessed with eye tracking tests of visual orienting, anticipatory looks, and attention to faces at 9 months, and more conventional tests of cognitive control (A-not-B), motor, language, and socioemotional development at 18 months. The results showed no associations between measures of infant attention at 9 months and cognitive skills at 18 months, either in analyses linking infant visual orienting with broad cognitive outcomes or analyses linking specific constructs between the two time points (i.e., switching of anticipatory looks and manual reaching responses), as correlations varied between -0.08 and 0.14. Measures of physical growth, and family socioeconomic characteristics were also not correlated with cognitive outcomes at 18 months in the current sample (correlations between -0.10 and 0.19). The results do not support the use of the current tests of infant visual attention as a predictive tool for 18-month-old infants' cognitive skills in the Malawian setting. The results are discussed in light of the potential limitations of the employed infant tests as well as potentially unique characteristics of early cognitive development in low-resource settings.

Background The complex interaction between malaria and undernutrition leads to increased mortality and morbidity rate among young children in malaria-endemic regions. Results from previous interventions suggest that improving nutritional status of young children may reduce the burden of malaria. This study tested a hypothesis that provision of lipid-based nutrient supplements (LNS) or corn-soy blend (CSB) supplementation to 6–18-month-old children in Malawi would reduce the prevalence of asymptomatic malaria among them. Methods A total of 840 6-month-old children were enrolled in a randomized trial. The participants received 12-month supplementation with three different daily dietary supplementations: CSB, soy-LNS, or milk-LNS, and one control group without supplementation. The prevalence rate of asymptomatic Plasmodium falciparum was determined by real-time PCR from the participant’s dried blood spots (DBS) collected at the baseline and every 3 months. The global null hypothesis was tested using modified Poisson regression to estimate the prevalence ratio (PR) between the control group and three intervention groups at all ages combined. All the models were adjusted for malaria at baseline, season of DBS sample collection, site of enrolment, and household asset Z-score. Results All children combined, the prevalence of P. falciparum was 14.1% at enrollment, 8.7% at 9 months, 11.2% at 12 months, 13.0% at 15 months and 22.4% at 18 months of age. Among all samples that were taken after enrolment, the prevalence was 12.1% in control group, 12.2% in milk-LNS, 14.0% in soy-LNS, and 17.2% in CSB group. Compared to children in the control group the prevalence ratio of positive malaria tests was 1.19 (95% CI 0.81–1.74; P = 0.372) in the milk-LNS group, 1.32 (95% CI 0.88–1.96; P = 0.177) in the soy-LNS group and 1.72 (95% CI 1.19–2.49; P = 0.004) in the CSB group. Conclusion The study findings do not support a hypothesis that LNS or CSB supplementation would reduce the prevalence of asymptomatic malaria among Malawian children. In contrast, there was a signal of a possible increase in malaria prevalence among children supplemented with CSB.

Low birth weight predisposes to the development of hypertension in middle- and high-income countries. We examined the relation of early life length-for-age score (Z-score) on cardiovascular function in young adults in Malawi, a low-income country. Capture of supine, seated, and standing brachial pulse waveforms (Mobil-O-Graph) were performed in 223 females and 152 males (mean age 21 years), and analyzed according to the length-for-age Z-score tertiles during the first month of life. Plasma LDL cholesterol in young adulthood was slightly lower in the lowest versus highest tertile. Otherwise, blood hemoglobin and plasma chemistry were similar in all tertiles. Irrespective of posture, blood pressure, forward and backward wave amplitudes, and pulse wave velocity were corresponding in all tertiles. In the three postures, the lowest tertile presented with 4.5% lower systemic vascular resistance than the highest tertile (p = 0.005), and 4.4% and 5.5% higher cardiac output than the middle and highest tertiles, respectively (p < 0.01). Left cardiac work was 6.8% and 6.9% higher in the lowest tertile than in the middle and highest tertiles, respectively (p < 0.01). To conclude, in a low-income environment, low length-for-age Z-score after birth predicted hyperdynamic circulation at 21 years of age without changes in blood pressure and metabolic variables.

Intermittent preventive treatment in pregnancy (IPTp) with azithromycin and monthly sulfadoxine-pyrimethamine increased the mean child weight, mid-upper arm and head circumference at four weeks of age in a rural low-income setting. Now we assess for how long these gains were sustained during 0-5 years of age. We enrolled 1320 pregnant Malawian women in a randomized trial and treated them with two doses of sulfadoxine-pyrimethamine (control) or monthly sulfadoxine-pyrimethamine as IPTp against malaria, or monthly sulfadoxine-pyrimethamine and two doses of azithromycin (AZI-SP) as IPTp against malaria and reproductive tract infections. Child weight, mid-upper arm circumference, head circumference and weight-for-height Z-score were recorded at one, six, 12, 24, 36, 48, and 60 months. Throughout follow-up, the mean child weight was approximately 100 g higher (difference in means 0.12 kg, 95% CI 0.04-0.20, P = 0.003 at one month; 0.19 kg, 95% CI 0.05-0.33, P = 0.007, at six months), mean head circumference 2 mm larger (0.3 cm, 95% CI 0.1 to 0.5, P = 0.004 at one month) and the cumulative incidence of underweight by five years of age was lower (hazard ratio 0.74, 95% CI 0.60 to 0.90, P = 0.002) in the AZI-SP group than in the control group. The 2 mm difference in the mean mid-upper arm circumference at one month (0.2 cm, 95% CI 0.0 to 0.3, P = 0.007) disappeared after three years of age. There was no difference in mean weight-for-height Z-score at any time point. In Malawi, IPTp with azithromycin and monthly sulfadoxine-pyrimethamine has a modest, 3-5-year positive impact on child weight, mid-upper arm circumference and head circumference, but not on weight-for-height Z-score.