Geographical variation, socioeconomic inequalities of low birth weight, and its relationship with maternal dietary diversity: Insights from the maternal infant and young child nutrition programme in Bangladesh.

Background: Globally, every year, 20 million neonates are born with weights below 2500 g and are considered low birth weight (LBW). About 90% of these births occur in low- and middle-income countries. Information regarding the geographical variation, socioeconomic inequalities of LBW neonates, and the relationship between maternal inadequate dietary diversity and LBW is limited in rural areas of Bangladesh. We aimed to explore the geographical disparities and socioeconomic inequalities in the prevalence of LBW and its association with inadequate maternal dietary diversity. Methods: We extracted data from a large-scale evaluation programme conducted as a part of the maternal infant and young child nutrition phase two in Bangladesh, implemented by BRAC. We used the concentration index (CIX) to measure the socioeconomic inequalities of LBW. We performed a cluster-adjusted multiple logistic regression analysis to determine the association between LBW and maternal dietary diversity. Results: A total of 4651 children aged <5 years with their mother's information were included. The overall prevalence of LBW was 13.5%. About 16% of mothers living in the poorest wealth quintile gave birth to LBW babies, whereas 10% of mothers living in the richest households gave birth to LBW babies. The CIX exhibited LBW babies were more prevalent among the socioeconomically worst-off (poorest) group (CIX = -0.08), indicating mothers of the poorest households are vulnerable to giving birth to normal-weight babies. An adjusted multiple logistic regression model indicated that mothers with inadequate dietary diversity had higher odds (adjusted odds ratio (AOR) = 1.27; 95% confidence interval (CI) = 1.04, 1.54) of giving birth to LBW babies. Notably, in the interaction of mothers' age and dietary diversity, we found that adolescent mothers (aged ≤ 19 years) with inadequate dietary diversity had 2.56 times (AOR = 2.56; 95% CI = 1.14, 5.76) higher odds of giving birth to LBW babies compared to adult mothers (aged >19 years) who consumed diversified foods. Conclusions: Intervention strategies for reducing LBW prevalence should target the poorest households. Also, interventions for improving the dietary diversity of adolescent pregnant mothers are expected to reduce the number of LBW babies from the rural areas of Bangladesh.

Women's participation in household decision-making: Qualitative findings from the Shonjibon Trial in rural Bangladesh.

A key element of women's empowerment is the ability to participate in household decision-making. This study presents the qualitative results from the Shonjibon Cash and Counselling Trial baseline process evaluation with the aim of exploring the status of women's decision-making at the trial's outset and to facilitate the exploration of any changes in women's empowerment over the course of the trial. Between January and March 2021, we conducted forty-one in-depth interviews with pregnant women in rural Bangladesh. The research team translated, transcribed, coded, and discussed the interviews. We used thematic analysis to examine women's experience and perceptions on household decision-making. The key findings that emerged; women jointly participated in financial decision-making with their husbands; men made the final decision regarding seeking healthcare, and women solely made choices regarding infant and young child feeding. Our findings revealed that women felt that they needed to discuss their plans to go outside the house with their husbands, many perceived a lack of importance in the community towards women's participation in decision-making. This study documents current contextual information on the status of women's involvement in household decision-making and intrahousehold power dynamics at the start of the Shonjibon Cash and Counselling Trial.

Feasibility and acceptability of bubble continuous positive airway pressure oxygen therapy for the treatment of childhood severe pneumonia and hypoxaemia in Bangladeshi children.

Background: Effective management of hypoxaemia is key to reducing pneumonia deaths in children. In an intensive care setting within a tertiary hospital in Bangladesh, bubble continuous positive airway pressure (bCPAP) oxygen therapy was beneficial in reducing deaths in this population. To inform a future trial, we investigated the feasibility of introducing bCPAP in this population in non-tertiary/district hospitals in Bangladesh. Methods: We conducted a qualitative assessment using a descriptive phenomenological approach to understand the structural and functional capacity of the non-tertiary hospitals (Institute of Child and Mother Health and Kushtia General Hospital) for the clinical use of bCPAP. We conducted interviews and focus group discussions (23 nurses, seven physicians, 14 parents). We retrospectively (12 months) and prospectively (three months) measured the prevalence of severe pneumonia and hypoxaemia in children attending the two study sites. For the feasibility phase, we enrolled 20 patients with severe pneumonia (age two to 24 months) to receive bCPAP, putting in place safeguards to identify risk. Results: Retrospectively, while 747 of 3012 (24.8%) children had a diagnosis of severe pneumonia, no pulse oxygen saturation information was available. Of 3008 children prospectively assessed with pulse oximetry when attending the two sites, 81 (3.7%) had severe pneumonia and hypoxaemia. The main structural challenges to implementation were the inadequate number of pulse oximeters, lack of power generator backup, high patient load with an inadequate number of hospital staff, and inadequate and non-functioning oxygen flow meters. Functional challenges were the rapid turnover of trained clinicians in the hospitals, limited post-admission routine care for in-patients by hospital clinicians due to their extreme workload (particularly after official hours). The study implemented a minimum of four hourly clinical reviews and provided oxygen concentrators (with backup oxygen cylinders), and automatic power generator backup. Twenty children with a mean age of 6.7 (standard deviation (SD) = 5.0)) months with severe pneumonia and hypoxaemia (median (md) SpO2 = 87% in room air, interquartile range (IQR) = 85-88)) with cough (100%) and severe respiratory difficulties (100%) received bCPAP oxygen therapy for a median of 16 hours (IQR = 6-16). There were no treatment failures or deaths. Conclusions: Implementation of low-cost bCPAP oxygen therapy is feasible in non-tertiary/district hospitals when additional training and resources are allocated.

COVID-19 among staff and their family members of a healthcare research institution in Bangladesh between March 2020 and April 2021: a test-negative case-control study.

OBJECTIVE: To identify factors associated with COVID-19 positivity among staff and their family members of icddr,b, a health research institute located in Bangladesh. SETTING: Dhaka, Bangladesh. PARTICIPANTS: A total of 4295 symptomatic people were tested for SARS-CoV-2 by reverse-transcription PCR between 19 March 2020 and 15 April 2021. Multivariable logistic regression was done to identify the factors associated with COVID-19 positivity by contrasting test positives with test negatives. RESULT: Forty-three per cent of the participants were tested positive for SARS-CoV-2. The median age was high in positive cases (37 years vs 34 years). Among the positive cases, 97% were recovered, 2.1% had reinfections, 24 died and 41 were active cases as of 15 April 2021. Multivariable regression analysis showed that age more than 60 years (adjusted OR (aOR)=2.1, 95% CI 1.3 to 3.3; p<0.05), blood group AB (aOR=1.5, 95% CI 1.1 to 2; p<0.05), fever (aOR=3.1, 95% CI 2.6 to 3.7; p<0.05), cough (aOR=1.3, 95% CI 1.1 to 1.6; p<0.05) and anosmia (aOR=2.7, 95% CI 1.3 to 5.7; p<0.05) were significantly associated with higher odds of being COVID-19 positive when compared with participants who were tested negative. CONCLUSIONS: The study findings suggest that older age, fever, cough and anosmia were associated with COVID-19 among the study participants.

Assessing the impact of a combined nutrition counselling and cash transfer intervention on women's empowerment in rural Bangladesh: a randomised control trial protocol.

INTRODUCTION: There is growing interest in assessing the impact of health interventions, particularly when women are the focus of the intervention, on women's empowerment. Globally, research has shown that interventions targeting nutrition, health and economic development can affect women's empowerment. Evidence suggests that women's empowerment is also an underlying determinant of nutrition outcomes. Depending on the focus of the intervention, different domains of women's empowerment will be influenced, for example, an increase in nutritional knowledge, or greater control over income and access to resources. OBJECTIVE: This study evaluates the impact of the Shonjibon Cash and Counselling (SCC) Trial that combines nutrition counselling and an unconditional cash transfer, delivered on a mobile platform, on women's empowerment in rural Bangladesh. METHODS AND ANALYSIS: We will use a mixed-methods approach, combining statistical analysis of quantitative data from 2840 women in a cluster randomised controlled trial examining the impact of nutrition behaviour change communications (BCCs) and cash transfers on child undernutrition. Pregnant participants will be given a smartphone with a customised app, delivering nutrition BCC messages, and will receive nutrition counselling via a call centre and an unconditional cash transfer. This study is a component of the SCC Trial and will measure women's empowerment using a composite indicator based on the Project-Level Women's Empowerment in Agriculture Index, with quantitative data collection at baseline and endline. Thematic analysis of qualitative data, collected through longitudinal interviews with women, husbands and mothers-in-law, will elicit a local understanding of women's empowerment and the linkages between the intervention and women's empowerment outcomes. This paper describes the study protocol to evaluate women's empowerment in a nutrition-specific and sensitive intervention using internationally validated, innovative tools and will help fill the evidence gap on pathways of impact, highlighting areas to target for future programming. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the International Centre for Diarrhoeal Disease Research (Ref. PR 17106) and The University of Sydney (Ref: 2019/840). Findings from this study will be shared in Bangladesh with dissemination sessions in-country and internationally at conferences, and will be published in peer-reviewed journals.

Respectful maternity care delivered within health facilities in Bangladesh, Ghana and Tanzania: a cross-sectional assessment preceding a quality improvement intervention.

OBJECTIVE: To assess respectful maternity care (RMC) in health facilities. DESIGN: Cross-sectional study. SETTING: Forty-three (43) facilities across 15 districts in Bangladesh, 16 in Ghana and 12 in Tanzania. PARTICIPANTS: Facility managers; 325 providers (nurses/midwives/doctors)-Bangladesh (158), Ghana (86) and Tanzania (81); and 849 recently delivered women-Bangladesh (295), Ghana (381) and Tanzania (173)-were interviewed. Observation of 641 client-provider interactions was conducted-Bangladesh (387), Ghana (134) and Tanzania (120). ASSESSMENT: Trained social scientists and clinicians assessed infrastructure, policies, provision and women's experiences of RMC (emotional support, respectful care and communication). PRIMARY OUTCOME: RMC provided and/or experienced by women. RESULTS: Three (20%) facilities in Bangladesh, four (25%) in Ghana and three (25%) in Tanzania had no maternity clients' toilets and one-half had no handwashing facilities. Policies for RMC such as identification of client abuses were available: 81% (Ghana), 73% (Bangladesh) and 50% (Tanzania), but response was poor. Ninety-four (60%) Bangladeshi, 26 (30%) Ghanaian and 20 (25%) Tanzanian providers were not RMC trained. They provided emotional support during labour care to 107 (80%) women in Ghana, 95 (79%) in Tanzania and 188 (48.5%) in Bangladesh, and were often courteous with them-236 (61%) in Bangladesh, 119 (89%) in Ghana and 108 (90%) in Tanzania. Due to structural challenges, 169 (44%) women in Bangladesh, 49 (36%) in Ghana and 77 (64%) in Tanzania had no privacy during labour. Care was refused to 13 (11%) Tanzanian and 2 Bangladeshi women who could not pay illegal charges. Twenty-five (7%) women in Ghana, nine (6%) in Bangladesh and eight (5%) in Tanzania were verbally abused during care. Providers in all countries highly rated their care provision (95%-100%), and 287 (97%) of Bangladeshi women, 368 (97%) Ghanaians and 152 (88%) Tanzanians reported 'satisfaction' with the care they received. However, based on their facility experiences, significant (p<0.001) percentages-20% (Ghana) to 57% (Bangladesh)-will not return to the same facilities for future childbirth. CONCLUSIONS: Facilities in Bangladesh, Ghana and Tanzania have foundational systems that facilitate RMC. Structural inadequacies and policy gaps pose challenges. Many women were, however, unwilling to return to the same facilities for future deliveries although they (and providers) highly rated these facilities.

Are childbirth location and mode of delivery associated with favorable early breastfeeding practices in hard to reach areas of Bangladesh?

BACKGROUND: Early initiation of breastfeeding within one hour of birth (EIBF) and no prelacteal feeding are WHO recommended practices for improving maternal and newborn health outcomes. Globally, EIBF can avert around 22% of newborn death. In recent years, Bangladesh has experienced increasing facility delivery coverage and cesarean section rates. However, the impact of these changes on early breastfeeding initiation in hard to reach areas (HtR) of the country is still poorly understood. Therefore, this study aimed to examine the independent associations between childbirth locations and mode of delivery with favorable early breastfeeding practices in four hard to reach areas of Bangladesh. METHOD: We extracted data from a cross-sectional study conducted in four HtR areas of Bangladesh in 2017. A total of 2768 women, having birth outcomes in the past 12 months of the survey, were interviewed using structured questionnaires. EIBF and no prelacteal feeding were considered as favorable early breastfeeding practices. The categories of childbirth locations were defined by the place of birth (home vs. facility) and the delivery sector (public/NGO vs. private). The mode of delivery was categorized into vaginal delivery and cesarean section. Generalized linear models were used to test the independent associations while adjusting for potential confounders. RESULTS: The prevalence of EIBF practices were 69.6%(95% CI:67.8-71.3); 72.2%(95% CI:67.8-71.3) among home births Vs 63.0%(95% CI:59.5%-66.4%) among facility births. Around 73.9% (95% CI:72.3-75.6) mother's in the study areas reported no-prelacteal feeding. Compared to home births, women delivering in the facilities had lower adjusted odds of EIBF (aOR = 0.51; 95%CI:0.35-0.75). Cesarean section was found to be negatively associated with EIBF (aOR = 0.20; 95%CI:0.12-0.35), after adjusting for potential confounders. We could not find any significant associations between the place of birth and mode of delivery with no prelacteal feeding. DISCUSSIONS: This study found that facility births and cesarean deliveries were negatively associated with EIBF. Although the implementation of "Baby-Friendly Hospital Initiatives" could be a potential solution for improving EIBF and no prelacteal feeding practices, the challenges of reduced service availability and accessibility in HtR areas must be considered while devising effective intervention strategies. Future studies can explore potential interventions to promote early breastfeeding for facility births and cesarean deliveries in HtR areas.

Early life risk factors of motor, cognitive and language development: a pooled analysis of studies from low/middle-income countries.

OBJECTIVE: To determine the magnitude of relationships of early life factors with child development in low/middle-income countries (LMICs). DESIGN: Meta-analyses of standardised mean differences (SMDs) estimated from published and unpublished data. DATA SOURCES: We searched Medline, bibliographies of key articles and reviews, and grey literature to identify studies from LMICs that collected data on early life exposures and child development. The most recent search was done on 4 November 2014. We then invited the first authors of the publications and investigators of unpublished studies to participate in the study. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies that assessed at least one domain of child development in at least 100 children under 7 years of age and collected at least one early life factor of interest were included in the study. ANALYSES: Linear regression models were used to assess SMDs in child development by parental and child factors within each study. We then produced pooled estimates across studies using random effects meta-analyses. RESULTS: We retrieved data from 21 studies including 20 882 children across 13 LMICs, to assess the associations of exposure to 14 major risk factors with child development. Children of mothers with secondary schooling had 0.14 SD (95% CI 0.05 to 0.25) higher cognitive scores compared with children whose mothers had primary education. Preterm birth was associated with 0.14 SD (-0.24 to -0.05) and 0.23 SD (-0.42 to -0.03) reductions in cognitive and motor scores, respectively. Maternal short stature, anaemia in infancy and lack of access to clean water and sanitation had significant negative associations with cognitive and motor development with effects ranging from -0.18 to -0.10 SDs. CONCLUSIONS: Differential parental, environmental and nutritional factors contribute to disparities in child development across LMICs. Targeting these factors from prepregnancy through childhood may improve health and development of children.

Relative importance of prenatal and postnatal determinants of stunting: data mining approaches to the MINIMat cohort, Bangladesh.

INTRODUCTION: WHO has set a goal to reduce the prevalence of stunted child growth by 40% by the year 2025. To reach this goal, it is imperative to establish the relative importance of risk factors for stunting to deliver appropriate interventions. Currently, most interventions take place in late infancy and early childhood. This study aimed to identify the most critical prenatal and postnatal determinants of linear growth 0-24 months and the risk factors for stunting at 2 years, and to identify subgroups with different growth trajectories and levels of stunting at 2 years. METHODS: Conditional inference tree-based methods were applied to the extensive Maternal and Infant Nutrition Interventions in Matlab trial database with 309 variables of 2723 children, their parents and living conditions, including socioeconomic, nutritional and other biological characteristics of the parents; maternal exposure to violence; household food security; breast and complementary feeding; and measurements of morbidity of the mothers during pregnancy and repeatedly of their children up to 24 months of age. Child anthropometry was measured monthly from birth to 12 months, thereafter quarterly to 24 months. RESULTS: Birth length and weight were the most critical factors for linear growth 0-24 months and stunting at 2 years, followed by maternal anthropometry and parental education. Conditions after birth, such as feeding practices and morbidity, were less strongly associated with linear growth trajectories and stunting at 2 years. CONCLUSION: The results of this study emphasise the benefit of interventions before conception and during pregnancy to reach a substantial reduction in stunting.

Evaluating the use of job aids and user instructions to improve adherence for the treatment of childhood pneumonia using amoxicillin dispersible tablets in a low-income setting: a mixed-method study.

OBJECTIVES: We conducted a study to evaluate the use of job aids and simple user instructions to improve adherence for the treatment of childhood pneumonia with amoxicillin dispersible tablet (DT). DESIGN: A mixed-method study implemented in three phases between October 2015 and February 2016. SETTINGS: The study was implemented in two subdistricts of Bangladesh. PARTICIPANTS: Caregivers of children aged 2-59 months, health service providers and key stakeholders at national and district level. INTERVENTIONS: An intervention including training and job aids and user-friendly instructions was introduced in one subdistrict while standard amoxicillin DT packaging and instructions with no training served as the control in the comparison subdistrict. PRIMARY OUTCOME: Adherence behaviour of caregivers of children aged 2-59 months for the treatment of childhood pneumonia with amoxicillin DT. METHODS: We conducted a survey with 56 caregivers in the intervention subdistrict and 38 caregivers in the comparison subdistrict. We also conducted 44 in-depth interviews to evaluate the job aids and user-friendly instructions with healthcare providers and caregivers to assess the feasibility, usability and acceptability of the tools in intervention subdistrict. RESULTS: For 5-day treatment course, 32.1% (95% CI 23.1% to 41.1%) of caregivers in the intervention subdistrict and 2.6% (95% CI 0.3% to 7.8%) in the comparison subdistrict maintained full adherence to the amoxicillin DT treatment for pneumonia. More children under 12 months were given age-appropriate treatment than older children. Key stakeholders and healthcare providers considered the use and integration of the tools into the health system to be feasible and acceptable. CONCLUSIONS: The provision of tools for the treatment of childhood pneumonia with amoxicillin DT had a positive influence on adherence behaviours. These tools can help close information gaps and overcome the barriers posed by medical illiteracy and remembering instructions from providers.

How can formative research inform the design of an iron-folic acid supplementation intervention starting in first trimester of pregnancy in Bangladesh?

BACKGROUND: The study objective was to understand community preparedness for iron and folic acid (IFA) supplementation early in pregnancy and to inform the design of a large-scale trial of early introduction of IFA supplementation in rural Bangladesh. METHODS: 66 in-depth interviews (pregnant women, husbands, and older women in the household), 20 key-informant interviews, 3 focus-group discussions (community health workers and adolescent female students), and observation of two community-based clinics were conducted. RESULTS: Most of the women who used IFA tablets during pregnancy reported better health and physical strength after taking them. Women perceived that IFA increased blood volume, leading to foetal nourishment and compensated for blood loss during delivery. However, a culturally informed perceived barrier was the belief that IFA supplementation will increase foetus size, leading to birth complications, hospitalisation, caesarean section and financial burden for the family. Community health workers (CHWs) of BRAC (a non-government organisation) were the main sources of IFA information and supplements, although knowledge of IFA tablets among women's social networks also helped to make it acceptable. Pregnant women felt that they could start taking IFA during the first trimester of pregnancy if advised by the CHWs. Programme managers and healthcare providers expressed concern about starting IFA supplementation early. CONCLUSION: Our study suggests that introduction of IFA supplementation early in pregnancy is feasible with support from CHWs. Promotion of IFA could benefit from efforts to include culturally sensitive reasons for usage; improvement of the CHW training modules; targeted home visits and counselling; and outreach to standardize messages.

Ascaris lumbricoids Infection as a Risk Factor for Asthma and Atopy in Rural Bangladeshi Children.

Controversy persists as to whether helminth infections cause or protect against asthma and atopy. The aim of this study was to investigate the effects of helminth infection on asthma and atopy among Bangladeshi children. A total of 912 children aged 4.5 years (mean = 54.4, range = 53.5-60.8 months) participated in a cross-sectional study nested into a randomized controlled trial in Bangladesh. Ever-asthma, ever-wheezing and current wheezing were identified using the International Study of Asthma and Allergies in Childhood questionnaire. Current helminth infection was defined by the presence of helminth eggs in stools, measured by routine microscopic examination. Repeated Ascaris infection was defined by the presence of anti-Ascaris IgE ≥ 0.70 UA/ml in serum measured by the CAP-FEIA method. Atopy was defined by specific IgE to house dust mite (anti-DP IgE) ≥ 0.70 UA/ml measured by the CAP-FEIA method and/or positive skin prick test (≥ 5 mm). Anti-Ascaris IgE was significantly associated with ever asthma (odds ratio (OR) = 1.86, 95% CI: 1.14-3.04, highest vs. lowest quartile; P for trend 0.016). Anti-Ascaris IgE was also significantly associated with positive anti-DP IgE (OR = 9.89, 95% CI: 6.52-15.00, highest vs. lowest; P for trend < 0.001) and positive skin prick test (OR = 1.69, 95% CI: 1.01-2.81, highest vs. lowest, P for trend 0.076). These findings suggest that repeated Ascaris infection is a risk factor for asthma and atopy in rural Bangladeshi children. Further analysis is required to examine the mechanism of developing asthma and atopy in relation to helminth infection.

Improving and sustaining quality of child health care through IMCI training and supervision: experience from rural Bangladesh.

BACKGROUND: The Integrated Management of Childhood Illness (IMCI) strategy includes guidelines for the management of sick children at first-level facilities. These guidelines intend to improve quality of care by ensuring a complete assessment of the child's health and by providing algorithms that combine presenting symptoms into a set of illness classifications for management by IMCI-trained service providers at first-level facilities. OBJECTIVES: To investigate the sustainability of improvements in under-five case management by two cadres of first-level government service providers with different levels of pre-service training following implementation of IMCI training and supportive supervision. METHODS: Twenty first-level health facilities in the rural sub-district of Matlab in Bangladesh were randomly assigned to IMCI intervention or comparison groups. Health workers in IMCI facilities received training in case management and monthly supportive supervision that involved observations of case management and reinforcement of skills by trained physicians. Health workers in comparison facilities were supervised according to Government of Bangladesh standards. Health facility surveys involving observations of case management were carried out at baseline (2000) and at two points (2003 and 2005) after implementation of IMCI in intervention facilities. FINDINGS: Improvement in the management of sick under-five children by IMCI trained service providers with only 18 months of pre-service training was equivalent to that of service providers with 4 years of pre-service training. The improvements in quality of care were sustained over a 2-year period across both cadres of providers in intervention facilities. CONCLUSION: IMCI training coupled with regular supervision can sustain improvements in the quality of child health care in first-level health facilities, even among workers with minimal pre-service training. These findings can guide government policy makers and provide further evidence to support the scale-up of regular supervision and task shifting the management of sick under-five children to lower-level service providers.

Thymus development and infant and child mortality in rural Bangladesh.

BACKGROUND: Data from West Africa indicate that a small thymus at birth and at 6 months of age is a strong and independent risk factor for infection-related mortality up to 24 and 36 months of age, respectively. We investigated the association between thymus size (thymic index, TI) in infancy and subsequent infant and child survival in a contemporary South Asian population. METHODS: The study focused on the follow-up of a randomized trial of prenatal nutritional interventions in rural Bangladesh (ISRCTN16581394), with TI measured longitudinally in infancy (at birth and weeks 8, 24 and 52 of age) and accurate recording of mortality up to 5 years of age. RESULTS: A total of 3267 infants were born into the Maternal and Infant Nutrition Interventions, Matlab study; data on TI were available for 1168 infants at birth, increasing to 2094 infants by 52 weeks of age. TI in relation to body size was largest at birth, decreasing through infancy. For infants with at least one measure of TI available, there were a total of 99 deaths up to the age of 5 years. No association was observed between TI and subsequent mortality when TI was measured at birth. However, an association with mortality was observed with TI at 8 weeks of age [odds ratio (OR) for change in mortality risk associated with 1 standard deviation change in TI: all deaths: OR = 0.64, 95% confidence interval (CI) 0.41, 0.98; P = 0.038; and infection-related deaths only: OR = 0.32, 95% CI 0.14, 0.74; P = 0.008]. For TI when measured at 24 and 52 weeks of age, the numbers of infection-related deaths were too few (3 and 1, respectively) for any meaningful association to be observed. CONCLUSION: These results confirm that thymus size in early infancy predicts subsequent survival in a lower mortality setting than West Africa. The absence of an effect at birth and its appearance at 8 weeks of age suggests early postnatal influences such as breast milk trophic factors.

IgA and neutralizing antibodies to influenza a virus in human milk: a randomized trial of antenatal influenza immunization.

BACKGROUND: Antenatal immunization of mothers with influenza vaccine increases serum antibodies and reduces the rates of influenza illness in mothers and their infants. We report the effect of antenatal immunization on the levels of specific anti-influenza IgA levels in human breast milk. (ClinicalTrials.gov identifier NCT00142389; http://clinicaltrials.gov/ct2/show/NCT00142389). METHODS AND FINDINGS: The Mother's Gift study was a prospective, blinded, randomized controlled trial that assigned 340 pregnant Bangladeshi mothers to receive either trivalent inactivated influenza vaccine, or 23-valent pneumococcal polysaccharide vaccine during the third trimester. We evaluated breast milk at birth, 6 weeks, 6 months, and 12 months, and serum at 10 weeks and 12 months. Milk and serum specimens from 57 subjects were assayed for specific IgA antibody to influenza A/New Caledonia (H1N1) using an enzyme-linked immunosorbent assay (ELISA) and a virus neutralization assay, and for total IgA using ELISA. Influenza-specific IgA levels in breast milk were significantly higher in influenza vaccinees than in pneumococcal controls for at least 6 months postpartum (p = 0.04). Geometric mean concentrations ranged from 8.0 to 91.1 ELISA units/ml in vaccinees, versus 2.3 to 13.7 ELISA units/mL in controls. Virus neutralization titers in milk were 1.2 to 3 fold greater in vaccinees, and correlated with influenza-specific IgA levels (r = 0.86). Greater exclusivity of breastfeeding in the first 6 months of life significantly decreased the expected number of respiratory illness with fever episodes in infants of influenza-vaccinated mothers (p = 0.0042) but not in infants of pneumococcal-vaccinated mothers (p = 0.4154). CONCLUSIONS: The sustained high levels of actively produced anti-influenza IgA in breast milk and the decreased infant episodes of respiratory illness with fever suggest that breastfeeding may provide local mucosal protection for the infant for at least 6 months. Studies are needed to determine the cellular and immunologic mechanisms of breast milk-mediated protection after antepartum immunization. TRIAL REGISTRATION: ClinicalTrials.gov NCT00142389.

Risk of childhood undernutrition related to small-for-gestational age and preterm birth in low- and middle-income countries.

BACKGROUND: Low- and middle-income countries continue to experience a large burden of stunting; 148 million children were estimated to be stunted, around 30-40% of all children in 2011. In many of these countries, foetal growth restriction (FGR) is common, as is subsequent growth faltering in the first 2 years. Although there is agreement that stunting involves both prenatal and postnatal growth failure, the extent to which FGR contributes to stunting and other indicators of nutritional status is uncertain. METHODS: Using extant longitudinal birth cohorts (n=19) with data on birthweight, gestational age and child anthropometry (12-60 months), we estimated study-specific and pooled risk estimates of stunting, wasting and underweight by small-for-gestational age (SGA) and preterm birth. RESULTS: We grouped children according to four combinations of SGA and gestational age: adequate size-for-gestational age (AGA) and preterm; SGA and term; SGA and preterm; and AGA and term (the reference group). Relative to AGA and term, the OR (95% confidence interval) for stunting associated with AGA and preterm, SGA and term, and SGA and preterm was 1.93 (1.71, 2.18), 2.43 (2.22, 2.66) and 4.51 (3.42, 5.93), respectively. A similar magnitude of risk was also observed for wasting and underweight. Low birthweight was associated with 2.5-3.5-fold higher odds of wasting, stunting and underweight. The population attributable risk for overall SGA for outcomes of childhood stunting and wasting was 20% and 30%, respectively. CONCLUSIONS: This analysis estimates that childhood undernutrition may have its origins in the foetal period, suggesting a need to intervene early, ideally during pregnancy, with interventions known to reduce FGR and preterm birth.

Combined effects of antenatal receipt of influenza vaccine by mothers and pneumococcal conjugate vaccine receipt by infants: results from a randomized, blinded, controlled trial.

A 2 × 2 factorial trial was performed to determine the efficacy of antennal influenza vaccination of mothers plus pneumococcal conjugate vaccination of their infants against respiratory illness during early infancy. The efficacy of trivalent inactivated influenza vaccine (TIV; delivered to mothers) plus 7-valent pneumococcal vaccine (PCV7; delivered to infants) was higher than the efficacy of TIV alone or PCV7 alone. During the period of the study in which influenza was circulating, the efficacy of TIV plus PCV7 was 72.4% (95% confidence interval, 30.2%-89.1%) against febrile respiratory illness and 66.4% (95% CI, 14.3%-86.9%) against medically attended acute respiratory illness.

The effect of exclusive breast-feeding on respiratory illness in young infants in a maternal immunization trial in Bangladesh.

BACKGROUND: Exclusive breast-feeding reduces the risk of respiratory illness in infants younger than 6 months of age in developing countries by approximately half. We evaluated the effect of exclusive breast-feeding on respiratory illness with fever (RIF) in Bangladeshi infants in the context of a randomized maternal influenza immunization trial. METHODS: Infants in a maternal vaccine trial in Dhaka, Bangladesh, were prospectively assessed at weekly intervals for 6 months after birth for breast-feeding practices and RIF. We estimated the risk of an RIF episode for infants who were exclusively breast-fed the prior week compared with infants not exclusively breast-fed the prior week using generalized estimating equations. RESULTS: We followed a total of 331 infants from birth to 24 weeks of age. The median weeks infants were exclusively breast-fed was 15 (interquartile range, 6-21). The adjusted independent odds of respiratory illness for exclusively breast-fed infants compared with nonexclusively breast-fed infants was 0.59 (95% confidence interval: 0.45-0.77) for an RIF episode. After adjusting for exclusive breast-feeding, we confirmed the previous report that maternal immunization with influenza vaccine had an independent protective effect against RIF (odds ratio, 0.72; 95% confidence interval: 0.55-0.93). No significant difference in the protective effect of exclusive breast-feeding was seen by maternal influenza immunization status. CONCLUSIONS: Exclusive breast-feeding during the first 6 months of life and maternal immunization with influenza vaccine independently and substantially reduced respiratory illness with fever in infants.

Early exposure to toxic metals has a limited effect on blood pressure or kidney function in later childhood, rural Bangladesh.

BACKGROUND: Chronic exposure to toxic metals such as arsenic and cadmium has been implicated in the development of kidney and cardiovascular diseases but few studies have directly measured exposure during inutero and early child development. METHODS: We investigated the impact of exposure to arsenic (mainly in drinking water) and cadmium (mainly in rice) during pregnancy on blood pressure and kidney function at 4.5 years of age in rural Bangladesh. The effect of arsenic exposure in infancy was also assessed. RESULTS: Within a cohort of 1887 children recruited into the MINIMat study, exposure to arsenic (maternal urinary arsenic, U-As), but not cadmium, during in utero development was associated with a minimal increase in blood pressure at 4.5 years. Each 1 mg/l increase in pregnancy U-As was associated with 3.69 mmHg (95% CI: 0.74, 6.63; P: 0.01) increase in child systolic and a 2.91 mmHg (95% CI: 0.41, 5.42; P: 0.02) increase in child diastolic blood pressure. Similarly, a 1 mg/l increase in child U-As at 18 months of age was associated with a 8.25 mmHg (95% CI: 1.37, 15.1; P: 0.02) increase in systolic blood pressure at 4.5 years. There was also a marginal inverse association between infancy U-As and glomerular filtration rate at 4.5 years (-33.4 ml/min/1.72 m(2); 95% CI: -70.2, 3.34; P: 0.08). No association was observed between early arsenic or cadmium exposure and kidney volume at 4.5 years assessed by ultrasound. CONCLUSIONS: These modest effect sizes provide some evidence that arsenic exposure in early life has long-term consequences for blood pressure and maybe kidney function.