Scaling-Up Access to Family Planning May Improve Linear Growth and Child Development in Low and Middle Income Countries

Background: A large literature has indicated a robust association between birth spacing and child survival, but evidence on the association of birth timing with physical growth in low and middle income countries (LMICs) remains limited. Methods and Results: Data from 153 cross-sectional Demographic and Health Surveys (DHS) across 61 LMICs conducted between 1990 and 2011 were combined to assess the association of birth timing with child stunting (height-for-age z-score <−2). A total of 623,789 children of birth order 1–5 contributed to the maternal age analysis, while the birth spacing dataset consisted of 584,226 children of birth order 2 and higher. Compared to 27–34 year old mothers, maternal age under 18 years was associated with a relative stunting risk of 1.35 (95% CI: 1.29–1.40) for firstborn children, whereas the relative risk was 1.24 (95% CI: 1.19–1.29) for mothers aged 18–19 years. The association of young maternal age with stunting was significantly greater for urban residents and those in the top 50% of household wealth. Birth intervals less than 12 months and 12–23 months had relative risks for stunting of 1.09 (95% CI: 1.06–1.12) and 1.06 (95% CI: 1.05–1.06) as compared to a 24–35 month inter-pregnancy interval, respectively. The strength of both teenage pregnancy and short birth interval associations showed substantial variation across WHO region. We estimate that 8.6% (6.9–10.3%) of stunted cases in the South Asian DHS sample would have been averted by jointly eliminating teen pregnancies and birth intervals less than 24 months, while only 3.6% (1.5–5.7%) of stunting cases would have prevented in the Middle East and North Africa sample. Conclusions: Postponing the age of first birth and increasing inter-pregnancy intervals has the potential to significantly reduce the prevalence of stunting and improve child development in LMICs

Anemia prevalence and etiology among women, men, and children in Ethiopia: a study protocol for a national population-based survey.

BACKGROUND: Anemia remains a public health challenge in Ethiopia, affecting an estimated 56% of children under age 5 years, 23% of women of reproductive age and 18% of adult men. However, anemia etiology and the relative contribution of underlying risk factors for anemia remains unclear and has hindered implementation of anemia control programs. METHODS/DESIGN: Anemia Etiology in Ethiopia (AnemEE) is a population-based cross-sectional survey of six regions of Ethiopia that includes children, women of reproductive age, and men from regionally representative households. The survey will include detailed assessment of anemia, iron, inflammatory and nutritional biomarkers, diet, comorbidities, and other factors. The objectives of AnemEE are 1) to generate evidence for decision-making on the etiology of anemia in Ethiopia among men, women and children and 2) to simulate the potential effect of iron fortification and other interventions on the prevalence of anemia and risk of iron overload. DISCUSSION: AnemEE will provide the most comprehensive evaluation of anemia etiology in Ethiopia to date due to its detailed assessment of diet, biomarkers, infections and other risk factors in a population-based sample. By generating evidence and simulating potential interventions, AnemEE will inform the development of high-impact anemia control programs and policies. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04002466 . Registered on 28 June 2019. Retrospectively registered

Evaluating implementation of LEAPS, a youth-led early childhood care and education intervention in rural Pakistan: Protocol for a stepped wedge cluster-randomized trial

Background: The Sustainable Development Goals (SDGs) highlight the importance of investments in early childhood care and education (ECCE) and youth development. Given Pakistan\u27s large young population, and gender and urban-rural inequalities in access to education, training, and employment, such investments offer opportunities. LEAPS is a youth-led ECCE program that trains female youth, 18-24 years, as Community Youth Leaders (CYLs) to deliver high-quality ECCE for children, 3.5-5.5 years, in rural Sindh, Pakistan.Methods: We use a stepped wedge cluster-randomized trial to evaluate implementation of LEAPS. Ninety-nine clusters will be randomized to receive the intervention in one of three 7-month steps (33 clusters/step). The primary outcome is children\u27s school readiness (indexed by the total score on the International Development and Early Learning Assessment (IDELA)). Secondary child outcomes are children\u27s IDELA domain scores and executive functions. Data are collected in cross-sectional surveys of 1089 children (11 children/cluster from 99 clusters) aged 4.5-5.5 years at four timepoints (baseline and at the end of each step). Additionally, we will enroll three non-randomized youth participant open cohorts, one per step (33 CYLs: 66 comparison youth per cohort; 99:198 in total). Youth cohorts will be assessed at enrollment and every 7 months thereafter to measure secondary outcomes of youth personal and professional development, depressive symptoms, and executive functions. A non-randomized school cohort of 330 LEAPS students (10 students/cluster from 33 clusters) will also be enrolled and assessed during Step 1 after intervention rollout and at endline. The quality of the learning environment will be assessed in each LEAPS ECCE center and in a comparison center at two timepoints midway following rollout and at endline. A concurrent mixed-methods implementation evaluation will assess program fidelity and quality, and the extent to which a technical support strategy is successful in strengthening systems for program expansion. A cost evaluation will assess cost per beneficiary. Data collection for implementation and cost evaluations will occur in Step 3.Discussion: Youth-led models for ECCE offer a promising approach to support young children and youth. This study will contribute to the evidence as a means to promote sustainable human development across multiple SDG targets.Trial registration: ClinicalTrials.gov NCT03764436 . Registered on December 5, 2018

Micronutrient Deficiencies among Breastfeeding Infants in Tanzania

Infant mortality accounts for the majority of child deaths in Tanzania, and malnutrition is an important underlying cause. The objectives of this cross-sectional study were to describe the micronutrient status of infants in Tanzania and assess predictors of infant micronutrient deficiency. We analyzed serum vitamin D, vitamin B12, folate, and ferritin levels from 446 infants at two weeks of age, 408 infants at three months of age, and 427 mothers three months post-partum. We used log-Poisson regression to estimate relative risk of being deficient in vitamin D and vitamin B12 for infants in each age group. The prevalence of vitamin D and vitamin B12 deficiency decreased from 60% and 30% at two weeks to 9% and 13% at three months respectively. Yet, the prevalence of insufficiency at three months was 49% for vitamin D and 17% for vitamin B12. Predictors of infant vitamin D deficiency were low birthweight, urban residence, maternal education, and maternal vitamin D status. Maternal vitamin B12 status was the main predictor for infant vitamin B12 deficiency. The majority of infants had sufficient levels of folate or ferritin. Further research is necessary to examine the potential benefits of improving infants' nutritional status through vitamin D and B12 supplements.</p

Population-level effective coverage of adolescent weekly iron and folic acid supplementation is low in rural West Bengal, India

Objective: To assess the coverage of the adolescent weekly iron and folic acid supplementation (WIFS) programme in rural West Bengal, India. Design: We conducted a population-based cross-sectional survey of intended WIFS programme beneficiaries (in-school adolescent girls and boys and out-of-school adolescent girls). Setting: Birbhum Health and Demographic Surveillance System. Participants: A total of 4448 adolescents 10–19 years of age participated in the study. Results: The percentage of adolescents who reported taking four WIFS tablets during the last month as intended by the national programme was 9·4 % among in-school girls, 7·1 % for in-school boys and 2·3 % for out-of-school girls. The low effective coverage was due to the combination of large deficits in WIFS provision and poor adherence. A large proportion of adolescents reported they were not provided any WIFS tablets in the last month: 61·7 % of in-school girls, 73·3 % of in-school boys and 97·1 % of out-of-school girls. In terms of adherence, only 41·6 % of in-school girls, 38·1 % of in-school boys and 47·4 % of out-of-school girls reported that they consumed all WIFS tablets they received. Counselling from teachers, administrators and school staff was the primary reason adolescents reported taking WIFS tablets, whereas the major reasons for non-adherence were lack of perceived benefit, peer suggestion not to take WIFS and a reported history of side effects. Conclusions: The effective coverage of the WIFS programme for in-school adolescents and out-of-school adolescent girls is low in rural Birbhum. Integrated supply- and demand-side strategies appear to be necessary to increase the effective coverage and potential benefits of the WIFS programme

Effectiveness of a multivitamin supplementation program among HIV-infected adults in Tanzania

Objective: The objective of this study was to assess the effectiveness of a routine multivitamin supplementation program for adults living with HIV in Tanzania. Design: We conducted a retrospective cohort study of 67,707 adults enrolled in the Dar es Salaam HIV care and treatment program during 2004-2012. Methods: The Dar es Salaam HIV care and treatment program intended to provide all adult patients with multivitamin supplements (vitamins B-complex, C, and E) free of charge; however, intermittent stockouts and other implementation issues did not afford universal coverage. We use Cox proportional hazard models to assess the time-varying association of multivitamin supplementation with mortality and clinical outcomes. Results: The study cohort contributed 41,540 and 129,315 person-years of follow-up time to the ART-naïve and ART-experienced analyses, respectively. Among 48,207 ART-naïve adults, provision of multivitamins reduced the risk of mortality (adjusted hazard ratio (aHR): 0.69; 95% CI: 0.59-0.81), incident tuberculosis (TB) (aHR: 0.83; 0.76-0.91), and meeting ART eligibility criteria (aHR: 0.78; 95% CI: 0.73-0.83) after adjustment for time-varying confounding. Among 46,977 ART-experienced patients, multivitamins reduced mortality (HR: 0.86; 95% CI: 0.80-0.92), incident TB (aHR: 0.78; 95% CI: 0.73-0.84), and immunologic failure (aHR: 0.70; 95% CI: 0.67-0.73). The survival benefits associated with provision multivitamins appeared to be greatest during the first year of ART and declined over time (p-value \u3c0.001). Conclusion: Multivitamin supplementation appears to be a simple, effective, safe, and scalable program to improve survival, reduce incidence of TB, and improve treatment outcomes for adult HIV patients in Tanzania

Effect of maternal vitamin D3 supplementation on maternal health, birth outcomes, and infant growth among HIV-infected Tanzanian pregnant women: study protocol for a randomized controlled trial

Background: Vitamin D has significant immunomodulatory effects on both adaptive and innate immune responses. Observational studies indicate that adults infected with HIV with low vitamin D status may be at increased risk of mortality, pulmonary tuberculosis, and HIV disease progression. Growing observational evidence also suggests that low vitamin D status in pregnancy may increase the risk of adverse birth and infant health outcomes. As a result, antiretroviral therapy (ART) adjunct vitamin D3 supplementation may improve the health of HIV-infected pregnant women and their children. Methods/design The Trial of Vitamins-5 (ToV5) is an individually randomized, double-blind, placebo-controlled trial of maternal vitamin D3 (cholecalciferol) supplementation conducted among 2300 HIV-infected pregnant women receiving triple-drug ART under Option B+ in Dar es Salaam, Tanzania. HIV-infected pregnant women of 12–27 weeks gestation are randomized to either: 1) 3000 IU vitamin D3 taken daily from randomization in pregnancy until trial discharge at 12 months postpartum; or 2) a matching placebo regimen. Maternal participants are followed-up at monthly clinic visits during pregnancy, at delivery, and then with their children at monthly postpartum clinic visits. The primary efficacy outcomes of the trial are: 1) maternal HIV disease progression or death; 2) risk of small-for-gestational age (SGA) births; and 3) risk of infant stunting at 1 year of age. The primary safety outcome of the trial is incident maternal hypercalcemia. Secondary outcomes include a range of clinical and biological maternal and child health outcomes. Discussion The ToV5 will provide causal evidence on the effect of vitamin D3 supplementation on HIV progression and death, SGA births, and infant stunting at 1 year of age. The results of the trial are likely generalizable to HIV-infected pregnant women and their children in similar resource-limited settings utilizing the Option B+ approach. Trial registration ClinicalTrials.gov identifier: NCT02305927. Registered on 29 October 2014. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2157-3) contains supplementary material, which is available to authorized users

current evidence and programmatic considerations

Funding Information: We are thankful to Ann Prentice for her critical review of the section ?Concerns in populations with low calcium intake.? The convenings of the Calcium Task Force and the development of this paper and its open access were supported by funding from The Children's Investment Fund Foundation to the Nutrition Science Program of the New York Academy of Sciences. Publisher Copyright: © 2022 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of New York Academy of Sciences.Most low- and middle-income countries present suboptimal intakes of calcium during pregnancy and high rates of mortality due to maternal hypertensive disorders. Calcium supplementation during pregnancy is known to reduce the risk of these disorders and associated complications, including preeclampsia, maternal morbidity, and preterm birth, and is, therefore, a recommended intervention for pregnant women in populations with low dietary calcium intake (e.g., where ≥25% of individuals in the population have intakes less than 800 mg calcium/day). However, this intervention is not widely implemented in part due to cost and logistical issues related to the large dose and burdensome dosing schedule (three to four 500-mg doses/day). WHO recommends 1.5–2 g/day but limited evidence suggests that less than 1 g/day may be sufficient and ongoing trials with low-dose calcium supplementation (500 mg/day) may point a path toward simplifying supplementation regimens. Calcium carbonate is likely to be the most cost-effective choice, and it is not necessary to counsel women to take calcium supplements separately from iron-containing supplements. In populations at highest risk for preeclampsia, a combination of calcium supplementation and food-based approaches, such as food fortification with calcium, may be required to improve calcium intakes before pregnancy and in early gestation.publishersversionpublishe

Effect of Multivitamin Supplementation on Measles Vaccine Response among HIV-exposed Uninfected Tanzanian Infants.

Immunization and nutritional interventions are mainstays of child health programs in sub-Saharan Africa, yet few published data exist on their interactions. HIV-exposed (but uninfected) infants enrolled in a randomized placebo-controlled trial of multivitamin supplements (vitamins B complex, C, and E) conducted in Tanzania were sampled for an assessment of measles IgG quantity and avidity at 15 to 18 months. Infants were vaccinated between 8.5 and 12 months of age, and all mothers received high-dose multivitamins as the standard of care. Of 201 HIV-exposed infants who were enrolled, 138 (68.7%) were seropositive for measles. There were no effects of infant multivitamin supplementation on measles seroconversion proportions, IgG concentrations, or IgG avidity (P > 0.05). The measles seroconversion proportion was greater for HIV-exposed infants vaccinated at 10 to 11 months of age than for those vaccinated at 8.5 to 10 months (P = 0.032) and greater for infants whose mothers had a CD4 T-cell count of <200 cells/μl than for infants whose mothers had a CD4 T-cell count of >350 cells/μl (P = 0.039). Stunted infants had a significantly decreased IgG quantity compared to nonstunted infants (P = 0.012). As for measles avidity, HIV-exposed infants vaccinated at 10 to 11 months had increased antibody avidity compared to those vaccinated at 8.5 to 10 months (P = 0.031). Maternal CD4 T-cell counts of <200 cells/μl were associated with decreased avidity compared to counts of >350 cells/μl (P = 0.047), as were lower infant height-for-age z-scores (P = 0.016). Supplementation with multivitamins containing B complex, C, and E does not appear to improve measles vaccine responses for HIV-exposed infants. Studies are needed to better characterize the impact of maternal HIV disease severity on the immune system development of HIV-exposed infants and the effect of malnutrition interventions on vaccine responses. (This study has been registered at ClinicalTrials.gov under registration no. NCT00197730.)

Does early vitamin B12 supplementation improve neurodevelopment and cognitive function in childhood and into school age: a study protocol for extended follow-ups from randomised controlled trials in India and Tanzania

Introduction: As many as 250 million children under the age of 5 may not be reaching their full developmental potential partly due to poor nutrition during pregnancy and the first 2 years of life. Micronutrients, including vitamin B12, are important for the development of brain structure and function; however, the timing, duration and severity of deficiencies may alter the impact on functional development outcomes. Consequently, to fully explore the effect of vitamin B12 on cognitive function, it is crucial to measure neurodevelopment at different ages, in different populations and with vitamin B12 supplementation at different times during the critical periods of neurodevelopment. Methods and analysis In this project, we follow up children from four recently completed randomised placebo-controlled trials of oral vitamin B12 supplementation, two in India and two in Tanzania, to explore the long-term effects on neurodevelopmental outcomes and growth. All the included trials provided at least two recommended dietary allowances of oral vitamin B12 daily for at least 6 months. Vitamin B12 was supplemented either during pregnancy, early infancy or early childhood. Primary outcomes are neurodevelopmental status, cognitive function and growth later in childhood. We apply validated and culturally appropriate instruments to identify relevant developmental outcomes. All statistical analyses will be done according to intention-to-treat principles. The project provides an excellent opportunity to examine the effect of vitamin B12 supplementation in different periods during early life and measure the outcomes later in childhood. Ethics and dissemination The study has received ethical approvals from all relevant authorities in Norway, USA, Tanzania and India and complies fully with ethical principles for medical research. Results will be presented at national and international research and policy meetings and published in peer-reviewed scientific journals, preferably open access. Trial registration number NCT00641862 (Bangalore); NCT00717730, updated CTRI/2016/11/007494 (Delhi); NCT00197548 and NCT00421668 (Dar es Salaam)