Infections and nutrient deficiencies during infancy predict impaired growth at 5 years: Findings from the MAL-ED study in Pakistan.

Background: Socio-economic, nutritional, and infectious factors have been associated with impaired infant growth, but how the presence of these factors during infancy affects growth around 5 years is not well understood. Methods: This secondary analysis of the MAL-ED cohort included 277 children from Pakistan for whom socio-demographic, breastfeeding, complementary foods, illness, nutritional biomarkers, stool pathogens and environmental enteropathy indicators between 0 and 11 months were recorded. We used linear regression models to analyze associations of these indicators with height-for-age (HAZ), weight-for-age (WAZ) and weight-for-height (WLZ) at 54-66 months (~5 years), and Poisson regression with robust standard errors to estimate risk ratios for stunting and underweight ~5 years, controlling for gender, first available weight, and income. Results: Among the 237 infants followed longitudinally and evaluated at about 5 years of age, exclusive breastfeeding was short (median = 14 days). Complementary feeding started before 6 months with rice, bread, noodles, or sugary foods. Roots, dairy products, fruits/vegetables, and animal-source foods were provided later than recommended (9-12 months). Anemia (70.9%), deficiencies in iron (22.0%), zinc (80.0%), vitamin A (53.4%) and iodine (13.3%) were common. Most infants (>90%) presented with diarrhea and respiratory infections in their first year. At ~5 years, low WAZ (mean-1.91 ± 0.06) and LAZ (-2.11 ± 0.06) resulted in high prevalence of stunting (55.5%) and underweight (44.4%) but a relatively low rate of wasting (5.5%). While 3.4% had concurrent stunting and wasting ~5 years, 37.8% of children had coexisting stunting and underweight. A higher income and receiving formula or dairy products during infancy were associated with a higher LAZ ~5 years, but infant's history of hospitalizations and more respiratory infections were associated with lower LAZ and higher risk of stunting ~5 years. Infants' intake of commercial baby foods and higher serum-transferrin receptors were associated with higher WAZ and lower risk of underweight ~5 years. Presence of Campylobacter and fecal neopterin >6.8 nmol/L in the first year were associated with increased risk of underweight ~5 years. Conclusion: Growth indicators ~5 years were associated with poverty, inappropriate complementary feeding, and infections during the first year of life, which supports the early start of public health interventions for preventing growth delay ~5 years.

Characteristics and birth outcomes of pregnant adolescents compared to older women: An analysis of individual level data from 140,000 mothers from 20 RCTs.

BACKGROUND: Adolescence is a critical period of maturation when nutrient needs are high, especially among adolescents entering pregnancy. Using individual-level data from 140,000 participants, we examined socioeconomic, nutrition, and pregnancy and birth outcomes for adolescent mothers (10-19 years) compared to older mothers in low and middle-income countries. METHODS: This study was conducted between March 16, 2018 and May 25, 2021. Data were obtained from 20 randomised controlled trials of micronutrient supplementation in pregnancy. Stratified analyses were conducted by age (10-14 years, 15-17 years, 18-19 years, 20-29 years, 30-39 years, 40+ years) and geographical region (Africa, Asia). Crude and confounder-adjusted means, prevalence and relative risks of pregnancy, nutrition and birth outcomes were estimated using multivariable linear and log-binomial regression models with 95% confidence intervals. FINDINGS: Adolescent mothers comprised 31.6% of our data. Preterm birth, small-for-gestational age (SGA), low birthweight (LBW) and newborn mortality followed a U-shaped trend in which prevalence was highest among the youngest mothers (10-14 years) and then reduced gradually, but increased again for older mothers (40+ years). When compared to mothers aged 20-29 years, there was a 23% increased risk of preterm birth, a 60% increased risk of perinatal mortality, a 63% increased risk of neonatal mortality, a 28% increased risk of LBW, and a 22% increased risk of SGA among mothers 10-14 years. Mothers 40+ years experienced a 22% increased risk of preterm birth and a 103% increased risk of stillbirth when compared to the 20-29 year group. INTERPRETATION: The youngest and oldest mothers suffer most from adverse pregnancy and birth outcomes. Policy and programming agendas should consider both biological and socioeconomic/environmental factors when targeting these populations. FUNDING: Bill and Melinda Gates Foundation (Grant No: OP1137750).

Optimal iron content in ready-to-use therapeutic foods for the treatment of severe acute malnutrition in the community settings: a protocol for the systematic review and meta-analysis.

INTRODUCTION: The current standard of care for children with severe acute malnutrition (SAM) involves using ready-to-use therapeutic food (RUTF) to promote growth; however, the precise formulation to achieve optimal recovery remains unclear. Emerging research suggests that alternative RUTF formulations may be more effective in correcting SAM-related complications such as anaemia and iron deficiency. This systematic review commissioned by the WHO aims to synthesise the most recent research on the iron content in RUTF and related products in the community-based treatment of uncomplicated severe malnutrition in children aged 6 months and older. METHODS AND ANALYSIS: We will search multiple electronic databases. We will include randomised controlled trials and non-randomised studies with a control arm. The intervention group will be infants who received RUTF treatments other than the current recommended guidelines set forth by the WHO. The comparison group is children receiving RUTF containing iron at the current WHO-recommended level of 1.9 mg/100 kcal (10-14 mg/100 g). The primary outcomes of interest include blood haemoglobin concentration, any anaemia, severe anaemia, iron-deficiency anaemia, recovery from SAM and any adverse outcomes. We will use meta-analysis to pool findings if sufficient homogeneity exists among included studies. The risk of bias in studies will be evaluated using the Cochrane risk of bias-2. We will use the Grading of Recommendations Assessment, Development, and Evaluation(GRADE) approach to examine the overall certainty of evidence. ETHICS AND DISSEMINATION: This is a systematic review and will not involve direct contact with human subjects. The findings of this review will be published in a peer-reviewed journal and will guide the WHO's recommendation on the optimal iron content in RUTFs for the treatment of SAM in children aged 6-59 months.

Prevalence and determinants of iron deficiency anemia among non-pregnant women of reproductive age in Pakistan.

BACKGROUND AND OBJECTIVES: Iron deficiency Anemia (IDA) in women of reproductive age is a recognized public health concern that impairs health and well-being in women and is associated with adverse reproductive outcomes. In Pakistan there is a dearth of up-to-date information on the prevalence and predictors of IDA. This study sought to investigate IDA in Pakistani women. METHODS AND STUDY DESIGN: Secondary analysis was performed using the National Nutrition Survey in Pakistan 2011- 2012. We used a pre-structured instrument to collect socio demographic, reproductive and nutritional data on women. We also collected anthropometric measurements and blood samples for micronutrient deficiencies. Univariate and multivariate logistic regression were used to analyse the data. RESULTS: A total of 7491 non-pregnant women aged between 15-49 years were included in the analysis. The prevalence of IDA was 18.1%. In the multivariate regression analysis; not using iron folic acid supplementation during the last pregnancy adjusted odds ratio (AOR) (95% CI) 1.31 (1.05, 1.64), a history of four or more pregnancies AOR (95% CI) 1.30 (1.04, 1.60), birth interval of <24 months AOR (95% CI) 1.27 (1.06, 1.71), household food insecurity AOR (95% CI) 1.42 (1.23, 1.63) and presence of clinical anemia AOR (95% CI) 5.82 (4.82, 7.02) were significantly associated with increased odds of IDA while with obesity AOR (95% CI) 0.60 (0.4, 0.88) showed a protective effect on IDA. CONCLUSION: To reduce IDA in Pakistani women, the country needs a multifaceted approach that incorporates iron supplementation, food fortification, improved family planning services and efforts to reduce food insecurity.

Effect of Vitamin D Supplementation on the Salivary Cytokines of Pregnant Women: A Randomized Placebo-Controlled Trial.

OBJECTIVE: We aimed to determine the salivary cytokine profiles of IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL-17 among pregnant women and determine if the cytokine profiles change upon administration of vitamin D to these women. METHODS: It was a community-based, blinded, placebo-controlled, randomized trial. The intervention group comprised pregnant females (n = 36) who received oral vitamin D 4000 IU/day for 6 months (starting from 12 - 16 weeks until the end of pregnancy). Controls comprised pregnant females who received placebo (n = 49) for the same duration. Probing depth (PD), attachment loss (AL) and bleeding on probing (BOP) were recorded. Saliva samples were subjected to multiplex ELISA analysis of cytokines. Serum vitamin D levels were determined. Outcome was assessed within 14 days post-partum. Periodontal examinations were done; blood and saliva samples were subjected to the set of tests described at baseline. SPSS 19.0 and Graph Pad 6.0 were used for analysis. The study was registered at www.clinicaltrials.gov with identifier number NCT01422122. RESULTS: The two study groups were comparable at the baseline. Although IL-6 showed wide variation, none of the pro-inflammatory cytokine levels was affected by six months of oral vitamin D supplementation. Similarly, the mean salivary levels of the anti-inflammatory cytokines IL-4 and IL-10 also remained unaffected in the two groups. CONCLUSION: There was no association between hypovitaminosis D and periodontal disease among the studied sample of pregnant women. None of the salivary cytokines showed any significant change after six months of oral vitamin D supplementation to the pregnant women.

Effect of multiple micronutrient versus iron-folate supplementation during pregnancy on intrauterine growth.

This review examines the effects of prenatal multiple micronutrient (MM) supplementation (≥5 micronutrients) on intrauterine growth. We identified publications from 16 randomized controlled trials through PubMed and EMBASE database searches. Meta-analyses were performed by pooling results, and sub-analyses by timing of intervention and amount of iron were also done. The primary outcome measures were birthweight, low birthweight (LBW; <2,500 g) and small for gestational age (SGA). Prenatal MM supplementation significantly reduced the incidence of LBW (risk ratio, RR: 0.86; 95% CI: 0.81-0.92) and SGA (RR: 0.83; 95% CI: 0.73-0.95) compared to iron-folate supplementation; mean birthweight was significantly higher by 55 g for MM with borderline increases in gestational age. MM supplementation was associated with larger decreases in the risk of LBW and SGA in the subgroup of trials that used supplements containing 60 mg of iron, but were not statistically significantly different from those for trials that used 30 mg iron. Prenatal MM supplementation improved intrauterine growth and can be recommended instead of prenatal IFA supplements in settings where micronutrient deficiencies are common.

Effect of multiple micronutrient supplementation on pregnancy and infant outcomes: a systematic review.

Supplementation with multiple micronutrients (MM) during pregnancy may result in improved pregnancy and infant outcomes. We conducted meta-analyses of randomised controlled trials that evaluated the effects of prenatal supplementation with MM (defined as containing at least five micronutrients and typically included iron or iron and folic acid). The outcomes of interest were low birthweight (<2500 g), birthweight, small-for-gestational age (SGA), gestational age, preterm birth (<37 weeks' gestation), stillbirth and neonatal death, maternal morbidity and mortality. We identified eligible studies through PubMed and EMBASE database searches. Meta-analyses were performed by pooling results for outcomes that were reported from more than one trial and sub-analyses were conducted to evaluate the effect of timing of intervention and amount of iron. We included published results from 16 trials in this review. Compared with control supplementation that was usually iron plus folic acid in most studies, MM supplementation resulted in a significant reduction in the incidence of low birthweight [pooled risk ratio (RR) 0.86; 95% confidence interval (CI) 0.81, 0.91] and SGA (pooled RR 0.83 [95% CI 0.73, 0.95]) and an increase in mean birthweight (weighted mean difference (WMD) 52.6 g [95% CI 43.2 g, 62.0 g]). There was no significant difference in the overall risk of preterm birth, stillbirth, and maternal or neonatal mortality, but we found an increased risk of neonatal death for the MM group compared with iron-folate in the subgroup of five trials that began the intervention after the first trimester (RR 1.38 [95% CI 1.05, 1.81]). None of the studies evaluated maternal morbidity. Compared with iron plus folic acid supplementation alone, prenatal maternal supplementation with MM resulted in a reduction in the incidence of low birthweight and SGA but increased risk of neonatal death in the subgroup of studies that began the intervention after the first trimester.

Global report on preterm birth and stillbirth (3 of 7): evidence for effectiveness of interventions.

INTRODUCTION: Interventions directed toward mothers before and during pregnancy and childbirth may help reduce preterm births and stillbirths. Survival of preterm newborns may also be improved with interventions given during these times or soon after birth. This comprehensive review assesses existing interventions for low- and middle-income countries (LMICs). METHODS: Approximately 2,000 intervention studies were systematically evaluated through December 31, 2008. They addressed preterm birth or low birth weight; stillbirth or perinatal mortality; and management of preterm newborns. Out of 82 identified interventions, 49 were relevant to LMICs and had reasonable amounts of evidence, and therefore selected for in-depth reviews. Each was classified and assessed by the quality of available evidence and its potential to treat or prevent preterm birth and stillbirth. Impacts on other maternal, fetal, newborn or child health outcomes were also considered. Assessments were based on an adaptation of the Grades of Recommendation Assessment, Development and Evaluation criteria. RESULTS: Most interventions require additional research to improve the quality of evidence. Others had little evidence of benefit and should be discontinued. The following are supported by moderate- to high-quality evidence and strongly recommended for LMICs: Two interventions prevent preterm births--smoking cessation and progesterone. Eight interventions prevent stillbirths--balanced protein energy supplementation, screening and treatment of syphilis, intermittant presumptive treatment for malaria during pregnancy, insecticide-treated mosquito nets, birth preparedness, emergency obstetric care, cesarean section for breech presentation, and elective induction for post-term delivery. Eleven interventions improve survival of preterm newborns--prophylactic steroids in preterm labor, antibiotics for PROM, vitamin K supplementation at delivery, case management of neonatal sepsis and pneumonia, delayed cord clamping, room air (vs. 100% oxygen) for resuscitation, hospital-based kangaroo mother care, early breastfeeding, thermal care, and surfactant therapy and application of continued distending pressure to the lungs for respiratory distress syndrome CONCLUSION: The research paradigm for discovery science and intervention development must be balanced to address prevention as well as improve morbidity and mortality in all settings. This review also reveals significant gaps in current knowledge of interventions spanning the continuum of maternal and fetal outcomes, and the critical need to generate further high-quality evidence for promising interventions.

Newborn resuscitation in resource-limited settings.

Every year, an estimated 4 million newborn infants die worldwide in the first 4 weeks of life. A large majority of these deaths occurs during the first day of life. One of the United Nations' eight Millennium Development Goals is to decrease child mortality; prevention of neonatal deaths by appropriate resuscitation will have a significant impact on achieving this goal. Newborn resuscitation needs to be carried out in all the settings where asphyxiated babies are born, including: community or domiciliary settings for home births; rural health centers/midwifery stations, where attendants with basic resuscitation skills might be available; district-level facilities where staff are available but skills vary; and urban referral and tertiary care centers. Individuals at all levels require training and seldomly used skills need to be maintained so that, when required, resuscitation can be carried out efficiently and effectively. Simple resuscitation techniques include: positioning, drying, and keeping the baby warm; assessing the heart rate, color, and respirations; recognizing the need for, and administering, assisted ventilation with a bag and mask or tube and mask. These maneuvers can be carried out with simple equipment and appropriate training. Research in developing countries remains sparse, with 90% of research being done in more developed parts of the world, which experience just 10% of the problems. The significant gaps in our understanding include: failing to agree on a definition of the term 'asphyxia', lack of knowledge of the impact of community approaches on the prevention and management of asphyxia, and a failure to recognize the best method to determine heart rate.

Effect of infections and environmental factors on growth and nutritional status in developing countries.

Despite numerous advances and improvements in child health globally, malnutrition remains a major problem and underlies a significant proportion of child deaths. A large proportion of the hidden burden of malnutrition is represented by widespread single and multiple micronutrient deficiencies. A number of factors may influence micronutrient deficiencies in developing countries, including poor body stores at birth, dietary deficiencies and high intake of inhibitors of absorption such as phytates and increased losses from the body. Although the effects of poor intake and increased micronutrient demands are well described, the potential effects of acute and chronic infections on the body's micronutrient status are less well appreciated. Even more obscure is the potential effect of immunostimulation and intercurrent infections on the micronutrient distribution and homeostasis. The association therefore of relatively higher rates of micronutrient deficiencies with infectious diseases may be reflective of both increased predisposition to infections in deficient populations as well as a direct effect of the infection itself on micronutrient status indicators. Recently the association of increased micronutrient losses such as those of zinc and copper with acute diarrhea has been recognized and a net negative balance of zinc has been shown in zinc metabolic studies in children with persistent diarrhea. It is also recognized that children with shigellosis can lose a significant amount of vitamin A in the urine, thus further aggravating preexisting subclinical vitamin A deficiency. Given the epidemiological association between micronutrient deficiencies and diarrhea, supplementation strategies in endemic areas are logical. The growing body of evidence on the key role of zinc supplementation in accelerating recovery from diarrheal illnesses in developing countries supports its use in public health strategies.