Birth weight, length and circumferences of the head, chest and arm are key measures of newborn size and health in developing countries. We assessed maternal socio-demographic factors associated with ...multiple measures of newborn size in a large rural population in Bangladesh using partial least squares (PLS) regression method. PLS regression, combining features from principal component analysis and multiple linear regression, is a multivariate technique with an ability to handle multicollinearity while simultaneously handling multiple dependent variables. We analyzed maternal and infant data from singletons (n = 14,506) born during a double-masked, cluster-randomized, placebo-controlled maternal vitamin A or β-carotene supplementation trial in rural northwest Bangladesh. PLS regression results identified numerous maternal factors (parity, age, early pregnancy MUAC, living standard index, years of education, number of antenatal care visits, preterm delivery and infant sex) significantly (p<0.001) associated with newborn size. Among them, preterm delivery had the largest negative influence on newborn size (Standardized β = -0.29 - -0.19; p<0.001). Scatter plots of the scores of first two PLS components also revealed an interaction between newborn sex and preterm delivery on birth size. PLS regression was found to be more parsimonious than both ordinary least squares regression and principal component regression. It also provided more stable estimates than the ordinary least squares regression and provided the effect measure of the covariates with greater accuracy as it accounts for the correlation among the covariates and outcomes. Therefore, PLS regression is recommended when either there are multiple outcome measurements in the same study, or the covariates are correlated, or both situations exist in a dataset.
Growth faltering in the first 2 years of life is high in South Asia where prevalence of stunting is estimated at 40-50%. Although nutrition counselling has shown modest benefits, few intervention ...trials of food supplementation exist showing improvements in growth and prevention of stunting.
A cluster-randomized controlled trial was conducted in rural Bangladesh to test the effect of two local, ready-to-use foods (chickpea and rice-lentil based) and a fortified blended food (wheat-soy-blend++, WSB++) compared with Plumpy'doz, all with nutrition counselling vs nutrition counselling alone (control) on outcomes of linear growth (length and length-for-age z-score, LAZ), stunting (LAZ < -2), weight-for-length z-score (WLZ) and wasting (WLZ < -2) in children 6-18 months of age. Children (n = 5536) were enrolled at 6 months of age and, in the food groups, provided with one of the allocated supplements daily for a year.
Growth deceleration occurred from 6 to 18 months of age but deceleration in LAZ was lower (by 0.02-0.04/month) in the Plumpy'doz (P = 0.02), rice-lentil (< 0.01), and chickpea (< 0.01) groups relative to control, whereas WLZ decline was lower only in Plumpy'doz and chickpea groups. WSB++ did not impact on these outcomes. The prevalence of stunting was 44% at 18 months in the control group, but lower by 5-6% (P ≤ 0.01) in those receiving Plumpy'doz and chickpea. Mean length and LAZ at 18 months were higher by 0.27-0.30 cm and 0.07-0.10 (all P < 0.05), respectively, in all four food groups relative to the control.
In rural Bangladesh, small amounts of daily fortified complementary foods, provided for a year in addition to nutrition counselling, modestly increased linear growth and reduced stunting at 18 months of age.
Micronutrient deficiencies are common among women in low-income and middle-income countries. Data from randomised trials suggest that maternal multiple micronutrient supplementation decreases the ...risk of low birthweight and potentially improves other infant health outcomes. However, heterogeneity across studies suggests influence from effect modifiers. We aimed to identify individual-level modifiers of the effect of multiple micronutrient supplements on stillbirth, birth outcomes, and infant mortality in low-income and middle-income countries.
This two-stage meta-analysis of individual patient included data from 17 randomised controlled trials done in 14 low-income and middle-income countries, which compared multiple micronutrient supplements containing iron-folic acid versus iron-folic acid alone in 112 953 pregnant women. We generated study-specific estimates and pooled subgroup estimates using fixed-effects models and assessed heterogeneity between subgroups with the χ2 test for heterogeneity. We did sensitivity analyses using random-effects models, stratifying by iron-folic acid dose, and exploring individual study effect.
Multiple micronutrient supplements containing iron-folic acid provided significantly greater reductions in neonatal mortality for female neonates compared with male neonates than did iron-folic acid supplementation alone (RR 0·85, 95% CI 0·75–0·96 vs 1·06, 0·95–1·17; p value for interaction 0·007). Multiple micronutrient supplements resulted in greater reductions in low birthweight (RR 0·81, 95% CI 0·74–0·89; p value for interaction 0·049), small-for-gestational-age births (0·92, 0·87–0·97; p=0·03), and 6-month mortality (0·71, 0·60–0·86; p=0·04) in anaemic pregnant women (haemoglobin <110g/L) as compared with non-anaemic pregnant women. Multiple micronutrient supplements also had a greater effect on preterm births among underweight pregnant women (BMI <18·5 kg/m2; RR 0·84, 95% CI 0·78–0·91; p=0·01). Initiation of multiple micronutrient supplements before 20 weeks gestation provided greater reductions in preterm birth (RR 0·89, 95% CI 0·85–0·93; p=0·03). Generally, the survival and birth outcome effects of multiple micronutrient supplementation were greater with high adherence (≥95%) to supplementation. Multiple micronutrient supplements did not significantly increase the risk of stillbirth or neonatal, 6-month, or infant mortality, neither overall or in any of the 26 examined subgroups.
Antenatal multiple micronutrient supplements improved survival for female neonates and provided greater birth-outcome benefits for infants born to undernourished and anaemic pregnant women. Early initiation in pregnancy and high adherence to multiple micronutrient supplements also provided greater overall benefits. Studies should now aim to elucidate the mechanisms accounting for differences in the effect of antenatal multiple micronutrient supplements on infant health by maternal nutrition status and sex.
None.
This study aimed to describe the timing and patterns of pubertal maturation of girls living in rural Bangladesh. Starting in September 2015, a total of 15,320 girls from a birth cohort, aged 9 to 15 ...years at initial encounter, were visited twice at about a one year interval, typically in their birth month. Participants were asked to self-report extent of pubertal maturation, including breast development, pubic hair growth and age at menarche, if applicable. Pubertal stage (abbreviated as B2 and B3-4 for breast development and PH2 and PH3-4 for pubic hair growth) was assigned. Data from both visits were pooled, yielding a total of 29,377 age-related observations per pubertal characteristic. Probit regression models were used to estimate distributions of age at which each stage of pubertal development was attained. Before age 8, <3% of the study population initiated pubertal maturation as indicated by onset of breast development (B2). The median (95% confidence interval) age of B2 and B3-4 was 11.02 (11.00-11.04) and 12.82 (12.80-12.83) years, respectively; and 12.93 (12.91-12.94) and 14.29 (14.27-14.31) years for the onset (PH2) and advanced stage (PH3-4) of pubic hair growth, respectively. Median age at menarche was 13.17 (13.15-13.19) years, with 2.15 years of timespan from B2 to menarche. Girls in rural Bangladesh progressed through puberty following a well-documented sequence of sexual maturation stages. The age at which each pubertal milestone took place was somewhat later, but the tempo from breast development to menarche was comparable to that observed elsewhere. Our findings present a current norm of pubertal maturation in a typical, rural adolescent population in South Asia, which could help inform future studies and interventions to preserve or improve early adolescent health and development.
An annualised linear growth velocity (LGV) reference can identify groups of children at risk of growing poorly. As a single velocity reference for all preschool ages does not exist, we present an ...interim tool, derived from published, normative growth studies, for detecting growth faltering, illustrating its use in Nepali preschoolers.
The WHO Child Growth Velocity Standard was adapted to derive 12-month increments and conjoined to the Tanner-Whitehouse Height Velocity Reference data yielding contiguous preschool linear growth annualised velocities. Linear restricted cubic spline regressions were fit to generate sex-specific median and standard normal deviate velocities for ages 0 through 59 months. LGV
-scores (LGVZ) were constructed, and growth faltering was defined as LGVZ < –2.
Use of the reference was illustrated with data from Nepal’s
region.
Children contributing the existing growth references and a cohort of 4276 Nepali children assessed from 2013 to 2016.
Fitted, smoothed LGV reference curves displayed monotonically decreasing 12-month LGV, exemplified by male/female annual medians of 26·4/25·3, 12·1/12·7, 9·1/9·4, 7·7/7·8 and 7/7 cm/years, starting at 0, 12, 24, 36 and 48 months, respectively. Applying the referent, 31·1 %, 28·6 % and 29·3 % of Nepali children <6, 6–11 and 12–23 months of age, and ∼6 % of children 24–59 months, exhibited growth faltering. Under 24 months, faltering velocities were more prevalent in girls (34·4 %) than boys (25·3 %) (
< 0·05) but comparable (∼6 %) in older preschoolers.
A LGV reference, concatenated from extant data, can identify preschool groups at-risk of growth faltering. Application and limitations are discussed.
Stunting (length‐for‐age z score < −2) before 2 years of age has shown associations with poor child developmental indicators, but information at the population level is scarce in South Asia, the ...region with the highest burden of stunting. We examined associations between z scores (i.e., height for age HAZ, weight for age WAZ, and weight for height WHZ) and undernutrition (i.e., stunting HAZ < −2, wasting WHZ < −2, and underweight WAZ < −2) with learning/cognition and social–emotional development among children 36–59 months of age. Data from Multiple Indicator Cluster Surveys in Bangladesh (n = 8,659), Bhutan (n = 2,038), Nepal (n = 2,253), and Pakistan (Punjab n = 11,369 and Sindh n = 6,718) were used. Children were considered developmentally “on‐track” in learning/cognition or social–emotional domains if they met specific early child development criteria. Meta‐analysis was conducted to examine regional associations, adjusting for socio‐economic status, early childhood education, and quality of care. In a pooled sample, on‐track learning/cognition development was positively associated with HAZ (OR = 1.17, 95% CI 1.07, 1.27) and WAZ (OR = 1.18, 95% CI 1.07, 1.31) and negatively associated with stunting (OR = 0.72, 95% CI 0.60, 0.86) and underweight (OR = 0.75, 95% CI 0.66, 0.86) but not associated with WHZ or wasting. On‐track development of social–emotional domain was not associated with any z scores or undernutrition indicators. Across several countries of South Asia, stunted children were less likely to be developmentally “on track” for learning/cognition. It is likely that interventions that prevent stunting may benefit child development, leading to significant individual and societal gains given the large burden of child stunting in regions like South Asia.
•Aflatoxin B1-lysine albumin biomarkers were measured in rural South Asian women during pregnancy and across the first 1000 days of life.
Aflatoxin B1 is a potent carcinogen, occurring from mold ...growth that contaminates staple grains in hot, humid environments. In this investigation, aflatoxin B1-lysine albumin biomarkers were measured by mass spectrometry in rural South Asian women, during the first and third trimester of pregnancy, and their children at birth and at two years of age. These subjects participated in randomized community trials of antenatal micronutrient supplementation in Sarlahi District, southern Nepal and Gaibandha District in northwestern Bangladesh. Findings from the Nepal samples demonstrated exposure to aflatoxin, with 94% detectable samples ranging from 0.45 to 2939.30 pg aflatoxin B1-lysine/mg albumin during pregnancy. In the Bangladesh samples the range was 1.56 to 63.22 pg aflatoxin B1-lysine/mg albumin in the first trimester, 3.37 to 72.8 pg aflatoxin B1-lysine/mg albumin in the third trimester, 4.62 to 76.69 pg aflatoxin B1-lysine/mg albumin at birth and 3.88 to 81.44 pg aflatoxin B1-lysine/mg albumin at age two years. Aflatoxin B1-lysine adducts in cord blood samples demonstrated that the fetus had the capacity to convert aflatoxin into toxicologically active compounds and the detection in the same 2-year-old children illustrates exposure over the first 1000 days of life.
This analysis was conducted to explore the association between 5 birth size measurements (weight, length and head, chest and mid-upper arm MUAC circumferences) as dependent variables and 10 maternal ...factors as independent variables using canonical correlation analysis (CCA). CCA considers simultaneously sets of dependent and independent variables and, thus, generates a substantially reduced type 1 error. Data were from women delivering a singleton live birth (n = 14,506) while participating in a double-masked, cluster-randomized, placebo-controlled maternal vitamin A or β-carotene supplementation trial in rural Bangladesh. The first canonical correlation was 0.42 (P<0.001), demonstrating a moderate positive correlation mainly between the 5 birth size measurements and 5 maternal factors (preterm delivery, early pregnancy MUAC, infant sex, age and parity). A significant interaction between infant sex and preterm delivery on birth size was also revealed from the score plot. Thirteen percent of birth size variability was explained by the composite score of the maternal factors (Redundancy, RY/X = 0.131). Given an ability to accommodate numerous relationships and reduce complexities of multiple comparisons, CCA identified the 5 maternal variables able to predict birth size in this rural Bangladesh setting. CCA may offer an efficient, practical and inclusive approach to assessing the association between two sets of variables, addressing the innate complexity of interactions.
Household food insecurity (HFI) can lead to a poor diet and malnutrition. Yet, little is known about the extent to which maternal diet covaries with food insecurity during pregnancy and lactation.
...Longitudinal associations between HFI and maternal dietary diversity from early pregnancy to 3 mo postpartum were examined in rural Bangladesh.
We repeatedly assessed dietary intake by using a 7-d food-frequency questionnaire in the first and third trimesters of pregnancy and at 3 mo postpartum among 14,600 women enrolled into an antenatal micronutrient supplementation trial. Maternal dietary diversity score (DDS) was constructed as the sum of 10 food groups reportedly consumed at each assessment. Households were classified at 6 mo postpartum as being food secure or having mild, moderate, or severe HFI on the basis of a 9-item standard scale. Generalized estimating equations were used to estimate the longitudinal relation between HFI status and DDS and the likelihood of individual food-group consumption, adjusting for confounders at the maternal and household levels.
The DDS decreased with progressively worse HFI, an association best explained by a derived household wealth index. Compared with women from food-secure households, women of mild, moderate, and severe HFI were less likely, in a dose-response fashion, to have consumed dairy products adjusted ORs (95% CIs): 0.73 (0.69, 0.78), 0.62 (0.58, 0.66), and 0.52 (0.48, 0.55), respectively, eggs 0.81 (0.76, 0.85), 0.73 (0.68, 0.77), and 0.61 (0.57, 0.65), meat 0.83 (0.79, 0.88), 0.73 (0.69, 0.78), and 0.60 (0.56, 0.64), fish 0.87 (0.80, 0.94), 0.76 (0.70, 0.83), and 0.59 (0.54, 0.65), legumes and nuts 0.88 (0.83, 0.93), 0.81 (0.76, 0.87), and 0.79 (0.74, 0.85), and yellow and orange fruit and vegetables 0.85 (0.80, 0.91), 0.78 (0.73, 0.84), and 0.72 (0.67, 0.78). Neither intakes of dark-green leafy vegetables nor of vegetable oil were associated with HFI status.
Antenatal and postnatal maternal dietary diversity, especially intakes of animal-source foods, fruit, and vegetables, declined with worsening food insecurity in rural Bangladesh.
Previously, we showed that antenatal micronutrient supplementation increases birth weight in a malnourished rural South Asian setting, but the long-term effects are unknown. Between 1999 and 2001, ...pregnant women were sector-randomized to receive from early pregnancy through 3 mo postpartum daily micronutrient supplements containing either vitamin A alone as the control or with folic acid; folic acid+iron; folic acid+iron+zinc; or a multiple micronutrient supplement that included the above nutrients plus 11 others. From 2006 to 2008, 3524 children (93% of surviving children) were revisited between the ages of 6 and 8 y. Blood pressure, BMI, waist circumference, glycated hemoglobin, cholesterol, triglycerides, glucose, insulin, and the urinary microalbumin:creatinine ratio were assessed among children. Insulin resistance was estimated using the homeostasis model assessment (HOMA) and metabolic syndrome was defined using a modified National Cholesterol Education Program definition. None of the micronutrient supplement combinations affected blood pressure, cholesterol, triglycerides, glucose, insulin, or HOMA. There was a reduced risk of microalbuminuria (greater-than-or-equal3.40 mg/mmol creatinine) in the folic acid odds ratio (OR), 0.56; 95%CI, 0.33-0.93; P = 0.02) and folic acid+iron+zinc (OR, 0.53; CI, 0.32-0.89; P = 0.02) groups and a reduced risk of metabolic syndrome in the folic acid group (OR, 0.63; CI, 0.41-0.97; P = 0.03). Maternal supplementation with folic acid or folic acid+iron+zinc reduced the risk of kidney dysfunction and, to some extent, metabolic syndrome among children at 6-8 y of age. Supplementation with multiple micronutrients had no such affect. Future follow-up studies are needed to examine long-term supplementation effects on risk of chronic diseases in adults.
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