O Yaw Addo

Maternal height and child growth patterns

Objective To examine associations between maternal height and child growth during 4 developmental periods: intrauterine, birth to age 2 years, age 2 years to mid-childhood (MC), and MC to adulthood. Study design Pooled analysis of maternal height and offspring growth using 7630 mother–child pairs from 5 birth cohorts (Brazil, Guatemala, India, the Philippines, and South Africa). We used conditional height measures that control for collinearity in height across periods. We estimated associations between maternal height and offspring growth using multivariate regression models adjusted for household income, child sex, birth order, and study site. Results Maternal height was associated with birth weight and with both height and conditional height at each age examined. The strongest associations with conditional heights were for adulthood and 2 years of age. A 1-cm increase in maternal height predicted a 0.024 (95% CI: 0.021-0.028) SD increase in offspring birth weight, a 0.037 (95% CI: 0.033-0.040) SD increase in conditional height at 2 years, a 0.025 (95% CI: 0.021-0.029 SD increase in conditional height in MC, and a 0.044 (95% CI: 0.040-0.048) SD increase in conditional height in adulthood. Short mothers (<150.1 cm) were more likely to have a child who was stunted at 2 years (prevalence ratio = 3.20 (95% CI: 2.80-3.60) and as an adult (prevalence ratio = 4.74, (95% CI: 4.13-5.44). There was no evidence of heterogeneity by site or sex. Conclusion Maternal height influences offspring linear growth over the growing period. These influences likely include genetic and non-genetic factors, including nutrition-related intergenerational influences on growth that prevent the attainment of genetic height potential in low- and middle-income countries.

Effectiveness evaluation of the food fortification program of Costa Rica: impact on anemia prevalence and hemoglobin concentrations in women and children

BACKGROUND Food fortification is one approach for addressing anemia, but information on program effectiveness is limited. OBJECTIVE We evaluated the impact of Costa Ricas fortification program on anemia in women aged 15-45 y and children aged 1-7 y. DESIGN Reduced iron, an ineffective fortificant, was replaced by ferrous fumarate in wheat flour in 2002, and ferrous bisglycinate was added to maize flour in 1999 and to liquid and powdered milk in 2001. We used a one-group pretest-posttest design and national survey data from 1996 (baseline; 910 women, 965 children) and 2008-2009 (endline; 863 women, 403 children) to assess changes in iron deficiency (children only) and anemia. Data were also available for sentinel sites (1 urban, 1 rural) for 1999-2000 (405 women, 404 children) and 2008-2009 (474 women, 195 children), including 24-h recall data in children. Monitoring of fortification levels was routine. RESULTS Foods were fortified as mandated. Fortification provided about one-half the estimated average requirement for iron in children, mostly and equally through wheat flour and milk. Anemia was reduced in children and women in national and sentinel site comparisons. At the national level, anemia declined in children from 19.3% (95% CI: 16.8%, 21.8%) to 4.0% (95% CI: 2.1%, 5.9%) and in women from 18.4% (95% CI: 15.8%, 20.9%) to 10.2% (95% CI: 8.2%, 12.2%). In children, iron deficiency declined from 26.9% (95% CI: 21.1%, 32.7%) to 6.8% (95% CI: 4.2%, 9.3%), and iron deficiency anemia, which was 6.2% (95% CI: 3.0%, 9.3%) at baseline, could no longer be detected at the endline. CONCLUSIONS A plausible impact pathway suggests that fortification improved iron status and reduced anemia. Although unlikely in the Costa Rican context, other explanations cannot be excluded in a pre/post comparison.

Age at hormonal onset of puberty based on luteinizing hormone, inhibin B, and body composition in preadolescent US girls

Background:Hormonal indicators could be useful for detecting early pubertal onset, but there is little research on how they are related to puberty in US girls. We determined median age at hormonal onset of puberty based on luteinizing hormone (LH) and inhibin B (InB) and explored the extent to which body composition moderates this timing process.Methods:We analyzed anthropometric and hormone data of 698 US peri-pubertal girls ages 6–11.99 y who had participated in the Third National Health and Nutrition Examination Survey (NHANES III), 1988–1994.Results:Median age of hormonal onset of puberty was 10.43 y by LH and 10.08 y by InB cut-offs (1.04 mIU/ml for LH and 17.89 pg/ml for InB). Postnatal weight gain modulated onset, making it earlier by 10–11 mo among the highest (greater than +1 SD) relative to normal weight gainers. Onset occurred first in non-Hispanic black (NHB) girls, 10.08 y (95% confidence interval (CI): 10.07–10.09), followed by Mexican-American (MXAM) at 10.64 y (95% CI: 10.63–10.65), and at 10.66 y (95% CI: 10.66–10.67) for non-Hispanic white (NHW) girls using LH. With InB, onset occurred first in MXAM girls at 9.9 y, and at 10.3 y and 10.4 y for their NHB and NHW peers, respectively.Conclusion:Preadolescent weight gain lowers the age at hormonal onset as defined by LH concentrations. Preventing obesity in childhood may also avert the earlier initiation of the maturation process even at the hormonal level.

The relative influence of maternal nutritional status before and during pregnancy on birth outcomes in Vietnam

OBJECTIVE This study aimed to: (1) examine the role of multiple measures of prepregnancy nutritional status (weight, height, body composition) on birth outcomes (low birth weight (LBW), small for gestational age (SGA), preterm, birth weight, birth length, infant head circumference and mid-upper arm circumference (MUAC)); (2) assess relative influence of maternal nutritional status before and during (gestational weight gain) pregnancy on birth outcomes. STUDY DESIGN We used prospective data on maternal body size and composition collected from women who participated in a randomized controlled trial evaluating the impact of preconceptional micronutrient supplements (PRECONCEPT) on birth outcomes in Thai Nguyen province, Vietnam (n=1436). Anthropometric measurements were obtained before conception through delivery by trained health workers. The relationship between prepregnancy nutritional status indicators, gestational weight gain (GWG) and birth outcomes were examined using generalized linear models, adjusting for potential confounding factors. RESULTS Maternal prepregnancy weight (PPW) was the strongest anthropometric indicator predicting infant birth size. A 1 standard deviation (SD) increase in PPW (5.4kg) was associated with a 283g (95%CI: 279-286) increase in birthweight. A similar and independent association was observed with birthweight for an increase of 1 SD in gestational weight gain (4kg) (250g; 95% CI: 245-255). Women with a PPW <43kg or who gained <8kg during their pregnancy were more likely to give birth to a SGA (OR 2.9: 95%CI 1.9-4.5, OR 3.3: 95%CI 2.2-5.1) or LBW infant (OR 3.1: 95%CI 1.5-6.2, OR 3.4: 95%CI 1.6-7.2), respectively. CONCLUSIONS These findings indicate that clinical care and programs aimed at improving birth outcomes will have the greatest impact if they address maternal nutrition both before and during pregnancy. Women with a PPW <43kg or a GWG <8kg are at greatest risk for poor birth outcomes in this setting. Preconception counseling and clinical care to obtain a healthy weight prior to pregnancy along with routine obstetric care on gestational weight gain is critical to improve birth outcomes. TRIAL REGISTRATION NCT01665378 (https://clinicaltrials.gov/show/NCT01665378).

Adjusting soluble transferrin receptor concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project

Background: Iron deficiency is thought to be one of the most prevalent micronutrient deficiencies globally, but an accurate assessment in populations who are frequently exposed to infections is impeded by the inflammatory response, which causes iron-biomarker alterations. Objectives: We assessed the relation between soluble transferrin receptor (sTfR) concentrations and inflammation and malaria in preschool children (PSC) (age range: 6–59 mo) and women of reproductive age (WRA) (age range: 15–49 y) and investigated adjustment algorithms to account for these effects. Design: Cross-sectional data from the Biomarkers Reflecting the Inflammation and Nutritional Determinants of Anemia (BRINDA) project from 11,913 PSC in 11 surveys and from 11,173 WRA in 7 surveys were analyzed individually and combined with the use of a meta-analysis. The following 3 adjustment approaches were compared with estimated iron-deficient erythropoiesis (sTfR concentration >8.3 mg/L): 1) the exclusion of individuals with C-reactive protein (CRP) concentrations >5 mg/L or α-1-acid glycoprotein (AGP) concentrations >1 g/L, 2) the application of arithmetic correction factors, and 3) the use of regression approaches. Results: The prevalence of elevated sTfR concentrations incrementally decreased as CRP and AGP deciles decreased for PSC and WRA, but the effect was more pronounced for AGP than for CRP. Depending on the approach used to adjust for inflammation, the estimated prevalence of iron-deficient erythropoiesis decreased by 4.4–14.6 and 0.3–9.5 percentage points in PSC and WRA, respectively, compared with unadjusted values. The correction-factor approach yielded a more modest reduction in the estimated prevalence of iron-deficient erythropoiesis than did the regression approach. Mostly, adjustment for malaria in addition to AGP did not significantly change the estimated prevalence of iron-deficient erythropoiesis. Conclusions: sTfR may be useful to assess iron-deficient erythropoiesis, but inflammation influences its interpretation, and adjustment of sTfR for inflammation and malaria should be considered. More research is warranted to evaluate the proposed approaches in different settings, but this study contributes to the evidence on how and when to adjust sTfR for inflammation and malaria.

Adjusting total body iron for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project

Background: Total body iron (TBI) that is calculated from ferritin and soluble transferrin receptor (sTfR) allows for the evaluation of the full range of iron status from deficiency to excess. However, both ferritin and sTfR are affected by inflammation and malaria, which may require a statistical adjustment. TBI has been used to assess iron status in the United States, but its use worldwide and in settings with inflammation has been limited. Objective: We examine whether inflammation-adjusted ferritin and sTfR concentrations affect TBI values and the prevalence of low TBI (<0 mg/kg) in preschool children (PSC) (age range: 6–59 mo) and women of reproductive age (WRA) (age range: 15–49 y). Design: Cross-sectional data for PSC (8 surveys; n = 8413) and WRA (4 surveys; n = 4258) from the Biomarkers Reflecting the Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed individually and combined. TBI and the prevalence of low TBI were compared following 3 adjustment approaches for ferritin and sTfR: 1) the exclusion of individuals with inflammation (C-reactive protein concentration >5 mg/L or α-1-acid glycoprotein concentration >1 g/L), 2) the application of arithmetic correction factors, and 3) the use of regression correction. Results: Regardless of the method that was used to adjust ferritin and sTfR for inflammation, the adjusted mean TBI decreased in both PSC and WRA compared with unadjusted values. Subsequently, inflammation-adjusted TBI increased the prevalence of low TBI by a median of 4–14 percentage points (pps) in PSC and 1–3 pps in WRA compared with unadjusted TBI. The regression approach resulted in a greater median increase than was achieved with the exclusion or correction-factor approaches, and accounting for malaria in addition to inflammation did not have an added effect on the prevalence estimates. Conclusion: The prevalence of low TBI is underestimated if it is not adjusted by inflammation, particularly in children living in areas with a high prevalence of inflammation.

Adjusting retinol-binding protein concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project

Background: The accurate estimation of the prevalence of vitamin A deficiency (VAD) is important in planning and implementing interventions. Retinol-binding protein (RBP) is often used in population surveys to measure vitamin A status, but its interpretation is challenging in settings where inflammation is common because RBP concentrations decrease during the acute-phase response. Objectives: We aimed to assess the relation between RBP concentrations and inflammation and malaria in preschool children (PSC) (age range: 6–59 mo) and women of reproductive age (WRA) (age range: 15–49 y) and to investigate adjustment algorithms to account for these effects. Design: Cross-sectional data from 8 surveys for PSC (n = 8803) and 4 surveys for WRA (n = 4191) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed individually and combined with the use of a meta-analysis. Several approaches were explored to adjust RBP concentrations in PSC in inflammation and malaria settings as follows: 1) the exclusion of subjects with C-reactive protein (CRP) concentrations >5 mg/L or α-1-acid glycoprotein (AGP) concentrations >1 g/L, 2) the application of arithmetic correction factors, and 3) the use of a regression correction approach. The impact of adjustment on the estimated prevalence of VAD (defined as <0.7 μmol/L) was examined in PSC. Results: The relation between estimated VAD and CRP and AGP deciles followed a linear pattern in PSC. In women, the correlations between RBP and CRP and AGP were too weak to justify adjustments for inflammation. Depending on the approach used to adjust for inflammation (CRP+AGP), the estimated prevalence of VAD decreased by a median of 11–18 percentage points in PSC compared with unadjusted values. There was no added effect of adjusting for malaria on the estimated VAD after adjusting for CRP and AGP. Conclusions: The use of regression correction (derived from internal data), which accounts for the severity of inflammation, to estimate the prevalence of VAD in PSC in regions with inflammation and malaria is supported by the analysis of the BRINDA data. These findings contribute to the evidence on adjusting for inflammation when estimating VAD with the use of RBP.

Is skinfold thickness as good as DXA when measuring adiposity contributions to insulin resistance in adolescents

We compared adiposity from triceps and subscapular skinfold thickness (SF) with total body fat from dual energy X‐ray absorptiometry (DXA) in their associations with HOMA insulin resistance for a large sample of US adolescents.

Predictors of anemia in preschool children: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project

Background: A lack of information on the etiology of anemia has hampered the design and monitoring of anemia-control efforts. Objective: We aimed to evaluate predictors of anemia in preschool children (PSC) (age range: 6–59 mo) by country and infection-burden category. Design: Cross-sectional data from 16 surveys (n = 29,293) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed separately and pooled by category of infection burden. We assessed relations between anemia (hemoglobin concentration <110 g/L) and severe anemia (hemoglobin concentration <70 g/L) and individual-level (age, anthropometric measures, micronutrient deficiencies, malaria, and inflammation) and household-level predictors; we also examined the proportion of anemia with concomitant iron deficiency (defined as an inflammation-adjusted ferritin concentration <12 μg/L). Countries were grouped into 4 categories on the basis of risk and burden of infectious disease, and a pooled multivariable logistic regression analysis was conducted for each group. Results: Iron deficiency, malaria, breastfeeding, stunting, underweight, inflammation, low socioeconomic status, and poor sanitation were each associated with anemia in >50% of surveys. Associations between breastfeeding and anemia were attenuated by controlling for child age, which was negatively associated with anemia. The most consistent predictors of severe anemia were malaria, poor sanitation, and underweight. In multivariable pooled models, child age, iron deficiency, and stunting independently predicted anemia and severe anemia. Inflammation was generally associated with anemia in the high- and very high–infection groups but not in the low- and medium-infection groups. In PSC with anemia, 50%, 30%, 55%, and 58% of children had concomitant iron deficiency in low-, medium-, high-, and very high–infection categories, respectively. Conclusions: Although causal inference is limited by cross-sectional survey data, results suggest anemia-control programs should address both iron deficiency and infections. The relative importance of factors that are associated with anemia varies by setting, and thus, country-specific data are needed to guide programs.

Patterns of Fetal Growth Based on Ultrasound Measurement and its Relationship with Small for Gestational Age at Birth in Rural Vietnam.

BACKGROUND Small for gestational age (SGA) is a global health problem. Identifying the timing of fetal growth faltering is critical for developing preventive interventions. We aim to describe patterns of fetal growth and to predict SGA at birth using fetal ultrasound measurements. METHODS We studied 1412 pregnant women enrolled in a randomised-controlled trial evaluating maternal micronutrient supplementation in Thai Nguyen province, Vietnam. Ultrasound examinations included biparietal diameter (BPD), head circumference (HC) and abdominal circumference (AC), and femur length (FL). Measures were assessed using the new international fetal growth standards (INTERGROWTH-21st Project). Generalised linear mixed logit regression models were used to examine the association between ultrasound measures and SGA at birth. RESULTS Overall fetal growth restriction began in early pregnancy and continued through delivery, but the timing of growth faltering varied by measure: it began by 20 weeks for HC, BPD and AC, earlier as compared to FL growth that started >30 weeks. SGA infants had significantly lower mean fetal growth parameters as early as 14 weeks. Ultrasound measures below the 10th percentile were associated with a two to four times higher risk of SGA at birth compared to fetuses greater than the 50th percentile, with the largest odds ratios for AC (OR 3.9, 95% confidence interval (CI) 2.7, 5.7). CONCLUSIONS Fetal growth faltering by ultrasound begins in early gestation among rural Vietnamese populations; these patterns clearly identified those to be born SGA. Efforts to prevent fetal growth faltering must begin early in pregnancy and perhaps even before pregnancy.