Landing M. A. Jarjou

Critical windows for nutritional interventions against stunting.

An analysis of early growth patterns in children from 54 resource-poor countries in Africa and Southeast Asia shows a rapid falloff in the height-for-age z score during the first 2 y of life and no recovery until ≥5 y of age. This finding has focused attention on the period −9 to 24 mo as a window of opportunity for interventions against stunting and has garnered considerable political backing for investment targeted at the first 1000 d. These important initiatives should not be undermined, but the objective of this study was to counteract the growing impression that interventions outside of this period cannot be effective. We illustrate our arguments using longitudinal data from the Consortium of Health Oriented Research in Transitioning collaboration (Brazil, Guatemala, India, Philippines, and South Africa) and our own cross-sectional and longitudinal growth data from rural Gambia. We show that substantial height catch-up occurs between 24 mo and midchildhood and again between midchildhood and adulthood, even in the absence of any interventions. Longitudinal growth data from rural Gambia also illustrate that an extended pubertal growth phase allows very considerable height recovery, especially in girls during adolescence. In light of the critical importance of maternal stature to her childrens health, our arguments are a reminder of the importance of the more comprehensive UNICEF/Sub-Committee on Nutrition Through the Life-Cycle approach. In particular, we argue that adolescence represents an additional window of opportunity during which substantial life cycle and intergenerational effects can be accrued. The regulation of such growth is complex and may be affected by nutritional interventions imposed many years previously.

Maternal plasma 25-hydroxyvitamin D concentration and birthweight, growth and bone mineral accretion of Gambian infants.

Maternal vitamin D deficiency during pregnancy is a recognized risk factor for rickets and osteomalacia in infancy (1). The circulating plasma concentration of 25-hydroxyvitamin D (25OHD), a long-lived metabolite of vitamin D, is used to judge vitamin D status; values below 25 nmol/L are associated with an increased risk of rickets and osteomalacia (1). There is evidence that a low maternal plasma 25OHD in pregnancy may influence the growth and bone mineral accrual of the offspring during foetal life, infancy and childhood. Positive associations have been reported between maternal vitamin D status in pregnancy and birthweight, birth length, length at 1 year and bone mineral accretion at 9 years (2–6), although evidence is conflicting (7,8). These relationships have been observed at concentrations of 25OHD higher than those associated with rickets and osteomalacia, and there are calls to raise the accepted lower threshold of vitamin D sufficiency for pregnant women, most recently to 80 nmol/L (9). On a population basis, plasma 25OHD concentrations above 80 nmol/L are relatively uncommon in countries at temperate latitudes but are more common among people living in the tropics who have abundant skin sunshine exposure (10). To contribute to the debate on the definition of vitamin D sufficiency in pregnancy, we have investigated the influence of maternal plasma 25OHD concentration on foetal and infant growth in a rural area of The Gambia, West Africa (13°N). In this region, there is tropical sunshine all year, the women are farmers who work out-of-doors for much of each day, and local female dress does not restrict regular sunshine exposure to the face, neck, shoulders, arms and feet, especially during farm work and gardening. The study was a secondary analysis of biochemical, anthropometric and bone data from a subset of 125 women and infants collected during a calcium supplementation study of blood pressure in pregnant Gambian women (International Trial Registry: ISRCTN96502494). No significant benefits for foetal and infant growth of maternal calcium supplementation were identified despite the low customary calcium intake in The Gambia (11). The protocol, methods, maternal characteristics and infant data from the detailed study have been published (11). Briefly, women from the rural villages of Keneba and Manduar, West Kiang, The Gambia were recruited at 20 weeks of pregnancy (P20) and randomized to a daily calcium supplement or a matching placebo tablet until parturition (1500 mg Ca as calcium carbonate and microcellulose-lactose, respectively; Nycomed Pharma AS, Asker, Norway). Fasting, early morning blood was collected and anthropometry performed at P20 and 36 weeks of pregnancy (P36). The mean (± SD) age, weight, height and dietary calcium intake of the women at P20 were 27.4 ± 7.5 years, 56.3 ± 6.7 kg, 1.61 ± 0.05 m and 356 ± 190 mg/day, respectively. The median parity (range) was 3 (0–10). Infant birthweight was measured within 24 h of delivery. Weight, crown-heel length and head circumference were measured at 2, 13 and 52 weeks postpartum. In addition, infant bone mineral content (BMC), bone mineral density (BMD) and bone width (BW) or bone area (BA), were measured by single photon absorptiometry of the midshaft radius (Lunar SP2, Lunar Corporation, Madison, WI, USA) and, for a subset (n = 44, 47 and 52 at 2, 13 and 52 weeks, respectively), by whole-body dual-energy X-ray absorptiometry (Lunar DPX+, software version 4.7b, Lunar Corporation). Plasma 25OHD was measured a using radioimmunometric assay (Diasorin Ltd, Wokingham, Berks, UK), with assay performance monitored through the Vitamin D External Quality Assessment Scheme (DEQAS; Endocrine/Oncology Laboratory, Charing Cross Hospital, London, UK). The intra- and inter-assay coefficients of variation were 4% and 100); possible trends in the data with p = 0.01–0.1 were noted. The analysis was conducted on 123 mother–infant pairs; blood samples from two subjects were not available. Mean ± SD 25OHD (range) was: P20 = 103 ± 25 (53–167) nmol/L; P36 = 111 ± 27 (51–189) nmol/L. No subject had a 25OHD value <50 nmol/L, 20% and 16% had 25OHD <80 nmol/L, at P20 and P36, respectively. There was a high degree of within-subject consistency in 25OHD at P20 and P36 (25OHDP36 = 33.2 + [0.79 ± 0.07]× 25OHDP20, p ≤ 0.001, R2 adjusted 51.5%, n = 121); 11% of women had 25OHD <80 nmol/L at both P20 and P36. The mean birthweight of the infants was 2.99 ± 0.36 kg. The infant anthropometric and bone measures during the first year are given in Table 1. No significant relationships or trends in the data were observed between maternal 25OHD concentration using the values at P20, P36 or the mean of the two and any of the following infant measures: birthweight, infant weight, length, head circumference, BMC, BW (or BA), BMD and size-adjusted BMC of the midshaft radius and whole body at any time postpartum. This is illustrated in Figure 1 for birthweight as a function of maternal 25OHD concentration at P20. Comparing the results for mothers with 25OHD above and below 80 nmol/L did not alter this finding. Table 1 Anthropometric and bone measures of Gambian infants Figure 1 Lack of a significant relationship between infant birthweight and maternal vitamin D status at 20 weeks of pregnancy (p = 0.8). Multiple regression model included season, maternal height, weight, weight gain, supplement group and sex of the infant. No significant interaction between supplement group and maternal 25OHD concentration was observed for any infant variable. Trends in the data were observed in a few instances for a supplement group × 25OHD interaction among the bone measures but no consistent picture emerged and they were considered to have arisen by chance. We conclude that there is no evidence for an influence of vitamin D status during pregnancy on infant growth and bone mineral accrual in the conditions prevailing in The Gambia. The children in this study, as is common in this region of The Gambia (13), were born small, grew well for the first months of life but experienced growth faltering during later infancy compared to Western children (11,14), as demonstrated by their weight and length SDS. The 25OHD concentrations of the women were >50 nmol/L in the second half of pregnancy, and no distinction could be drawn in infant outcomes between mothers with concentrations above or below 80 nmol/L. Thus, our study suggests that, for women with regular, adventitious UVB sunshine exposure and in situations where foetal and infant growth may be constrained by multiple factors, there would be no benefit for foetal and infant growth or bone mineral accrual in aiming to increase the vitamin D status of individual mothers during pregnancy above 50 or 80 nmol/L.

The calcium and phosphorus intakes of rural Gambian women during pregnancy and lactation

The Ca and P intakes of 148 pregnant and lactating women in a rural village in The Gambia, West Africa, have been estimated by direct weighing of food on a total of 4188 d. The Ca and P contents of local foods were determined by analysis of raw ingredients, snack foods and prepared dishes. Information about the contribution of mineral-rich seasonings was obtained. Efforts were made to discover unusual sources of Ca that might not be perceived as food by subject or observer. The main contributors to daily Ca intake were shown to be leaves, fish, cereals, groundnuts and local salt. Cows milk accounted for only 5% of Ca intake. Unusual sources of Ca were discovered, namely baobab (Adansonia digitata) fruit and selected earths, but these were consumed infrequently and their contributions to Ca intakes were small. Cereals and groundnuts were the main sources of P. Ca and P intakes (mg/d) were shown to average 404 (SD 110) and 887 (SD 219) respectively. Seasonal changes in the availability of leaves, cereals and groundnuts resulted in variations in Ca and P intakes. The rainy season was associated with increased Ca intakes (by 16%) but decreased P consumption (by 15%). No difference was observed in Ca intake between pregnant and lactating women but P intake in lactation was 11% higher than that in pregnancy during the post-harvest season. The implications of these low Ca intakes require investigation.

The nutritional role of breast-milk IgA and lactoferrin.

ABSTRACT. The nutritional enigma concerning the extent to which breast‐milk immune proteins are digested has been investigated by measuring the intakes and faecal outputs of IgA and lactoferrin over 7 days in 10 exclusively breast‐fed (BF) and 9 formula‐fed (FF) fullterm infants at 6 and 12 weeks post‐partum. BF outputs (mg/day) greatly exceeded FF values (p<0.001): at 6 weeks secretory‐IgA BF=160±28, FF=14±2, lactoferrin BF=M±2, FF=0.9±0.1; at 12 weeks secretory‐IgA BF=94±17, FF=25±5, lactoferrin BF=7±1, FF=1±0.3. Secretory‐IgA represented 42% and 27% of BF faecal protein at 6 and 12 weeks compared with 6% for FF infants at both ages. BF secretory‐IgA outputs were highly correlated with intakes (r=0.83, p<0.001). IgA and lactoferrin outputs and the presence of faecal secretory‐IgA fragments in BF and FF infants were influenced by defaecation rate, suggesting that partial degradation occurred in the large intestine. By 6 weeks post‐partum only 1% lactoferrin and 17% secretory‐IgA intakes appeared in the faeces and 95% breast‐milk protein could be regarded as nutritionally available. The elevated BF outputs of IgA and lactoferrin relative to endogenous excretion suggest, however, that breast‐milk may still make a considerable contribution to intestinal defence mechanisms after the neonatal period despite the small proportion of daily intake which escapes digestion. The protective action of IgA and lactoferrin may also depend on their site of degradation and the nature of fragments.

Effect of calcium supplementation in pregnancy on maternal bone outcomes in women with a low calcium intake

Background: Mobilization of maternal bone mineral partly supplies calcium for fetal and neonatal bone growth and development. Objective: We investigated whether pregnant women with low calcium intakes may have a more extensive skeletal response postpartum that may compromise their short- or long-term bone health. Design: In a subset of participants (n = 125) in a double-blind, randomized, placebo-controlled trial (International Trial Registry: ISRCTN96502494) in pregnant women in The Gambia, West Africa, with low calcium intakes (≈350 mg Ca/d), we measured bone mineral status of the whole body, lumbar spine, and hip by using dual-energy X-ray absorptiometry and measured bone mineral status of the forearm by using single-photon absorptiometry at 2, 13, and 52 wk lactation. We collected blood and urine from the subjects at 20 wk gestation and at 13 wk postpartum. Participants received calcium carbonate (1500 mg Ca/d) or a matching placebo from 20 wk gestation to parturition; participants did not consume supplements during lactation. Results: Women who received the calcium supplement in pregnancy had significantly lower bone mineral content (BMC), bone area (BA), and bone mineral density (BMD) at the hip throughout 12 mo lactation (mean ± SE difference: BMC = −10.7 ± 3.7%, P = 0.005; BA = −3.8 ± 1.9%, P = 0.05; BMD = −6.9 ± 2.6%, P = 0.01). The women also experienced greater decreases in bone mineral during lactation at the lumbar spine and distal radius and had biochemical changes consistent with greater bone mineral mobilization. Conclusions: Calcium supplementation in pregnant women with low calcium intakes may disrupt metabolic adaptation and may not benefit maternal bone health. Further study is required to determine if such effects persist long term or elicit compensatory changes in bone structure.

Calcium economy in human pregnancy and lactation

Pregnancy and lactation are times of additional demand for Ca. Ca is transferred across the placenta for fetal skeletal mineralisation, and supplied to the mammary gland for secretion into breast milk. In theory, these additional maternal requirements could be met through mobilisation of Ca from the skeleton, increased intestinal Ca absorption efficiency, enhanced renal Ca retention or greater dietary Ca intake. The extent to which any or all of these apply, the underpinning biological mechanisms and the possible consequences for maternal and infant bone health in the short and long term are the focus of the present review. The complexities in the methodological aspects of interpreting the literature in this area are highlighted and the inter-individual variation in the response to pregnancy and lactation is reviewed. In summary, human pregnancy and lactation are associated with changes in Ca and bone metabolism that support the transfer of Ca between mother and child. The changes generally appear to be independent of maternal Ca supply in populations where Ca intakes are close to current recommendations. Evidence suggests that the processes are physiological in humans and that they provide sufficient Ca for fetal growth and breast-milk production, without relying on an increase in dietary Ca intake or compromising long-term maternal bone health. Further research is needed to determine the limitations of the maternal response to the Ca demands of pregnancy and lactation, especially among mothers with marginal and low dietary Ca intake, and to define vitamin D adequacy for reproductive women.

Vitamin D Deficiency and Its Health Consequences in Africa

Africa is heterogeneous in latitude, geography, climate, food availability, religious and cultural practices, and skin pigmentation. It is expected, therefore, that prevalence of vitamin D deficiency varies widely, in line with influences on skin exposure to UVB sunshine. Furthermore, low calcium intakes and heavy burden of infectious disease common in many countries may increase vitamin D utilization and turnover. Studies of plasma 25OHD concentration indicate a spectrum from clinical deficiency to values at the high end of the physiological range; however, data are limited. Representative studies of status in different countries, using comparable analytical techniques, and of relationships between vitamin D status and risk of infectious and chronic diseases relevant to the African context are needed. Public health measures to secure vitamin D adequacy cannot encompass the whole continent and need to be developed locally.

Use of bioelectrical impedance analysis to assess body composition in rural Gambian children.

Objective:To validate the Tanita BC-418MA Segmental Body Composition Analyser and four-site skinfold measurements for the prediction of total body water (TBW), percentage fat-free mass (%FFM) and percentage body fat (%BF) in a population of rural Gambian children.Subjects/Methods:One hundred and thirty-three healthy Gambian children (65 males and 68 females). FFM estimated by the inbuilt equations supplied with the Tanita system was assessed by comparison with deuterium oxide dilution and novel prediction equations were produced. Deuterium oxide dilution was also used to develop equations for %BF based on four-site skinfolds (biceps, triceps, subscapular and suprailiac).Results:The inbuilt equations underestimated FFM compared to deuterium oxide dilution in all the sex and age categories (P<0.003), with greater accuracy in younger children and in males. The best prediction of %FFM was obtained from the variables height, weight, sex, impedance, age and four skinfold thickness measurements (adjusted R 2=0.84, root mean square error (MSE)=2.07%).Conclusions:These data suggest that the Tanita instrument may be a reliable field assessment technique in African children, when using population and gender-specific equations to convert impedance measurements into estimates of FFM.

Vitamin D Status Does Not Influence the Breast-Milk Calcium Concentration of Lactating Mothers Accustomed to a Low Calcium Intake

Plasma 25‐hydroxy‐vitamin D and breast‐milk calcium concentration were measured at 3 months of lactation in 60 Gambian mothers accustomed to a low calcium diet, of whom 30 were consuming a calcium supplement and 30 were receiving a placebo, and in 48 British mothers. The plasma 25‐hydroxy‐vitamin D concentration of the Gambian women was not affected by either calcium supplementation (supplemented, 64. 4 ± 2. 5 nmol 1‐1; placebo, 64. 9 ± 3. 5 nmol l‐1; mean ± SE) or season. The British average was lower (53. 9 ± 3. 0 nmol 1‐1, p= 0. 004), owing to marked seasonal effects. The breast‐milk calcium concentration was lower in The Gambia (supplemented, 5. 38 ± 0. 13 mmol 1‐1; placebo, 5. 10 ± 0. 13mmol 1‐1; British, 6. 93 ± 0. 15 mmol 1‐1, p < 0. 0001). There was no relationship between plasma 25‐hydroxy‐vitamin D and breast‐milk calcium concentration in any group. There was no trend towards lower breast‐milk calcium concentration in women with vitamin D status towards the bottom of the normal range or in British women during the winter. This study provides no support for the hypothesis that breast‐milk calcium concentration is influenced by vitamin D status or that lactating women with a low calcium intake are at particular risk of vitamin D deficiency.

The effect of long-term calcium supplementation on indices of iron, zinc and magnesium status in lactating Gambian women

The effect of long-term supplementation with CaCO3 on indices of Fe, Zn and Mg status was investigated in a randomized, double-blind intervention study of sixty lactating Gambian women. The supplement contained 1000 mg Ca and was consumed between meals 5 d/week, for 1 year starting 1.5 weeks postpartum. Compliance was 100%. Plasma ferritin concentration, plasma Zn concentration and urinary Mg output were measured before, during and after supplementation at 1.5, 13, 52 and 78 weeks postpartum. No significant differences in mineral status were observed at any time between women in the supplement and placebo groups. Analysis of the longitudinal data series showed that plasma ferritin and Mg excretion were characteristic of the individual (P < 0.001). Within individuals, ferritin concentration was higher at 1.5 weeks postpartum than later in lactation (P = 0.002). Plasma Zn concentration was lower at 1.5 weeks postpartum than at other times (P < 0.001), an effect which disappeared after albumin correction. Low plasma concentrations of ferritin and Zn indicated that the Gambian women were at high risk of Fe and Zn deficiency. Measurements of alpha 1-antichymotrypsin suggested that the results were not confounded by acute-phase responses. The results of the present study indicate that 1000 mg Ca as CaCO3 given between meals does not deleteriously affect plasma ferritin and Zn concentrations or urinary Mg excretion in women who are at risk of Fe and Zn deficiency.