Effects of maternal calcium supplementation on offspring blood pressure and growth in childhood and adolescence in a population with a low-calcium intake: follow-up study of a randomized controlled trial.

BACKGROUND: The World Health Organization recommends calcium supplementation (1500-2000 mg/d) during pregnancy for women with a low-calcium intake. OBJECTIVES: The purpose of this study was to investigate whether pregnancy calcium supplementation affects offspring blood pressure and growth in The Gambia where calcium intakes are low (300-400 mg/d). METHODS: Follow-up of offspring born during a randomized controlled trial of pregnancy calcium supplementation (ISRCTN96502494, 1996-2000) in which mothers were randomly assigned to 1500 mg Ca/d (Ca) or placebo (P) from 20 wk pregnancy to delivery. Offspring were enrolled at age 3 y in studies where blood pressure and anthropometry were measured under standardized conditions at approximately 2-yearly intervals. Mean blood pressure and growth curves were fitted for females and males separately, using the longitudinal SuperImposition by Translation and Rotation (SITAR) mixed effects model. This generates 3 individual-specific random effects: size, timing, and intensity, reflecting differences in size, age at peak velocity, and peak velocity through puberty relative to the mean curve, respectively. RESULTS: Five hundred twenty-three singleton infants were born during the trial (maternal group assignment: Ca/P = 259/264). Four hundred ninety-one were enrolled as children (females: F-Ca/F-P = 122/129 and males: M-Ca/M-P = 119/121) and measured regularly from 3.0 y to mean age 18.4 y; 90% were measured on ≥8 occasions. SITAR revealed differences in the systolic blood pressure and height curves between pregnancy supplement groups in females, but not in males. F-Ca had lower systolic blood pressure than F-P at all ages (size = -2.1 ± SE 0.8 mmHg; P = 0.005) and lower peak height velocity (intensity = -2.9 ± SE 1.1%, P = 0.009). No significant pregnancy supplement effects were seen for other measures. CONCLUSIONS: This study showed, in female offspring, that pregnancy calcium supplementation may lower systolic blood pressure and slow linear growth in childhood and adolescence, adding to evidence of offspring sexual dimorphism in responses to maternal supplementation. Further research is warranted on the long-term and intergenerational effects of antenatal supplementations. This trial was registered at ISRCTN Registry as ISRCTN96502494.

Cross-Calibration of iDXA and pQCT Scanners at Rural and Urban Research Sites in The Gambia, West Africa.

Between-scanner differences in measures of bone and body composition can obscure or exaggerate physiological differences in multi-site studies or the magnitude of changes in longitudinal studies. We conducted a cross-calibration study at two bone imaging centres in The Gambia, West Africa where DXA (dual-energy X-ray absorptiometry) and pQCT (peripheral Quantitative-Computed Tomography) are routinely used. Repeat scans were obtained from 64 Gambian adults (58% Male) aged Mean(SD) 30.9 (13.5) years with Mean(SD) body mass index (BMI) 21.7 (4.0) kg/m2, using DXA (GE Lunar iDXA, whole body [WB], total hip [TH], lumbar spine [LS]) and pQCT (Stratec XCT2000L/XCT2000, tibia 4%, 50% sites). Between-scanner differences were tested using paired t tests (p < 0.05). Between-scanner correlation was explored with linear regression, and cross-calibration equations derived. Bland-Altman analysis investigated machine trend/bias. When differences were detected (p < 0.05), cross-calibration equations were applied to urban values, with t tests and Bland Altman analysis repeated. Between-scanner differences exceeded the predefined level of statistical significance (p < 0.05) for WB aBMD and BA; all pQCT measures vBMD, BMC, cortical cross-sectional area (CSA) and stress-strain index (SSI). Between-scanner correlation was high (R2:0.92-0.99), except pQCT Mu.Den (R2 = 0.51). Bland Altman plots indicated bias increased with increasing BMD. Cross-calibration equations attenuated all between-scanner differences and systematic bias. Cross-calibration, particularly of pQCT scanners, is an important consideration in multi-site studies particularly where between population comparisons are intended. Our experiences and findings may be generalisable to other resource-limited settings where the logistics of sourcing parts and in-country repair may result in lengthy scanner downtime.

Longitudinal Change in Bone Density, Geometry, and Estimated Bone Strength in Older Men and Women From The Gambia: Findings From the Gambian Bone and Muscle Aging Study (GamBAS).

Musculoskeletal aging in the most resource-limited countries has not been quantified, and longitudinal data are urgently needed to inform policy. The aim of this prospective study was to describe musculoskeletal aging in Gambian adults. A total of 488 participants were recruited stratified by sex and 5-year age band (aged 40 years and older); 386 attended follow-up 1.7 years later. Outcomes were dual-energy X-ray absorptiometry (DXA) (n = 383) total hip areal bone mineral density (aBMD), bone mineral content (BMC), bone area (BA); peripheral quantitative computed tomography (pQCT) diaphyseal and epiphyseal radius and tibia (n = 313) total volumetric BMD (vBMD), trabecular vBMD, estimated bone strength indices (BSIc), cross-sectional area (CSA), BMC, and cortical vBMD. Mean annualized percentage change in bone outcomes was assessed in 10-year age bands and linear trends for age assessed. Bone turnover markers, parathyroid hormone (PTH), and 25-hydroxyvitamin D (25(OH)D) were explored as predictors of change in bone. Bone loss was observed at all sites, with an annual loss of total hip aBMD of 1.2% in women after age 50 years and in men at age 70 years plus. Greater loss in vBMD and BSIc was found at the radius in both men and women; strength was reduced by 4% per year in women and 3% per year in men (p trend 0.02, 0.03, respectively). At cortical sites, reductions in BMC, CSA, and vBMD were observed, being greatest in BMC in women, between 1.4% and 2.0% per annum. Higher CTX and PINP predicted greater loss of trabecular vBMD in women and BMC in men at the radius, and higher 25(OH)D with less loss of tibial trabecular vBMD and CSA in women. The magnitude of bone loss was like those reported in countries where fragility fracture rates are much higher. Given the predicted rise in fracture rates in resource-poor countries such as The Gambia, these data provide important insights into musculoskeletal health in this population. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Sex-specific associations between cardiovascular risk factors and physical function: the Gambian Bone and Muscle Ageing Study.

BACKGROUND: In Sub-Saharan Africa, the prevalence of obesity, cardiovascular disease (CVD) and impaired physical function are increasing due to rapid urbanization. We investigated sex differences in associations between cardiac workload, arterial stiffness, peripheral vascular calcification (PVC) and physical function in Gambian adults. METHODS: A total of 488 Gambians aged 40-75+ years were recruited (men: 239; and women: 249). Supine blood pressure and heart rate were measured to calculate rate pressure product and pulse pressure. Presence of PVC was determined from tibia peripheral quantitative computed tomography scans. Physical function was assessed by chair rise test (CRT), single two-legged jump (s2LJ) and hand grip strength (HGS). Body composition was measured by dual-energy x-ray absorptiometry; body size corrections were used to calculate fat mass index (FMI) and appendicular lean mass index (ALMI). Estimated glomerular filtration rate (eGFR) was measured from fasting blood samples. The relationship between rate pressure product, pulse pressure or presence of PVC (independent variable) with physical function parameters (dependent variable) was tested using linear regression. Sex-interactions were tested (p-int) adjusting for age, eGFR and ALMI/FMI. Results were expressed as mean differences between men and women with 95% confidence intervals. Mediation analyses used ALMI/FMI as mediator. RESULTS: Women weighed less (54.7 kg ± 10.3 vs. 59.9 kg ± 10.3) and were shorter (157.8 cm ± 6.0 vs. 169.2 cm ± 7.0) compared with men (both P < 0.0001). Women had higher FMI (6.8 kg/m2  ± 2.9 vs. 2.9 kg/m2  ± 2.0, P < 0.0001) and eGFR (263.7 mL/min/1.73 m2  ± 133.1 vs. 237.6 mL/min/1.73 m2  ± 134.6), but lower ALMI (6.2 kg/m2  ± 0.7 vs. 8.02 kg/m2  ± 1.0, P < 0.0001) compared with men. There were significant mean differences between men and women in rate pressure product and s2LJ power (-1.08 [-1.21, -0.95]) and force (-0.57 [-0.63, -0.51]), only after adjusting for age, eGFR and FMI. There were significant mean differences in the associations between pulse pressure and CRT power (-0.28 [-0.31, -0.25]), s2LJ power (-1.07 [-1.20, -0.93]) and HGS (-11.94 [-13.35, -10.54]); these differences were greater after adjusting for age, eGFR and FMI, than ALMI. There were similar differences in the associations between PVC and physical function parameters. In men, FMI mediated the association between rate pressuree product and CRT power (P = 0.002), s2LJ force (P < 0.001) and s2LJ power (P = 0.001). ALMI did not mediate associations for either men or women. CONCLUSIONS: Multiple risk factors for CVD were associated with poorer physical function in men and were mediated by FMI. There is a need to identify strategies to slow/prevent the rising CVD burden and poor physical function in Sub-Saharan Africa.

Pregnancy-Related Change in pQCT and Bone Biochemistry in a Population With a Habitually Low Calcium Intake.

In pregnancy, changes in maternal calcium (Ca) economy occur to satisfy fetal Ca demand. It is unclear whether maternal mineral reserves facilitate these requirements and no data exist from sub-Saharan Africa. The aim was to determine skeletal changes with peripheral quantitative computed tomography (pQCT) and bone biochemistry between early second and third trimesters. Pregnant rural Gambians aged 18 to 45 years (n = 467) participating in a trial of antenatal nutritional supplements (ISRCTN49285450) had pQCT scans and blood collections at mean (SD) 14 (3) and 31 (1) weeks' gestation. Outcomes were pQCT: radius/tibia 4% total volumetric bone mineral density (vBMD), trabecular vBMD, total cross-sectional area (CSA), 33%/38% radius/tibia cortical vBMD, bone mineral content (BMC), total CSA; biochemistry: collagen type 1 cross-linked ß-C-telopeptide (ß-CTX), type 1 procollagen N-terminal (P1NP), parathyroid hormone (PTH), and 1,25(OH)2 D. Independent t tests tested whether pooled or within-group changes differed from 0. Multiple regression was performed adjusting for age. Data for change are expressed as mean (confidence interval [CI] 2.5, 97.5%). Radius trabecular vBMD, cortical vBMD, and BMC increased by 1.15 (0.55, 1.75)%, 0.41 (0.24, 0.58)%, and 0.47 (0.25, 0.69)%. Tibia total and trabecular vBMD increased by 0.34 (0.15, 0.54)% and 0.46 (0.17, 0.74)%, while tibia cortical vBMD, BMC, and cortical CSA increased by 0.35 (0.26, 0.44)%, 0.55 (0.41, 0.68)% and 0.20 (0.09, 0.31)%, respectively. CTX, PTH, and 1,25(OH)2 D increased by 23.0 (15.09, 29.29)%, 13.2 (8.44, 19.34)%, and 21.0 (17.67, 24.29)%, while P1NP decreased by 32.4 (-37.19, -28.17)%. No evidence of mobilization was observed in the peripheral skeleton. Resorption, although higher in late versus early gestation, was lower throughout pregnancy compared with non-pregnant non-lactating (NPNL) in the same community. Formation was lower in late pregnancy than in early, and below NPNL levels. This suggests a shift in the ratio of resorption to formation. Despite some evidence of change in bone metabolism, in this population, with habitually low Ca intakes, the peripheral skeleton was not mobilized as a Ca source for the fetus. © 2021 crown copyright . Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). The article published with the permission of the Controller of HMSO and the Queen's Printer of Scotland..

Sex-Specific Associations Between Cardiac Workload, Peripheral Vascular Calcification, and Bone Mineral Density: The Gambian Bone and Muscle Aging Study.

Noncommunicable diseases (NCD) are rapidly rising in Africa, with multimorbidity increasing the burden on health and social care. Osteoporosis and cardiovascular disease (CVD) share common risk factors; both often remain undiagnosed until a major life-threatening event occurs. We investigated the associations between cardiac workload, peripheral vascular calcification (PVC), and bone parameters in Gambian adults. The Gambian Bone and Muscle Aging Study (GamBAS) recruited 249 women and 239 men aged 40 to 75+ years. Body composition and areal bone mineral density (aBMD) were measured using dual-energy X-ray absorptiometry; peripheral quantitative computed tomography (pQCT) scans were performed at the radius and tibia. Supine blood pressure and heart rate were measured and used to calculate rate pressure product and pulse pressure. Presence of PVC was determined from tibia pQCT scans. Sex interactions were tested (denoted as p-int); adjustments were made for residuals of appendicular lean mass (ALM) and fat mass (FM). There were negative associations between rate pressure product and aBMD in women only, all p-int < .05; after adjustment for ALM residuals, for every 10% increase in rate pressure product, aBMD was lower at the whole body (-0.6% [-1.2, -0.1]), femoral neck (-0.9% [-1.8, -0.05]), L1 to L4 (-0.6% [-1.7, 0.5]), and radius (-1.9% [-2.8, -0.9]); there were similar associations when adjusted for FM residuals. Similar negative associations were found between pulse pressure and aBMD in women only. PVC were found in 26.6% men and 22.5% women; women but not men with calcification had poorer cardiac health and negative associations with aBMD (all sites p-int < .001). There were consistent associations with cardiac parameters and pQCT outcomes at the radius and tibia in women only. Multiple markers of cardiac health are associated with poorer bone health in Gambian women. In the context of epidemiological transition and changing NCD burden, there is a need to identify preventative strategies to slow/prevent the rising burden in CVD and osteoporosis in Sub-Saharan Africa. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Exploring influences on adolescent diet and physical activity in rural Gambia, West Africa: food insecurity, culture and the natural environment.

OBJECTIVE: To explore, from the perspectives of adolescents and caregivers, and using qualitative methods, influences on adolescent diet and physical activity in rural Gambia. DESIGN: Six focus group discussions (FGD) with adolescents and caregivers were conducted. Thematic analysis was employed across the data set. SETTING: Rural region of The Gambia, West Africa. PARTICIPANTS: Participants were selected using purposive sampling. Four FGD, conducted with forty adolescents, comprised: girls aged 10-12 years; boys aged 10-12 years; girls aged 15-17 years, boys aged 15-17 years. Twenty caregivers also participated in two FGD (mothers and fathers). RESULTS: All participants expressed an understanding of the association between salt and hypertension, sugary foods and diabetes, and dental health. Adolescents and caregivers suggested that adolescent nutrition and health were shaped by economic, social and cultural factors and the local environment. Adolescent diet was thought to be influenced by: affordability, seasonality and the receipt of remittances; gender norms, including differences in opportunities afforded to girls, and mother-led decision-making; cultural ceremonies and school holidays. Adolescent physical activity included walking or cycling to school, playing football and farming. Participants felt adolescent engagement in physical activity was influenced by gender, seasonality, cultural ceremonies and, to some extent, the availability of digital media. CONCLUSIONS: These novel insights into local understanding should be considered when formulating future interventions. Interventions need to address these interrelated factors, including misconceptions regarding diet and physical activity that may be harmful to health.

The prevalence of sarcopenia and relationships between muscle and bone in ageing West-African Gambian men and women.

BACKGROUND: The rapidly rising ageing population in low and middle-income countries (LMIC) will lead to a concurrent increase in musculoskeletal diseases. Sarcopenia is a disease caused by progressive loss of skeletal muscle mass and strength, leading to adverse outcomes including frailty, falls, fractures, and premature mortality. We investigated the prevalence of sarcopenia, assessed the suitability of current diagnostic guidelines and explored muscle-bone relationships in ageing men and women from rural Gambia. METHODS: A total of 249 women and 239 men aged 40-75+ years were recruited. Body composition was measured using dual energy X-ray absorptiometry. Comparisons of the Foundations for the National Institutes of Health (FNIH) and European Working Group On Sarcopenia (EWGSOP) definitions of sarcopenia to define prevalence and to identify poor physical capability were determined. Functional ability was assessed by jumping mechanography to calculate lower limb muscle force and power; grip strength was assessed by a hand dynamometer. Peripheral quantitative computed tomography was used to assess muscle-bone relationships. RESULTS: The prevalence of sarcopenia in Gambian men and women significantly varied depending on the definition used; in men 20% and 19% and in women 45% and 10% for FNIH and EWGSOP, respectively. The FNIH appendicular lean mass cut-off had greatest sensitivity and specificity in identifying low functional ability in Gambian adults. Muscle force was positively associated with measures of tibial bone size, strength, and mineral content. CONCLUSIONS: The variation in the prevalence of sarcopenia depends on the definition used and highlights the importance of measuring functional capability across ethnic populations.

Corrigendum: The Gambian Bone and Muscle Ageing Study: Baseline Data From a Prospective Observational African Sub-Saharan Study.

[This corrects the article on p. 219 in vol. 8, PMID: 28912754.].

The Gambian Bone and Muscle Ageing Study: Baseline Data from a Prospective Observational African Sub-Saharan Study.

The Gambian Bone and Muscle Ageing Study is a prospective observational study investigating bone and muscle ageing in men and women from a poor, subsistence farming community of The Gambia, West Africa. Musculoskeletal diseases, including osteoporosis and sarcopenia, form a major part of the current global non-communicable disease burden. By 2050, the vast majority of the world's ageing population will live in low- and middle-income countries with an estimated two-fold rise in osteoporotic fracture. The study design was to characterise change in bone and muscle outcomes and to identify possible preventative strategies for fracture and sarcopenia in the increasing ageing population. Men and women aged ≥40 years from the Kiang West region of The Gambia were recruited with stratified sampling by sex and age. Baseline measurements were completed in 488 participants in 2012 who were randomly assigned to follow-up between 1.5 and 2 years later. Follow-up measurements were performed on 465 participants approximately 1.7 years after baseline measurements. The data set comprises a wide range of measurements on bone, muscle strength, anthropometry, biochemistry, and dietary intake. Questionnaires were used to obtain information on health, lifestyle, musculoskeletal pain, and reproductive status. Baseline cross-sectional data show preliminary evidence for bone mineral density and muscle loss with age. Men had greater negative differences in total body lean mass with age than women following adjustments for body size. From peripheral quantitative computed tomography scans, greater negative associations between bone outcomes and age at the radius and tibia were shown in women than in men. Ultimately, the findings from The Gambian Bone and Muscle Ageing Study will contribute to the understanding of musculoskeletal health in a transitioning population and better characterise fracture and sarcopenia incidence in The Gambia with an aim to the development of preventative strategies against both.

Diurnal rhythms of vitamin D binding protein and total and free vitamin D metabolites.

Vitamin D binding protein (DBP) concentration is known to influence the availability and bioactivity of vitamin D metabolites but its diurnal rhythm (DR), its inter-relationships with the DRs of vitamin D metabolites and its influence on free vitamin D metabolite concentrations are not well described. The DRs of plasma total 25(OH)D, total 1,25(OH)2D, DBP, albumin and calculated free 25(OH)D and free 1,25(OH)2D were measured in men and women aged 60-75 years and resident in the UK (n 30), Gambia (n 31) and China (n 30) with differences in lifestyle, dietary intake and vitamin D status. Blood samples were collected every 4h for 24h and DRs statistically analysed with Fourier regression. Gambians had significantly higher plasma concentrations of vitamin D metabolites and lower albumin concentration compared to the British and Chinese. Significant DRs were observed for all analytes and calculated free vitamin D metabolites (P<0.01). The pattern of DRs was similar between countries. The magnitude of the DRs of free 1,25(OH)2D was attenuated compared to that of total 1,25(OH)2D whereas it was not different between total and free 25(OH)D. Relationships between the DRs were generally weak. There was no phase shift between 1,25(OH)2D and DBP with the strongest cross correlation at 0h time lag (r=0.15, P=<0.001). In comparison, 25(OH)D correlated less well with DBP (1h time lag, r=0.07, P=0.12). These data demonstrate a relationship between the DRs of 1,25(OH)2D and DBP, possibly to maintain free 1,25(OH)2D concentrations. In contrast, the DRs of total and free 25(OH)D appeared to be less influenced by DBP, suggesting that DBP has comparatively less effect on 25(OH)D concentration and 25(OH)D availability. This work highlights the importance of standardisation in timing of sample collection particularly for the assessment of plasma protein concentrations.

Long-term effects of maternal calcium supplementation on childhood growth differ between males and females in a population accustomed to a low calcium intake.

The importance of adequate calcium intakes for healthy growth and bone development has long been recognised. Recent evidence suggests that calcium supplementation may have sex-specific effects on bone growth in childhood. The aim was to describe the long-term effects of calcium supplementation in pregnant Gambian women with a low calcium intake (ISCRTN96502494) on offspring height, weight, bone and body composition in childhood, and whether the effects differ by sex. Children of mothers who participated in the original calcium supplementation trial were measured at age 8-12years using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Linear models tested for sex*supplement interactions before and after adjusting for current age and size in early life. 447 children, aged 9.2(SD 0.9) years, were measured. Significant sex*supplement interactions (p<0.05) were observed for many of the anthropometric and bone outcomes, Females whose mothers received calcium (F-Ca) were shorter, lighter with smaller bones and less bone mineral than those whose mothers received placebo (F-P), differences (SE) ranged from height=-1.0 (0.5)% to hip BMC -5.5 (2.3)%. Males from mothers in the calcium group (M-Ca) had greater mid-upper arm circumference (MUAC) (+2.0 (1.0)%, p=0.05) and fat mass (+11.6 (5.1)%, p=0.02) and tended towards greater BMC and size than those whose mothers were in the placebo group (M-P). The differences in anthropometry and body composition were robust to adjustment for current height and weight, whereas all bone differences became non-significant. F-P were taller with more BMC than M-P, whereas F-Ca had similar sized bones and mineral content to M-Ca. Calcium supplementation of pregnant women with low calcium intakes altered the childhood trajectories of growth and bone and body composition development of their offspring in a sex-specific manner, resulting in slower growth among females compared to placebo and accelerated growth among males by age 8-12years.

Diurnal Rhythms of Bone Turnover Markers in Three Ethnic Groups.

CONTEXT: Ethnic groups differ in fragility fracture risk and bone metabolism. Differences in diurnal rhythms (DRs) of bone turnover and PTH may play a role. OBJECTIVE: We investigated the DRs of plasma bone turnover markers (BTMs), PTH, and 1,25(OH)2D in three groups with pronounced differences in bone metabolism and plasma PTH. PARTICIPANTS: Healthy Gambian, Chinese, and white British adults (ages 60-75 years; 30 per country). INTERVENTIONS: Observational study with sample collection every 4 hours for 24 hours. MAIN OUTCOMES: Levels of plasma C-terminal telopeptide of type I collagen, procollagen type-1 N-propeptide, N-mid osteocalcin, bone alkaline phosphatase, PTH, and 1,25-dihydroxyvitamin D were measured. DRs were analyzed with random-effects Fourier regression and cross-correlation and regression analyses to assess associations between DRs and fasting and 24-hour means of BTMs and PTH. RESULTS: Concentrations of BTMs, PTH, and 1,25-dihydroxyvitamin D were higher in Gambians compared to other groups (P < .05). The DRs were significant for all variables and groups (P < .03) and were unimodal, with a nocturnal peak and a daytime nadir for BTMs, whereas PTH had two peaks. The DRs of BTMs and PTH were significantly cross-correlated for all groups (P < .05). There was a significant positive association between C-terminal telopeptide of type I collagen and PTH in the British and Gambian groups (P = .03), but not the Chinese group. CONCLUSIONS: Despite ethnic differences in plasma BTMs and PTH, DRs were similar. This indicates that alteration of rhythmicity and loss of coupling of bone resorption and formation associated with an elevated PTH in other studies may not uniformly occur across different populations and needs to be considered in the interpretation of PTH as a risk factor of increased bone loss.

Randomized, placebo-controlled, calcium supplementation trial in pregnant Gambian women accustomed to a low calcium intake: effects on maternal blood pressure and infant growth.

BACKGROUND: Dietary calcium intake in rural Gambian women is very low (∼350 mg/d) compared with international recommendations. Studies have suggested that calcium supplementation of women receiving low-calcium diets significantly reduces risk of pregnancy hypertension. OBJECTIVE: We tested the effects on blood pressure (BP) of calcium carbonate supplementation (1500 mg Ca/d) in pregnant, rural Gambian women. DESIGN: The study was a randomized, double-blind, parallel, placebo-controlled supplementation trial from 20 wk of gestation (P20) until delivery (calcium: n = 330; placebo; n = 332). BP and anthropometric measures were taken at P20 and then 4 weekly until 36 wk of gestation (P36), and infant anthropometric measures were taken at 2, 13, and 52 wk postdelivery. RESULTS: A total of 525 (calcium: n = 260; placebo: n = 265) women had BP measured at P36 and subsequently delivered a healthy term singleton infant. Mean compliance was 97%, and urinary calcium measures confirmed the group allocation. At P20, the mean (±SD) systolic blood pressure (SBP) was 101.2 ± 9.0 and 102.1 ± 9.3 mm Hg, and diastolic blood pressure (DBP) was 54.5 ± 7.3 and 55.8 ± 7.8 mm Hg, in the calcium and placebo groups, respectively. The intention-to-treat analysis that was adjusted for confounders showed no significant effect of calcium supplementation on the change between P20 and P36 (calcium compared with placebo; mean ± SEM) in SBP (-0.64 ± 0.65%; P = 0.3) or DBP (-0.22 ± 1.15%; P = 0.8). There was no significant effect of supplementation on BP, pregnancy weight gain, weight postpartum, or infant weight, length, and other measures of growth. However, the comparability of the original randomly assigned groups may have been compromised by the exclusion of 20.7% of women from the final analysis. CONCLUSIONS: Calcium supplementation did not affect BP in pregnancy. This result may have been because the Gambian women were adapted to a low dietary calcium intake, and/or obesity, high gestational weight gain, high underlying BP, tobacco use, alcohol consumption, and sedentary lifestyles were rare. This trial was registered at the International Standard Randomized Controlled Trial Register (www.controlled-trials.com/mrct/) as ISRCTN96502494.

Unexpected long-term effects of calcium supplementation in pregnancy on maternal bone outcomes in women with a low calcium intake: a follow-up study.

BACKGROUND: Calcium supplementation of pregnant Gambian women with a low calcium intake results in lower maternal bone mineral content in the subsequent lactation. OBJECTIVE: The objective was to investigate whether the lower bone mineral content persists long term. DESIGN: All women in the calcium supplementation trial (International Trial Registry ISRCTN96502494) who had been scanned with dual-energy X-ray absorptiometry at 52 wk of lactation (L52; n = 79) were invited for follow-up when neither pregnant nor lactating for ≥3 mo (NPNL) or at 52 wk postpartum in a future lactation (F52). Bone scans and anthropometric and dietary assessments were conducted. RESULTS: Sixty-eight women participated (35 at both NPNL and F52 and 33 at only one time point): n = 59 NPNL (n = 31 calcium, n = 28 placebo) and n = 44 F52 (n = 24 calcium, n = 20 placebo). The mean (±SD) time from L52 was 4.9 ± 1.9 y for NPNL and 5.0 ± 1.3 y for F52. Size-adjusted bone mineral content (SA-BMC) was greater at NPNL than at L52 in the placebo group (P ≤ 0.001) but not in the calcium group (P for time-by-group interaction: lumbar spine, 0.002; total hip, 0.03; whole body, 0.03). No significant changes in SA-BMC from L52 to F52 were observed in either group. Consequently, the lower SA-BMC in the calcium group at L52 persisted at NPNL and F52 (P ≤ 0.001): NPNL (lumbar spine, -7.5 ± 0.7%; total hip, -10.5 ± 1.0%; whole body, -3.6 ± 0.5%) and F52 (lumbar spine, -6.2 ± 0.9%; total hip, -10.3 ± 1.4%; whole body, -3.2 ± 0.6%). CONCLUSION: In rural Gambian women with a low-calcium diet, a calcium supplement of 1500 mg/d during pregnancy resulted in lower maternal bone mineral content in the subsequent lactation that persisted long term. This trial was registered at www/controlled-trials.com/mrct/ as ISRCTN96502494.

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 children's 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.

A randomized trial to investigate the effects of pre-natal and infant nutritional supplementation on infant immune development in rural Gambia: the ENID trial: Early Nutrition and Immune Development.

BACKGROUND: Recent observational research indicates that immune development may be programmed by nutritional exposures early in life. Such findings require replication from trials specifically designed to assess the impact of nutritional intervention during pregnancy on infant immune development. The current trial seeks to establish: (a) which combination of protein-energy (PE) and multiple-micronutrient (MMN) supplements would be most effective; and (b) the most critical periods for intervention in pregnancy and infancy, for optimal immune development in infancy. METHODS/DESIGN: The ENID Trial is a 2 x 2 x 2 factorial randomized, partially blind trial to assess whether nutritional supplementation to pregnant women (from < 20 weeks gestation to term) and their infants (from 6 to 12 months of age) can enhance infant immune development. Eligible pregnant women from the West Kiang region of The Gambia (pregnancy dated by ultrasound examination) are randomized on entry to 4 intervention groups (Iron-folate (FeFol = standard care), multiple micronutrients (MMN), protein-energy (PE), PE + MMN). Women are visited at home weekly for supplement administration and morbidity assessment and seen at MRC Keneba at 20 and 30 weeks gestation for a detailed antenatal examination, including ultrasound. At delivery, cord blood and placental samples are collected, with detailed infant anthropometry collected within 72 hours. Infants are visited weekly thereafter for a morbidity questionnaire. From 6 to 12 months of age, infants are further randomized to a lipid-based nutritional supplement, with or without additional MMN. The primary outcome measures of this study are thymic development during infancy, and antibody response to vaccination. Measures of cellular markers of immunity will be made in a selected sub-cohort. Subsidiary studies to the main trial will additionally assess the impact of supplementation on infant growth and development to 24 months of age. DISCUSSION: The proposed trial is designed to test whether nutritional repletion can enhance early immune development and, if so, to help determine the most efficacious form of nutritional support. Where there is evidence of benefit from a specific intervention/combination of interventions, future research should focus on refining the supplements to achieve the optimal, most cost-effective balance of interventions for improved health outcomes.

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.