Growth in achondroplasia including stature, weight, weight-for-height and head circumference from CLARITY: achondroplasia natural history study-a multi-center retrospective cohort study of achondroplasia in the US.

BACKGROUND: Achondroplasia is the most common genetic skeletal disorder causing disproportionate short stature/dwarfism. Common additional features include spinal stenosis, midface retrusion, macrocephaly and a generalized spondylometaphyseal dysplasia which manifest as spinal cord compression, sleep disordered breathing, delayed motor skill acquisition and genu varus with musculoskeletal pain. To better understand the interactions and health outcomes of these potential complications, we embarked on a multi-center, natural history study entitled CLARITY (achondroplasia natural history study). One of the CLARITY objectives was to develop growth curves (length/height, weight, head circumference, weight-for-height) and corresponding reference tables of mean and standard deviations at 1 month increments from birth through 18 years for clinical use and research for achondroplasia patients. METHODS: All available retrospective anthropometry data including length/height, weight and head circumference from achondroplasia patients were collected at 4 US skeletal dysplasia centers (Johns Hopkins University, AI DuPont Hospital for Children, McGovern Medical School University of Texas Health, University of Wisconsin School of Medicine and Public Health). Weight-for-age values beyond 3 SD above the mean were excluded from the weight-for-height and weight-for-age curves to create a stricter tool for weight assessment in this population. RESULTS: Over 37,000 length/height, weight and head circumference measures from 1374 patients with achondroplasia from birth through 75 years of age were compiled in a REDCap database. Stature and weight data from birth through 18 years of age and head circumference from birth through 5 years of age were utilized to construct new length/height-for-age, weight-for-age, head circumference-for-age and weight-for-height curves. CONCLUSION: Achondroplasia-specific growth curves are essential for clinical care of growing infants and children with this condition. In an effort to provide prescriptive, rather than purely descriptive, references for weight in this population, extreme weight values were omitted from the weight-for-age and weight-for-height curves. This well-phenotyped cohort may be studied with other global achondroplasia populations (e.g. Europe, Argentina, Australia, Japan) to gain further insight into environmental or ethnic influences on growth.

Achondroplasia Natural History Study (CLARITY): a multicenter retrospective cohort study of achondroplasia in the United States.

PURPOSE: Achondroplasia is the most common short stature skeletal dysplasia (1:20,000-30,000), but the risk of adverse health outcomes from cardiovascular diseases, pain, poor function, excess weight, and sleep apnea is unclear. A multicenter retrospective natural history study was conducted to understand medical and surgical practices in achondroplasia. METHODS: Data from patients with achondroplasia evaluated by clinical geneticists at Johns Hopkins University, A.I. duPont Hospital for Children, McGovern Medical School UTHealth, and University of Wisconsin were populated into a REDCap database. All available retrospective medical records of anthropometry (length/height, weight, occipitofrontal circumference), surgery, polysomnography (PSG), and imaging (e.g., X-ray, magnetic resonance imaging) were included. RESULTS: Data from 1,374 patients (48.8% female; mean age 15.4 ± 13.9 years) constitute the primary achondroplasia cohort (PAC) with 496 subjects remaining clinically active and eligible for prospective studies. Within the PAC, 76.0% had a de novo FGFR3 pathologic variant and 1,094 (79.6%) had one or more achondroplasia-related surgeries. There are ≥37,000 anthropometry values, 1,631 PSGs and 10,727 imaging studies. CONCLUSION: This is the largest multicenter achondroplasia natural history study, providing a vast array of medical information for use in caring for these patients. This well-phenotyped cohort is a reference population against which future medical and surgical interventions can be compared.

Newborn micronutrient status biomarkers in a cluster-randomized trial of antenatal multiple micronutrient compared with iron folic acid supplementation in rural Bangladesh.

BACKGROUND: Daily antenatal multiple micronutrient (MM) compared with iron folic acid (IFA) supplementation from early pregnancy improved birth outcomes and maternal micronutrient status in rural Bangladesh, but effects on newborn status are unknown. OBJECTIVE: We examined cord blood micronutrient biomarkers in relation to antenatal MM and IFA supplementation and maternal gestational micronutrient status in rural Bangladeshi newborns. DESIGN: In a double-blinded, cluster-randomized trial of antenatal IFA or MM (with the same IFA content), we analyzed cord blood plasma from 333 singleton births, and corresponding maternal plasma at 32.5 ± 2.6 wk of gestation, for ferritin (iron stores), folate, cobalamin (vitamin B-12), retinol (vitamin A), 25-hydroxyvitamin D [25(OH)D, vitamin D status], α-tocopherol (vitamin E), zinc, thyroglobulin, and free thyroxine (iodine status). Intervention effects and associations were determined using linear regression, exploring maternal status as a mediator of intervention effects on cord biomarkers. RESULTS: The MM intervention increased cord ferritin (mean: +12.4%; 95% CI: 1.3, 24.6%), 25(OH)D (mean: +14.7%; 95% CI: 4.8, 25.6%), and zinc (mean: +5.8%; 95% CI: 1.0, 10.8%). Cord folate (mean: +26.8%; 95% CI: 19.6, 34.5%), cobalamin (mean: +31.3%; 95% CI: 24.6, 38.3%), 25(OH)D (mean: +26.7%; 95% CI: 23.2, 30.3%), α-tocopherol (mean: +8.7%; 95% CI: 3.6, 13.7%), zinc (mean: +2.3%; 95% CI: 0.5, 4.2%), thyroglobulin (mean: +20.1%; 95% CI: 9.0, 32.2%) and thyroxine (mean: +1.5%; 95% CI: 0.0, 3.0%) increased per 1-SD increment in maternal status (all P < 0.05); ferritin and retinol changed by +2.0%; 95% CI: -8.9, 14.3%; P = 0.72; and +3.5%; 95% CI: -0.4, 7.3%; P = 0.07, respectively. Ferritin, folate, cobalamin, zinc, and thyroglobulin averaged 1.57-6.75 times higher and retinol, α-tocopherol, and 25(OH)D 0.30-0.84 times lower in cord than maternal plasma, suggesting preferential maternal-fetal transfer of iron, folate, cobalamin, and zinc; limited transfer of fat-soluble vitamins; and high fetal iodine demand. CONCLUSIONS: Antenatal MM supplementation increased newborn ferritin, 25(OH)D, and zinc, while maternal and newborn folate, vitamins B-12, D, and E, zinc, and iodine biomarkers were positively related. Despite limited effects of MM, better maternal micronutrient status was associated with improved micronutrient status of Bangladeshi newborns. This trial was registered at clinicaltrials.gov as NCT00860470.

Relative Contributions of Malaria, Inflammation, and Deficiencies of Iron and Vitamin A to the Burden of Anemia during Low and High Malaria Seasons in Rural Zambian Children.

OBJECTIVE: To estimate the burden of anemia attributable to malaria, inflammation, and deficiency of iron or vitamin A during low and high malaria seasons among Zambian children. STUDY DESIGN: From a cohort of children (n = 820), 4-8 years of age participating in a randomized controlled trial of pro-vitamin A, we estimated attributable fractions for anemia (hemoglobin of <110 or 115 g/L, by age) owing to current malaria or inflammation (C-reactive protein of >5 mg/L, or α-1 acid glycoprotein of >1 g/L, or both), and current or prior iron deficiency (ID; defined as low ferritin [<12 or 15 µg/L for age <5 or >5 years] or functional ID [soluble transferrin receptor of >8.3 mg/L] or both) and vitamin A deficiency (retinol of <0.7 µmol/L), during low and high malaria seasons, using multivariate logistic regression. Serum ferritin, soluble transferrin receptor, and retinol were adjusted for inflammation. RESULTS: The burden of anemia independently associated with current malaria, inflammation, ID, and vitamin A deficiency in the low malaria season were 12% (P < .001), 6% (P = .005), 14% (P = .001), and 2% (P = .07), respectively, and 32% (P < .001), 15% (P < .001), 10% (P = .06), and 2% (P = .06), respectively, in the high malaria season. In both seasons, functional ID was independently associated with more anemia (approximately 11%) than low ferritin (approximately 4%). Anemia and ID in the low malaria season, accounted for 20% (P < .001) and 4% (P = .095) of the anemia in the subsequent high malaria season. CONCLUSIONS: Anemia in this population is strongly linked to malaria, inflammation, and functional ID, and to a lesser extent, low iron stores. Integrated control strategies are needed.

Antenatal Multiple Micronutrient Supplementation Compared to Iron-Folic Acid Affects Micronutrient Status but Does Not Eliminate Deficiencies in a Randomized Controlled Trial Among Pregnant Women of Rural Bangladesh.

BACKGROUND: Antenatal multiple micronutrient (MM) supplementation improves birth outcomes relative to iron-folic acid (IFA) in developing countries, but limited data exist on its impact on pregnancy micronutrient status. OBJECTIVE: We assessed the efficacy of a daily MM (15 nutrients) compared with IFA supplement, each providing approximately 1 RDA of nutrients and given beginning at pregnancy ascertainment, on late pregnancy micronutrient status of women in rural Bangladesh. Secondarily, we explored other contributors to pregnancy micronutrient status. METHODS: Within a double-masked trial (JiVitA-3) among 44,500 pregnant women, micronutrient status indicators were assessed in n = 1526 women, allocated by cluster to receive daily MM (n = 749) or IFA (n = 777), at 10 wk (baseline: before supplementation) and 32 wk (during supplementation) gestation. Efficacy of MM supplementation on micronutrient status indicators at 32 wk was assessed, controlling for baseline status and other covariates (e.g., inflammation and season), in regression models. RESULTS: Baseline status was comparable by intervention. Prevalence of deficiency among all participants was as follows: anemia, 20.6%; iron by ferritin, 4.0%; iron by transferrin receptor, 4.7%; folate, 2.5%; vitamin B-12, 35.4%; vitamin A, 6.7%; vitamin E, 57.7%; vitamin D, 64.0%; zinc, 13.4%; and iodine, 2.6%. At 32 wk gestation, vitamin B-12, A, and D and zinc status indicators were 3.7-13.7% higher, and ferritin, γ-tocopherol, and thyroglobulin indicators were 8.7-16.6% lower, for the MM group compared with the IFA group, with a 15-38% lower prevalence of deficiencies of vitamins B-12, A, and D and zinc (all P < 0.05). However, indicators typically suggested worsening status during pregnancy, even with supplementation, and baseline status or other covariates were more strongly associated with late pregnancy indicators than was MM supplementation. CONCLUSIONS: Rural Bangladeshi women commonly entered pregnancy deficient in micronutrients other than iron and folic acid. Supplementation with MM improved micronutrient status, although deficiencies persisted. Preconception supplementation or higher nutrient doses may be warranted to support nutritional demands of pregnancy in undernourished populations. This trial was registered at clinicaltrials.gov as NCT00860470.

Malaria exacerbates inflammation-associated elevation in ferritin and soluble transferrin receptor with only modest effects on iron deficiency and iron deficiency anaemia among rural Zambian children.

OBJECTIVE: In 4- to 8-year-old Zambian children (n = 744), we evaluated the effects of adjusting for inflammation (α1-acid glycoprotein >1 g/l), with or without additional adjustment for malaria, on prevalence estimates of iron deficiency (ID) and iron deficiency anaemia (IDA) during low malaria (LowM) and high malaria (HighM) transmission seasons. METHODS: To estimate adjustment factors, children were classified as: (i) reference (malaria negative without inflammation), (ii) inflammation without malaria (I), (iii) malaria without inflammation (M) and (iv) inflammation with malaria (IM). We estimated the unadjusted ID or IDA prevalence, and then adjusted for inflammation alone (IDI or IDAI ) or inflammation and malaria (IDIM or IDAIM ). RESULTS: Mean ferritin was 38 (reference), 45 (I), 43 (M) and 54 µg/l (IM) in LowM, increasing to 44, 56, 96 and 167 µg/l, respectively, in HighM. Corresponding mean sTfR was 6.4, 6.9, 7.9 and 8.4 mg/l in LowM, increasing to 8.2, 9.2. 8.7 and 9.7 mg/l in HighM. Ferritin-based ID, IDI and IDIM were 7.8%, 8.7% or 9.1%, respectively, in LowM and 4.6%, 10.0% or 11.7%, respectively, in HighM. Corresponding soluble transferrin receptor (sTfR)-based estimates were 27.0%, 24.1% and 19.1%, respectively, in LowM, increasing to 53.6%, 46.5% and 45.3%, respectively, in HighM. Additional adjustment for malaria resulted in a ~1- to 2-percentage point change in IDA, depending on biomarker and season. CONCLUSIONS: In this population, malaria substantially increased ferritin and sTfR concentrations, with modest effects on ID and IDA prevalence estimates.

High Iron Stores in the Low Malaria Season Increase Malaria Risk in the High Transmission Season in a Prospective Cohort of Rural Zambian Children.

Background: Higher iron stores, defined by serum ferritin (SF) concentration, may increase malaria risk.Objective: We evaluated the association between SF assessed during low malaria season and the risk of malaria during high malaria season, controlling for inflammation.Methods: Data for this prospective study were collected from children aged 4-8 y (n = 745) participating in a biofortified maize efficacy trial in rural Zambia. All malaria cases were treated at baseline (September 2012). We used baseline SF and malaria status indicated by positive microscopy at endline (March 2013) to define exposure and outcome, respectively. Iron status was defined as deficient (corrected or uncorrected SF <12 or <15 µg/L, depending on age <5 or ≥5 y, respectively), moderate (<75 µg/L, excluding deficient), or high (≥75 µg/L). We used a modified Poisson regression to model the risk of malaria in the high transmission seasons (endline) as a function of iron status assessed in the low malaria seasons (baseline).Results: We observed an age-dependent, positive dose-response association between ferritin in the low malaria season and malaria incidence during the high malaria season in younger children. In children aged <6 y (but not older children), we observed a relative increase in malaria risk in the moderate iron status [incidence rate ratio (IRR) with SF: 1.56; 95% CI: 0.64, 3.86; IRR with inflammation-corrected SF: 1.92; 95% CI: 0.75, 4.93] and high iron status (IRR with SF: 2.66; 95% CI: 1.10, 6.43; or IRR with corrected SF: 2.93; 95% CI: 1.17, 7.33) categories compared with the deficient iron status category. The relative increase in malaria risk for children with high iron status was statistically significant only among those with a concurrently normal serum soluble transferrin receptor concentration (<8.3 mg/L; IRR: 1.97; 95% CI: 1.20, 7.37).Conclusions: Iron adequacy in 4- to 8-y-old children in rural Zambia was associated with increased malaria risk. Our findings underscore the need to integrate iron interventions with malaria control programs. This trial was registered at clinicaltrials.gov as NCT01695148.

Effect of maternal multiple micronutrient vs iron-folic acid supplementation on infant mortality and adverse birth outcomes in rural Bangladesh: the JiVitA-3 randomized trial.

IMPORTANCE: Maternal micronutrient deficiencies may adversely affect fetal and infant health, yet there is insufficient evidence of effects on these outcomes to guide antenatal micronutrient supplementation in South Asia. OBJECTIVE: To assess effects of antenatal multiple micronutrient vs iron-folic acid supplementation on 6-month infant mortality and adverse birth outcomes. DESIGN, SETTING, AND PARTICIPANTS: Cluster randomized, double-masked trial in Bangladesh, with pregnancy surveillance starting December 4, 2007, and recruitment on January 11, 2008. Six-month infant follow-up ended August 30, 2012. Surveillance included 127,282 women; 44,567 became pregnant and were included in the analysis and delivered 28,516 live-born infants. Median gestation at enrollment was 9 weeks (interquartile range, 7-12). INTERVENTIONS: Women were provided supplements containing 15 micronutrients or iron-folic acid alone, taken daily from early pregnancy to 12 weeks postpartum. MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause infant mortality through 6 months (180 days). Prespecified secondary outcomes in this analysis included stillbirth, preterm birth (<37 weeks), and low birth weight (<2500 g). To maintain overall significance of α = .05, a Bonferroni-corrected α = .01 was calculated to evaluate statistical significance of primary and 4 secondary risk outcomes (.05/5). RESULTS: Among the 22,405 pregnancies in the multiple micronutrient group and the 22,162 pregnancies in the iron-folic acid group, there were 14,374 and 14,142 live-born infants, respectively, included in the analysis. At 6 months, multiple micronutrients did not significantly reduce infant mortality; there were 764 deaths (54.0 per 1000 live births) in the iron-folic acid group and 741 deaths (51.6 per 1000 live births) in the multiple micronutrient group (relative risk [RR], 0.95; 95% CI, 0.86-1.06). Multiple micronutrient supplementation resulted in a non-statistically significant reduction in stillbirths (43.1 vs 48.2 per 1000 births; RR, 0.89; 95% CI, 0.81-0.99; P = .02) and significant reductions in preterm births (18.6 vs 21.8 per 100 live births; RR, 0.85; 95% CI, 0.80-0.91; P < .001) and low birth weight (40.2 vs 45.7 per 100 live births; RR, 0.88; 95% CI, 0.85-0.91; P < .001). CONCLUSIONS AND RELEVANCE: In Bangladesh, antenatal multiple micronutrient compared with iron-folic acid supplementation did not reduce all-cause infant mortality to age 6 months but resulted in a non-statistically significant reduction in stillbirths and significant reductions in preterm births and low birth weight. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00860470.

Aflatoxin exposure during the first 1000 days of life in rural South Asia assessed by aflatoxin B1-lysine albumin biomarkers.

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.

A cross-sectional study of the prevalence and risk factors for hypertension in rural Nepali women.

BACKGROUND: The prevalence of hypertension is increasing in much of the South Asian region, including Nepal. This paper reports the prevalence and risk factors of hypertension and pre-hypertension among adult women in a rural community of Nepal. METHODS: Cross-sectional data on socioeconomic status (SES), lifestyle factors and blood pressure (BP) were collected from a cohort of 15,934 women in rural Nepal in 2006-08. Among a subsample (n = 1679), anthropometry and biomarkers of cardiovascular risk were measured. RESULTS: The mean age of women was 34.2 years (range 16.4-71.2 years). More than three percent (3.3%) had hypertension and 14.4% had pre-hypertension. In an adjusted analysis, lower SES, especially lower household farm assets and storage of food for long term consumption, was associated with increased odds of hypertension (OR = 1.14 for mid-level SES and OR = 1.40 for low SES; p for trend < 0.01). Smoking, alcohol use and not working outside the home were also associated with higher risk. In a subsample, both systolic BP (SBP) and diastolic BP (DBP) were positively associated with high triglycerides (SBP ß = 4.1 mm Hg; DBP ß =3.6 mm Hg), high HbA1c (SBP ß = 14.0; DBP ß = 9.2), raised fasting glucose (SBP ß = 10.0; DBP ß = 6.9), high BMI (SBP ß = 6.7; DBP ß = 5.1) and high waist circumference (SBP ß = 6.2; DBP ß = 5.3) after adjusting for potential confounders (p for all <0.01). CONCLUSIONS: Although the prevalence of hypertension was low in this cohort, it was more prevalent among the poorer women and was strongly associated with other cardiovascular risks. These associations at a relatively young age may confer greater risk for cardiovascular disease among women in later life, indicating the need for interventions to reduce the progression from pre-hypertension to hypertension.

Hepcidin and iron status among pregnant women in Bangladesh.

Although hepcidin, a recently discovered peptide hormone, is considered a major regulator of iron metabolism and anemia in chronic inflammation, its role in anemia during pregnancy has not been characterized. Our objective was to characterize the role of hepcidin in anemia during pregnancy. We examined the relationships between urinary hepcidin, iron status indicators, hemoglobin, erythropoietin, alpha-1 acid glycoprotein, and C-reactive protein in a cross-sectional study conducted among 149 pregnant rural Bangladeshi women with biospecimens obtained during home visits. Urinary hepcidin was measured using surface-enhanced laser desorption/ ionization time-of-flight mass spectrometry. Urinary hepcidin, as log(intensity per mmol/L creatinine), was correlated with log ferritin (r = 0.33, p <0.001), the transferrin receptor index (r = -0.22, p = 0.007), and log alpha-1 acid glycoprotein (r = 0.20, p = 0.01), but not hemoglobin (r = 0.07, p= 0.40), log transferrin receptor (r = -0.07, p = 0.41), log erythropoietin (r = -0.01, p = 0.88) or log C-reactive protein (r = 0.06, p = 0.48). The strength of the relationship between hepcidin and ferritin was maintained in multiple linear regression analyses after enhancing the sample with data from women selected for low iron stores (n = 41). Among pregnant women in a community-based study in rural Bangladesh, urinary hepcidin levels were related to iron status and AGP but not hemoglobin, erythropoietin, or C-reactive protein.

Age-appropriate body mass index in children with achondroplasia: interpretation in relation to indexes of height.

BACKGROUND: Achondroplasia is the most common short stature skeletal dysplasia, with an estimated worldwide prevalence of 250 000. Body mass index (BMI)-for-age references are required for weight management guidance for children with achondroplasia, whose body proportions are unlike those of the average stature population. OBJECTIVE: This study used weight and height data in a clinical setting to derive smoothed BMI-for-age percentile curves for children with achondroplasia and explored the relation of BMI with its components, weight and height. DESIGN: This was a longitudinal observational study of anthropometric measures of children with achondroplasia from birth through 16 y of age. RESULTS: The analysis included 1807 BMI data points from 280 children (155 boys, 125 girls) with achondroplasia. As compared with the BMI of peers of average stature, the BMI in children with achondroplasia is higher at birth, lacks a steep increase in infancy and a later nadir between 1 and 2 y of age, and remains substantially higher through 16 y of age in both sexes. Patterns of change in height and weight in children with achondroplasia are unique in that there is no overlap in the height distribution after 6 mo of age and no spike in height velocity during infancy or puberty-the 2 periods of greatest linear growth in individuals of average stature. CONCLUSIONS: Sex- and age-specific BMI curves are available for children with achondroplasia (birth to 16 y of age) for health surveillance and future research to determine associations with health outcomes (eg, cardiovascular disease, diabetes, and indication for and outcome of surgery).

Calcium kinetics are altered in clinically stable girls with cystic fibrosis.

Reduced bone mass in individuals with cystic fibrosis (CF) may result from alterations in calcium metabolism. Bone calcium deposition and resorption rates, calcium balance, and markers of bone turnover were assessed using stable isotopes of calcium in 22 prepubertal and pubertal girls with CF. Bone calcium deposition was associated with the availability of dietary calcium, total serum osteocalcin, and leptin concentrations. Reduced bone mass in individuals with CF may result from inadequate bone calcium (Ca) deposition, and excessive resorption, although these parameters have not been directly assessed in children with CF. We used stable Ca isotopes to measure rates of bone Ca deposition (Vo+), resorption, and retention in 22 clinically stable girls with CF (aged 7-18 yr). Rates of bone Ca deposition were determined by mathematically modeling the disappearance of iv Ca stable isotope ((42)Ca) for 6 d post dosing. Indirect markers of bone turnover and hormones associated with pubertal development were also assessed. Rates of bone Ca deposition and retention were highest during early puberty (Tanner stages 2 and 3). Calcium deposition rates in prepubertal (Tanner 1) and postmenarchal girls (Tanner stages 4 and 5) did not support substantial bone Ca retention. Net absorption of dietary Ca and serum osteocalcin and leptin concentrations were positively associated with Vo+. Time post menarche and serum leptin concentrations explained 91% of the variability in Vo+ (P = 0.0007). Serum total osteocalcin was low (10.9 +/- 5.4 ng/ml), and a substantial percentage of osteocalcin was undercarboxylated (54.3 +/- 11.8%). We concluded that increased calcium absorption and serum leptin concentrations were significantly associated with rates of bone Ca deposition, demonstrating an impact of nutritional status on this process. Rates of bone Ca deposition were lower than typically reported in healthy children, as were indirect markers of bone formation. These alterations in bone turnover contribute to reduced bone mass in girls with CF.

Endogenous fecal losses of calcium compromise calcium balance in pancreatic-insufficient girls with cystic fibrosis.

OBJECTIVE: Bone mineral density is compromised in individuals with cystic fibrosis (CF); calcium is the major bone mineral. This study examined the impact of endogenous fecal calcium (V(endo)) losses on calcium balance in girls with CF. Study design V(endo) was measured in 12 girls with CF (aged 7-18 years): 7 younger, premenarcheal girls with compromised nutritional status; and 5 older, postmenarcheal girls with adequate nutritional status. V(endo) was measured as the amount of intravenously administered (42)Ca, a calcium stable isotope, in stool relative to urine over 6 days. V(endo) was compared between pre- and postmenarcheal girls by Student's t test. Actual calcium balance [absorbed calcium-(urinary calcium (V(u))+V(endo))] was compared with estimated balance (assuming V(endo)=1.6 mg/kg/day calcium) by paired t test. RESULTS: V(endo) was 99.3+/-42.3 mg/day. By body weight, V(endo) was highest among premenarcheal girls (3.37+/-1.09 mg/kg/day), resulting in excess losses (>1.6 mg/kg/day) of 55.0+/-45.7 mg/day. Over 1 year, this represents 20.1+/-16.7 g of unattained bone calcium or 6.7+/-4.2% of the bone calcium content of these girls. CONCLUSIONS: V(endo) is a significant source of calcium loss in individuals with CF and may limit calcium availability for bone mineral deposition.

Efficiency of calcium absorption is not compromised in clinically stable prepubertal and pubertal girls with cystic fibrosis.

BACKGROUND: Reduced bone mass is common in both children and adults with cystic fibrosis (CF) and may be a consequence of inadequate calcium absorption. The effect of CF on intestinal calcium absorption and retention has not been described in children. OBJECTIVE: Calcium absorption and urinary losses were characterized in clinically stable girls with CF consuming self-selected diets and following usual pancreatic enzyme regimens. DESIGN: The percentage of calcium absorption was assessed in 23 girls (aged 7-18 y) with CF by using oral ((44)Ca) and intravenous ((42)Ca) stable isotopes. Girls were grouped according to Tanner stage of breast development. True calcium absorption (V(a)) was determined as the product of percentage calcium absorption and average 4-d daily calcium intake. Calcium balance was estimated by subtracting urinary calcium and estimated endogenous fecal losses from the measure of V(a). Analysis of variance was used to compare outcomes among pubertal groups, and regression analysis was used to describe the relations of percentage and total calcium absorption to calcium intake and of urinary calcium to sodium excretion. RESULTS: Percentage calcium absorption was inversely related to calcium intake. Percentage absorption and V(a) were similar to values observed in healthy girls in other studies. Total calcium absorption and estimated calcium balance were significantly greater among girls in early puberty (Tanner stages 2-3) than in prepubertal or late-pubertal girls (P < 0.05). Urinary calcium was positively related to urinary sodium excretion (P = 0.02). CONCLUSION: The efficiency of calcium absorption was not compromised in clinically stable girls with CF.