Generalized metabolic bone disease and fracture risk in Rothmund-Thomson syndrome.

Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by poikiloderma, small stature, sparse hair, skeletal abnormalities, increased risk of osteosarcoma, and decreased bone mass. To date, there has not been a comprehensive evaluation of the prevalence and extent of metabolic bone disease in RTS. Furthermore, the mechanisms that result in this phenotype are largely unknown. In this report, we provide a detailed evaluation of 29 individuals with RTS with respect to their metabolic bone status including bone mineral density, calcium kinetics studies, and markers of bone remodeling. We show that individuals with RTS have decreased areal bone mineral density. Additionally, we demonstrate that the presence of pathogenic variants in RECQL4 and low bone mineral density correlate with the history of increased risk of fractures. Using a RECQL4-deficient mouse model that recapitulates skeletal abnormalities seen in individuals with RTS, we demonstrate that generalized skeletal involvement is likely due to decreased osteogenesis. Our findings are clinically relevant as they may help in the risk stratification of patients with RTS and also in the identification of individuals who may benefit from additional surveillance and management of metabolic bone disease.

Oxytocin, a main breastfeeding hormone, prevents hypertension acquired in utero: A therapeutics preview.

Hypertension is a major risk factor for ischemic heart disease and stroke, leading causes of morbidity and death worldwide. Intrauterine growth restriction (IUGR), caused by an excess of glucocorticoid exposure to the fetus, produces an imbalance in oxidative stress altering many biochemical and epigenetic gene transcription processes exposing the fetus and neonate to the 'thrifty' phenotype and pervasive polymorphisms appearance damaging health, cognitive, and behavioral processes in later life. OT is a major regulator of oxidative stress radicals that plays a major role in neonatal maturation of the central nervous system and many peripheral tissues expressing oxytocin/oxytocin-receptor (OT/OTR) system in the early postnatal period. OT and OTR are damaged by IUGR and early stress. This review highlights the fact that hypertension is likely to be a legacy of preterm birth due to IUGR and failure to meet nutritional needs in early infancy when fed formula instead of breastfeeding or human milk.

Delayed Introduction of Parenteral Phosphorus Is Associated with Hypercalcemia in Extremely Preterm Infants.

BACKGROUND: Early parenteral nutrition (PN) provides essential macro- and micronutrients for extremely low birth weight (ELBW) infants <1000 g. Frequent cases of hypercalcemia [whole blood ionized calcium (iCa) > 1.45 mmol/L] in the first week of life while receiving PN solutions at our large quaternary center prompted investigation and 2 plan-do-study-act (PDSA) cycles to reduce rates of hypercalcemia. OBJECTIVE: We compared 2 cohorts of ELBW infants separated by PDSA cycles to evaluate and reduce the incidence of abnormal iCa concentration. METHODS: Data were recorded for 150 premature infants with mean birth weight of 726 ± 164 g, 48% male, and mean gestational age of 26 ± 2.1 wk. This process included an internal practice analysis and PDSA cycles monitored prospectively over 3 y. From December 2011 to September 2012, 66 infants received 0-1.2 mmol parenteral phosphorus supplementation/(kg ⋅ d) beginning at 72 h of life. In the second protocol, 84 infants born September 2012 to July 2013 received earlier phosphorus supplementation within 24 h of life. The peak whole blood iCa and serum phosphorus concentrations in the first week of life were monitored. RESULTS: Early introduction of phosphorus was significantly associated with a decreased mean peak iCa (1.64 ± 0.27 mmol/L to 1.50 ± 0.23 mmol/L, P = 0.001), and the incidence of severe hypercalcemia (iCa > 1.60 mmol/L) decreased from 50.0% to 21.4% (P = 0.002) in the first week of life. There was no difference in mortality, bronchopulmonary dysplasia, renal calcifications, seizures within 7 d of birth, brain calcifications, or intracranial hemorrhage between cohorts. CONCLUSION: Early introduction of phosphorus in PN solutions is associated with reduced incidence of whole blood iCa abnormalities in the first week of life and should be considered for ELBW infants. Ongoing evaluation of optimal mineral provision to this population after birth should be performed.

Randomized trial of human milk cream as a supplement to standard fortification of an exclusive human milk-based diet in infants 750-1250 g birth weight.

OBJECTIVE: To evaluate whether premature infants who received an exclusive human milk (HM)-based diet and a HM-derived cream supplement (cream) would have weight gain (g/kg/d) at least as good as infants receiving a standard feeding regimen (control). STUDY DESIGN: In a prospective noninferiority, randomized, unmasked study, infants with a birth weight 750-1250 g were randomly assigned to the control or cream group. The control group received mother's own milk or donor HM with donor HM-derived fortifier. The cream group received a HM-derived cream supplement if the energy density of the HM tested <20 kcal/oz using a near infrared HM analyzer. Infants were continued on the protocol until 36 weeks postmenstrual age. Primary outcomes included growth velocities and amount of donor HM-derived fortifier used. The hypothesis of noninferiority was established if the lower bound of the one-sided 95% CI for the difference in weight velocities exceeded -3 g/kg/day. RESULTS: There were no differences between groups in baseline demographics for the 78 infants studied except racial distribution (P = .02). The cream group (n = 39) had superior weight (14.0 ± 2.5 vs 12.4 ± 3.0 g/kg/d, P = .03) and length (1.03 ± 0.33 vs 0.83 ± 0.41 cm/wk, P = .02) velocity compared with the control group (n = 39). There were no significant differences in amount of fortifier used between study groups. The 1-sided 95% lower bound of the CI for the difference in mean velocity (cream-control) was 0.38 g/kg/d. CONCLUSIONS: Premature infants who received HM-derived cream to fortified HM had improved weight and length velocity compared with the control group. HM-derived cream should be considered an adjunctive supplement to an exclusive HM-based diet to improve growth rates in premature infants.

Malnutrition in Spinal Muscular Atrophy Type I: Case Report of a Novel Nutritional Intervention With Improved Growth and Function While Receiving Parallel Gene Splicing Therapies.

Children with spinal muscular atrophy (SMA) frequently experience feeding intolerance and diminished growth. Although splicing modulators to prevent symptoms are available worldwide, adequate nutrition to support growth, development, and improved quality of life remains essential. We present a case study of a one-year-old malnourished male with SMA type I who achieved improved growth and feeding tolerance with a human milk (HM)-derived nutrition intervention. Despite feeding with appropriately balanced semielemental formula, he remained severely malnourished after two months of hospitalization. Feeds were partially replaced with HM-based diet plus a HM-based fat modular. Feeding tolerance, fecal calprotectin levels, and z scores for weight and length improved while receiving the HM-based intervention. We hypothesize that the HM-based feeding reduced intestinal inflammation by diminishing pathogenic elements of his microbiome. Owing to their aberrant fatty acid metabolism, patients with SMA are uniquely positioned to benefit from HM-based nutrient acquisition even while receiving splicing modulators to stabilize the disease process.

High rates of resolution of cholestasis in parenteral nutrition-associated liver disease with fish oil-based lipid emulsion monotherapy.

OBJECTIVE: To determine factors leading to resolution of cholestasis in patients with parenteral nutrition-associated liver disease treated with fish oil-based lipid emulsion (FOLE). STUDY DESIGN: Prospective observational study of 57 infants <6 months of age with parenteral nutrition-associated liver disease who received parenteral FOLE as monotherapy. RESULTS: Median gestational age of subjects at birth was 28 weeks (range 22.7-39.5). Median conjugated bilirubin level at initiation of therapy with FOLE was 7.5 mg/dL (range 2.1-25). Resolution of hyperbilirubinemia (conjugated bilirubin <2.0 mg/dL) and survival to hospital discharge occurred in 47 (82.5%) infants. Median number of days to resolution of cholestasis was 35 (range 7-129). Ten infants (17.5%) died. Non-survivors showed a trend towards being more premature than survivors at birth (25.9 vs 29.1 weeks, P = .056). Infants with higher conjugated bilirubin at initiation of therapy (>10.0 compared with <5.0 mg/dL) had longer times to resolution (98 vs 56 days, P < .005). Time to resolution correlated inversely with gestational age at birth (r(2) = 0.14, P = .02) and directly with time to receive 100% calories enterally (r(2) = 0.12, P = .03). CONCLUSIONS: Younger gestational age infants demonstrated higher degree of cholestasis, longer time to resolution of cholestasis, and increased mortality. Higher levels of cholestasis were associated with longer time to resolution. FOLE monotherapy led to resolution of cholestasis in all surviving infants.

Inclusion of guava enhances non-heme iron bioavailability but not fractional zinc absorption from a rice-based meal in adolescents.

Assessing the bioavailability of non-heme iron and zinc is essential for recommending diets that meet the increased growth-related demand for these nutrients. We studied the bioavailability of iron and zinc from a rice-based meal in 16 adolescent boys and girls, 13-15 y of age, from 2 government-run residential schools. Participants were given a standardized rice meal (regular) and the same meal with 100 g of guava fruit (modified) with (57)Fe on 2 consecutive days. A single oral dose of (58)Fe in orange juice was given at a separate time as a reference dose. Zinc absorption was assessed by using (70)Zn, administered intravenously, and (67)Zn given orally with meals. The mean hemoglobin concentration was similar in girls (129 ± 7.8 g/L) and boys (126 ± 7.1 g/L). There were no sex differences in the indicators of iron and zinc status except for a higher hepcidin concentration in boys (P < 0.05). The regular and modified meals were similar in total iron (10-13 mg/meal) and zinc (2.7 mg/meal) content. The molar ratio of iron to phytic acid was >1:1, but the modified diet had 20 times greater ascorbic acid content. The absorption of (57)Fe from the modified meal, compared with regular meal, was significantly (P < 0.05) greater in both girls (23.9 ± 11.2 vs. 9.7 ± 6.5%) and boys (19.2 ± 8.4 vs. 8.6 ± 4.1%). Fractional zinc absorption was similar between the regular and modified meals in both sexes. Hepcidin was found to be a significant predictor of iron absorption (standardized ß = -0.63, P = 0.001, R(2) = 0.40) from the reference dose. There was no significant effect of sex on iron and zinc bioavailability from meals. We conclude that simultaneous ingestion of guava fruit with a habitual rice-based meal enhances iron bioavailability in adolescents.

Effects of ethnicity and vitamin D supplementation on vitamin D status and changes in bone mineral content in infants.

BACKGROUND: To evaluate the effects on serum 25(OH)D and bone mineralization of supplementation of breast-fed Hispanic and non-Hispanic Caucasian infants with vitamin D in infants in Houston, Texas. METHODS: We measured cord serum 25(OH)D levels, bone mineral content (BMC), bone mineral density (BMD) and their changes over 3 months of life with 400 IU/day of vitamin D3 supplementation. RESULTS: Cord serum 25(OH)D was significantly lower in Hispanic than non-Hispanic Caucasian infants (16.4 ± 6.5 ng/mL, n = 27, vs 22.3 ± 9.4 n = 22, p = 0.013). Among 38 infants who completed a 3 month vitamin D supplementation intervention, provision of 400 IU/day of vitamin D increased final 25(OH)D to a higher level in non-Hispanic Caucasian compared to Hispanic infants. There was no significant relationship between cord serum 25(OH)D and BMC or BMD in the first week of life (n = 49) or after 3 months of vitamin D supplementation. CONCLUSION: Low cord 25(OH)D levels are seen in Hispanic infants, but their functional significance is uncertain related to bone health in a southern US setting. Daily vitamin D intake of 400 IU during the first months of life appears adequate to increase serum 25(OH)D and support BMC increases despite low initial 25(OH)D levels in some infants. TRIAL REGISTRATION: ClincalTrials.gov NCT00697294.

Total calcium absorption is similar from infant formulas with and without prebiotics and exceeds that in human milk-fed infants.

BACKGROUND: 1) To evaluate calcium absorption in infants fed a formula containing prebiotics (PF) and one without prebiotics (CF). 2) To compare calcium absorption from these formulas with a group of human milk-fed (HM) infants. METHODS: A dual tracer stable isotope method was used to assess calcium absorption in infants exclusively fed CF (n = 30), PF (n = 25) or HM (n = 19). Analysis of variance was used to analyze calcium intake, fractional calcium absorption, and the amount of calcium absorbed. RESULTS: Calcium intake (Mean ± SEM) for PF was 534 ± 17 mg/d and 557 ± 16 mg/d for CF (p = 0.33). Fractional calcium absorption was 56.8 ± 2.6 % for PF and 59.2 ± 2.3 % for CF (p = 0.49). Total calcium absorbed for PF was 300 ± 14 mg/d and 328 ± 13 mg/d for CF (p = 0.16). For HM infants calcium intake was 246 ± 20 mg/d, fractional calcium absorption was 76.0 ± 2.9 % and total calcium absorbed was 187 ± 16 mg/d (p <0.001, compared to either PF or CF). CONCLUSIONS: Despite lower fractional calcium absorption of CF and PF compared to HM, higher calcium content in both led to higher total calcium absorption compared to HM infants. No significant effect of prebiotics was observed on calcium absorption or other markers of bone mineral metabolism.

Neurodevelopmental outcomes of extremely preterm infants fed an exclusive human milk-based diet versus a mixed human milk + bovine milk-based diet: a multi-center study.

OBJECTIVE: The objective of this multi-center study was to compare, in infants ≤1250 g birth weight (BW) with neurodevelopmental assessment at 18-22 months of corrected age (CA), whether their neurodevelopmental outcomes differed based on exposure to an exclusive human milk-based (HUM) or to a bovine milk-based fortifier and/or preterm formula (BOV). STUDY DESIGN: Retrospective multi-center cohort study of infants undergoing neurodevelopmental assessment as to whether HUM or BOV exposure related to differences in outcomes of infants at 18-22 months CA, using the Bayley Scales of Infant Development III (BSID-III). BSID-III cognitive, language, and motor scores were adjusted for BW, sex, study site, and necrotizing enterocolitis. RESULTS: 252 infants from 6 centers were included. BSID-III cognitive scores were higher in the HUM group (96.5 ± 15.1 vs 89.6 ± 14.1, adjusted p = 0.0001). Mean BSID-III language scores were 85.5 ± 15.0 in HUM and 82.2 ± 14.1 in BOV (adjusted p = 0.09). Mean BSID-III motor scores were 92.9 ± 11.7 in HUM and 91.4 ± 14.6 in BOV (adjusted p = 0.32). CONCLUSION: In this cohort of infants undergoing neurodevelopmental assessment, infants receiving HUM diet had significantly higher cognitive BSID-III scores at 18-22 months CA. Further investigation is needed of this potential for HUM to positively influence infant cognitive outcomes.

Calcium absorption in very low birth weight infants with and without bronchopulmonary dysplasia.

OBJECTIVE: To evaluate the effects of early bronchopulmonary dysplasia (BPD) on calcium (Ca) metabolism and growth in very low birth weight (VLBW) infants. STUDY DESIGN: A dual-tracer, stable isotope method was used to assess Ca absorption in VLBW infants. Infants with early BPD received energy-dense feedings and mild fluid restriction. RESULTS: Sixteen of 41 preterm infants were classified as having early BPD. Fractional Ca absorption (early BPD, 58.4 ± 4.6% versus no early BPD, 50.3 ± 4.0%, P = .2), total Ca absorption (early BPD, 127 ± 14 mg/kg/d versus no early BPD, 104 ± 9 mg/kg/d, P = .9), and Ca retention (early BPD, 99.6 ± 10.0 mg/kg/d versus no early BPD, 91.0 ± 9.8 mg/kg/d, P = .2) were similar among groups. There was no significant difference in weight gain, linear growth, or head circumference growth between groups. CONCLUSIONS: The ability of VLBW infants with early BPD and fluid restriction to grow and accrete calcium is similar to those without early BPD. The use of high caloric density feedings in VLBW infants with early BPD can help achieve bone and overall growth outcomes close to those achievable in utero.

Nutritional impact of elevated calcium transport activity in carrots.

Nutrition recommendations worldwide emphasize ingestion of plant-based diets rather than diets that rely primarily on animal products. However, this plant-based diet could limit the intake of essential nutrients such as calcium. Osteoporosis is one of the world's most prevalent nutritional disorders, and inadequate dietary calcium is a known contributor to the pathophysiology of this condition. Previously, we have modified carrots to express increased levels of a plant calcium transporter (sCAX1), and these plants contain approximately 2-fold-higher calcium content in the edible portions of the carrots. However, it was unproven whether this change would increase the total amount of bioavailable calcium. In randomized trials, we labeled these modified carrots with isotopic calcium and fed them to mice and humans to assess calcium bioavailability. In mice feeding regimes (n = 120), we measured (45)Ca incorporation into bones and determined that mice required twice the serving size of control carrots to obtain the calcium found in sCAX1 carrots. We used a dual-stable isotope method with (42)Ca-labeled carrots and i.v. (46)Ca to determine the absorption of calcium from these carrots in humans. In a cross-over study of 15 male and 15 female adults, we found that when people were fed sCAX1 and control carrots, total calcium absorption per 100 g of carrots was 41% +/- 2% higher in sCAX1 carrots. Both the mice and human feeding studies demonstrate increased calcium absorption from sCAX1-expressing carrots compared with controls. These results demonstrate an alternative means of fortifying vegetables with bioavailable calcium.

Growth outcomes of small for gestational age preterm infants before and after implementation of an exclusive human milk-based diet.

OBJECTIVE: Small for gestational age (SGA) preterm infants (PT) are at greatest risk for growth failure. Our objective was to assess the impact of an exclusive human milk diet (HUM) on growth velocities and neonatal morbidities from birth to discharge in a SGA population. STUDY DESIGN: Multicenter, retrospective cohort study, subgroup analysis of SGA PT comparing a cow's milk diet (CMD) with HUM diet. RESULTS: At birth 420 PT were classified as SGA (197 CMD group, 223 HUM group). Demographics and anthropometric measurements were similar. HUM group PT showed improvement in length Z score at discharge (p = 0.024) and reduction in necrotizing enterocolitis (NEC) (p = 0.004). CONCLUSION: SGA PT fed a HUM diet had significantly decreased incidence of NEC, surgical NEC, and late-onset sepsis. Due to concerns about growth in a HUM diet, it is reassuring SGA infants fed the HUM diet had similar growth to CMD diet with trends toward improvement.

Human milk-based fortifier is associated with less alteration of milk fat globule size than cow milk-based fortifier.

We aimed to evaluate if human milk-based fortifier (HMBF) affects human milk fat globule (MFG) size less than cow milk-based fortifier (CMBF), which may impact overall infant feeding tolerance. Measurements of donated human milk were performed before fortification as well as at 1 hour, 24 hours, and 48 hours after fortification with CMBF or HMBF. MFG size in each sample of fortified milk was measured by laser light scattering. MFG size in the fortified milks increased gradually over time. At 24 and 48 hours after fortification, MFG size in the milk with CMBF was larger than that in the milk with HMBF (4.8 ± 0.5 vs 4.3 ± 0.3 µm, p<0.01, 5.1 ± 0.7 vs 4.5 ± 0.4 µm, p = 0.03, respectively). HMBF is associated with less alteration of MFG size than CMBF. This may have an impact on feeding tolerance of very preterm infants.

Orange but not apple juice enhances ferrous fumarate absorption in small children.

OBJECTIVE: Ferrous fumarate is a common, inexpensive iron form increasingly used instead of ferrous sulfate as a food iron supplement. However, few data exist as to whether juices enhance iron absorption from ferrous fumarate. SUBJECTS AND METHODS: We studied 21 children, ages 4.0 to 7.9 years using a randomized crossover design. Subjects consumed a small meal including a muffin containing 4 mg Fe as ferrous fumarate and either apple (no ascorbic acid) or orange juice (25 mg ascorbic acid). They were separately given a reference dose of Fe (ferrous sulfate) with ascorbic acid. RESULTS: Iron absorption increased from 5.5% +/- 0.7% to 8.2% +/- 1.2%, P < 0.001 from the muffins given with orange juice compared with muffins given with apple juice. The absorption of ferrous fumarate given with orange juice and enhancement of absorption by the presence of juice were significantly positively related to height, weight, and age (P < 0.01 for each). Although iron absorption from ferrous fumarate given with apple juice was significantly inversely associated with the (log transformed) serum ferritin, the difference in absorption between juice types was not (P > 0.9). CONCLUSIONS: These data demonstrate an overall benefit to iron absorption from ferrous fumarate provided with orange juice. The effect was age related such that in children older than 6 years of age, there was a nearly 2-fold increase in iron absorption from ferrous fumarate given with orange juice.

High Level of Food Insecurity among Families with Children Seeking Routine Care at Federally Qualified Health Centers during the Coronavirus Disease 2019 Pandemic.

OBJECTIVE: To assess food insecurity during pediatric visits to federally qualified health centers (FQHCs) during the coronavirus disease-19 pandemic. STUDY DESIGN: Interviews using the validated American Academy of Pediatrics 2-question food insecurity screen were performed with 200 consecutive families presenting for pediatric care to 2 FQHC in Central Texas from April 14 to May 20, 2020, during the initial phase of the pandemic in Texas. Brief qualitative interviews were conducted to determine whether families found a worsening of food insecurity during the pandemic. RESULTS: Overall, 47% of families had a positive food insecurity screen. More than 90% of these were worrying about food running out and about 60% were positive for the question related to food not lasting. Among families with food insecurity, 94% indicated this had begun or worsened during the pandemic. Of the 115 families volunteering information about employment, 46% reported job loss during this time period. Both ethnicity (P < .001) and Special Supplementation Nutrition Program for Women, Infants and Children (WIC) participation (P = .03) were associated with greater levels of food insecurity. Among primarily Spanish-speaking families participating in the WIC program, 64% reported food insecurity. CONCLUSIONS: Approximately one-half of families receiving routine pediatric care at a FQHC during the coronavirus disease-19 pandemic reported food insecurity and this was associated with loss of jobs during the pandemic. Participation in the WIC program was not protective against food insecurity. Increased frequency of food insecurity was detected in Hispanic and Spanish-speaking families. Screening of families at an FQHC should be strongly considered as a part of routine pediatric care. Knowledge of community resources is important for providers to share with patients. (J Pediatr: X 2020;4:100044). TRIAL REGISTRATION: ClinicalTrials.gov: NCT04378595.

Growth, Body Composition, and Neurodevelopmental Outcomes at 2 Years Among Preterm Infants Fed an Exclusive Human Milk Diet in the Neonatal Intensive Care Unit: A Pilot Study.

Background: Long-term outcomes of preterm infants fed an exclusive human milk-based (EHM) diet using a donor human milk-based fortifier are not well defined. Materials and Methods: Infants ≤1,250 g birth weight (BW) were studied prospectively at two outpatient visits: 12-15 and 18-22 months corrected age (CA). Dual-energy X-ray absorptiometry and Bayley Scales of Infant and Toddler Development III (BSID-III) were performed at 18-22 months CA. Results: In this pilot study, 51 preterm infants (gestational age 27.8 ± 2.6 weeks and BW 893 ± 204 g) were evaluated. While anthropometric z-scores were significantly lower at discharge compared with birth, z-scores returned to birth levels by 12-15 months CA (length and head circumference [HC]) and 18-22 months CA (weight). Body composition at 2 years of age was similar to term-matched controls. Inpatient growth was significantly correlated with bone density, lean mass (LM), and fat-free mass at 18-22 months CA. Increased mother's own milk (MOM) was significantly correlated with decreased fat mass indices. BSID-III showed that 0% of cognitive composite scores were <70. Conclusions: In addition to returning to BW, length, and HC z-scores by 2 years of age, body composition analysis revealed that increase in body size was appropriate as reflected by LM and bone density similar to matched term controls without an increase in fat mass. No child had severe cognitive developmental delay using a cutoff score of 70. Inpatient growth and increased receipt of MOM correlated with favorable growth and body composition outcomes. Positive outcomes as shown in this study to confirm postdischarge safety of an EHM diet during hospitalization.

High frequencies of elevated alkaline phosphatase activity and rickets exist in extremely low birth weight infants despite current nutritional support.

BACKGROUND: Osteopenia and rickets are common among extremely low birth weight infants (ELBW, <1000 g birth weight) despite current practices of vitamin and mineral supplementation. Few data are available evaluating the usual course of markers of mineral status in this population. Our objectives in this study were to determine the relationship between birth weight (BW) and peak serum alkaline phosphatase activity (P-APA) in ELBW infants and evaluate our experience with the diagnosis of rickets in these infants. METHODS: We evaluated all ELBW infants admitted to Texas Children's Hospital NICU in 2006 and 2007. Of 211 admissions, we excluded 98 patients who were admitted at >30 days of age or did not survive/stay for >6 weeks. Bone radiographs obtained in 32 infants were reviewed by a radiologist masked to laboratory values. RESULTS: In this cohort of 113 infants, P-APA was found to have a significant inverse relationship with BW, gestational age and serum phosphorus. In paired comparisons, P-APA of infants <600 g (957 +/- 346 IU/L, n = 20) and infants 600-800 g (808 +/- 323 IU/L, n = 43) were both significantly higher than P-APA of infants 800-1000 g (615 +/- 252 IU/L, n = 50), p < 0.01. Thirty-two patients had radiographic evaluation for evidence of rickets, based on P-APA greater than 800 IU/L, parenteral nutrition greater than 3 to 4 weeks, or clinical suspicion. Of these, 18 showed radiologic rickets and 14 showed osteopenia without rickets. Infants with BW <600 g were more likely to have radiologic rickets (10/20 infants) compared to those with BW 600-800 g (6/43 infants) and BW 800-1000 g (2/50 infants), p < 0.01 for each. P-APA was not significantly higher in infants with radiologic rickets (1078 +/- 356 IU/L) compared to those without radiologic evidence of rickets (943 +/- 346, p = 0.18). CONCLUSION: Elevation of P-APA >600 IU/L was very common in ELBW infants. BW was significantly inversely related to both P-APA and radiologic rickets. No single value of P-APA was related to radiological findings of rickets. Given the very high risk of osteopenia and rickets among ELBW infants, we recommend consideration of early screening and early mineral supplementation, especially among infants <600 g BW.

Premature small for gestational age infants fed an exclusive human milk-based diet achieve catch-up growth without metabolic consequences at 2 years of age.

OBJECTIVE: To compare postdischarge growth, adiposity and metabolic outcomes of appropriate for gestational age (AGA) versus small for gestational age (SGA) premature infants fed an exclusive human milk (HM)-based diet in the neonatal intensive care unit. DESIGN: Premature infants (birth weight ≤1250 g) fed an exclusive HM-based diet were examined at 12-15 months corrected gestational age (CGA) (visit 1) for anthropometrics, serum glucose and non-fasting insulin, and at 18-22 months CGA (visit 2) for body composition by dual-energy X-ray absorptiometry. RESULTS: Of 51 children, 33 were AGA and 18 were SGA at birth. The SGA group had weight gain (g/day) equal to AGA group during the follow-up period. SGA had a significantly greater body mass index (BMI) z-score gain from visit 1 to visit 2 (0.25±1.10 vs -0.21±0.84, p=0.02) reflecting catch-up growth. There were no significant differences in total fat mass (FM) and trunk FM between groups. SGA had significantly lower insulin level (5.0±3.7 vs 17.3±15.1 µU/mL, p=0.02) and homeostatic model of assessment-insulin resistance (1.1±0.9 vs 4.3±4.1, p=0.02). Although regional trunk FM correlated with insulin levels in SGA (r=0.893, p=0.04), they had lower insulin level compared with AGA and no difference in adiposity. CONCLUSIONS: SGA premature infants who received an exclusive HM-based diet exhibited greater catch-up growth without increased adiposity or elevated insulin resistance compared with AGA at 2 years of age. An exclusive HM-based diet may improve long-term body composition and metabolic outcomes of premature infants with ≤1250 g birth weight, specifically SGA.

Magnesium retention in 12 to 48 month-old children.

OBJECTIVES: In adults, adaptation to changes in magnesium intake is largely due to changes in fractional magnesium absorption and urinary magnesium excretion. We sought to examine whether these homeostatic mechanism also occurred in young children. METHODS: Children, 12-48 m old were studied (n=30). They were adapted to a home diet representative of their usual magnesium intake for 7 d then admitted for a stable isotope study. Children received 5 mg Mg-25 intravenously, and 10 mg Mg-26 orally (5 mg with breakfast and 5 mg with lunch). Magnesium absorption was calculated from the relative fractional excretion of the oral and intravenous isotopes in the urine samples. Endogenous fecal magnesium absorption was calculated in a subgroup from the fecal and urinary excretion of the intravenous tracer. RESULTS: Magnesium intake (mean +/- SD; 106 +/- 25 mg/d) was significantly greater than the Estimated Average Requirement (EAR) described by the Institute of Medicine in the US (65 mg/d, p < 0.0001). Across the range of intake studied, fractional magnesium absorption was significantly (P = 0.0383) but weakly (r(2) = 0.144) related to magnesium intake. Absolute magnesium absorption (the product of fractional absorption and intake) significantly increased as intake increased (r(2) = 0.566, P < 0.0001). Urinary magnesium excretion was unrelated to magnesium intake (r(2) = 0.036, P = 0.31). Endogenous fecal magnesium excretion tended to increase as magnesium intake increased (r(2) = 0.312, P = 0.12). Magnesium retention (absolute absorption minus urinary and fecal losses) was positive in 26 of the 30 subjects studied, and was linearly related to magnesium intake (r(2) = 0.157, P = 0.0304). A magnesium intake of 52-78 mg/d would appear to be required to meet the needs for absorbed magnesium for half the children at this age range, suggesting that the current EAR is broadly appropriate. CONCLUSIONS: In young children, consuming magnesium intakes typical of the US population, fractional magnesium absorption is a major site of magnesium homeostasis, but magnesium retention increased linearly across the intake range studied. Our results support at EAR for magnesium of 55-80 mg/d and an RDA of 70-100 mg/d.