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.

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.

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.

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.

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.

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.

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.

Growth of Infants with Intestinal Failure or Feeding Intolerance Does Not Follow Standard Growth Curves.

Objective. Infants with intestinal failure or feeding intolerance are nutritionally compromised and are at risk for extrauterine growth restriction. The aim of the study was to evaluate growth velocities of infants with intestinal failure and feeding intolerance for the first three months of age and to determine growth percentiles at birth and at 40-week postmenstrual age (PMA). Methods. A chart review of infants followed by the Texas Children's Hospital Intestinal Rehabilitation Team was conducted from April 2012 to October 2014. Weekly weight, length, and head circumference growth velocities were calculated. Growth data were compared to Olsen growth curves to determine exact percentiles. Results. Data from infants (n = 164) revealed that average growth velocities of 3-month-old infants (weight gain, 19.97 g/d; length, 0.81 cm/week; head circumference, 0.52 cm/week) fluctuated and all were below expected norms. At discharge or death, average growth velocities had further decreased (length, 0.69 cm/week; head circumference, 0.45 cm/week) except for weight, which showed a slight increase (weight, 20.56 g/d). Weight, length, and head circumference percentiles significantly decreased from birth to 40-week PMA (P < 0.001). Conclusions. Growth of infants with intestinal failure or feeding intolerance did not follow standard growth curves.

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.

Premature Infants 750-1,250 g Birth Weight Supplemented with a Novel Human Milk-Derived Cream Are Discharged Sooner.

OBJECTIVE: Infants may benefit from early nutritional intervention to decrease hospital stay. To evaluate the effects of adding a human milk (HM)-derived cream (Cream) product to a standard feeding regimen in preterm infants. MATERIALS AND METHODS: In a prospective multicenter randomized study, infants with birth weights 750-1,250 g were assigned to a Control or Cream group. The Control group received a standard feeding regimen consisting of mother's own milk or donor HM with donor HM-derived fortifier. The Cream group received the standard feeding regimen along with an additional HM-derived cream supplement when the HM they received was <20 kcal/oz. Primary outcomes of this secondary analysis included comorbidities, length of stay (LOS), and postmenstrual age (PMA) at discharge. RESULTS: We enrolled 75 infants (Control n = 37, Cream n = 38) with gestational age 27.7 ± 1.8 weeks and birth weight 973 ± 145 g (mean ± SD). After adjusting for gestational age, birth weight, and presence of bronchopulmonary dysplasia (BPD), the Cream group had a decreased PMA at discharge (39.9 ± 4.8 versus 38.2 ± 2.7 weeks, p = 0.03) and LOS (86 ± 39 versus 74 ± 22 days, p = 0.05). For 21 infants with BPD, these values trended toward significance for PMA at discharge (44.2 ± 6.1 versus 41.3 ± 2.7 weeks, p = 0.08) and LOS (121 ± 49 versus 104 ± 23 days, p = 0.08). CONCLUSIONS: Very preterm infants who received an HM-derived cream supplement were discharged earlier. Infants with BPD may have benefited the most.

Beyond Necrotizing Enterocolitis Prevention: Improving Outcomes with an Exclusive Human Milk-Based Diet.

OBJECTIVE: The aim of this study was to compare outcomes of infants pre and post initiation of a feeding protocol providing an exclusive human milk-based diet (HUM). MATERIALS AND METHODS: In a multicenter retrospective cohort study, infants with a birth weight <1,250 g who received a bovine-based diet (BOV) of mother's own milk fortified with bovine fortifier and/or preterm formula were compared to infants who received a newly introduced HUM feeding protocol. Infants were excluded if they had major congenital anomalies or died in the first 12 hours of life. Data were collected 2-3 years prior to and after introduction of an exclusive HUM diet. Primary outcomes were necrotizing enterocolitis (NEC) and mortality. Secondary outcomes included late-onset sepsis, retinopathy of prematurity (ROP), and bronchopulmonary dysplasia (BPD). RESULTS: A total of 1,587 infants were included from four centers in Texas, Illinois, Florida, and California. There were no differences in baseline demographics or growth of infants. The HUM group had significantly lower incidence of proven NEC (16.7% versus 6.9%, p < 0.00001), mortality (17.2% versus 13.6%, p = 0.04), late-onset sepsis (30.3% versus 19.0%, p < 0.00001), ROP (9% versus 5.2%, p = 0.003), and BPD (56.3% versus 47.7%, p = 0.0015) compared with the BOV group. CONCLUSIONS: Extremely premature infants who received an exclusive HUM diet had a significantly lower incidence of NEC and mortality. The HUM group also had a reduction in late-onset sepsis, BPD, and ROP. This multicenter study further emphasizes the many benefits of an exclusive HUM diet, and demonstrates multiple improved outcomes after implementation of such a feeding protocol.

A Novel Approach to Improving Fat Delivery in Neonatal Enteral Feeding.

Continuous infusion systems used for enteral nutrition support in the neonatal intensive care unit deliver as little as 60% of the fat in human milk to the neonate. This study determined the effect of mixing common feedings for preterm infants in the feeding bag and tubing on fat losses during enteral feeding. Laboratory models were developed to assess the contribution of various mixing techniques to delivered fat content. Fat content was measured periodically during feeding and compared to baseline measurements. A multistage approach incorporating a feeding bag inverter and a tubing circulation loop delivered >90% of milk fat when used in conjunction with a commercial continuous infusion system. With unfortified human milk, this approach delivered 91.9% ± 1.5% of fat content over a one hour feed, significantly greater (p < 0.01) than 77.5% ± 2.2% delivered by continuous infusion controls (Mean ± SEM). With fortified human milk, this approach delivered 92.1% ± 2.4% of fat content, significantly greater (p < 0.01) than 79.4% ± 1.0% delivered by a non-adapted infusion system (Mean ± SEM). Mixing human milk during continuous infusion improves fat delivery, which may improve nutrition and growth outcomes in low birth weight neonates.

Serum phosphorus levels in premature infants receiving a donor human milk derived fortifier.

An elevated serum phosphorus (P) has been anecdotally described in premature infants receiving human milk fortified with donor human milk-derived fortifier (HMDF). No studies have prospectively investigated serum P in premature infants receiving this fortification strategy. In this single center prospective observational cohort study, extremely premature infants ≤ 1250 grams (g) birth weight (BW) were fed an exclusive human milk-based diet receiving HMDF and serum P levels were obtained. We evaluated 93 infants with a mean gestational age of 27.5 ± 2.0 weeks (Mean ± SD) and BW of 904 ± 178 g. Seventeen infants (18.3%) had at least one high serum P level with a mean serum P of 9.2 ± 1.1 mg/dL occurring at 19 ± 11 days of life. For all infants, the highest serum P was inversely correlated to the day of life of the infant (p < 0.001, R2 = 0.175) and positively correlated with energy density of HMDF (p = 0.035). Serum P was not significantly related to gender, BW, gestational age, or days to full feeds. We conclude that the incidence of hyperphosphatemia was mild and transient in this population. The risk decreased with infant age and was unrelated to gender, BW, or ethnicity.

A systematic review of controlled trials of lower-protein or energy-containing infant formulas for use by healthy full-term infants.

Infant formulas have historically been developed based on providing macronutrients at intake concentrations approximately matching the composition of human milk. In most countries, targets of 1.4-1.5 g of protein/dL and 20 kcal/oz (67-68 kcal/dL) have been set as the protein and energy concentrations for formulas during the first year of life, although this may be an overestimation of these contents. Recent introduction of lower-protein and -energy formulas in full-term infants led us to systematically review the literature for its effects on growth. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, our inclusion criteria were studies that enrolled healthy full-term infants and evaluated lower-protein or lower-energy formula, reported anthropometric outcomes including weight and length, and followed infants for at least 6 mo. Six studies were eligible for inclusion. These studies varied in the content of nutrients provided in the intervention and control groups, by additional dietary components in the study groups, and the timing and length of the intervention, which limit their usefulness for interpreting newly introduced lower-protein and -energy formulas in the United States. These studies suggest adequate growth during infancy and early childhood with infant formulas with concentrations of protein and energy slightly below historical standards in the United States. Further long-term research is needed to assess the impact of the use of lower-protein and/or lower-energy products, especially for nutritionally at-risk populations such as preterm infants and infants who are born small for gestational age.

Fortifier and cream improve fat delivery in continuous enteral infant feeding of breast milk.

Premature and high-risk infants require accurate delivery of nutrients to promote appropriate growth. Continuous enteral feeding methods may result in significant fat and micronutrient loss. This study evaluated fat loss in enteral nutrition using current strategies for providing high-risk infants fortified human milk (HM). The fat content of HM was measured by IR analyzer in a simulated feeding system using the Kangaroo epumpTM and the MedFusionTM 2010 pump. Comparisons in fat loss were made between HM, HM supplemented with donor HM-derived fortifier Prolacta+H2MFTM (H2MF), and HM supplemented with H2MF and donor HM-derived cream ProlactCRTM (cream). When using the Kangaroo epumpTM, the addition of H2MF and cream to HM increased fat delivery efficiency from 75.0%±1.2% to 83.7%±1.0% (p<0.0001). When using the MedFusionTM 2010 pump, the addition of H2MF to HM increased fat delivery efficiency from 83.2%±2.8% to 88.8%±0.8% (p<0.05), and the addition of H2MF and cream increased fat delivery efficiency to 92.0%±0.3% (p<0.01). The addition of H2MF and cream to HM provides both the benefits of bioactive elements from mother's milk and increased fat delivery, making the addition of H2MF and cream an appropriate method to improve infant weight gain.

Bioavailability of enteric-coated microencapsulated calcium during pregnancy: a randomized crossover trial in Bangladesh.

BACKGROUND: Prenatal calcium and iron supplements are recommended in settings of low dietary calcium intake and high prevalence of anemia. However, calcium administration may inhibit iron absorption. To overcome calcium-iron interactions, we developed a multi-micronutrient powder containing iron (60 mg), folic acid (400 µg), and calcium carbonate granules microencapsulated with a pH-sensitive enteric coating to delay intestinal release. OBJECTIVES: We aimed to establish in vivo evidence that enteric-coated (EC) calcium is bioavailable in pregnant women and to explore the dose-responsiveness of fractional calcium absorption (FCA) in pregnancy. DESIGN: This was a randomized crossover trial in pregnant women (26-28 wk of gestation) in Dhaka, Bangladesh. Participants were allocated to 1 of 3 dose groups (500, 1000, or 1500 mg elemental Ca). FCA was estimated in random order for EC and non-EC (control) granules by a dual-stable-isotope method ((44)Ca-labeled granules and intravenous (42)Ca) on the basis of the relative recovery of (44)Ca compared with (42)Ca in urine over 48 h. RESULTS: Forty-nine participants with FCA for both EC and non-EC granules were included in the primary analyses. FCA geometric means were as follows: 21.8% (500 mg), 9.2% (1000 mg), and 11.7% (1500 mg) for non-EC granules compared with 3.3% (500 mg), 1.2% (1000 mg), and 2.1% for EC granules. Cumulative 48-h FCA of EC calcium was 85% lower (P < 0.001) than that of non-EC calcium, after adjustment for dose. In comparison to 500 mg, the FCA for the 1000-mg dose was 61% lower (P < 0.001) and was 42% lower (P = 0.002) for the 1500-mg dose, after adjustment for formulation. CONCLUSIONS: A pH-sensitive enteric coating substantially reduced calcium absorption from a prenatal multi-micronutrient powder. In its current formulation, this novel supplement is not suitable for clinical use. FCA was highly dose-dependent, such that doses of 1000 and 1500 mg delivered only negligibly more bioavailable calcium than the 500-mg dose. This trial was registered at clinicaltrials.gov as NCT01678079.

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.

Micronutrient requirements of high-risk infants.

Micronutrient requirements are well-established for healthy full-term infants. However, few such recommendations exist for high-risk infants, including full-term infants with a variety of medical disorders or very preterm infants. Key micronutrients considered in this review are calcium, phosphorus, magnesium, iron, and zinc. The ongoing unresolved shortages, especially of intravenous forms of these minerals, remain a major problem. Considered are some aspects of how the nutrient shortages may be managed, recognizing the complexity and changing nature of the supply.