Vegan/vegetarian diet and human milk donation: An EMBA survey across European milk banks.

The nutritional adequacy of human milk (HM) from vegan/vegetarian mothers has been a matter of debate, and a variety of recommendations regarding the eligibility of these mothers as human milk donors exists. According to the latest evidence, HM from vegans/vegetarians is similar in its composition to that from omnivores, however, some differences may be observed regarding vitamin B12 and omega-3 fatty acids concentrations. Maternal supplementation of these compounds has been proven effective in increasing their HM concentration. With this survey, we aimed to explore the practices currently in use in European human milk banks (HMBs) regarding potential donors following vegan/vegetarian diets. The online survey was distributed to European HMBs between January and July 2022. A total of 188 HMBs were contacted, and 118 replied (response rate 63%). Vegan and vegetarian mothers were recommended supplements of vitamin B12 to be accepted as donors in 27% and 26% of HMBs, respectively. Additional omega-3 fatty acid supplementation was required in 8% HMBs. In the remaining HMBs, these mothers were either systematically excluded or included regardless of supplementation. The dosage of the recommended supplements was extremely variable. Fifty-one percent of HMBs were following recommendations to guide their practice, national or local recommendations mainly. Great variability in European HMBs practices towards potential donors following vegan/vegetarian diets exists. Some of these practices can result in loss of donors and/or in potential nutritional deficiencies. Standardised evidence-based recommendations on this issue and their implementation in daily HMB practice are needed.

Mode of Neonatal Delivery Influences the Nutrient Composition of Human Milk: Results From a Multicenter European Cohort of Lactating Women.

Background: The effect of the mode of neonatal delivery (cesarean or vaginal) on the nutrient composition of human milk (HM) has rarely been studied. Given the increasing prevalence of cesarean section (C-section) globally, understanding the impact of C-section vs. vaginal delivery on the nutrient composition of HM is fundamental when HM is the preferred source of infant food during the first 4 postnatal months. Objective: This study aimed to evaluate the association between mode of delivery and nutrient composition of HM in the first 4 months of life. Design: Milk samples were obtained from 317 healthy lactating mothers as part of an exploratory analyses within a multicenter European longitudinal cohort (ATLAS cohort) to study the HM composition, and its potential association with the mode of delivery. We employed traditional mixed models to study individual nutrient associations adjusted for mother's country, infant birth weight, parity, and gestational age, and complemented it, for the first time, with a multidimensional data analyses approach (non-negative tensor factorization, NTF) to examine holistically how patterns of multiple nutrients and changes over time are associated with the delivery mode. Results: Over the first 4 months, nutrient profiles in the milk of mothers who delivered vaginally (n = 237) showed significantly higher levels of palmitoleic acid (16:1n-7), stearic acid (18:0), oleic acid (18:1n-9), arachidic acid (20:0), alpha-linolenic acid (18:3n-3), eicosapentaenoic acid (20:5n-3), docosahexenoic acid (22:6n-3), erucic acid (22:1n-9), monounsaturated fatty acids (MUFA)%, calcium, and phosphorus, whereas the ratios of arachidonic acid/docosahexaenoic acid (ARA/DHA) and n-6/n-3, as well as polyunsaturated fatty acids (PUFA)% were higher in milk from women who had C-sections, in the unadjusted analyses (p < 0.05 for all), but did not retain significance when adjusted for confounders in the mixed models. Using a complementary multidimension data analyses approach (NTF), we show few similar patterns wherein a group of mothers with a high density of C-sections showed increased values for PUFA%, n-6/n-3, and ARA/DHA ratios, but decreased values of MUFA%, 20:1n-9, iodine, and fucosyl-sialyl-lacto-N-tetraose 2 during the first 4 months of lactation. Conclusion: Our data provide preliminary insights on differences in concentrations of several HM nutrients (predominantly fatty acids) among women who delivered via C-section. Although these effects tend to disappear after adjustment for confounders, given the similar patterns observed using two different data analytical approaches, these preliminary findings warrant further confirmation and additional insight on the biological and clinical effects related to such differences early in life.

Nephrocalcinosis in very low birth weight infants: incidence, associated factors, and natural course.

BACKGROUND: Preterm kidney is exposed to various exogenous factors that may impact its function such as nephrotoxic drugs or nephrocalcinosis. We investigated prevalence and risk factors of nephrocalcinosis (NC) in recently born very low birth weight (VLBW) infants submitted to improved biological monitoring. METHODS: Retrospective, case-control study in very preterm infants (< 32 + 6 weeks, ≤ 1500 g) admitted to a tertiary care unit during a 6-year period. Each case (ultrasound-diagnosed NC) was matched with two controls (no NC). Data were collected at days 15 and 30 of life and 35 weeks corrected age, with follow-up at 18 months and 3 years. RESULTS: Of 525 eligible infants, overall prevalence of NC was 17.1% at 35 weeks corrected age. Prevalence was halved between 2012 (26.1%) and 2017 (11.8%). We included 265 infants, more than half being born before 28 weeks. Cases presented with more severe morbidity than controls, but reached statistical significance only in infants born < 28 weeks (88.2% vs. 68.3%, P = 0.01). Protein, energy, calcium, phosphorus, and vitamin D intakes were similar in the two groups and did not change significantly over the study period. Weight gain was similar in the two groups. Exposure to furosemide (OR [IC95%]: 1.26 [1.02; 1.57]) and postnatal growth (1.65 [1.04; 2.67]) were independent risk factors of NC. NC resolved 12-18 months after diagnosis in 61% of infants. CONCLUSION: Prevalence of NC is significant but can be reduced. Furosemide should be cautiously prescribed in VLBW infants, and nutritional support must be well monitored to support postnatal growth and limit risk of nephrocalcinosis. TRIAL REGISTRATION: ClinicalTrials.gov: NCT 04,860,583. A higher resolution version of the Graphical abstract is available as Supplementary information.

Sex-Specific Effects of Nutritional Supplements for Infants Born Early or Small: An Individual Participant Data Meta-Analysis (ESSENCE IPD-MA) I-Cognitive Function and Metabolic Risk.

Neonatal nutritional supplements are widely used to improve growth and development but may increase risk of later metabolic disease, and effects may differ by sex. We assessed effects of supplements on later development and metabolism. We searched databases and clinical trials registers up to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter cognitive impairment in toddlers (13 trials, n = 1410; adjusted relative risk (aRR) 0.88 [95% CI 0.68, 1.13]; p = 0.31) or older ages, nor alter metabolic risk beyond 3 years (5 trials, n = 438; aRR 0.94 [0.76, 1.17]; p = 0.59). However, supplementation reduced motor impairment in toddlers (13 trials, n = 1406; aRR 0.76 [0.60, 0.97]; p = 0.03), and improved motor scores overall (13 trials, n = 1406; adjusted mean difference 1.57 [0.14, 2.99]; p = 0.03) and in girls not boys (p = 0.03 for interaction). Supplementation lowered triglyceride concentrations but did not affect other metabolic outcomes (high-density and low-density lipoproteins, cholesterol, fasting glucose, blood pressure, body mass index). Macronutrient supplementation for infants born small may not alter later cognitive function or metabolic risk, but may improve early motor function, especially for girls.

Sex-Specific Effects of Nutritional Supplements for Infants Born Early or Small: An Individual Participant Data Meta-Analysis (ESSENCE IPD-MA) II: Growth.

Neonatal nutritional supplements may improve early growth for infants born small, but effects on long-term growth are unclear and may differ by sex. We assessed the effects of early macronutrient supplements on later growth. We searched databases and clinical trials registers from inception to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter BMI in childhood (kg/m2: adjusted mean difference (aMD) -0.11[95% CI -0.47, 0.25], p = 0.54; 3 trials, n = 333). Supplementation increased length (cm: aMD 0.37[0.01, 0.72], p = 0.04; 18 trials, n = 2008) and bone mineral content (g: aMD 10.22[0.52, 19.92], p = 0.04; 6 trials, n = 313) in infancy, but not at older ages. There were no differences between supplemented and unsupplemented groups for other outcomes. In subgroup analysis, supplementation increased the height z-score in male toddlers (aMD 0.20[0.02, 0.37], p = 0.03; 10 trials, n = 595) but not in females, and no significant sex interaction was observed (p = 0.21). Macronutrient supplementation for infants born small may not alter BMI in childhood. Supplementation increased growth in infancy, but these effects did not persist in later life. The effects did not differ between boys and girls.

Association Between Early Amino Acid Intake and Full-Scale IQ at Age 5 Years Among Infants Born at Less Than 30 Weeks' Gestation.

Importance: An international expert committee recently revised its recommendations on amino acid intake for very preterm infants, suggesting that more than 3.50 g/kg/d should be administered only to preterm infants in clinical trials. However, the optimal amino acid intake during the first week after birth in these infants is unknown. Objective: To evaluate the association between early amino acid intake and cognitive outcomes at age 5 years. Design, Setting, and Participants: Using the EPIPAGE-2 (Epidemiologic Study on Small-for-Gestational-Age Children-Follow-up at Five and a Half Years) cohort, a nationwide prospective population-based cohort study conducted at 63 neonatal intensive care units in France, a propensity score-matched analysis was performed comparing infants born at less than 30 weeks' gestation who had high amino acid intake (3.51-4.50 g/kg/d) at 7 days after birth with infants who did not. Participants were recruited between April 1 and December 31, 2011, and followed up from September 1, 2016, to December 31, 2017. Full-scale IQ (FSIQ) was assessed at age 5 years. A confirmatory analysis used neonatal intensive care unit preference for high early amino acid intake as an instrumental variable to account for unmeasured confounding. Statistical analysis was performed from January 15 to May 15, 2021. Exposures: Amino acid intake at 7 days after birth. Main Outcomes and Measures: The primary outcome was an FSIQ score greater than -1 SD (ie, ≥93 points) at age 5 years. A complementary analysis was performed to explore the association between amino acid intake at day 7 as a continuous variable and FSIQ score at age 5 years. Data from cerebral magnetic resonance imaging at term were available for a subgroup of preterm infants who participated in the EPIRMEX (Cerebral Abnormalities Detected by MRI, Realized at the Age of Term and the Emergence of Executive Functions) ancillary study. Results: Among 1789 preterm infants (929 boys [51.9%]; mean [SD] gestational age, 27.17 [1.50] weeks) with data available to determine exposure to amino acid intake of 3.51 to 4.50 g/kg/d at 7 days after birth, 938 infants were exposed, and 851 infants were not; 717 infants from each group could be paired. The primary outcome was known in 396 of 646 exposed infants and 379 of 644 nonexposed infants who were alive at age 5 years and was observed more frequently among exposed vs nonexposed infants (243 infants [61.4%] vs 206 infants [54.4%], respectively; odds ratio [OR], 1.33 [95% CI, 1.00-1.71]; absolute risk increase in events [ie, the likelihood of having an FSIQ score >-1 SD at age 5 years] per 100 infants, 7.01 [95% CI, 0.06-13.87]; P = .048). In the matched cohort, correlation was found between amino acid intake per 1.00 g/kg/d at day 7 and FSIQ score at age 5 years (n = 775; ß = 2.43 per 1-point increase in FSIQ; 95% CI, 0.27-4.59; P = .03), white matter area (n = 134; ß = 144 per mm2; 95% CI, 3-285 per mm2; P = .045), anisotropy of the corpus callosum (n = 50; ß = 0.018; 95% CI, 0.016-0.021; P < .001), left superior longitudinal fasciculus (n = 42; ß = 0.018; 95% CI, 0.010-0.025; P < .001), and right superior longitudinal fasciculus (n = 42; ß = 0.014 [95% CI, 0.005-0.024; P = .003) based on magnetic resonance imaging at term. Confirmatory and sensitivity analyses confirmed these results. For example, the adjusted OR for the association between the exposure and the primary outcome was 1.30 (95% CI, 1.16-1.46) using the instrumental variable approach among 978 participants in the overall cohort, and the adjusted OR was 1.35 (95% CI, 1.05-1.75) using multiple imputations among 1290 participants in the matched cohort. Conclusions and Relevance: In this cohort study, high amino acid intake at 7 days after birth was associated with an increased likelihood of an FSIQ score greater than -1 SD at age 5 years. Well-designed randomized studies with long-term follow-up are needed to confirm the benefit of this nutritional approach.

Early Effect of Supplemented Infant Formulae on Intestinal Biomarkers and Microbiota: A Randomized Clinical Trial.

BACKGROUND: Post-natal gut maturation in infants interrelates maturation of the morphology, digestive, and immunological functions and gut microbiota development. Here, we explored both microbiota development and markers of gut barrier and maturation in healthy term infants during their early life to assess the interconnection of gut functions during different infant formulae regimes. METHODS: A total of 203 infants were enrolled in this randomized double-blind controlled trial including a breastfed reference group. Infants were fed starter formulae for the first four weeks of life, supplemented with different combination of nutrients (lactoferrin, probiotics (Bifidobacterium animal subsp. Lactis) and prebiotics (Bovine Milk-derived Oligosaccharides-BMOS)) and subsequently fed the control formula up to eight weeks of life. Stool microbiota profiles and biomarkers of early gut maturation, calprotectin (primary outcome), elastase, α-1 antitrypsin (AAT) and neopterin were measured in feces at one, two, four, and eight weeks. RESULTS: Infants fed formula containing BMOS had lower mean calprotectin levels over the first two to four weeks compared to the other formula groups. Elastase and AAT levels were closer to levels observed in breastfed infants. No differences were observed for neopterin. Global differences between the bacterial communities of all groups were assessed by constrained multivariate analysis with hypothesis testing. The canonical correspondence analysis (CCA) at genus level showed overlap between microbiota profiles at one and four weeks of age in the BMOS supplemented formula group with the breastfed reference, dominated by bifidobacteria. Microbiota profiles of all groups at four weeks were significantly associated with the calprotectin levels at 4 (CCA, p = 0.018) and eight weeks of age (CCA, p = 0.026). CONCLUSION: A meaningful correlation was observed between changes in microbiota composition and gut maturation marker calprotectin. The supplementation with BMOS seems to favor gut maturation closer to that of breastfed infants.

Fortification of Human Milk for Preterm Infants: Update and Recommendations of the European Milk Bank Association (EMBA) Working Group on Human Milk Fortification.

Evidence indicates that human milk (HM) is the best form of nutrition uniquely suited not only to term but also to preterm infants conferring health benefits in both the short and long-term. However, HM does not provide sufficient nutrition for the very low birth weight (VLBW) infant when fed at the usual feeding volumes leading to slow growth with the risk of neurocognitive impairment and other poor health outcomes such as retinopathy and bronchopulmonary dysplasia. HM should be supplemented (fortified) with the nutrients in short supply, particularly with protein, calcium, and phosphate to meet the high requirements of this group of babies. In this paper the European Milk Bank Association (EMBA) Working Group on HM Fortification discusses the existing evidence in this field, gives an overview of different fortification approaches and definitions, outlines the gaps in knowledge and gives recommendations for practice and suggestions for future research. EMBA recognizes that "Standard Fortification," which is currently the most utilized regimen in neonatal intensive care units, still falls short in supplying sufficient protein for some VLBW infants. EMBA encourages the use of "Individualized Fortification" to optimize nutrient intake. "Adjustable Fortification" and "Targeted Fortification" are 2 methods of individualized fortification. The quality and source of human milk fortifiers constitute another important topic. There is work looking at human milk derived fortifiers, but it is still too early to draw precise conclusions about their use. The pros and cons are discussed in this Commentary in addition to the evidence around use of fortifiers post discharge.

Reply: "Letter to the Editor Re: Billeaud et al. Nutrients 2018, 10, 690".

We thank Bernard and colleagues for their careful reading and interest in our article Effects on Fatty Acid Metabolism of a New Powdered Human Milk Fortifier Containing Medium-Chain Triacylglycerols and Docosahexaenoic Acid in Preterm Infants [...].

Effects on Fatty Acid Metabolism of a New Powdered Human Milk Fortifier Containing Medium-Chain Triacylglycerols and Docosahexaenoic Acid in Preterm Infants.

Preterm infants require fortification of human milk (HM) with essential fatty acids (FA) to ensure adequate post-natal development. As part of a larger randomized controlled study, we investigated FA metabolism in a subset of 47 clinically stable preterm infants (birth weight ≤1500 g or gestational age ≤32 weeks). Infants were randomized to receive HM supplemented with either a new HM fortifier (nHMF; n = 26) containing 12.5 g medium-chain FA (MCFA), 958 mg linoleic acid (LA), 417 mg α-linolenic acid (ALA), and 157 mg docosahexaenoic acid (DHA) per 100 g of powder (in compliance with the latest guidelines) or a fat-free HMF (cHMF; n = 21). Plasma phospholipid (PL) and triacylglycerol (TAG), and red blood cell phosphatidylcholine (RBC-PC) and phosphatidylethanolamine (RBC-PE) FA profiles were assessed before and after 21 days of feeding. In the nHMF group, significantly increased levels of n-9 monounsaturated fatty acids were observed, formed most likely by elongation and desaturation of dietary saturated fatty acids present in HM. ALA fortification increased ALA assimilation into plasma TAG. Similarly, DHA fortification enriched the DHA content in RBC-PE, which, in this compartment, was not associated with lower arachidonic acid levels as observed in plasma TAG and phospholipids. RBC-PE, a reliable indicator of FA metabolism and accretion, was the most sensitive compartment in this study.

Role of Lactoferrin in Neonates and Infants: An Update.

Lactoferrin is one of the most represented and important bioactive proteins in human and mammal milk. In humans, lactoferrin is responsible for several actions targeting anti-infective, immunological, and gastrointestinal domains in neonates, infants, and young children. Evidence-based data vouch for the ability of supplemented lactoferrin to prevent sepsis and necrotizing enterocolitis in preterm infants and to reduce the burden of morbidity related to gastrointestinal and respiratory pathogens in young children. However, several issues remain pending regarding answers and clarification related to quality control, correct intakes, optimal schedules and schemes of supplementations, interactions with probiotics, and different types of milk and formulas. This review summarizes the current evidence regarding lactoferrin and discusses the areas in need of further guidance prior to the adoption of strategies that include a routine use of lactoferrin in neonates and young children.

Growth and Nutritional Biomarkers of Preterm Infants Fed a New Powdered Human Milk Fortifier: A Randomized Trial.

OBJECTIVES: The aim of this study was to assess growth and nutritional biomarkers of preterm infants fed human milk (HM) supplemented with a new powdered HM fortifier (nHMF) or a control HM fortifier (cHMF). The nHMF provides similar energy content, 16% more protein (partially hydrolyzed whey), and higher micronutrient levels than the cHMF, along with medium-chain triglycerides and docosahexaenoic acid. METHODS: In this controlled, multicenter, double-blind study, a sample of preterm infants ≤32 weeks or ≤1500 g were randomized to receive nHMF (n = 77) or cHMF (n = 76) for a minimum of 21 days. Weight gain was evaluated for noninferiority (margin = -1 g/day) and superiority (margin = 0 g/day). Nutritional status and gut inflammation were assessed by blood, urine, and fecal biochemistries. Adverse events were monitored. RESULTS: Adjusted mean weight gain (analysis of covariance) was 2.3 g/day greater in nHMF versus cHMF; the lower limit of the 95% CI (0.4 g/day) exceeded both noninferiority (P < 0.001) and superiority margins (P = 0.01). Weight gain rate (unadjusted) was 18.3 (nHMF) and 16.8 g ·â€Škg ·â€Šday (cHMF) between study days 1 and 21 (D1-D21). Length and head circumference (HC) gains between D1 and D21 were not different. Adjusted weight-for-age z score at D21 and HC-for-age z score at week 40 corrected age were greater in nHMF versus cHMF (P = 0.013, P = 0.003 respectively). nHMF had higher serum blood urea nitrogen, pre-albumin, alkaline phosphatase, and calcium (all within normal ranges; all P ≤ 0.019) at D21 versus cHMF. Both HMFs were well tolerated with similar incidence of gastrointestinal adverse events. CONCLUSIONS: nHMF providing more protein and fat compared to a control fortifier is safe, well-tolerated, and improves the weight gain of preterm infants.

Effects of Maternal Supplementation With Omega-3 Precursors on Human Milk Composition.

BACKGROUND: Long-chain polyunsaturated fatty acids (LC-PUFAs) are important for newborn neurosensory development. Supplementation of breastfeeding mothers' diets with omega-3 PUFAs, such as alpha-linolenic acid (ALA), may increase their concentration in human milk. Research aim: This study aimed to assess human milk composition after 15-day supplementation regimens containing either omega-3 PUFAs or olive oil, which does not provide ALA. METHODS: A multicenter factorial randomized trial was conducted with four groups of breastfeeding women, with each group containing 19 to 22 women. After a 15-day ALA washout period, three groups received supplementation with omega-3 precursors for 15 days: an enriched margarine (M), a rapeseed oil (R), and a margarine and rapeseed oil (MR). The fourth was unexposed to omega-3 precursors (olive oil control diet, O). After 15 days, blind determination of human milk fatty acid (FA) composition was assessed by gas chromatography, and the FA composition was compared among groups using variance analyses. RESULTS: Alpha-linolenic acid content, expressed as the mean (standard deviation) total human milk FA percentage, was significantly higher after diet supplementation with omega-3 PUFAs, with values of 2.2% (0.7%) (MR), 1.3% (0.5%) (R), 1.1% (0.4%) (M), and 0.8% (0.3%) (O at D30) ( p < .003 for each comparison). The lowest LA-ALA ratio (5.5) was found in the MR group ( p < .001). Docosahexaenoic acid and trans FA concentrations did not differ among groups. CONCLUSION: In lactating women, omega-3 supplementation via the combination of enriched margarine and rapeseed oil increased the ALA content of human milk and generated the most favorable LA-ALA ratio for LC-PUFA synthesis.

In situ simulation training for neonatal resuscitation: an RCT.

OBJECTIVES: High-fidelity simulation is an effective tool in teaching neonatal resuscitation skills to professionals. We aimed to determine whether in situ simulation training (for ∼80% of the delivery room staff) improved neonatal resuscitation performed by the staff at maternities. METHODS: A baseline evaluation of 12 maternities was performed: a random sample of 10 professionals in each unit was presented with 2 standardized scenarios played on a neonatal high-fidelity simulator. The medical procedures were video recorded for later assessments. The 12 maternities were then randomly assigned to receive the intervention (a 4-hour simulation training session delivered in situ for multidisciplinary groups of 6 professionals) or not receive it. All maternities were evaluated again at 3 months after the intervention. The videos were assessed by 2 neonatologists blinded to the pre-/postintervention as well as to the intervention/control groups. The performance was assessed using a technical score and a team score. RESULTS: After intervention, the median technical score was significantly higher for scenarios 1 and 2 for the intervention group compared with the control group (P = .01 and 0.004, respectively), the median team score was significantly higher (P < .001) for both scenarios. In the intervention group, the frequency of achieving a heart rate >90 per minute at 3 minutes improved significantly (P = .003), and the number of hazardous events decreased significantly (P < .001). CONCLUSIONS: In situ simulation training with multidisciplinary teams can effectively improve technical skills and teamwork in neonatal resuscitation.

Severe hypothyroidism after contrast enema in premature infants.

Premature newborns are particularly vulnerable to iatrogenic hypothyroidism due to iodine exposure, usually through skin absorption of iodine-containing disinfectants or intravenous administration of iodinated contrast agents. We report here a case of severe iatrogenic hypothyroidism with goiter and cholestasis, discovered six weeks after a contrast enema using sodium ioxitalamate, an iodinated contrast agent. Prematurity, intrauterine growth retardation, and enteral feeding intolerance could explain why this complication occurred after contrast enema. Our observations suggest that indications of contrast enema in neonates need to be carefully considered, and when necessary, thyroid function should be monitored, especially in very premature infants.

Growth and bone mineralization in preterm infants fed preterm formula or standard term formula after discharge.

OBJECTIVE: To evaluate growth and bone mineralization in very low birth weight (VLBW) infants fed preterm formula (PF) or term formula (TF). STUDY DESIGN: In a double-blind prospective study, 49 preterm infants of gestational age 33 weeks or less were randomly fed PF or TF for 2 months after discharge, then all of the infants were fed TF for the next 2 months. Anthropometric and dual-energy x-ray absorptiometry data were collected at discharge and at 2 months and 4 months after discharge. Anthropometric data also were collected at 12 months postterm. RESULTS: Four months after discharge, both body weight (6139 +/- 1254 g vs 5540 +/- 863 g; P = .03) and bone mineral content (104.4 +/- 29.2 g vs 87.5 +/- 17.1 g; P = .01) were significantly higher in the PF group compared with the TF group. At 12 months postterm, mean body weight, length, and head circumference remained higher in the PF group than in the TF group, and body mass index was similar and within the normal range in the 2 groups. CONCLUSIONS: At 4 months after discharge, growth and mineralization were better in the VLBW infants who were fed PF during the first 2 months after discharge compared with those who were fed TF, suggesting that PF may be particularly valuable at this early stage of development.

Influence of dietary cholesterol on vitamin d metabolism in formula-fed preterm neonates.

OBJECTIVES: Supplementation of preterm formulas with cholesterol could help to mimic the fat composition of human milk. However, this could possibly influence vitamin D 25-hydroxylation because this reaction is catalyzed in part by the mitochondrial cytochrome P-450, the enzyme responsible for the 27-hydroxylation of cholesterol. The purpose of this study was to verify whether the addition of cholesterol to preterm formulas could interfere with vitamin D metabolism in preterm neonates. METHODS: In a prospective study, 30 preterm neonates were randomly assigned to a low (< 0.03 g/L), medium (0.15 g/L), or high (0.30 g/L) cholesterol-content preterm formula until theoretical term (i.e., 40 weeks post-conceptional age). Anthropometric data and serum hydroxy-vitamin D and 1,25 dihydroxy-vitamin D concentrations were measured at study entry and theoretical term. In a subgroup of 14 subjects, serum cholesterol and lymphocyte 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA were also assessed. RESULTS: (median [25, 75 centiles]): At theoretical term, there were no significant differences in serum hydroxy-vitamin D concentrations among the three groups, even after adjustment for confounding variables (65 [50, 78] nmol/L, 79 [59, 86] nmol/L, and 67 [43, 103] nmol/L, respectively, = 0.65) or 1,25 dihydroxy-vitamin D ( = 0.88). Furthermore, there were no significant differences in 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA copy numbers. CONCLUSIONS: In preterm neonates fed formulas with a cholesterol content similar to or higher than that of human milk, we did not observe deleterious effects on vitamin D metabolism. However, long-term effects of cholesterol supplementation require further studies.

Nitrogen utilization and bone mineralization in very low birth weight infants fed partially hydrolyzed preterm formula.

Partialy hydrolyzed formulas have been proposed for term and preterm infants, but decreased nitrogen and calcium intestinal absorption rates, together with plasma amino acid imbalances have been reported in preterm infants. We evaluated a new formula with modified nitrogen and calcium sources (glycerophosphate). During their second week of life, 16 preterm infants were randomly assigned to 1 of 2 groups: 9 were fed the new partially hydrolyzed formula and 7 a conventional formula. A nutrient balance was performed at the end of the first month of life. Amino acid concentrations and whole-body mineralization were measured at the end of study period (theoretical term). Birth weight and gestational age (mean +/- SD) were similar in the 2 groups (28.9 +/- 7.0 wks and 1,183 +/- 242 g v 27.7 +/- 1.0 wks and 1,139 +/- 162 g). Median nitrogen absorption rate (85% v 89%; P = .03) was lower in infants fed the new formula than in those fed the conventional one. After correction for difference in nitrogen intake, there was no significant difference in N retained between the 2 groups (P = .11). Plasma amino acid concentrations were also similar in the 2 groups. At theoretical term, median bone mineral content was not significantly different between the 2 groups (50 g/kg v 55 g/kg; P = .17) and it was close to the reference values obtained in term neonates just after birth. As long as nitrogen content is 10% higher in protein hydrolyzed formula than in entire protein formula, appropriate nitrogen retention, plasma amino acid profile can be achieved with the new partially hydrolyzed formula. In both groups, bone mineralization at theoretical term was close to the mineralization observed term neonates just after birth.