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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Breastfeeding &#40;BF&#41; is the gold standard for nutrition of preterm &#40;PT&#41; infants due to its short- and long-term health benefits&#46; If the mother&#39;s own milk is not available&#44; banked donor human milk &#40;DHM&#41; is considered the best alternative&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">1</span></a> However&#44; in many instances DHM alone does not meet the full nutritional requirements of the infant&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">1&#8211;3</span></a> To optimise nutrient intake in this group to improve growth and development outcomes&#44; fortifiers have been developed to add to human milk to contribute energy&#44; protein&#44; minerals and vitamins&#46; Most fortifiers are multicomponent preparations derived from bovine milk&#44; although there are also fortifiers made from DHM and single-component fortifiers in the market&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">4</span></a> These products are widely used in neonatal units&#44; with a standardised approach or with an individualised approach whereby the addition of fortifiers is adjusted based on the analysis of milk composition or blood urea nitrogen &#40;BUN&#41; levels&#46; Early studies comparing this nutritional management in PT infants with conventional BF found improvement in anthropometric measures&#44; nitrogen balance and BUN levels&#44; serum albumin&#44; total protein and prealbumin levels&#44; and normalisation of bone markers&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">5&#44;6</span></a> However&#44; a recent review only found a difference in anthropometric outcomes during the hospital stay&#44; but no other relevant benefits&#44; complications or adverse effects&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">5</span></a> Nevertheless&#44; fortification of human milk is not free of drawbacks&#44; as processing the milk results in a decreased absorption of fats and an increase in milk osmolality&#46; Osmolarity and osmolality are terms used to express the total concentration of solutes&#44; or osmols&#44; of a solution&#46; Broadly speaking&#44; osmolality measures concentration based on the osmols of solute per kilogram of solvent&#44; expressed as mOsm&#47;kg&#44; while osmolarity refers to the osmols of solute per litre of solvent&#44; expressed as mOsm&#47;L&#46; Since the volume of the solution changes with the addition of solute and with changes in temperature and pressure&#44; the osmolarity is difficult to measure&#46; In contrast&#44; the mass of solvent remains constant regardless of changes in temperature or pressure&#44; so osmolality is easier to evaluate and therefore used more widely&#44; and it is currently considered the standard measure of concentration&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">7</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The association between a high osmolality in the nutritional intake and the risk of gastrointestinal problems and necrotising enterocolitis &#40;NEC&#41; is a source of concern&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">7</span></a> To reduce this risk&#44; the American Academy of Pediatrics &#40;AAP&#41; recommends a maximum threshold of 450<span class="elsevierStyleHsp" style=""></span>mOsm&#47;kg &#40;approximately 400<span class="elsevierStyleHsp" style=""></span>mOsm&#47;L&#41;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">8</span></a> in infant nutrition&#46; The scientific evidence in support of this recommendation is scarce and questionable&#44; as it seems that its clinical impact is little more than a slowing down of gastric emptying&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">7</span></a> However&#44; there is evidence that osmolalities greater than 700<span class="elsevierStyleHsp" style=""></span>mOsm&#47;kg in therapeutic fluids or radiological contrasts are associated with an increased incidence of NEC&#44;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">9</span></a> and therefore a theoretical threshold of 400&#8211;600<span class="elsevierStyleHsp" style=""></span>mOsm&#47;kg is widely applied&#44; although there is no evidence to support it&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">10</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Pasteurised and frozen DHM is widely used in neonatal units&#46; It has been demonstrated that these processes affect the osmolality of human milk&#46; While pasteurisation decreases the osmolality&#44; freezing increases it&#44; although not significantly&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">6</span></a> Published data on the kinetics of the changes in osmolality in samples of fortified human milk are contradictory&#46; The most recent studies suggest that the main factor contributing to the increase is the instant addition of solutes that takes place on adding the fortifier&#44;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">11&#44;12</span></a> after which the increase in osmolality over time is not that significant&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In our neonatal unit&#44; the general approach to the nutrition of PT infants is administration of maternal milk or DHM when the mother&#39;s own milk is not available&#44; with routine fortification with a multicomponent fortifier and the addition on a case-by-case basis of a modular protein supplement if needed&#46; The protocol of the unit also calls for administration of a multivitamin to patients that do not receive fortified human milk&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">We did not find any studies in the literature analysing the increases in osmolality associated with the addition of the fortifiers used in our unit to DHM&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">For this reason&#44; we designed this study to analyse changes in the osmolality of DHM after the addition of a multicomponent bovine milk protein fortifier&#44; a modular protein supplement and a multivitamin&#46; In order to match everyday clinical practice&#44; we analysed changes in osmolality through time&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study design</span><p id="par0035" class="elsevierStylePara elsevierViewall">Prospective study conducted by the departments of neonatology and pharmacy of the Hospital Universitario y Polit&#233;cnico La Fe in Valencia&#44; Spain&#44; between May 2018 and February 2019&#46; We analysed the osmolality of human milk donated to the regional milk bank &#40;Banco de Leche Materna de la Comunidad Valenciana&#44; BLMCV&#41;&#44; which did not meet the criteria established by the bank to be administered to patients&#44; but whose donors signed an informed consent form allowing its use in research&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Analysis of the composition of donor human milk</span><p id="par0040" class="elsevierStylePara elsevierViewall">We analysed the macronutrient contents of the milk &#40;fat&#44; protein and lactose&#41; by infrared transmission spectroscopy with a Miris HMA&#169; analyser &#40;Miris Holding AB&#44; Uppsala&#44; Sweden&#41;&#59; the results are presented in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Samples were thawed&#44; heated to 40<span class="elsevierStyleHsp" style=""></span>&#176;C and homogenised &#40;for 1&#46;5<span class="elsevierStyleHsp" style=""></span>s per 1<span class="elsevierStyleHsp" style=""></span>mL of milk&#41; with an ultrasonic processor &#40;VCX 130&#59; Sonics &#38; Material&#44; Newtown&#44; CT&#44; USA&#41; before the analysis&#46; In adherence with the protocol of the unit&#44; we made a single measurement&#44; and if the value was not in the normal range&#44; we repeated the measurement&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Types of fortification</span><p id="par0045" class="elsevierStylePara elsevierViewall">Fortification of DHM adhered to the protocol of the unit and manufacturer recommendations&#46; We used the PreNAN FM85&#169; fortifier &#40;Nestl&#233; Infant Nutrition&#59; Vevey&#44; Switzerland&#41;&#44; the Resource&#169; Instant Protein supplement &#40;Nestl&#233; Health Science&#59; Vevey&#44; Switzerland&#41; and the Hidropolivit&#169; multivitamin supplement &#40;Grupo Menarini&#59; Badalona&#44; Spain&#41; &#40;compositions presented in <a class="elsevierStyleCrossRefs" href="#tbl0010">Tables 2 and 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">We analysed each of the samples without any additives &#40;fortification A&#58; unfortified DHM&#41; and with 4 different types of fortification&#58; addition of 4 drops of Hidropolivit&#169; multivitamin to 25<span class="elsevierStyleHsp" style=""></span>mL of DHM &#40;fortification B&#41;&#44; addition of 1<span class="elsevierStyleHsp" style=""></span>g of PreNAN FM85&#169; to 25<span class="elsevierStyleHsp" style=""></span>mL of DHM &#40;fortification C&#41;&#44; addition of 1<span class="elsevierStyleHsp" style=""></span>g of PreNAN FM85&#169; and 0&#46;1<span class="elsevierStyleHsp" style=""></span>g of Resource&#169; Instant Protein to 25<span class="elsevierStyleHsp" style=""></span>mL of DHM &#40;fortification D&#41;&#44; and addition of 1<span class="elsevierStyleHsp" style=""></span>g of PreNAN FM85&#169; and 0&#46;2<span class="elsevierStyleHsp" style=""></span>g of Resource&#169; Instant Protein to 25<span class="elsevierStyleHsp" style=""></span>mL of DHM &#40;fortification E&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">We stored the DHM frozen at &#8722;20<span class="elsevierStyleHsp" style=""></span>&#176;C from the moment of extraction to the moment of its use&#59; DHM was thawed at room temperature before its preparation&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Fortifiers were added with a stepwise procedure&#44; mixing the preparation with a vortex shaker &#40;Vortamix&#44; Argos Technologies&#44; South Scottsdale Court&#44; USA&#41; until the solution became homogeneous&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Osmometer and measurement of osmolality</span><p id="par0065" class="elsevierStylePara elsevierViewall">We measured osmolality with a Fiske 210 osmometer &#40;Advanced Instruments Inc&#46;&#59; Norwood&#44; MA&#44; USA&#41; that determines the osmolality of solutions using freezing point depression&#46; It uses high-precision thermistors to measure the temperature of the sample&#44; freezing the sample while monitoring for potential overcooling and measuring the freezing point&#44; and it is accurate to 1<span class="elsevierStyleHsp" style=""></span>mOsm&#47;kg H<span class="elsevierStyleInf">2</span>O&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">13</span></a> Freezing-point depression osmometry is the industry-preferred solution and the criterion standard in clinical chemistry laboratories and pharmaceutical research&#46; It provides quick and accurate measurements and it is the most widely referenced and practiced technique for osmolarity testing&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">6</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">We calibrated the instrument with 20<span class="elsevierStyleHsp" style=""></span>&#956;L of Accuref 290 reference solution &#40;Advanced Instruments Inc&#46;&#59; Norwood&#44; MA&#44; USA&#41;&#46; We prepared all samples taking aliquots of 25<span class="elsevierStyleHsp" style=""></span>mL&#44; and then transformed the data to calculate values corresponding to 100<span class="elsevierStyleHsp" style=""></span>mL of human milk&#46; To ensure that the aliquots were representative of the DHM&#44; we homogenised the samples &#40;25<span class="elsevierStyleHsp" style=""></span>mL&#41; by mixing for 30<span class="elsevierStyleHsp" style=""></span>s with a vortex shaker &#40;Vortamix&#44; Argos Technologies&#44; South Scottsdale Court&#44; USA&#41;&#46; We measured the osmolality of the DHM unfortified and with different types of fortification&#44; making 3 measurements for each sample at baseline &#40;<span class="elsevierStyleItalic">t</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44; immediately after addition of the fortifier&#41;&#44; 4&#44; 9 and 24<span class="elsevierStyleHsp" style=""></span>h&#46; Between measurements&#44; DHM was stored at 2&#8211;8<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; and samples were brought to room temperature before each measurement&#46; Each measurement used 20<span class="elsevierStyleHsp" style=""></span>&#956;L of milk&#44; and we have expressed results as total osmolality in mOsm&#47;kg&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical analysis</span><p id="par0075" class="elsevierStylePara elsevierViewall">We performed the statistical analysis with the software R software &#40;version 3&#46;5&#46;1&#41; and the packages CliCR &#40;version 0&#46;4&#46;22&#41; and lme4 &#40;version 1&#46;1-18-1&#41; &#40;The Freesoftware Foundation&#44; Boston&#44; USA&#41;&#46; We have summarised numerical data as mean and standard deviation &#40;SD&#41; and median and interquartile range&#44; and qualitative data as absolute frequencies and percentages&#46; To analyse the changes of the osmolality over time in each aliquot&#44; we fitted a mixed linear regression model&#44; introducing each milk preparation as a random factor and applying the interaction between the type of fortification and time&#46; We took into account the composition of the different samples of DHM and entered the fat&#44; protein and lactose contents as confounding variables&#46; To analyse changes in the milk based on its composition&#44; we fitted a linear regression model in which each milk was a random factor&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><p id="par0080" class="elsevierStylePara elsevierViewall">We analysed a total of 30 samples of DHM from 6 healthy mothers&#44; unfortified and with 4 fortification schemes&#46; We analysed each sample at 4 time points&#44; taking each measurement 3 times&#44; which resulted in a total of 360 measurements&#46; The mean osmolality of the DHM at baseline &#40;<span class="elsevierStyleItalic">t</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>18&#41; was 301<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;2<span class="elsevierStyleHsp" style=""></span>mOsm&#47;kg&#44; which was consistent with the previous literature&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">4&#44;6&#44;14</span></a> The osmolality of DHM &#40;fortification A&#41; stored in a refrigerator at a temperature of 2&#8211;8<span class="elsevierStyleHsp" style=""></span>&#176;C increased slightly over time&#44; reaching a mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD at 24<span class="elsevierStyleHsp" style=""></span>h of 308&#46;11<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;21<span class="elsevierStyleHsp" style=""></span>mOsm&#47;kg &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;021&#41;&#44; within the safe range for administration to PT infants&#46; The addition of vitamins &#40;fortification B&#41; did not increase the osmolality to a clinically relevant degree compared to unfortified DHM&#44; with a baseline osmolality of 347&#46;33<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19&#46;22 that increased over time to up to 354&#46;11<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19&#46;12<span class="elsevierStyleHsp" style=""></span>mOsm&#47;kg at 24<span class="elsevierStyleHsp" style=""></span>h&#44; and the differences in the comparison with unfortified milk were not significant &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;971&#41;&#46; The addition of modular protein &#40;PreNAN FM85&#169;&#41; did result in a significant increase in the baseline osmolality that also increased significantly more over time &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#44; &#46;007 and &#46;007 in the comparison of fortification type A with types C&#44; D and E&#44; respectively&#41;&#44; but there were no differences in osmolality between fortification schemes C&#44; D and E &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> and <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">When we fortified DHM with PreNAN FM85&#169; &#40;type C&#41; following the recommendations of the manufacturer&#44; the baseline osmolality at <span class="elsevierStyleItalic">t</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0 was 432&#46;33<span class="elsevierStyleHsp" style=""></span>mOsm&#47;kg &#40;SD&#44; 14&#46;49&#41;&#44; different from the osmolality reported in the summary of product characteristics &#40;osmolarity<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>339<span class="elsevierStyleHsp" style=""></span>mOsm&#47;L&#44; which is equivalent to 381<span class="elsevierStyleHsp" style=""></span>mOsm&#47;kg&#41;&#44; but it was still within a range considered to be safe&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discussion</span><p id="par0090" class="elsevierStylePara elsevierViewall">The high nutritional requirements of PT infants are not fully met by human milk&#44; and therefore fortification is recommended&#46; But fortification has been associated with an increase in gastrointestinal intolerance and gastro-oesophageal reflux&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">15</span></a> The association with more severe disease&#44; such as NEC&#44; is under debate and there is no clear evidence on the subject&#46; Necrotising enterocolitis is a multifactorial disease&#44; and it has been hypothesised that human milk fortifiers could contribute to its development by increasing the osmolality in the intestinal lumen&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">11</span></a> Although there is a growing body of evidence contradicting this hypothesis&#44; caution should be exerted in choosing a fortification scheme to keep from exposing patients to a risk that has yet to be ruled out&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">7</span></a> Early studies on the osmolality of fortified human milk found concerning values higher than the 450<span class="elsevierStyleHsp" style=""></span>mOsm&#47;kg threshold considered safe by the AAP&#46; Today&#44; with the development of new fortification preparations and strategies that sometimes combine several preparations&#44; there is a lack of data on the associated changes in the osmolality of human milk and of banked DHM&#44; which also undergoes processing that affects its osmolality&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">A recent survey of several level III neonatal units in Europe and another nationwide survey of neonatal units in Spain revealed substantial variation in human milk processing practices&#44; including fortification&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">16&#44;17</span></a> The differences in organisational structure&#44; staffing&#44; availability of DHM and the products available to fortify milk entail a need to establish protocols for the use of maternal milk and DHM and their fortification&#44; aiming to maximise effectiveness and safety&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">The routine approach in our tertiary care unit is to strive to achieve feeding of all very low birth weight PT infants with maternal milk&#44; and DHM sourced from the BLMCV is also available for patients if the mother&#39;s own milk is not available or does not suffice to meet the infant&#39;s requirements&#46; Before administration&#44; DHM was pasteurised following the protocol of the milk bank &#40;Holder pasteurisation&#44; 62&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C for 30<span class="elsevierStyleHsp" style=""></span>min&#41; and stored frozen until its administration&#46; We also used a standard fortification strategy&#44; starting out systematically with a multicomponent fortifier&#44; and then adjusting the protein content in select cases with the addition of a modular protein individualised based on the analysis of amino acid metabolism or the nutritional composition of maternal or donor human milk&#46; Individualised fortification is recommended in PT infants that do not meet the expected growth rate&#44; especially those fed with DHM&#44; given the variability in its composition&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">18</span></a> We performed the macronutrient analysis by means of infrared spectroscopy&#44; which had proven useful in a previous study by our group&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">19</span></a> Kreissl et al&#46; reported an increase in the osmolality of human milk of 297&#8211;436<span class="elsevierStyleHsp" style=""></span>mOsm&#47;L with the addition of a bovine whey protein fortifier&#44; and an additional increase of 23&#46;5<span class="elsevierStyleHsp" style=""></span>mOsm&#47;L per 0&#46;5<span class="elsevierStyleHsp" style=""></span>g step of protein supplementation&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">6</span></a> This study used protein fortification amounts that far exceeded the recommendations for supplementation in PT infants published by the European Society for Paediatric Gastroenterology Hepatology and Nutrition &#40;ESPGHAN&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">2</span></a> We did not find any data in the literature on the use of the new multicomponent human milk fortifier preparation&#44; PreNAN FM85&#169;&#44; added to banked DHM that has been subjected to pasteurisation and freezing&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Based on the analysis of the samples&#44; we can assert that the maximum level of fortification used routinely in our unit&#44; while exceeding the 450<span class="elsevierStyleHsp" style=""></span>mOsm&#47;kg safety threshold proposed by the AAP with a maximum osmolality of 459&#46;18<span class="elsevierStyleHsp" style=""></span>mOsm&#47;kg&#44;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">8&#44;18</span></a> it never exceeded 600<span class="elsevierStyleHsp" style=""></span>mOsm&#47;kg&#44; which is within the range considered safe for nutrition of PT infants&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">10</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Our findings suggest a tendency towards a decrease in osmolality with the increase of modular protein supplementation&#46; The dosage was &#43;0&#46;1 to &#43;0&#46;2<span class="elsevierStyleHsp" style=""></span>g of protein per 25<span class="elsevierStyleHsp" style=""></span>mL of DHM&#44; which did not result in a significant increase in the total protein content of the sample&#44; and in fact we did not find statistically significant differences between fortification schemes C&#44; D and E&#46; This was consistent with the results of a previous study that reported an average increase in osmolality of 38<span class="elsevierStyleHsp" style=""></span>mOsm&#47;kg with the addition of 1<span class="elsevierStyleHsp" style=""></span>g of hydrolysed protein per 100<span class="elsevierStyleHsp" style=""></span>mL milk&#44;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">20</span></a> the same amount of protein contained in the fortifier used in our study&#44; which would correspond to differences 3&#46;8<span class="elsevierStyleHsp" style=""></span>mOsm&#47;kg between fortification schemes C&#44; D and E in our study&#44; which are not clinically significant and would also account for the absence of statistically significant differences in the analysis&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">When it comes to supplementation with a multivitamin&#44; as long as a full dose of enteral nutrition is delivered&#44; with a feed volume greater than 20<span class="elsevierStyleHsp" style=""></span>mL&#44; this is a safe practice that reduces the amount of handling and does not pose a risk of feeding intolerance secondary to an increase in osmolality&#46; Our findings were consistent with those of previous studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">21&#44;22</span></a> In case of smaller feed volumes&#44; a possible approach could be to split the total daily dose into smaller doses to reduce the resulting osmolality in each of the feeds&#46; If maternal milk or DHM are fortified with PreNAN FM85&#169; and the infant receives more than 100<span class="elsevierStyleHsp" style=""></span>mL&#47;kg per day&#44; addition of a multivitamin is unnecessary&#44; as recommended vitamin intakes are met by the fortifier and it is better to avoid combining different products&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">As for the kinetics of the changes in osmolality&#44; our findings were consistent with those published previously by other authors&#44;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">11&#44;12</span></a> as we found a rapid increase in osmolality right after the addition of the fortifier &#40;86&#37; of the total increase&#41;&#44; while refrigeration in the 24<span class="elsevierStyleHsp" style=""></span>h that followed accounted for 14&#37; of the total increase&#46; Fortification accounted for most of the increase in osmolality through the direct addition of solute&#44; as the degradation over time of milk or fortifier components&#44; mainly through the effect of the amylase present in human milk that releases molecules with a higher osmolality &#40;monosaccharides or disaccharides&#41;&#44; is a much slower process that thus contributes less to the increase in osmolality and accounts for the increase observed in the preparation over time&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">11</span></a> These data support the recommendation of dedicating an area within neonatal intensive care units to the preparation of PT infant nutrition under safe conditions to prevent contamination&#46; Also&#44; although preparation immediately before administration is preferable&#44; it would be acceptable to prepare the nutrition to be delivered in a 24<span class="elsevierStyleHsp" style=""></span>h-period in a single session per day&#44; by a single member of the staff&#44; allocating to the task the time needed to minimise errors&#44; avoid contamination&#44; etc&#46;&#44; which would not be detrimental to the safety of the patient as far as osmolality is concerned&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conclusions</span><p id="par0135" class="elsevierStylePara elsevierViewall">The osmolality values found in thawed DHM samples were similar to those reported by other authors&#46; Increases in osmolality resulting from storage of thawed DHM at temperatures of 2&#8211;8<span class="elsevierStyleHsp" style=""></span>&#176;C were within the range generally accepted as safe&#44; so it is possible to prepare the milk for PT infants in the neonatal intensive care unit once a day and keep it refrigerated without it resulting in a dangerous increase in osmolality by the time of administration&#46; The increase in osmolality associated with the addition of a multivitamin to DHM free from any other fortifiers does not exceed the threshold considered safe for nutrition of PT infants&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflicts of interest</span><p id="par0140" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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              "titulo" => "Analysis of the composition of donor human milk"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The fortification of maternal milk &#40;MM&#41; is a standard practice in order to achieve the requirements needed for the growth and development of the premature newborn&#46; However&#44; its osmolality could increase&#46; According to the American Paediatrics Academy&#44; it is recommended not to exceed 450<span class="elsevierStyleHsp" style=""></span>mOsm&#47;kg &#40;approximately 400<span class="elsevierStyleHsp" style=""></span>mOsm&#47;L&#41; in the diet of the infant&#44; even though the safety limit is estimated to be between 400 and 600<span class="elsevierStyleHsp" style=""></span>mOsm&#47;kg&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The aim of this study is to determine the osmolality of thawed and fortified donated MM &#40;DMM&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Method</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">An analysis was performed on DMM of 6 healthy mothers&#44; without fortifying&#44; and with 4 levels of fortification&#46; Measurement of the samples was carried out in triplicate at 0&#44; 4&#44; 9&#44; and 24<span class="elsevierStyleHsp" style=""></span>h after their preparation&#46; They were stored refrigerated &#40;2&#8211;8<span class="elsevierStyleHsp" style=""></span>&#176;C&#41; between measurements&#46; The study groups were&#58; &#40;A&#41; non-fortified DMM&#59; &#40;B&#41; DMM with vitamins added&#59; &#40;C&#41; with the addition of a fortifier&#59; &#40;D&#41; with the addition of a low-dose protein formula&#59; and &#40;E&#41; with the addition of a high-dose protein formula&#46; The osmolality determinations were carried out using a freezing-point osmometer&#46; The data analysis was performed using R software &#40;v&#46;3&#46;5&#46;1&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A total of 30 samples were analysed with 360 measurements&#46; The osmolality of the DMM at <span class="elsevierStyleItalic">t</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0<span class="elsevierStyleHsp" style=""></span>h was 301<span class="elsevierStyleHsp" style=""></span>mOsm&#47;kg &#40;SD 5&#46;2&#41; and slightly increased with time to 308&#46;11<span class="elsevierStyleHsp" style=""></span>mOsm&#47;kg &#40;SD 5&#46;21&#41; after 24<span class="elsevierStyleHsp" style=""></span>h &#40;<span class="elsevierStyleItalic">t</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>24<span class="elsevierStyleHsp" style=""></span>h&#41;&#44; being maintained within the safety limits&#46; The addition of vitamins &#40;Group B&#41; did not significantly increase the osmolality&#46; The addition of a fortifier &#40;C&#41; and a low dose &#40;D&#41; or high dose &#40;E&#41; protein formula produced an increase in the baseline osmolality that increased statistically significantly in time &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;007&#41;&#44; but with no differences between the C&#44; D&#44; and E types&#46; There were differences between the osmolality at <span class="elsevierStyleItalic">t</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0 with the fortification according to the manufacturer&#39;s data sheet &#40;339<span class="elsevierStyleHsp" style=""></span>mOsm&#47;L&#41; and the findings in our laboratory &#40;432&#46;33<span class="elsevierStyleHsp" style=""></span>mOsm&#47;L&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The osmolality values found in the thawed DMM samples were similar to those of other studies&#46; The fortification of the DMM samples and their storage refrigerated at 2&#8211;8<span class="elsevierStyleHsp" style=""></span>&#176;C for 24<span class="elsevierStyleHsp" style=""></span>h increased the osmolality&#44; but keeping them within the safety limits&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n y objetivos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">La fortificaci&#243;n de la leche materna &#40;LM&#41; es una pr&#225;ctica habitual para alcanzar los aportes necesarios para el crecimiento y desarrollo del reci&#233;n nacido prematuro&#46; Sin embargo&#44; puede aumentar su osmolalidad&#46; Seg&#250;n la Academia Americana de Pediatr&#237;a&#44; se recomienda no superar 450 mOsm&#47;kg &#40;aproximadamente 400 mOsm&#47;l&#41; en la alimentaci&#243;n del lactante&#44; aunque el l&#237;mite de la seguridad se estima entre 400-600 mOsm&#47;kg&#46;</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El objetivo de este estudio es determinar la osmolalidad de la LM donada &#40;LMD&#41; descongelada y fortificada&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todo</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se analiz&#243; la LMD de 6 madres sanas&#44; sin fortificar y con 4 pautas de fortificaci&#243;n&#44; realizando mediciones por triplicado de las muestras a tiempo 0&#44; 4&#44; 9 y 24 h tras su preparaci&#243;n&#46; Entre mediciones se almacen&#243; refrigerada &#40;2-8<span class="elsevierStyleHsp" style=""></span>&#176;C&#41;&#46; Los grupos de estudio fueron&#58; <span class="elsevierStyleItalic">1&#41;</span> A&#58; LMD no fortificada&#59; <span class="elsevierStyleItalic">2&#41;</span> B&#58; LMD con adici&#243;n de vitaminas&#59; <span class="elsevierStyleItalic">3&#41;</span> C&#58; con adici&#243;n de fortificante&#59; <span class="elsevierStyleItalic">4&#41;</span> D&#58; con adici&#243;n de m&#243;dulo proteico a dosis baja&#44; y <span class="elsevierStyleItalic">5&#41;</span> E&#58; con adici&#243;n de m&#243;dulo proteico a dosis alta&#46; Las determinaciones de osmolalidad se realizaron un osm&#243;metro criosc&#243;pico&#46; El an&#225;lisis de datos se realiz&#243; con R software &#40;v&#46;3&#46;5&#46;1&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Se analizaron un total de 30 muestras &#40;360 mediciones&#41;&#46; La osmolalidad de la LMD a t<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0<span class="elsevierStyleHsp" style=""></span>h fue 301 mOsm&#47;kg &#40;DE 5&#44;2&#41; y aument&#243; ligeramente con el tiempo a 308&#44;11 mOsm&#47;kg &#40;DE 5&#44;21&#41; despu&#233;s de 24 h &#40;t<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>24<span class="elsevierStyleHsp" style=""></span>h&#41;&#44; manteni&#233;ndose en los l&#237;mites de seguridad&#46; La adici&#243;n de vitaminas no aument&#243; la osmolalidad de manera significativa &#40;grupo B&#41;&#46; La adici&#243;n de fortificante &#40;C&#41; y m&#243;dulo de prote&#237;nas con dosis baja &#40;D&#41; o dosis alta &#40;E&#41; produjo un aumento de osmolalidad basal que se increment&#243; en el tiempo de manera estad&#237;sticamente significativa &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;007&#41; pero sin diferencias entre los tipos C&#44; D y E&#46; Hubo diferencias entre la osmolalidad en t<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0 con la fortificaci&#243;n seg&#250;n la ficha t&#233;cnica del fabricante &#40;339 mOsm&#47;l&#41; y los hallazgos en nuestro laboratorio &#40;432&#44;33 mOsm&#47;l&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Los valores de osmolalidad hallados en las muestras de LMD descongelada son similares a los de otros estudios&#46; La fortificaci&#243;n de la LMD y su conservaci&#243;n refrigerada entre 2-8<span class="elsevierStyleHsp" style=""></span>&#176;C durante 24<span class="elsevierStyleHsp" style=""></span>h aumenta la osmolalidad&#44; pero manteni&#233;ndose dentro de los l&#237;mites de seguridad&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Please cite this article as&#58; Torres Mart&#237;nez E&#44; Garc&#237;a Robles AA&#44; Gormaz Moreno M&#44; Gimeno Navarro A&#44; Izquierdo Maci&#225;n I&#44; Poveda Andr&#233;s JL&#44; et al&#46; Efecto de la adici&#243;n de fortificantes y de m&#243;dulo de prote&#237;nas en la osmolalidad de la leche materna donada&#46; An Pediatr &#40;Barc&#41;&#46; 2020&#59;93&#58;297&#8211;304&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Previous presentation&#58; brief oral presentation at the XXVII Congress of Neonatology and Perinatal Medicine&#59; October 2&#8211;4&#44; 2019&#59; Madrid&#44; Spain&#46;</p>"
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Zn&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#46;5<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cu&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;3<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">45<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Se&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">93<span class="elsevierStyleHsp" style=""></span>&#956;g&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Energy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">435<span class="elsevierStyleHsp" style=""></span>kcal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">371<span class="elsevierStyleHsp" style=""></span>kcal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Osmolarity&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">339<span class="elsevierStyleHsp" style=""></span>mOsm&#47;L<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                  <table border="0" frame="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Hidropolivit&#169;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Component&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1<span class="elsevierStyleHsp" style=""></span>mL<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>28 drops&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 drops&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1<span class="elsevierStyleHsp" style=""></span>g&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retinol &#40;vit&#46; A&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1500<span class="elsevierStyleHsp" style=""></span>IU&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">214<span class="elsevierStyleHsp" style=""></span>IU&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">297<span class="elsevierStyleHsp" style=""></span>IU&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Riboflavin &#40;vit&#46; B2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;3<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;05<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nicotinamide &#40;vit&#46; PP&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#46;5<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;8<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pyridoxine &#40;vit&#46; B6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;6<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;2<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;03<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Biotin &#40;vit&#46; H&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;125<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;018<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;001<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ascorbic acid &#40;vit&#46; C&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;14<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cholecalciferol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">600<span class="elsevierStyleHsp" style=""></span>IU&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">85<span class="elsevierStyleHsp" style=""></span>IU&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36<span class="elsevierStyleHsp" style=""></span>IU&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleSmallCaps">dl</span>-&#945;-tocopherol acetate &#40;vit&#46; E&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;4<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                  \t\t\t\t">354&#46;11<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19&#46;12&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">459&#46;18<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;18&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">445&#46;22<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;64&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">447&#46;89<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;24&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">454&#46;28<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;74&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#46;02&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation of the osmolality &#40;mOsm&#47;kg&#41; at each time point by type of fortification&#46;</p>"
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                      "titulo" => "Human milk in feeding premature infants&#58; consensus statement"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46;E&#46; Moro"
                            1 => "S&#46; Arslanoglu"
                            2 => "E&#46; Bertino"
                            3 => "L&#46; Corvaglia"
                            4 => "R&#46; Montirosso"
                            5 => "J&#46;C&#46; Picaud"
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                    0 => array:2 [
                      "doi" => "10.1097/01.mpg.0000471460.08792.4d"
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                        "tituloSerie" => "J Pediatr Gastroenterol Nutr"
                        "fecha" => "2015"
                        "volumen" => "61"
                        "paginaInicial" => "S16"
                        "paginaFinal" => "S19"
                        "link" => array:1 [
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26295999"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Enteral nutrient supply for preterm infants&#58; Commentary from the ESPGHAN Committee on Nutrition"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "for the ESPGHAN Committee on Nutrition"
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Agostoni"
                            1 => "G&#46; Buonocore"
                            2 => "V&#46;P&#46; Carnielli"
                            3 => "M&#46; de Curtis"
                            4 => "D&#46; Darmaun"
                            5 => "T&#46; Decsi"
                          ]
                        ]
                      ]
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                  ]
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                    0 => array:2 [
                      "doi" => "10.1097/MPG.0b013e3181adaee0"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Pediatr Gastroenterol Nutr"
                        "fecha" => "2010"
                        "volumen" => "50"
                        "paginaInicial" => "85"
                        "paginaFinal" => "91"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19881390"
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                      "titulo" => "Metabolic bone disease of prematurity"
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                          "etal" => false
                          "autores" => array:3 [
                            0 => "S&#46;E&#46; Rustico"
                            1 => "A&#46;C&#46; Calabria"
                            2 => "S&#46;J&#46; Garber"
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Clin Transl Endocrinol"
                        "fecha" => "2014"
                        "volumen" => "1"
                        "paginaInicial" => "85"
                        "paginaFinal" => "91"
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                0 => array:2 [
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                      "titulo" => "Fortification of human milk for preterm infants&#58; update and recommendations of the European Milk Bank Association &#40;EMBA&#41; Working Group on human milk fortification"
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                          "etal" => true
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                            0 => "S&#46; Arslanoglu"
                            1 => "C&#46;-Y&#46; Boquien"
                            2 => "C&#46; King"
                            3 => "D&#46; Lamireau"
                            4 => "P&#46; Tonetto"
                            5 => "D&#46; Barnett"
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