Fortified Breast Milk Research Articles

Fortification of Breast Milk With Preterm Formula Powder vs Human Milk Fortifier in Preterm Neonates

Fortification of expressed breast milk (EBM) using commercially available human milk fortifiers (HMF) increases short-term weight and length in preterm very low-birth-weight (VLBW) neonates. However, the high cost and increased risk of feed intolerance limit their widespread use. Preterm formula powder fortification (PTF) might be a better alternative in resource-limited settings. To demonstrate that fortification of EBM by preterm formula powder is noninferior to fortification by HMF, in terms of short-term weight gain, in VLBW neonates. Open-label, noninferiority, randomized trial conducted from December 2017 to June 2019 at a level 3 neonatal unit in India. The trial enrolled preterm (born at or before 34 weeks of gestation) VLBW neonates receiving at least 100 mL/kg/d of feeds and consuming 75% of milk or more as EBM. Neonates were randomly assigned to receive fortification by either PTF or HMF. Calcium, phosphorus, iron, vitamin D, and multivitamins were supplemented in PTF and only vitamin D in the HMF group to meet the recommended dietary allowances. The primary outcome was the weight gain until discharge from the hospital or 40 weeks' postmenstrual age, whichever was earlier; the prespecified noninferiority margin was 2 g/kg/d. Secondary outcomes included morbidities such as necrotizing enterocolitis, feed intolerance, and extrauterine growth restriction (<10th percentile on the Fenton chart at 40 weeks' postmenstrual age). Of the 123 neonates enrolled, 60 and 63 were randomized to the PTF and HMF groups, respectively. The mean gestation (30.5 vs 29.9 weeks) and birth weight (1161 vs 1119 g) were comparable between the groups. There was no difference in the mean (SD) weight gain between the PTF and HMF groups (15.7 [3.9] vs 16.3 [4.0] g/kg/d; mean difference, -0.5 g/kg/d; 95% CI, -1.9 to 0.7). The lower bound of 95% CI did not cross the noninferiority margin. The incidence of feed intolerance was lower in the PTF group (1.4 vs 6.8 per 1000 patient-days; incidence rate ratio 0.19; 95% CI, 0.04 to 0.95), and fewer neonates required withholding of fortification for 24 hours or more (5% vs 22%; risk ratio, 0.22; 95% CI, 0.07 to 0.75). The incidence of necrotizing enterocolitis stage II or more (0 vs 5%) and extrauterine growth restriction (73% vs 81%) was comparable between the groups. Fortification with preterm formula powder is not inferior to fortification with human milk fortifiers in preterm neonates. Given the possible reduction in feed intolerance and lower costs, preterm formula might be a better option for fortification, especially in resource-restricted settings. Clinical Trial Registry, India Identifier: CTRI/2017/11/010593.

Breast milk protein content at week 3 after birth and neurodevelopmental outcome in preterm infants fed fortified breast milk.

Feeding supplemented mother milk during hospital stay improves neurodevelopment in preterm infants. Yet the composition of mother milk varies widely between subjects. The relationship between this variation and outcome is unknown. To determine whether the protein content in native breast milk (BM) correlates with 2-year infant outcome. In a monocentric prospective observational study, LACTACOL, preterm infants born between 28 and 34weeks of gestation, whose mothers decided to exclusively breastfeed, were enrolled during the first week of life. Samples of expressed breast milk obtained at several times of the day were pooled over a 24-h period, and such pool was used for macronutrient analysis, using mid-infrared analyzer. Age and Stages questionnaire (ASQ) was used to assess 2-year neurodevelopmental outcome. We analyzed the relationship between protein content in BM, and (i) infant neurodevelopment at 2-year (primary outcome), and (ii) growth until 2-year (secondary outcome). 138 infants were enrolled. The main analysis concerned 130 infants (including 40 twin infants) and 110 mothers with BM samples collected at week 3 after birth. Native BM samples were ranked in three tertiles of protein content (g/100ml): 0.91 ± 0.09 (lower), 1.14 ± 0.05 (middle) and 1.40 ± 0.15 (upper); 48, 47 and 35 infants were ranked, respectively, in these three tertiles. Infants in the upper tertile were more often singleton (P = 0.012) and were born with lower birth weight and head circumference Z-scores (P = 0.005 and 0.002, respectively). Differences in weight and head circumference were no longer observed at 2-year. ASQ score at age 2 did not differ betweenthe three tertiles (P = 0.780). Sensitivity analyses with imputations, including all 138 infants, confirmed the main analysis as well as analyses based on fortified BM as exposure. Protein content of BM (native or fortified) is not associated with preterm infant neurodevelopment at 2-year. Higher protein content was associated with a lower birth weight.

The role of breast milk fortifier in the post-discharge nutrition of preterm infants.

Infants born prematurely are often discharged from hospital before 37 weeks post-menstrual age. While breastfeeding will meet all the nutritional requirements of full-term infants, these preterm infants may need enhanced levels of protein, minerals and possibly energy to ensure optimum growth, bone mineralisation and neurological development. To meet these additional nutrient needs in the neonatal unit, it is currently recommended that multinutrient breast milk fortifier is added to maternal breast milk. There may also be benefits in continuing to provide fortified milk after discharge, potentially including improved growth and preserving breastfeeding, and this is increasingly becoming a recognised practice in some neonatal units. This article presents the discussion and consensus of a multidisciplinary panel of neonatologists, neonatal dietitians, a GP and a neonatal outreach sister. The aim is to develop guidance on providing safe and effective nutritional supplementation for preterm infants after discharge in order to maintain optimal growth. This guidance is aimed at community healthcare staff and is based on the limited evidence available, using shared best practice and expertise.

Sudden Onset of a Unilateral Erythematous Preauricular Mass in a Preterm Infant.

A 71-day-old 24 5/7-week gestation female infant in the NICU presents with right periauricular induration and erythema. ### Prenatal and Birth Histories ### Initial Hospital Course The infant was given endotracheal surfactant and placed on high-frequency jet ventilation. Blood and respiratory culture specimens were obtained and empiric antibiotics initiated. Respiratory culture was positive for Eikenella corrodens and placental pathology demonstrated necrotizing funisitis and chorioamnionitis. Antibiotics were switched to cefepime after sensitivities became available. At 8 days of age, she had an acute cardiopulmonary arrest in the setting of cardiac tamponade because of a hemorrhagic pericardial effusion. A pericardial pigtail catheter was placed and removed on day 12 with echocardiography demonstrating resolution of the effusion. Echocardiography also revealed a small ventricular septal defect and large patent ductus arteriosus, which was treated with 2 courses of indomethacin followed by acetaminophen. Respiratory support was weaned and the infant underwent extubation to continuous positive airway pressure on day 34. Central lines were removed on day 16 following advancement of enteral fortified breast milk feedings. Cranial ultrasonography …

Effect of targeted vs standard fortification of breast milk on growth and development of preterm infants (\u2264\u200932\u2009weeks): study protocol for a randomized controlled trial

BackgroundHuman milk is recommended for all very low birth weight infants. Breastmilk is highly variable in nutrient content, failing to meet the nutritional demands of this group. Fortification of human milk is recommended to prevent extrauterine growth retardation and associated poor neurodevelopmental outcome. However, standard fortification with fixed dose multicomponent fortifier does not account for the variability in milk composition. Targeted fortification is a promising alternative and needs further investigation.MethodsThis randomized controlled trial will recruit preterm infants (≤ 32 weeks of gestation) within the first 7 days of life. After reaching 80 ml/kg/day of enteral feeding, patients will be randomized to receive standard fortification (HMF, Nutricia) or targeted fortification (modular components: Bebilon Bialka, Nutricia—protein; Polycal, Nutricia—carbohydrates; Calogen, Nutricia—lipids). The intervention will continue until 37 weeks of post-conception age or hospital discharge. Parents and outcome assessors will be blinded to the intervention. The primary outcome measure is velocity of weight, length, and head growth until 36 weeks post-conceptional age or discharge. Secondary outcomes include neurodevelopment at 12 months assessed with Bayley Scale of Development III, repeated at 36 months; body composition at discharge and at 4 months; and incidence of necrotizing enterocolitis, sepsis, retinopathy of prematurity, and bronchopulmonary dysplasia.DiscussionTargeted fortification has previously been shown as doable in the neonatal intensive care unit context. If it shows to improve growth and neonatal outcome, choosing the targeted fortification as a first line nutritional approach in very low birth weight infants may become a recommendation.Trial registrationClinicalTrials.govNCT03775785, Registered on July 2019.

The use of Breast Milk Fortifier in Preterm Infants by paediatric dietitians in the UK.

Breast milk is the feed of choice for premature infants, although its nutritional composition is not always sufficient to meet their raised nutritional requirements. The addition of a multi-nutrient breast milk fortifier (BMF) to breastmilk is recommended; however, international guidelines on the use of BMF are inconsistent. The present study aimed to explore the use of BMF in preterm infants by paediatric dietitians in the UK. A questionnaire was designed and sent to members of the British Dietetic Association neonatal specialist group (n=100) using a secure online platform. Descriptive statistics were calculated. Forty dietitians completed the survey, all of whom used BMF. Local hospital BMF guidelines were available to 77.5% (n=31). The most commonly used criteria for commencing BMF were: tolerating a feed volume of 150mLkg-1 day-1 (72.5%, n=29), a gestational age <34weeks (67.5%, n=27) and a birth weight <1500g (60%, n=24). The primary contraindication for the use of BMF was necrotising enterocolitis (NEC). The majority of respondents used standard fortification, with individualised fortification available to only 12.5% (n=5). The most common indicators for discontinuing BMF were on discharge home (67.5%, n=27), satisfactory growth (65%, n=26) or feeding directly from the breast (62.5%, n=25). Although BMF is used more proactively in UK neonatal units than previously, variation in practice remains. Individualised fortification is very uncommon and caution remains regarding risk of NEC. The development of national guidelines on the use of BMF would help to standardise nutritional care in neonatal units.

P12 Evaluation of energy and protein intake in neonates using SCAMP regimen

AimsOur neonatal unit recently updated their parenteral and enteral feeding guideline and started using a standardised parenteral nutrition regimen (SCAMP).1The aim of this study was to observe the amount of energy and protein that was being delivered to patients using the SCAMP regimen and to evaluate whether it met the recommendations made by ESGPHAN in terms of energy and protein intake.2MethodsA data collection form was designed using Excel. Patients were identified using BadgerNet digital software. All required patient parameters were recorded from Badgernet. Data was anonymised and the Excel spreadsheet was password protected. A single investigator collected data over a 28 day period in October/November 2018. Only patients on the SCAMP regimen were included in the study. Patient data was collected from first day of SCAMP regimen until baby was discharged, or ceased parenteral nutrition.Results22 patients were identified for inclusion in the study. Of these, 17/22 (77%) weighed &lt; 1 kg.Majority of babies (20/22; 91%) were aged &lt; 31 weeks corrected gestational age when SCAMP was initiated.Majority of babies were on the SCAMP regimen due to prematurity; 4/22 (18%) had a surgical condition, that required PN to be initiated.1 patient had a complex congenital cardiac anomaly.Average length of time babies remained on SCAMP was 19 days (range 5–28 days).Majority of babies were enterally fed using breastmilk. Some babies were on alternative formula feeds.Mean amount of energy delivered to each patient was calculated. The amount of energy delivered increased daily over the first week, and by day 10 of life had reached the target range (110–135 kcal/kg/day). Recommended energy intake was then maintained for the rest of the 28–day study period.Target amount of protein intake varied for babies weighing &lt;1 kg and &gt;1 kg. For babies &lt;1 kg, a gradual increase occurred over the first 5 days of life. Recommended protein intake was met between days 5–10 of life, then there was a gradual decline.For babies weighing between 1–1.8 kg, the recommended protein intake was achieved within 24–48 hours. Higher than recommended amounts of protein were being delivered between days 5–10 of life. Mean protein intake remained within ESPGHAN recommendations (3.5–4 g/kg/day) during weeks 3 and 4 of life.The results are encouraging and demonstrate that neonates are managing to achieve the recommended amounts of energy intake from day 10 of life.LimitationsThis study focused solely on energy and protein intake – it did not include observations of growth. Future studies should consider looking at more patient-focused outcomes.ConclusionsSCAMP regimen is delivering the recommended amounts of energy for babies on the neonatal unit – target levels are achieved by day 10 of life.Future work should focus on observing growth in babies on SCAMPEarlier introduction of breast–milk fortifier may be helpful to increase protein intake in babies &lt; 1 kg – potential benefits need to be evaluated against risk of adverse effects.ReferencesMorgan C, Herwitker S, Badhawi I, et al. SCAMP: standardised, concentrated, additional macronutrients, parenteral nutrition in very preterm infants: a phase IV randomised, controlled exploratory study of macronutrient intake, growth and other aspects of neonatal care. BMC Pediatrics 2011;11:53.Koletzo B, Goulet O, Hunt J, et al. Guidelines on paediatric parenteral nutrition of the European society of paediatric gastroenterology, hepatology and nutrition (ESPGHAN) and the European society for clinical nutrition and metabolism (ESPEN), supported by the European society of paediatric research (ESPR). J Pediatr Gastroenterol Nutr 2005;41 (Suppl 2):S1–87.

Breastfeeding in hospitalised preterm infants: A survey from 18 tertiary neonatal intensive care units across mainland China.

To understand the use of breast milk and breastfeeding in preterm infants in neonatal intensive care units (NICUs) in mainland China. An online questionnaire survey of reported practices was conducted among 18 tertiary NICUs distributed across all seven districts in mainland China. The items of the questionnaire consisted of the following areas: breastfeeding rate of preterm infants (<37 weeks' gestation) at discharge, the standards used for guiding the clinical practice and the use of breast milk and breastfeeding. On average, across all hospitals, breastfeeding rate for preterm infants at discharge was 65%, with 41% preterm infants being exclusively breastfed during the hospitalisation prior to discharge. Sixteen (89%) NICUs had policies designating breast milk as the preferred first feed for preterm infants. Donor milk was available in 3 of 18 (17%) NICUs. Kangaroo care was provided in 11 of 18 (61%) NICUs, and 14 of 18 (78%) allowed parental access to the hospitalised preterm infants. A large variation was found in clinical practices around the breast milk testing, breast milk storage and transportation and breast milk fortification methods among different NICUs. The use of breast milk in hospitalised preterm infants has increased greatly but still needs to be further improved. A recommendation is made to conduct high-quality original trials to find evidence of the controversial problems, develop evidence-based guidelines, promote the best implementation of the guidelines and provide updated breastfeeding education to health-care providers in order to standardise the use of breast milk and breastfeeding in hospitalised preterm infants.

Evidence that informs feeding practices in very low birthweight and very preterm infants in sub-Saharan Africa: an overview of systematic reviews

BackgroundOptimal feeding of very low birthweight (VLBW <1500 g)/very preterm (gestation <32 weeks) infants in resource-limited settings in sub-Saharan Africa (sSA) is critical to reducing high mortality and poor outcomes.ObjectiveTo...

Comparison of Types of Breast Milk Fortification at Discharge from the Neonatal Intensive Care Unit and Breast Milk Feeding Rates and Growth at 4 Months Corrected Age.

Background: Effects of breast milk (BM) enhancement on long-term BM feeding in preterm infants discharged from the neonatal intensive care unit (NICU) have not been examined previously. This study compares any BM feeding rates at 4 months corrected age (CA) in preterm infants discharged from the NICU on BM enhancement by fortification of expressed BM with infant formula additives (BM-F) versus BM supplemented with infant formula feeds (BM-S). Subjects and Methods: We compared infants born between January 1, 2013, and December 31, 2017, with gestational age <32 weeks or birth weight <1500 g, discharged home on BM-F or BM-S from two NICUs and followed at 4 months CA. Multivariate logistic regression with propensity scoring estimated the adjusted associations between nutrition at discharge and any BM feeding at 4 months CA. Results: Two hundred eighty-five infants were followed at 4 months CA. Infants discharged on BM-F were more likely to have mothers with multiple gestation, private insurance and not Caucasian, initiate feeds of human milk, be discharged from NICU-1, and receive any BM at 4 months CA (p < 0.03). No significant difference in growth parameters <10th percentile at 4 months CA was observed between the two groups. After adjusting for confounding factors, discharge from the NICU on BM-F was significantly associated with BM feeding at 4 months CA (odds ratio: 3.89, 95% confidence interval 1.66-9.14, p = 0.002). Conclusion: In this observational study, preterm infants receiving BM fortified with formula powder additives at discharge from the NICU had better BM feeding outcomes without poor growth at 4 months CA relative to those infants receiving BM supplemented with infant formula feeds.

Earlier Nutrient Fortification of Breastmilk Fed LBW Infants Improves Jaundice Related Outcomes.

This study aimed to evaluate jaundice outcomes of low-birthweight premature infants commenced on earlier versus later nutrient supplementation (80 mL/kg/day vs. 160 mL/kg/day; total fluid intake, F80 vs. F160). Demographics, feeding regimens, and clinical outcomes data were collected. Infant and maternal characteristics were similar. Earlier nutrient supplementation was associated with multiple improved jaundice outcomes: total (TSBR), unconjugated and conjugated (CSBR) serum bilirubin values (196 ± 46 vs. 228 ± 52, 184 ± 44 vs. 212 ± 50, 12 ± 4 vs. 16 ± 5, respectively, all p < 0.001); phototherapy (39% vs. 64%, p < 0.0001). % CSBR/TSBR ratio was similar between groups. For those on phototherapy, duration and median irradiance were similar. F80 infants experienced reduced: feeding intolerance (26.0% vs. 45.2%, p = 0.007); length of stay (16.0 ± 0.64 vs. 18.8 ± 0.74 days, p = 0.03), maximum weight loss as % birth weight (5% vs. 6%, p = 0.03); decrease in weight Z-score at 10 days (−0.70 ± 0.03 vs. −0.79 ± 0.03, p = 0.01). F80 infants regained birthweight earlier (10.0 ± 0.3 days vs. 11.5 ± 0.3 days, p < 0.0001) and had no differences in adverse clinical outcomes. We speculate that earlier nutrient supplementation improved jaundice outcomes due to enhanced excretion/elimination of bilirubin.

Early fortification of enteral feedings for infants

BACKGROUND:An exclusive human milk diet (EHM) including fortification with a human milk-based fortifier has been shown to decrease the occurrence of necrotizing enterocolitis (NEC) but growth velocity may be less for infants receiving EHM compared to a bovine diet.OBJECTIVE:The objective of this study was to determine if growth is improved by earlier fortification of breast milk for preterm infants supported with a human milk based fortifier.STUDY DESIGN:A multi-center retrospective cohort study of the outcomes of infants of 500– 1250 g birth weight whose breast milk feedings were fortified at >60 mL/kg/day (late) versus <60 mL/kg/day (early) of enteral feeding volume.RESULTS:Median±IQR range for gestational age (27.6±3.4 vs 27.0±2.9 weeks, p = 0.03) and chronic lung disease (CLD: 42.6 vs 27.6%, p = 0.008) were higher, and weight gain (12.9±2.6 vs 13.3±2.6 g/kg/day, p = 0.03) was lower in the late (N = 102) vs the early (N = 292) group. Adjusted multiple linear regression analysis found that early fortification was associated with improved growth velocity for weight (p = 0.007) and head circumference (HC) (p = 0.021) and less negative changes in z-scores for weight (p = 0.022) and HC (p = 0.046) from birth to discharge. Adjusted multiple logistic regression found that early fortification was associated with decreased occurrence of CLD (p = 0.004). No other outcomes, including NEC, were associated with early versus late fortification.CONCLUSION:The study results suggested that early HM fortification appears to positively affect growth for infants whose human milk feedings are fortified with a human milk based fortifier without adverse effects. The incidence of CLD was also reduced in the early fortification group.

Multi-nutrient fortification of human milk for preterm infants.

Human breast milk-fed preterm infants can accumulate nutrient deficits leading to extrauterine growth restriction. Feeding preterm infants with multi-nutrient fortified human milk could increase nutrient accretion and growth rates and improve neurodevelopmental outcomes. Concern exists, however, that multi-nutrient fortifiers are associated with adverse events such as feed intolerance and necrotising enterocolitis. To determine whether multi-nutrient fortified human milk, compared with unfortified human milk, affects important outcomes (including growth rate and neurodevelopment) of preterm infants without increasing the risk of adverse effects (such as feed intolerance and necrotising enterocolitis). We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 9), MEDLINE via PubMed (1966 to 26 September 2019), Embase (1980 to 26 September 2019), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 26 September 2019). We searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Randomised and quasi-randomised controlled trials that compared feeding preterm infants with multi-nutrient (protein and energy plus minerals, vitamins, or other nutrients) fortified human breast milk versus unfortified (no added protein or energy) breast milk. We used the standard methods of Cochrane Neonatal. Two review authors separately evaluated trial quality, extracted data, and synthesised effect estimates using risk ratios (RRs), risk differences, and mean differences (MDs). We assessed the certainty of the body of evidence at the outcome level using "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) methods. We identified 18 trials in which a total of 1456 preterm infants participated. These trials were generally small and methodologically weak. Meta-analyses provided low- to moderate-certainty evidence showing that multi-nutrient fortification of human milk increases in-hospital rate of weight gain (MD 1.76 g/kg/d, 95% confidence interval (CI) 1.30 to 2.22), body length (MD 0.11 cm/week, 95% CI 0.08 to 0.15), or head circumference (MD 0.06 cm/week, 95% CI 0.03 to 0.08) among preterm infants. Few data on growth and developmental outcomes assessed beyond infancy are available, and these do not show effects of multi-nutrient fortification. The data do not suggest other benefits or harms and provide low-certainty evidence suggesting effects of multi-nutrient fortification on the risk of necrotising enterocolitis in preterm infants (typical RR 1.37, 95% CI 0.72 to 2.63; 13 studies, 1110 infants). Feeding preterm infants with multi-nutrient fortified human breast milk compared with unfortified human breast milk is associated with modest increases in in-hospital growth rates. Evidence is insufficient to show whether multi-nutrient fortification has any effect on long-term growth or neurodevelopment.

Fortifier selection and dosage enables control of breast milk osmolarity.

BackgroundHuman breast milk (BM) fortification is required to feed preterm newborns with less than 32 weeks of gestation. However, addition of fortifiers increases osmolarity and osmolarity values higher than 450 mOsm/kg may be related to gastrointestinal pathology. Hence, fortifier selection and dosage are key to achieve optimal feeding.ObjectivesTo compare the effect on osmolality of adding different fortifications, including recently developed formulations, to BM and to study evolution of osmolarity over time in supplemented BM.MethodsFrozen mature BM from 10 healthy mothers of premature newborns was fortified with each of the following human milk fortifiers (HMF): AlmirónFortifier®, NANFM85®, or PreNANFM85®. In addition, fortified BMs were modified with one of the following nutritional supplements (NS): Duocal MCT®, Nutricia® AminoAcids Mix, or Maxijul®. Osmolality of BM alone, fortified and/or supplemented was measured at 1 and 22 hours after their preparation. All samples were kept at 4°C throughout the study.ResultsOsmolality of BM alone was close to 300 mOsm/kg and did not change over 22 hours. When equicaloric amounts of HMF AlmirónFortifier®, NANFM85®, and PreNANFM85® were added to BM, osmolality increased roughly to 480 mOsm/kg with the first two fortifiers and only to 433±6 mOsm/kg with the third one. Upon addition of any of four different NSs to BM modified with AlmirónFortifier® and NANFM85®, osmolality reached values greater than 520 mOsm/kg, while osmolality of PreNANFM85® with two out of the four NSs remained below 490 mOsm/kg. NSs supplementing carbohydrates and hydrolysed proteins resulted into a higher increase of BM osmolarity. Osmolality increased significantly with time and, after 22h, only BM modified with PreNANFM85® remained below 450 mOsm/kg.ConclusionsUpon addition of the HMFs tested, BM osmolality increases significantly and keeps raising over time. All HMFs but the recently developed PreNAN FM85® at 4% exceed the AAP recommended threshold for osmolarity of 450 mOsm/kg. Addition of NSs to PreNAN FM85® at 4% significantly increases osmolality above 450 mOsm/Kg. Thus, using PreNAN FM85® at 5% may be preferable to adding nutritional supplements since nutritional recommendations by the ESPGHAN are reached with a lower increase in osmolality.

Early versus late fortification of breast milk in preterm infants: a systematic review and meta-analysis.

This systematic review and meta-analysis assessed the effects of early fortification (EF) versus late fortification (LF) of breast milk (BM) on growth of preterm infants. Randomized and quasi-randomized controlled trials (RCTs) dealing with the effects of EF versus LF on growth parameters, incidence of adverse events, and duration of hospital stay in preterm infants were included. Data were pooled using the RevMan 5.3 software. Quality of evidence for predefined outcomes was analyzed by GRADE. Available evidence (3 RCTs, 309 preterm infants) showed no statistically significant difference between EF and LF of BM for any of the growth parameters-weight (standardized mean difference (SMD) 0.13; 95% confidence interval (CI) - 0.09, 0.36); length (SMD 0.02; 95% CI - 0.20, 0.25); and head circumference (SMD - 0.10; 95% CI - 0.33, 0.12). Total parenteral nutrition days were similar. Duration of hospital stay was significantly higher with EF (MD 4.29; 95% CI 0.84, 7.75) with a trend of non-significant increase in feed intolerance and necrotizing enterocolitis (NEC).Conclusion: Very low quality evidence did not find any significant difference in growth parameters of preterm infants in association with EF or LF of BM. A significant increase in hospital stay and non-significant increase in feed intolerance and NEC were associated with EF.PROSPERO registration number: CRD42019139235What is Known:• Fortification of breast milk with essential macro- and micronutrients is necessary for optimization of nutrition in preterm infants.• There is no consensus regarding the breast milk feeding volume at which fortification should be initiated.What is New:• Very low quality evidence showed no significant difference between early and late fortification of breast milk on growth parameters of preterm infants.• Early fortification was associated with non-significant increase in feed intolerance and necrotizing enterocolitis and a significant increase in hospital stay.

Proportionate Postnatal Growth in Preterm Neonates on Expressed Breast Milk Feeding With Selected Fortification.

Preterm neonates not fed an exclusive human-milk diet in the neonatal intensive care unit (NICU) show disproportionate postnatal growth. There are scant data on postnatal growth in neonates from India fed an exclusive expressed breast milk (EBM) diet. This study describes the postnatal changes in weight, length, and head circumference in preterm neonates given EBM with selected fortification. The study had a prospective observational design. Exclusive EBM feeding, early initiation, and standardized progression of feeds was followed. Fortification of breast milk with human milk fortifier (HMF) or liquid calcium phosphate and multivitamins (CALVIT) or hindmilk (HM) was done based on the gestational age. Monitoring for weight, length, and head circumference was done from admission to discharge. Ninety-three preterm neonates were included in the study, of which 34 (36.6%) were small for gestational age. Thirty-two (34.3%) neonates received EBM with HMF, 35 (35.7%) received EBM fortified with CALVIT and 26 (28%) neonates received HM fortification. There was a significant difference in the change in z-scores from birth to discharge for the weight, length, and head circumference (P= .001). The mean increase in daily weight ranged from 8.8 to 9.5 g/d, whereas weekly change in length was 0.8-0.9 cm/wk, and head circumference was 0.7 cm/wk. Postnatal growth of preterm neonates during NICU admission on exclusive EBM feeding with selected fortification resulted in a proportionate increase in weight, length, and head circumference.

Individualized target fortification of breast milk with protein, carbohydrates, and fat for preterm infants: A double-blind randomized controlled trial.

In preterm infants, natural variation of breast milk composition makes it difficult to achieve recommended macronutrient intakes with standard fortification. Evidence suggests that nutritional deficiency induces poor postnatal growth. This study investigates impacts of target fortification on preterm growth and metabolism by adjusting breast milk macronutrients. This study was conducted as a single-centre, double-blind, randomized controlled trial for infants <30 gestational weeks. The control group received standard fortification and the intervention group received standard plus target fortification adding modular protein, lipids, and carbohydrates. Breast milk content was measured 3x/week using a validated near-infrared bedside spectrometer (NIRS). Modulars were added to achieve recommended values. To assess total nutrient intake, all 2810 native breast milk samples were analyzed - protein and fat using bedside-NIRS, lactose using tandem mass spectrometry (UPLC-MS/MS). Body composition was measured using air displacement plethysmography. Primary outcome was weight gain during the first 21 days of intervention. Baseline characteristics, morbidities, and total fluid intake were not different between groups (intervention n=52, control n=51). The intervention group infants had higher macronutrient intakes, weight gain (21.2±2.5 vs 19.3±2.4g/kg/d, mean difference: 1.9g/kg/d, 95% CI: 0.9 - 2.9), and body weight. Infants in the intervention group from mothers with below-average breast milk protein content showed greatest impact on weight at 36 weeks (2580±280g vs 2210±300g), length, head circumference, fat, and fat-free mass. Also, feeding intolerance was less frequent, blood urea was higher, and triglycerides were lower. This study provides evidence that target fortification of breast milk with low macronutrient content enhances the quality of nutrition and growth and is feasible in clinical routine.

Targeted Breast Milk Fortification for Very Low Birth Weight (VLBW) Infants: Nutritional Intake, Growth Outcome and Body Composition.

Despite improvements in nutritional management, preterm infants continue to face high rates of postnatal growth restriction. Because variability in breast milk composition may result in protein and energy deficits, targeted fortification has been advocated. We conducted an interventional study to compare body composition and growth outcomes of very low birth weight infants fed targeted protein-fortified human milk (HM) with those fed standard fortified HM. If mother’s own milk was not available, donor milk was used. Weekly analysis of HM with mid-infrared spectroscopy was conducted and additional protein was added to the fortified HM to ensure a protein intake of 4 g/kg/day. Weekly anthropometric measurements were done. Prior to discharge or at 37 weeks, corrected age skinfold thickness (SFT) measurements as well as body composition measurement using air displacement plethysmography were done. Among 36 preterm infants enrolled, those in the targeted group (n = 17) received more protein and had a larger flank SFT at study end than those in the standard group (n = 19). A pilot post-hoc analysis of subjects having at least 30 intervention days showed a 3% higher fat-free mass in the targeted group. Use of a targeted fortification strategy resulted in a higher protein intake and fat-free mass among those receiving longer intervention.

Targeted Fortification of Donor Breast Milk in Preterm Infants

Targeted Fortification of Donor Breast Milk in Preterm Infants

Clinical high-risk factors of metabolic bone disease in very low birth weight infants

Objective To explore the high-risk factors of metabolic bone disease(MBD)in premature infants by retrospective analysis of the clinical data so as to provide evidence for optimal clinical management. Methods Clinical data of premature infants with birth weight 500 IU/L and blood phosphorus <1.5 mmol/L were selected as MBD group and premature infants with birth weight <1 500 g were selected randomly as non-MBD group. General data, pulmonary surfactant, continuous positive airway pressure, mechanical ventilation, start time of enteral nutrition, parenteral nutrition (PN) time, breast feeding time and breast milk fortifier adding, drug usage, hospitalization time and complications were recorded and compared between the two groups. Results A total of 440 premature infants with birth weight <1 500 g were admitted to the hospital during the study period. 58[13.2%(58/440)] infants were enrolled in the MBD group, among which infants with birth weight <1 000 g accounting for 56.9%(33/58). High birth weight (OR=0.62, 95% CI: 0.389-0.990) was an independent protective factor of MBD in premature infants. The higher the birth weight, the lower the risk of MBD in premature infants. The longer duration of breast feeding time(OR= 2.191, 95% CI: 1.628-2.950), later initial time of enteral feeding(OR=2.695, 95% CI: 1.710-4.248), longer duration of PN(OR=6.205, 95% CI: 3.359-11.463) time, longer duration of respiratory supporting time(OR=1.046, 95% CI: 1.026-.067), longer hospital stay time(OR=1.703, 95% CI: 1.109-2.615) and small for gestational age(OR=2.965, 95% CI: 1.163-5.658) were independent risk factors of MBD in premature infants. The duration of PN was the most important independent risk factor of MBD in premature infants(OR=6.205, 95% CI: 3.359-11.463). Conclusion Multiple factors can lead to MBD of premature infants. The high birth weight is an independent protective factor of MBD and the duration of PN is the most important independent risk factor of MBD in premature infants. Key words: Premature infant; Metabolic bone disease; High risk factor