Preterm Formula Research Articles

Early human milk feeding: Relationship to intestinal barrier maturation and postnatal growth.

Early exposure to mother's own milk (MOM) promotes intestinal barrier maturation in preterm infants. We hypothesized (1) donor human milk (DHM) supplementation reduces intestinal permeability (IP) similar to exclusive MOM and (2) early HM exposure and low IP at 7-10 days postnatal age (PNA) are associated with improved growth outcomes. IP was measured by the standard sugar absorption test (SAT) in infants <33 weeks gestation between 7-10 days PNA. Nutritional and anthropometric data were recorded. Postnatal growth failure (PNGF) was defined as a decrease in weight z-score >1 from birth to discharge to home. Of 158 preterm infants, the mean (SD) gestational age was 29.9(2.3) weeks and birthweight 1388(424) g. Diet prior to SAT was exclusive MOM [N = 55(35%)], DHM ± MOM [N = 52(33%)], or preterm formula±MOM [N = 51(32%)]. The mean Lactulose(La)/Rhamnose(Rh) ratio was lower in the exclusive MOM [0.06(0.07)] and DBM ± MOM [0.05(0.07)] groups compared to the preterm formula±MOM group [0.11(0.11)], p < 0.01). Cumulative intake >150 ml/kg MOM ± DHM, but not preterm formula within 7-10 days PNA was associated with early intestinal barrier maturation. Low IP was not associated with lower risk of PNGF at discharge. Low IP is associated with cumulative intake of MOM alone or supplemented with DHM > 150 ml/kg within 7-10 days PNA. Clinicaltrials.gov NCT01756040 ; web link to study on registry: https://clinicaltrials.gov/study/NCT01756040 . Key message Early intestinal barrier maturation is associated with cumulative intake of exclusive MOM alone or supplemented with DHM > 150 ml/kg within 7-10 days after birth, but is not associated with lower risk of PNGF at time of discharge. What it adds to existing literature? This observational study is the first study to demonstrate that supplemental DHM promotes intestinal barrier maturation similar to MOM alone. What is the impact? The findings underscore the importance of early introduction of human milk feeds as MOM or MOM supplemented with DHM in sufficient volume to promote early intestinal barrier maturation.

Influence of Early Total Enteral Feeding in Preterm Infants with Respiratory Distress Syndrome

Plain Language SummaryThe objective of this secondary analysis of data from the randomized trial comparing less invasive surfactant therapy (LISA) with InSurE method of surfactant administration among preterm infants with respiratory distress syndrome (RDS) is to demonstrate the feasibility of ETEF in hemodynamically stable preterm neonates on respiratory support.In this randomized control trial comparing LISA versus InSurE among preterm infants with RDS between 26 and 34 weeks of gestation, 150 infants were enrolled with 117 being hemodynamically stable. In 33 patients, early total enteral feeding could not be started due to various reasons – 7 babies had absence/reversal of end-diastolic flow (A/REDF) on antenatal Doppler, 15 babies had shock and required inotropic support on day 1 of life, 8 babies had higher ventilatory settings at the time of admission, and in the 3 babies, the abdomen was not soft to start total enteral feeding. Full-volume enteral feeding without any parenteral supplementation was started on day 1 of life using the mother’s own milk (MoM) or donor human milk (≤32 weeks of GA) and MoM or preterm formula (33–34 weeks of GA). The data were analyzed to assess the proportion of babies developing feed intolerance and/or NEC and factors associated with failure of ETEF. Out of these 117 babies, 102 tolerated ETEF, and 15 had one or more episodes of FI requiring parenteral supplementation, but none developed NEC. There was a statistically significantly increased incidence of culture-positive sepsis as well as the requirement of antibiotic therapy for possible sepsis in babies with failure of ETEF. There was no difference in the morbidities noted such as intraventricular hemorrhage grade 2 or more, patent ductus arteriosus requiring medical or surgical management, retinopathy of prematurity requiring treatment, and NEC stage II or more. Our study suggests that hemodynamically stable preterm infants with RDS on respiratory support can be successfully fed with exclusive enteral feeds started immediately post-birth. ETEF results in early attainment of full feeding and reduces the incidence of sepsis and the duration of hospital stay without increasing the risk of NEC.

Bovine colostrum prevents formula-induced gut microbiota dysbiosis in preterm pigs.

Preterm birth and formula feeding increase the risk of necrotizing enterocolitis (NEC), a gut inflammatory disease known to be associated with gut microbiota (GM) changes in infants. Supplemental bovine colostrum may protect against formula-induced NEC via GM changes. We hypothesised that feeding colostrum before, after, or during formula feeding affects NEC sensitivity via changes to GM. Colonic GM (profiled by 16S ribosomal RNA gene amplicon sequencing) was compared in preterm pigs fed colostrum for 4 days, either before, after, or together with formula feeding for 4 days. Correlations between GM and gut parameters were assessed on day 5 or 9. Both exclusive and partial colostrum feeding induced higher GM diversity, lower Enterococcus abundance, and improved intestinal maturation parameters (villus structure, digestive enzymeactivities, permeability), relative to exclusive formula feeding (all p < 0.05). Across feeding regimens, Enterococcus abundance was inversely correlated with intestinal maturation parameters. Conversely, there was no correlation between GM changes and early NEC lesions. Bovine colostrum inhibits formula-induced Enterococcus overgrowth and gut dysfunctions just after preterm birth but these effects are not causally linked. Optimising diet-related host responses, not GM, may be critical to prevent NEC in preterm newborn pigs and infants. Supplement of bovine colostrum to formula feeding modified the gut microbiota by increasing species diversity and reducing Enterococcus abundance, while concurrently improving intestinal functions in preterm pigs. Diet-related changes to the gut microbiota were not clearly associated with development of necrotizing enterocolitis (NEC) in preterm pigs, suggesting that diet-related gut microbiota effects are not critical for diet-related NEC protection. The study highlights the potential to use bovine colostrum as a supplement to formula feeding for preterm infants lacking human milk.

Enteral nutrition practices among very preterm infants in neonatal units: a cross-country comparative study

PurposeThe objective of this study was to delineate and compare enteral nutrition (EN) practices among neonatal units across the Arabian Gulf countries.Design/methodology/approachA cross-sectional study was conducted by recruiting 255 clinicians working in neonatal units in the Arabian Gulf countries.FindingsOut of 255 invited clinicians, 73 (29%) participated in the survey. Neonatal units used varied EN strategies, where feeding practices exhibited variability. The majority (74%) of units had a local standard feeding protocol, while 18% followed international protocols, and 8% did not adhere to a specific protocol. When maternal milk was not used, the main alternatives were preterm formula (67%) and predigested formula (14%). The age at which the first EN was commenced and the reported advancement rate showed significant variations among different units (p < 0.001). The initiation of fortification was primarily driven by reaching a specific enteral volume (commonly reported as 100 mL/kg/day) and addressing poor postnatal growth. Fortification practices did not differ significantly among professions, except for the initial fortification strength, where none of the dietitians and only 8.3% of neonatologists preferred full strength, compared to 28.6% and 21.4% of medical residents and nurses, respectively (p = 0.033).Originality/valueThis study marks the first exploration of EN practices in neonatal units, examining their local and cross-country variations. It provides valuable insights to guide local trials and foster global collaboration among neonatal units to establish a unified knowledge base, standardized practices and promote research and innovation, ultimately contributing to optimal feeding practices for very preterm infants.

Exploring lipid digestion discrepancies between preterm formula and human milk: Insights from in vitro gastrointestinal digestion and the impact of added milk fat

Lipids play a pivotal role in the nutrition of preterm infants, acting as a primary energy source. Due to their underdeveloped gastrointestinal systems, lipid malabsorption is common, leading to insufficient energy intake and slowed growth. Therefore, it is critical to explore the reasons behind the low lipid absorption rate in formulas for preterm infants. This study utilized a simulated in intro gastrointestinal digestion model to assess the differences in lipid digestion between preterm human milk and various infant formulas. Results showed that the fatty acid release rates for formulas IF3, IF5, and IF7 were 58.90 %, 56.58 %, and 66.71 %, respectively, lower than human milk's 72.31 %. The primary free fatty acids (FFA) and 2-monoacylglycerol (2-MAG) released during digestion were C14:0, C16:0, C18:0, C18:1n-9, and C18:2n-6, in both human milk and formulas. Notably, the higher release of C16:0 in formulas may disrupt fatty acid balance, impacting lipid absorption. Further investigations are necessary to elucidate lipid absorption differences, which will inform the optimization of lipid content in preterm infant formulas.

Neurodevelopmental Outcomes of Extremely Preterm Infants Fed Donor Milk or Preterm Infant Formula

Maternal milk feeding of extremely preterm infants during the birth hospitalization has been associated with better neurodevelopmental outcomes compared with preterm formula. For infants receiving no or minimal maternal milk, it is unknown whether donor human milk conveys similar neurodevelopmental advantages vs preterm formula. To determine if nutrient-fortified, pasteurized donor human milk improves neurodevelopmental outcomes at 22 to 26 months' corrected age compared with preterm infant formula among extremely preterm infants who received minimal maternal milk. Double-blind, randomized clinical trial conducted at 15 US academic medical centers within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants younger than 29 weeks 0 days' gestation or with a birth weight of less than 1000 g were enrolled between September 2012 and March 2019. Preterm formula or donor human milk feeding from randomization to 120 days of age, death, or hospital discharge. The primary outcome was the Bayley Scales of Infant and Toddler Development (BSID) cognitive score measured at 22 to 26 months' corrected age; a score of 54 (score range, 54-155; a score of ≥85 indicates no neurodevelopmental delay) was assigned to infants who died between randomization and 22 to 26 months' corrected age. The 24 secondary outcomes included BSID language and motor scores, in-hospital growth, necrotizing enterocolitis, and death. Of 1965 eligible infants, 483 were randomized (239 in the donor milk group and 244 in the preterm formula group); the median gestational age was 26 weeks (IQR, 25-27 weeks), the median birth weight was 840 g (IQR, 676-986 g), and 52% were female. The birthing parent's race was self-reported as Black for 52% (247/478), White for 43% (206/478), and other for 5% (25/478). There were 54 infants who died prior to follow-up; 88% (376/429) of survivors were assessed at 22 to 26 months' corrected age. The adjusted mean BSID cognitive score was 80.7 (SD, 17.4) for the donor milk group vs 81.1 (SD, 16.7) for the preterm formula group (adjusted mean difference, -0.77 [95% CI, -3.93 to 2.39], which was not significant); the adjusted mean BSID language and motor scores also did not differ. Mortality (death prior to follow-up) was 13% (29/231) in the donor milk group vs 11% (25/233) in the preterm formula group (adjusted risk difference, -1% [95% CI, -4% to 2%]). Necrotizing enterocolitis occurred in 4.2% of infants (10/239) in the donor milk group vs 9.0% of infants (22/244) in the preterm formula group (adjusted risk difference, -5% [95% CI, -9% to -2%]). Weight gain was slower in the donor milk group (22.3 g/kg/d [95% CI, 21.3 to 23.3 g/kg/d]) compared with the preterm formula group (24.6 g/kg/d [95% CI, 23.6 to 25.6 g/kg/d]). Among extremely preterm neonates fed minimal maternal milk, neurodevelopmental outcomes at 22 to 26 months' corrected age did not differ between infants fed donor milk or preterm formula. ClinicalTrials.gov Identifier: NCT01534481.

Comparative Growth Outcomes in Very Low Birth Weight Infants: Evaluating Different Feeding Strategies.

To assess the growth pattern of preterm, very low birth weight (VLBW) appropriate for gestational age (AGA) infants on three different feeding regimens. This prospective open label three-arm parallel randomized controlled trial was conducted at neonatal intensive care unit, Kasturba Hospital, Manipal. One hundred twenty VLBW (weight between 1000-1500g and gestational age 28-32 wk) preterm AGA infants admitted from April 2021 through September 2022 were included. Three feeding regimens were compared: Expressed breast milk (EBM); EBM supplemented with Human milk fortifier (HMF); EBM supplemented with Preterm formula feed (PTF). Primary outcome measure was assessing the growth parameters such as weight, length, head circumference on three different feeding regimens at birth 2, 3, 4, 5 and 6 wk/discharge. Secondary outcomes included incidence of co-morbidities and cost-effectiveness. Of 112 infants analyzed, Group 2 supplemented with HMF showed superior growth outcomes by 6th wk/discharge of intervention, with mean weight of 2053±251g, mean length of 44.6±1.9cm, and mean head circumference of 32.9±1.4cm. However, infants in Group 3, supplemented with PTF, registered mean weight of 1968±203g, mean length of 43.6±2.0cm, and mean head circumference of 32.0±1.6cm. Infants exclusively on EBM presented with mean weight of 1873±256g, mean length of 43.0±2.0cm and mean head circumference of 31.4±1.6cm. Addition of 1 g of HMF to 25 ml of EBM in neonates weighing 1000-1500 g showed better weight gain and head circumference at 6 wk/discharge, which was statistically significant. However, no significant differences in these parameters were observed at postnatal or 2, 3, 4, and 5 wk.

Growth and micronutrient status parameters of Nigerian preterm infants consuming preterm formula or breastmilk.

Moderate-to-late preterm infants (32-34 weeks GA) have increased risk of neonatal morbidities compared to term infants, however dedicated nutritional guidelines are lacking. Moderate-to-late preterm infants received a preterm formula (n = 17) or breastmilk (n = 24) from age 2-10 weeks in a non-randomized, open-label observational study. Anthropometric measurements were assessed bi-weekly. Blood concentrations of hemoglobin, ferritin, serum retinol, and 25-hydroxy-vitamin D (25OHD) were analyzed at age 2 and 10 weeks. Average growth per day was 14.7 g/kg BW/day in formula-fed and 12.8 g/kg BW/day in breastmilk-fed infants but not different from each other. Length and head circumference in both groups were in line with the median reference values of the Fenton growth chart. At 10 weeks of age, hemoglobin tended to be higher in the formula-fed group (10.2 g/dL vs. 9.6 g/dL, p = 0.053). 25OHD increased in formula- and breastmilk-fed infants from 73.8 to 180.9 nmol/L and from 70.7 to 97.6 nmol/L, respectively. Serum retinol only increased in the formula-fed group (0.63 to 1.02 µmol/L, p < 0.001). Breastfeeding resulted in adequate growth in moderate-late preterm infants but was limiting in some micronutrients. The preterm formula provided adequate micronutrients, but weight gain velocity was higher than the Fenton reference value. Unfortified breastmilk resulted in adequate growth in weight, length and head circumference in Nigerian moderate to late preterm infants during an study period of 8 weeks, but status of vitamin D, vitamin A and iron needs to be monitored. The high-energy formula, developed for very preterm infants, resulted in higher growth in body weight in moderate to late preterm infants than the median of the Fenton preterm growth chart. This study supports the necessity of dedicated nutritional guidelines, and regular monitoring of growth and nutritional status of moderate to late preterm infants.

Breast-feeding as protective factor against bronchopulmonary dysplasia in preterm infants.

Breast-feeding is associated with fewer comorbidities in very-low-birth-weight (VLBW) preterm infants. Bronchopulmonary dysplasia (BPD) of VLBW infants is a multifactorial pathology in which nutritional aspects may be of special importance. The aim of this study is to determine, in a cohort of VLBW infants, whether breast milk nutrition is associated with a reduced prevalence and severity of BPD. A retrospective study was conducted to record the intake of mother's own milk (MOM), pasteurised donor human milk or preterm formula milk in the first 2 weeks of postnatal life of 566 VLBW newborns at our hospital during the period January 2008-December 2021. After applying the relevant exclusion criteria, data for 489 VLBW infants were analysed; 195 developed some degree of BPD. Moderate or severe BPD is associated with less weight gain. Moreover, the preferential ingestion of breast milk in the first and second postnatal weeks had effects associated with lower OR for BPD, which were statistically demonstrable for mild (OR 0·16; 95 % CI 0·03, 0·71) and severe (OR 0·08; 95 % CI 0·009, 0·91) BPD. Breast-feeding during the first weeks of postnatal life is associated with a reduced prevalence of BPD, which is frequently associated with less weight gain as a result of greater respiratory effort with greater energy expenditure.

Analyzing the Responses of Enteric Bacteria to Neonatal Intensive Care Supplements.

In the neonatal intensive care unit, adequate nutrition requires various enteral products, including human milk and formula. Human milk is typically fortified to meet increased calorie goals, and infants commonly receive vitamin mixes, iron supplements, and less frequently, thickening agents. We examined the growth of 16 commensal microbes and 10 pathobionts found in the premature infant gut and found that formula, freshly pasteurized milk, and donated banked milk generally increased bacterial growth. Fortification of human milk significantly elevated the growth of all microbes. Supplementation with thickeners or NaCl in general did not stimulate additional growth. Vitamin mix promoted the growth of several commensals, while iron promoted growth of pathobionts. These data indicate that pathobionts in the preterm gut have significant growth advantage with preterm formula, fortified donor milk, and supplemented iron and suggest that the choice of milk and supplements may impact the infant gut microbiota.

Growth of Extremely Low Birth Weight Infants (ELBW) born at a Tertiary Hospital: Statural catch-up growth continues during the 3rd year of life

Background: Extremely low birth weight (ELBW) infants, with birth weights less than 1000 g, often experience challenges in postnatal growth. This study aimed to assess the growth patterns of ELBW infants over a 3-year period, focusing on statural catch-up growth. Methods: Anthropometric measures (z-scores) were obtained at birth, 2, 4, 6, 12, 18, 24, and 36 months for 87 ELBW infants born between September 2016 and September 2018. Their growth data was compared to WHO growth standards without adjusting for gestational age. All preterm infants received preterm formula for an average of 4-6 months. Results: ELBW infants showed significant catch-up growth in weight-for-age (WAZ) and length-for-age (LAZ) during the first two years of life, while weight-for-length (WLZ) showed an initial increase followed by a mild decline. By age 3, a substantial proportion of infants achieved normal growth parameters. Specifically, 78% had normal WAZ, 90% had normal LAZ, 87% had normal WLZ, and 91.5% had normal head circumference z-scores (HCZ). Overweight was observed in 7.4% of ELBW infants at age 3. Conclusion: ELBW infants fed preterm formula for 4-6 months demonstrated significant catch-up growth during the first 12-18 months of life, with continued catch-up in LAZ during the third year. A high percentage of these infants achieved normal growth parameters by age 3, emphasizing the effectiveness of early interventions in improving postnatal growth in ELBW infants.

Preterm Formula, Fortified or Unfortified Human Milk for Very Preterm Infants, the PREMFOOD Study: A Parallel Randomised Feasibility Trial

Objective: Uncertainty exists regarding optimal supplemental diet for very preterm infants if the mother’s own milk (MM) is insufficient. We evaluated feasibility for a randomised controlled trial (RCT) powered to detect important differences in health outcomes. Methods: In this open, parallel, feasibility trial, we randomised infants 25+0–31+6 weeks of gestation by opt-out consent to one of three diets: unfortified human milk (UHM) (unfortified MM and/or unfortified pasteurised human donor milk (DM) supplement), fortified human milk (FHM) (fortified MM and/or fortified DM supplement), and unfortified MM and/or preterm formula (PTF) supplement from birth to 35+0 weeks post menstrual age. Feasibility outcomes included opt-outs, adherence rates, and slow growth safety criteria. We also obtained anthropometry, and magnetic resonance imaging body composition data at term and term plus 6 weeks (opt-in consent). Results: Of 35 infants randomised to UHM, 34 to FHM, and 34 to PTF groups, 21, 19, and 24 infants completed imaging at term, respectively. Study entry opt-out rate was 38%; 6% of parents subsequently withdrew from feeding intervention. Two infants met predefined slow weight gain thresholds. There were no significant between-group differences in term total adipose tissue volume (mean [SD]: UHM: 0.870 L [0.35 L]; FHM: 0.889 L [0.31 L]; PTF: 0.809 L [0.25 L], p = 0.66), nor in any other body composition measure or anthropometry at either timepoint. Conclusions: Randomisation to UHM, FHM, and PTF diets by opt-out consent was acceptable to parents and clinical teams, associated with safe growth profiles and no significant differences in body composition. Our data provide justification to proceed to a larger RCT.

Comparison of Effect of Human Milk Fortification with Preterm Formula Powder Vs Human Milk Fortification with Human Milk Fortifier on the Growth of Very Low Birth Weight Newborns

Aim: The primary aim of this scientific inquiry was to comprehensively assess how the nourishment of Very Low Birth Weight (VLBW) newborns could be improved by supplementing their diet with either human milk fortifier or preterm formula powder. Methods: A randomized controlled trial was carried out at RTEH Muzaffargarh NICU, which involved the participation of 72 preterm infants weighing between 1.2 kg and 1.6 kg at birth. The infants were randomly allocated into two groups: one received human milk fortified with preterm formula powder. In contrast, the other group received human milk fortified with a human milk fortifier. Throughout the study, weight, length, and head circumference measurements were taken for all participants. Results: There were no significant differences in gestational ages between HMF and preterm formula groups (p=0.057), nor in gender distribution (p=0.369 for males). Post-intervention, Group A experienced significant increases in birth weight (p=0.0021) and head circumference (p=0.004), but not in length. In the control group, changes in weight, head circumference, and length did not reach statistical significance. Conclusion: Human milk fortification with preterm formula powder appears to promote similar or even better growth outcomes in VLBW infants when compared to traditional fortification with human milk fortifier. However, more research is needed to confirm these findings and assess any potential long-term impacts. Keywords: Human Milk Fortification, Preterm Formula Powder, Very Low Birth Weight Infants, Growth Outcomes, Randomized Controlled Trial.

Effects of processing on component interactions and peptide profiles of preterm infant formula based on peptidomics by Q Exactive plus analysis

The study aimed to investigate the effects of processing on the component interactions, the peptide profile as well as the bioactive peptides of preterm infant formula after digestion through EASY-nLC1200 Q Exactive Plus system. Results indicated that whey proteins and caseins transferred from serum and pellet fractions to fat fraction to recombine the milk fat globule membrane destroyed after homogenization. Protein interactions caused the changes of nitrogen distribution, protein profiles, and morphology after pasteurization and spray drying. Peptidomics analysis demonstrated that the component interactions of preterm infant formula affected the peptide profiles after digestion shown by the different peptide intensities of certain amino acid compositions and the totally different abundance of the peptides in heatmap. The hydrolysates of five groups exhibited 334, 274, 421, 214, and 265 unique peptides belonging to 144, 116, 185, 101, and 231 master accession proteins respectively. The top 8 abundant proteins identified were β-casein, Lipocln, αS1-casein, αS2-casein, κ-casein, bovine Glycosylation-dependent cell adhesion molecule, α-lactalbumin, and Albumin. The number of bioactive peptides increased after processing but were different from each other. In total, component interactions during processing of preterm infant formula could change the peptide profile and bioactive peptides after in vitro digestion.

Outcomes in very preterm infants receiving an exclusive human milk diet, or their own mother's milk supplemented with preterm formula

BackgroundAn infant's Own Mother's Milk (OMM) is the mainstay of very preterm nutrition. When a supplement is required, preterm formula and pasteurised human donor milk (pHDM), are options. Which is optimal is unknown. Aims and outcome measuresComparison of “survival to 34 weeks postmenstrual age (PMA) without surgery for necrotising enterocolitis (NEC)” and other outcomes, in infants receiving OMM supplemented with pHDM without bovine macronutrient fortification (exclusive human milk diet), and infants receiving OMM supplemented with preterm formula. DesignCohort analysis of observational data from the National Neonatal Research Database; data-adaptive Super Learner approach with Targeted Maximum Likelihood Estimation to calculate Adjusted Risk Differences (ARD) between the groups. ParticipantsInfants born below 32 weeks gestation admitted to neonatal units in England and Wales between 01 and 06-2017 and 31-05-2022. ResultsCompared to the formula supplemented group (n = 7133), infants receiving an exclusive human milk diet (n = 1007), had lower survival to 34 weeks PMA without NEC surgery (ARD -9.8 %, 95%CI -11.4 to −8.2), higher all-cause (10.7 %, 9.1 to 12.2) and NEC-related mortality (1.0 %, 0.4 to 1.5), and lower rates of treated retinopathy of prematurity (−2.8 %, −3.4 to −2.3) and bronchopulmonary dysplasia (−12.1 %, −14.0 to −10.1). ConclusionsThe lower survival to 34 weeks PMA without NEC surgery in infants receiving an exclusive human milk diet is unexpected. We adjusted for factors that influence outcomes but cannot exclude the possibility of confounding, hence our data justify a randomised controlled trial to identify optimal supplementary feeds for very preterm infants.

Effect of Breast Milk on the Frequency of Bronchopulmonary Dysplasia in Very Low Birth Weight Premature Infants: A Meta-analysis.

Purpose: To analyze the effect of different feeding types on bronchopulmonary dysplasia (BPD) in very low birth weight preterm infants. Methods: The Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, China Biomedical Literature Database (CBM) were searched for literature related to breastfeeding and BPD, with a search period from their inception to January 2023. Two researchers independently screened the literature, extracted data, and assessed the quality of included studies before analyzing the data using Stata16 and RevMan5.4.1 software. Results: A total of 17 studies were included. The results showed that there was no significant difference in the frequency of BPD between human milk (HM) and donor human milk (DHM) (OR = 0.54, 95% CI: 0.29-1.03, p = 0.07). However, DHM had a significant effect in reducing the frequency of BPD compared to preterm formula (PF) (OR = 0.62, 95% CI: 0.41-0.94, p = 0.02). Exclusive HM also had a significant effect in reducing the frequency of BPD compared to exclusive PF (OR = 0.51, 95% CI: 0.34-0.78, p = 0.002), as well as compared to any PF (OR = 0.57, 95% CI: 0.37-0.88, p = 0.01). Furthermore, mainly (>50%) HM had a significant effect in reducing the frequency of BPD compared to mainly PF (OR = 0.72, 95% CI: 0.55-0.93, p = 0.01). However, there was no statistically significant difference between any HM and exclusive PF (OR = 0.88, 95% CI: 0.62-1.23, p = 0.46). Conclusions: Our study findings suggest that both HM and DHM have a significant protective effect in reducing the frequency of BPD occurrence compared to PF. Furthermore, even when the amount of HM is insufficient, feeding more than 50% of the HM volume still provides a protective effect against the frequency of BPD. Therefore, we recommend feeding infants with more than 50% of HM to harness the protective effect of HM against BPD occurrence.

Bovine colostrum to supplement the first feeding of very preterm infants: The PreColos randomized controlled trial

Gut immaturity leads to feeding difficulties in very preterm infants (<32 weeks gestation at birth). Maternal milk (MM) is the optimal diet but often absent or insufficient. We hypothesized that bovine colostrum (BC), rich in protein and bioactive components, improves enteral feeding progression, relative to preterm formula (PF), when supplemented to MM. Aim of the study is to determine whether BC supplementation to MM during the first 14 days of life shortens the time to full enteral feeding (120mL/kg/d, TFF120). This was a multicenter, randomized, controlled trial at seven hospitals in South China without access to human donor milk and with slow feeding progression. Infants were randomly assigned to receive BC or PF when MM was insufficient. Volume of BC was restricted by recommended protein intake (4-4.5g/kg/d). Primary outcome was TFF120. Feeding intolerance, growth, morbidities and blood parameters were recorded to assess safety. A total of 350 infants were recruited. BC supplementation had no effect on TFF120 in intention-to-treat analysis [n (BC)=171, n (PF)=179; adjusted hazard ratio, aHR: 0.82 (95% CI: 0.64, 1.06); P=0.13]. Body growth and morbidities did not differ, but more cases of periventricular leukomalacia were detected in the infants fed BC (5/155 vs. 0/181, P=0.06). Blood chemistry and hematology data were similar between the intervention groups. BC supplementation during the first two weeks of life did not reduce TFF120 and had only marginal effects on clinical variables. Clinical effects of BC supplementation on very preterm infants in the first weeks of life may depend on feeding regimen and remaining milk diet. http://www. gov: NCT03085277.

Probiotics and Human Milk Differentially Influence the Gut Microbiome and NEC Incidence in Preterm Pigs.

Necrotizing enterocolitis (NEC) is the leading cause of death caused by gastrointestinal disease in preterm infants. Major risk factors include prematurity, formula feeding, and gut microbial colonization. Microbes have been linked to NEC, yet there is no evidence of causal species, and select probiotics have been shown to reduce NEC incidence in infants. In this study, we evaluated the effect of the probiotic Bifidobacterium longum subsp. infantis (BL. infantis), alone and in combination with a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on the microbiome, and the incidence of NEC in preterm piglets fed an infant formula diet. We studied 50 preterm piglets randomized between 5 treatments: (1) Preterm infant formula, (2) Donor human milk (DHM), (3) Infant formula + 3'SL, (4) Infant formula + BL. infantis, and (5) Infant formula and BL. infantis + 3'SL. NEC incidence and severity were assessed through the evaluation of tissue from all the segments of the GI tract. The gut microbiota composition was assessed both daily and terminally through 16S and whole-genome sequencing (WGS) of rectal stool samples and intestinal contents. Dietary BL. infantis and 3'SL supplementation had no effect, yet DHM significantly reduced the incidence of NEC. The abundance of BL. infantis in the gut contents negatively correlated with disease severity. Clostridium sensu stricto 1 and Clostridium perfringens were significantly more abundant in NEC and positively correlated with disease severity. Our results suggest that pre- and probiotics are not sufficient for protection from NEC in an exclusively formula-based diet. The results highlight the differences in microbial species positively associated with both diet and NEC incidence.

Insulin, Testosterone, and Albumin in Term and Preterm Breast Milk, Donor Milk, and Infant Formula

Infants have three options for feeding: their own mother's breast milk, donor milk, or infant formula. Insulin, testosterone, total protein, and albumin levels were measured in breast milk samples from the first 6 months of lactation, in donor milk samples, and in different infant formulas. Mothers who gave birth to term (n = 19) or preterm (n = 19) infants were recruited to collect breast milk samples during the first 6 months of lactation. The Breast Milk Collection Center (Unified Health Institution, Pécs, Hungary) provided 96 donor milk (DM) samples for analysis in our study. Insulin, testosterone, total protein, and albumin levels were measured in breast milk, donor milk, and infant formulas. During the first 2 months of lactation, the concentration of insulin was lower (-27.4%) while the testosterone concentration was higher (+20.8%) compared to the period between the 3rd and 6th months only in the preterm breast milk samples. The infant formulas examined did not contain insulin or testosterone. Holder pasteurization (HoP) did not influence the level of testosterone in human milk, although HoP decreased the insulin (-53.6%) and albumin (-38.6%) concentrations. Diet impacts the hormone intake of infants, underlining the importance of breastfeeding and the possible supplementation of formula-fed infants.

Exploring Human Milk, Nutrition, Growth, and Breastfeeding Rates at Discharge(HUMMINGBIRD Study): a protocol for a pilot randomised controlled trial

IntroductionMother’s own breast milk (MOM) is the optimal nutrition for preterm infants as it reduces the incidence of key neonatal morbidities and improves long-term outcomes. However, MOM shortfall is common...