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Objectives The safety and feasibility of human milk fortification with bovine colostrum (BC) were investigated in very preterm infants (FortiColos trial, NCT03537365). The BC product contained lower calcium, phosphate, and iron levels compared to the conventional fortifier (CF). We tested whether fortification with BC plus extra phosphate was sufficient to support the infants' mineral status assessed by blood biochemistry. Methods In a randomised controlled trial (FortiColos, NCT03537365), mineral status was compared after fortification with BC versus CF. Blood calcium, phosphate, and haemoglobin were determined before and up to 3 weeks after the start of fortification (at the mean age of 8–9 days). The maximum supplemental doses of calcium, phosphate, and iron given were retrieved from patient medical records. Results were adjusted for gestational age, birth weight, and enteral nutrition with the mother's own milk and/or donor human milk. Results Blood values of calcium, phosphate, and haemoglobin were similar between groups. Infants in both groups required supplementation with calcium and phosphate, but infants fed BC required higher maximum doses of phosphate and calcium (p < 0.05) to maintain acceptable blood values. Regardless of fortification groups, the most immature (<29 weeks of gestation) and small for gestational age infants showed a higher risk for requiring additional phosphate (OR: 3.9, p < 0.001; OR: 2.14, p = 0.07, respectively). Conclusions The use of BC as a fortifier for human milk requires additional phosphate and calcium relative to a CF. Regardless of the fortification product, the most immature and small infants require additional mineral supplementation., Objectives: The safety and feasibility of human milk fortification with bovine colostrum (BC) were investigated in very preterm infants (FortiColos trial, NCT03537365). The BC product contained lower calcium, phosphate, and iron levels compared to the conventional fortifier (CF). We tested whether fortification with BC plus extra phosphate was sufficient to support the infants' mineral status assessed by blood biochemistry. Methods: In a randomised controlled trial (FortiColos, NCT03537365), mineral status was compared after fortification with BC versus CF. Blood calcium, phosphate, and haemoglobin were determined before and up to 3 weeks after the start of fortification (at the mean age of 8–9 days). The maximum supplemental doses of calcium, phosphate, and iron given were retrieved from patient medical records. Results were adjusted for gestational age, birth weight, and enteral nutrition with the mother's own milk and/or donor human milk. Results: Blood values of calcium, phosphate, and haemoglobin were similar between groups. Infants in both groups required supplementation with calcium and phosphate, but infants fed BC required higher maximum doses of phosphate and calcium (p < 0.05) to maintain acceptable blood values. Regardless of fortification groups, the most immature (<29 weeks of gestation) and small for gestational age infants showed a higher risk for requiring additional phosphate (OR: 3.9, p < 0.001; OR: 2.14, p = 0.07, respectively). Conclusions: The use of BC as a fortifier for human milk requires additional phosphate and calcium relative to a CF. Regardless of the fortification product, the most immature and small infants require additional mineral supplementation.

Introduction: Using pre-procedure analgesia with the risk of apnoea may complicate the Less Invasive Surfactant Administration (LISA) procedure or reduce the effect of LISA. Methods: The NONA-LISA trial (ClinicalTrials.gov, NCT05609877) is a multicentre, blinded, randomised controlled trial aiming at including 324 infants born before 30 gestational weeks, meeting the criteria for surfactant treatment by LISA. Infants will be randomised to LISA after administration of fentanyl 0.5–1 mcg/kg intravenously (fentanyl group) or isotonic saline solution intravenously (saline group). All infants will receive standardised non-pharmacological comfort care before and during the LISA procedure. Additional analgesics will be provided at the clinician’s discretion. The primary outcome is the need for invasive ventilation, meaning mechanical or manual ventilation via an endotracheal tube, for at least 30 min (cumulated) within 24 h of the procedure. Secondary outcomes include the modified COMFORTneo score during the procedure, bronchopulmonary dysplasia at 36 weeks, and mortality at 36 weeks. Discussion: The NONA-LISA trial has the potential to provide evidence for a standardised approach to relief from discomfort in preterm infants during LISA and to reduce invasive ventilation. The results may affect future clinical practice. Impact: Pre-procedure analgesia is associated with apnoea and may complicate procedures that rely on regular spontaneous breathing, such as Less Invasive Surfactant Administration (LISA).This randomised controlled trial addresses the effect of analgesic premedication in LISA by comparing fentanyl with a placebo (isotonic saline) in infants undergoing the LISA procedure. All infants will receive standardised non-pharmacological comfort.The NONA-LISA trial has the potential to provide evidence for a standardised approach to relief from discomfort or pain in preterm infants during LISA and to reduce invasive ventilation. The results may affect future clinic

Surfactant deficiency remains a significant cause of mortality and morbidity in preterm infants.1 The Less Invasive Surfactant Administration (LISA) procedure involves laryngoscopy and intratracheal surfactant administration via a thin catheter during spontaneous breathing supported by nasal CPAP or other types of non-invasive support or ventilation.2 In a recent study including 153 international LISA experts from 14 countries, 41% indicated no use of analgesic premedication for LISA, while 49% reported using fentanyl.3 On the contrary, non-pharmacological comfort care was used extensively for LISA but with no standardized approach.

Breastfed infants have different growth patterns to formula-fed infants and are less likely to develop obesity later in life. Nesfatin-1 is an anorexigenic adipokine that was discovered in human milk more than a decade ago, and its role in infant appetite regulation is not clear. Our aim was to describe nesfatin-1 levels in human milk collected 3–4 months postpartum, associations with infant anthropometry, and factors (maternal pre-pregnancy body mass index (mBMI), high weight gain during pregnancy, milk fat, and energy content) possibly influencing nesfatin-1 levels. We hypothesized that nesfatin-1 levels in mother’s milk would differ for infants that were large (high weight-for-age Z-score (WAZ)) or small (low WAZ) at the time of milk sample collection. We used enzyme-linked immunosorbent assay to detect the nesfatin-1 concentration in milk samples from mothers to high WAZ (n = 50) and low WAZ (n = 50) infants. We investigated associations between nesfatin-1 levels and infant anthropometry at 3–4 months of age and growth since birth, using linear regression adjusted for mBMI, birth weight, infant sex, and exclusivity of breastfeeding. We found no difference in nesfatin-1 levels between the two groups and no association with infant anthropometry, even after adjusting for potential confounders. However, high nesfatin-1 levels were correlated with low mBMI. Future research should investigate serum nesfatin-1 level in both mothers, infants and associations with growth in breastfed children.

Objectives: To review the current literature and develop consensus conclusions and recommendations on nutrient intakes and nutritional practice in preterm infants with birthweight <1800 g. Methods: The European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Committee of Nutrition (CoN) led a process that included CoN members and invited experts. Invited experts with specific expertise were chosen to represent as broad a geographical spread as possible. A list of topics was developed, and individual leads were assigned to topics along with other members, who reviewed the current literature. A single face-To-face meeting was held in February 2020. Provisional conclusions and recommendations were developed between 2020 and 2021, and these were voted on electronically by all members of the working group between 2021 and 2022. Where >90% consensus was not achieved, online discussion meetings were held, along with further voting until agreement was reached. Results: In general, there is a lack of strong evidence for most nutrients and topics. The summary paper is supported by additional supplementary digital content that provide a fuller explanation of the literature and relevant physiology: introduction and overview; human milk reference data; intakes of water, protein, energy, lipid, carbohydrate, electrolytes, minerals, trace elements, water soluble vitamins, and fat soluble vitamins; feeding mode including mineral enteral feeding, feed advancement, management of gastric residuals, gastric tube placement and bolus or continuous feeding; growth; breastmilk buccal colostrum, donor human milk, and risks of cytomegalovirus infection; hydrolyzed protein and osmolality; supplemental bionutrients; and use of breastmilk fortifier. Conclusions: We provide updated ESPGHAN CoN consensus-based conclusions and recommendations on nutrient intakes and nutritional management for preterm infants.

Aim: To determine if trial-related blood sampling increases the risk of later red blood cell (RBC) transfusion in very preterm infants, we compared the volume of clinical- and trial-related blood samples, in a specific trial and correlated to subsequent RBC transfusion. Methods: For 193 very preterm infants, participating in the FortiColos trial (NCT03537365), trial-related blood volume drawn was in accordance with ethical considerations established by the European Commission. Medical records were reviewed to assess the number and accumulated volume (mL/kg) of blood samples (both clinical- and trial-related). Data were compared with the need of RBC transfusions during the first 28 days of life. Results: Mean (SD) gestational age and birth weight was 28 ± 1 weeks and 1168 ± 301 g. In total, 11% of total blood volume was drawn for sampling (8.1 ± 5.1 mL/kg) and trial-related sampling accounted for 1.6 ± 0.6 mL/kg. Trial-related blood sampling had no impact on RBC transfusion (p = 0.9). Conclusion: Clinical blood sampling in very preterm infants is associated with blood loss and subsequent need for RBC transfusions. In a specific trial requiring blood samples, we found no additional burden of trial-related blood sampling. The study suggests that trial-related sampling is safe if European criteria are followed.

Background & aims: 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 (120 mL/kg/d, TFF120). Methods: 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 (4–4.5 g/kg/d). Primary outcome was TFF120. Feeding intolerance, growth, morbidities and blood parameters were recorded to assess safety. Results: 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. Conclusions: 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. Trial Registration: http://www.clinicaltrials.gov: NCT03085277.

Breastfed infants have different growth patterns to formula-fed infants and are less likely to develop obesity later in life. Nesfatin-1 is an anorexigenic adipokine that was discovered in human milk more than a decade ago, and its role in infant appetite regulation is not clear. Our aim was to describe nesfatin-1 levels in human milk collected 3-4 months postpartum, associations with infant anthropometry, and factors (maternal pre-pregnancy body mass index (mBMI), high weight gain during pregnancy, milk fat, and energy content) possibly influencing nesfatin-1 levels. We hypothesized that nesfatin-1 levels in mother's milk would differ for infants that were large (high weight-for-age Z-score (WAZ)) or small (low WAZ) at the time of milk sample collection. We used enzyme-linked immunosorbent assay to detect the nesfatin-1 concentration in milk samples from mothers to high WAZ (n = 50) and low WAZ (n = 50) infants. We investigated associations between nesfatin-1 levels and infant anthropometry at 3-4 months of age and growth since birth, using linear regression adjusted for mBMI, birth weight, infant sex, and exclusivity of breastfeeding. We found no difference in nesfatin-1 levels between the two groups and no association with infant anthropometry, even after adjusting for potential confounders. However, high nesfatin-1 levels were correlated with low mBMI. Future research should investigate serum nesfatin-1 level in both mothers, infants and associations with growth in breastfed children.

Aim: Our aim was to investigate the rates of preterm births, live births and stillbirths in Denmark during the first year of the COVID-19 pandemic. Methods: This was a national, cross-sectional registry-based study that used the Danish Newborn Quality database, which covers all births in Denmark. The proportions of preterm births were compared between the COVID-19 pandemic period of 1 March 2020 to 28 February 2021 and the preceding 4-year pre-pandemic period. Results: We studied 60 323 and 244 481 newborn infants from the pandemic and pre-pandemic periods, respectively. The proportion of preterm live births and stillbirths declined slightly, from 6.29% during the pre-pandemic period to 6.02% during the pandemic period. This corresponded to a relative risk (RR) of 0.96, with a 95% confidence interval (CI) of 0.93–0.99 during the pandemic. The RRs for extremely preterm, very preterm and moderately preterm infants were 0.88 (95% CI 0.76–1.02), 0.91 (95% CI 0.82–1.02) and 0.97 (95% CI 0.93–1.01), respectively. Conclusion: This comparative study showed a small reduction in just over 4%, from 6.29 to 6.02% in the proportion of all preterm births during the pandemic period, compared with the previous four pandemic-free years. There were no differences between subcategories of preterm births.

Background: Human milk does not meet the nutritional needs to support optimal growth of very preterm infants during the first weeks of life. Nutrient fortifiers are therefore added to human milk, though these products are suspected to increase gut dysmotility. The objective was to evaluate whether fortification with bovine colostrum (BC) improves bowel habits compared to a conventional fortifier (CF) in very preterm infants. Methods: In an unblinded, randomized study, 242 preterm infants (26-31 weeks of gestation) were randomized to receive BC (BC, Biofiber Damino, Gesten, Denmark) or CF (FM85 PreNAN, Nestle, Vevey, Switzerland) as a fortifier. Stools (Amsterdam Stool Scale), bowel gas restlessness, stomach appearance score, volume, and frequency of gastric residuals were recorded before each meal until 35 weeks post-menstrual age. Results: As intake of fortifiers increased, stools became harder in both groups (p < 0.01) though less in BC infants (p < 0.05). The incidence of bowel gas restlessness increased with laxative treatments and days of fortification in both groups (p < 0.01), but laxatives were prescribed later in BC infants (p < 0.01). With advancing age, stomach appearance scores improved, but more so in BC infants (p < 0.01). Conclusions: Although there are limitations, a minimally processed, bioactive milk product such as BC induced similar or slightly improved bowel habits in preterm infants.