Background: The tendency of premature infants to develop an excessive inflammation in the intestines can lead to morbidities such as necrotizing enterocolitis (NEC) or sepsis. Lactoferrin theoretically can downregulate the intestinal inflammatory status of preterm newborns. In a randomized study, we investigated the effect of enteral bovine lactoferrin (bLF) supplementation on fecal calprotectin (FC) levels in premature infants.

Methods: The study included 26 preterm neonates with a gestational age of ≤ 32 weeks and a birthweight of ≤1500 g. All babies were aged less than 72 h and tolerating minimal enteral feeds. Eleven infants were receiving bLF at a dose of 100 mg/day with enteral feeds until postmenstrual age (PMA) of 36 weeks (lactoferrin group), 15 infants were receiving standard medical care (control group). Stool samples were collected twice: during the first 7 days of life (before administration of bLF) and at PMA of 36 weeks. FC measurements were done with an ELISA method.

Results: The baseline characteristics of the groups were not different. The initial median (IQR) FC level was lower in the lactoferrin group, but the difference was not statistically significant (264.9 (211.0–689.4) vs. 413.5 (274.2–800.0) μg/g, respectively, p > 0.05). At PMA of 36 weeks, FC concentrations increased in the lactoferrin group (p > 0.05) but were not different as compared to the control group (631.1 (232.0–800.0) vs 274.7 (144.8-599.6) μg/g, respectively, p > 0.05). Initial FC concentrations were higher in infants with early-onset sepsis (EOS) (rS = 0.44; p < 0.05) but did not correlate with the incidence of NEC or late-onset sepsis (LOS). FC levels were not significantly different in patients with NEC or LOS compared to infants without these morbidities, both initially and at PMA of 36 weeks. Supplementation with bLF did not affect the incidence of either NEC or sepsis.

Conclusions: Daily enteral intake bLF at a dose of 100 mg until PMA of 36 weeks was associated with the increase of FC levels but this effect was not statistically significant. FC levels during the first week of life do not predict the development of NEC or LOS but might be an additional tool for diagnosing EOS.

INTRODUCTION
Invasive mechanical ventilation (MV) remains a widely used respiratory support for the sickest very-low-birth-weight (VLBW) infants. However, prolonged exposure to this invasive treatment can be associated with adverse outcomes. It is essential to establish the factors which influence the duration of MV. The study aimed to determine the factors affecting the duration of MV in VLBW infants.
MATERIALS AND METHODS
Data obtained from a prospectively created computer database were used in a retrospective cohort study. The database included information about 1,086 VLBW infants < 32 weeks of gestation who were intubated and mechanically ventilated at any time during their hospital stay at Lviv Regional Clinical Hospital between January 2010 and December 2020.
RESULTS
The infants had a mean (SD) gestational age of 27.6 (2.2) weeks and birth weight of 1,007 (262) g. 43% of them were delivered by cesarean section, 26% from multiple pregnancies, 58% were intubated and ventilated at birth, and 49% were treated with surfactant. Severe intraventricular hemorrhages (IVH) occurred in 179 (16%), periventricular leukomalacia (PVL) in 60 (6%), bronchopulmonary dysplasia (BPD) in 135 (12%), and necrotizing enterocolitis (NEC) in 41 (4%) infants. In 49 (5%) cases, the BPD was severe. 678 (62%) patients survived until discharge. The median (IQR) duration of endotracheal MV was 47 (10-103) hours. BPD (rS = 0.32, p < 0.05), severe BPD (rS = 0.418, p < 0.05), pneumothorax (rS = 0.06, p = 0.05), severe IVH (rS = 0.255, p < 0.05), PVL (rS = 0.15, p < 0.05), sepsis (rS = 0.087, p < 0.05), NEC (rS = 0.088, p < 0.05), antibiotic therapy duration (rS = 0.168, p < 0.05), and smaller gestational age (rS = -0.118, p < 0.05) were reliably associated with longer duration of MV in VLBW infants.
Based on a one-way analysis of covariance, only severe BPD (F = 20.898, p < 0.0001) and PVL (F = 5.989, p < 0.05) significantly and independently increased the duration of MV.
CONCLUSIONS
Severe lung injury and brain injury are the main factors affecting the duration of MV in our 10-year cohort of VLBW infants.

Introduction: Patent ductus arteriosus (PDA) is one of the most common cardiovascular problems that occur in preterm infants. This trial aimed to investigate whether acetaminophen is non-inferior to ibuprofen in closing PDA in very preterm infants.

Patients and Methods: A randomized non-inferiority trial was conducted on preterm infants with a gestational age <32 weeks, birth weight <1500 g, postnatal age <72 h, and PDA size >1.5 mm. Infants were randomly assigned to receive either intravenous acetaminophen (n=52) or rectal ibuprofen (n=52). The primary study outcome was the ductus closure within 24 hours after completion of the first and/or second course of pharmacological treatment. Results: The incidence of PDA closure after completion of the first and/or second course of pharmacological treatment was identical 81% (42/52). After the first course of treatment, PDA closed in 37 infants (71%) in the ibuprofen group and 41 patients (79%) in the acetaminophen group (p>0.05). The median age (IQR) at the time of ductus closure was also the same in both groups, 5 (5-6) days. There were no statistically significant differences between the groups in the incidence of severe complications associated with preterm birth and mortality (p>0.05). No side effects related to pharmacological treatment were detected.

Conclusions: Acetaminophen is non-inferior to ibuprofen for the closure of PDA in very preterm infants.

Keywords: patent ductus arteriosus; PDA; acetaminophen; ibuprofen; very preterm infants

Premature infants are at high risk for diseases associated with impaired adaptation of the immature digestive tract, such as necrotizing enterocolitis (NEC) or late-onset sepsis (LOS), as well as severe neonatal morbidities associated with these diseases. This study was aimed to evaluate the effectiveness of prophylactic enteral use of bovine lactoferrin for the prevention of severe neonatal diseases in premature infants. The prospective cohort study included 117 premature infants with gestational age (GA) of ≤32 weeks, a birth weight of ≤1,500 g, and an age of ≤72 hours. 27 infants who were receiving enteral feeds were randomized to receive lactoferrin at a dose of 100 mg/day until postmenstrual age (PMA) of 36 weeks or discharge (at least 4 weeks). 90 infants formed the control group and received standard treatment. The primary outcome was the incidence of LOS, the secondary outcomes were the incidence of necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), severe brain damage, bronchopulmonary dysplasia (BPD), overall mortality, as well as the age of achieving full enteral feeds, duration of antibacterial therapy, length of stay in NICU and the total length of hospital stay. Enteral lactoferrin supplementation did not reduce the incidence of LOS (29.6% in the lactoferrin group against 22.7% in the control group; p=0.85), NEC (5.6% vs. 1.8%, respectively; p=0.11) and overall mortality (18.5% vs. 9.1%, respectively; p=0.06), as well as the incidence of severe intraventricular hemorrhages (18.5% vs. 9.8%, respectively; p=0.17), PVL (11.1% vs. 2.2%, respectively; p=0.17) and BPD (14.8% vs. 25.6%, respectively; p = 0.25). Infants receiving lactoferrin were achieving full enteral feeds significantly faster compared to the control group (14 (10-17) days vs. 19 (13-32) days, respectively; p=0.007). The total length of hospital stay of infants with GA ≤28 weeks in the lactoferrin group was significantly shorter compared to the control group (74 (68-89) vs. 98 (83-109) days, respectively; p=0.048). Enteral lactoferrin supplementation at a dose of 100 mg/day does not affect the main morbidity and mortality of prematurely born infants with GA ≤ 32 weeks but may facilitate significantly faster achievement of the full enteral feeds and the reduction of the length of hospital stay in the tiniest infants.