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Background: Red blood cell (RBC) transfusions have been implicated in the development of necrotizing enterocolitis (NEC) in premature infants. Some evidence exists to support that withholding feedings during transfusion reduces the risk of subsequent NEC development.Purpose: To review the most recent literature on this topic to determine best evidence-based practice regarding withholding or not withholding feedings during RBC transfusions.Methods/search Strategy: Four databases were searched using keywords and MeSH terms including "necrotizing enterocolitis," "NEC," "NPO," and "transfusion," with specifications limiting the search to articles published in the last 10 years and limiting the population to neonates.Findings: Four studies did not demonstrate a reduction in transfusion-associated necrotizing enterocolitis (TANEC) with the implementation of feeding protocols during packed red blood cell (PRBC) transfusions. One study concluded that it could not confirm the benefit of withholding feeds during transfusion to reduce the risk of TANEC. A 2020 randomized controlled trial (RCT) found no difference in splanchnic oxygenation when enteral feeds are withheld, continued, or restricted during a PRBC transfusion. Holding feedings during PRBC transfusions did not result in adverse nutritional outcomes.Implications For Practice: To determine best evidence-based practice surrounding feeding protocols during RBC transfusions in very low-birth-weight and premature infants less than 37 weeks' gestation.Implications For Research: It is recommended that large, multicentered, adequately powered RCTs be conducted in this area. Individual institutions should standardize their practice to improve quality, safety, and patient outcomes. [ABSTRACT FROM AUTHOR]

Objective: Surfactant administration is usually performed by endotracheal intubation under mechanical ventilation. Less invasive surfactant administration (LISA) technique has became widespread in recent years, in order to prevent the risk of barotrauma and volutrauma caused by mechanical ventilation and intubation. The aim of this prospective study is to evaluate the effectiveness of surfactant administration via a thin catheter during spontaneous breathing on NIPPV and to compare with INSURE method. Method: Seventy-eight preterm infants who were born at university hospital with less than 34 weeks of gestational age and who received surfactant therapy were enrolled. The intratracheal administration of poractant alfa (CUROSURF®) was performed using umbilical catheters in LISA group (n= 42). INSURE group had 36 infants who were intubated, received surfactant then extubated and placed on NIPPV. Results: There were no statistically significant differences between two groups in terms of intubation in the first 72 hours and re-administration of surfactant, the duration of NIPPV and the occurrence of pneumothorax, pulmonary hemorrhage, patent ductus arteriosus, intraventricular hemorrhage, early onset neonatal sepsis, necrotising enterocolitis, bronchopulmonary dsyplasia and mortality (p>0.05). The pCO2 values decreased faster in LISA group when compared to INSURE group and this difference was statistically significant (p<0.05). Conclusions: LISA procedure under NIPPV seems to provide better pCO2 levels and does not increased the mortality and morbidity due to technique. Although the results seem to be promising, we need further investigations and larger series. [ABSTRACT FROM AUTHOR]

Objective: To compare rates of necrotising enterocolitis (NEC), late-onset sepsis, and mortality in 5-year epochs before and after implementation of routine daily multistrain probiotics administration in high-risk neonates.Design: Single-centre retrospective observational study over the 10-year period from 1 January 2008 to 31 December 2017.Setting: Level 3 neonatal intensive care unit (NICU) of the Norfolk and Norwich University Hospital, UK.Patients: Preterm neonates at high risk of NEC: admitted to NICU within 3 days of birth at <32 weeks' gestation or at 32-36 weeks' gestation and of birth weight <1500 g.Intervention: Prior to 1 January 2013 probiotics were not used. Thereafter, dual-species Lactobacillus acidophilus and Bifidobacterium bifidum combination probiotics were routinely administered daily to high-risk neonates; from April 2016 triple-species probiotics (L. acidophilus, B. bifidum, and B. longum subspecies infantis) were used.Main Outcome Measures: Incidence of NEC (modified Bell's stage 2a or greater), late-onset sepsis, and mortality.Results: Rates of NEC fell from 7.5% (35/469 neonates) in the pre-implementation epoch to 3.1% (16/513 neonates) in the routine probiotics epoch (adjusted sub-hazard ratio=0.44, 95% CI 0.23 to 0.85, p=0.014). The more than halving of NEC rates after probiotics introduction was independent of any measured covariates, including breast milk feeding rates. Cases of late-onset sepsis fell from 106/469 (22.6%) to 59/513 (11.5%) (p<0.0001), and there was no episode of sepsis due to Lactobacillus or Bifidobacterium. All-cause mortality also fell in the routine probiotics epoch, from 67/469 (14.3%) to 47/513 (9.2%), although this was not statistically significant after multivariable adjustment (adjusted sub-hazard ratio=0.74, 95% CI 0.49 to 1.12, p=0.155).Conclusions: Administration of multispecies Lactobacillus and Bifidobacterium probiotics has been associated with a significantly decreased risk of NEC and late-onset sepsis in our neonatal unit, and no safety issues. Our data are consistent with routine use of Lactobacillus and Bifidobacterium combination probiotics having a beneficial effect on NEC prevention in very preterm neonates. [ABSTRACT FROM AUTHOR]

Background: Systemic fungal infection (SFI) is one of leading causes of morbidity and mortality in very low birth weight (VLBW) preterm infants. Because early diagnosis of SFI is challenging due to nonspecific manifestations, prophylaxis becomes crucial. This study aimed to assess effectiveness of oral nystatin as an antifungal prophylaxis to prevent SFI in VLBW preterm infants.Methods: A prospective, open-labelled, randomized controlled trial was performed in a neonatal intensive care unit (NICU) of an academic hospital in Indonesia. Infants with a gestational age ≤ 32 weeks and/or birth weight of ≤ 1500 g with risk factors for fungal infection were assessed for eligibility and randomized to either an intervention group (nystatin) or control group. The intervention group received 1 ml of oral nystatin three times a day, and the control group received a dose of 1 ml of sterile water three times a day. The incidence of fungal colonization and SFI were observed and evaluated during the six-week study period. Overall mortality rates and nystatin-related adverse drug reactions during the study period were also documented.Results: A total of 95 patients were enrolled. The incidence of fungal colonization was lower among infants in nystatin group compared to those in control group (29.8 and 56.3%, respectively; relative risk 0.559; 95% confidence interval 0.357-0.899; p-value = 0.009). There were five cases of SFI, all of which were found in the control group (p-value = 0.056). There was no difference in overall mortality between the two groups. No adverse drug reactions were noted during the study period.Conclusions: Nystatin is effective and safe as an antifungal prophylactic medication in reducing colonization rates in the study population. Whilst the use of nystatin showed a potential protective effect against SFI among VLBW preterm infants, there was no statistical significant difference in SFI rates between groups.Trial Registration: NCT03390374. Registered 4 January 2018 - Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Preterm delivery <32-week gestation is associated with significant neurodevelopmental morbidity ranging from mild delay to profound disability. Several randomized trials have shown that magnesium sulfate (MgSO4) is an effective neuroprotectant, demonstrating reduced rates of cerebral palsy, death, and gross motor dysfunction for the neonate or infant. Dosing was not consistent among the major trials and the onus was placed on institutions by ACOG to develop and implement protocols with respect to MgSO4 as a neuroprotectant. A recent study demonstrated that MgSO4 exposure <12 h prior to delivery was associated with a decrease in CP compared to more remote exposure.Objective: To assess impact of dosing schedule on uptake of neuroprotective MgSO4 in patients delivering <32 weeks gestational age.Study design: A retrospective cohort study of all deliveries occurring <32 weeks' gestation at a single academic center between March-December 2014 and March-December 2015 was conducted. Institutional policy shifted in 2015 from MgSO4 bolus with continuous infusion based on the BEAM trial to a single bolus dose based on the PREMAG trial. Patients with preeclampsia, known fetal anomalies, and/or stillbirth were excluded from this analysis. Patients were identified through query of the Medical University of South Carolina Perinatal Information System (PINS) database with respect to whether or not they had received MgSO4 within 12 h of delivery. Chi-squared analysis was performed to compare the overall rate of MgSO4 exposure and MgSO4 exposure <12 h prior to delivery between groups. Fisher's exact test was used to evaluate maternal, obstetric, and neonatal variables among those receiving MgSO4 within 12 h of delivery in each cohort. Binary logistic regression analysis was performed to control for co-linear or potential confounding variables.Results: A total of 224 patients were identified, 115 delivered between March-December 2014 and 109 delivered between March-December 2015. With respect to MgSO4 exposure prior to delivery, 27 (23.5%) received MgSO4 in the 2014 cohort compared to 44 (40.4%) in the 2015 cohort (OR: 2.2, p < .01). Of those being exposed within 12 h of delivery, there were 16 (13.9%) maternal exposures in the 2014 cohort versus 28 (26.7%) in the 2015 cohort (OR: 2.15, p = .02). Of the 18 neonates delivered in 2014 there were four cases of grade III or IV intraventricular hemorrhage versus one case among the 36 neonates (2.7%) born in 2015 (0.04). This finding holds after controlling for race, preterm labor, gestational age, corticosteroid, birthweight, and indomethacin exposure.Conclusions: Dosing of neuroprotective MgSO4 according to PREMAG trial specifications was associated with a significantly greater percentage of patients having received neuroprotective magnesium at any point prior to delivery or within the 12 h prior to delivery when compared to dosing according to BEAM trial specifications. [ABSTRACT FROM AUTHOR]

Objective: To describe the trend and risk factors for severe intraventricular haemorrhage (IVH) among infants <32 weeks gestation.Design: Population-based cohort study.Setting: Australia and New Zealand.Patients: All preterm infants <32 weeks gestation in the Australian and New Zealand Neonatal Network (ANZNN) from 1995 to 2012.Interventions: Comparison of IVH incidence between 6-year epochs.Main Outcome Measures: Overall IVH and severe IVH incidence.Results: A total of 60 068 infants were included, and overall survival to discharge increased from 89% to 93% over the three epochs. As the percentage of infants with IVH decreased from 23.6% to 21.3% and 21.4% (p<0.001) from epoch 1 to 3, respectively, fewer survivors had severe IVH (4.0%, 3.3% and 2.8%, respectively, p<0.001). Over time, there were fewer antenatal complications, higher antenatal steroid usage and more caesarean-section births. Fewer infants were intubated at birth, had low 5 min Apgar score, had sepsis or pneumothorax needing drainage. Adjusted for perinatal confounders, there was significant reduction in odds of severe IVH from epoch 1 to 3 (adjusted OR (AOR) 0.8, 95% CI 0.7 to 0.9). Factors associated with development of severe IVH include no antenatal steroids (AOR 1.7, 95% CI 1.5 to 1.9), male (AOR 1.3, 95% CI 1.2 to 1.4), 5 min Apgar score <7 (AOR 2.0, 95% CI 1.9 to 2.2), intubated at birth (AOR 2.0, 95% CI 1.8 to 2.2), extremely low gestational age (AOR 4.0, 95% CI 3.7 to 4.4), outborn (AOR 1.6, 95% CI 1.5 to 1.8) and vaginal delivery (AOR 1.4, 95% CI 1.3 to 1.6).Conclusions: Along with increased survival among infants born <32 weeks gestation, the incidence of severe IVH has decreased over the 18 years, especially in the most recent period. This coincided with reduction in rates of risk factors for severe IVH development. [ABSTRACT FROM AUTHOR]

Background: Observational data have shown that slow advancement of enteral feeding volumes in preterm infants is associated with a reduced risk of necrotizing enterocolitis but an increased risk of late-onset sepsis. However, data from randomized trials are limited.Methods: We randomly assigned very preterm or very-low-birth-weight infants to daily milk increments of 30 ml per kilogram of body weight (faster increment) or 18 ml per kilogram (slower increment) until reaching full feeding volumes. The primary outcome was survival without moderate or severe neurodevelopmental disability at 24 months. Secondary outcomes included components of the primary outcome, confirmed or suspected late-onset sepsis, necrotizing enterocolitis, and cerebral palsy.Results: Among 2804 infants who underwent randomization, the primary outcome could be assessed in 1224 (87.4%) assigned to the faster increment and 1246 (88.7%) assigned to the slower increment. Survival without moderate or severe neurodevelopmental disability at 24 months occurred in 802 of 1224 infants (65.5%) assigned to the faster increment and 848 of 1246 (68.1%) assigned to the slower increment (adjusted risk ratio, 0.96; 95% confidence interval [CI], 0.92 to 1.01; P = 0.16). Late-onset sepsis occurred in 414 of 1389 infants (29.8%) in the faster-increment group and 434 of 1397 (31.1%) in the slower-increment group (adjusted risk ratio, 0.96; 95% CI, 0.86 to 1.07). Necrotizing enterocolitis occurred in 70 of 1394 infants (5.0%) in the faster-increment group and 78 of 1399 (5.6%) in the slower-increment group (adjusted risk ratio, 0.88; 95% CI, 0.68 to 1.16).Conclusions: There was no significant difference in survival without moderate or severe neurodevelopmental disability at 24 months in very preterm or very-low-birth-weight infants with a strategy of advancing milk feeding volumes in daily increments of 30 ml per kilogram as compared with 18 ml per kilogram. (Funded by the Health Technology Assessment Programme of the National Institute for Health Research; SIFT Current Controlled Trials number, ISRCTN76463425.). [ABSTRACT FROM AUTHOR]

Preterm infants are at risk of increased trans-epidermal water loss and infections due to epidermal immaturity. The emollient and anti-infective properties of coconut oil make it a potentially beneficial topical agent for this population. We aimed to systematically review randomised trials assessing the effects of topical coconut oil in preterm infants. Medline, EMBASE, Cochrane Central Register of Controlled Trials and CINAHL were searched. Seven trials (n = 727 infants) were included. The majority of trials included relatively mature infants (gestation > 32 weeks, birth weight > 1200 g). The duration of intervention (5-31 days) and outcomes of interest varied among included studies. Meta-analysis using random effects model found significantly lower incidence of hospital-acquired blood stream infections (HABSI) in the coconut oil group (11/164 vs 32/166; relative risk 0.35, 95% confidence interval 0.18, 0.67, p = 0.001; I2 = 0%, two RCTs). Overall, infants in the coconut oil group had decreased water loss, decreased infection rates, better growth and skin condition. There were no significant adverse effects associated with coconut oil application. The overall quality of evidence was considered moderate for the outcome of HABSI and low for the outcome of physical growth based on GRADE guidelines.Conclusion: Topical coconut oil application to the skin may be beneficial in preterm infants, but the quality of evidence is low to moderate. Adequately powered randomised controlled trials, especially in very preterm (< 32 weeks) and extremely preterm (< 28 weeks) infants, are needed. What is Known: • Coconut oil has been used traditionally for topical application in terms of infants in Asian countries What is New: • This systematic review found that topical application of coconut oil may reduce the risk of infection and improve weight gain and skin condition in preterm infants. However, the quality of evidence was considered to be moderate to low based on GRADE guidelines. [ABSTRACT FROM AUTHOR]

Background: Retinopathy of prematurity (ROP) is a disorder of the retina of low-birth-weight preterm infants that potentially leads to blindness. Docosahexaenoic acid (DHA), is protective in experimental models, but its administration as part of parenteral nutrition has shown inconsistent results. We test the effect of enteral DHA to prevent ROP and/or severity and to reduce hospital stay.Methods: This was a double-blind parallel clinical trial. Preterm infants (n = 110; 55 per group) with birth weight <1500 g but ≥1000 g were recruited in a neonatal intensive care unit. Infants were randomized to receive 75 mg of DHA/kg/d (DHA group) or high oleic sunflower oil (control group) for 14 days by enteral feeding. The effect of DHA was evaluated on any stage of ROP, severe ROP (stage ≥3) incidence, and hospital stay. Groups were compared with relative risk (RR) and 95% confidence interval (CI), Fisher's exact test, Student's t-test, or Mann-Whitney U-test, as appropriate. Logistic regression was applied to adjust for confounders.Results: There was no difference between the DHA and control groups in ROP risk (RR for DHA = 0.79; 95% CI, 0.49-1.27; P = 0.33). However, patients who received DHA showed lower risk for stage 3 ROP (RR for DHA = 0.66; 95% CI, 0.44-0.99; P = 0.03). After adjusting for confounders, this decreased risk remained significant (adjusted odds ratio = 0.10; 95% CI, 0.011-0.886; P = 0.04). Hospital stay was similar between groups.Conclusion: Enteral DHA may reduce the incidence of stage 3 ROP. [ABSTRACT FROM AUTHOR]

Aims: To evaluate whether antenatal MgSO4 is beneficial or harmful in very preterm and extremely preterm neonates.Materials and Methods: We retrieved published literature through searches of PubMed or Medline, CINAHL, and the Cochrane Library. Results were restricted to systematic reviews, meta-analysis, randomized controlled trials (RCTs), and relevant observational studies.Results: Evidence revealed that antenatal MgSO4 has neuroprotective role in preterm neonates and it decreased the risk of cerebral palsy and gross motor dysfunction. Evidences regarding association of antenatal MgSO4 with feed intolerance, NEC and SIP were from cohort studies and controversial.Conclusions: We should continue use antenatal MgSO4 to all eligible patients according to protocol till the more robust evidence will suggest association with gastrointestinal complications. In the meantime, we should have a high index of suspicion of gastrointestinal complications in extremely preterms particularly <26 weeks of gestation. [ABSTRACT FROM AUTHOR]

Background: Administrating a single course of antenatal corticosteroids to women at risk of preterm birth between 24 and 34 weeks of gestation has been shown to decrease neonatal morbidity and mortality. There is evidence that the optimal timing for the administration of antenatal corticosteroids is within 1-7 days before birth as the effect of antenatal corticosteroids has been shown to decline 7 days after administration. Therefore, given that antenatal corticosteroids are the single most effective intervention in cases of preterm birth, efforts should be made to optimize the timing of administration of antenatal corticosteroids.Objective: To test the hypothesis that the timing of antenatal corticosteroids in women with vaginal bleeding due to placenta previa or low-lying placenta can be optimized by identifying women at low risk of imminent delivery.Study Design: This was a retrospective cohort study of all women admitted to a tertiary referral center at 24-34 weeks' gestation with vaginal bleeding due to placenta previa or low-lying placenta between 2003 and 2014. Multivariable logistic regression analysis was used to identify factors that are independently associated with delivery within 14 days from admission.Results: A total of 202 women who met the inclusion criteria were admitted with vaginal bleeding in the presence of placenta previa or low-lying placenta during the study period, of whom 31 (15.3%) and 44 (21.8%) gave birth within 7 and 14 days from admission, respectively. The following factors were independently associated with delivery within 14 days from admission: complete placenta previa (odds (OR) 3.57, 95%CI 1.57-9.03), severe bleeding at presentation (OR 17.14, 95%CI 2.92-100.70), uterine contractions at presentation (OR 6.02, 95%CI 1.91-19.00), and cervical length <25 mm at presentation (OR 6.33, 95%CI 1.37-29.11). A predictive test based on the presence of ≥1 of these risk factors was associated with a sensitivity of 90.9% and a negative predictive value of 94.6% for delivery within 14 days of presentation.Conclusions: In women presenting with vaginal bleeding due to placenta previa or low-lying placenta, it seems possible to identify a subgroup of women in whom the likelihood of delivery within 14 days is low. This information may allow for selective (rather than routine) administration of antenatal corticosteroids in this scenario, and may thereby contribute to the optimization of the timing of administration of antenatal corticosteroids. [ABSTRACT FROM AUTHOR]

Background: Administrating a single course of antenatal corticosteroids to women at risk of preterm birth between 24 and 34 weeks of gestation has been shown to decrease neonatal morbidity and mortality. There is evidence that the optimal timing for the administration of antenatal corticosteroids is within 1-7 days before birth as the effect of antenatal corticosteroids has been shown to decline 7 days after administration. Therefore, given that antenatal corticosteroids are the single most effective intervention in cases of preterm birth, efforts should be made to optimize the timing of administration of antenatal corticosteroids.Objective: To test the hypothesis that the timing of antenatal corticosteroids in women with vaginal bleeding due to placenta previa or low-lying placenta can be optimized by identifying women at low risk of imminent delivery.Study Design: This was a retrospective cohort study of all women admitted to a tertiary referral center at 24-34 weeks' gestation with vaginal bleeding due to placenta previa or low-lying placenta between 2003 and 2014. Multivariable logistic regression analysis was used to identify factors that are independently associated with delivery within 14 days from admission.Results: A total of 202 women who met the inclusion criteria were admitted with vaginal bleeding in the presence of placenta previa or low-lying placenta during the study period, of whom 31 (15.3%) and 44 (21.8%) gave birth within 7 and 14 days from admission, respectively. The following factors were independently associated with delivery within 14 days from admission: complete placenta previa (odds (OR) 3.57, 95%CI 1.57-9.03), severe bleeding at presentation (OR 17.14, 95%CI 2.92-100.70), uterine contractions at presentation (OR 6.02, 95%CI 1.91-19.00), and cervical length <25 mm at presentation (OR 6.33, 95%CI 1.37-29.11). A predictive test based on the presence of ≥1 of these risk factors was associated with a sensitivity of 90.9% and a negative predictive value of 94.6% for delivery within 14 days of presentation.Conclusions: In women presenting with vaginal bleeding due to placenta previa or low-lying placenta, it seems possible to identify a subgroup of women in whom the likelihood of delivery within 14 days is low. This information may allow for selective (rather than routine) administration of antenatal corticosteroids in this scenario, and may thereby contribute to the optimization of the timing of administration of antenatal corticosteroids. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study is to evaluate a feeding regimen routinely providing >180 ml/kg/d fortified human milk to very preterm infants and impact on in-hospital growth, osteopenia, and neurodevelopment.Method: Retrospective population-based descriptive study of infants <30-week gestation admitted within 24 h of birth and discharged during the 6-year period 2005-2010. Growth and neurodevelopment was assessed until 2 years corrected age, and cerebral palsy up to 4 years corrected age Results: Ninety-nine infants below 30-week gestation were admitted within 24 h of birth during the 6-year period, of which 84 (85%) survived to discharge. Two infants had surgical necrotizing enterocolitis, both survived to 2 years follow up. Seventy-eight infants (mean 27 weeks) had complete growth data until discharge. Full enteral feeds were tolerated after mean 10 d. Average milk volumes were 193 ml/kg/d from 15 to 42 d of life. Rates of weight below 10th centile were 10% at birth and 14% at discharge. Head circumference Z-scores were stable from birth to discharge. Blood values did not indicate osteopenia. Increasing head circumference Z-scores were associated with improved language development.Conclusions: This high enteral feeding volume regimen was associated with low rates of in-hospital growth restriction and good head growth. High enteral volume intake seems safe and may improve nutritional status of very preterm infants. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to determine the efficacy of polyethylene skin wrapping on thermoregulation in preterm neonates.Methods: Total 151 neonates were enrolled in this randomized control trial. In the control group, neonates were transferred to the radiant warmer and covered with warm cloth after initial care. In the study group, neonates were transferred to the radiant warmer and placed in a food-grade polyethylene bag for 1 h. Axillary temperature of all neonates was recorded for first 24 h at frequent time intervals.Results: Mean temperature reached to normal range earlier and remained significantly higher in the study group for most time intervals, and this difference persisted even at 24 h. Significantly less number of preterm newborns suffered from hypothermia in the study group as compared with the control group [50 (67.6%) vs. 67 (87%), p = 0.004].Conclusions: Polyethylene wraps achieved rapid, sustained thermal control and were effective in preventing hypothermia in preterm newborns. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this review is to describe the historical and scientific basis of antenatal corticosteroids (ACS) therapy, to improve the management of preterm birth and decreasing rates of respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis and perinatal mortality in premature infants.Study Design: We searched MEDLINE/PubMed electronic database, the Cochrane Library, using medical subheading search words such as "ACS", "corticosteroids", "betamethasone" or "dexamethasone", matching with "preterm birth".Results: This practice was initiated by Liggins and Howie in 1972 and is supported by the initial comprehensive meta-analysis of Crowley, Chambers and Keirse, in 1990, the NIH Consensus Development Conference in 1994, the second Consensus Conference to evaluate repeated courses of corticosteroids in 2000 and the practice recommendations of obstetric societies worldwide. ACS therapy before anticipated preterm birth is one of the most important antenatal therapies and an important evidence-based practice for reducing mortality, and decreasing rates of complications in premature infants.Conclusions: Today, there is no controversy that women with preterm birth <34 weeks should be ACS treated. Actually, rescue courses are recommended; while multiple, serial, repeated or weekly courses, are not recommended. In any clinical conditions, as preterm premature rupture of membranes, multiple pregnancies, severe preeclampsia/HELLP syndrome and fetal growth restriction; ACS is recommended. [ABSTRACT FROM AUTHOR]

Background: Infections acquired in hospital are an important cause of morbidity and mortality in very preterm infants. Several small trials have suggested that supplementing the enteral diet of very preterm infants with lactoferrin, an antimicrobial protein processed from cow's milk, prevents infections and associated complications. The aim of this large randomised controlled trial was to collect data to enhance the validity and applicability of the evidence from previous trials to inform practice.Methods: In this randomised placebo-controlled trial, we recruited very preterm infants born before 32 weeks' gestation in 37 UK hospitals and younger than 72 h at randomisation. Exclusion criteria were presence of a severe congenital anomaly, anticipated enteral fasting for longer than 14 days, or no realistic prospect of survival. Eligible infants were randomly assigned (1:1) to receive either enteral bovine lactoferrin (150 mg/kg per day; maximum 300 mg/day; lactoferrin group) or sucrose (same dose; control group) once daily until 34 weeks' postmenstrual age. Web-based randomisation minimised for recruitment site, gestation (completed weeks), sex, and single versus multifetal pregnancy. Parents, caregivers, and outcome assessors were unaware of group assignment. The primary outcome was microbiologically confirmed or clinically suspected late-onset infection (occurring >72 h after birth), which was assessed in all participants for whom primary outcome data was available by calculating the relative risk ratio with 95% CI between the two groups. The trial is registered with the International Standard Randomised Controlled Trial Number 88261002.Findings: We recruited 2203 participants between May 7, 2014, and Sept 28, 2017, of whom 1099 were assigned to the lactoferrin group and 1104 to the control group. Four infants had consent withdrawn or unconfirmed, leaving 1098 infants in the lactoferrin group and 1101 in the sucrose group. Primary outcome data for 2182 infants (1093 [99·5%] of 1098 in the lactoferrin group and 1089 [99·0] of 1101 in the control group) were available for inclusion in the modified intention-to-treat analyses. 316 (29%) of 1093 infants in the intervention group acquired a late-onset infection versus 334 (31%) of 1089 in the control group. The risk ratio adjusted for minimisation factors was 0·95 (95% CI 0·86-1·04; p=0·233). During the trial there were 16 serious adverse events for infants in the lactoferrin group and 10 for infants in the control group. Two events in the lactoferrin group (one case of blood in stool and one death after intestinal perforation) were assessed as being possibly related to the trial intervention.Interpretation: Enteral supplementation with bovine lactoferrin does not reduce the risk of late-onset infection in very preterm infants. These data do not support its routine use to prevent late-onset infection and associated morbidity or mortality in very preterm infants.Funding: UK National Institute for Health Research Health Technology Assessment programme (10/57/49). [ABSTRACT FROM AUTHOR]

Importance: Dexamethasone initiated after the first week of life reduces the rate of death or bronchopulmonary dysplasia (BPD) but may cause long-term adverse effects in very preterm infants. Hydrocortisone is increasingly used as an alternative, but evidence supporting its efficacy and safety is lacking.Objective: To assess the effect of hydrocortisone initiated between 7 and 14 days after birth on death or BPD in very preterm infants.Design, Setting, and Participants: Double-blind, placebo-controlled randomized trial conducted in 19 neonatal intensive care units in the Netherlands and Belgium from November 15, 2011, to December 23, 2016, among preterm infants with a gestational age of less than 30 weeks and/or birth weight of less than 1250 g who were ventilator dependent between 7 and 14 days of life, with follow-up to hospital discharge ending December 12, 2017.Interventions: Infants were randomly assigned to receive a 22-day course of systemic hydrocortisone (cumulative dose, 72.5 mg/kg) (n = 182) or placebo (n = 190).Main Outcomes and Measures: The primary outcome was a composite of death or BPD assessed at 36 weeks' postmenstrual age. Twenty-nine secondary outcomes were analyzed up to hospital discharge, including death and BPD at 36 weeks' postmenstrual age.Results: Among 372 patients randomized (mean gestational age, 26 weeks; 55% male), 371 completed the trial; parents withdrew consent for 1 child treated with hydrocortisone. Death or BPD occurred in 128 of 181 infants (70.7%) randomized to hydrocortisone and in 140 of 190 infants (73.7%) randomized to placebo (adjusted risk difference, -3.6% [95% CI, -12.7% to 5.4%]; adjusted odds ratio, 0.87 [95% CI, 0.54-1.38]; P = .54). Of 29 secondary outcomes, 8 showed significant differences, including death at 36 weeks' postmenstrual age (15.5% with hydrocortisone vs 23.7% with placebo; risk difference, -8.2% [95% CI, -16.2% to -0.1%]; odds ratio, 0.59 [95% CI, 0.35-0.995]; P = .048). Twenty-one outcomes showed nonsignificant differences, including BPD (55.2% with hydrocortisone vs 50.0% with placebo; risk difference, 5.2% [95% CI, -4.9% to 15.2%]; odds ratio, 1.24 [95% CI, 0.82-1.86]; P = .31). Hyperglycemia requiring insulin therapy was the only adverse effect reported more often in the hydrocortisone group (18.2%) than in the placebo group (7.9%).Conclusions and Relevance: Among mechanically ventilated very preterm infants, administration of hydrocortisone between 7 and 14 days after birth, compared with placebo, did not improve the composite outcome of death or BPD at 36 weeks' postmenstrual age. These findings do not support the use of hydrocortisone for this indication.Trial Registration: Netherlands National Trial Register Identifier: NTR2768. [ABSTRACT FROM AUTHOR]

Objective: To determine whether early hydrocortisone treatment in extremely preterm infants affects neurodevelopmental outcomes at 2 years of age according to gestational age at birth.Patients and Methods: This is an exploratory analysis of neurodevelopmental outcomes by gestational age strata from the PREMILOC trial, in which patients were randomly assigned to receive either placebo or low-dose hydrocortisone and randomisation was stratified by gestational age groups (24-25 and 26-27 weeks of gestation). Neurodevelopmental impairment (NDI) was assessed using a standardised neurological examination and the revised Brunet-Lézine scale at 22 months of corrected age.Results: A total of 379 of 406 survivors were evaluated, 96/98 in the gestational age group of 24-25 weeks and 283/308 in the gestational age group of 26-27 weeks. Among surviving infants born at 24-25 weeks, significant improvement in global neurological assessment was observed in the hydrocortisone group compared with the placebo group (P=0.02) with a risk of moderate-to-severe NDI of 2% and 18%, respectively (risk difference 16 (95% CI -28% to -5%)). In contrast, no statistically significant difference between treatment groups was observed in infants born at 26-27 weeks (P=0.95) with a similar risk of moderate-to-severe NDI of 9% in both groups. The incidence of cerebral palsy or other major neurological impairments were found similar between treatment groups in each gestational group.Conclusions: In an exploratory analysis of neurodevelopmental outcomes from the PREMILOC trial, early low-dose hydrocortisone was associated with a statistically significant improvement in neurodevelopmental outcomes in infants born at 24 and 25 weeks of gestation. [ABSTRACT FROM AUTHOR]

Background/objectives: Ventilator associated pneumonia (VAP) is a leading cause of death. Nebulized hypertonic saline solution (HSS) has been used to improve pulmonary clearance and reduce infection in intubated patients. This study examines whether nebulized HSS may reduce VAP in intubated premature infants.Methods: We analyzed results of 100 intubated premature infants who completed the study. Infants were divided into: (a) the "Control" group, where VAP prevention protocol was implemented and (b) the "Intervention" group, where nebulized HSS twice daily was added to the package of care. Clinical, radiologic, and laboratory evidence of VAP, endotracheal aspirate and blood cultures, and days on mechanical ventilation were compared between groups.Results: VAP occurred in 18% in the intervention group compared to 52% in the control group, relative risk 0.35 (CI:0.18-0.66, p = .001). VAP incidence density was 16/1000 patient-ventilator days in intervention group versus 30/1000 in control group. There was a significant reduction in the days of mechanical ventilation in the intervention group (10.7 ± 8.6 and 16.9 ± 3.4, p < .001).Conclusions: Nebulized HSS may help preserving lung clearance mechanisms and therefore reduce VAP in premature infants. Multi center, double blinded, randomized, controlled, trial is needed to confirm safety and efficacy of such intervention. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether neonates at risk for neurodevelopmental impairment have improved neurodevelopment after docosahexaenoic acid, choline, and uridine-5-monophosphate supplementation versus controls.Method: Recruitment was from UK neonatal units. Eligible for inclusion were infants born at less than 31 weeks' gestation with a weight less than the ninth centile; infants born at less than 31 weeks' gestation with a grade II or higher intraventricular haemorrhage/preterm white matter injury; infants born between 31 weeks' and 40 weeks' gestation plus 28 days with a grade II or higher intraventricular haemorrhage/preterm white matter injury, moderate or severe hypoxic-ischaemic encephalopathy, or defined neuroimaging abnormalities. Treatment/control supplementation was for 2 years (double-blind, randomized, controlled design). Infants were stratified according to sex, gestation, and brain injury severity. Primary outcome was cognitive composite score (CCS) of the Bayley Scales of Infant Development, Third Edition (Bayley-III at 24mo). Secondary outcomes were language composite score (LCS) of the Bayley-III, motor composite score (MCS) of the Bayley-III, and Vineland Adaptive Behaviour Scales, Second Edition (VABS-II) score.Results: Sixty-two neonates were recruited, 59 were randomized (34 males, 25 females). Fifty-three started supplementation. Most families found supplementation acceptable. The treatment group CCS-Bayley-III scores were non-significantly higher than controls (mean score difference at 24mo: 9.0; 95% confidence interval -0.2 to 18.2). Language and VABS-II scores, but not motor score, were non-significantly higher in the treatment group.Interpretation: Most families found supplementation feasible. Improved neurodevelopmental outcomes in the treatment group were not statistically significant. A larger multicentre trial exploration is warranted.What This Paper Adds: Dietary supplementation of neonates at risk of neurodevelopmental impairment is feasible. No statistically significant neurodevelopmental advantages were identified for the treatment group compared to controls. Treatment group cognitive and language advantage are of a clinically meaningful magnitude. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the efficacy of antenatal corticosteroid (ACS) therapy on short-term neonatal outcomes in preterm twins, and further document the influence of the ACS-to-delivery interval.Design: EPIPAGE-2 is a nationwide observational multicentre prospective cohort study of neonates born between 22 and 34 completed weeks of gestation.Setting: All French maternity units, except in a single administrative region, between March and December 2011.Population: A total of 750 twin neonates born between 24 and 31 weeks of gestation.Methods: Exposure to ACSs was examined in four groups: single complete course, with an ACS administration-to-delivery interval of ≤7 days; single complete course, with an ACS-to-delivery interval of >7 days; repeated courses; or no ACS treatment.Main Outcome Measures: Neonatal outcomes analysed were severe bronchopulmonary dysplasia, periventricular leukomalacia or intraventricular haemorrhage grade III/IV, in-hospital mortality, and a composite indicator of severe outcomes.Results: Compared with no ACSs, in multivariable analysis, a single course of ACSs with an administration-to-delivery interval of ≤7 days was significantly associated with a reduced rate of periventricular leukomalacia or intraventricular haemorrhage grade III/IV (aOR 0.2; CI 95% 0.1-0.5), in-hospital mortality (0.3; 0.1-0.6), and the composite indicator (0.1; 0.1-0.3), whereas a single course of ACDs with an administration-to-delivery interval of >7 days did not significantly reduce the frequency of in-hospital mortality (0.7; 0.3-1.8). No significant differences in terms of benefit or risk were found when comparing repeated courses with a single complete course.Conclusion: In preterm twins, a single complete course of antenatal corticosteroids was associated with an improvement of severe neurological outcome, whereas reduced in-hospital mortality was seen only when the ACS-to-delivery interval was ≤7 days.Tweetable Abstract: A single complete course of antenatal steroids reduced severe neurological morbidity in preterm twins (24-31 weeks). [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) is one of the most serious gastrointestinal emergencies in very low birth weight (VLBW) preterm neonates, affecting 7-14% of these neonates. Due to the seriousness of the disease, prevention of NEC is the most important goal. Current evidence from systematic review and meta-analysis revealed that probiotics are the most promising intervention in reduction of the incidence of NEC in VLBW neonates. As per the evidence, prebiotics modulate the composition of human intestine microflora to the benefit of the host by suppression of colonization of harmful microorganism and/or the stimulation of bifidobacterial growth, decreased stool viscosity, reduced gastrointestinal transit time, and better feed tolerance. Prebiotics may be potential alternatives or adjunctive therapies to probiotics, despite a lack of evidence supporting its clinical efficacy in prevention of NEC. In this article, we discuss evidence-based physiological effects of prebiotics and its therapeutic role in prevention of NEC. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to delineate whether patient-related or prescriber-related factors account for the prolongation of antibiotic therapy beyond 48 h in premature infants whose initial blood cultures are negative.Methods: Retrospective review of infants born <29 weeks born between January 2011 and December 2012. Infants who had positive blood cultures or who died in the first 48 h were excluded from analysis. Antibiotic courses were categorized as prolonged if antibiotics were continued for greater than 48 h and not prolonged if antibiotics were stopped by 48 h. Neonatologists were classified as high prescribers if they prolonged antibiotics for more than the median rate for the overall group.Results: Seventeen of 59 (29%) infants had empiric antibiotics continued for greater than 48 h despite negative blood cultures. Both patient-related factors and the neonatologist at 48 h of life were significantly associated with prolongation of antibiotics. Patient-related factors associated with prolongation of empiric antibiotics were positive maternal Group B streptococcus (GBS) status (5/17 versus 4/42); p = .054), white blood count >25,000 (7/17 versus 1/42); p < .001), rupture of membranes (ROM) duration (187 ± 253 h versus 47 ± 89 h; p = .015). Increased number of risk factors was associated with increased likelihood of prolongation. Risk factors for sepsis were similar between high and low prescribing neonatologists with high prescribers prolonging antibiotics with a lower number of risk factors.Conclusions: The decision to prolong empiric antibiotics in culture negative preterm infants is related both to patient and prescriber-related factors. [ABSTRACT FROM AUTHOR]

Objective: Brain injury in neonates born prematurely is associated strongly with poor neurodevelopmental outcome. The aim of this study was to evaluate whether tocolysis with nifedipine or atosiban in women with threatened preterm birth can reduce the incidence of overall brain injury in neonates born prematurely. Methods: This was a secondary analysis of the APOSTEL‐III trial (Dutch Clinical Trial Registry, no. NTR2947), a randomized clinical trial in which women with threatened preterm labor between 25 and 34 weeks of gestation were allocated to treatment with nifedipine or atosiban. In this secondary analysis, women delivered at ≤ 32 weeks of gestational age in the two main contributing centers were included. Primary outcome was the presence of neonatal brain injury, which was defined as presence of abnormalities on ultrasound investigation and classified into mild and severe. To evaluate type and severity of brain injury, all neonatal ultrasounds performed during neonatal intensive and medium care admission were analyzed. To test the robustness of our results, a sensitivity analysis was performed assessing differences in baseline or known risk factors for brain injury. Results: A total of 117 neonates (from 102 women) were studied, of which 51 had been exposed to nifedipine and 66 to atosiban. Brain injury was observed in 22 (43.1%) neonates in the nifedipine group compared with 37 (56.1%) in the atosiban group (OR, 0.60; 95% CI, 0.29–1.24). Presence of mild brain injury was comparable between the nifedipine (33.3%) and atosiban (48.5%) groups (OR, 0.53; 95% CI, 0.25–1.13). Severe brain injury was also comparable between the groups, observed in 9.8% of neonates in the nifedipine vs 7.6% of those in the atosiban group (OR, 1.33; 95% CI, 0.36–4.85). Intraventricular hemorrhage (≥ Grade I) was the most frequently seen ultrasound abnormality, observed in 18 (35.3%) neonates in the nifedipine group vs 25 (37.9%) in the atosiban group (OR, 0.90; 95% CI, 0.42–1.91). The sensitivity analysis, with adjustment for maternal age and gestational age at randomization, showed no statistical difference between the groups for presence of brain injury (OR, 0.58; 95% CI, 0.27–1.27). Conclusion: In children born before 32 weeks of gestation after the use of tocolytics, the prevalence of brain injury was high. No significant differences were found with respect to overall brain injury between neonates exposed to nifedipine and those exposed to atosiban. However, as this study was a secondary analysis of the APOSTEL III trial, it was underpowered for brain injury. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Background and Aim: Caffeine improves neurodevelopmental outcome of preterm infants. This study analyses the effects of caffeine on the neonatal brain. We hypothesized that caffeine has a neuroprotective effect through an increase in oxygen metabolism; reflected by increased cerebral oxygen extraction, electrical function, and perfusion.Methods: Preterm infants <32 weeks gestation (GA) receiving their primary dose caffeine-base (10 mg/kg) were included. Ten minutes of stable monitoring were selected before, during, and every hour up to 6 h after caffeine. Near-infrared spectroscopy monitored regional cerebral oxygenation (rScO2) and extraction (FTOE). Amplitude-integrated electroencephalogram (aEEG) monitored minimum, mean and maximum amplitudes. Spontaneous activity transients (SAT) rate and the interval between SATs (ISI) were calculated. Mean arterial blood pressure (MABP), heart rate (HR) and arterial oxygen saturation (SaO2) were monitored. Arterial pCO2's were collected before and 4 h after caffeine. Brain perfusion was assessed 1 h before and 3 h after caffeine by Doppler-measured resistance-index (RI), peak systolic velocity (PSV) and end-diastolic velocity (EDV), in the anterior cerebral artery (ACA) and internal carotid artery (ICA). Results were presented in mean ± SD.Results: 34 infants, mean GA 28.8 ± 2.1 wk, were included. rScO2 significantly decreased from 69 ± 11 to 63 ± 12 1 h after caffeine, and recovered at 6 h (66 ± 10). FTOE increased correspondingly. MABP and HR increased significantly. PSV in the ACA decreased slightly. Other Doppler variables, aEEG parameters, and SaO2 were unaffected.Conclusion: Caffeine increases oxygen extraction, suggesting a (transient) stimulating effect on brain metabolism. However, no substantial changes were found in brain perfusion and in electrical brain activity. [ABSTRACT FROM AUTHOR]

Purpose:To compare the effect of antenatal corticosteroids (ACS) on neonatal outcomes among singleton and twin pregnancies and the impact of completeness and timing of ministration. Materials and methods:Retrospective cohort study involving 951 preterm deliveries (25+0–34+6 weeks), between 2006 and 2015. Neonatal outcomes were evaluated according to completeness of ACS (“Complete”n = 441; “Rescue”n = 38; “Incomplete”n = 175; “No ACS”n = 98) and timing of therapy related to delivery (“Before 7 days”n = 260; “After 7 days”n = 181). Results:On respiratory distress syndrome (RDS), odds ratio (OR) for twins was 0.172, 95% confidence interval (CI) was 0.047; 0.591 and for singletons 0.390 (95%CI 0.214; 0.703) for complete or rescue courses, and 0.280 (95%CI 0.069; 1.066) for twins and 0.906 (95%CI 0.482; 1.698) for singletons for incomplete courses. About the need for mechanical ventilation (MV), twins had an OR of 0.189 (95%CI 0.052; 0.642) and singletons of 0.404 (95%CI 0.222; 0.727) for complete or rescue courses and twins had OR = 0.225 (95%CI 0.053; 0.874) and singletons of 0.404 (95%CI 0.222; 0.727) for incomplete courses. About timing, group “After 7 days” had OR = 2.00 for RDS (95%CI 1.21; 3.30) and 2.32 (95%CI 1.42; 3.78) for MV. Conclusions:ACS improves neonatal outcomes both in singleton and twins. Delivering 7 days after a complete course decreased neonatal morbidity. [ABSTRACT FROM PUBLISHER]

Antibiotic treatment is common practice in the neonatal ward for the prevention and treatment of sepsis, which is one of the leading causes of mortality and morbidity in preterm infants. Although the effect of antibiotic treatment on microbiota development is well recognised, little attention has been paid to treatment duration. We studied the effect of short and long intravenous antibiotic administration on intestinal microbiota development in preterm infants. Faecal samples from 15 preterm infants (35 ± 1 weeks gestation and 2871 ± 260 g birth weight) exposed to no, short (≤ 3 days) or long (≥ 5 days) treatment with amoxicillin/ceftazidime were collected during the first six postnatal weeks. Microbiota composition was determined through 16S rRNA gene sequencing and by quantitative polymerase chain reaction (qPCR). Short and long antibiotic treat ment significantly lowered the abundance of Bifidobacterium right after treatment (p = 0.027) till postnatal week three (p = 0.028). Long treatment caused Bifidobacterium abundance to remain decreased till postnatal week six (p = 0.009). Antibiotic treatment was effective against members of the Enterobacteriaceae family, but allowed Enterococcus to thrive and remain dominant for up to two weeks after antibiotic treatment discontinuation. Community richness and diversity were not affected by antibiotic treatment, but were positively associated with postnatal age (p < 0.023) and with abundance of Bifidobacterium (p = 0.003). Intravenous antibiotic administration during the first postnatal week greatly affects the infant’s gastrointestinal microbiota. However, quick antibiotic treatment cessation allows for its recovery. Disturbances in microbiota development caused by short and, more extensively, by long antibiotic treatment could affect healthy development of the infant via interference with maturation of the immune system and gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Objectives:To assess the associations between antenatal corticosteroid use (ACU), mortality and severe morbidities in preterm, twin neonates and compare these between small for gestational age (SGA) and non-SGA twins. Materials and methods:Population-based study using data collected by the Israel National Very Low Birth Weight infant database from 1995 to 2012, comprising twin infants of 24–31 weeks' gestation, without major malformations. Univariate and multivariable logistic regression analyses were performed. Results:Among the 6195 study twin infants, 784 were SGA. Among SGA neonates, ACU were associated with decreased mortality (23.9% vs. 39.2%,p < 0.0001) and composite adverse outcome including mortality or severe neonatal morbidity (43.8% vs. 56.8%,p = 0.0015), similar to the effect in non-SGA neonates (mortality 13.0% vs. 24.5%,p < 0.0001; composite outcome 34.2% vs. 44.8%,p < 0.0001). In the multivariable logistic regression analyses, ACU were associated with an almost 50% reduced mortality risk among SGA twin neonates (OR = 0.52, 95% CI 0.31–0.88) similar to the effect in non-SGA twin neonates (OR = 0.56, 95% CI 0.45–0.70),Pinteraction = 0.69. Composite adverse outcome risk was also reduced in SGA (OR = 0.78, 95% CI 0.50–1.23) and non-SGA groups (OR = 0.78, 95% CI 0.65–0.95),Pinteraction = 0.95. Conclusions:ACU should be considered in all mothers with twin gestation, at risk for preterm delivery at 24–31 weeks, in order to improve perinatal outcome. [ABSTRACT FROM PUBLISHER]

The objective of the paper is to assess the cost-effectiveness of targeted respiratory syncytial virus (RSV) prophylaxis based on a validated prediction rule with 1-year time horizon in moderately preterm infants compared to no prophylaxis. Data on health care consumption were derived from a randomised clinical trial on wheeze reduction following RSV prophylaxis and a large birth cohort study on risk prediction of RSV hospitalisation. We calculated the incremental cost-effectiveness ratio (ICER) of targeted RSV prophylaxis vs. no prophylaxis per quality-adjusted life year (QALYs) using a societal perspective, including medical and parental costs and effects. Costs and health outcomes were modelled in a decision tree analysis with sensitivity analyses. Targeted RSV prophylaxis in infants with a first-year RSV hospitalisation risk of > 10% resulted in a QALY gain of 0.02 (0.931 vs. 0.929) per patient against additional cost of €472 compared to no prophylaxis (ICER €214,748/QALY). The ICER falls below a threshold of €80,000 per QALY when RSV prophylaxis cost would be lowered from €928 (baseline) to €406 per unit. At a unit cost of €97, RSV prophylaxis would be cost saving.Conclusions: Targeted RSV prophylaxis is not cost-effective in reducing RSV burden of disease in moderately preterm infants, but it can become cost-effective if lower priced biosimilar palivizumab or a vaccine would be available. [ABSTRACT FROM AUTHOR]

The ability of recombinant human erythropoietin (rhEPO) to protect preterm infants against perinatal intrauterine herpes virus infection-induced brain injury was studied. In total, 120 women infected with perinatal intrauterine herpes virus were randomized into four groups: A, B, C and D, and were given 1,500 IU (mother, pre-partum), 3,000 IU (mother, pre-partum), 250 IU/kg (infant, post-natal), and no rhEPO, respectively. Hemoglobin (Hb), reticulocyte (Ret), hematocrit (Hct), neuron specific enolase (NSE), myelin basic protein (MBP), and S100 protein B (S100B) levels were measured immediately (T0) and at 1 week (T1), 2 weeks (T2), and 4 weeks (T3) post-delivery. Linear regression analysis was performed to analyze inter-indicator correlation, and ROC risk models were established to determine the predictive value of Hb, Ret and Hct for brain injury immediately after delivery. The brain injury incidence rate of group A (10%) was significantly lower than group D (33.3%) and group B (6.7%) significantly lower than groups C (26.7%) and D. At T0, Hb, Ret and Hct in groups A and B were significantly higher than in group C and D, while from T1 to T3, groups A, B and C showed significantly higher values than group D. NSE, MBP and S100B showed an inverse trend, with groups A and B lower at T0 and groups A, B and C lower from T1-T3. Hb and NSE, MBP and S100B were negatively correlated, while no correlation was found between Ret and NSE, MBP and S100B. Finally, Hct and NSE, MBP and S100B were negatively correlated. The optimal cut-off values for Hb and Hct for brain injury diagnosis immediately post-partum were 170 g/l (sensitivity 99%, specificity 95.7%) and 28.5% (sensitivity 79.4%, specificity 100%), respectively. Ret did not show predictive value. In conclusion, pre-partum rhEPO treatment showed greater protective effects than post-natal administration, and this may be the regulation of Hb and Hct levels in post-natal preterm infants. In addition, a dose-dependent effect was displayed. [ABSTRACT FROM AUTHOR]

Aim: Pulmonary interstitial emphysema is a severe complication of mechanical ventilation in preterm infants that leads to air leakage and, or, chronic lung disease. We determined the associated risk factors.Methods: This was a retrospective case-control study from 2005 to 2014 at a regional referral centre in Valencia, Spain. The cases were 54 preterm infants up to 30 weeks' gestation and, or, born weighing less than 1500 g, who were diagnosed with pulmonary interstitial emphysema (PIE). The 54 controls were preterm infants without PIE matched by gestational age. Univariate analysis and multivariate analysis were performed to assess the independent predicting factors.Results: Infants with PIE had been resuscitated with higher mean fractional inspired oxygen concentration (FiO2 ) (p = 0.008), had received higher peak mean positive end expiratory pressure (p = 0.00) and higher mean airway pressure (p = 0.026) 24 hours before diagnosis. PIE patients also received more surfactant (p = 0.00) and had higher mortality (p = 0.034). A Cox regression model identified that independent risk factors were the total amount of surfactant administered and the mean FiO2 during the 24 hours before diagnosis.Conclusion: Independent risk factors for pulmonary interstitial emphysema in preterm infants were higher oxygen during resuscitation and a higher need for surfactant and ventilatory pressures before diagnosis. [ABSTRACT FROM AUTHOR]

Purpose Of Review: The recommended method of handling the umbilical cord has undergone a complete 360° turn over the years and current knowledge and research has led the direction to delayed clamping and cord milking. This practice has also been supported by American College of Obstetrics and Gynecology (ACOG) in 2012. This review is a summary of current evidence on delayed cord clamping (DCC), umbilical cord milking (UCM), and comparison between the two and future directions.Recent Findings: Multiple studies have been published establishing the safety of umbilical cord milking. Data comparing UCM to DCC favor milking specifically in terms of improved systemic perfusion and higher hemoglobin concentrations.Summary: UCM is emerging as a safe, quick alternative to DCC and more advantageous especially among premature infants and those delivered via cesarean section. [ABSTRACT FROM AUTHOR]

Background: Limited data exist regarding the neonatal and neurodevelopmental outcomes of infants exposed to marijuana (MJ) in-utero, particularly among preterm infants. We hypothesized that MJ-exposed preterm infants would have worse neonatal and childhood developmental outcomes compared to MJ-unexposed infants.Methods: Secondary analysis of multicenter randomized-controlled trial of antenatal magnesium sulfate for the prevention of cerebral palsy was conducted. Singleton nonanomalous infants delivered <35 weeks exposed to MJ in-utero were compared to MJ-unexposed. Primary neonatal outcome was death, grade 3/4 intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, and/or stage II/III necrotizing enterocolitis before discharge. Primary childhood outcome was death, moderate/severe cerebral palsy, or/and Bayley II Scales <70 at age 2. Backward-stepwise regression used to estimate odds of primary outcomes.Results: 1867 infants met inclusion criteria; 135(7.2%) were MJ-exposed. There were no differences in neonatal (20% vs. 26%, p = 0.14) or childhood (26% vs. 21%, p = 0.21) outcomes in MJ-exposed infants compared to MJ-unexposed infants. In adjusted models, MJ-exposure was not associated with adverse neonatal outcomes (aOR 0.83 95% CI 0.47,1.44) or early childhood outcomes (aOR 1.47, 95% CI 0.97,2.23).Conclusions: Among infants born <35 weeks of gestation, MJ-exposure was not associated with adverse neonatal or childhood outcomes. Long-term follow-up studies are needed to assess later childhood neurodevelopmental outcomes following MJ-exposure. [ABSTRACT FROM AUTHOR]

Cholesterol is of vital importance for normal function of organisms. However, a high serum level is associated with an increased risk of cardiovascular disease. In this review an overview is presented of the different known monogenetic disorders of the cholesterol metabolism which lead to unfavourable lipid profiles form childhood onwards and premature cardiovascular disease. Since these monogenetic disorders have a large variety in clinical presentation, ranging from scarcely any to extreme premature cardiovascular disease, the frequency is underestimated and often the correct diagnosis is not made. This results into a missed opportunity for optimal treatment as well as for appropriate counselling of family members. Therefore, greater awareness among physicians is needed. [ABSTRACT FROM AUTHOR]

Objective: Antenatal corticosteroid (ACS) has long been regarded as the standard of care for women at risk of preterm labour. There are, however, varying practices and regimes in ACS administration. It is unclear if "a window of efficacy" truly exists and if the benefits of ACS would diminish after 7 days from the first dose. The objective of this study is to determine if the time interval between antenatal corticosteroids and delivery influences the neonatal outcomes in preterm deliveries from 23+5 to 36+6 weeks' gestation.Methods: This is a retrospective analysis of 302 women and 352 infants who delivered from 23+5 to 36+6 weeks' gestation in KK Women's and Children's Hospital from 1st November 2014 to 31st January 2015. The timings of the first two doses of corticosteroids and the delivery were retrieved. Neonatal outcomes were compared between those delivering within 7 days and those delivering beyond 7 days of first dose of ACS.Results: 61.2% of preterm infants received at least one dose of antenatal corticosteroids, of which 23.6% received it within the window of efficacy. Overall incidence of respiratory distress asyndrome in our study is 17.6%. Significantly, neonates with ACS exposure beyond 7 days were seven times more likely to have RDS as compared to those exposed to ACS within the window of efficacy (RR 0.535, 95% CI 0.166-1.72), after adjusting for potential confounders.Conclusion: The results of this study support the current practice among obstetricians to aim to administer ACS within 7 days of delivery. [ABSTRACT FROM AUTHOR]

Aim: This study evaluated whether an early aggressive nutrition (EAN) strategy could limit extrauterine growth restriction (EUGR) in a cohort of preterm infants.Methods: This prospective nonrandomised interventional study was carried out in the neonatal intensive care unit of an Italian hospital from January 2013 to December 2015. The prevalence of EUGR was assessed in 100 infants with a gestational age of ≤34 weeks, 50 after the introduction of an EAN regimen in October 2014 and 50 before.Results: The prevalence of EUGR at discharge was significantly lower after the introduction of EAN than before for weight (34% vs. 66%), head circumference (22% vs. 42%) and length at discharge (20% vs. 48%). The Z-scores for all measurements were significantly higher after the introduction of EAN. In the EAN group, weight velocity was significantly higher and maximum weight loss and negative changes in the Z-scores from birth to discharge for weight were lower than in the pre-intervention controls. In extremely low birthweight subjects, the weight Z-score and weight velocity were significantly higher in the EAN group than the control group.Conclusion: The use of EAN at a very early age reduced EUGR and improved auxological outcomes in preterm infants. [ABSTRACT FROM AUTHOR]

Background: The effects of antenatal corticosteroids (ANS) in multiple pregnancies are disputed. In this article, we examined whether estimated effects differ in singletons and multiples and in small for gestational age (SGA) preterm infants.Methods: We studied 17 073 singletons (81% treated with ANS) and 8274 multiples (86% treated) born at 24-33 weeks from the Italian Neonatal Network (2005-2013). We used Poisson regression models with robust variance to estimate adjusted risk ratios (RR) of in-hospital death, severe intraventricular haemorrhage (IVH), periventricular leukomalacia (PVL), and the composite outcome of severe IVH and death.Results: Mortality was lower among ANS-treated vs. ANS-untreated infants, both in singletons (RR 0.63, 95% confidence interval (CI) 0.58, 0.68) and in multiples (RR 0.85, 95% CI 0.73, 0.98). IVH and the composite outcome of IVH and death, but not PVL, also occurred less frequently among ANS-treated infants. For these outcomes, the effect of ANS was stronger in singletons than in multiples (+35%, +32%, and +22% for death, IVH, and the composite outcome, respectively). Also among SGA infants, singletons, and multiples, ANS-treated infants had lower risk of death, IVH and of composite outcome than untreated ones.Conclusions: In this large cohort of preterm infants, both multiples and singletons treated with ANS had a lower risk of mortality, of severe IVH, and of composite outcome of IVH and death, both in the overall sample and in SGA infants. Although ANS effect was weaker in multiples, our results support current recommendations to administer ANS prophylaxis in multiple pregnancies at risk of preterm delivery. [ABSTRACT FROM AUTHOR]

Objective: To identify the factors that increase risk of metabolic bone disease of prematurity (MBD).Study Design: A retrospective case-control study of infants born between January 2013-April 2014 with gestation age <30weeks and birth weight <1000g. MBD was defined as serum alkaline phosphatase above 500U/L and characteristic radiographic changes. Information was obtained on the presence of specific comorbidities.Results: Of 76 infants evaluated, 40 met criteria for MBD. Median gestational age was 25weeks in both groups (p=0.512). Median birth weight of infants with MBD was significantly lower than that of controls (560 vs. 765g, p<0.01). Longer period of parenteral nutrition and dexamethasone use was observed in MBD group. Cholestasis was associated with the highest likelihood of MBD (OR 16.6, 95% CI 4.8-56.9). Seizures (OR 5.2, 95% CI 1.3-20.5) and the prolonged use of diuretics (OR 2.6, 95% CI 1.0-7.0) also significantly increased the likelihood of MBD. Only cholestasis remained significant (OR 9.6, 95% CI 2.1-45.3) after multiple regression analysis.Conclusion: Cholestasis is a significant risk factor for the development of MBD. Our future studies will be directed towards determining the causal relationship between cholestasis and MBD. [ABSTRACT FROM AUTHOR]

Background: Studies of preterm and term-born infants have shown absent fidgety movements and an abnormal movement character to be related to brain lesions and unfavourable neurological outcomes.Aims: The present study examines what effect a parent-administered early intervention program applied to preterm infants in a randomised control trial (RCT) between 34 and 36weeks gestational age has on their fidgety movements and overall movement character at three months of age.Study Design: The study was part of the RCT in an early intervention programme including preterm infants born between 2010 and 2014 at three Norwegian university hospitals.Subjects: 130 preterm infants participated in the study, with 59 of them in the control group and 71 in the intervention group.Outcome Measures: Fidgety movements and overall movement character at three months corrected age.Results: No difference was found between the intervention group and the control group in terms of fidgety movements or movement character. Approximately half of the infants in both groups showed an abnormal movement character.Conclusion: No evidence was found in this RCT to suggest that an intervention at 34 to 37weeks gestational age has a significant effect on the fidgety movements or overall movement character of preterm infants. This is in line with the assumption that absent fidgety movements and an abnormal movement character are due to permanent brain injury and are therefore good predictors for later neurological impairments. [ABSTRACT FROM AUTHOR]

Background: Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating condition resulting from a sustained lack of oxygen during birth. The interest in identifying a relevant biomarker of HIE has thrown into limelight the role of protein S100B as a clinical diagnostic marker of hypoxic brain damage in neonates.Aims: To evaluate the diagnostic value of protein S100B, measured in umbilical cord blood immediately after birth, as a useful biomarker in the diagnosis of HIE Sarnat stages II-III as well as a marker for long-term mortality and morbidity.Study Design: Protein S100B was analyzed in cord blood sampled at birth from 13 newborns later diagnosed with stage II-III HIE and compared with 21 healthy controls. S100B concentrations were related to cord artery pH, amplitude-integrated electroencephalography (aEEG), stage of HIE, and death/sequelae up to an age of 6years. Both parametric and non-parametric statistics were used with a two-sided P<0.05 considered significant.Results: The difference in S100B concentration was marginally statistically significant between HIE cases and controls (P=0.056). Cord blood acidosis (P=0.046), aEEG pattern severity (P=0.030), HIE severity (P=0.027), and condition at 6-year follow-up (healthy/permanent sequelae/death; P=0.027) were all related to an increase in S100B concentration.Conclusions: Protein S100B in neonates suffering from HIE stages II-III appeared elevated in umbilical cord blood at birth. The S100B concentrations were positively associated to the severity of disease and the risk of suffering from neurodevelopmental sequelae and even death. [ABSTRACT FROM AUTHOR]

Background: Lactoferrin (LF) is present in breast milk and have numerous properties including antimicrobial, antiviral, antifungal, and anticancer. Recent studies have emphasized the role of LF in neonatal care Aims and objective: To evaluate the various roles of LF in neonatal care in preterm infants.Search Methods: The literature search was done for this systematic review by searching the electronic database namely Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, Scopus, Index Copernicus, African Index Medicus (AIM), Thomson Reuters (ESCI), Chemical Abstracts Service (CAS), SCIWIN (Scientific World Index), Google Scholar, Latin American and Caribbean Health Sciences Information System (LILACS), Index Medicus for the Eastern Mediterranean Region (IMEMR), Index Medicus for the South-East Asian Region (IMSEAR), Western Pacific Region Index Medicus (WPRIM), various sites for ongoing trials namely clinical trial registry ( www.clinicaltrials.gov , www.controlled-trials.com , Australian and New Zealand Clinical Trials Registry ( http://www.anzctr.org.au ), Indian Clinical Trials Registry ( http://ctri.nic.in/Clinicaltrials ), and the World Health Organization (WHO) International Clinical Trials Registry, and Platform ( http://www.who.int/ictrp/search/en/ ) and abstracts of conferences namely proceedings of Pediatric Academic Societies (American Pediatric Society, Society for Pediatric Research, and European Society for Pediatric Research).Results: Nine eligible studies were analyzed that fulfilled the inclusion criteria of the systematic review. Six duplicate publications were excluded from review. Four studies were excluded due to nonfulfillment of inclusion criteria. All of the studies had more than one outcome of interest. Four studies showed reduction in late onset sepsis (LOS), one showed reduction in invasive fungal infection (IFI), three showed significant decrease in incidence of necrotizing enterocolitis (NEC), one showed reduction in NEC scares, and two showed decrease in mortality, and one showed decrease in combined death and/or NEC. Only one study evaluated role of LF for ventilator-associated pneumonia (VAP) reduction and showed lower rate of VAP. Still the role of LF in Bronchopulmonary dysplasia (BPD) and Retinopathy of prematurity (ROP) is unclear.Conclusion: LF has shown to be promising agent for reduction of LOS and NEC. The role of LF in prevention of neonatal mortality, BPD, and ROP needs further studies. The trials that are going on around the world may be able to give reply of this question in future. [ABSTRACT FROM AUTHOR]

Background: Preterm Premature Rupture of Membranes (PPROM) precedes many deliveries and experts agree with expectant management until 34 weeks gestation. However, there is controversy regarding the gestational age (GA) for administration of corticosteroids.Study Design: We performed a retrospective cohort study in the University of California Fetal Consortium (UCfC). We searched available charts of singleton pregnancies with PPROM between 32 and 33 6/7 weeks GA. Outcomes from the groups were analyzed.Results: Of 191 women with PPROM at 32 to 33 6/7 weeks, 150 received corticosteroids. The median GA at admission was earlier for the exposed versus unexposed group (32 4/7 versus 33 0/7 weeks, respectively, p = 0.001). The mean GA at delivery in the exposed was 33 2/7 (32 0/7 to 35 0/7) weeks versus 33 5/7 (32 0/7 to 36 1/7) weeks in the unexposed (p = 0.001). There was no difference in chorioamnionitis or RDS.Conclusion: In women with PPROM at 32 to 33 6/7 weeks, our data suggests that corticosteroids are associated with similar outcomes despite earlier GA at delivery and no differences in major morbidities. A larger prospective study is needed to determine if the benefit of corticosteroids outweighs the potential risks in PPROM. [ABSTRACT FROM AUTHOR]

Background: Preterm Premature Rupture of Membranes (PPROM) precedes many deliveries and experts agree with expectant management until 34 weeks gestation. However, there is controversy regarding the gestational age (GA) for administration of corticosteroids.Study Design: We performed a retrospective cohort study in the University of California Fetal Consortium (UCfC). We searched available charts of singleton pregnancies with PPROM between 32 and 33 6/7 weeks GA. Outcomes from the groups were analyzed.Results: Of 191 women with PPROM at 32 to 33 6/7 weeks, 150 received corticosteroids. The median GA at admission was earlier for the exposed versus unexposed group (32 4/7 versus 33 0/7 weeks, respectively, p = 0.001). The mean GA at delivery in the exposed was 33 2/7 (32 0/7 to 35 0/7) weeks versus 33 5/7 (32 0/7 to 36 1/7) weeks in the unexposed (p = 0.001). There was no difference in chorioamnionitis or RDS.Conclusion: In women with PPROM at 32 to 33 6/7 weeks, our data suggests that corticosteroids are associated with similar outcomes despite earlier GA at delivery and no differences in major morbidities. A larger prospective study is needed to determine if the benefit of corticosteroids outweighs the potential risks in PPROM. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVE: Management of asymptomatic infants ≥35 weeks' gestation born to mothers with chorioamnionitis remains controversial, with many clinicians considering the need for changes to the current guidelines. The study objective was to evaluate the outcomes of asymptomatic chorioamnionitis-exposed neonates without the use of immediate empirical antibiotics. METHODS: A retrospective data review was conducted from May 2008 to December 2014, including asymptomatic infants ≥35 weeks' gestation with a maternal diagnosis of clinical chorioamnionitis. RESULTS: A total of 240 asymptomatic infants with chorioamnionitis exposure were identified. The majority of asymptomatic chorioamnionitis-exposed infants, 162 (67.5%), remained well in the mother-infant unit with a median stay of 2 days. There were 78 (32.5%) infants admitted to the NICU and exposed to antibiotics due to abnormal laboratory data or development of clinical symptoms. Of those infants admitted to the NICU, 19 (24%) received antibiotics for <72 hours, 47 (60%) were treated for culture-negative clinical sepsis, and 12 (15%) for culture-positive sepsis, with a median NICU stay of 7 days. CONCLUSIONS: Nonroutine use of empirical antibiotics in asymptomatic newborns ≥35 weeks' gestation with maternal chorioamninonitis prevented NICU admission in two-thirds of these infants. This prevented unnecessary antibiotic exposure, increased hospitalization costs, and disruption of mother-infant bonding and breastfeeding. Laboratory evaluation and clinical observation without immediate antibiotic administration may be incorporated into a management approach in asymptomatic chorioamnionitis-exposed neonates. Additional studies are needed to establish the safety of this approach. [ABSTRACT FROM AUTHOR]

Background: The literature supports minimizing duration of invasive ventilation to decrease lung injury in premature infants. Neonatal Resuscitation Program recommended use of non-invasive ventilation (NIV) in delivery room for infants requiring prolonged respiratory support.Objective: To evaluate the impact of implementation of non-invasive ventilation (NIV) using nasal intermittent positive pressure ventilation (NIPPV) for resuscitation in very low birth infants.Study Design: Retrospective study was performed after NIPPV was introduced in the delivery room and compared with infants receiving face mask to provide positive pressure ventilation for resuscitation of very low birth weight infants prior to its use. Data collected from 119 infants resuscitated using NIPPV and 102 infants resuscitated with a face mask in a single institution. The primary outcome was the need for endotracheal intubation in the delivery room. Data was analyzed using IBM SPSS Statistics software version 24.Results: A total of 31% of infants were intubated in the delivery room in the NIPPV group compared to 85% in the Face mask group (p=<0.001). Chest compression rates were 11% in the NIPPV group and 31% in the Face mask group (p<0.001). Epinephrine administration was also lower in NIPPV group (2% vs. 8%; P=0.03). Only 38% infants remained intubated at 24hours of age in the NIPPV group compared to 66% in the Face mask group (p<0.001). Median duration of invasive ventilation in the NIPPV group was shorter (2days) compared to the Face mask group (11days) (p=0.01). The incidence of air-leaks was not significant between the two groups.Conclusion: NIPPV was safely and effectively used in the delivery room settings to provide respiratory support for VLBW infants with less need for intubation, chest compressions, epinephrine administration and subsequent invasive ventilation. [ABSTRACT FROM AUTHOR]

Background: Late-onset sepsis (LOS), defined as sepsis occurring after 48 h of age causes substantial mortality and morbidity in very low birth weight infants. Risk factors for LOS include immaturity, intravascular catheters, mechanical ventilation, and prolonged parenteral nutrition (PN). Little attention has been paid to studying the effects of PN administration methods. The aim of the study was to compare a bundle of measures for PN line management incorporating a strict aseptic technique with standard line management on LOS in very low birth weight infants.Methods: Infants <1500 g birth weight who required PN were randomised to either a bundle of a strict aseptic technique for line management together with single use intravascular catheter for PN or a standard technique. The primary outcome was the incidence of LOS in the first 28 days of life. Secondary outcomes were mortality, neonatal morbidities and developmental outcome at 12 months of age.Results: There were 126 infants in the aseptic technique group and 123 in the standard technique group. Forty (31.8%) infants in the aseptic technique group and 36 (29.3%) in the standard technique group had an episode of sepsis (p = 0.77). This corresponds to incidences of 15.8 and 14.2 episodes of sepsis per 1000 patient days respectively. Subgroup analyses for infants <1000 g also revealed no difference in the rate of sepsis between the intervention and control groups. (p = 0.43). There were no significant differences in secondary outcomes and development between the groups.Conclusion: A bundle of measures including strict aseptic technique for parenteral nutrition line management did not result in a reduction in LOS when compared to a standard technique. There is no evidence to recommend this as routine practice.Trial Registration: Interdisciplinary Maternal Perinatal Australasian Collaborative Trials (IMPACT) Network, TRN registration number: PT0363. Date: 06/03/2001; Australian New Zealand Clinical Trials Registry (ANZCTR), TRN registration number: ACTRN12617000455369 . Date: 28/03/2017 (retrospectively registered). [ABSTRACT FROM AUTHOR]

Improving neurodevelopmental outcome for preterm infants is an important challenge for neonatal medicine. The disruption of normal brain growth and neurological development is a significant consequence of preterm birth and can result in physical and cognitive impairments. While advances in neonatal medicine have led to progressively better survival rates for preterm infants, there has only been a modest improvement in the proportion of surviving infants without neurological impairment, and no change in the proportion with severe disability. The overall number of children with neurodisability due to prematurity is increasing. Trials investigating novel therapies are underway and many have promising early results; however, in the interim, current treatments and management strategies that have proven benefit for neurodevelopment or reduction in neonatal brain injury are often underutilised. We collate the evidence for the efficacy of such interventions, recommended by guidelines or supported by large meta-analysis or randomised control trials. We address controversies that have hindered uptake and problems with translating research into practice. We then look to the future of preterm neuroprotective care. [ABSTRACT FROM AUTHOR]

Objective: To study the efficacy of bovine colostrum in prevention of necrotizing enterocolitis (NEC) and sepsis in very low birth weight (VLBW) infants.Study Design: Randomized, double-blind, placebo-controlled pilot trial.Participants: Neonates with birth weight ≤1500 g, gestation ≤32 weeks and postnatal age ≤96 h.Intervention: Enteral bovine colostrum or placebo, four times a day, till 21 days of life or discharge or death.Main Outcome Measures: Definite NEC. Secondary outcomes included sepsis, mortality and stool interleukin-6 (IL-6) levels.Results: Of the total 86 subjects (43 in each group), there were no statistically significant in the main outcome measures. In the colostrum group, there were trends toward higher stool IL-6 values and higher incidence of ileus and radiological signs of NEC.Conclusion: The use of prophylactic enteral bovine colostrum in VLBW infants shows a trend toward increased stool IL-6 and features of NEC. We were unable to detect clinical benefits. [ABSTRACT FROM AUTHOR]