A French nationwide survey of phototherapy in very preterm and moderately preterm infants.

Phototherapy for jaundice in preterm infants should always be administered in accordance with specific guidelines. However, guidelines on phototherapy in very preterm and moderately preterm infants are currently lacking in France. We performed a nationwide quality improvement study of the management of jaundice in these preterm infants and compared the results with the international guidelines. Of the 275 maternity units initially contacted, 165 (60.0%) replied. Our results showed that clinical practice differs markedly from one unit to another - notably with regard to the prescription, administration, and monitoring of phototherapy and the reference curves used. Even though there is limited evidence on the safety and efficacy of phototherapy in very or moderately preterm infants, a French expert committee should be encouraged to develop consensus guidelines and thus improve quality of care in this setting.

Umbilical cord milking in nonvigorous infants: a cluster-randomized crossover trial.

BACKGROUND: Delayed cord clamping and umbilical cord milking provide placental transfusion to vigorous newborns. Delayed cord clamping in nonvigorous newborns may not be provided owing to a perceived need for immediate resuscitation. Umbilical cord milking is an alternative, as it can be performed more quickly than delayed cord clamping and may confer similar benefits. OBJECTIVE: We hypothesized that umbilical cord milking would reduce admission to the neonatal intensive care unit compared with early cord clamping in nonvigorous newborns born between 35 and 42 weeks' gestation. STUDY DESIGN: This was a pragmatic cluster-randomized crossover trial of infants born at 35 to 42 weeks' gestation in 10 medical centers in 3 countries between January 2019 and May 2021. The centers were randomized to umbilical cord milking or early cord clamping for approximately 1 year and then crossed over for an additional year or until the required number of consented subjects was reached. Waiver of consent as obtained in all centers to implement the intervention. Infants were eligible if nonvigorous at birth (poor tone, pale color, or lack of breathing in the first 15 seconds after birth) and were assigned to umbilical cord milking or early cord clamping according to their birth hospital randomization assignment. The baseline characteristics and outcomes were collected following deferred informed consent. The primary outcome was admission to the neonatal intensive care unit for predefined criteria. The main safety outcome was hypoxic-ischemic encephalopathy. Data were analyzed by the intention-to-treat concept. RESULTS: Among 16,234 screened newborns, 1780 were eligible (905 umbilical cord milking, 875 early cord clamping), and 1730 had primary outcome data for analysis (97% of eligible; 872 umbilical cord milking, 858 early cord clamping) either via informed consent (606 umbilical cord milking, 601 early cord clamping) or waiver of informed consent (266 umbilical cord milking, 257 early cord clamping). The difference in the frequency of neonatal intensive care unit admission using predefined criteria between the umbilical cord milking (23%) and early cord clamping (28%) groups did not reach statistical significance (modeled odds ratio, 0.69; 95% confidence interval, 0.41-1.14). Umbilical cord milking was associated with predefined secondary outcomes, including higher hemoglobin (modeled mean difference between umbilical cord milking and early cord clamping groups 0.68 g/dL, 95% confidence interval, 0.31-1.05), lower odds of abnormal 1-minute Apgar scores (Apgar ≤3, 30% vs 34%, crude odds ratio, 0.72; 95% confidence interval, 0.56-0.92); cardiorespiratory support at delivery (61% vs 71%, modeled odds ratio, 0.57; 95% confidence interval, 0.33-0.99), and therapeutic hypothermia (3% vs 4%, crude odds ratio, 0.57; 95% confidence interval, 0.33-0.99). Moderate-to-severe hypoxic-ischemic encephalopathy was significantly less common with umbilical cord milking (1% vs 3%, crude odds ratio, 0.48; 95% confidence interval, 0.24-0.96). No significant differences were observed for normal saline bolus, phototherapy, abnormal 5-minute Apgar scores (Apgar ≤6, 15.7% vs 18.8%, crude odds ratio, 0.81; 95% confidence interval, 0.62-1.06), or a serious adverse event composite of death before discharge. CONCLUSION: Among nonvigorous infants born at 35 to 42 weeks' gestation, umbilical cord milking did not reduce neonatal intensive care unit admission for predefined criteria. However, infants in the umbilical cord milking arm had higher hemoglobin, received less delivery room cardiorespiratory support, had a lower incidence of moderate-to-severe hypoxic-ischemic encephalopathy, and received less therapeutic hypothermia. These data may provide the first randomized controlled trial evidence that umbilical cord milking in nonvigorous infants is feasible, safe and, superior to early cord clamping.

Prematuridad tardía: recomendaciones para el seguimiento a largo plazo / Late preterm newborn: follow-up recommendations

La tasa de prematuridad global, según laOrganización Mundial de la Salud (OMS),muestra un aumento progresivo; su principal componente es el grupo de prematuros tardíos. Este grupo de pacientes suele tener buen peso al nacer, lo que hace que no se perciba muchas veces el riesgo de presentar un espectro de morbilidades del desarrollo, conductuales einmadurez de diferentes órganos y sistemasque impactan en la evolución a corto y largo plazo y aumentan la morbimortalidad. A su vez, tienen un efecto sustancial en los servicios de atención médica. El objetivo de esta publicación es discutir algunosaspectos relacionados con la salud de este grupo de pacientes y sugerir su seguimiento con un enfoque holístico e interdisciplinario.

The WHO states that prematurity rates have increased mainly due to late preterm births. Since these babies are usually born with appropriate weight for their gestational age, their risk for morbidities such as neurodevelopmental delays, behavioral problems and organ systems immaturity are overlooked. Further, these clinical findings have an impact on short and long term outcomes (i.e., morbidities, mortality, and higher healthcare costs). The aim of this publication is to discuss topics related to late-preterm newborns' health, including a holistic and interdisciplinary approach to follow up care.

[Late preterm newborn: follow-up recommendations]. / Prematuridad tardía: recomendaciones para el seguimiento a largo plazo.

The WHO states that prematurity rates have increased mainly due to late preterm births. Since these babies are usually born with appropriate weight for their gestational age, their risk for morbidities such as neurodevelopmental delays, behavioral problems and organ systems immaturity are overlooked. Further, these clinical findings have an impact on short and long term outcomes (i.e., morbidities, mortality, and higher healthcare costs). The aim of this publication is to discuss topics related to late-preterm newborns' health, including a holistic and interdisciplinary approach to follow up care.

La tasa de prematuridad global, según la Organización Mundial de la Salud (OMS), muestra un aumento progresivo; su principal componente es el grupo de prematuros tardíos. Este grupo de pacientes suele tener buen peso al nacer, lo que hace que no se perciba muchas veces el riesgo de presentar un espectro de morbilidades del desarrollo, conductuales e inmadurez de diferentes órganos y sistemas que impactan en la evolución a corto y largo plazo y aumentan la morbimortalidad. A su vez, tienen un efecto sustancial en los servicios de atención médica. El objetivo de esta publicación es discutir algunos aspectos relacionados con la salud de este grupo de pacientes y sugerir su seguimiento con un enfoque holístico e interdisciplinario.

Intravenous Fluid Supplementation for Preterm Infants With Hyperbilirubinemia: A Retrospective Cohort Study.

BACKGROUND: Hyperbilirubinemia is one of the most frequently occurring problems in the neonatal period, and phototherapy has remained the primary treatment of choice. Fluid supplementation has been proposed to reduce serum bilirubin levels. PURPOSE: To assess the risks and benefits of fluid supplementation compared with standard fluid management in preterm infants with unconjugated hyperbilirubinemia under conventional phototherapy. METHODS: A retrospective cohort study of preterm infants (gestational ages ≥28 to ≤32 weeks) admitted to the neonatal intensive care unit at the Maternity and Children Hospital in Jeddah, Saudi Arabia, from January 1, 2017, to December 31, 2017, and required the initiation of phototherapy in the first week of life. RESULTS: One hundred and fifteen infants were included; 51 received fluid supplementation, and 64 received standard fluid management. There were no significant differences in demographic characteristics between groups. The infants who received fluid supplementation had a significantly larger decline in the total serum bilirubin level per day and a shorter phototherapy duration ( P < .01). There were no significant differences in weight ( P = .14), or sodium ( P = .79) change per day or the need for exchange transfusion between groups. The prematurity-related inhospital morbidities were similar between groups. IMPLICATIONS FOR PRACTICE AND RESEARCH: Fluid supplementation in preterm infants receiving conventional phototherapy resulted in a faster decline in the bilirubin level and a shorter duration of phototherapy, without increasing prematurity-related morbidities. Future randomized controlled trials to assess the benefits and risks of fluid supplementation during conventional phototherapy in preterm infants are needed.

Feeding intolerance during phototherapy in preterm infants.

OBJECTIVE: Many very preterm infants are treated with phototherapy (PT) for hyperbilirubinemia and it has been reported that PT can negatively affect gut perfusion. Thus, our aim was to evaluate the occurrence of feeding intolerance in the course of PT in these patients. METHODS: We retrospectively studied infants born at 25+0-31+6 weeks from November 2017 to April 2020 who required PT during the first two weeks of life. Patients were used as their own controls recording for each one the occurrence of feeding intolerance after starting PT and the resumption of feeding tolerance after its termination. RESULTS: We studied 125 preterm infants of whom 58 (46%) developed a feeding intolerance which disappeared in 47 (81%) of them at the end of PT. Regression analysis showed a trend toward a not significant decrease of risk of feeding intolerance in infants with higher birth weight and age at the start of the first course of PT. CONCLUSION: We found that about half of our patients developed a transient feeding intolerance during PT that ceased in the vast majority of them after termination of the therapy. Further studies are necessary to confirm the correlation between PT and feeding intolerance.

Use of Probiotics in Preterm Infants.

Probiotic products in the United States are available for use in the general category of dietary supplements, bypassing the rigor of the US Food and Drug Administration (FDA) approval process in safety, efficacy, and manufacturing standards. As a result, currently available probiotics lack FDA-approved drug labeling and cannot be marketed to treat or prevent disease in preterm infants, including necrotizing enterocolitis and late-onset sepsis. Despite lack of availability of a pharmaceutical-grade product, the number of preterm infants receiving probiotics in the United States and Canada is steadily increasing. According to recent reports from large collaborative databases in the United States, approximately 10% of extremely low gestational age neonates receive a probiotic preparation during their stay in the NICU, with wide variation in practice among units. In sum, more than 10 000 preterm infants have been enrolled in randomized clinical trials of probiotic supplementation worldwide. Methodologic differences among study protocols included different strains and combinations of therapy, masking of trials, and a priori definitions of the primary outcome measure. Large meta-analyses of these trials have demonstrated the efficacy of multiple-strain probiotics in reducing necrotizing enterocolitis and all-cause mortality, whereas the efficacy of single-strain probiotic preparations is less certain. In the absence of an appropriate medical-grade product in the United States, dietary supplement-grade probiotics, some of which have been the subject of recent recalls for contamination, are being prescribed. Given the lack of FDA-regulated pharmaceutical-grade products in the United States, conflicting data on safety and efficacy, and potential for harm in a highly vulnerable population, current evidence does not support the routine, universal administration of probiotics to preterm infants, particularly those with a birth weight of <1000 g.

Zinc Supplementation in Preterm Neonates with Jaundice: Is it Beneficial?

BACKGROUND: Neonatal jaundice is a common neonatal disease that has adverse effects on neonates, especially preterm neonates, when indirect bilirubin level is adequately high to pass the blood-brain barrier, causing bilirubin encephalopathy or kernicterus. AIM: This study aimed to investigate the value of zinc (Zn) supplementation in preterm neonates with jaundice and whether it will be beneficial. PATIENTS AND METHODS: A prospective randomized clinical trial, with the identification number TCTR20200504007, was conducted at Tanta University Hospital from July 2016 to March 2018 on 200 preterm neonates with jaundice. The studied neonates were divided into two groups: group 1, which received Zn and phototherapy, and group 2, which received phototherapy only and did not receive Zn. In group 1, 100 preterm neonates with jaundice received Zn as 0.6 mL (cm3) of zinc origin/kg/day orally through the oro-nasogastric tube divided into two doses (every 12 h), which was equal to 1.2 mg elemental zinc/kg/day orally for 10 days. RESULTS: There was no significant difference in serum bilirubin level between the two groups on the 2nd, 4th, and 6th days of admission, while the serum bilirubin level was significantly decreased in group 1 compared with that in group 2 only on the 8th, 9th, and 10th days of admission. The p-- values were 0.045*, 0.027*, and 0.004*, respectively. CONCLUSION: Zn administration to preterm neonates with jaundice was found to be beneficial in decreasing serum bilirubin level. RECOMMENDATION: Zn supplementation should be provided to preterm neonates with jaundice.

Unbound bilirubin levels in phototherapy-treated preterm infants receiving soy-based lipid emulsion.

BACKGROUND: Phototherapy is an effective treatment for neonatal jaundice. Treatment indication uses total serum bilirubin (TSB), although unbound bilirubin (Bf) more accurately predicts disability risk. The goals of this investigation were to examine the response of Bf and TSB to phototherapy in preterm infants, and we hypothesized that (i) TSB and Bf respond differently; (ii) the relationship between TSB and Bf is altered; and (iii) unexpected Bf elevations are found. METHODS: One hundred and seventeen preterm infants <2 kg at birth and receiving (IL) were enrolled; and measurements of TSB and Bf were obtained. TSB was measured by the diazo method and Bf with a fluorescent Bf sensor BL22P1B11-Rh. RESULTS: Initial mean (± SD) TSB and Bf levels (41.4 ± 6.9 h) were 8.0 ± 9.0 mg/dL and 16.9 ± 12.4 nmol/L (P < 0.05). The rates of rise (ROR) were 0.21 ± 0.10 mg/dL/h for TSB and 0.38 ± 0.33 nmol/L/h for Bf. Phototherapy reduced TSB from 8.0 ± 9.0 to 5.8 ± 9.4 mg/dL (P = 0.068) but Bf did not change (16.9 ± 12.4 to 14.1 ± 9.4 nmol/L P = n.s.). Bf levels were >11 nmol/L in 64, >17 nmol/L in 18, and >22 nmol/L in 7 infants. CONCLUSIONS: Bf and TSB responded differently. While TSB and Bf correlated well before phototherapy, they did not correlate during phototherapy. TSB showed a trend toward a reduction with treatment, Bf did not. While TSB ROR information is not helpful, ROR Bf data can be utilized to anticipate treatment. Potentially high Bf levels existed before and after phototherapy and the mean Bf level at phototherapy termination remained elevated in a significant proportion of infants.

Blue LED phototherapy in preterm infants: effects on an oxidative marker of DNA damage.

BACKGROUND: Phototherapy is used on the majority of preterm infants with unconjugated hyperbilirubinaemia. The use of fluorescent tube phototherapy is known to induce oxidative DNA damage in infants and has largely been replaced by blue light-emitting diode phototherapy (BLP). To date, it is unknown whether BLP also induces oxidative DNA damage in preterm infants. OBJECTIVE: To determine whether BLP in preterm infants induces oxidative DNA damage as indicated by 8-hydroxy-2'deoxyguanosine (8-OHdG). DESIGN: Observational cohort study. METHODS: Urine samples (n=481) were collected in a cohort of 40 preterm infants (24-32 weeks' gestational age) during the first week after birth. Urine was analysed for the oxidative marker of DNA damage 8-OHdG and for creatinine, and the 8-OHdG/creatinine ratio was calculated. Durations of phototherapy and levels of irradiance were monitored as well as total serum bilirubin concentrations. RESULTS: BLP did not alter urinary 8-OHdG/creatinine ratios (B=0.2, 95% CI -6.2 to 6.6) at either low (10-30 µW/cm2/nm) or high (>30 µW/cm2/nm) irradiance: (B=2.3, 95% CI -5.7 to 10.2 and B=-3.0, 95% CI -11.7 to 5.6, respectively). Also, the 8-OHdG/creatinine ratios were independent on phototherapy duration (B=-0.1, 95% CI -0.3 to 0.1). CONCLUSIONS: BLP at irradiances up to 35 µW/cm2/nm given to preterm infants ≤32 weeks' gestation does not affect 8-OHdG, an oxidative marker of DNA damage.

Oropharyngeal Colostrum Positively Modulates the Inflammatory Response in Preterm Neonates.

During the first days of life, premature infants have physiological difficulties swallowing, thereby missing out on the benefits of breastfeeding. The aim of this study is to assess the effects of oropharyngeal mother's milk administration in the inflammatory signaling of extremely premature infants. Neonates (n = 100) (<32 week's gestation and/or <1500 g) were divided into two groups: mother's milk group (n = 48), receiving 0.2 mL of oropharyngeal mother's milk every 4 h for the first 15 days of life, and a control group (n = 52), not receiving oropharyngeal mother's milk. Serum concentrations of interleukin (IL) IL-6, IL-8, IL-10, IL-1ra, tumor necrosis factor alpha (TNF-α), and interferón gamma (IFN-γ) were assessed at 1, 3, 15, and 30 days of postnatal life. Maternal and neonatal outcomes were collected. The rate of common neonatal morbidities in both groups was similar. The mother's milk group achieved full enteral feeding earlier, and showed a decrease in Il-6 on days 15 and 30, in IL-8 on day 30, and in TNF-α and INF-γ on day 15, as well as an increase in IL-1ra on days 3 and 15 and in IL-10 on day 30. Oropharyngeal mother's milk administration for 15 days decreases the pro-inflammatory state of preterm neonates and provides full enteral nutrition earlier, which could have a positive influence on the development of the immune system and inflammatory response, thereby positively influencing other developmental outcomes.

Systematic Review of the Effects of Skin-to-Skin Care on Short-Term Physiologic Stress Outcomes in Preterm Infants in the Neonatal Intensive Care Unit.

BACKGROUND: Infants in the neonatal intensive care unit (NICU) are exposed to many stressors. There is growing evidence that chronic stress early in life has long-term neurodevelopmental implications. Skin-to-skin care (SSC) is an intervention used to reduce stress in the NICU. CLINICAL QUESTION: In premature infants in the NICU, what is the available evidence that SSC improves short-term physiologic stress outcomes compared with incubator care? SEARCH STRATEGY: PubMed and CINAHL were searched for terms related to SSC, stress, physiology, and premature infants. Of 1280 unique articles, 19 were identified that reported on research studies comparing SSC with incubator care in the NICU and reported stress-related physiologic outcome measures. RESULTS: Although there have been some mixed findings, the research supports that SSC improves short-term cardiorespiratory stress outcomes compared with incubator care. The evidence is clearer for studies reporting stress hormone outcomes, with strong evidence that SSC reduces cortisol and increases oxytocin levels in preterm infants. IMPLICATIONS FOR PRACTICE AND RESEARCH: SSC is safe and has stress-reducing benefits. SSC should be considered an essential component to providing optimal care in the NICU. More research is needed to determine the timing of initiation, duration, and frequency of SSC to optimize the stress-reducing benefits. Future research should include the most fragile infants, who are most likely to benefit from SSC, utilize power analyses to ensure adequate sample sizes, and use sophisticated data collection and analysis techniques to more accurately evaluate the effect of SSC on infants in the NICU.

Sixty years of phototherapy for neonatal jaundice - from serendipitous observation to standardized treatment and rescue for millions.

A breakthrough discovery 60 years ago by Cremer et al. has since changed the way we treat infants with hyperbilirubinemia and saved the lives of millions from death and disabilities. "Photobiology" has evolved by inquiry of diverse light sources: fluorescent tubes (wavelength range of 400-520 nm; halogen spotlights that emit circular footprints of light; fiberoptic pads/blankets (mostly, 400-550 nm range) that can be placed in direct contact with skin; and the current narrow-band blue light-emitting diode (LED) light (450-470 nm), which overlaps the peak absorption wavelength (458 nm) for bilirubin photoisomerization. Excessive bombardment with photons has raised concerns for oxidative stress in very low birthweight versus term infants treated aggressively with phototherapy. Increased emphasis on prescribing phototherapy as a "drug" that is dosed cautiously and judiciously is needed. In this historical review, we chronicled the basic to the neurotoxic components of severe neonatal hyperbilirubinemia and the use of standardized interventions.

Longitudinal Study of music Therapy's Effectiveness for Premature infants and their caregivers (LongSTEP): protocol for an international randomised trial.

INTRODUCTION: Preterm birth has major medical, psychological and socioeconomic consequences worldwide. Music therapy (MT) has positive effects on physiological measures of preterm infants and maternal anxiety, but rigorous studies including long-term follow-up are missing. Drawing on caregivers' inherent resources, this study emphasises caregiver involvement in MT to promote attuned, developmentally appropriate musical interactions that may be of mutual benefit to infant and parent. This study will determine whether MT, as delivered by a qualified music therapist during neonatal intensive care unit (NICU) hospitalisation and/or in home/municipal settings following discharge, is superior to standard care in improving bonding between primary caregivers and preterm infants, parent well-being and infant development. METHODS AND ANALYSIS: Design: international multicentre, assessor-blind, 2×2 factorial, pragmatic randomised controlled trial; informed by a completed feasibility study. Participants: 250 preterm infants and their parents. Intervention: MT focusing on parental singing specifically tailored to infant responses, will be delivered during NICU and/or during a postdischarge 6-month period. Primary outcome: changes in mother-infant bonding at 6-month corrected age (CA), as measured by the Postpartum Bonding Questionnaire. Secondary outcomes: mother-infant bonding at discharge and at 12-month CA; child development over 24 months; and parental depression, anxiety and stress, and infant rehospitalisation, all over 12 months. ETHICS AND DISSEMINATION: The Regional Committees for Medical and Health Research Ethics approved the study (2018/994/REK Nord, 03 July 2018). Service users were involved in development of the study and will be involved in implementation and dissemination. Dissemination of findings will apply to local, national and international levels. TRIAL REGISTRATION NUMBER: NCT03564184.

A Simpler Prediction Rule for Rebound Hyperbilirubinemia.

OBJECTIVES: We previously reported a clinical prediction rule to estimate the probability of rebound hyperbilirubinemia using gestational age (GA), age at phototherapy initiation, and total serum bilirubin (TSB) relative to the treatment threshold at phototherapy termination. We investigated (1) how a simpler 2-variable model would perform and (2) the absolute rebound risk if phototherapy were stopped at 2 mg/dL below the threshold for treatment initiation. METHODS: Subjects for this retrospective cohort study were infants born 2012-2014 at ≥35 weeks' gestation at 1 of 17 Kaiser Permanente hospitals who underwent inpatient phototherapy before age 14 days. TSB reaching the phototherapy threshold within 72 hours of phototherapy termination was considered rebound. We simplified by using the difference between the TSB level at the time of phototherapy termination and the treatment threshold at the time of phototherapy initiation as 1 predictor, and kept GA as the other predictor. RESULTS: Of the 7048 infants treated with phototherapy, 4.6% had rebound hyperbilirubinemia. The area under the receiver operating characteristic curve was 0.876 (95% confidence interval, 0.854 to 0.899) for the 2-variable model versus 0.881 (95% confidence interval, 0.859 to 0.903) for the 3-variable model. The rebound probability after stopping phototherapy at 2 mg/dL below the starting threshold was 2.5% for infants ≥38 weeks' GA and 10.2% for infants <38 weeks' GA. CONCLUSIONS: Rebound hyperbilirubinemia can be predicted by a simpler 2-variable model consisting of GA and the starting threshold-ending TSB difference. Infants <38 weeks' gestation may need longer phototherapy because of their higher rebound risk.

New Nutritional and Therapeutical Strategies of NEC.

Necrotizing enterocolitis (NEC) is an acquired severe disease of the digestive system affecting mostly premature babies, possibly fatal and frequently associated to systemic complications. Because of the severity of this condition and the possible long-term consequences on the child's development, many studies have aimed at preventing the occurrence of the primary events at the level of the bowel wall (ischemia and necrosis followed by sepsis) by modifying or manipulating the diet (breast milk versus formula) and/or the feeding pattern (time for initiation after birth, continuous versus bolus feeding, modulation of intake according clinical events). Feeding have been investigated so far in order to prevent NEC. However, currently well-established and shared clinical nutritional practices are not available in preventing NEC. Nutritional and surgical treatments of NEC are instead well defined. In selected cases surgery is a therapeutic option of NEC, requiring sometimes partial intestinal resection responsible for short bowel syndrome. In this paper we will investigate the available options for treating NEC according to the Walsh and Kliegman classification, focusing on feeding practices in managing short bowel syndrome that can complicate NEC. We will also analyze the proposed ways of preventing NEC.

Enteral Docosahexaenoic Acid and Retinopathy of Prematurity: A Randomized Clinical Trial.

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.

Extrauterine Growth Restriction in Low Birth Weight Infants.

Extrauterine growth restriction (EUGR) affects a significant number of very low birth weight (VLBW) infants and has the potential to impact neurodevelopmental outcome as well as other aspects of long-term health. More aggressive nutritional approaches have reduced the incidence of postnatal growth failure but many questions remain about the expected rate of growth for very preterm infants, the best ways to measure growth velocity, and the optimal approaches to supporting growth. This article examines some of the outstanding issues regarding postnatal growth failure and summarizes current practice recommendations.

Intravenous Lipid Emulsions in Infants: Is Balanced Better?

Parenteral nutrition (PN) is frequently required by extremely preterm infants due to gastrointestinal immaturity and complications of prematurity. Parenteral nutrition-associated cholestasis (PNAC) and intestinal failure-associated liver disease (IFALD) are common complications of prolonged PN. Plant-based intravenous lipid emulsions, containing proinflammatory omega-6 fatty acids and phytosterols, may contribute to these conditions as well as other comorbidities such as bronchopulmonary dysplasia and retinopathy of prematurity. Intravenous lipid emulsions containing animal-based fats, such as fish oil, contain fewer proinflammatory omega-6 fatty acids and more anti-inflammatory omega-3 fatty acids and antioxidants. SMOFlipid, recently Food and Drug Administration (FDA)-approved for adult use, is a blend of plant- and animal-based lipid emulsions with a favorable omega-6:omega-3 ratio that may prevent the development and progression of PNAC/IFALD in infants. Careful review of data supporting this alternative intravenous lipid emulsion is required prior to widespread use in neonatal intensive care.