Vitamin K and ECMO for neonatal hypoxic respiratory failure.

INTRODUCTION: The objectives of this retrospective cohort study were to examine the effect of vitamin K administration on hemorrhagic and thrombotic complications, blood product utilization, and outcomes in neonatal extracorporeal membrane oxygenation (ECMO). METHODS: In the pilot study, complications, blood product use, and outcome data for neonates who received (n = 21) or did not receive (n = 18) a single dose of vitamin K (5 mg) immediately after initiation of ECMO for respiratory failure between 2006 and 2010 were compared. In the validation cohort, complications and outcomes were compared for 74 consecutive neonates supported with ECMO for respiratory failure who received (n = 45) or did not receive (n = 29) additional vitamin K once daily for prothrombin time (PT) ⩾14 seconds during ECMO from 2014 to 2019. RESULTS: In the pilot study, vitamin K at ECMO initiation was associated with fewer thrombotic complications and similar hemorrhagic complications. The volume of fresh frozen plasma was higher in neonates who received vitamin K, but total blood product and other component volume did not differ between groups. ECMO run time, survival off ECMO, survival to discharge, and length of stay did not differ between cohorts. In the validation cohort, neonates who received additional vitamin K during ECMO had longer ECMO run time and length of stay, but no difference in mortality was observed. Further, thrombotic and hemorrhagic complications as well as blood product exposure were similar between cohorts. CONCLUSIONS: These data suggest that routine vitamin K administration may have limited or no benefit during neonatal ECMO.

Synthetic Surfactant CHF5633 Compared with Poractant Alfa in the Treatment of Neonatal Respiratory Distress Syndrome: A Multicenter, Double-Blind, Randomized, Controlled Clinical Trial.

OBJECTIVE: To compare efficacy and safety of a new synthetic surfactant, CHF5633, enriched with surfactant proteins, SP-B and SP-C peptide analogues, with porcine surfactant, poractant alfa, for the treatment of respiratory distress syndrome in infants born preterm. STUDY DESIGN: Neonates born preterm on respiratory support requiring fraction of inspired oxygen (FiO2) ≥0.30 from 240/7 to 266/7 weeks and FiO2 ≥0.35 from 270/7 to 296/7 weeks of gestation to maintain 88%-95% oxygen saturation were randomized to receive 200 mg/kg of CHF5633 or poractant alfa. If necessary, redosing was given at 100 mg/kg. Efficacy end points were oxygen requirement (FiO2, respiratory severity score [FiO2 × mean airway pressure]) in the first 24 hours, 7 and 28 days, discharge home, and/or 36 weeks of postmenstrual age; mortality and bronchopulmonary dysplasia at 28 days and 36 weeks of PMA. Adverse events and immunogenicity were monitored for safety. RESULTS: Of the 123 randomized neonates, 113 were treated (56 and 57 in CHF5633 and poractant alfa groups, respectively). In both arms, FiO2 and respiratory severity score decreased from baseline at all time points (P < .001) with no statistically significant differences between groups. Rescue surfactant use (19 [33.9%] vs 17 [29.8%]), bronchopulmonary dysplasia (31 [55.4%] and 32 [56.1%]), and mortality at day 28 (4 [7.1%] and 3 [5.3%]) were similar in the CHF5633 and poractant alfa groups, respectively. In 2 (3.4%) and 1 (1.7%) neonates, adverse drug reactions were reported in CHF5633 and poractant alfa groups, respectively. No immunogenicity was detected. CONCLUSIONS: Treatment with CHF5633 showed similar efficacy and safety as poractant alfa in neonates born preterm with moderate-to-severe respiratory distress syndrome. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02452476.

The utility of cranial ultrasound as a screening tool for neonatal ECMO.

Background Neurologic complications including hemorrhage, ischemia, and infarction are often identified in neonates undergoing extracorporeal membrane oxygenation (ECMO) and may contribute to the high morbidity observed in ECMO survivors. Screening for intracranial complications is reliant on bedside transcranial ultrasound (CUS) prior to and during ECMO therapy, and advanced imaging [i.e. computed tomography (CT)/magnetic resonance imaging (MRI)] is recommended after completion of ECMO support. The goal of this study is to describe the correlation of intracranial complications identified on CUS during ECMO and MRI after completion of ECMO. Methods Fifty-five neonates underwent ECMO support at the Children's Hospital of Georgia at Augusta University from January 1, 2012 to December 31, 2017. Forty-four (80%) had a brain MRI performed prior to transfer or discharge. Ultrasound studies were reviewed by a single blinded pediatric radiologist and MRIs were reviewed by a single blinded neuro-radiologist. Results Of the 44 neonates with post-ECMO MRI, CUS during ECMO identified intracranial lesions in nine neonates, which were all confirmed on post-ECMO MRI. Sixteen subjects (46%) with unremarkable CUS during ECMO had identifiable lesions on post-ECMO MRI, yielding a sensitivity of 36% and a specificity of 100% for CUS in the detection of intracranial lesions. Despite the lack of correlation between CUS and MR, 84.6% of survivors exhibited normal development at 24 months of age. Conclusion While necessary for the identification of intracranial lesions during neonatal ECMO, CUS demonstrated low correlation with post-ECMO MRI in the identification of intracranial lesions, which supports Extracorporeal Life Support Organization (ELSO) recommendations.

Rapid Assessment of the Neonate With Sonography (RANS) Scan.

The use of point-of-care sonography in clinical settings such as emergency medicine and intensive care units has increased, but adoption in neonatology has been slow. Unlike the focused assessment with sonography for trauma scan used in adults, a quick bedside scan to rapidly evaluate an acutely deteriorating neonate does not exist. The objective of our article is to introduce a focused bedside ultrasound scan that is easy to learn, rapidly performed, and relatively inexpensive.© 2018 by the American Institute of Ultrasound in Medicine.

Urinary Biomarkers to Predict Neonatal Acute Kidney Injury: A Review of the Science.

Acute kidney injury (AKI) occurs in approximately 30% of all infants hospitalized in the neonatal intensive care unit. About 40% of very low-birth-weight infants develop AKI, with an estimated mortality rate of 50% to 80%. Very low-birth-weight survivors have twice the risk of developing chronic renal disease later in life compared with their term counterparts. Current diagnostic modalities for AKI include serum creatinine and urine output; however, recent studies suggest that these measures are imprecise, as they may not change until 25% to 50% of renal function is lost. Urinary biomarkers may more accurately identify infants at risk for early AKI development. The purpose of this review is to discuss current research findings related to neonatal AKI risk factors, provide an overview of short- and long-term outcomes, describe innovative diagnostic approaches, and identify future research direction needed to improve prediction and intervention strategies associated with renal impairment.

Comparison of transfusion thresholds during neonatal extracorporeal membrane oxygenation.

BACKGROUND: The objective of this study was to assess complications and patient outcomes associated with a lower reflexive red blood cell (RBC) transfusion threshold for neonates undergoing extracorporeal membrane oxygenation (ECMO) for hypoxic respiratory failure. STUDY DESIGN AND METHODS: A retrospective cohort study was conducted at a single tertiary neonatal intensive care unit of neonates undergoing ECMO support for refractory hypoxic respiratory failure for more than 24 hours between December 2009 and December 2014. Seventy-two neonates received ECMO support for hypoxic respiratory failure for longer than 24 hours during the study period. Patient cohorts were determined based on transfusion threshold of hematocrit (Hct) level of less than 40% (December 2009-October 2012) and Hct level of less than 35% (November 2012-December 2014). RESULTS: Patients who had a lower threshold for transfusion (Hct < 35) had a lower mean Hct (38.3% vs. 41.4%, p < 0.0001) and received less total RBC transfusion volume (10.4 mL/kg/day vs. 13.3 mL/kg/day, p = 0.002) while undergoing ECMO support. Survival off ECMO, survival to discharge, and complication rates were similar between the cohorts. CONCLUSIONS: A lower Hct threshold of 35% is associated with a reduction in RBC transfusion volume and does not appear to alter complication rates or patient outcomes for neonates receiving ECMO support for respiratory failure.

Fluconazole Prophylaxis for the Prevention of Candidiasis in Premature Infants: A Meta-analysis Using Patient-level Data.

BACKGROUND: Invasive candidiasis (IC) is an important cause of sepsis in premature infants and is associated with a high risk of death and neurodevelopmental impairment. Prevention of IC has become a major focus in very low birth weight infants, with fluconazole increasingly used as prophylaxis. METHODS: We identified all randomized, placebo-controlled trials evaluating fluconazole prophylaxis in premature infants conducted in the United States. We obtained patient-level data from the study investigators and performed an aggregated analysis. The occurrence of each endpoint in infants who received prophylaxis with fluconazole vs placebo was compared. Endpoints evaluated were IC or death, IC, death, Candida colonization, and fluconazole resistance among tested isolates. Safety endpoints evaluated included clinical and laboratory parameters. RESULTS: Fluconazole prophylaxis reduced the odds of IC or death, IC, and Candida colonization during the drug exposure period compared with infants given placebo: odds ratios of 0.48 (95% confidence interval [CI], .30-.78), 0.20 (95% CI, .08-.51), and 0.28 (95% CI, .18-.41), respectively. The incidence of clinical and laboratory adverse events was similar for infants who received fluconazole compared with placebo. There was no statistically significant difference in the proportion of tested isolates that were resistant to fluconazole between the fluconazole and placebo groups. CONCLUSIONS: Fluconazole prophylaxis is effective and safe in reducing IC and Candida colonization in premature infants, and has no impact on resistance.

Nonlinear Relationship between Birth Weight and Visceral Fat in Adolescents.

OBJECTIVE: To determine the association of birth weight with abdominal fat distribution and markers known to increase risk for cardiovascular disease and type 2 diabetes in adolescents. STUDY DESIGN: In 575 adolescents aged 14-18 years (52% female, 46% black), birth weight was obtained by parental recall. Fasting blood samples were measured for glucose, insulin, lipids, adiponectin, leptin, and C-reactive protein. Subcutaneous abdominal adipose tissue and visceral adipose tissue were assessed by magnetic resonance imaging. RESULTS: When we compared markers of cardiometabolic risk across tertiles of birth weight, adjusting for age, sex, race, Tanner stage, physical activity, socioeconomic status, and body mass index, there were significant U-shaped trends for homeostasis model assessment of insulin resistance, leptin, and visceral adipose tissue (all Pquadratic < .05). A significant linear downward trend across tertiles of birth weight was observed for triglycerides (Plinear = .03). There were no differences in fasting glucose, blood pressure, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, adiponectin, C-reactive protein, or subcutaneous abdominal adipose tissue across tertiles of birth weight. CONCLUSIONS: Our data suggest that both low and high birth weights are associated with greater visceral adiposity and biomarkers implicated in insulin resistance and inflammation in adolescents.

Variable Clinical Presentations of ABO Incompatibility in Dizygotic Twins.

Newborns with ABO blood group incompatibility can have a spectrum of clinical presentations from remaining asymptomatic to severe hemolytic anemia with jaundice. This case presentation discusses dizygotic twins who demonstrated both ends of the clinical spectrum. Similar cases in which there is such extreme variation between twins were not attainable in the current literature, which prompted the authors to present it as a rare occurrence and one that was unexpected based on their past experience with ABO incompatibility both in singletons and in twins.

Hydrolyzed formulas for allergy prevention.

OBJECTIVES: The aim of the present review was to provide recommendations on the use of hydrolysates in infants when formula feeding is initiated. METHODS: We performed an overview of reviews followed by a systematic review of subsequently published trials. RESULTS: We found 8 systematic reviews; only 1 study of limited quality was published afterwards. Certain extensively hydrolyzed casein and certain partially hydrolyzed whey formulas are appropriate for reducing the risk of allergy in infants at high risk when formula feeding is initiated. CONCLUSIONS: In high-risk infants, when breast-feeding is not possible, hydrolysates of documented safety and efficacy have an indication in infant feeding up to the age 4 to 6 months.

Growth curves: how to best measure growth of the preterm infant.

Birth weight is one of the most important anthropometric measures in the evaluation of an infant. For the full-term infant, birth weight is compared with reference or standard growth curves that are constructed by plotting weight, length, and head circumference against postnatal age. Following a similar approach for preterm infants is less effective for a variety of reasons. Birth weight and other anthropometric measures used to evaluate an infant at birth are influenced by various maternal characteristics, the intrauterine milieu, and duration of gestation. Second, the causes of premature birth and their impact on birth weight are largely unknown. Third, gestational age is difficult to determine with full certainty. One approach that has been used to circumvent these issues is to use intrauterine growth reference curves. However, these curves do not really reflect "normal" growth because they were constructed using cross-sectional data from infants born prematurely and, as such, do not reflect the normal condition. Thus, there is a need to develop normative growth curves derived from "healthy" preterm infants that can be applied to neonates born prematurely. These should be updated periodically to reflect secular trends in maternal body weight, height, and overall health.

Evaluation of adequacy of protein and energy.

Growth assessment is the most common measure of nutritional adequacy in pediatrics, especially when evaluating nutrition of preterm neonates. The American Academy of Pediatrics defines postnatal nutrient intake to promote growth as one that "approximates the rate of growth...for a normal fetus of the same post-menstrual age." It is known that in the fetus, fat and lean body mass are accreted progressively as gestation progresses, whereas postnatal growth and observed accretion of fat and lean body mass differ. This review discusses anthropometric measures used to assess growth, biochemical markers used to monitor nutritional sufficiency, and the effect of growth trajectory in preterm infants on health outcomes later in life.

Selected macro/micronutrient needs of the routine preterm infant.

Requirements for optimal nutrition, especially for micronutrients, are not well defined for premature infants. The "reference fetus," developed by Ziegler et al,(1) has served as a model to define nutritional needs and studies designed to determine nutrient requirements. Revision of nutrient requirements and provision of optimal nutrition may lead to improved outcomes in preterm infants. Appropriate provision of nutrients also may help prevent nutritional disorders, such as metabolic bone disease and anemia. In this review, we discuss calcium, phosphorus, magnesium, vitamin D, iron, and copper, and define optimal intakes based on the available published data.

Human milk and the premature infant.

Human milk is the preferred feeding for both term and preterm infants. While being considered optimal for term infants, human milk, even from mothers delivering preterm infants, is lacking in protein, energy, sodium, calcium, and phosphorus, resulting in poorer growth and nutrient deficiencies when compared to formulas designed for these high-risk infants. Further, the lack of growth is associated with long-term adverse consequences. Since human milk has unique properties in promoting gastrointestinal maturation and immunological benefits, it is prudent to implement strategies to fortify it appropriately to realize its benefits which include reduced rates of necrotizing enterocolitis, fewer episodes of sepsis and urinary tract infections, and improved visual and neurocognitive development. Donor human milk is being widely used when mothers' own milk is not available or is in short supply. While it retains some of the biological properties and clinical benefits of mothers' own milk, it requires additional care in fortification, especially if the donor milk is from a pool of term human milk. As nutritional strategies improve, the ultimate goal is to minimize extrauterine growth restriction and promote appropriate growth after regaining birth weight.

NTP-CERHR expert panel report on the developmental toxicity of soy infant formula.

Soy infant formula contains soy protein isolates and is fed to infants as a supplement to or replacement for human milk or cow milk. Soy protein isolates contains estrogenic isoflavones (phytoestrogens) that occur naturally in some legumes, especially soybeans. Phytoestrogens are nonsteroidal, estrogenic compounds. In plants, nearly all phytoestrogens are bound to sugar molecules and these phytoestrogen-sugar complexes are not generally considered hormonally active. Phytoestrogens are found in many food products in addition to soy infant formula, especially soy-based foods such as tofu, soy milk, and in some over-the-counter dietary supplements. Soy infant formula was selected for National Toxicology Program (NTP) evaluation because of (1) the availability of large number of developmental toxicity studies in laboratory animals exposed to the isoflavones found in soy infant formula (namely, genistein) or other soy products, as well as few studies on human infants fed soy infant formula, (2) the availability of information on exposures in infants fed soy infant formula, and (3) public concern for effects on infant or child development. On October 2, 2008 (73 FR 57360), the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) announced its intention to conduct an updated review of soy infant formula to complete a previous evaluation that was initiated in 2005. Both the current and previous evaluations relied on expert panels to assist the NTP in developing its conclusions on the potential developmental effects associated with the use of soy infant formula, presented in the NTP Brief on Soy Infant Formula. The initial expert panel met on March 15 to 17, 2006, to reach conclusions on the potential developmental and reproductive toxicities of soy infant formula and its predominant isoflavone constituent genistein. The expert panel reports were released for public comment on May 5, 2006 (71 FR 28368). On November 8, 2006 (71 FR 65537), CERHR staff released draft NTP Briefs on Genistein and Soy Formula that provided the NTP's interpretation of the potential for genistein and soy infant formula to cause adverse reproductive and/or developmental effects in exposed humans. However, CERHR did not complete these evaluations, finalize the briefs, or issue NTP Monographs on these substances based on this initial evaluation. Between 2006 and 2009, a substantial number of new publications related to human exposure or reproductive and/or developmental toxicity were published for these substances. Thus, CERHR determined that updated evaluations of genistein and soy infant formula were needed. However, the current evaluation focuses only on soy infant formula and the potential developmental toxicity of its major isoflavone components, e.g. genistein, daidzein (and estrogenic metabolite, equol), and glycitein. This updated evaluation does not include an assessment on the potential reproductive toxicity of genistein following exposures during adulthood as was carried out in the 2006 evaluation. CERHR narrowed the scope of the evaluation because the assessment of reproductive effects of genistein following exposure to adults was not considered relevant to the consideration of soy infant formula use in infants during the 2006 evaluation. To obtain updated information about soy infant formula for the CERHR evaluation, the PubMed (Medline) database was searched from February 2006 to August 2009 with genistein/genistin, daidzein/daidzin, glycitein/glycitin, equol, soy, and other relevant keywords. References were also identified from the bibliographies of published literature. The updated expert panel report represents the efforts of a 14-member panel of government and nongovernment scientists, and was prepared with assistance from NTP staff. The finalized report, released on January 15, 2010 (75 FR 2545), reflects consideration of public comments received on a draft report that was released on October 19, 2009, for public comment and discussions that occurred at a public meeting of the expert panel held December 16 to 18, 2009 (74 FR 53509). The finalized report presents conclusions on (1) the strength of scientific evidence that soy infant formula or its isoflavone constituents are developmental toxicants based on data from in vitro, animal, or human studies; (2) the extent of exposures in infants fed soy infant formula; (3) the assessment of the scientific evidence that adverse developmental health effects may be associated with such exposures; and (4) knowledge gaps that will help establish research and testing priorities to reduce uncertainties and increase confidence in future evaluations. The Expert Panel expressed minimal concern for adverse developmental effects in infants fed soy infant formula. This level of concern represents a "2" on the five-level scale of concern used by the NTP that ranges from negligible concern ("1") to serious concern ("5"). The Expert Panel Report on Soy Infant Formula was considered extensively by NTP staff in preparing the 2010 NTP Brief on Soy Infant Formula, which represents the NTP's opinion on the potential for exposure to soy infant formula to cause adverse developmental effects in humans. The NTP concurred with the expert panel that there is minimal concern for adverse effects on development in infants who consume soy infant formula. This conclusion was based on information about soy infant formula provided in the expert panel report, public comments received during the course of the expert panel evaluation, additional scientific information made available since the expert panel meeting, and peer reviewer critiques of the draft NTP Brief by the NTP Board of Scientific Counselors (BSC) on May 10, 2010 (Meeting materials are available at http://ntp.niehs.nih.gov/go/9741.). The BSC voted in favor of the minimal concern conclusion with 7 yes votes, 3 no votes, and 0 abstentions. One member thought that the conclusion should be negligible concern and two members thought that the level of concern should be higher than minimal concern. The NTP's response to the May 10, 2010 review ("peer-review report") is available on the NTP website at http://ntp.niehs.nih.gov/go/9741. The monograph includes the NTP Brief on Soy Infant Formula as well as the entire final Expert Panel Report on Soy Infant Formula. Public comments received as part of the NTP's evaluation of soy infant formula and other background materials are available at http://cerhr.niehs.nih.gov/evals/index.html.

Antibiotic Administration Prior to Central Venous Catheter Removal in Neonates.

BACKGROUND: Central venous catheter infection and sepsis are significant causes of morbidity and mortality in neonatal intensive care unit patients. This complication may result in a significant cost burden, prolonged antibiotic treatment, and increased length of stay. OBJECTIVES: The objective of this study was to determine the difference in post-catheter removal clinical sepsis (PCRCS) in neonatal intensive care unit patients who received antibiotics prior to central venous catheter removal when compared to those who did not. METHODS: This was a retrospective cohort study of 200 critically ill neonates comparing those who received one-time doses of vancomycin and cefazolin prior to central venous catheter removal to those who did not. RESULTS: There was no statistically significant association between antibiotic treatment and PCRCS when the analysis was controlled for gender, time the catheter was in place, birth weight, gestational age, or type of central catheter (OR 1.19; 95% CI: 0.18-8.00; P = .8558). No statistical difference was seen in adverse renal outcomes or total antibiotic treatment received for the treatment of PCRCS. CONCLUSIONS: Administration of one-time doses of vancomycin and cefazolin did not reduce the incidence of PCRCS when administered to critically ill neonates prior to umbilical venous catheter or peripherally inserted central catheter removal.

Unnecessary workup of asymptomatic neonates in the era of group B streptococcus prophylaxis.

Asymptomatic term neonates born to mothers who are Group B Streptococcus (GBS) unknown or GBS positive but "inadequately" treated prior to delivery do not require invasive laboratory evaluation. We conducted a retrospective cohort study of mother/baby dyads born from January 1, 2005 until September 30, 2007 at the Medical College of Georgia. Their current protocol is to obtain a Complete Blood Count with Differential (CBC with D), Blood Culture (BC), and C-reactive protein (CRP) after birth. Mother/baby dyads (n = 242) that met inclusion criteria were reviewed. Of these 242 babies 25 (10%) were started on antibiotics after the initial lab values were known. None of the blood cultures were positive and the CRP's were normal. The 2002 GBS guidelines call for laboratory evaluation of "at-risk" neonates, but the workup of these babies is not only costly, it does not provide any advantage over old fashioned clinical observation for the evaluation and treatment of early onset GBS sepsis.