Calcium chloride in neonatal parenteral nutrition: A 15 year experience.

OBJECTIVE: The objective of this study was to determine if outcomes at our neonatal intensive care units (NICUs) since we began using calcium chloride (CaCl2) as our preferred calcium additive in order to reduce aluminum (Al) exposure are within expected outcome ranges for NICUs in the U.S. where calcium gluconate in glass vials (CaGlu-Gl) has been the preferred additive. STUDY DESIGN: A retrospective study of very low birth weight infants born between January 1, 2000 and December 31, 2014. Outcomes in two intensive care units (NICUs) using CaCl2 were compared to all U.S. NICUs in the Vermont Oxford Network. Primary outcomes were chronic lung disease (CLD), percent requiring supplemental oxygen at 28 days, and mortality excluding early deaths (MEED). The incidence of IV infiltrates of all admissions to the study NICUs in 2013-2014 was compared to the literature. RESULTS: The incidence of CLD and those requiring oxygen at 28 days were 24.0% vs 28.6% and 46.2% vs 51.8% for the study NICUs compared to all U.S. NICUs, respectively (both p < 0.0001). The MEED was 8.7% vs 10.3% (p < 0.002). All major morbidities were lower at the study NICUs. The incidence of infiltrates was lower than that in the literature. CONCLUSION: The use of CaCl2 was not associated with any detectable adverse effects. Calcium chloride appears to be a safe alternative to the use of CaGlu-Gl based upon studies of clinical outcomes.

The quest for sustained multiple morbidity reduction in very low-birth-weight infants: the Antifragility project.

OBJECTIVE: Can a comprehensive, explicitly directive evidence-based guideline for all therapies that might affect the major morbidities of very low-birth-weight (VLBW) infants help a neonatal intensive care unit (NICU) further improve generally favorable morbidity rates? Can Antifragility principles of provider adaptive growth from stressors, enhanced infant risk assessment and adherence to effective therapies minimize unproven treatments and reduce all morbidities? STUDY DESIGN: Prospectively planned observational trial in VLBW infants: control group born October 2011 to September 2013 and study group October 2013 to September 2015. Multi-disciplinary evidence-based review assigned all NICU treatments into one of four distinct categories: (1) always employ this therapy for VLBW infants, (2) never use this therapy, (3) employ this questionable therapy thoughtfully, only in certain circumstances and (4) this therapy has insufficient evidence of efficacy and safety. Extensive staff education emphasized evidence-based potentially better practice (PBP) selection with compliance checks, appreciation of intertwined co-morbidities and prioritizing infant risk reduction strategies. RESULTS: Control included 221 infants, mean (s.d.) age 29 (2.6) weeks, birth weight 1129 (257) g and Study included 197 infants, 29 (2.7) weeks, 1093 (292) g. One hundred and four distinct therapies were placed into categories 1 to 4, with 32 specific compliance checks. Overall mean compliance with the process checks during the second era was 70%, high: 100% (exclusive breast milk use), low: 24% (correct pulse oximetry alarm settings). Morbidity and mortality rates did not significantly change during the second era. CONCLUSIONS: In our NICU with favorable morbidity rates, an expanded effort using a comprehensive therapy guideline for VLBW infants did not further improve outcomes. We need deeper understanding of continuous quality improvement (CQI) fundamentals, therapy compliance, co-morbidity relationships and enhanced sensitivity of risk assessment. Our innovative Antifragility PBP guideline could be useful to other NICUs seeking improvement in VLBW infant morbidities, as we offer a reasoned and concise template of a broad array of therapies categorized efficiently for transparency and review, designed to enhance responsible CQI decision-making.

Extremely premature birth and the choice of neonatal intensive care versus palliative comfort care: an 18-year single-center experience.

OBJECTIVE: Review all live births 22 0/7 through 26 6/7 weeks gestation born 1996 through 2013 at our institution to describe the decision process and immediate outcomes of palliative comfort care (PCC) versus neonatal intensive care (NICU) and whether any significant family complaints or quality assurance concerns arose. STUDY DESIGN: Retrospective chart review, physician and ethicist interview process and database review focused upon our established periviability counseling guidelines that are directive of PCC at 22 weeks gestation and NICU at 26 weeks but supportive of informed family choice of either option at 23, 24 and 25 weeks. RESULT: At 22 weeks--all 54 infants had PCC; at 23 weeks--29/78 (37%) chose NICU care, 6/29 (21%) infants survived; at 24 weeks--79/108 (73%) chose NICU care, 47/79 (59%) survived; at 25 weeks--147/153 (96%) chose NICU care, 115/147 (78%) survived; and at 26 weeks--all infants had NICU care, 176/203 (87%) survived. Over 18 years and 606 births, we identified only three significant concerns from families and/or physicians that required formal review. CONCLUSION: Most pregnant women and families choose NICU care for their extremely premature infant, but if given the option via shared decision making, a significant proportion will choose PCC at gestational ages that some NICUs mandate resuscitation. We support a reasoned dialogue and bioethical framework that recognizes human values to be irreducibly diverse, sometimes conflicting, and ultimately incommensurable--value pluralism. Respectful shared decision making requires thoughtful and compassionate flexibility, nuanced and individualized suggestions for PCC or NICU and the reduction of hierarchical directives from physicians to families. We continue to advocate and rely upon informed family preference between 23 and 25 weeks gestation in our updated 2015 periviability guidelines.

What happens when the patent ductus arteriosus is treated less aggressively in very low birth weight infants?

OBJECTIVE: It remains unclear whether indomethacin (INDO) and/or surgical ligation (LIGATE) are necessary to improve outcomes in premature infants with a patent ductus arteriosus (PDA). We have adopted a conservative approach to PDA management that emphasizes waiting for spontaneous closure unless certain cardiorespiratory distress criteria are met. STUDY DESIGN: This was a before-after observational study in infants born 501 to 1,500 g in two distinct epochs. Era 1 (January 2005 to December 2007) featured traditional management with INDO and LIGATE used early to close all moderate and large PDAs in infants receiving any respiratory support. Era 2 (January 2008 to June 2009) emphasized modest fluid restriction, watchful waiting and limited INDO and LIGATE to only those infants with large PDAs who met certain cardiorespiratory distress criteria. RESULT: Era 1 included 139 infants with a PDA, mean (s.d.) gestational age 27.5 (2) weeks; Era 2 72 infants, mean (s.d.) gestational age 27.5 (2) weeks. In Era 2, INDO use significantly decreased (79% of infants to 26%, P<0.001), and 28 day total fluids decreased (140 vs. 130 ml kg(-1) day(-1), P<0.001). LIGATE rate was 45% in Era 1, 33% in Era 2 (P=0.11). There were no significant differences in supplemental oxygen, nasal continuous positive airway pressure, or mechanical ventilation days. There were no significant differences in mortality or individual morbidities. The combined outcome of chronic lung disease (CLD) or mortality after Day 7 significantly increased (Era 1, 40%, Era 2, 54%, P=0.04). More infants were discharged home with a PDA in Era 2, but most resolved spontaneously and the need for closure therapy after discharge from the neonatal intensive care unit (NICU) did not increase. Multiple regression analysis demonstrated Era 2 management did not predict an increased risk of one or more interlinked morbidities. CONCLUSION: Tolerance of the PDA with watchful waiting for spontaneous closure, modest fluid reduction, and less INDO use is a reasonable treatment strategy that is not associated with significant changes in NICU mortality or individual morbidities. We did note an increase in the combined outcome of CLD or mortality after Day 7, thus our investigation supports the urgency of a randomized controlled trial comparing traditional PDA management with a true control group similar to our Era 2 management to answer important questions of short and long-term outcomes.

Hyperglycemia, insulin and slower growth velocity may increase the risk of retinopathy of prematurity.

OBJECTIVE: Strategies to reduce Retinopathy of Prematurity (ROP) have focused primarily on respiratory management. Hyperglycemia (HG) and insulin use, risk factors for adult diabetic retinopathy, as well as growth rates may be modifiable variables useful to reduce ROP. STUDY DESIGN: This was a retrospective chart review of all infants born at <30 weeks gestation from 2003 to 2007 who survived to discharge in our neonatal intensive care unit (NICU). All whole-blood glucose values (BG in mg dl(-1)) done in the first 29 days of life were collected for analysis. RESULT: BGs were done at least every 3 to 6 h for the first 48 to 96 h of life, then every 6 to 24 h thereafter, as long as infants remained on hyperalimentation. Hyperglycemia was defined as mild (BG 151 to 180), moderate (181 to 210) or severe (>210). Insulin use (given if BG>180 to 210) was also noted for each simultaneous BG. ROP was classified as none, mild (stage 1 to 2) or severe (stage 3 to 4). Growth velocity (g kg(-1) per day), length and head circumference were also analyzed. In all, 372 infants mean (s.d.) gestational age 27.6 (1.4) weeks, mean (s.d.) birth weight 994 (242)g had 18,649 BGs analyzed. 103 (28%) of the infants had mild ROP and 29 (8%) had severe ROP. 137 (37%) of the infants received at least 1 day of exogenous insulin (median days 9, range 1 to 26). Higher cumulative mean BG, more episodes of HG, and more insulin exposure were associated with an increased incidence and severity of ROP. Ordinal logistic regression identified lower gestational age, male gender, fetal growth restriction, slower NICU growth velocity, and higher BG as predictors for severity of ROP. However, insulin use was a stronger predictor than BG, and replaced it in the risk model. CONCLUSION: After adjusting for important risk factors, HG and especially insulin use in premature infants may increase the risk of ROP. In addition, slower NICU growth velocity, but not rates of head or length growth, was predictive of ROP.

PCO2 and room air saturation values in premature infants at risk for bronchopulmonary dysplasia.

OBJECTIVE: To determine the capillary partial pressure of carbon dioxide (PCO(2)) and room air transcutaneous hemoglobin saturation (RA SAT) at 36 weeks' postmenstrual age (PMA) in infants born with weight between 501 and 1250 g. STUDY DESIGN: Multicenter, prospective investigation with primary data collection within 72 h of 36 weeks PMA or discharge, whichever first. PCO(2) and RA SAT determinations were done at rest on infants not requiring mechanical ventilation or nasal continuous positive airway pressure (NCPAP). RESULT: A total of 220 infants were enrolled (mean gestational age 27.7 weeks, mean birthweight 951 g). In infants with traditionally defined chronic lung disease (CLD) compared to those without CLD, the mean PCO(2) was significantly higher (54 versus 45 mm Hg) and the median RA SAT significantly lower (<80 versus 97%). In infants with the new classification of bronchopulmonary dysplasia (BPD), there was a significant linear trend toward increasing PCO(2) with increasing severity of BPD (45, 47, 54 and 62 mm Hg in No, Mild, Moderate and Severe BPD). There was a significant linear trend toward decreasing RA SAT with increasing severity of BPD (97, 95 <80, <80% in No, Mild, Moderate and Severe BPD). CONCLUSION: Defining CLD as BPD based upon a RA SAT test is a more discriminate, objective method to categorize lung injury. PCO(2) is an objective measure of lung function that inversely correlates with RA SAT. These determinations done together at 36 weeks PMA may provide more precise and accurate estimates of lung injury that might allow for better understanding of pulmonary therapies and clearer comparison of BPD rates and severities among NICUs.

Developing a frenotomy policy at one medical center: a case study approach.

The objective of this study was to change procedures in our medical center regarding frenotomy for ankyloglossia (tongue-tie). The medical and breastfeeding outcomes of 36 fullterm infants who received frenotomies were studied. The information was used to develop frenotomy eligibility standards that would guide other physicians and insure timely treatment to avoid breastfeeding cessation.

Antenatal phenobarbital for the prevention of periventricular and intraventricular hemorrhage: a double-blind, randomized, placebo-controlled, multihospital trial.

To determine whether the neuroprotective properties of phenobarbital would alter the incidence and severity of intracranial hemorrhage in premature infants, we randomly assigned 110 women at less than 31 weeks of gestation to receive 10 mg/kg phenobarbital or placebo in a blinded fashion before delivery. Infants were examined postnatally with real-time ultrasonography for evidence of intracranial hemorrhage. Maternal demographics, pregnancy complications, antenatal management, and route of delivery did not differ between the phenobarbital group (n = 50) and the placebo group (n = 60). The total incidence of periventricular-intraventricular hemorrhage did not differ between the phenobarbital-treated (n = 54) and the placebo-treated (n = 67) infants. However, the frequency of grade 3 and grade 4 hemorrhages was 15% (10 infants) in the placebo group and 3.7% (2 infants) in the phenobarbital group (p less than 0.05). There were no differences in the severity of associated conditions in the babies to explain the difference in the incidence of severe hemorrhage between the study groups. We conclude that antenatal administration of phenobarbital appears to be effective in decreasing the severity of periventricular-intraventricular hemorrhage in infants delivered at less than 31 weeks of gestation.

Galactose clearance and carbohydrate metabolism across the gastrointestinal tract in the newborn lamb.

We prepared 16 newborn lambs with chronically indwelling catheters in the portal vein, mesenteric vein, femoral vein, and femoral artery to study galactose clearance, portal venous blood flow, and carbohydrate metabolism across the gastrointestinal (GI) tract. Galactose clearance was measured by infusing galactose into the femoral vein to achieve a steady-state galactose concentration in the femoral artery. We observed a curvilinear relationship between galactose clearance and the steady-state galactose concentration. The relationship could be modeled as an apparent Michaelis-Menten system: Clearance = Vmax/(Km + [Gal]ssa), where Vmax = 17.0 +/- 2.5 mg/min/kg body weight and Km = 11.0 +/- 0.4 mg/dL. Substrate/oxygen quotients across the viscera drained by the portal vein were measured in the fasted state and during systemic galactose infusion. A net uptake of glucose and galactose by the GI tract was found with quotients of 0.19 +/- 0.07 and 0.05 +/- 0.02, respectively. There was a relatively large net efflux of lactate across the portal circulation, with a quotient of -0.13 +/- 0.03. The indicator-dilution technique was used to estimate portal venous blood flow (PVBF) in the neonatal period with a resting, fasted state value of 92.8 +/- 4.4 mL/min/kg body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Galactose, glucose, and lactate concentrations in the portal venous and arterial circulations of newborn lambs after nursing.

We have used the newborn lamb prepared with chronic indwelling catheters to study carbohydrate metabolism in the unstressed, postprandial state. Lambs were fasted 5 h and then allowed to nurse ad libitum from their mothers for 20 min. Serial determinations of whole blood galactose, glucose, and lactate concentration were then made from the portal venous and arterial circulations. Portal venous galactose concentration increased significantly after milk ingestion, but arterial galactose concentration did not increase from baseline unless the portal venous galactose concentration exceeded 10-12 mg/dl suggesting a threshold effect for hepatic galactose clearance. Glucose concentration increased significantly in both circulations with portal venous galactose concentration greater than arterial galactose concentration in all cases. Galactose and glucose were absorbed from the intestine at approximately equal rates. Lactate was not absorbed into the portal venous circulation to any great extent after lactose ingestion.