Neonatal Total Parenteral Nutrition Research Articles

Gene Editing of Swine Myosin Vb Induces Microvillus Inclusion Disease and Loss of Apical Sodium Transporters with Maintenance of CFTR in Enterocytes

BackgroundThe human genetic disorder Microvillus Inclusion Disease (MVID) results from inactivating mutations in Myosin Vb (MYO5B). MVID is characterized by severe, unremitting diarrhea that typically presents shortly after birth. The necessity of implementing total parenteral nutrition (TPN) and the long‐term administration of TPN in neonates with MVID presents challenges to elucidating the complex pathogenesis of MVID in humans. Thus, a large animal model of MVID that closely recapitulates human physiology is needed. To better understand the pathophysiology of MVID we created a large animal model that closely mimics human MVID.MethodsPigs were cloned using somatic cell nuclear transfer of primary pig fibroblasts edited with TALEN to express a P663L mutation of the MYO5B gene. This swine P663L mutation, referred to as MYO5B(P663L), corresponds to the Navajo P660L mutation seen in MVID patients. Neonatal pigs were euthanized within 1 day of birth and tissue was collected for analysis and generation of intestinal enteroids.ResultsThe MYO5B(P663L) pigs developed diarrhea shortly after birth, similar to patients with MVID. Immunostaining for brush border components F‐actin, ezrin, CD10 and DPPIV showed the presence of subapical intracellular inclusions in enterocytes of MYO5B P663L pigs. Transmission electron microscopy confirmed the presence of inclusions lined with microvilli in the MYO5B(P663L) pigs. Immunostaining for NHE3 and SGLT1, drivers of intestinal sodium and water absorption, showed decreased apical expression and diffuse sub‐apical expression in the MYO5B(P663L) pigs compared to control pigs. In contrast to decreased expression of sodium transporters, CFTR was maintained on the apical membrane of MYO5B(P663L) pigs. Enteroids generated from the proximal small intestine of neonatal control and MYO5B(P663L) pigs grew at similar rates, but showed differences in the brush border. Enteroids derived from MYO5B(P663L) pigs had sub‐apical expression of intestinal alkaline phosphatase and DPPIV and decreased apical expression of NHE3 compared to control enteroids. Administration of forskolin resulted in increased swelling in MYO5B(P663L) enteroids (170.8% ± 15.9) compared to control enteroids (90.4% ± 4.6), indicative of functional Cl− secretion.ConclusionsCollectively, these data suggest that decreased apical expression of NHE3 and SGLT1, which are required for water absorption, are likely responsible for the MVID diarrhea disorder. Moreover, maintenance of functional CFTR on the apical membrane of enterocytes in the MYO5B(P663L) pig may further exacerbate the development of diarrhea by actively secreting Cl−, thus driving further water loss by facilitating fluid secretion. This novel large animal model of MVID could provide an important vehicle for testing novel therapeutic approaches for patients with MVID.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Neonatal Total Parenteral Nutrition: Initiative and implementation of standardized formulation in Saudi Arabia

The total parental nutrition considered as high alert medications for neonates population and others. Several medications safety institutions and international with national accreditation organization recommended setting prevention measure of medical error events. The new medications safety project initiative was neonates standardized parental nutrition formulation. The formulation contained all requirements of American Parenteral and Enteral Nutrition and European Parental and Enteral Nutrition standard. Also, to the United State Pharmacopeia 797 stranded. The formulation is suitable for neonates with formal renal and hepatic functions with common neonate’s requirements Parenteral Nutrition in Saudi Arabia. The new initiative’s project may implement through explored project management tools with close measurements of performance indicators outcome. The neonate’s standardized formulation of parental nutrition new programs at Ministry of Health hospitals in the Kingdom of Saudi Arabia with Gulf and Middle East counties.

Maximization of calcium and phosphate in neonatal total parenteral nutrition.

Appropriate calcium and phosphate supplementation is essential for bone growth in preterm infants. Using Rehabix-K2™ (AY Pharmaceuticals, Tokyo, Japan) and Pleamin-P Injection™ (Fuso Pharmaceutical Industries, Osaka, Japan) as the total parenteral nutrition (TPN) and amino acid solution, respectively, we investigated ways of maximizing calcium and phosphate in the TPN solution. Rehabix-K2, Pleamin-P, calcium gluconate, sodium phosphate, 50% glucose, and water were mixed in varying proportions to create 16 formulations. Precipitation assessment was done three times for each of the 16 formulations, and was based on the Japanese Pharmacopeia. Precipitation was observed 24h after mixing when the calcium and phosphate were 60mEq/L and 30mmol/L or 80mEq/L and 40 mmol/L, respectively. No precipitation was observed when the calcium and phosphate were 20mEq/L and 10mmol/L, respectively. Precipitation was observed once out of three times, when the calcium and phosphate were 40mEq/L and 20mmol/L, respectively, and the amino acids were 2% and 3% (mean pH, 6.13 and 6.26, respectively). No precipitation was observed, however, when the calcium and phosphate were 40mEq/L and 20mmol/L, respectively, and the amino acids were 0% and 1% (mean pH, 5.88 and 6.05, respectively). Not only the concentration of calcium and phosphate, but also the pH of the TPN solution, are crucial factors for precipitation. Based on these results, a well-balanced TPN solution maximizing calcium and phosphate availability will be able to be formulated.

Position Statement on Heparin Safety Concerns.

Position Statement on Heparin Safety Concerns.

Total parenteral nutrition induces sustained hypomethylation of DNA in newborn guinea pigs

Neonatal total parenteral nutrition (TPN) is associated with animals with low glucose tolerance, body weight, and physical activity at adulthood. The early life origin of adult metabolic perturbations suggests a reprogramming of metabolism following epigenetic modifications induced by a change in the pattern of DNA expression. We hypothesized that peroxides contaminating TPN inhibit the activity of DNA methyltransferase (DNMT), leading to a modified DNA methylation state. Three groups of 3-d-old guinea pigs with catheters in their jugular veins were compared: (i) control: enterally fed with regular chow; (ii) TPN: fed exclusively with TPN (dextrose, amino acids, lipids, multivitamins, contaminated with 350 ± 29 μmol/l peroxides); (iii) H2O2: control + 350 μmol/l H2O2 intravenously. After 4 d, infusions were stopped and animals enterally fed. Half the animals were killed immediately after treatments and half were killed 8 wk later (n = 4-6 per group) for hepatic determination of DNMT activities and of 5'-methyl-2'-deoxycytidine (5MedCyd) levels, a marker of DNA methylation. At 1 wk, DNMT and 5MedCyd were lower in the TPN and H2O2 groups as compared with controls. At 9 wk, DNMT remained lower in the TPN group, whereas 5MedCyd was lower in the TPN and H2O2 groups. Administration of TPN or H2O2 early in life in guinea pigs induces a sustained hypomethylation of DNA following inhibition of DNMT activity.

The mode of administration of total parenteral nutrition and nature of lipid content influence the generation of peroxides and aldehydes

The absence of light protection of neonatal total parenteral nutrition (PN) contributes to the generation of 4-hydroxynonenal and peroxides. 4-Hydroxynonenal is suspected to be involved in PN-related liver complications. To find a practical modality to reduce 4-hydroxynonenal in PN and assess in vivo the impact of PN containing low 4-hydroxynonenal concentration. Six modalities of delivering PN were compared for the in vitro generation of peroxides and 4-hydroxynonenal: 1) MV-AA-L: light-protected (-L) solution containing multivitamin (MV) mixed with amino acids + dextrose (AA); 2) MV-AA+L: MV-AA without photo-protection (+L); 3) MV-LIP+L: MV mixed with lipid emulsion (LIP). LIP was a) Intralipid20%(®) or b) Omegaven(®). Hepatic markers of oxidative stress (glutathione, F(2α)-isoprostanes, GS-HNE) and inflammation (mRNA of TNF-α and IL-1) were measured in newborn guinea pigs infused during 4-days with MV-AA+L compounded with Intralipid20%(®) or Omegaven(®). Hydroperoxides and 4-hydroxynonenal were the lowest in MV-AA-L and the highest in MV-LIP+L. MV-AA+L with Omegaven(®) was associated with the lowest levels of markers of oxidative stress and inflammation. Compared to Intralipid20%(®), Omegaven(®) reduces oxidative stress associated with PN and prevents liver inflammation. These findings offer an alternative strategy to light protection of PN, which in the clinical setting is a cumbersome modality.

18 TOTAL PARENTERAL NUTRITION DURING NEONATAL CARE OF THE FIRST BITRANSGENIC FEMALE BOVINE CLONE

This work describes the treatment with total parenteral nutrition (TPN) of a 37-day cloned calf after suffering ruminal acidosis by ingestion of milk. Cells for SCNT were obtained by using a bicistronic vector for human lysozyme and lactoferrin. We obtained 7 embryos and 2 pregnancies. Only one fetus was born alive weighing 47 kg and it was presented to the neonatal unit of INTA showing a deep depression, diarrhoea, dehydration (10%), hyperthermia and inability to stand (Table 1). A 20-cm-length 20-Ga-diameter catheter (Arrow) was placed in the jugular vein. Blood samples from catheter and brachial artery showed leukocytosis, hypoglycemia and metabolic acidosis (Table 1). Esophageal tube was placed to remove 5 L of ruminal content and for the administration of 2 L of a solution of sodium bicarbonate (40 g L–1 of water). Saline (NaCl, 9 g L–1), sodium bicarbonate (8.4 g/100 mL) and 10% dextrose were administered IV until dehydration; blood pH and glucose were corrected. Ceftriaxone 1 g IM/12 h (Acantex, Roche) to prevent bacterial translocation, 1.175 mg of flunixin meglumine (PharmaVet) as anti-endotoxic dose and 80 mg of ranitidine IV/12h (Vetanco) to prevent laminitis were also administered. Two litres of bovine plasma were administered during the first 2 days and, after this, we began with a TPN regimen due to lack of sucking reflex and animal anorexia. Kabiven (Fresenius Kabi AV) was administered at 1 g of lipids/kg/24 h by a regimen of 18 drops min–1 to prevent hyperlipidemia at the recommended dose for humans. For this reason, we also administered dextrose 25% 12.5 drops min–1 and amino acids 11.5% 504 mL (Rivero), to reach a dose of 10 g/kg/24 h and 2 g/kg/24 h, respectively. Saline (NaCl, 9 g L–1) and vitamin complex (Rivial Paediatrics, Rivero) was also administered to cover water and vitamin requirements. The TPN therapy lasted 24 days during which the animal regularized its metabolic functions, reversed signs of ruminal acidosis and learned to eat a balanced ration and hay. To our knowledge, no information is available on such a long period of TPN in bovine neonates. This work shows that TPN can increase the survival chances of high risk animals and thus the final efficiency of cloning and transgenesis. Table 1.Clinical and haematological responses to 24-day total parenteral nutrition in a 37-day cloned female calf The authors thank Fresenius Kavi and Rivero Laboratories for their support.

Audit of pharmacy TPN services on the neonatal intensive care unit (NICU)

<h3>Objective</h3> At The Whittington Hospital, pharmacy is responsible for providing a total parenteral nutrition (TPN) service to neonatal intensive care unit (NICU). The aims are to deliver a safe and beneficial service to patients, which is also cost-effective to the Trust. Neonatal TPN bags are manufactured off-site, and there are two main types of bag procured: Standard Stock Bags and Tailor-Made Bags. This audit was designed to investigate the management and delivery of TPN to NICU in the Trust over a 12-week period, focusing on the type of bag prescribed, usage and the expenditure. This in turn helped to determine new local standards of management with the aim of optimising the TPN service, with reduced costs and wastage. <h3>Methods</h3> Data was collected over 12-weeks (19 October 2009 to 8 January 2010) and expenditure calculated with pricing adapted from JAC and the Service Level Agreement held with external suppliers. <h3>Results</h3> Table 1 summarises the types and cost of bag used over the audit period and the number of which incurred wastage. Where there were differences in the TPN prescription compared to the standard formula, tailor-made bags were ordered. Table 2 summarises the main changes made. <h3>Conclusion</h3> Findings from the audit showed a high usage of tailor-made TPN compared to stock TPN, most of which were bespoke bags (bags with additions made to the standard stock formula). Since conducting the audit practice has been reviewed: a new stock order level has been put in place, in addition a new TPN prescription has been developed, which helps distinguish between the different bags available. Although TPN requirements are based on the individual patient, the audit suggests that the stock bag may need to be reviewed for a more favourable alternative (and in-line with the latest ESPGHAN recommendations). A re-audit is intended, where it is hoped that optimised management of the pharmacy TPN service to NICU will be demonstrated.

PP-162. Neonatal total parenteral nutrition ascites following umbilical venous catheterization in a preterm newborn

PP-162. Neonatal total parenteral nutrition ascites following umbilical venous catheterization in a preterm newborn

Physical compatibility of neonatal total parenteral nutrition admixtures containing organic calcium and inorganic phosphate salts in a simulated infusion at 37°C*

Within an incubator environment at 37 degrees C, we evaluated the physical compatibility of calcium (Ca) and phosphate (P) in simulated neonatal total parenteral nutrition (TPN) infusions. Representative neonatal TPN formulas containing four concentrations of amino acids [AA] (1-4 g/dL) and two levels of dextrose [D] (5 and 10 g/dL) were monitored for calcium-phosphate precipitate formation over 24 hours using a laser-based particle counting technique. Research Laboratory. None. Of the eight AA-D combinations studied, two formulas containing 1 g/dL AA with either 5 g/dL or 10 g/dL of D and high amounts of Ca and P resulted in significant increases in particle counts and visibly evident precipitation during the 24-hour infusion. Precipitation was noted only after the infusion passed through the incubator, but not in the TPN bags, demonstrating the heightened risk of calcium-phosphate incompatibility with increased temperatures. Low AA concentrations and high temperatures are significant risk factors for the precipitation of the insoluble dibasic calcium phosphate that may be fatal upon intravenous infusion. When thermoregulation is required, the AA concentration of the TPN formula should not be less than 1.5 g/dL (and ideally > or =3 g/dL) when high intakes of calcium (60 mg/dL) and phosphate (46.5 mg/dL) are prescribed.

Percutaneously Inserted Central Catheter for Total Parenteral Nutrition in Neonates: Complications Rates Related to Upper Versus Lower Extremity Insertion

The objective of this study was to compare the complication rates of upper versus lower extremity percutaneously inserted central catheters used for total parenteral nutrition in neonates. During a 48-month study period, 396 neonates were identified as having had percutaneously inserted central venous catheters. A total of 370 catheters were inserted from the upper and 107 from the lower extremity. Data retrieved and analyzed were birth weight, gestational age, age at placement, duration in place, duration of total parenteral nutrition, type of infusates, catheter-related bloodstream infection, phlebitis, leakage, occlusion, necrotizing enterocolitis, intraventricular hemorrhage, serum creatinine, liver function tests, and length of hospitalization. The median birth weight and gestational age were 940 g and 28 weeks. The rate of catheter-related bloodstream infection was 11.6% for the upper and 9.3% in the lower extremity catheters. The most common organism was coagulase-negative Staphylococcus for both upper and lower extremity catheters and significantly higher with catheters from the upper extremity. Lower extremity catheters were in place longer, and the time from insertion to complication was also longer. The rate of cholestasis was higher for the upper extremity catheters. Multiple regression analysis showed that the most significant contributor to cholestasis was duration of time the catheters were in place and the duration of total parenteral nutrition administration. Receiver operating characteristics curve demonstrated higher sensitivity for duration of catheters in predicting cholestasis with duration of total parenteral nutrition being more specific. Lower extremity percutaneously inserted central venous catheters had lower rates of catheter-related bloodstream infection, longer time to first complication, and lower cholestasis despite longer duration of total parenteral nutrition. When possible, lower extremity inserted catheters should be used for the administration of total parenteral nutrition.

Threonine Requirement in Neonates Receiving Total Parenteral Nutrition (TPN)

Current neonatal threonine (THR) enteral requirement is 87 mg·kg‐1·d‐1. The THR requirement of the parenterally (TPN) fed human neonate has never been experimentally determined. Concentrations of THR in commercially available TPN solutions are derived from concentrations in cord blood, plasma amino acid profile during TPN feeding, or human milk, and are 30 to 80% higher than the enteral requirement. We showed in piglets that the neonatal TPN requirement for THR was 55% lower than the enteral requirement.Our objective was to determine the human neonatal TPN requirement for THR in post‐surgical neonates using the indicator amino acid oxidation technique with L[1–13C]phenylalanine. Neonates were randomized to receive one of twelve THR intakes ranging from 10 to 100 mg· kg‐1·d‐1. Preliminary data indicate a mean THR requirement between 30 and 40 mg·kg‐1·d‐1, only 30% of the THR concentration in the lowest THR containing TPN solution. We conclude that the THR requirement for TPN fed human neonates is significantly lower than the THR present in current TPN solutions and the recommended intake for orally fed infants. High THR intakes are a concern; THR is potentially neurotoxic and neonates are unable to oxidize excess

Aminophylline Compatibility with Neonatal Total Parenteral Nutrition

Aminophylline has proven useful for treating renal failure in preterm infants. Previous reports state that aminophylline is incompatible with some neonatal total parenteral nutrition (TPN) solutions. If this is correct, administration of aminophylline doses would be complicated by the need to hold TPN and provide flush solution after each aminophylline dose. Our experience with administering aminophylline over 30 minutes concurrently with TPN was that this was not problematic. We therefore examined the in vitro compatibility of aminophylline and TPN solutions used in our neonates over a 30-minute interval to see if our policy of allowing concurrent mixing of these products was appropriate. TPN solutions (2.5 mL) were mixed with 1 mL of intravenous aminophylline 2.5 mg/mL in a glass vial. Three different TPN solutions used in our NICU were collected for the study, and five samples of each combination were prepared. Samples were watched for 60 minutes to see if precipitation occurred. Although the aminophylline and TPN solutions were not miscible, no turbidity or precipitation was observed. This study supports that aminophylline is physically compatible with neonatal TPN for 60 minutes.

Evaluation of the total parenteral nutrition service at Universiti Sains Malaysia Hospital

Summary Background & aims: Total parenteral nutrition (TPN) has been practised in Universiti Sains Malaysia Hospital (HUSM), Malaysia, since 1986. Unfortunately, there are no published data on the cost, complications and outcomes of patients treated with TPN in HUSM. This study was carried out to evaluate the cost, complications and outcomes of TPN. Methods: Retrospective data were obtained from patient medical records, and 215 TPN cases from 2003 to 2005 were evaluated. The data were analyzed using SPSS version 11. Results: The demographics of the TPN cases were neonates 22.8%, pediatric 11%, adults 64.6%, males 52.6%, females 46.1%. Malays comprise 87.4%, Chinese 6.0% and Indians 1.9%. The average cost for TPN in neonates is RM 98746, pediatric RM 2107121 and adult RM 3987103. TPN-associated complications were electrolyte complications (56.5%), acid– base imbalance (5.5%), renal complications (14.5%), liver complications (12.4%), hyperglycemia (9%), hyperlipidemia (0.7%) and hypoglycemia (0.7%). The outcomes were that 71.2% cases tolerated oral nutrition and 1.8% expired. The study showed a significant difference in the cost of TPN in each group of patients (P ¼ 0.000). Conclusion: The cost and outcomes of TPN services in HUSM were similar to other centers, however, it was associated with relatively high TPN-related complications. & 2007 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

Of Lobsters, Electronic Medical Records, and Neonatal Total Parenteral Nutrition

At the Mayo Health System in LaCrosse, Wisconsin, there are >1000 infant total parenteral nutrition (TPN) orders placed per year. It is the most complicated order that the pharmacy fills, so a recent peer-review article in Pediatrics moved a group of us to action at our center to buy or develop a TPN calculator. We did this because no stand-alone commercial calculators were available to us, and expensive electronic medical records typically do not include TPN calculators for neonatal patients. The new software includes decision support, and the orders are consistently legible. The physician performs fewer calculations, and there are no mathematical errors. This article examines the broader significance of providers having to write their own TPN software.

Computer Assisted Total Parenteral Nutrition for Pre-term and Sick Term Neonates

Over the past few years, the use of total parenteral nutrition (TPN) has been established for pre-term and sick term neonates. At 'IASO' Hospital, a series of protocols implemented through the use of a computer programme has been developed to assist in the time consuming task of prescribing and preparing TPN in neonates. The algorithms used for neonates of a different gestational age are based on the protocols created through screening of literature and personal experience. This is important because it heralds a uniformity of the prescription of TPN at IASO and other hospitals where these protocols have been implemented. The objective is to determine the extent of error occurrence of the manual method as opposed to the new computerized procedure of TPN formulation, and to assess the immediate benefits stemming from the computer programme's use, in terms of personnel time reduction. Furthermore, the usefulness of the automated compounder in the computer driven process of TPN solution formulation was also assessed. Gynaecology Hospital 'IASO'. For a period of 6 months, sick and prematurely born babies were included in the study. Calculations regarding the composition of TPN solutions were conducted both by computer and manually. The time needed to complete the procedure and the results' accuracy were measured and compared. Implementation of the protocols into practice via this computer programme has been found to reduce the time spent by the physician and the pharmacist on TPN solution preparation, but the most important contribution is the virtual elimination (no errors in computerized calculation) of errors in the complex task of prescribing and formulating TPN solutions. For example, the average time taken to prepare the individual TPN solutions was 5.2 min while the computerized procedure took 15.4 min. Use of this system can optimize pharmacists' and physicians' work and help prevent prescription and preparation errors.

Complications of umbilical vein catheterization: Neonatal total parenteral nutrition ascites after surgical repair of congenital diaphragmatic hernia

A 2-day-old girl was admitted to surgery for repair of a left-sided diaphragmatic hernia (CDH). Preoperatively, an umbilical vein catheter (UVC) was inserted with the tip in the left hypochondrium. The UVC tip position was unchanged radiographically peroperatively. At the fifth postopertive day abdominal distension and signs of gastric outlet obstruction appeared. Explorative laparotomy found liver necrosis at the site of the catheter tip and parenteral nutrition ascites. J Pediatr Surg 37:E21. Copyright 2002, Elsevier Science (USA). All rights reserved.

Contribution of multivitamins, air, and light in the generation of peroxides in adult and neonatal parenteral nutrition solutions.

To compare the concentrations of peroxides between adult and neonatal total parenteral nutrition (TPN) solutions in response to protection against inducers of peroxidation such as multivitamins and exposure to light or air. Peroxide concentrations were measured in freshly prepared adult and neonatal solutions of fat-free TPN in four settings: with or without an air inlet, and protected or unprotected from ambient light. An oxygen washout was performed by exposing a fat-free neonatal TPN solution to a continuous flow of nitrogen. Globally, light was the main inducer of peroxides in adult and neonatal solutions. However, in adult solutions the concentration of peroxides remained <15 micromol/L, while in neonatal solutions the peroxide concentration was as high as 300 micromol/L in ambient light. Although the oxygen washout did prevent the generation of peroxides, avoiding air inlet was not as effective as was photoprotection in decreasing the important peroxide load in the neonatal TPN solution. The higher concentration of peroxides found in neonatal solutions compared with adult solutions is explained by the differences in nutrient composition between the two solutions. Contamination of parenteral solutions by air during compounding accounts for the photoinduced generation of peroxides in TPN solutions. It is more convenient to protect TPN solutions from light exposure after the admixture of the multivitamin solution than to avoid contact with oxygen.

Oxalogenesis in parenteral nutrition solution components.

Oxalate has been implicated in the etiology of nephrocalcinosis in premature infants as well as in the formation of insoluble precipitates in total parenteral nutrition (TPN) intravenous tubing. Oxidation of ascorbate to oxalate, especially in the presence of catalysts such as copper and iron, has been implicated in formation of these precipitates. The purpose of this project was to measure oxalate formation in certain TPN components separately and in combination. Neonatal TPN solution components in combination were infused at 5 mL/h under simulated clinical conditions used in a neonatal intensive care unit. Aliquots were assayed at intervals for oxalate by capillary electrophoresis. Oxalate is present in one TPN mixture at concentrations up to 8 ppm. The addition of ascorbate to an aqueous solution of trace metals may promote oxalogenesis.

Sporadic Congenital Infantile Cortical Hyperostosis (Caffey's Disease)

Prognosis of congenital infantile cortical hyperostosis (Caffey's disease) is poor particularly in premature babies. Two cases are presented of congenital Caffey's disease in premature babies. The first baby was hydropic at birth and had cortical hyperostosis involving the mandible and long bones of right upper limb and both lower limbs. The second baby had cortical hyperostosis of the nasal bones causing severe nasal nonchoanal stenosis that needed surgery, in addition to involvement of long bones of the four extremities. Both babies recovered from the disease and were discharged home well. These cases suggest that the improved outcome of congenital of infantile cortical hyperostosis may reflect improvement of neonatal mechanical ventilation and availability of neonatal total parenteral nutrition.