Core outcome set for perinatal interventions for congenital diaphragmatic hernia.

OBJECTIVE: To develop a core set of prenatal and neonatal outcomes for clinical studies evaluating perinatal interventions for congenital diaphragmatic hernia, using a validated consensus-building method. METHODS: An international steering group comprising 13 leading maternal-fetal medicine specialists, neonatologists, pediatric surgeons, patient representatives, researchers and methodologists guided the development of this core outcome set. Potential outcomes were collected through a systematic review of the literature and entered into a two-round online Delphi survey. A call was made for stakeholders with experience of congenital diaphragmatic hernia to review the list and score outcomes based on their perceived relevance. Outcomes that fulfilled the consensus criteria defined a priori were discussed subsequently in online breakout meetings. Results were reviewed in a consensus meeting, during which the core outcome set was defined. Finally, the definitions, measurement methods and aspirational outcomes were defined in online and in-person definition meetings by a selection of 45 stakeholders. RESULTS: Overall, 221 stakeholders participated in the Delphi survey and 198 completed both rounds. Fifty outcomes met the consensus criteria and were discussed and rescored by 78 stakeholders in the breakout meetings. During the consensus meeting, 93 stakeholders agreed eventually on eight outcomes, which constituted the core outcome set. Maternal and obstetric outcomes included maternal morbidity related to the intervention and gestational age at delivery. Fetal outcomes included intrauterine demise, interval between intervention and delivery and change in lung size in utero around the time of the intervention. Neonatal outcomes included neonatal mortality, pulmonary hypertension and use of extracorporeal membrane oxygenation. Definitions and measurement methods were formulated by 45 stakeholders, who also added three aspirational outcomes: duration of invasive ventilation, duration of oxygen supplementation and use of pulmonary vasodilators at discharge. CONCLUSIONS: We developed with relevant stakeholders a core outcome set for studies evaluating perinatal interventions in congenital diaphragmatic hernia. Its implementation should facilitate the comparison and combination of trial results, enabling future research to better guide clinical practice. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Association of timing of congenital diaphragmatic hernia repair with survival and morbidity for patients not requiring extra-corporeal life support.

BACKGROUND: While physiologic stabilization followed by repair has become the accepted paradigm for management of congenital diaphragmatic hernia (CDH), few studies have examined the effect of incremental changes in operative timing on patient outcomes. We hypothesized that later repair would be associated with higher morbidity and mortality. METHODS: Data were queried from the CDH Study Group (CDHSG) from 2007-2020. Patients with chromosomal or cardiac abnormalities and those who were never repaired or required pre-repair extra-corporeal life support (ECLS) were excluded. Time to repair was analyzed both as a continuous variable and by splitting the cohort into top/bottom percentiles. The primary outcome of interest was in-hospital mortality. Secondary outcomes included need for and duration of post-repair ventilatory and nutritional support. RESULTS: A total of 4,104 CDH infants were included. Median time to repair was 4 days (IQR 2-6). On multivariable analysis, high-risk (CDHSG stage C/D) defects and lower birthweight predicted later repair. Overall, in-hospital mortality was 6%. On univariate analysis, there was no difference in the number of days to repair between survivors and non-survivors. On risk-adjusted analysis, single-day changes in day of repair were not associated with increased mortality. Later repair was associated with longer time to reach full oral feeds, increased post-repair ventilator days, and increased need for tube feeds and supplementary oxygen at discharge. CONCLUSIONS: For infants with isolated CDH not requiring pre-operative ECLS, there is no difference in mortality based on timing of repair, but single-day delays in repair are associated with increased post-repair duration of ventilatory and nutritional support.

Prenatally diagnosed congenital diaphragmatic hernia: optimal mode of delivery?

OBJECTIVE: To evaluate if the delivery mode of infants with prenatally diagnosed congenital diaphragmatic hernia (CDH) affects the outcome. STUDY DESIGN: Data from the CDH Study Group database of infants with prenatal diagnosis between 2001-2015 were divided into four delivery mode groups: vaginal spontaneous, vaginal induced, elective caesarean section, and emergent caesarean section. Outcomes were analyzed in relation to the time of day of delivery and the gestational age at birth. RESULTS: A total of 3906 cases of prenatally diagnosed CDH were assessed, with an overall survival of 64%. There were no differences in patient characteristics, requirement for extracorporeal membrane oxygenation, length of hospital stay or intubation, requirement for O2 at 30 days or overall survival. The time of day at birth did not affect the outcome. There was no difference in outcome between the different delivery modes at similar gestational age (GA) at birth, with worse outcomes at lower GA. CONCLUSIONS: Neither the mode nor time of delivery seems to affect the overall outcome for patients with prenatally diagnosed CDH. Outcome is strongly associated with the GA at birth.

Tissue Engineering to Repair Diaphragmatic Defect in a Rat Model.

Tissue engineering is an emerging strategy for repairing damaged tissues or organs. The current study explored using decellularized rat diaphragm scaffolds combined with human amniotic fluid-derived multipotent stromal cells (hAFMSC) to provide a scaffold, stem cell construct that would allow structural barrier function during tissue ingrowth/regeneration. We created an innovative cell infusion system that allowed hAFMSC to embed into scaffolds and then implanted the composite tissues into rats with surgically created left-sided diaphragmatic defects. Control rats received decellularized diaphragm scaffolds alone. We found that the composite tissues that combined hAFMSCs demonstrated improved physiological function as well as the muscular-tendon structure, compared with the native contralateral hemidiaphragm of the same rat. Our results indicate that the decellularized diaphragm scaffolds are a potential support material for diaphragmatic hernia repair and the composite grafts with hAFMSC are able to accelerate the functional recovery of diaphragmatic hernia.

Hyperglycemia and morbidity and mortality in extremely low birth weight infants.

OBJECTIVE: The purpose of this study was to determine the association between hyperglycemia and mortality and late-onset infections (>72 h) in extremely low birth weight (ELBW) infants. STUDY DESIGN: Retrospective analysis of a prospective cohort study of 201 ELBW infants who survived greater than 3 days after birth. Mean morning glucose levels were categorized as normoglycemia (<120 mg/dl), mild-moderate hyperglycemia (120 to 179 mg/dl) and severe hyperglycemia (> or =180 mg/dl). Hyperglycemia was further divided into early (first 3 days of age) and persistent (first week of age). Logistic regression was performed to assess whether hyperglycemia was associated with either mortality or late-onset culture-proven infection, measured after 3 and 7 days of age. RESULTS: Adjusting for age, the odds ratio (OR) for either dying or developing a late infection was 5.07 (95% confidence interval (CI): 1.06 to 24.3) for infants with early severe hyperglycemia and 6.26 (95% CI: 0.73 to 54.0) for infants with persistent severe hyperglycemia. Adjusting for age, both severe early and persistent hyperglycemia were associated with increased mortality. Among survivors, there was no significant association between hyperglycemia and length of mechanical ventilation or length of hospital stay. Persistent severe hyperglycemia was associated with the development of Stage II/III necrotizing enterocolitis, after adjusting for age and male gender (OR: 9.49, 95% CI: 1.52 to 59.3). CONCLUSION: Severe hyperglycemia in the first few days after birth is associated with increased odds of death and sepsis in ELBW infants.

Open lung biopsy in the critically ill newborn.

Experience with 17 open lung biopsies in critically ill premature neonates was reviewed. Despite their small size, prematurity, and near maximal ventilator requirements, the infants suffered no significant complications. In three cases, an infectious agent was identified. In one case end-stage lung fibrosis associated with persistent (greater than 3 months), severe respiratory failure prompted termination of support. In the remainder of the cases, definitively ruling out infection allowed the confident trial of a course of steroids in an attempt to treat bronchopulmonary dysplasia. Unlike older patients, the definitive diagnosis of no infection in the premature neonate is just as informative as the diagnosis of an infection. Used judiciously, open lung biopsy can be performed in the premature infant with acceptable morbidity and mortality.

Perioperative factors affecting the outcome following repair of biliary atresia.

The records of all patients with biliary atresia seen at the Childrens Hospital of Los Angeles during a 14-year period were reviewed. Of the 41 patients who could be evaluated, 32 were treated with trimethoprim and sulfamethoxazole prophylaxis, five were given other agents, and four received no prophylaxis after surgery. At least one episode of cholangitis occurred in nine patients. With one exception, all patients destined to have cholangitis did so within 9 months of surgery. Of the nine patients, five were receiving prophylaxis at the time the disease developed, but two were no longer receiving any prophylaxis. The other two patients in whom cholangitis developed never received antibiotic prophylaxis. In the 24 patients who had a Kasai type of portoenterostomy, cholangitis developed in three of the five (60%) with a Roux-en-Y limb length less than 40 cm and in two of the 19 (10.5%) with limb lengths greater than 40 cm (P less than .02). When performed earlier than 61 days after birth, surgery resulted in adequate bile flow in 64.7% (11/17) of patients who could be evaluated as compared with 31.8% (7/22) for surgery at 61 days or later (P less than .05). Of the patients with adequate biliary drainage 11 had no apparent liver disease, but only two of the patients with poor drainage were free of clinical liver disease. The conclusion from this series is that a combination of timely surgery, intestinal conduit at least 40 cm in length, and subsequent long-term antibiotic prophylaxis favors the best bile flow and reduces the occurrence of cholangitis, resulting in the best outcome.

Evaluation of a new thin-walled endotracheal tube for use in children.

Conventional endotracheal tubes have high intrinsic resistive properties due to their high outer-to-inner diameter ratio. This has significant disadvantages in the treatment of the small neonatal or pediatric patient as work of breathing increases with decreasing internal radius. Diagnostic and therapeutic procedures, including suctioning, may be very difficult in patients with small endotracheal tubes. We therefore measured airway resistance and pressure differential during simulated mechanical ventilation using proximal and distal endotracheal tube flow transducers. Conventional and new, ultrathin-walled endotracheal tubes reinforced with flat stainless steel or a novel, crush-proof nickel-titanium alloy were compared using fixed ventilator settings. Ventilation through the ultrathin-walled tubes resulted in a significantly reduced airway resistance (p < or = 0.01). These new ultrathin-walled endotracheal tubes showed flow characteristics typical of much larger conventional endotracheal tubes: the 3.2-mm internal diameter had an airway resistance (Raw) of 36, while a standard 2.5-mm internal diameter endotracheal tube had a Raw of 146. Both endotracheal tubes have identical external diameters of 3.6 mm. We conclude that ultrathin-walled endotracheal tubes could have a significant role in the treatment of the ventilated child by facilitating interactive ventilation and maintenance of airway patency and may make procedures such as fiberoptic endoscopy and intrapulmonary ventilation using reverse-thrust catheters possible in the small child.

Ureaplasma urealyticum demonstrated by open lung biopsy in newborns with chronic lung disease.

Lung biopsy tissue from eight infants with chronic lung disease was evaluated for the presence of Ureaplasma urealyticum. Specimens from four infants grew the organism. Pleural fluid cultures matched lung tissue but tracheal cultures were negative in two babies with positive lung tissue. There were no distinguishing pathologic findings in the four culture-positive infants which could be used to identify them vs. the culture-negative infants. Three culture-positive infants improved clinically after therapy directed at Ureaplasma even though two remained culture-positive. Ureaplasma grows in lung tissue of infants with chronic lung disease, it does not demonstrate any specific standard pathologic findings and tissue cultures do not match endotracheal cultures.

Iliac artery pseudoaneurysm following umbilical artery catheterization.

We report a case of a large iliac artery pseudoaneurysm in a newborn infant following umbilical artery catheterization. The aneurysm was excised and a primary repair was performed with limb salvage and reestablishment of normal blood flow to the foot. While these aneurysms are rare, prompt surgical repair should be performed as soon as the diagnosis is made because the associated mortality is high.

A second course of extracorporeal membrane oxygenation in the neonate--is there a benefit?

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is an effective therapy for infants with severe respiratory failure and pulmonary hypertension. In most patients once the disease reverses, it does not recur. However, in some patients pulmonary hypertension recurs and these infants meet criteria for a second course of ECMO. We evaluated the survival rate and feasibility of a second course of ECMO in neonates. METHODS: A questionnaire was sent to all active ECMO programs that requested data about patients who received two courses of ECMO. A retrospective review of the results from responding centers was performed to evaluate indications and outcome. RESULTS: The overall survival rate for the 58 neonates was 40%. Thirty-four patients with congenital diaphragmatic hernia had a survival rate of 47%, and 12 infants with primary persistent pulmonary hypertension had an 8% survival rate (p < 0.05). Most patients were treated with venoarterial ECMO for both courses. CONCLUSIONS: There is a reasonable survival rate for selected neonates who are treated with a second course of ECMO. Infants with primary persistent pulmonary hypertension should be carefully examined before institution of a second course of ECMO.

Anastomotic obstruction after stapled enteroanastomosis.

We have recently treated two cases of anastomotic obstruction after side-to-side stapled enteroanastomosis. Complete obstruction of a stapled small-bowel anastomosis has not been reported to our knowledge. The mechanism of the obstruction appears to be the healing together of the cut edges of viable bowel beyond the inverted stapled lines. An alternative method of constructing the functional end-to-end enteroanastomosis that is offered is intended to prevent the occurrence of postoperative anastomotic obstruction.

Congenital diaphragmatic hernia survival and use of extracorporeal life support at selected level III nurseries with multimodality support.

BACKGROUND: Congenital diaphragmatic hernia (CDH) has been cited to have a mortality rate of 50%. There have been multiple studies at individual institutions demonstrating potential benefits from various strategies including extracorporeal life support (ECLS), delayed repair, and lower levels of ventilator support. There has been no multicenter survey of institutions offering these modalities to describe the current use of ECLS and survival of these infants. In addition, the relationship between the number of patients with CDH managed at an individual institution and outcome has not been evaluated. METHODS: We queried 16 level III neonatal intensive care centers on the use of ECLS and survival of infants with CDH who were treated during 2 consecutive years (1993 to 1995). Data are presented as mean +/- SEM, median, and range. RESULTS: Data were collected on 411 patients. Of these, 71% +/- 8% were outborn and 8% +/- 3% were considered nonviable. Overall survival of CDH infants was 69% +/- 4% (range, 39% to 95%). The survival rate of infants on ECLS was 55% +/- 4%, whereas survival of infants not requiring ECLS was significantly increased at 81% +/- 5% (p = 0.005). The mean rate of ECLS use was 46% +/- 2%. There was no correlation between the number of cases per year at an individual institution and overall survival, ECLS survival, or ECLS use (r = 0.341, 0.305, and 0.287, respectively). There was also no correlation between case volume at an individual institution and ECLS survival (r = 0.271). CONCLUSIONS: The current survival rate and rate of ECLS use in infants with CDH at level III neonatal intensive care units in the United States are 69% +/- 4% and 46% +/- 2%, respectively. There is no correlation between the yearly individual center experience with managing CDH and rate of ECLS use or outcome.

The Hubbard tank as an adjunct to drainage in overwhelming intra-abdominal sepsis.

Open drainage of the peritoneal cavity for severe intra-abdominal sepsis has been gaining popularity. We had a patient whose overwhelming intra-abdominal infection did not respond to open drainage but was controlled by frequent immersion in a Hubbard tank. Use of the Hubbard tank should be considered in patients with uncontrolled intra-abdominal infection refractory to standard therapy.

Comparison of different techniques of stapled bowel anastomoses in a canine model.

OBJECTIVE: To evaluate different methods of creating a stapled enteroanastomosis and to determine which method would create a larger anastomosis. DESIGN: Prospective comparison of three groups with a total of 17 mongrel dogs. SETTING: Clinical investigation facility. MAIN OUTCOME MEASURES: Stapled side-to-side enteroanastomoses were created with the stapled edges touching or separated. Anastomoses were created in both functional bowel and in a defunctionalized limb. The anastomotic circumference was measured in a blinded fashion after 28 days. The third group had anastomoses created and measured the same day. Groups were compared using the t test. RESULTS: There was significant narrowing after healing with both types of anastomoses. Anastomoses created by separating the stapled lines were larger than those fashioned with the cut edges touching, both immediately and after healing. CONCLUSIONS: While clinically significant narrowing of a stapled anastomosis is uncommon, separating the staple lines of a functional end-to-end anastomosis may be the preferable method.

Mesenchymal hamartoma of the liver. A 35-year review.

Mesenchymal hamartoma of the liver occurs almost exclusively in infancy and childhood, with approximately 140 total cases reported. We report the experience with 18 patients at the Childrens Hospital of Los Angeles (Calif) during the past 35 years. The charts of all patients with mesenchymal hamartoma were retrospectively reviewed. The mean age at presentation was 16 months. Thirteen patients were symptomatic, presenting with increasing abdominal distention. Physical examination revealed an abdominal mass or hepatomegaly. Ultrasonography and computed tomography were the most useful diagnostic tests. Fourteen patients underwent resection; 9 underwent hepatic resection and 5 underwent excision of the tumor only. One patient had marsupialization, 1 underwent a biopsy only, and 2 died of unrelated causes and the hamartoma was found incidentally at autopsy. In all instances, a large cystic mass with well-demarcated margins was found. Three patients were unavailable for follow-up and 13 patients were alive and well 1 month to 24 years (mean, 5 years) after diagnosis. Recurrence or malignant transformation was not noted. A presumptive diagnosis can be made preoperatively by normal laboratory values and a combination of ultrasonography and computed tomography. We recommend excision of the tumor in all patients once the diagnosis is made, with the expectation of complete recovery.

A comparison of staging methods for Hodgkin's disease in children.

Potential long-term complications of radiotherapy and chemotherapy in the pediatric patient with Hodgkin's disease necessitate accurate staging. To determine the accuracy of abdominal computed tomography (CT) and gallium citrate Ga 67 scans in staging Hodgkin's disease, we reviewed the charts of all children with Hodgkin's disease seen at Childrens Hospital of Los Angeles from 1975 to 1985. Patients with pathologically proved stage IV disease (ie, bone marrow involvement) and those who only underwent staging laparotomy were excluded. A total of 40 children underwent staging by laparotomy and staging by abdominal CT and/or 67Ga scan. The CT and 67Ga scans were reviewed by radiologists in a blinded manner and compared with the results of a formal staging laparotomy. Of the 38 patients whose disease was staged with 67Ga scan, disease in ten was understaged and in four overstaged, for a 37% incorrect staging rate. Of the 14 patients whose disease was staged by CT scan, disease in three was understaged and in one overstaged, for a 29% incorrect staging rate. In view of the inaccuracy of noninvasive studies and the impact of incorrect staging on treatment, we recommend that a staging laparotomy be performed in all children with Hodgkin's disease who are not proved to have stage IV disease.

Tracheal reconstruction with polytetrafluoroethylene graft in dogs.

Use of prosthetic materials for long-segment tracheal reconstruction has been limited owing to infection, graft migration, ingrowth of fibrous tissue, and stenosis. Polytetrafluoroethylene (PTFE) is flexible and porous, and it may resist infection more than previously used materials. We evaluated PTFE for use in long-segment tracheal reconstruction. A 5-cm segment of trachea was resected in 9 dogs and replaced with a 20-mm reinforced PTFE graft using 4-0 Vicryl sutures. In 2 control dogs, one tracheal arch was resected and a primary anastomosis was performed. The animals were followed up with weekly bronchoscopy and endoscopic photography. Euthanasia was performed at 16 weeks or when signs of respiratory distress developed. At postmorten examination, the anastomoses were examined grossly and with light and scanning electron microscopy. In all 9 dogs that underwent tracheal replacement with PTFE, granulation tissue developed at the anastomoses resulting in airway obstruction after 3 to 8 weeks. No epithelial growth occurred over the graft between the anastomoses. The control animals did well. We conclude that granulation tissue formation at the anastomosis and the lack of respiratory epithelial ingrowth across the graft makes PTFE unsuitable for long-segment tracheal reconstruction.

Hamartomas of the chest wall in infants.

Chest wall hamartomas in infancy are rare lesions with distinct clinical, radiologic, and pathologic characteristics. Four cases treated at Children's Hospital of Los Angeles are presented and previously reported cases are reviewed. Chest wall hamartomas arise antenatally and present as hard, immobile masses, which may cause respiratory insufficiency. An extrapleural mass arising from the ribs can be seen radiographically. Histologically, these lesions are hypercellular and consist of a disorganized array of mesenchymal tissues endogenous to the chest wall. Rapid growth may occur, but usually is self-limited. Chest wall hamartomas are usually benign. This series includes the malignant transformation of one of these lesions. En bloc resection is curative, but the large residual chest wall defect frequently results in scoliosis.

Supraumbilical skin-fold incision for pyloromyotomy.

We describe our experience with a supraumbilical skin-fold incision for pyloromyotomy in infants. Our technique uses a vertical fascial incision. This approach provides excellent exposure to the pylorus, allows greater operative flexibility, and results in a superior cosmetic outcome compared to the traditional right upper-quadrant incision.