Holly L. Hedrick

Necrotizing enterocolitis in neonates with congenital heart disease: risk factors and outcomes.

Objective. Necrotizing enterocolitis (NEC) is primarily a disease of the premature infant. Among children born at term, however, congenital heart disease may be an important predisposing factor for this condition. To determine risk factors for NEC in patients with congenital heart disease, we conducted a case–control study of neonates with cardiac disease admitted to the cardiac intensive care unit at our center during the 4-year period from January 1995 to December 1998. Methods. Cardiac diagnosis and age at admission were analyzed for association with NEC among the 643-patient inception cohort. Demographic, preoperative, and operative variables were recorded retrospectively in 21 neonates with congenital heart disease who developed NEC and 70 control neonates matched by diagnosis and age at admission. Using parametric and nonparametric analysis, cases and controls were compared with respect to previously identified risk factors for NEC. Results. Among the entire cohort of 643 neonates with heart disease admitted to the cardiac intensive care unit, diagnoses of hypoplastic left heart syndrome (odds ratio [OR] = 3.8 [1.6–9.1]) and truncus arteriosus or aortopulmonary window (OR = 6.3 [1.7–23.6]) were independently associated with development of NEC by multivariable analysis. In the case–control analysis, earlier gestational age at birth (36.7 ± 2.7 weeks vs 38.1 ± 2.3 weeks), prematurity (OR = 3.9 [1.2–12.5]), highest dose of prostaglandin >0.05 μg/kg/minute (OR = 3.9 [1.2–12.5]), and episodes of low cardiac output (meeting specific laboratory criteria) or clinical shock (OR = 6.5 [1.8–23.5]) correlated with the development of NEC. Earlier gestational age and episodes of low output were the only factors that remained significantly associated with NEC by multivariable analysis. Although there was no difference in hospital mortality between patients with and without NEC, mean hospital stay was significantly longer in those who developed NEC (36 ± 22 days vs 19 ± 14 days). Conclusions. The risk of NEC in neonates with congenital heart disease is substantial. Factors associated with an elevated risk of NEC in infants with heart disease include premature birth, hypoplastic left heart syndrome, truncus arteriosus, and episodes of poor systemic perfusion or shock. Heightened suspicion is warranted in newborns with these risk factors.

Long-term outcomes in children treated by prenatal vesicoamniotic shunting for lower urinary tract obstruction.

Objective: Limited information is available about long-term outcomes in children treated prenatally for lower urinary tract obstruction. Our aim was to evaluate outcomes in children treated in utero with vesicoamniotic shunts. Methods: Clinical outcomes in 20 pregnancies with a singleton male fetus, oligo/anhydramnios, and lower urinary tract obstruction were studied using chart review and phone and written clinical questionnaire for parents, pediatricians, and urologists. Results: Overall 1-year survival was 91%. Two neonatal deaths occurred from pulmonary hypoplasia. Mean gestational age at delivery was 34.6 weeks, mean days from shunting to delivery were 84.4, and mean birth weight was 2,574 g. Prenatal urinary prognosis was good in 13, borderline in 2, and poor in 3 of the survivors. Mean age at follow-up was 5.83 years. Posterior urethral valves were confirmed in 7 males, urethral atresia in 4, and prune belly syndrome in 7. Eight children had acceptable renal function, 4 had mild insufficiency, and 6 required dialysis and eventual renal transplant. Eleven children had normal bladder function with spontaneous voiding, 6 required catheterization, and 1 child still had a vesicostomy. Height and weight were below the 25th percentile in 9 children. Persistent respiratory problems were present in 8, musculoskeletal problems in 9, and frequent urinary tract infections were reported in 9. Health-related quality of life results in our group with lower urinary tract obstruction were similar to those in a healthy child population. Conclusion: Male children who underwent prenatal bladder shunting were neurodevelopmentally normal. Although one third of the surviving babies required dialysis and transplantation, the majority have acceptable renal and bladder function and report satisfactory quality of life. Level of Evidence: III

Congenital high airway obstruction syndrome: natural history and management

BACKGROUND Congenital high airway obstruction syndrome (CHAOS) is a life-threatening condition with a poorly understood natural history. METHODS A retrospective review of five patients with CHAOS between 1997 and 2002 was performed. RESULTS All fetuses had large echogenic lungs, dilated airways, inverted diaphragms, and massive ascites. One fetus with a laryngeal cyst was terminated at 22 weeks. A twin fetus with findings suggestive of a tracheal web had progressive hydrops, which led to fetal demise. The remaining 3 patients delivered via the ex utero intrapartum treatment (EXIT) procedure survived. The first patient tolerated progressive hydrops for 12 weeks in utero. He had tracheal atresia but underwent laryngotracheoplasty successfully. He is the first long-term CHAOS survivor and is speaking at 5 years of age. The 2 patients with relatively stable lung volumes prenatally have laryngeal atresia with a pinpoint posterior laryngeal fistula. Their postnatal clinical courses were much more benign than the first survivor. CONCLUSIONS The prenatal natural history and postnatal course of CHAOS depends on whether the airway obstruction is complete. The EXIT procedure offers the potential for salvage of this otherwise lethal condition. Hydrops may be well tolerated prenatally for weeks with potential resolution if airway fistulization is present.

Cystic adenomatoid malformation of the lung: Review of genetics, prenatal diagnosis, and in utero treatment

Prenatal identification of lung abnormalities has increased with prenatal surveillance. Treatment usually requires serial ultrasound observation but in rare situations in utero therapy may be required for fetal survival. We review the genetics, prenatal evaluation, and treatment of lung abnormalities with congenital cystic adenomatoid malformation (CCAM). Other lung lesions, bronchopulmonary sequestration (BPS), hybrid lesions involving both malformations, congenital lobar emphysema (CLE), are briefly included as differential diagnosis options. Outcome of fetuses identified to have CCAM lung abnormalities resulting in fetal hydrops and having in utero therapy (thoracoamniotic shunting, fetal thoracotomy, EXIT delivery) are discussed. In the appropriate situation, this maternal fetal surgery approach for CCAM is life‐saving for the affected fetus with acceptable maternal morbidity risks in the present and future pregnancies.

Thoracoamniotic Shunts: Fetal Treatment of Pleural Effusions and Congenital Cystic Adenomatoid Malformations

Objective: To determine whether fetuses that underwent thoracoamniotic shunt placement for treatment of pleural effusion (PE) or macrocystic congenital cystic adenomatoid malformation (CCAM) have an improved outcome as compared with an untreated population. Methods: A retrospective review from a single tertiary center was performed using thoracoamniotic shunt placement to treat PE or macrocystic CCAM between 1998 and 2001. Thoracoamniotic shunts were used on 26 occasions in 19 pregnancies. Results: The average gestational age at the diagnosis of PE and CCAM was 22 + 4 and 20 + 0 weeks, respectively. Shunts were offered in pregnancies complicated by hydrops or at significant risk for pulmonary hypoplasia. Shunts were placed at 26 + 2 weeks (average) and 23 + 1 weeks (average) in the PE and CCAM groups, respectively. In CCAM patients, the mean pre- and postshunting mass volumes were 50.5 and 25.7 cm3, representing a 51% reduction in mass volume following shunt placement. In the PE group, the average delivery age was 33 + 5 weeks, with an average shunt placement to delivery time of 7 + 3 weeks. In the CCAM group, the average delivery was 33 + 3 weeks, with an average shunt placement to delivery time of 10 + 2 weeks. The postnatal survival rates were 67% (6/9) and 70% (7/10) in the PE and CCAM groups, respectively. Conclusions: (1) Thoracoamniotic shunts should be considered as a treatment option for selected PE or macrocystic CCAM fetuses with hydrops or a significant risk for pulmonary hypoplasia; (2) the neonatal survival with shunting was similar for PE and CCAM groups and was improved as compared with literature reports, and (3) fetuses with CCAM presented earlier with hydrops than those with PE. Successful shunting resulted in a prolongation of pregnancy into the 3rd trimester in both groups.

Effect of Maternal Betamethasone Administration on Prenatal Congenital Cystic Adenomatoid Malformation Growth and Fetal Survival

Objective: To evaluate the effect of prenatal steroid treatment on the growth of congenital cystic adenomatoid malformations (CCAM) and survival in affected fetuses not amenable to other percutaneous ultrasound-guided prenatal interventions. Methods: A retrospective review of patients with a CCAM or hybrid lesion treated with two maternal prenatal betamethasone injections was performed. Patients receiving cyst aspiration or thoracoamniotic shunting at the time of or after steroid administration were excluded. Growth rates and survival data were compared to historical non-steroid treated controls. Results: Eleven patients were treated with prenatal steroids (10 microcystic and 1 macrocystic). Survival was 100% in fetuses with hydrops (5/5) or a CCAM volume ratio (CVR) >1.6 (7/7) at the time of steroid administration. This compares to a mortality of 100 and 56.2% respectively in historical non-treated controls. Resolution of hydrops was seen in 80% (4/5) of steroid-treated patients. CCAM growth rates were variable after steroid administration. However, when compared to historical data where CVR and CCAM volume have been documented to increase until 28 weeks’ gestation, the CVR and CCAM volume growth rates decreased in 72.73% and 50% of patients respectively from the time of steroid administration to 28 weeks’ gestation. Conclusions: In the fetus with a CCAM, the presence of hydrops fetalis or a CVR >1.6 is indicative of poor fetal outcome without prenatal intervention. The observed effect of antenatal steroid treatment on CCAM growth is variable, but its potential to improve survival in these high-risk groups is encouraging and warrants further controlled evaluations.

Appendicitis in the young child: A continuing diagnostic challenge

Objective The purpose of this review was to examine the presenting signs and symptoms of children 5 years of age or less who underwent operation for appendicitis. In addition, we sought to determine the rate of perforation of the appendix and the effect on outcome in this age group. Methods Medical records for the period September 1987 to September 1998 were reviewed for all children 5 years of age or less who underwent appendectomy for appendicitis. Data gathered included age at operation, gender, care sought prior to admission for appendectomy, duration of symptoms, signs and symptoms at the time of admission, and length of postoperative hospital stay. Symptoms of diarrhea, emesis, fever, pain, and anorexia were recorded. Physical signs of an abdominal mass, guarding, rebound tenderness, rigidity, and diffuse or focal tenderness were recorded. Diagnostic information included white blood cell count with differential, and radiographic imaging, if obtained. The presence or absence of perforation of the appendix, and abscess formation were based on the intraoperative impression of the operating surgeon. Results For the 11-year period, 120 patients 5 years of age or less required an operation for appendicitis and had a complete medical database. The mean age was 3.6 ± 1.3 years; 53% were male. Patients underwent a separate medical evaluation prior to arriving at a definitive diagnosis in 44.2% cases. The most common presenting symptom was abdominal pain (94%); the most common sign was abdominal tenderness (95.8%). Tenderness was generally diffuse if perforation had occurred (62%) or focal in the nonperforated group (61%). The duration of symptoms in patients with perforation was more than double that of the nonperforated patients (4.7 vs 2.1 days, respectively). The mean white blood cell count (WBC) was 18.3 ± 7.4 cells/mm3, and did not differ significantly between the perforated and nonperforated groups. A left shift detected in the WBC differential was present in 91%. An abdominal radiograph was obtained in 87%, and demonstrated a fecalith in 18%. A preoperative ultrasound was obtained in 38%, a computed tomographic scan in 7%. At the time of surgery, 74% were found to have evidence of perforation. An abscess was found at the initial surgery in 47% of patients with appendiceal perforation, but in no patient in whom perforation had not occurred. The rate of perforation increased as the age of the patient decreased (100% perforation for age 1 (n= 10) to 69% for age 5, (n= 35). Perforation was associated with a longer hospital length of stay as compared to the nonperforated appendix (median 9 days vs. 3 days, respectively, P< 0.001). There were no deaths in this series. Conclusion Appendiceal perforation continues to be a common occurrence in the young child and increases in frequency as the age of the patient decreases and the duration of symptoms lengthens. Perforation results in a significant increase in hospital length of stay and rate of abscess formation.

Postnatal management and long-term outcome for survivors with congenital diaphragmatic hernia

Significant advances in the postnatal management of patients with congenital diaphragmatic hernia (CDH) have resulted in a remarkable improvement in survival rates over the past two decades. The success of current postnatal management of CDH patients has rendered fetal intervention to be limited to the most severe cases, and the role for prenatal treatment of CDH patients remains unclear. The adoption of lung‐preserving strategies including high‐frequency oscillatory ventilation (HFOV) and extracorporeal membrane oxygenation (ECMO) have improved CDH outcomes especially in those patients with significant ventilatory or circulatory compromise. Survival rates of up to 90% are being reported in some high‐volume centers. However, the increased survival in CDH patients has been accompanied by an increase in neurological, nutritional and musculoskeletal morbidity among the long‐term survivors. This has resulted in the need to provide resources for the long‐term follow‐up and support of this patient population. In this article, the postnatal management strategies and primary and secondary outcomes of high‐volume international pediatric surgical centers will be reviewed. Finally, the role of a multidisciplinary management team for the follow‐up of long‐term CDH survivors will be discussed. Copyright

Acute Cardiovascular Effects of Fetal Surgery in the Human

Background—Prenatal surgery for congenital anomalies can prevent fetal demise or alter the course of organ development, resulting in a more favorable condition at birth. The indications for fetal surgery continue to expand, yet little is known about the acute sequelae of fetal surgery on the human cardiovascular system. Methods and Results—Echocardiography was used to evaluate the heart before, during, and early after fetal surgery for congenital anomalies, including repair of myelomeningocele (MMC, n=51), resection of intrathoracic masses (ITM, n=15), tracheal occlusion for congenital diaphragmatic hernia (CDH, n=13), and resection of sacrococcygeal teratoma (SCT, n=4). Fetuses with MMC all had normal cardiovascular systems entering into fetal surgery, whereas those with ITM, CDH, and SCT all exhibited secondary cardiovascular sequelae of the anomaly present. At fetal surgery, heart rate increased acutely, and combined cardiac output diminished at the time of fetal incision for all groups including those with MMC, which suggests diminished stroke volume. Ventricular dysfunction and valvular dysfunction were identified in all groups, as was acute constriction of the ductus arteriosus. Fetuses with ITM and SCT had the most significant changes at surgery. Conclusions—Acute cardiovascular changes take place during fetal surgery that are likely a consequence of the physiology of the anomaly and the general effects of surgical stress, tocolytic agents, and anesthesia. Echocardiographic monitoring during fetal surgery is an important adjunct in the management of these patients.

Ex utero intrapartum therapy

The hallmark of ex utero intrapartum therapy (EXIT) procedure is the maintenance of uteroplacental blood flow and gas exchange. This goal is achieved with the use of inhalational agents to relax uterine tone, a continuous amnioinfusion to stabilize uterine volume, and partial exposure of the fetus. From March 1996 to December 2002, 43 EXIT procedures were performed at the Childrens Hospital of Philadelphia (CHOP). Indications included airway obstruction from fetal neck masses (n = 19), reversal of tracheal occlusion for congenital diaphragmatic hernia (CDH; n = 13), resection of massive congenital cystic adenomatoid malformation of the lung (n = 5), congenital high airway obstruction syndrome (n = 3), EXIT-to-extracorporeal membrane oxygenation for a fetus with CDH and a cardiac defect (n = 1), unilateral pulmonary agenesis (n = 1), and thoracoomphalopagus conjoined twins (n = 1). Eight fetuses required initial tracheotomy at the time of EXIT to secure the airway. One death occurred during the EXIT procedure secondary to inability to secure the airway with parental refusal for tracheotomy. In all cases, the EXIT procedure provided time on uteroplacental gas exchange to perform procedures such as direct laryngoscopy, bronchoscopy, tracheotomy, arterial and venous access, resection of neck or lung masses, and ECMO cannulation, thereby converting an emergent crisis into a controlled situation.