CAPSNet Background

• Mission Statement
• Primary Goals
• Background
• What is Gastroschisis?
• What is CDH?

Mission Statement

"To be a collaborative network working together to conduct influential and informative research dedicated to improving perinatal surgical health care delivery in Canada."

Primary Goals

1. Establish and maintain a flagship, national pediatric surgical database. Thus providing an infrastructure to facilitate and encourage collaborative national research.
2. Identify variations in clinical practices among Canadian perinatal centres and identify which practices are associated with favourable and unfavourable patient outcomes. As a result, putting forward new recommendations for targeted practice intervention for care of these patients.
3. Study the impact of clinical practice decisions on resource use and its implications for improving patient outcomes. Consequently, furthering our understanding of the cost-benefit concerns of the Canadian health care system.

CAPSNet’s preliminary project will focus on the clinical practices and outcomes associated with two specific, yet relatively common congenital defects: gastroschisis (GS) and congenital diaphragmatic hernia (CDH).

Background

Birth defects are the most common cause of infant mortality in industrialized nations. In addition, among infants admitted to neonatal intensive care units, those with birth defects requiring major surgery consume disproportionate health care resources. Gastroschisis (GS) and congenital diaphragmatic hernia (CDH) are among the most important birth defects requiring surgery due to their relative frequency (compared with other birth defects), morbidity and mortality, and resource intensive, multidisciplinary care needs. However, since the number of cases of GS and CDH treated by single centres is small, and because therapeutic opinion varies from centre to centre, traditional "evidence" upon which decisions for care of these patients is made has been based on single or combined institutional case reports. These reports are collected over long periods of time during which therapies are applied to a heterogeneous patient group in a non-uniform manner. It is therefore not surprising that there is a distinct lack of therapeutic consensus for what constitutes "best" multi­disciplinary care for these infants. This lack of consensus extends from prenatal diagnosis to postnatal treatment and is compounded by the lack of validated, diagnosis-specific, illness severity instruments for risk adjustment. Furthermore, the reporting of birth defect prevalence is inaccurate because of exclusion of terminated pregnancies and stillbirths. Thus, there is an urgent need for research to evaluate this knowledge gap and address questions that have been thus far unanswerable by traditional reporting from single institutions.

The CAPSNet project "Establishing best perinatal practices for Gastroschisis and Congenital Diaphragmatic Hernia" is significant because it will allow us the opportunity to critically determine best practices for GS and CDH patients that can be used to target practice change and improve the quality of care for these infants throughout Canada and potentially elsewhere. In addition, this study model would be applicable to other complex and infrequent neonatal problems that are not appropriately addressed by small cohort studies.

What is Gastroschisis?

Gastroschisis is the most common congenital defect of the anterior abdominal wall, (~1 per 2500 pregnancies) and is usually detected by routine maternal serum and ultrasound screening. This defect of unknown origin results in the extrusion of part or all of the intestines in utero alongside the umbilical cord and into the amniotic space. Prenatal care involves follow-up ultrasound imaging and an arranged delivery at a perinatal centre. Treatment after birth consists of either early or delayed primary surgical closure of the defect, followed by hospitalization in a neonatal intensive care unit (NICU) for several weeks. Infants usually require ventilatory support, nutritional support, antibiotics and other pharmacological therapies. Post-operative survival now approaches 90%. The most problematic complication of Gastroschisis post-operatively is intestinal injury and/or "failure". Intestinal injury occurs as a result of bowel damage sustained in utero, when the developing bowel is exposed to amniotic fluid.

Treatment for Gastroschisis: Variations and Controversies

There is considerable controversy regarding the perinatal care of fetuses with antenatally diagnosed Gastroschisis. Since intestinal injury is believed to occur before birth, many recommend planned preterm delivery, in the belief that any potential consequence of prematurity is offset by reduction in intestinal injury achieved by early delivery. However, others report no advantage to early delivery. Route of delivery (vaginal versus Cesarean section) is also controversial. Some pediatric surgeons and obstetricians have advocated planned cesarean delivery, believing that conditions favouring primary abdominal wall closure are optimal immediately after birth. Primary repair of the Gastroschisis defect occurs immediately following birth in the delivery room. Yet others recommend routine placement of a plastic silo for bowel protection and delayed primary repair. Still others advocate selective, primary awake repair using analgesia (where patient is conscious but feels no pain), rather than repair under general anesthesia (patient completely unconscious), since the latter often results in a potentially avoidable period of mechanical ventilation. As such, it is extremely evident that there is currently no consensus on what the "best" surgical care is for these patients. In addition, recognising that antenatal bowel injury occurs in utero, and based on experimental work in fetal animal models suggesting that urinary and gastrointestinal products in amniotic fluid cause this injury, some obstetricians are performing serial prenatal amniotic fluid exchange with normal saline in an attempt to attenuate bowel injury and improve post-natal outcome.

Difficulties with Illness Severity and Outcome Assessment for Gastroschisis

Historical data suggest that both pre and postnatal factors may predictably contribute to outcome in Gastroschisis. Prenatal factors thought to have predictive value include: fetal growth profile, amniotic fluid volume, fetal bowel dilation and wall thickness, and superior mesenteric artery pulsatility index. Postnatal variables thought to contribute to outcome include: birth weight, lack of prenatal diagnosis and elapsed time to abdominal closure, need for mechanical ventilation, presence of severe bowel injury, early introduction of enteral feedings, use of abdominal silo and presence of sepsis. Unfortunately, these data are generated from single institutions with small patient numbers, which suffer from both time and treatment biases, and do not offer a consensus opinion on how Gastroschisis patients should be stratified according to their level of illness severity or treated. Currently, there is no validated illness severity instrument available to accurately assess how sick a Gastroschisis patient is. This type of stratification is important because it has an impact on both research, in helping to understand Gastroschisis and on clinical management, in determining the best course of treatment for a specific patient.

What is Congenital Diaphragmatic Hernia (CDH)?

CDH is a developmental defect in the diaphragm (most commonly on the left side), which occurs in 1 per 2200 births and results in protrusion of the abdominal contents into the developing chest cavity, restricting fetal heart and lung development. Infants born with CDH suffer from variable degrees of pulmonary hypoplasia (underdeveloped lungs) and pulmonary hypertension (elevated blood pressure in the lungs). They may require substantial levels of cardio­pulmonary support, including extra­corporeal membrane oxygenation (ECMO), a heart-lung bypass that circulates blood through a machine to be oxygenated in patients with total respiratory and cardiac failure. Surgical treatment involves reducing the protruding abdominal contents back into the abdomen, followed by closure of the diaphragmatic defect with either autologous tissue (diaphragmatic muscle) or a prosthetic "patch". Outcome is largely determined by the severity of pulmonary hypoplasia and accompanying pulmonary hypertension. The best current estimate of postnatal survival reported an overall survival of 63%. However, neonates who survive the postnatal period without major complications can be expected to have a good long term outcome, due to the lung’s postnatal growth potential.

Treatment of CDH: Variations and Controversies

CDH was once thought to represent a dire emergency requiring immediate surgical treatment. Over the past 2 decades, there has been a shift in ideas over treatment towards initial respiratory "stabilization" and delayed diaphragmatic repair, following a seminal Canadian report demonstrating equivalent outcomes in CDH infants treated by "delayed" surgery as compared to "urgent" surgery. The impact of delayed surgical treatment of CDH has been generally favourable, with most centres reporting improved survival. However this experience has not been universal, as some studies have failed to show a survival advantage as a result of delayed surgery. Another recent therapeutic trend has been the adoption of less aggressive ventilatory strategies to lessen lung injury among these patients. Some studies have reported that in comparison with historical controls, CDH patients treated with high frequency oscillatory ventilation (HFOV) and permissive hypercapnea to reduce barotrauma, demonstrate improved outcomes, while other studies have not. Other therapeutic controversies include the use of inhaled nitric oxide and other pulmonary vasodilators in treatment of pulmonary hypertension, the role of steroids and surfactant, the role of ECMO and the timing of surgical repair in relation to ECMO, and the use of new ventilatory adjuncts, including liquid ventilation. For all of these treatment modalities, clinical practices are not standardized, and vary tremendously from one institution to another.
Fetal surgery: Prenatal diagnosis of CDH includes careful evaluation for associated somatic or chromosomal defects, and may help couples in their decision regarding pregnancy continuation. The recognition that some fetuses with isolated CDH develop non-survivable pulmonary hypoplasia has been a stimulus for the therapeutic possibilities of in utero surgery, however prenatal variables that accurately predict the likelihood of postnatal survival have been difficult to determine.

Quality of Available data: CDH Acuity Stratification and Outcome

There has been a much effort to develop consensus criteria which would predict the severity of CDH-associated pulmonary hypoplasia (PH), so that those fetuses with "non-survivable" PH could be identified prenatally. Unfortunately, the data on prognostic variables including: gestational age at prenatal diagnosis, presence of the stomach in the fetal thorax, co-existent polyhydramnios, and presence of associated malformations excluding major cardiac defects, yield conflicting results. Furthermore, the measured outcome in most studies is survival, which is, by necessity treatment-dependent and therefore does not exclusively reflect the severity of pulmonary hypoplasia present at birth. Recent data suggests that the best prenatal predictors of the severity of postnatal pulmonary hypoplasia may be: i) presence of liver in the left hemithorax (for left sided CDH), ii) lung-head ratio (cross-sectional area of the contralateral lung divided by head circumference, and iii) an undersized fetal left ventricle. Although encouraging, these prognostic variables have not yet been validated beyond the small, single institution reports in which they first appeared.