Congenital diaphragmatic hernia (CDH) still remains. Outcome at 2 Years of Infants With Congenital Diaphragmatic Hernia: A Population-Based Study

Transcription

1 Outcome at 2 Years of Infants With Congenital Diaphragmatic Hernia: A Population-Based Study Sophie M. Jaillard, MD, Véronique Pierrat, MD, Angélina Dubois, MD, Patrick Truffert, MD, Pierre Lequien, MD, Alain J. Wurtz, MD, and Laurent Storme, MD Departments of Thoracic Surgery and Neonatology, University Hospital of Lille, Lille, France Background. Management of neonates with congenital diaphragmatic hernia (CDH) has undergone many changes associated with increased survival of high-risk CDH. However, little is known about the long-term outcome of CDH infants. Methods. Follow-up was performed in 85 newborn infants with CDH admitted in our neonatal intensive care unit between January 1991 and December Early (< 2 months) and late mortality (> 2 months), and respiratory, nutritional, musculoskeletal, and neurosensory outcome at 2 years were recorded. Results. Surgical repair was performed in 59 infants (69%) at a median postnatal age of 124 (range, 38 to 246) hours. Extracorporeal membrane oxygenation was used in 26 (30%) newborn infants. Survival at 2 years was 51 of 85 (60%) (early death, 28/85 [33%]; late death, 6/85 [7%]). Late deaths occurred because of persistent pulmonary hypertension or iatrogenic complications. Twelve of 51 (24%) newborn infants were oxygen dependant at the postnatal age of 28 days, and 1 of 51 (1.9%) was still oxygen dependant at 2 years. Growth failure was noted in 9 of 51 (18%), mainly related to severe gastroesophageal reflux and oral aversion. Scoliosis was diagnosed in 2 infants. Neurologic examination at 2 years was normal in 45 of 51 (88%). Cerebral palsy and developmental delay were observed in 2 and 4 infants, respectively. Four infants (8%) experienced associated problems. Respiratory, nutritional, and musculoskeletal morbidity was higher in infants treated by extracorporeal membrane oxygenation (p < 0.05). Conclusions. CDH infants are at risk for adverse nutritional and respiratory outcome. Despite severe respiratory failure at birth, prolonged oxygen therapy above 2 years of age is uncommon. Conversely, failure to thrive related at least in part to gastroesophageal reflux and oral dysfunction remains the major problem at 2 years of age. However, both nutritional and respiratory problems tend to improve with age. (Ann Thorac Surg 2003;75:250 6) 2003 by The Society of Thoracic Surgeons Congenital diaphragmatic hernia (CDH) still remains a challenging problem for both surgeons and neonatologists. Improved knowledge in pathophysiology mechanisms explaining the respiratory failure has led to changes in the management of newborn infants with CDH. However, uniform standards for management do not exist. Since 1990, a protocolized approach has been progressively adopted at our institution, which is the only referral center for infants with CDH in the Nord Pas-de-Calais area in France. This involves antenatal steroids, planned delivery at our perinatal center, prophylactic administration of surfactant, gentle ventilation with permissive hypercapnea, high-frequency oscillatory ventilation to decrease the barotrauma, inhaled nitric oxide, extracorporeal membrane oxygenation (ECMO) for those infants failing to achieve adequate oxygenation, and delayed surgery after stabilization of respiratory and hemodynamic status. Despite these recent innovations, the rate of death for infants with CDH presenting within the first 12 hours of life remains high [1, 2], although survival can be as close as 90% at advanced centers. Accepted for publication Aug 8, Address reprint requests to Dr Jaillard, Clinique Chirurgicale, Hôpital Calmette, Centre Hôpitalier Régional et Universitaire de Lille, Lille, France; sjaillard@chru-lille.fr. Long-term survival is, however, rarely described [3], and survivors of CDH have predictable pulmonary [4], gastrointestinal [5], nutritional [6], and developmental problems [7 10]. However, the current focus of most follow-up studies is on a relatively narrow range of outcomes, and fails to capture health along a variety of dimensions. Since 1990, all the surviving newborn infants with CDH admitted at our institution are prospectively enrolled into a follow-up study. The aim of our study was to assess the outcome at 2 years of infants with CDH since the introduction of new management strategies, and to identify children with multidisciplinary health problems. Mortality and respiratory, nutritional, musculoskeletal abnormalities, and neurosensory outcome at 2 years were recorded. Patients and Methods All the patients with CDH born in the North Pas-de- Calais area in France are referred to the neonatal intensive care unit (NICU) of the University Teaching Hospital at Lille. This institution is the only referral center for pediatric surgery and ECMO for a population of 4.5 million inhabitants. Inborn patients were defined as those born at our perinatal center by The Society of Thoracic Surgeons /03/$30.00 Published by Elsevier Science Inc PII S (02)

2 Ann Thorac Surg JAILLARD ET AL 2003;75:250 6 OUTCOME OF CONGENITAL DIAPHRAGMATIC HERNIA 251 Fig 1. Early and late mortality in a population of 85 neonates with congenital diaphragmatic hernia (CDH). Early deaths were defined as those occurring before 2 months, and late deaths as those occurring between 2 months and 2 years. *Overall mortality rate at 2 years in extracorporeal membrane oxygenation (ECMO) and non- ECMO patients. ECMO was used in case of severe hypoxemia (postductal PaO 2 40 mm Hg or postductal SpO 2 85% for more than 2 hours) despite optimal medical management, including the use of inotropic drugs, inhaled nitric oxide, high-frequency oscillatory ventilation, and exogenous surfactant. Both venovenous (before 1993) and venoarterial ECMO were used. Exclusion criteria for ECMO or surgery were birth weight below 1,800 g or gestational age less than 34 weeks, lack of honeymoon period defined by postductal PaO 2 above 60 mm Hg and PaCO 2 less than 50 mm Hg despite optimal medical management, and severe intra cranial complications. Right common carotid artery (RCCA) was reconstructed after venoarterial ECMO. Surgery was performed in the NICU and was always conducted under the control of the same surgeon (SJ). Repair was usually carried out within 24 hours of stability. A transabdominal approach was systematically used. A large oversized prosthetic patch (Gore-Tex; W.L. and Associates, Inc, Flagstaff, AZ) was used as soon as diaphragmatic repair would create a tension. Gentle suction was achieved through a chest tube according to mediastinal shift. Early and late mortality was recorded. Early death was arbitrarily defined as a death within the first 2 months of life, and late death as a death after this period. All the surviving infants were included into a follow-up study. Respiratory, nutritional, musculosqueletal, and neurosensory outcomes were assessed at 2 years. Chronic lung disease was defined as any requirement for supplemental oxygen 28 days after birth. Growth, including weight, length, and head circumference, was compared with the reference curves of Sempé [11]. Growth retardation was defined as weight less than fifth percentile. An esophageal ph monitoring was systematically performed to detect gastro-esophageal reflux (GER) before discharge, or controlled if clinically indicated. Oral dysfunction was defined as sucking-swallowing reflex anomalies with oral aversion. Assessment of neurologic outcome was made using items from Touwen [12] and Amiel-Tison and Grenier [13]. Neurologic outcome was defined as normal, developmental delay [14], or cerebral palsy according to Hagberg and associates [15]. All the infants treated by ECMO were evaluated by a psychologist in order to measure the developmental quotient (DQ) with the Brunet-Lezine scale [16]. Neurosensorial evaluation was systematically performed, including ocular and fundus oculi examination, hearing evaluation by Boel test, and brainstem auditory-evoked potential (BEAP). Statistical analysis was performed using the SAS software (Statistical Software, Cary, NC) for comparison of means with the Student s t test, and difference of proportions with 2 test or Fisher s exact test. Mann-Whitney test was used for the comparison of groups of patients. A p 0.05 was considered significant. Results Ninety-four consecutive newborn infants with CDH were admitted between January 1990 and December Nine patients were excluded from analysis on the basis of associated lethal congenital anomalies. Therefore, the study group included 85 newborn infants. Thirty-four (40%) were inborn. Twenty-six among the 85 CDH infants (30%) failed to reach operation (Fig 1) for the following reasons. (1) Twenty infants had severe respiratory failure noted immediately after birth, in whom preductal PaO 2 more than 60 mm Hg and PaCO 2 less than 50 mm Hg were never reached despite optimal ventilatory and hemodynamic management using high-frequency oscillatory ventilation, inhaled NO, surfactant, et cetera. The use of ECMO or surgery was precluded because of lack of reasonable expectation of potential reversible respiratory failure. (2) Three infants had severe anoxo-ischemic brain injury precluding the use of ECMO or surgical repair. (3) Three other infants died without surgical repair while on ECMO support (n 1) or immediately after ECMO was discontinued (n 2) from extensive superior caval syndrome or recurrent refractory hypoxemia.

3 252 JAILLARD ET AL Ann Thorac Surg OUTCOME OF CONGENITAL DIAPHRAGMATIC HERNIA 2003;75:250 6 Table 1. Perinatal Population Characteristics and Survival at 2 Years Population (N 85) Survivors (n 51) Non-Survivors (n 34) p a Prenatal diagnosis 44 (52%) 30 (59%) 14 (41%) NS Gestational age at prenatal NS diagnosis (weeks) Polyhydramnios 10 (12%) 2 (3.9%) 8 (23%) 0.01 Inborn 34 (40%) 25 (49%) 9 (26%) 0.05 Gestational age (weeks) NS Birth weight (g) 3, , , Males 49 (58%) 26 (51%) 23 (67%) NS Left-sided 68 (80%) 40 (78%) 28 (82%) NS 5-minute Apgar score NS Admission PaCO 2 (mm Hg) NS Best PaO 2 (mm Hg) b Oxygenation index (OI) c Best PaCO 2 (mm Hg) b a p in survivors vs nonsurvivors. b Best value during the first 2 days. c OI related to the best PaO 2. Results are means SD. OI [(mean airway pressure FiO 2 )/PaO 2 ] 100. ECMO was performed in 26 newborn infants (30%), and was venovenous in 4 patients and venoarterial in 22. Median duration of ECMO was 7 (range, 5 to 14) days. Surgical repair was performed in 59 infants (70%). Median age at surgery was 124 (range, 38 to 246) hours. A prosthetic diaphragmatic patch was used in 37%. Surgery was performed before ECMO in 9 infants, during ECMO in 2 infants, and after ECMO in 12 infants. Eight surgical complications developed as well: 4 infants were reoperated on because of bowel obstruction (one midgut volvulus, one gastric volvulus, and two adhesive bowel obstructions); 3 had chylothorax that resolved by feeding with formula containing medium chain triglycerides; and 1 infant developed a superficial wound infection. Recurrence of CDH occurred in 5 infants, with reintervention between 3 and 18 months: four with diaphragmatic agenesis, and one caused by thinning of the posterior diaphragm crossed by an abnormal systemic artery associated with a lung extralobar sequestration (resected during the initial repair). Fifty-seven infants (67%) were alive at 2 months. Mortality rates are summarized in Figure 1. Six late deaths were observed. Five of these 6 infants were treated by ECMO in the neonatal period. These late deaths were due to severe respiratory failure in 3 infants, with death between 5 and 18 months. Two infants died during late surgical intervention, 1 during general anesthesia for jejunostomy at 12 months, and 1 with mediastinal hemorrhage after insertion of a central venous line at 24 months. One infant, who did not required ECMO initially, died from sudden infant death at 3 months. Thus, 51 infants (60%) were alive at 2 years. Among the inborn population, survival rate was 73% (25/34) at 2 years. Among all the 2-year survivors, median age at discharge was 34 (range, 12 to 930) days, median time to extubation was 10 (range, 1 to 930) days, and median duration of oxygen therapy was 12 (range, 1 to 930) days. The use of ECMO was associated with an increase risk of death at 2 years (31% vs 8.3%, p 0.04 by Fisher s exact test). Perinatal risk factors for overall mortality are summarized in Table 1. A decreased survival was also observed with the use of a patch during initial surgery (Table 2). Twenty-eight infants (55%) were free of sequelae at 2 years (Table 3). Recovery without sequelae was significantly lower in infants requiring ECMO (p 0.001). Twelve infants were oxygen dependant at the postnatal age of 28 days, and 2 required tracheostomy for prolonged mechanical ventilation. One died at 18 months from obstruction of the tracheostomy tube. All but 1 of the survivors were weaned from oxygen therapy at 2 years of age. Growth retardation and symptomatic GER were noted in 9 and 14 infants, respectively. Nutritional support was necessary in 4 infants (7% of infants alive at 2 months). Two died between 2 months and 2 years from iatrogenic complications. Two growth-retarded infants still required either intravenous parenteral nutrition or gastrostomy tube feeding at 2 years. Three out of the 14 infants with GER required hiatal reconstruction. These antireflux procedures were disappointing, with only one effective improvement and two failures due to persistent distension and motility disorders of the esophagus. Beside GER, oral aversion, observed in 25% of the population, contributed largely to the growth failure. Two infants developed scoliosis, and both needed a patch Table 2. Surgical Characteristics of the Population No. of surgical patients 59 (69%) Patch repair 22/59 (37%) Patch/survivors at 2 years 15/51 (29.4%) a Patch/nonsurvivors at 2 years 7/8 (87%) Median age at surgery (hours) 124 (range, ) a p 0.01 in survivors vs nonsurvivors.

4 Ann Thorac Surg JAILLARD ET AL 2003;75:250 6 OUTCOME OF CONGENITAL DIAPHRAGMATIC HERNIA 253 Table 3. Outcome at 2 Years (N 51) Survivors (n 51) Without ECMO Treatment (n 33) With ECMO Treatment (n 18) p a Recovery without sequelae 28 (55%) 24 (73%) 4 (22%) Neurological outcome Cerebral palsy 2 (4%) 1 (3%) 1 (6%) NS Developmental delay 4 (8%) 1 (3%) 3 (17%) NS Nutritional outcome Growth retardation 9 (18%) 1 (3%) 8 (44%) Gastroesophageal reflux 14 (27%) 5 (15%) 9 (50%) 0.05 Nutritional support 2 (4%) 0 2 (11%) NS Respiratory outcome Chronic lung disease 11 (22%) 1 (3%) 10 (56%) Needing tracheostomy 1 (2%) 0 1 (5.5%) NS Oxygen requirement 1 (2%) 0 1 (5.5%) NS Musculoskeletal outcome Scoliosis 2 (4%) 0 2 (11%) NS a p with ECMO treatment vs without ECMO treatment. ECMO extracorporeal membrane oxygenation. during initial surgery. Respiratory and nutritional morbidity was higher in infants treated by ECMO (Table 3). Neurologic examination at 2 years was within normal range in 45 of 51 (88%). Cerebral palsy and developmental delay were observed in 2 and 4 infants, respectively. Developmental delay was always associated with growth failure and hypotonia. Mean DQ in the ECMO survivors was 96 (range, 77 to 113). No neurosensorial loss (visual or hearing anomalies) was recorded. Four infants (8%) experienced multiple disorders, including failure to thrive, gastroesophageal reflux, chronic lung disease, scoliosis, or poor neurologic outcome. Relationships between perinatal factors and occurrence of gastroesophageal reflux or chronic lung disease at 2 years are summarized in Table 4. ECMO, patch repair, and high oxygenation index are related to poor long-term outcome. Comment Medical management and surgical strategies of CDH infants underwent many changes since 1990, including preoperative stabilization with delayed repair, use of exogenous surfactant, inhaled nitric oxide, highfrequency oscillatory ventilation, and ECMO. These changes were associated with increased survival of high- Table 4. Factors Related to Specific Morbidity at 2 Years (N 51) Population (N 51) Gastroesophageal Reflux Chronic Lung Disease Yes (n 14) No (n 37) Yes (n 11) No (n 40) Prenatal diagnosis 30 (59%) 6 (43%) 8 (57%) 9 (82%) 2 (18%) Gestational age at prenatal diagnosis (weeks) a Polyhydramnios 2 (3.9%) Inborn 25 (49%) 8 (57%) 6 (43%) 5 (46%) 6 (54%) Gestational age (weeks) Birth weight (g) 3, , , , , Males 26 (51%) 6 (43%) 8 5 (45%) 6 (55%) Left-sided 40 (78%) 12 (86%) 2 10 (91%) 1 (9%) Patch repair 15 (29.4%) 11 (79%) d 3 (21%) 7 (64%) e 4 (26%) Best PaO 2 (mm Hg) b Oxygenation index (OI) c e Best PaCO 2 (mm Hg) b ECMO treatment 18 (35%) 9 (64%) e 5 (36%) 10 (91%) d 1 (9%) a Prenatal diagnosis was performed in only 30 survivors. b Best value during the first 2 days. c OI related to the best PaO 2. d p e p Results are means SD. OI [(mean airway pressure FiO 2 )/PaO 2 ] 100; ECMO extracorporeal membrane oxygenation.

5 254 JAILLARD ET AL Ann Thorac Surg OUTCOME OF CONGENITAL DIAPHRAGMATIC HERNIA 2003;75:250 6 risk CDH [17 19]. In our institution, survival rates at 2 months increased from 33% between 1985 and 1990 [20] to 67% between 1990 and This is less than the 82% overall survival observed in western Canada [21] during the same period of time and in a population with similar rates of prenatal diagnosis (46%), number of patients born at the ECMO center (24.2%), and requirement for ECMO (30%). The main difference, however, was in the number of deaths within 24 hours of life before ECMO or surgery in infants who had obviously a very severe respiratory failure. This population represented 27% of our cohort compared with 13% in the Canadian study. The hidden postnatal mortality [1] may be higher in western Canada given the low population density and the great distances between level III NICUs compared with our area, which is densely populated with smaller distances between the units. From 1990 to 1998, one death only was reported outside our ECMO center (personal data). Deaths after the neonatal period are rarely mentioned in the literature. Boloker and asociates [22], in a cohort of 120 infants with CDH, reported two deaths at 4 and 7 months in infants with oxygen dependency. In our group of patients, apart from late deaths in infants with chronic lung disease, deaths from iatrogenic complications of surgery were noticeable and were observed in infants who required multiple interventions. Obviously, children who died after the neonatal period experienced a lot of medical complications and a very poor quality of life. Our follow-up study highlights that significant longterm morbidity exists in CDH infants. Half of the surviving infants presented adverse pulmonary, gastrointestinal, nutritional, or musculoskeletal outcome at 2 years. Not surprisingly, the need for ECMO was predictive of more significant morbidity. These results are consistent with recent reported experiences from the multidisciplinary follow-up team of the Boston Children s Hospital [4, 6]. The earlier studies reported by Van Meurs and associates [10], then later by d Agostino and associates [7], on the long-term respiratory outcome in neonates treated by ECMO showed, respectively, a 67% and 63% chronic lung disease rate. The authors found that diagnosis of CDH further increases the risk of chronic lung disease in infants treated by ECMO. More recently, Muratore and associates [4] have shown that the need for ECMO and the presence of a patch repair are both predictive of more significant pulmonary morbidity, but that non-ecmo CDH survivors also require frequent attention to pulmonary issues beyond the neonatal period. Furthermore, obstructive airway disease was found in about 25% of CDH infants at 5 years of age. Our data are in accordance with these results [4, 10] and support the findings that the rate of chronic lung disease was higher when patch repair was required. Chronic lung disease in CDH appears mainly related to pulmonary hypoplasia [23] and to lung damage due to mechanical ventilation [24]. Supporting this, our group of infants with chronic lung disease had higher oxygenation index during the first 2 days of life. Nutritional morbidity has been more recently described in this population [6, 25]. It seems, however, to have been highly underestimated, and in our cohort, nearly 20% of our patients and 40% of the ECMO survivors experienced growth retardation with a weight less than the fifth percentile at 2 years of age. The pathophysiology of this growth retardation is complex, including catabolic stress in the neonatal period, oral aversion, GER, and persistant pulmonary morbidity [6]. The management of these patients is difficult, and there is no overall agreement in the literature. In his cohort, Muratore and associates [6] found that 56% of the CDH patients was below the 25th percentile for height and weight during the first year of life and one-third of the population required monthly visits to the multidisciplinary clinic for day-to-day management of growth and nutritional issues. Thirty-three percent of the patients required a gastrostomy tube, which is, much more than our 7% of patients. We were very restrictive to perform gastrostomy, as this generally increases oral aversion. However, this policy needs to be more carefully evaluated and counterbalanced with new hypotheses concerning maturation of the sucking-swallowing reflex [26]. Clinical evaluation by speech therapist revealed a hypersensibility of the oral zone and of the nauseous reflex, suggesting significant oral dysfunction. Whether early oral rehabilitation could prevent such oral problems remains speculative, but prevention with feeding protocols inspired by those recently described for preterm babies [27] should be discussed. GER plays a major role in the appearance of nutritional morbidity. In previous series, its incidence ranges from 12% to 69% in CDH infants [5, 28]. Obviously, the incidence of GER depends on the diagnostic methods. In some studies, systematic ph probe and acid clearance were performed [28]. In other studies, only symptomatic GER were recorded. Nagaya and associates [5] explained GER in CDH infants by slow pulmonary expansion of the affected side with a mediastinal shift, increase in intraabdominal pressure, and malposition of the stomach. An oversimplification of GER pathophysiology is based on the utero changes associated with the diaphragmatic defect. Mass effect created by the herniated viscera into the thorax is presumed to give an obstruction of the distal esophagus [29]. Stolar and associates [28] also reported serious anatomic and functional abnormalities of the esophagus observed on plain chest roentgenogram as a mediastinal mass. Contrast studies may identify the mediastinal anomalies as ectatic esophagus. Low gastric emptying and gut dysmotility increase the nutritional problem, and may require prolonged enteral tube feeding for the most unfavorable cases [3, 30]. As previously described [3, 7], we found that GER was more frequent in CDH infants who required ECMO. Moreover, 79% of the severe GER in CDH survivors were found in infants treated with a prosthetic patch. Most of them had either a large diaphragmatic defect or diaphragmatic agenesis. Accordingly, during recent surgical repair, anatomical findings urge us to propose antireflux surgery in these forms. The principle consists of esophagus fixation on the pillar of the healthy diaphragm (the other pillar is fragile or used

6 Ann Thorac Surg JAILLARD ET AL 2003;75:250 6 OUTCOME OF CONGENITAL DIAPHRAGMATIC HERNIA 255 for prosthetic patch fixing) to prevent the lower esophagus from sliding [5]. Then, we choose to perform a hemi-nissen (Thal fundoplication), because the gastric fundus is abnormal and too small to be wrapped circumferentially around the esophagus. Although this added surgical procedure seems to reduce symptomatic GER during the postoperative course, long-term results are presently unknown. Orthopedics anomalies such pectus deformities and scoliosis were also found in CDH infants [30]. Only two cases of scoliosis were observed in our population. These two infants had associated GER and growth failure, which increased the difficulties in management. It is likely that other orthopedics anomalies may occur later with development. As suggested by Lund and associates [30], scoliosis or pectus deformities may be related to diaphragmatic tension when closing hernia defect. Most of our CDH infants (45/51) were found functionally normal on motor testing at 2 years of age, and ECMO did not alter the neurologic outcome. Our rate of cerebral palsy (CP) (4%) was in accordance with those described by Graziani and associates (9%) [31] or Glas and associates (5%) [32] in two cohorts of infants treated by ECMO. Some studies have suggested that infants with an initial diagnosis of CDH requiring ECMO presented poor neurodevelopmental outcome [3, 8], but follow-up was less than 2 years of age. Lund and associates [30] noted that motor delays improve with age, and for Graziani and associates [31], early delay in motor skills noted in infants with CDH was not predictive of cognitive development at school age. Follow-up is still in progress to assess school performances and quality of life at a later age in this cohort. We were concerned by the absence of hearing loss in our group of patients. A striking high rate of hearing dysfunction was reported in CDH infants, whether treated or not by ECMO [9, 34]. Prolonged use of pancuronium [35] as well as diuretics in infants with chronic lung disease [9] have been mentioned as possible risk factors. Both of these medications are rarely used in our unit, and this could explain at least in part the lack of hearing disorders in our cohort. However, the progressive nature of the loss in the ECMO survivors [36] requires a long-term follow-up to precisely appreciate the whole hearing ability. The most striking feature of our results was the occurrence of associated problems in nearly 8% of our patients. In all of the cases, management was very complex, with intricacy between oral aversion, GER, growth failure, chronic lung disease, and developmental delay, associated with an increase parental stress. This has been underestimated because of the lack of coordinated follow-up programs in most of the cohorts studied. As already mentioned by Muratore and associates [6], this leads to fragmented and inefficient care of complex issues by community pediatricians who are often unfamiliar with these problems. The key for optimal care and management of infants with CDH probably lies in the development of multidisciplinary follow-up programs, which could also be allowed to evaluate management protocols. In conclusion, CDH infants are at risk of multiple medical problems whose management remains complex and unsolved. Oral aversion is probably one of the most difficult issues to prevent at present and requires specific evaluation. Late deaths can occur because of persistent pulmonary hypertension or iatrogenic complications. Although both nutritional and respiratory problems tend to improve with age, long-term follow-up by a multidisciplinary team is still required in CDH infants survivors to determine through adolescence and early adulthood the need for additional services and the health-related quality of life. References 1. Skari H, Blornland K, Haugen G, Egeland T, Emblen R. Congenital diaphragmatic hernia: a meta-analysis of mortality factors. J Pediatr Surg 2000;35: Beresford MW, Shaw NJ. Outcome of congenital diaphragmatic hernia. Pediatr Pulmonol 2000;30: Bernbaum J, Schwartz IP, Gerdes M, D Agostino JA, Coburn CE, Polin RA. Survivors of extracorporeal membrane oxygenation at 1 year of age: the relationship of primary diagnosis with health and neurodevelopmental sequelae. Pediatrics 1995;96: Muratore CS, Kharasch V, Lund DP, et al. Pulmonary morbidity in 100 survivors of congenital diaphragmatic hernia monitored in a multidisciplinary clinic. J Ped Surg 2001;36: Nagaya M, Akatsuka H, Kato J. Gastroesophageal reflux occurring after repair of congenital diaphragmatic hernia. J Pediatr Surg 1994;29: Muratore CS, Utter S, Jaksic T, Lund DP, Wilson JM. Nutritional morbidity in survivors of congenital diaphragmatic hernia. J Pediatr Surg 2001;36: D Agostino JA, Bernbaum JC, Gerdes M, et al. Outcome for infants with congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation: the first year. J Pediatr Surg 1995;30: McGahren ED, Mallik K, Rodgers BM. Neurological outcome is diminished in survivors of congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation. J Pediatr Surg 1997;32: Rasheed A, Tindall S, Cueny DL, Klein MD, Delaney-Black V. Neurodevelopmental outcome after congenital diaphragmatic hernia: extracorporeal membrane oxygenation before and after surgery. J Pediatr Surg 2001;36: Van Meurs KP, Newman KD, Anderson KD, Short BL. Effect of extracorporeal membrane oxygenation on survival of infants with congenital diaphragmatic hernia. J Pediatr 1990; 117: Sempé M. Study of growth from birth to 18 months. Arch Fr Pediatr 1977;34: Touwen BCL. Examination of the child with minor neurological dysfunction. Clinics in developmental medicine. London: SIMP/Heinemann, 1979 no. 71:. 13. Amiel-Tison C, Grenier A. Evaluation neurologique du nouveau-né et du nourisson. Paris: Masson, Fawer CL, Calame A. Assessment of neurodevelopmental outcome. In: Levene MI, Bennett MJ, Punt J, eds. Fetal and neonatal neurology and neurosurgery. Edinburgh: Churchill Livingstone, 1988: Hagberg B, Hagberg G, Olow I. The changing panorama of cerebral palsy in Sweden II. Analysis of various syndromes. Acta Paed Scand 1975;64: Brunet-Lezine I. Le developpement psychologique de la première enfance. Paris: PUF, West KW, Bengston K, Rescorla FJ, Engle WA, Grosfeld JL.

7 256 JAILLARD ET AL Ann Thorac Surg OUTCOME OF CONGENITAL DIAPHRAGMATIC HERNIA 2003;75:250 6 Delayed surgical repair and ECMO improves survival in congenital diaphragmatic hernia. Ann Surg 1992;216: vd Staak FH, de Haan AF, Geven WB, Doesburg WH, Festen C. Improving survival for patients with high-risk congenital diaphragmatic hernia by using extracorporeal membrane oxygenation. J Pediatr Surg 1995;30: Frenckner B, Ehren H, Granholm T, Linden V, Palmer K. Improved results in patients who have congenital diaphragmatic hernia using preoperative stabilization, extracorporeal membrane oxygenation, and delayed surgery. J Ped Surg 1997;32: Dubois A, Storme L, Jaillard S, et al. Congenital hernia of the diaphragm: a retrospective study of 123 cases recorded in the Neonatal Medicine Department, URHC in Lille between 1985 and Arch Pediatr 2000;7: Sreenan C, Etches P, Osiovich H. The western Canadian experience with congenital diaphragmatic hernia: perinatal factors predictive of extracorporeal membrane oxygenation and death. Pediatr Surg Int 2001;17: Boloker J, Bateman DA, Wung JT, Stolar CJH. Congenital diaphragmatic hernia in 120 infants treated consecutively with permissive hypercapnea/spontaneous respiration/ elective repair. J Pediatr Surg 2000;37: Nguyen L, Guttman FM, De Chadarévian JP, et al. The mortality of congenital diaphragmatic hernia: is total pulmonary mass inadequate, no matter what? Ann Surg 1983;198: Miguet D, Claris O, Lapillone A, Bakr A, Chappuis J-P, Salle BL. Preoperative stabilization using high-frequency oscillatory ventilation in the management of congenital diaphragmatic hernia. Crit Care Med 1988;22(Suppl):S Van Meurs KP, Robbins ST, Reed VL, et al. Congenital diaphragmatic hernia: long-term outcome in neonates treated with extracorporeal membrane oxygenation. J Pediatr 1993;122: Ramsay M, Gisel EG. Neonatal sucking and maternal feeding practices. Dev Med Child Neurol 1996;38: Gail C, Gartside PS, Greenberg JM, Wright Lott J. A feeding protocol for healthy preterm infants that shortens time to oral feeding. J Pediatr 2001;139: Stolar CJH, Levy JP, Dillon PW, Reyes C, Belamarich P, Berdon WE. Anatomic and functional abnormalities of the esophagus in infants surviving. Am J Surg 1990;159: Muratore CS, Wilson JM. Congenital diaphragmatic hernia: where are we and where do we go from here? Seminar Perinatol 2000;24: Lund DP, Mitchell J, Kharasch V, Quigley S, Kuehn M, Wilson JM. Congenital diaphragmatic hernia: the hidden morbidity. J Pediatr Surg 1994;29: Graziani LJ, Gringlas M, Baumgart S. Cerebrovascular complications and neurodevelopmental sequelae of neonatal ECMO. Clin Perinatol 1997;24: Glass P, Wagner AE, Papero PH, et al. Neurodevelopmental status at age five years of neonates treated with extracorporeal membrane oxygenation. J Pediatr 1995;127: Miceli PJ, Goeke-Morey MC, Whitman TL, Kolberg KS, Miller-Loncar C, White RD. Brief report: birth status, medical complications, and social environment: individual differences in development of preterm, very low birth weight infants. J Pediatr Psychol 2000;25: Rasheed A, Robertson CMT, Cheung P, et al. High prevalence of sensorineural hearing loss among survivors of neonatal congenital diaphragmatic hernia. Am J Otol 1998; 19: Cheung PY, Tyebkhan JM, Peliowski A, Ainsworth W, Robertson CMT. Prolonged use of pancuronium bromide and sensorineural hearing loss in childhood survivors of congenital diaphragmatic hernia. J Pediatr 1999;135: Lasky RE, Wiorek L, Becker TR. Hearing loss in survivors of neonatal extracorporeal membrane oxygenation (ECMO) therapy and high-frequency oscillatory (HFO) therapy. J Am Acad Audiol 1998;9:47 58.