Since the 1980s delayed surgery has become an accepted method for the treatment of CDH after Sakai et al. [9] reported that early surgical repair worsened the cardiopulmonary function. Although improved survival of up to 90% has been reported in some centers using delayed surgery [1–3], this has not been the experience of other groups [5, 15]. Delayed surgery allows for stabilization of CDH newborns with pulmonary hypoplasia and associated pulmonary hypertension and also avoids surgery in newborns that are most likely to die. Reickert et al. [2] and Boloker et al. [8] reported that with the mean age at repair of 8.9 and 4.5 days, respectively, survival improved without increasing morbidity with less demand for ECMO. The optimal timing of surgery is still not universally accepted. Recently, Rozmiarek et al. [16] reported that cardiac defects, renal failure and the initial blood gases are the significant factors that influence survival and not the timing of surgery. Therefore to improve the outcome of CDH newborns, timing of surgery should be based on optimizing these clinical parameters as opposed to a specific time period. This conclusion supports our policy to delay surgery until the newborn is hemodynamically stable, the acidosis corrected and the oxygenation satisfactory and, furthermore, explains why 11/45 (24%) newborns were never taken to surgery. In this series of delayed surgery, the survival rate of 67% in newborns with isolated CDH compares favorably with the results from other institutions [2, 8, 10, 16–18].
Twelve (86%) early deaths (before discharge) were from pulmonary hypoplasia and associated pulmonary hypertension and two from lethal complex anomalies. Thus, pulmonary hypoplasia is the major determinant of survival and also explains why, despite all the new therapies available to treat pulmonary hypotension, the mortality rate with CDH has not changed [19]. Seven of 13 newborns (54%) died despite the use of HFOV. These were very sick patients with overwhelming pulmonary hypoplasia and associated hypertension. The role of HFOV in CDH remains uncertain because of conflicting results [4, 20, 21]. Inhaled NO was given to only two patients and the benefit in the management of CDH in this series is uncertain. Inhaled NO for CDH newborns has been associated with good outcome in some centers, but other groups have had disappointing results [5, 19, 20]. Exogenous surfactant use has had satisfactory reports from various institutions but is not accepted worldwide [6, 8, 22]. The role of these therapeutic agents is still uncertain and prospective controlled trials are required for clarification. Reports of combination of different modalities of treatment have shown a good survival rate from 76 to 96% [8, 23, 24].
Sepsis in newborns with CDH is rarely reported. Staphylococci are a common cause of hospital-acquired infections in many NICUs [25]. Al-Hathal et al. [1] reported coagulase-negative staphylococci as the causative organism in approximately 82% of CDH patients with proven sepsis. In this series, the same organism was the cause of sepsis in 24% of newborns with CDH. The risk factors for staphylococcal infection in newborns in NICU include: birth weight; illness; presence of indwelling catheters such as central venous catheter (CVC), chest tubes and endotracheal intubation; and the length of hospital stay. The risk has been shown to increase if the CVC is used to administer parenteral nutrition, especially lipids [26]. Although perioperative course of antibiotics is given to CDH patients, careful handling of patients is necessary to minimize the risk of sepsis. Strict use of sterile techniques with procedures such as insertion of CVCs, insertion of chest tubes, endotracheal intubations and suctioning and hand washing may reduce the incidence of sepsis in CDH patients in the NICU.
This study reveals ongoing morbidity among 27/31 survivors (87%) including adverse pulmonary, nutritional and growth, neuro-developmental and musculoskeletal outcome and/or required further surgical management. Ongoing problems in CDH survivors have been reported as 12%–61% and depend on the duration of follow-up [10–14, 27].
Pulmonary problems are a major source of morbidity in CDH survivors. The problems may be due to a combination of factors: the degree of pulmonary hypoplasia; iatrogenic barotrauma; oxygen toxicity; recurrent pneumonias; chronic lung disease; hyperactive airway disease; scoliosis; pectus excavatum; and chronic aspiration from GER. Approximately 45% of our long-term survivors had chronic respiratory symptoms such as hyperactive airway disease and required inhaled bronchodilators and/or steroids. Due to ineffective breathing, CDH children are admitted frequently to hospital with recurrent pneumonias and/or hyperactive airway disease [20, 28], and this occurred in three children in this series. Stefanutti et al. [28] have reported that the presence of residual lung hypoplasia in several long-term CDH survivors, and the initial ventilatory management may contribute to pulmonary morbidity. Pulmonary morbidity may continue in some children for many years after repair and in this series resulted in two late deaths. Muratore et al. [14] reported that 16% of their survivors required supplemental oxygen at discharge, but this was not our experience.
Nutritional and growth problems are particularly common in the first year of life of CDH infants [11, 27]. Fourteen of 31 survivors (45%) had nutritional and growth problems. Seven children (23%) had a weight below the 5th percentile, which is within the range of 20–40% reported by Jaillard et al. [13]. Persistent gastrointestinal, respiratory symptoms or food aversion may contribute to growth failure in CDH survivors [12, 13, 20, 29]. Two of seven children (29%) with FTT were having chronic respiratory problems but there was no obvious cause in four children. The last child with GER gained weight after fundoplication. The incidence of GER in CDH survivors ranges from 12 to 69% [29, 30]. Seven newborns developed GER soon after the repair of CDH but only one required surgery. Eight of 31 survivors (26%) had GER with 2/8 (25%) needing fundoplication. Therefore most CDH survivors with GER can be managed by anti-reflux measures and medication. Factors that contribute to GER include weak diaphragmatic crura, hiatus hernia, increased intra-abdominal pressure, ectasia of the esophagus shortening of intra-abdominal esophagus, and disruption of the angle of His [1]. Jaillard et al. [13] and Muratore et al. [27] reported food aversion in 7 and 33% of their patients, respectively, with gastrostomy being required for feeding. In this series, one newborn required a feeding gastrostomy to increase calorie intake whilst undergoing fundoplication for GER but not for food aversion. Food aversion is not a problem in this series.
Neuro-developmental outcome is a concern in all CDH children, especially after the use of ECMO [20]. Nearly a quarter of the infants in this series had neuro-developmental problems of speech delay, developmental delay, and hearing loss. Jaillard et al. [13] found neurological examination to be normal at 2 years of age in 45/51 CDH children (88%), however 6 had cerebral palsy or developmental delay irrespective of the use of ECMO or not. McGahren et al. [31], however, reported significant evidence of neurological delay in 67% of CDH patients who required ECMO compared with 24% in a non-ECMO group. Contributory factors to developmental delay include: a primary neurological disorder; the result of the severity of CHD; the degree and duration of acidosis and hypoxia; and the type of treatment particularly ECMO. In this series four children had global developmental delay in addition to speech and or hearing loss. Follow-up studies have revealed hearing loss in 20–40% of CDH survivors [32, 33]. In this series 2/31 children (6%) have hearing loss and wear hearing aids. Because of the lack of coordinated follow-up, it is possible that not all patients with hearing loss have been diagnosed. Rasheed et al. [33] found hearing loss in six of six survivors (100%) stabilized with ECMO compared to two of nine (22%) of those needing ECMO postoperatively [33]. The risk factors for hearing loss in CDH children include the use of ototoxic medications such as aminoglycosides and diuretics, HFOV, ECMO, hyperventilation and pancuronium, hypoxia, prolonged mechanical ventilation, family history and other factors [10, 11,32]. Regular hearing screening of CDH survivors is necessary to pick up patients with sensorineural hearing loss.
Pectus and scoliosis are chest wall deformities that may occur in CDH children and persist into adulthood [11, 12]. Falconer et al. [34] reported an incidence of 21 and 11% of pectus excavatum and scoliosis, respectively, in survivors of CDH. In this series, three children with pectus excavatum have been followed up in the clinic with none requiring surgical treatment. A child with scoliosis wears a thoracic brace. These chest wall deformities may be related to diaphragmatic tension at closure of the defect or to the smaller thoracic cavity and smaller lung in the affected side [11, 12].
In this series diaphragmatic hernia recurrence rate is 12%, which is within the reported range of 5–50% [11, 35]. Although prosthetic patches were used for primary closure in 5/34 newborns (15%), none recurred. However, repair of a recurrence using prosthetic patch failed. In centers where prosthetic patches and ECMO are used routinely, recurrence rate is on the increase [35]. There are concerns about patch durability over the long term, and we believe that primary repair or the use of muscle flaps such as latissimus dorsi, split abdominal wall muscle flaps or pedicle flap of abdominal muscle may be undertaken whenever possible [36]. Patch repair should be reserved for the severe CDH defect and agenesis. Although our patients with recurrent CDH were symptomatic, some recurrences may be asymptomatic and may be found on routine chest X-rays. Therefore serial X-ray examination of the chest, especially those with patch repair, should be recommended [11, 36].
Survivors of CDH may require surgery for small bowel obstruction [11]. Seven children (23%) presented with adhesive small bowel obstruction, three of the seven (43%) requiring laparotomy. Other surgical procedures included orchiopexy, inguinal herniotomy and Spigelian hernia repair.
Since this study is a retrospective review of medical records, it has its flaws. These include lack of coordinated follow-up and inadequate charting details. Furthermore, our patients may have been treated at other hospitals. Autopsies were not performed and so the cause of mortality was based on the clinical findings.
In conclusion, delayed surgery is a satisfactory method of management for isolated CDH newborns with an overall survival rate of 67%. The most common cause of mortality is severe pulmonary hypoplasia. Long-term survivors have significant continuing medical and surgical problems and late deaths can occur from pulmonary complications. Coordinated multidisciplinary follow-up of CDH survivors in our hospital is essential to detect morbidity early and to improve the long-term outcome.