Neonatal tracheal changes following in utero fetoscopic balloon tracheal occlusion in severe congenital diaphragmatic hernia

Objective

To report postnatal tracheal changes after in utero fetoscopic balloon tracheal occlusion in severe congenital diaphragmatic hernia (CDH).

Design

Case series.

Setting

Tertiary care center, CDH National Reference Center.

Patients

Seven consecutive newborn infants with severe CDH who underwent fetoscopic balloon tracheal occlusion.

Interventions

Flexible laryngotracheoscopy and histological aspect observed at necropsy in 2 nonsurvivors.

Results

All infants displayed elongation and relaxation of the posterior tracheal wall, intermittently obstructing the lumen during tidal breathing. Whereas the cartilage displayed adequate rigidity, the pars membranacea appeared both flaccid and loose. Tracheal widening (tracheomegaly) was seen in all cases. Histology (n = 2) pointed to structural modifications throughout the pars membranacea, that is, loss of epithelial folding and of longitudinal elastic network and focal muscular disruption. The cartilage displayed no visible or histologic changes. The above tracheal changes were not symptomatic, except for a barking cough during increased respiratory efforts.

Conclusions

Tracheal widening and intermittent collapse of the posterior wall of the trachea during tidal breathing was found in 7 consecutive newborns who underwent fetoscopic balloon tracheal occlusion, causing mild clinical symptoms. Endoscopic tracheal assessment might provide useful information in children with CDH, in particular, when they underwent in utero fetoscopic balloon tracheal occlusion.     

Survival of severe congenital diaphragmatic hernia has morbid consequences

Background/Purpose

Fetal tracheal occlusion (TO) was developed in an attempt to enhance prenatal lung growth and improve survival in fetuses with severe congenital diaphragmatic hernia (CDH). We conducted a randomized, controlled clinical trial in 24 fetuses with severe left CDH (liver herniated into the thorax and low lung-to-head ratio) to compare survival after endoscopic fetal TO vs standard perinatal care (control) and prospectively followed up the 16 survivors (9 control, 7 TO) to compare neurodevelopmental, respiratory, surgical, growth, and nutritional outcomes.

Methods

At 1 and 2 years old, subjects underwent evaluation consisting of medical and neurological history and physical, developmental testing, nutritional assessment, oxygen saturation and pulmonary function testing, chest radiograph, and echocardiogram. Growth and developmental measures were corrected for prematurity. Data were analyzed by Mann-Whitney rank sum test, Fisher's Exact test, and logistic and linear regression.

Results

Infants with TO were significantly more premature at birth (control vs TO, 37.4 ± 1.0 vs 31.1 ± 1.7 weeks; P < .01). Growth failure (z score for weight <2 SDs below mean) was severe in both groups at 1 year of age (control vs TO, 56% vs 86%; P = .31). There was considerable catch-up growth by age 2 years (growth failure: control vs TO, 22% vs 33%; P = .19). There were no differences in other growth parameters. There were also no differences in neurodevelopmental outcome at 1 and 2 years. Supplemental oxygen at hospital discharge was a significant predictor of worse neurodevelopmental outcome at 1 and 2 years old (P = .05 and P = .02, respectively). Hearing loss requiring amplification has been diagnosed in 44% of the group (control vs TO, 44% vs 43%; P = 1.0).

Conclusions

In this group of infants with severe CDH, there were no differences in outcome at 2 years old despite significant prematurity in the TO group. Oxygen supplementation at hospital discharge identified the most vulnerable group with respect to neurodevelopmental outcome, but all infants had significant growth failure, and hearing impairment is a substantial problem in this population. Severe CDH carries significant risk of chronic morbidity.     

Fetal tracheal occlusion for severe congenital diaphragmatic hernia in humans: a morphometric study of lung parenchyma and muscularization of pulmonary arterioles

Objective

The aim of this study is to examine structure of lung parenchyma (Pp) and muscularization of pulmonary arterioles (PAs) in human fetuses that underwent tracheal occlusion (TO) therapy for severe congenital diaphragmatic hernia (CDH).

Material

Fifteen fetuses underwent TO, with 5 survivors (Am J Obstet Gynecol. 2000:183;1059-1066). Paraffin-embedded lung specimens from 7 of 10 nonsurvivors (CDH-TO) and 6 age-matched fetuses (CDH) were available for morphometric analysis, which included measurements of point fraction of lung Pp and surface density. The PAs were categorized according to external diameter (<70 μm and 70 ≤ 140 μm). Percent medial wall thickness (%MWT) was calculated by dividing raw measurements of MWT by external diameter.

Results

Gestational age at TO was 27.6 ± 0.9 weeks with a mean duration of TO of 32.6 ± 6.8 days. Gestational age at delivery (CDH-TO 31.9 ± 0.9 vs CDH 35.4 ± 1.8 weeks; P = .18) and postnatal survival time (CDH-TO 20.5 ± 6.0 vs CDH 18.6 ± 7.8 days; P = .85) were not significantly different between groups. Tracheal occlusion significantly increased the lung-to-body weight ratio (CDH-TO 13.0 ± 2.2 vs CDH 6.6 ± 0.9; P = .02). Tracheal occlusion tended to decrease right-lung Pp (CDH-TO 54.6% ± 2.6% vs CDH 65.7% ± 5.9%; P = .05), whereas left-lung Pp was not different between groups (CDH-TO 63.0% ± 3.5% vs CDH 66.7% ± 4.1%; P = .51). Surface density of airspaces was not different between groups in either left (CDH-TO 171.3 ± 16.1 cm⁻¹ vs CDH 151.1 ± 8.1 cm⁻¹; P = .34) or right (CDH-TO 172.0 ± 10.6 cm⁻¹ vs CDH 160.8 ± 3.6 cm⁻¹; P = .33) lungs. The %MWT in small and large PA was similar between groups.

Conclusions

Open prenatal TO in human fetuses increased lung growth, as evidenced by an increase in lung weight, but did not improve parenchymal structure or muscularization of PAs.     

Dynamic tracheal occlusion improves lung morphometrics and function in the fetal lamb model of congenital diaphragmatic hernia

Background

Congenital diaphragmatic hernia (CDH) is associated with significant neonatal morbidity and mortality. Although prenatal complete tracheal occlusion (cTO) causes hypoplastic CDH lungs to enlarge, improved lung function has not been demonstrated. Furthermore, cTO interferes with the dynamic pressure change and fluid flow associated with fetal breathing.

Purpose

The purpose of the study was to assess a novel dynamic tracheal occlusion (dTO) device that preserves pressure changes and fluid flow.

Methods

In this pilot study, CDH was created in fetal lambs at 65 days of gestational age (GA). At 110 days GA, a cTO device (n = 3) or a dTO device (n = 4) was placed in the fetal trachea. At 135 days GA, lambs were delivered and resuscitated. Unoperated lamb co-twins (n = 5), sham thoracotomy lambs (n = 2), and untreated CDH lambs (n = 3) served as controls.

Results

Tracheal opening pressure, lung volume, lung fluid total protein, and phospholipid were significantly higher in the cTO group than in the dTO and unoperated control groups. Maximal oxygenation and lung compliance were significantly lower in the cTO group when compared with the unoperated control and dTO groups.

Conclusion

Preliminary results suggest that in the fetal lamb CDH model, dTO restores normal lung morphometrics and function, whereas cTO leads to enlarged but less functional lungs.     

Effect of epidermal growth factor on pulmonary hypoplasia in experimental diaphragmatic hernia

Background/purpose

Currently, tracheal occlusion (TO) is a potent stimulus for fetal lung growth but also a rather invasive and high-risk procedure. The aim of this study was to investigate a new and much less invasive therapeutic strategy, namely the maternal intraperitoneal administration of epidermal growth factor (EGF) and its effect on pulmonary hypoplasia in the nitrofen-induced congenital diaphragmatic hernia (CDH) rat model, especially its effect on type II pneumocytes.

Methods

CDH was induced by maternal administration of a single oral dose (100 mg) of nitrofen on day 8.5 of pregnancy. Four groups of pregnant rats were designed on day 18.5: normal control (n = 4), CDH (n = 4), CDH plus Dex (n = 4), CDH plus EGF (n = 8). All fetuses were delivered by cesarean section on day 21. Accordingly, there were 4 groups of fetuses: normal controls (n = 33), nitrofen-induced CDH (n = 19), CDH plus Dex treatment (n = 15), and CDH plus EGF treatment (n = 24). Lung tissue weight (LW) and body weight (BW) of each fetus were recorded, lung histologic and morphometric evaluations were performed, and image analysis was combined after lung processing. Transmission electron microscopy was used for ultrastructural observation, especially type II pneumocytes.

Results

CDH was observed in 58 of the 94 rat fetuses (61.7%). Lw/Bw of CDH group was significantly lower than those of Dex and EGF (P < .05). The lungs of CDH fetuses showed marked hypoplasia, in contrast to improved mesenchymal differentiation in that of Dex and EGF fetuses. Statistical differences of these morphologic parameters (RAC, MTBD, interstitial%, and alveoli%) were found (P < .05). As to ultrastructural features, type II cells of CDH lungs had few if any lamellar bodies and cytoplasmic organelles, and showed evidence of abundant glycogen granules. The sparse type II cells also showed cytoplasmic degenerative changes. By contrast, type II cells of EGF lungs showed numerous mitochondria, abundant lamellar bodies (surfactant) and deficiency of glycogen granules, and displayed prominent microvillous projections and pitlike depressions. The density of type II pneumocyte were 65 ± 4.5, 31 ± 3.1, and 8 ± 1.5 for EGF, Dex, and CDH, respectively (EGF v Dex, P < .05; EGF v CDH, P < 0.01).

Conclusions

Compared with TO, prenatal EGF administration as a much less-invasive therapeutic strategy had shown marked improvement in pulmonary hypoplasia and promotion of type II pneumocyte differentiation in the nitrofen-induced CDH rat model. Thus, EGF could improve the prognosis of CDH by means of promoting pulmonary hypoplasia and improving the surfactant deficiency, which suggested a potential role in the clinical treatment of CDH.     

Lung function in lambs with diaphragmatic hernia after reversible fetal tracheal occlusion

Background/Purpose

Short-duration resuscitation (≤4 hours) of lambs with diaphragmatic hernia treated in utero with tracheal occlusion have shown improved lung function compared with untreated diaphragmatic hernia. This may be a transient phenomenon in the treated diaphragmatic hernia lambs because of surfactant deficiency. Our objective was to analyze the effect of fetal tracheal occlusion with or without release of the occlusion 1 week before delivery on pulmonary function during a longer period of resuscitation (8 hours) in the diaphragmatic hernia lamb model.

Methods

Four groups were compared: diaphragmatic hernia (n = 5), diaphragmatic hernia and tracheal occlusion until delivery (n = 5), diaphragmatic hernia and tracheal occlusion with release of the occlusion 1 week before delivery (n = 5), and normal controls (n = 4).

Results

Despite persistently decreased surfactant levels, diaphragmatic hernia lambs treated with tracheal occlusion had normal-sized lungs with marked improvement in lung function and gas exchange over 8 hours when compared with untreated lambs with diaphragmatic hernia. Release of the tracheal occlusion 1 week before delivery added no benefit.

Conclusions

It appears that surfactant-independent mechanisms such as pulmonary growth and structural changes are of foremost importance in relating to improved compliance, oxygenation, and ventilation of diaphragmatic hernia lambs treated with tracheal occlusion.     

Expression of apoptosis-related genes after fetal tracheal occlusion in rabbits

Background/purpose

Late-gestation lung remodeling is associated with alveolar type II cell apoptosis early in the saccular stage (day 28 in fetal rabbits). Intrauterine tracheal occlusion (TO), a potent stimulus of fetal lung growth and maturation, significantly increases type II cell apoptosis. The aim of this study was to determine the effect of fetal TO on the spatiotemporal expression of key apoptosis-related signaling molecules.

Methods

Tracheal occlusion of fetal rabbits was performed at gestational day 25 (term, 31 days), and apoptotic gene expression was studied between days 26 and 28.

Results

At days 26 and 27, the protein levels of Fas and Fas-ligand (FasL) in lung lysates were similar in TO fetuses and sham-operated controls. At day 28, however, synchronous with the onset of TO-induced pulmonary distension and type II cell apoptosis, the FasL protein content was 8-fold higher in TO lungs compared with controls (P < .01), whereas Fas levels were comparable. In contrast, Bax and Bcl-2 protein levels were similar in TO and control fetuses at all time-points. TO significantly increased the cellular concentration of immunoreactive FasL in type II cells and bronchial epithelial Clara cells. Furthermore, bronchoalveolar lavage fluid (BAL) from TO fetuses at day 28 induced significantly more type II cell apoptosis in vitro compared with control BAL, an effect that was inhibited by neutralizing anti-FasL antibody.

Conclusions

Our findings show that TO results in time-specific increase of both cellular and soluble FasL in fetal lungs and implicate the Fas/FasL pathway as a pivotal autocrine and/or paracrine regulator of TO- induced type II cell apoptosis.     

Postnatal lung mechanics, lung composition, and surfactant synthesis after tracheal occlusion vs prenatal intrapulmonary instillation of perfluorocarbon in fetal rabbits

Background/Purpose

Fetal tracheal occlusion (TO) accelerates lung growth but decreases surfactant production. We have previously shown that instillation of perfluorooctylbromide (PFOB) into fetal rabbit lungs leads to lung growth similar to TO. This study compares neonatal lung mechanics and surfactant production after prenatal intrapulmonary PFOB instillation vs TO.

Methods

In each of 18 pregnant rabbits on gestational day 27, sets of 4 fetuses underwent either (1) intrapulmonary instillation of 1 mL PFOB, (2) TO, (3) instillation of 1 mL 0.9% NaCl (saline), and (4) hysteroamniotomy without fetal manipulation (control). Fetuses were born by cesarean delivery after 48 hours. Fetuses of 12 rabbits were mechanically ventilated for 15 minutes to evaluate lung compliance and airway resistance. Pulmonary surfactant protein B (SP-B) was quantified by immunohistochemistry in fetuses of the remaining 6 rabbits.

Results

Compliance was decreased in the TO group after cesarean delivery (0.33 ± 0.13 mL/cm H₂O) compared with PFOB (0.59 ± 0.12 mL/cm H₂O), saline (0.50 ± 0.12 mL/cm H₂O), and control (0.52 ± 0.10 mL/cm H₂O) fetuses. Mean fetal lung to body weight ratio was higher in TO and PFOB fetuses compared with saline and control. Higher water content and lower numbers of surfactant protein B-positive cells were found in the TO-treated fetuses.

Conclusions

Both prenatal intrapulmonary instillation of PFOB and TO accelerate lung growth, but TO is associated with decreased postnatal lung compliance, possibly influenced by decreased surfactant production and increased fluid retention. Conversely, instillation of PFOB preserved lung compliance and surfactant synthesis.     

Predictors of gastroesophageal reflux in neonates with congenital diaphragmatic hernia

Purpose

Gastroesophageal reflux (GER) is observed in 22% to 81% of neonates with congenital diaphragmatic hernia (CDH). The purpose of this study was to identify factors that may predict GER requiring fundoplication in neonates with CDH.

Methods

A retrospective chart review was performed on all neonates with CDH treated at our hospital from June 1997 to June 2005. Preoperative respiratory status, side of the CDH, and method of repair were assessed as predictors of GER and the need for fundoplication.

Results

Of the 42 patients with CDH, 3 died before intervention, leaving 39 patients eligible for study. All but 1 patient survived until discharge. Twenty-one (54%) developed GER of whom 9 (23%) required fundoplication. Although the side of the CDH was not a determinant of GER or the need for fundoplication, patch repair and the need for extracorporeal life support were determinants of both.

Conclusions

Gastroesophageal reflux is common among babies with CDH, although symptoms often resolve without surgical intervention. Infants with CDH defects requiring a patch repair and those requiring advanced physiologic support, especially extracorporeal life support, are likely to develop severe GER necessitating fundoplication. Early recognition and treatment of GER among high-risk patients may shorten hospital stay and minimize patient morbidity. Early fundoplication should be considered for those patients at the highest risk.     

Outcomes of multigestational pregnancies affected by congenital diaphragmatic hernia

Background/purpose

The prognosis for multiple vs singleton pregnancies affected by congenital diaphragmatic hernia (CDH) is not known. To improve the counseling of families with multiple gestation pregnancies complicated by CDH, we examined outcomes of a consecutive series of CDH cases occurring in multiple gestation pregnancy referrals.

Methods

Clinical characteristics and morbidity and mortality data were gathered for a consecutive series of infants with CDH from 16 multiple gestation pregnancies. Outcomes were compared to a cohort of 91 patients with CDH from singleton pregnancies. Multivariate regression was also used in an attempt to determine whether multiple gestation pregnancy was independently predictive of subsequent long-term adverse outcomes.

Results

Four pregnancies were lost to follow-up, and 1 underwent selective reduction. Overall mortality for live-born multiple gestation fetuses affected by CDH was 30% and was 8% for unaffected siblings. No pregnancy was concordant. Clinical features were not different between the case series and control infants, except median gestational age at delivery, which was significantly lower for the multigestational infants (34 [range, 32-36] vs 38 [range, 28-41] weeks) (P = .02). Long-term morbidity was comparable between cases and controls.

Conclusions

In terms of mortality, outcomes of multigestational pregnancies affected by CDH are no worse than for CDH pregnancies in general. Long-term risk may depend more on CDH severity rather than the presence of multiple fetuses.     

Rapidly polymerizing hydrogel prevents balloon dislodgement in a model of fetal tracheal occlusion

Background/purpose

This study examined whether an injectable hydrogel could buttress the balloon used in fetal tracheal occlusion, thus preventing its displacement.

Methods

Fetal lambs (n = 11) underwent tracheal occlusion through local delivery of a detachable silicone balloon and were divided in 2 groups: group I had no further manipulations, and group II received an intratracheal injection of a rapidly polymerizing hydrogel, cranially to the balloon. Near term, balloon placement was examined, the lung volume—to—body weight ratio (LV:BW) was determined, and tracheal histology was performed. Statistical analysis was by the Fisher’s Exact test, with significance set at P < .05.

Results

Complete tracheal occlusion was achieved in all fetuses intraoperatively. The rate of balloon dislodgement was significantly higher in group I (4 of 7, or 57.1%) than in group II (0 of 4). In group II, balloons were recovered in situ with a column of residual hydrogel reinforcing their cephalad position. Animals in which balloon occlusion was maintained had significantly higher LV:BW, with no evidence of tracheal damage.

Conclusions

Intratracheal delivery of a rapidly polymerizing hydrogel cephalad to detachable silicone balloons results in improved fetal tracheal occlusion, with no harmful effects to the trachea. This adjuvant principle may enhance minimally invasive balloon tracheal occlusion for treatment of severe fetal pulmonary hypoplasia.     

Tracheal innervation is abnormal in rats with experimental congenital diaphragmatic hernia

Background

Tracheobronchial motility influences lung development. Lung hypoplasia and lung sequelae accompany congenital diaphragmatic hernia (CDH) in which the vagus nerves and esophageal innervation are abnormal. As the vagus supplies tracheal innervation, this study tested the hypothesis that it might also be abnormal in rats with CDH.

Material and Methods

Intrinsic ganglia were counted and measured in whole mount acetylcholinesterase-stained tracheas from CDH and control E21 fetal rats. The relative surfaces occupied by neural structures were measured in tracheal sections immunostained for p75^NTR and PGP 9.5. PGP 9.5 protein and mRNA expression were determined. Mann-Whitney tests were used for comparisons between groups using P < .05 as significant.

Results

p75^NTR staining showed the neural crest origin of tracheal innervation. Scarce neural structures and smaller ganglia were found in CDH fetuses. PGP 9.5 protein expression was decreased in CDH fetuses, whereas PGP 9.5 mRNA levels were increased in comparison with controls.

Conclusions

Decreased density of neural structures and size of intramural ganglia, reduced expression of neural tissue and PGP 9.5 protein, and increased levels of PGP 9.5 mRNA reveal deficient tracheal innervation in rats with CDH. If similar anomalies exist in the human condition, they could contribute to explaining the pathogenesis of lung hypoplasia and bronchopulmonary sequelae.     

Current consequences of prenatal diagnosis of congenital diaphragmatic hernia

Background

Today, the diagnosis of congenital diaphragmatic hernia (CDH) can readily be made in the prenatal period during screening ultrasound examination. Patients ought to be referred to rule out associated anomalies, and in isolated cases, prognosis is poor when the liver is intrathoracic and the lung-to-head ratio (LHR) is less than 1. In these patients, prenatal intervention aiming to reverse pulmonary hypoplasia can be considered.

Methods

We present our current algorithm for counselling patients presenting with CDH. Patients with a poor prognosis are offered percutaneous fetal endoluminal tracheal occlusion (FETO) with a balloon, inserted at 26 to 28 weeks. We report on the evolution of technique and results in a consecutive homogeneous case series and compare outcome in cases with similar severity managed in the postnatal period.

Results

Within a period of 28 months, FETO was performed between 26 and 28 weeks in 24 fetuses with severe left-sided CDH. Under general (n = 5), epidural (n = 17) or local (n = 2) anesthesia, the balloon was successfully positioned at first surgery (23/24) with a mean operation time of 20 minutes (range, 3-60 minutes). There were no serious maternal complications or direct fetal adverse effects. In the first 2 weeks after FETO, LHR increased from 0.7 to 1.7. Premature prelabour rupture of the membrane (PPROM) occurred in 16.7% and 33.3% at 28 and 32 weeks or earlier, respectively. Gestational age at delivery was 33.5 weeks. Patency of airways was restored either in the prenatal (n = 12) or perinatal period (n = 12). Early (7 days) and late (28 days) survival, and survival at discharge were 75% (18/24), 58.3% (14/24) and 50% (12/24), respectively. Half of nonsurvivors (n = 6) died of pulmonary hypoplasia and hypertension, in combination with PPROM and preterm delivery (n = 4) and balloon dislodgement (n = 2), which coincided with a short tracheal occlusion (TO) period (12 days). In the other 6, TO period was comparable to that in the 12 survivors (47 vs 42 days, respectively). In that group of 6 babies, only 2 died of pulmonary problems. Late neonatal survival (28 days) was higher with prenatal vs perinatal balloon retrieval 83.3% vs 33.3% (P = .013). In a multicentre study validating the criteria, survival till discharge in 37 comparable cases was 9% (3/32) and 13% (5/37) of parents opted for termination.

Conclusion

Fetuses with isolated left-sided CDH, liver herniation, and LHR of less than 1 have a poor prognosis. Percutaneous FETO is minimally invasive and may improve the outcome in these highly selected cases. Airways can be restored before birth, allowing vaginal delivery and return to the referring tertiary unit and may improve survival rate. The procedure carries a risk for PPROM, although that may decrease with experience.     

Ex utero intrapartum treatment with extracorporeal membrane oxygenation for severe congenital diaphragmatic hernia

Purpose

The purpose of this study was to determine whether ex utero intrapartum treatment with extracorporeal membrane oxygenation (EXIT to ECMO) is a reasonable approach for managing patients antenatally diagnosed with severe congenital diaphragmatic hernia (CDH).

Methods

A 6-year retrospective review was performed on fetuses with severe CDH (liver herniation and a lung/head ratio <1.4, percentage of predicted lung volume <15, and/or congenital heart disease). Fourteen of the patients underwent EXIT with a trial of ventilation. Fetuses with poor preductal oxygen saturations despite mechanical ventilation received ECMO before their delivery. Maternal-fetal outcomes were analyzed.

Results

There were no maternal-reported complications. Three babies passed the ventilation trial and survived, but 2 of them required ECMO within 48 hours. The remaining 11 fetuses received ECMO before their delivery. Overall survival after EXIT-to-ECMO was 64%. At 1-year follow-up, all survivors had weaned off supplemental oxygen, but 57% required diuretics and/or bronchodilators.

Conclusion

This is the largest reported experience using EXIT to ECMO in the management of severe CDH. The EXIT-to-ECMO procedure is associated with favorable survival rates and acceptable pulmonary morbidity in fetuses expected to have a poor prognosis under conventional management.     

The hidden mortality of congenital diaphragmatic hernia: a 20-year review

Aims

The true mortality associated with congenital diaphragmatic hernia (CDH) is hidden because survival analyses do not include fetuses with CDH. A retrospective review of all postmortems (PMs) with a diagnosis of CDH over a 20-year period was carried out to highlight this hidden mortality and also measure the nature and number of associated anomalies.

Methods

Postmortem case record details were reviewed for the period January 1986 to December 2005. Data were collected on live birth, stillbirth, therapeutic abortion, and spontaneous abortion.

Results

There was a decline in the annual number of PMs during the period of the study. The median for the four 5-year intervals being 609 (570-657), 528 (488-565), 515 (413-537), and 373 (357-388). A total of 130 PMs were identified, which included a diagnosis of CDH; 97 (75%) were left sided, 22 (17%) were right sided, and 11 (8%) were bilateral. There were 69 live births, 46 therapeutic abortions, 10 stillbirths, and 5 intrauterine deaths; 22% were right sided/bilateral in the live and therapeutic abortion groups, whereas 53% were right sided/bilateral in the latter 2 groups. Of 130, 82 (63%) had major associated anomalies, and 50% of these had at least 1 further major anomaly. The commonest categories of anomalies were cardiac (30), gastrointestinal/abdominal wall defect (28), and neural tube defects (25).

Conclusions

The true incidence of CDH is considerably higher than that seen in neonatal surgical practice. The decline in number of PMs in our region will exacerbate the underestimation of the true incidence. There is a higher incidence of right-sided/bilateral hernias and more than one major anomaly in those who die in utero.     

Predicting perinatal outcome in isolated congenital diaphragmatic hernia using fetal pulmonary artery diameters

Objective

The aim of the study was to evaluate the potential of fetal pulmonary artery (PA) diameters to predict perinatal death and pulmonary arterial hypertension (PAH) in congenital diaphragmatic hernia (CDH).

Study Design

In this prospective observational study, observed PA (main, right, and left) diameters were measured at the level of the 3 vessels in 21 fetuses with isolated CDH and in 85 controls at 22 to 36 weeks. The observed/expected (o/e) diameters of the main, contralateral, and ipsilateral PAs were calculated by comparing these measurements with reference values obtained in our previous study and correlated with perinatal death and postnatal PAH.

Results

The o/e PA diameters were significantly reduced in fetuses with CDH compared to controls (P < .001) and in fetuses with CDH who died (P < .050). However, there was no significant association between PA diameters and PAH (P ≥ .050).

Conclusions

The PA diameters might be useful to predict perinatal death in isolated CDH but not postnatal PAH, suggesting that PA diameters are probably related to the severity of pulmonary hypoplasia.     

Right congenital diaphragmatic hernia: Prenatal assessment and outcome

Purpose

To understand the natural history of right congenital diaphragmatic hernia (CDH), the authors retrospectively reviewed 27 cases of right CDH that presented for prenatal evaluation or postnatal treatment.

Methods

Between 1995 and September 2002, a total of 194 cases of fetal CDH were evaluated and included 22 right-sided defects. The authors reviewed prenatal diagnostic studies (ultrasound scan, magnetic resonance imaging [MRI] echocardiography) and pre- and postnatal outcomes in these 22 cases of right CDH. Five additional cases of right CDH without a prenatal diagnosis were reviewed.

Results

The mean gestational age at evaluation was 26.1 weeks. The lung area to head circumference ratio (LHR) ranged from 0.32 to 2.5. In all cases, the fetal liver was herniated into the right chest. Associated anomalies were common. There were no karyotype abnormalities (17 of 22 tested). There were 4 terminations. Nine of the 18 (50%) continuing pregnancies had polyhydramnios, premature rupture of membranes, or preterm labor. The mean gestational age at birth was 36.8 weeks. One patient underwent tracheal occlusion at 27 weeks, and 2 patients died before postnatal repair. Overall survival rate (22 prenatal plus 5 postnatal diagnoses) was 19 of 27 (70%). Postnatal survival rate was 19 of 23 (83%). A Gore-tex (W. L. Gore and Associates, Flagstaff, AZ) patch was utilized in 14 of 21 neonates undergoing surgery. Twelve of 23 (52%) required extracorporeal membrane oxygenation (ECMO) with a 75% survival rate. Significant morbidity occurred in 10 of 19 survivors and included neurologic sequelae in 6 of 19 (32%).

Conclusions

MRI was helpful in the determination of liver position and confirmation of diagnosis. The high incidence of preterm complications, frequent need for ECMO, and high prevalence of comorbidities are indicative of the severity of this CDH population and warrant close prenatal surveillance and delivery at a tertiary care center with ECMO capability.     

Slide tracheoplasty for the management of complete tracheal rings

Background/purpose

Although rare, complete tracheal rings are the most common cause of congenital tracheal stenosis. The last 2 decades have seen an evolution in management, with increasing awareness of the potential advantages of slide tracheoplasty.

Methods

Between March 2001 and August 2002, 11 children had complete tracheal rings corrected by slide tracheoplasty. Ages ranged from newborn to 15 years, and weight ranged from 1.8 to 57 kg. Length of stenosis ranged from 3 rings to virtually the whole length of the trachea. The most narrow point in the airway varied from less than 1.9 mm to 4.8 mm. Eight children had other congenital anomalies, severe in one child. Most children underwent repair on cardiopulmonary bypass.

Results

Nine children are asymptomatic or minimally symptomatic, although 2 have endoscopic evidence of mild residual tracheal stenosis. One child, who had been unstable pre-operatively, died of multiple organ failure 7 weeks postoperatively. A second child required a tracheotomy for bronchomalacia at 6 months and died at 9 months with tracheotomy tube occlusion. Both children had adequate tracheal repairs. Complications have included lateral tracheal stenosis (the “Figure 8” trachea) and recurrent laryngeal nerve damage.

Conclusions

Our management of complete tracheal rings has evolved over the last decade, and slide tracheoplasty currently is our preferred surgical approach for tracheal stenosis regardless of the length of narrowing.     

Early repair of congenital diaphragmatic hernia on extracorporeal membrane oxygenation

Background

Timing of repair of congenital diaphragmatic hernia (CDH) in babies that require stabilization on extracorporeal membrane oxygenation (ECMO) remains controversial. Although many centers delay operation until physiologic stabilization has occurred or ECMO is no longer needed, we repair soon after ECMO has been initiated. The purpose of this study is to determine if our approach has achieved acceptable morbidity and mortality.

Methods

Charts of live-born babies with CDH treated at our institution between 1993 and 2007 were retrospectively reviewed. Data were then compared with The Congenital Diaphragmatic Hernia Study Group and Extracorporeal Life Support Organization registries.

Results

Forty-eight (39%) patients required ECMO Thirty-four of these 48 neonates were cannulated before operative repair. Venoarterial ECMO was used exclusively. The mean (SD) time of repair from cannulation was 55 (21) hours. Survival for this subset of patients was 71%. Three patients (8.8%) who underwent repair on ECMO experienced surgical site hemorrhage that required intervention.

Conclusion

Early repair of CDH in neonates on ECMO can be accomplished with acceptable rates of morbidity and mortality.