Cases Of Congenital Diaphragmatic Hernia Research Articles

Immunohistochemical distribution of surfactant apoprotein-A in congenital diaphragmatic hernia

The high mortality for congenital diaphragmatic hernia (CDH) has been attributed to a combination of pulmonary hypoplasia and persistent pulmonary hypertension. Recent experimental studies suggest that surfactant deficiency may also contribute to CDH pathophysiology. In this report, the authors immunohistochemically and morphometrically examined whether or not the hypoplastic lungs of CDH are associated with the immaturity of the surfactant system, especially alveolar type II cell function. Nine autopsy cases with CDH were immunohistochemically examined for the expression of surfactant apoprotein, using anti-IgG against human surfactant apoprotein A (SP-A), and the findings were compared with those in a gestational and postnatal age-matched control group. The lung/body weight ratio in the CDH was less than that in the controls (0.010 ± 0.005 versus 0.021 ± 0.013, P < .01). The radial alveolar count (RAC) of the CDH cases were also significantly less than that of the control cases (2.10 ± 0.52 versus 3.48 ± 0.39, P < .01). In the CDH cases, the RAC of the lung on the affected side were also significantly less than that of the lung on the unaffected side (1.71 ± 0.34 versus 2.50 ± 0.26, P < .01). In the immunohistochemical distribution of SP-A, compared with the control cases, the number of SP-A-positive cells on the alveolar septa of the CDH cases decreased in number, and this immunohistochemical reaction was weak even in positive type II cells. In addition, the immunoreaction observed in the alveolar type II cells of the unaffected side lungs in the four CDH cases was stronger than that of the unaffected side lungs. These results suggest that in the lungs of the CDH cases, especially on the affected side, there is a possible delay in both the structural growth and functional maturation or development of SP-A synthesis by alveolar type II cells, and this retardation of the functional maturation in alveolar type II cells is also considered to play a role in postnatal respiratory insufficiency in CDH patients.

Tracheal fluid (TF) saturated phosphatidylcholine (Sat. PC) and surfactant protein A (SP-A) in newborns with congenital diaphragmatic hernia (CDH)† 980

We have reported recently that the amniotic fluid concentrations of the surfactant components Sat. PC and SP-A are decreased in pregnancies with fetuses diagnosed with CDH (Am J Ob Gyn 173:1401, 1995). In addition, it has been suggested that surfactant therapy may be beneficial in the treatment of CDH. However, there is limited data on actual measurements of surfactant components in TF from infants with CDH. The aim of our study was to determine the concentrations of Sat. PC using thin-layer chromatography after osmium tetroxide treatment, and of SP-A by an ELISA method using a rabbit anti-human SP-A polyclonal antibody, in TF obtained during the first day after birth from intubated neonates with CDH (n= 10, mean GA 37.2 weeks, range 29-40 weeks). Also, we made similar determinations in TF samples from preterm infants with respiratory distress syndrome (RDS, n= 10, mean GA 28.4 weeks, range 26-32 weeks) and term neonates intubated for meconium aspiration syndrome (MAS, n=11, mean GA 40.5 weeks, range 37-43 weeks). All cases of CDH occurred on the left side and 6 of them died. Results are shown in the Table as mean ± SEM (* p < 0.05 by Kruskal-Wallis). As we reported previously (Am J Resp Crit Care Med 150:1672, 1994), all infants with RDS had low concentrations of SP-A in TF, compared with none of the neonates with CDH or MAS. Levels of Sat. PC in TF were quite variable and did not differ between groups. The concentrations fo SP-A and Sat. PC were not different in neonates with CDH that survived or died. These data show that deficiency of surfactant components in TF from neonates with CDH is uncommon and does not correlate with outcome.

Can blood gas values predict pulmonary hypoplasia in antenatally diagnosed congenital diaphragmatic hernia?

The prognosis of antenatally diagnosed congenital diaphragmatic hernias (CDH) is clearly related to the degree of pulmonary hypoplasia (PH). After birth, controversies remain regarding the implementation of various therapies, especially the use of extracorporeal membrane oxygenation (ECMO). In the literature, the persistence of a Pa o 2 below 100 mm Hg and of Pa co 2 above 40 mm Hg despite optimal conventional therapy indicates poor prognosis. Therefore, since 1992, published and personal experiences led the authors to exlude CDH patients from ECMO when conventional therapy (including high-frequency oscillatory ventilation and nitric oxide) did not obtain Pa o 2 of above 80 mm Hg and Pa co 2 of below 60 mm Hg. The aim of this retrospective study is to determine whether blood gas results correlate with postmortem findings. Between July 1990 and July 1994, 32 cases of CDH were monitored antenatally and managed postnatally at the authors' institution. Six patients survived; 26 died, including one immediately at birth. Thirteen were treated by ECMO. Seventeen had a best Pa o 2 of above 80 mm Hg, including the six survivors. Fourteen did not reach this level, and none of them survived. Twenty-three infants underwent postmortem examination. PH was assessed using two criteria: (1) lung weight to body weight ratio ( LW BW ) and (2) radial alveolar count (RAC). Two patients did not have hypoplasia ( LW BW > 0.018 ). Twenty-one patients had PH; 12 of them had an LW BW ratio of less than .009; for 9, the LW BW ratio was between .009 and .018, and the RAC (<3.1) confirmed PH. All infants with a best Pa o 2 of less than 80 mm Hg had PH. Patients with a best Pa o 2 of greater than 80 mm Hg included two infants who died from complications without PH, eight infants with demonstrated PH, and the six survivors. In conclusion. (1) No infant with nonhypoplastic lungs has been deprived of ECMO by the authors' criteria. (2) Adequate values of blood gases may not eliminate PH. Therefore, this probably justifies starting ECMO when conventional therapy fails. (3) Conversely, permanent poor values of Pa o 2 allowed the prediction of PH in all cases. Such patients probably can be excluded from ECMO treatment.

ECMO in evolution: The impact of changing patient demographics and alternative therapies on ECMO

The incidence of neonatal extracorporeal membrane oxygenation (ECMO) is decreasing nationally. This decrease is presumed to be a result of the emergence of alternative technologies such as high-frequency oscillatory ventilation (HFOV), nitric oxide (NO), and surfactant therapy as well as others. The purposes of the present report were to determine just how rapidly the demographics of ECMO are changing and to determine the impact of competing technologies on ECMO use. The authors reviewed their entire ECMO experience of 455 cases (370 neonatal, 38 pediatric, and 47 cardiac). The neonatal cases also were separated into diagnostic groups: MAS (meconium aspiration syndrome), PPHN (persistent pulmonary hypertension of the newborn), RDS (respiratory distress syndrome), and sepsis. To allow statistical comparison, the patients were divided into four chronological groups, of equal 3-year duration, spanning the 12 years that ECMO has been available. The results of the analysis demonstrated four principle findings. (1) The total number of patients receiving ECMO per year was declining (P = .0001). This decline was attributable to a reduction in the total number of neonatal patients, with the exception of cases of congenital diaphragmatic hernia. (2) The complexity of each ECMO run was increasing, as evidenced by substantial increases in mean ECMO duration per patient and an increase in the incidence of patient complications on ECMO (P = .0001). (3) There has been a significant decrease in the overall survival rate for patients treated with ECMO (P = .0001). (4) The ECMO population mix has shifted away from straightforward neonatal cases and toward the more complex pediatric and cardiac cases. This demographic shift has occurred as a result of improvements in pre-ECMO management of neonatal patients, and is primarily responsible for the findings noted above. However, there also has been a worsening of condition severity within each diagnostic group, which also is partly responsible for the changes noted. If these trends continue, pediatric, cardiac, and CDH patients will likely account for the majority of ECMO patients. Consequently, existing ECMO centers must be prepared to adapt to the changing demographics by evolving programs that support pediatric, cardiac, and adult patients, in addition to neonates. Furthermore, the complexity associated with transporting these unstable older patients and the likelihood that the number of active ECMO centers will decline may require remaining ECMO centers to develop long-distance ECMO transport capabilities.

Fetal diaphragmatic hernia without visceral herniation

Many cases of congenital diaphragmatic hernia (CDH) are currently detected before birth. The authors hypothesized that there is a subgroup of patients with CDH who have no evidence of visceral herniation in utero and who would be expected to have less pulmonary hypoplasia and a good prognosis. Among 41 neonates with left-sided CDH treated between January 1990 and October 1993, 17 cases were diagnosed after birth. Ten of the 17 had undergone detailed fetal sonographic imaging at or after 20 weeks' gestation. After independent review of the prenatal scans of these 10 patients, one was found to have evidence of a diaphragmatic hernia and was excluded from further analysis. The other nine fetuses survived, and prosthetic repair of the diaphragmatic defect and extracorporeal membrane oxygenation (ECMO) were each required in only one patient. This contrasted with the outcome for 18 control patients with prenatally diagnosed CDH: 4 (22%) died, 13 (72%) required prosthetic repair, 9 (50%) were supported with ECMO and the duration of ventilatory support and hospital stay were significantly longer. There is a spectrum of severity among both pre and postnatally diagnosed cases of CDH. In the neonate with an isolated left-sided diaphragmatic hernia, a good prognosis is to be expected if the condition was not detectable by detailed prenatal sonography in the second half of pregnancy.

Alternative treatment may lower the need for use of extracorporeal membrane oxygenation.

Access to artificial surfactant and high frequency oscillatory ventilation (HFO) in Japan seems to affect the actual indications for extracorporeal membrane oxygenation (ECMO). The relation between the methods of treatment and survival and/or neurological sequelae of 27 neonates with severe respiratory failure who would have met the US ECMO entry criteria in the Neonatal Intensive Care Unit of National Children's Hospital, Tokyo between January 1988 and May 1992 were retrospectively analyzed. Out of 27 neonates, conventional treatment including artificial surfactant was successful in 6 cases (22%). High frequency oscillatory ventilation was used for the 21 cases who did not respond to conventional treatment and it was effective in 5 cases (19% of total). Extracorporeal membrane oxygenation was used on 11 (40% of total) of 16 cases who did not respond to HFO. Eight (29% of total or 73% of ECMO cases) of these cases survived and 3 cases (11% of total) died. The remaining 5 cases (19% of total) who met the exclusion criteria of ECMO died. No patient with respiratory distress syndrome (RDS) became ill enough to meet the US ECMO entry criteria. Six out of 8 congenital diaphragmatic hernia cases were saved on a delayed surgery protocol with HFO. Only about 1% of the neonates who were admitted to our NICU during the last 4 years needed ECMO treatment. Forty-one per cent of the patients who would have met the US ECMO entry criteria were treated successfully without ECMO. The necessity for ECMO is less in Japan than in the US because other methods can often be used successfully to treat severe respiratory disorders.

Gastroesophageal reflux occurring after repair of congenital diaphragmatic hernia

Over the past 2 decades, 110 patients with congenital diaphragmatic hernia (CDH) were treated in the authors' hospital. Eighty-six survived; of these, 10 patients (11.6%) had gastroesophageal reflux (GER) after repair of CDH. Seven occurred in the past 5 years, during which time advanced intensive care including extracorporeal membrane oxygenation (ECMO) was used. Vomiting started within 4 weeks after repair of CDH in eight cases, and hiatal hernia was demonstrated in six cases. Three patients responded to conservative therapy; the other seven required antireflux surgery. Several factors are believed to be possible causes of the development of GER in CDH cases. Among them, slow pulmonary expansion of the affected side was thought to be the most important. Namely, in a case of CDH associated with severe hypoplastic lung, the esophagus may be deviated to the affected side before the lung is expanded. After expansion, the abdominal esophagus shortens, and GER or a hiatal hernia can occur in severe cases. There were seven such patients in our series of 10. With the increase in the survival rate of CDH cases associated with severe hypoplastic lung, the number of such patients also may increase. Therefore, some additional procedure to prevent the lower esophagus from sliding will be necessary in the repair of diaphragmatic hernia.

FOUR CASES OF CONGENITAL DIAPHRAGMATIC HERNIA TREATED WITH EXTRACORPOREAL MEMBRANE OXYGENATION (ECMO)

Four critical cases of congenital diaphragmatic hernia (CDH) were treated with extracorporeal membrane oxygenation (ECMO). The indications, complications, and results of the use of ECMO, and the efficacy of respiratory management with high frequency oscillation (HFO) and delayed surgical repair of CDH are presented. One case was placed on ECMO for persistent fetal circulation (PFC), and other three cases were plased on ECMO for another complications such as elevated PaCO2, obstruction of the airway tract and circulatory disturbance in addition to PFC. All cases had complications that were hemorrhage related to systemic heparinization. There were endobronchial bleeding in three cases, gastric bleeding in one case and thoracic cavity bleeding in one case. One case died due to pulmonary bleeding ten days after weaning from ECMO. Other three cases survived and well grow thereafter. We tried respiratory management with HFO in three cases and delayed surgical repair of CDH in two cases before the use of ECMO, but these therapeutic methods were ineffective for them. These results show that ECMO is the effective method in the management of critical patients with CDH.

Prognosis in Fetal Diaphragmatic Hernia

The reported mortality for prenatally detected congenital diaphragmatic hernia is high. Polyhydramnios and presentation in early pregnancy have been suggested as high-risk factors adversely affecting outcome. We retrospectively reviewed 55 cases of congenital diaphragmatic hernia diagnosed prenatally in our unit. There was an overall mortality of 73%. The mortality in cases with presentation before 25 weeks' gestation was 74%, if the cases resulting in termination of pregnancy are excluded, compared with a mortality of 60% in those seen after this gestational age. Underdevelopment of left-sided cardiac structures was found to be a helpful prognostic factor. We were unable to confirm the predictive nature of hydramnios. Associated chromosomal anomalies were found in two fetuses and major congenital heart disease in nine. Although diagnosis before 25 weeks' gestation is associated with a higher mortality than in cases detected later, it is not universally fatal. If congenital heart disease and chromosomal anomalies are excluded and there is little or no evidence of left heart underdevelopment, the odds for survival will improve. This should be taken into account when the management of these cases is planned.

Congenital diaphragmatic hernia: influence of associated malformations on survival.

The medical records of 116 consecutive cases of congenital diaphragmatic hernia (CHD) among 368,772 live births at the three maternity hospitals in Dublin were examined and the incidence of associated malformations and their impact on survival analysed. The patients were divided into two groups: group I included 64 (55%) patients who died during resuscitation and stabilisation before surgery at a mean age of 11.2 hours and group II included 52 (45%) patients who were operated upon. All patients in group I underwent detailed postmortem examination as did the 45% patients who died in group II. The mean (SD) gestational age for group I patients (36.1 (4.5) weeks) was significantly lower than the mean gestational age of group II patients (39.0 (2.4) weeks). Similarly, the mean birth weight of group I patients (2415 (906) g) was significantly lower than that of group II patients (3140 (563) g). Of the newborns who died before surgery, 40 (62.5%) patients had 79 associated malformations. The major associated anomalies were: cardiac (n = 16), neural tube defects (n = 15), skeletal (n = 8), chromosomal (n = 5), urinary tract (n = 6), gastrointestinal (n = 3), omphalocele (n = 4), craniofacial (n = 5), pulmonary (n = 2), and syndromes (n = 2). Sixteen (40%) of these patients were found to have multiple anomalies. Of the 52 patients who were operated upon, only four (7.7%) had associated malformations. Our data shows that associated malformations in neonates with CDH is a major factor influencing outcome in this congenital malformation.

Familial congenital diaphragmatic hernia in the pig--studies on pathology and heredity.

Thirteen cases of congenital diaphragmatic hernia were encountered in one of the three pig families, established by us as a disease model of ano-rectal malformations. Five were males and 8 were females. The age at the onset of symptoms ranged between one and 4 months after birth. On the laterality, 7 had right side, 5 had left side and one had bilateral hernias. No hernial sac was observed. Herniated organs were intestine in the right and stomach in the left side. Thus congenital origin with late onset was suggested as a cause of the disease. In the studies of the heredity, there was no linkage between ano-rectal malformations and diaphragmatic hernia. Double recessive genes were supposed as a mode of inheritance, according to the statistical calculation. An effort is being made to produce a model of congenital diaphragmatic hernia from the pig family.

Prognosis in fetal diaphragmatic hernia

The reported mortality for prenatally detected congenital diaphragmatic hernia is high. Polyhydramnios and presentation in early pregnancy have been suggested as high-risk factors adversely affecting outcome. We retrospectively reviewed 55 cases of congenital diaphragmatic hernia diagnosed prenatally in our unit. There was an overall mortality of 73%. The mortality in cases with presentation before 25 weeks' gestation was 74%, if the cases resulting in termination of pregnancy are excluded, compared with a mortality of 60% in those seen after this gestational age. Underdevelopment of left-sided cardiac structures was found to be a helpful prognostic factor. We were unable to confirm the predictive nature of hydramnios. Associated chromosomal anomalies were found in two fetuses and major congenital heart disease in nine. Although diagnosis before 25 weeks' gestation is associated with a higher mortality than in cases detected later, it is not universally fatal. If congenital heart disease and chromosomal anomalies are excluded and there is little or no evidence of left heart underdevelopment, the odds for survival will improve. This should be taken into account when the management of these cases is planned.

A CASE OF RIGHT CONGENITAL DIAPHRAGMATIC HERNIA WITH MULTIPLE DIAPHRAGMATIC DEFECTS

We describe a case of congenital diaphragmatic hernia, in which multiple defects were found in the right diaphragm and through 3 defects of them the liver protruded. The case was a 42-year-old male who was referred to our department for minute examination for an abnormal shadow on a chest X-ray film and was admitted. Chest X-ray film revealed polyp-like tumor shadow protruding upward. CT, MRI, and scintigraphy of the liver failed to offer any definite diagnosis. Exploratory thoracotomy was carried out. Operative findings included 3 protrusions of the liver covered with parietal pleura in the central tendon of the diaphragm, and a large number of several mm-sized defects around the main defects. Only a case of congenital diaphragmatic hernia, in which multiple diaphragmatic defects associated with several liver protrusions has been reported up to now as possible as we can review.

Pathophysiology of congenital diaphragmatic hernia: I. Renal enlargement suggests feedback modulation by pulmonary derived renotropins — A unifying hypothesis to explain pulmonary hypoplasia, polyhydramnios, and renal enlargement in the fetus/newborn with congenital diaphragmatic hernia

Survival of newborns with congenital diaphragmatic hernia (CDH) is largely dependent on the severity of pulmonary hypoplasia (PH) present at birth. Intrathoracic compression by the herniated abdominal viscera is thought to be the primary factor involved in the pathogenesis of the PH in CDH. Humoral and/or amniotic pulmonary growth factors (PGF) have been hypothesized to play a role in normal fetal pulmonary development and may be involved in the pathogenesis of CDH as well. The hypothesis of this paper is that growth of the fetal lung is stimulated by a PGF produced by the kidneys, which is modulated by a feedback signal from the lungs, a pulmonary derived renotropin (PDR). In the fetus with CDH, the lungs may be unable to respond to PGF due to compression by the herniated abdominal viscera. Theoretically, PH associated with CDH would maximally stimulate this feedback loop to release more PDR, resulting in continual stimulation of the kidneys and renal enlargement. If such a schema plays a role in the in utero pathophysiology of CDH, then newborns with CDH should have enlarged kidneys. To investigate this hypothesis, we reviewed 30 autopsy cases of newborns with CDH and analyzed their kidney weights versus body weights, using historical data as a control. Kidney weights in CDH cases were greater than the control population in 77% of the cases; 57% of kidney weights were more than one standard deviation above control values. Adjusted group mean kidney weights were 29.8 g (±1.0 SE) in CDH cases and 25.9 g (±1.5 SE) in the control population ( P < .04). These data support our hypothesis and demonstrate that in newborns with CDH and morphologically normal kidneys, there is significant renal enlargement associated with CDH. The presumed mechanism of this renal enlargement, as well as its relationship to normal and aberrant pulmonary growth and regulation are discussed. If such a selective PGF exists, its therapeutic implications for fetuses and newborns with PH are considerable.

Extracorporeal membrane oxygenation ? succesful treatment after repair of congenital diaphragmatic hernia

A case of congenital diaphragmatic hernia successfully treated by extracorporeal membrane oxygenation (ECMO) is reported. A female baby weighing 3.4 kg was admitted 3 h after birth because of respiratory distress. Her left diaphragmatic hernia was repaired 5 h after birth by laparotomy. The AaDO2 levels were higher than 500 mmHg before and after the operation. She was managed by high-frequency ventilation and administration of tolazoine for the first 58 h. These effects were temporary, however, and she reverted into persistent fetal circulation three times. Therefore, ECMO was started at 59 h after birth. When the flow rate of ECMO reached 320 ml/min, the newborn entered a state of complete lung rest. Her general condition improved slowly, and ECMO was successfully terminated after 60 h of bypass. This was the first successful case in Japan.

Natural history of congenital diaphragmatic hernia: implications for management

Advances in ultrasonography have made it possible to accurately diagnose congenital diaphragmatic hernia (CDH) prenatally, and recently interest has been expressed in in-utero correction of CDH as a solution to the problem of high mortality. In an attempt to elucidate the natural history of CDH, we analysed the incidence and mortality of this disorder in a large maternity hospital with an autopsy rate of 100% for all stillbirths and neonatal deaths. Between 1973 and 1985, there were 47 cases of CDH among 99,062 births, an incidence of 1 in 2,107 birhts. There were 15 (32%) stillbirths and 32 (68%) live births. All 15 stillborns had lethal associated non-pulmonary anomalies. Of the 32 liveborn patients, 17 died prior to transfer to the referral centre and 11 of these had major associated anomalies. Prematurity was a feature in 65% of patients who died prior to transfer to the referral centre. Nine of the 15 patients who arrived at the referral centre survived. Our date suggest that the only patient who may benefit from prenatal correction of CDH is a fetus who has serious persistent pulmonary hypertension. However, in the absence of reliable criteria for the in-utero prediction of persistent pulmonary hypertension in association with CDH, surgical correction of CDH prenatally is not practicable at present even for this group of patients. Newer therapeutic approaches in the management of persistent pulmonary hypertension should be addressed as the most promising approach in the management of a CDH patient who develops respiratory failure in the first few hours of life.

Fetal diaphragmatic hernia: Ultrasound diagnosis and clinical outcome in 19 cases

Nineteon cases of congenital diaphragmatic hernia diagnosed in utero are reported with emphasis on sonographic findings, associated congenital and karyotypic abnormalities, the presence or absence of polyhydramnios, and clinical outcome. The survival of these infants was very poor despite accurate prenatal diagnosis, maximal surgical and medical treatment and maximal postnatal care. The overall survival rate was 10.5%, and for fetuses who lived beyond delivery the survival rate was 20%.

A Case of Congenital Diaphragmatic Hernia Successfully Treated by Extracorporeal Membrane Oxygenation (ECMO)

A Case of Congenital Diaphragmatic Hernia Successfully Treated by Extracorporeal Membrane Oxygenation (ECMO)

Prenatal diagnosis and management of some fetal intrathoracic abnormalities

Nine cases of fetal intrathoracic anomalies detected in utero and followed to birth are reviewed. There were 6 congenital diaphragmatic hernias (CDH), one congenital pleural effusion and two isolated cysts of the lung. All these conditions were potentially responsible for neonatal respiratory distress and received early intensive treatment after maternal transport and delivery had been arranged in a center with thoracic surgical facilities available. The risks of a delayed or missed diagnosis were thus avoided, especially for CDH. Despite intensive, traditional, respiratory support, started in the delivery room, mortality among prenatally detected cases of CDH was paradoxically high (83%), compared to mortality among 7 cases of CDH not detected in utero, referred in the same period to our Institution, and symptomatic within 6 h from birth (63%). With prenatal diagnosis the total number of CDH cases referred to a surgical center before birth increases. Many cases which would never have been treated in the past because of death before referral and treatment for severe pulmonary hypoplasia not compatible with life are thus observed and sometimes treated. Nevertheless, lung development continues to be a determining factor for survival even when intensive treatment at birth is available. Responsiveness to therapy is unpredictable before birth and proposed antenatal treatment is still far from being a realistic option. For the other three newborns, where a pleural effusion and pulmonary cysts were found, prenatal diagnosis helped to start appropriate treatment and to prevent neonatal hypoxia in two of them. In the third case, with an incommunicant, isolated pulmonary cyst, the outcome would have been favourable even without a prenatal diagnosis.

Congenital diaphragmatic hernia in monozygotic twins

This is the third reported instance of identical twins, each with left-sided posterolateral congenital diaphragmatic hernia (CDH) (Bochdalek type), who have been operated upon successfully. The associated anomalies were mirror image undescended testicles. Comparative review of familial and sporadic cases of CDH revealed that males were more commonly affected in the former, while females were more commonly affected in the latter. There was no known etiology in either type. Both familial and sporadic cases shared a high incidence of associated anomalies (40% to 50%). Three anomalies were equally found in both types, mainly pulmonary hypoplasia, intestinal malrotation, and patent ductus arteriosus. Central nervous system anomalies were highly prevalent in the sporadic cases (55% to 75%), while cardiovascular and genitourinary anomalies (30% each) were the more common anomalies encountered in the familial cases.