Prenatal diagnosis of isolated congenital pyloric atresia in a sibling.

Although familial occurrence of congenital pyloric atresia (CPA) has been frequently reported in the past, many of these cases were associated with epidermolysis bullosa (EB), and familial isolated CPA was a relatively rare condition. We prenatally diagnosed and successfully treated a sibling of a subject with isolated CPA, who was diagnosed prenatally by fetal ultrasonography based on the findings of a distended stomach combined with polyhydramnios. The first case was a 2398-g female infant born at 36 weeks of gestation, who had been prenatally diagnosed as CPA. The second case, a younger sister of the first case, was a female infant weighing 2434 g, who had been also diagnosed as CPA by fetal ultrasonography at the check-up for the polyhydramnios of the same mother. Neither of the infants showed dermal lesions such as EB, and both underwent pyloroplasty with an excision of the pyloric membrane successfully after birth.

Radiographic changes in the diaphragm after repair of congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: The growth and function of the repaired diaphragm have not been well elucidated, which may contribute to pulmonary function and chest wall deformity. We measured the lower lung diameter at the top of the diaphragm (LLD), diaphragmatic diameter (DD), and diaphragmatic height (DH) on the posteroanterior plain chest radiograph using a picture archive and communication system. METHODS: Thirty-six children aged 10.4 +/- 4.8 years with congenital diaphragmatic hernia underwent clinical evaluation, including plain chest radiograph and a lung ventilation/perfusion scan. As a control, chest radiographs of 89 children aged 9.0 +/- 5.5 years with minor surgery were analyzed. RESULTS: The LLD, DD, and DH in controls were significantly correlated with age; each value was then expressed as a percentage of age-based estimated values. Ipsilateral LLD and DD were significantly decreased. The perfusion of the ipsilateral lung was best correlated with ipsilateral DD. Five patients had chest wall deformity, and 7 had scoliosis (Cobb angle >10 degrees ). Patients with scoliosis had decreased ipsilateral LLD, DD, and DH. The Cobb angle was correlated with LLD and DD. CONCLUSION: The growth of the repaired diaphragm may be impaired, which contributes to decreased perfusion of the ipsilateral lung and scoliosis. The LLD and DD are simple but useful parameters in the follow-up of patients with CDH.

Prenatal detection of pulmonary hypoplasia in giant omphalocele.

Respiratory insufficiency has sometimes been reported in giant omphalocele. To determine whether ultrasonic fetal lung measurements including lung/thorax transverse area ratio (L/T) and chest/trunk length ratio (C/T) may be useful in predicting associated pulmonary hypoplasia, 28 fetuses with abdominal wall defects between 1991 and 2003 were reviewed. Nine patients with gastroschisis and 19 with omphalocele were classified into three groups. A group with neonatal death and postmortem lung/body weight ratio below 0.012, which was defined as pulmonary hypoplasia (PH group), included two ruptured giant omphaloceles and two giant omphaloceles with intact covering membrane in utero. A group with artificial ventilation more than 3 months, which was defined as prolonged ventilation (PV group), included one ruptured giant omphalocele and three giant omphaloceles with intact covering membrane. Others were defined as ordinary group. In 12 fetuses with giant omphalocele, the evisceration rate of the liver (LER) was measured in the fetal transverse abdominal dimension including the base of the liver. The L/T in PH group was significantly decreased to other groups. The C/T in PH group was significantly increased to ordinary group. There was no significant difference in the LER among three groups. A measurement of L/T may be useful in predicting associated pulmonary hypoplasia in giant omphalocele. However, antenatal detection of patients required prolonged ventilation may be difficult and require further study.

Relationship between L/T ratio and LHR in the prenatal assessment of pulmonary hypoplasia in congenital diaphragmatic hernia.

The lung to thorax transverse area ratio (L/T ratio) and the lung area to head circumference ratio (LHR) have been widely used for the assessment of pulmonary hypoplasia in fetal congenital diaphragmatic hernia (CDH). The aim of this study was to evaluate the relationship between the L/T ratio and the LHR, and to clarify the characteristics of these two indicators as prognostic predictors by means of retrospective concurrent measurements from the same subjects with prenatally diagnosed fetal CDH. The medical records of 55 fetuses who had undergone a prenatal evaluation of isolated CDH from 1988 to 2006 were studied. The L/T ratio and the LHR were determined as the early values (earliest measurement performed earlier than 33 weeks of gestation) and as the late values (latest measurement performed later than 34 weeks of gestation) and analyzed, as well as the clinical data. Of the 55 infants, 13 died resulting in a 76.4% survival rate. A correlation expressed in the linear equation [(LHR) = 14.4 x (L/T ratio) - 0.11] was recognized between the early L/T ratio and the early LHR. All cases with an early L/T ratio of less than 0.08, or with an early LHR less than 1.2, died. Of the 13 cases, 5 with an early L/T ratio not lower than 0.08, but less than 0.13, died. Of the 17 cases, 4 with an early LHR not lower than 1.2, but less than 2.0, died. All cases with an early L/T ratio not lower than 0.13, or with an early LHR not lower than 2.0, survived. In 24 cases, the late values, which were measured at an interval of more than 4 weeks, were compared with the early values. Although the L/T ratio was consistent, the LHR increased in the late value compared to the early value. A good linear correlation was recognized between the L/T ratio and the LHR in the early phase of gestation, and the cutoff point of the prognostic prediction was determined in both indicators. In contrast to the L/T ratio, a definite cutoff point throughout the gestation may not be available in the LHR, because there is a natural increase of the LHR in the late phase of gestation.

Long-term outcome in patients with prenatally diagnosed cystic lung disease: special reference to ventilation and perfusion scan in the affected lung.

BACKGROUND/PURPOSE: The natural history of cystic lung disease (CLD) such as congenital cystic adenomatoid malformation (CCAM) and pulmonary sequestration has been altered by the advent of prenatal diagnosis. Although recent advances including fetal therapy have gradually improved outcome, the long-term course and the function of the residual lung have not been well clarified. METHODS: Twenty-two patients with CLD who had been prenatally diagnosed and treated between 1990 and 2004 were reviewed. The clinical outcome and growth measurements were established, and, where possible, all infants underwent ventilation and perfusion lung scan. RESULTS: Mediastinal shift was present in 14 fetuses. Fetal hydrops was present in 5 fetuses. Antenatal intervention was performed for hydrops in 2 fetuses (cyst-amniotic shunt and aspiration). Twenty-one infants underwent appropriate excisional surgery. Final diagnosis included CCAM (n = 12) and pulmonary sequestration (n = 7). No late death was observed. Common complications were failure to thrive (n = 5), frequent respiratory tract infection (n = 4), and asthmatic attack (n = 4). A significant decrease in lung ventilation and perfusion on the affected side was observed in patients with hydrops, lobectomy, and CCAM. CONCLUSION: Long-term follow-up including respiratory care and growth assessment should be performed in prenatally diagnosed patients with CLD, especially those who present with hydrops.

Long-term follow-up of patients with high-risk congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: Recent advances including prenatal diagnosis, high-frequency oscillatory ventilation, and nitric oxide inhalation therapy have gradually improved the survival of high-risk congenital diaphragmatic hernia. However, the factors affecting the long-term outcome of these patients have not been well established. METHODS: Thirty-three children with ages 4.1 +/- 2.5 years underwent clinical examination including growth measurements, echocardiography, ventilation, and perfusion scintigraphy. RESULTS: No late death was observed. Common complications were frequent respiratory tract infection (13 patients) and bowel obstruction (5 patients underwent surgery). Although frequent respiratory tract infection decreased with increasing age, patients with frequent respiratory tract infection had a decreased uptake of lung ventilation and perfusion scintigraphy on the affected side and had a decreased height for age and weight for height. No significant difference in lung ventilation and perfusion scintigraphy was observed between patients treated with and without extracorporeal membrane oxygenation, those requiring oxygen more than 1 month, and between those with and without prenatal diagnosis. Patients with a patch repair had decreased uptake on lung perfusion scintigraphy. Although frequent respiratory tract infection may be owing to hypoplasia of the ipsilateral lung, it may impair recovery of the hypoplastic lung. CONCLUSION: These results indicate that monitoring for respiratory tract infection in addition to nutritional assessment should be required in the follow-up of patients with congenital diaphragmatic hernia at high risk.

Adrenomedullin is up-regulated in nitrofen-induced fetal pulmonary hypoplasia.

BACKGROUND/PURPOSE: Pulmonary hypoplasia associated with congenital diaphragmatic hernia remains a major therapeutic problem. Adrenomedullin (AM), a multifunctional regulatory peptide, has been suggested to play a role in the mechanisms of fetal lung differentiation and maturation. The aim of this study was to investigate the pulmonary expression of AM in nitrofen-induced fetal pulmonary hypoplasia. MATERIALS AND METHODS: Pulmonary hypoplasia was induced in timed-pregnant Sprague-Dawley rats after administration of 100 mg nitrofen on day 9.5 of gestation. Fetal and neonatal lungs were excised on gestational days 16.5, 19, and 21 and 1 hour after birth and divided into the following 3 groups: nitrofen with diaphragmatic defect, nitrofen without diaphragmatic defect, and control (without nitrofen). Pulmonary levels of AM and AM messenger RNA expression were measured by radioimmunoassay and real time quantitative reverse transcriptase polymerase chain reaction, respectively. Localization of pulmonary AM was identified by immunohistochemical staining. RESULTS: There was a significant increase in pulmonary level of AM in the nitrofen-treated groups on gestational days 19 and 21. Real time quantitative reverse transcriptase polymerase chain reaction on gestational day 19 confirmed an increase of AM gene expression in the nitrofen-treated groups. Adrenomedullin immunoreactivity was more strongly expressed in airway epithelial cells in the nitrofen-treated groups than in the control. CONCLUSION: Nitrofen up-regulates expression of AM in the fetal lung, which suggests that AM has some pathophysiological role in the differentiation and/or maturation processes of pulmonary hypoplasia in congenital diaphragmatic hernia.

Surgical management for posterior laryngeal cleft developing subglottic airway obstruction.

A 3-year-old boy associated with Opitz syndrome including hypospadias and anorectal anomaly was transferred to Osaka University Hospital with orotracheal intubation because of respiratory distress after respiratory infection. He had laryngeal cleft diagnosed in the neonatal period because of symptoms including stridor and aspiration. After 2 attempts at extubation, tracheostomy was performed. Fiberscopic examination demonstrated obstruction of the airway from the vocal cord to subglottic space by inspired esophageal redundant mucosa. There was no improvement observed for 3 months. He underwent anterior repair of cleft, anterior laryngotracheoplasty with costal cartilage graft, closure of tracheostomy, and endoscopic Nissen fundoplication. The postoperative course during the subsequent year was uneventful without feeding or speaking disorders. Subglottic airway obstruction caused by inspired redundant mucosa is a rare complication in laryngeal cleft. Anterior laryngotracheoplasty and Nissen fundoplication should be considered for this complication, in addition to the usual procedure for cleft repair.

Assessment of obstructive apnea by using polysomnography and surgical treatment in patients with Beckwith-Wiedemann syndrome.

PURPOSE: Obstructive apnea is sometimes seen in patients with Beckwith-Wiedemann syndrome. The cause of apnea is not limited to macroglossia, and the surgical indication for obstructive apnea has not yet been established. The authors performed polysomnography for the assessment of apnea. METHOD: Overnight polysomnograms were obtained in 2 patients who developed obstructive apnea after 1-stage repair for omphalocele. CASE 1: Apnea index (AI), defined as apneic events per hour, indicated 17.3, and SpO2 below 95% occupied 80% of the total sleep time. Computed tomography and magnetic resonance imaging indicated obstruction of the airway between macroglossia and the hypopharynx. Central tongue resection and the division of the frenulum linguae for associated ankyloglossia were performed 97 days after birth. One month after surgery, apneic events disappeared and SpO2 below 95% occupied only 1% of the total sleep time. CASE 2: Obstructive AI indicated 28.1. Division of the frenulum linguae and anterior glossopexy were performed 55 days after birth. Postoperative polysomnogram indicated a marked reduction of AI. CONCLUSIONS: These results indicated that polysomnography was useful for evaluating obstructive apnea and that advancement of the tongue by division of the frenulum linguae may be recommended for the treatment of obstructive apnea in patients with Beckwith-Wiedemann syndrome.

Application of memory metallic stents to urinary tract disorders in pediatric patients.

The use of memory metallic stents for the urinary tract in pediatric patients has not been reported. The authors report on 2 patients with urinary tract disorders who were successfully treated with a memory metallic stent. A thermoexpandable, nickel-titanium alloy stent was placed at the urethroureteral junction of a 4-year-old boy with ureteral stenosis associated with cloacal exstrophy for 18 months and at the urethra of a 2-year-old girl with ischuria after a repair of cloacal anomaly for 6 months. Temporary insertion of a memory metallic stent is a safe and effective alternative for organic stricture or functional obstruction of the urinary tract in pediatric patients.

A novel association of alveolar capillary dysplasia and duodenal atresia with paradoxical dilatation of the duodenum.

BACKGROUND/PURPOSE: The authors experienced 3 cases of persistent pulmonary hypertension of the neonate (PPHN) associated with duodenal atresia with paradoxical dilatation of the distal blind end of the duodenum. The aim of this study was to clarify the characteristics of this novel association. METHODS: The medical charts of the patients were reviewed retrospectively. RESULTS: Case 1 was a 2,862-g male infant with a prenatal diagnosis of duodenal atresia. The dilated intestine was identified as the distal blind end of the duodenum during duodeno- duodenostomy. PPHN developed after surgery, and the patient died despite treatment with inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO). Lung biopsy results showed alveolar capillary dysplasia (ACD) with misalignment of pulmonary vessels. Case 2 was a 2,244-g female infant with duodenal atresia. Surgery could not be performed because of refractory PPHN, which resulted in death. Autopsy results showed ACD with misalignment of pulmonary vessels and duodenal atresia associated with dilatation of the distal blind end. Case 3 was a 2,462-g female infant with a prenatal diagnosis of duodenal atresia associated with dilatation of the distal blind end. Enlarged echogenic fetal lungs were noted antenatally. PPHN developed after surgery, and she was extubated successfully under combined therapy with iNO and intravenous prostacyclin. Unfortunately, she finally died of refractory PPHN. A retrospective review of the prenatal ultrasonographic findings showed enlarged echogenic fetal lungs as in the first 2 cases. CONCLUSIONS: The characteristics of this novel association are enlarged echogenic fetal lungs, duodenal atresia associated with paradoxical dilatation of the distal blind end, and refractory PPHN resistant to iNO.

Outcome predictors for infants with cystic lung disease.

BACKGROUND/PURPOSE: This study aimed at identifying characteristic features indicating congenital cystic adenomatoid malformation of the lung (CCAM) and evaluating the outcome predictors to identify prenatally subgroups of fetuses with significantly different probabilities of mortality or severe respiratory difficulty. METHODS: Twenty-eight neonates who had undergone antenatal evaluation for cystic lung disease (CLD) were reviewed retrospectively. The patients were divided into 3 groups according to the severity of their clinical course; mild (n = 7), moderate (n = 13), and severe (n = 8). Ultrasonographic findings in the fetus and their pulmonary lesion were evaluated. The normal lung to thorax transverse area ratio (L/T) was measured by ultrasonography. RESULTS: High echogenicity of the lesion throughout pregnancy and polyhydramnios were frequently seen in CCAM. All of the patients with other CLD showed isoechogenicity at the end of pregnancy. All patients in the severe group had both polyhydramnios and fetal hydrops. L/T was increased in mild and moderate groups, whereas no patient in the severe group had an increase in L/T at the final measurement. Each value of final L/T in the severe group was less than 0.25. CONCLUSIONS: The subgroup of fetuses with an increased probability of mortality or severe respiratory difficulty could be predicted from the combination of polyhydramnios, fetal hydrops, and a final L/T value of less than 0.25.

Is adrenomedullin involved in the pathophysiology of persistent pulmonary hypertension of the newborn?

Although adrenomedullin (ADM) is a potent vasodilating peptide reported to play a possible role in the mechanisms of fetal lung differentiation and maturation, the ADM blood level in fetuses and in neonates with persistent pulmonary hypertension (PPHN) and pulmonary hypoplasia is not known. Therefore, we examined 15 patients with PPHN: 10 with congenital diaphragmatic hernia, four with congenital cystic adenomatoid malformation of the lung, and one with misalignment of pulmonary vessels with alveolar capillary dysplasia. Eight surgical patients with neonatal conditions such as intestinal atresia served as controls. Blood samples were drawn from the umbilical artery and vein at birth, and arterial blood was drawn from patients with PPHN on the 3rd and 6th days after birth. Plasma levels of ADM were measured by radiometric assay. Plasma levels of ADM in the umbilical artery and vein were elevated in patients with PPHN compared with controls, and in all groups the levels in the umbilical vein were higher than those in the umbilical artery. The arterial levels in patients with poor prognoses were elevated on the 3rd and 6th days after birth compared with those in survivors. These results indicate that ADM may be involved in the pathophysiology of PPHN and in the mechanisms of lung differentiation and/or maturation.

Scimitar syndrome treated with pneumonectomy: a case associated with bronchospastic attack.

Scimitar syndrome, which involves total or partial anomalous venous drainage of the right lung to the inferior vena cava, is relatively rare and often results in pulmonary hypertension, heart failure and right lung infection. We report here the case of a 1-year-old girl who suffered repeated attacks of bronchospasm after developing pneumonia. She underwent resection of the hypoplastic right lung and showed rapid recovery.

Toriello-Carey syndrome associated with respiratory failure and non-mechanical ileus.

Toriello-Carey syndrome comprises agenesis of the corpus callosum, telecanthus, small palpebral fissures, Pierre Robin sequence, abnormal ears, and cardiac defects. We report a boy who has some additional findings, including a severe respiratory failure and intestinal dysmotility. The boy died of these two disorders at age 13 months. Histological examination revealed pulmonary immaturity and a defect of smooth muscle cells in the longitudinal muscle coat of the intestinal musculature, both of which might explain some aspects of the pathophysiology of the patient.

Fetal mesenchymal hamartoma of the liver: report of a case.

The authors report a case of hepatic mesenchymal hamartoma diagnosed prenatally with ultrasound scan and magnetic resonance imaging (MRI) and confirmed histologically postdelivery. The fetus had a multicystic mass in the left upper abdomen, which showed a rapid enlargement accompanying maternal hypertension and preterm labor. The patient was delivered by cesarian section at 30 weeks and 5 days weighing 1,190 g, and, at birth, a large abdominal mass and severe anemia were noted. Surgical resection and neonatal management were successful, and the patient is alive in a good condition after 3 years follow-up. Although histologically benign, because this lesion frequently results in perinatal complications such as fetal hydrops, maternal toxemia, and preterm labor, early careful fetal ultrasonography should improve the prognosis of this lesion.

Umbilical cord ulcer associated with fetal jejunal atresia: report of 2 cases.

We report 2 cases of umbilical cord ulcer associated with fetal jejunal atresia. Both of them developed a severe intrauterine hemorrhage, followed by fetal heart rate decelerations, and underwent emergency cesarean section. Bloody amniotic fluid and umbilical cord ulcers were observed in both cases. Although both cases were successfully resuscitated, neurological impairment and renal failure developed in 1 case due to prolonged asphyxia. In a review of the literature, umbilical cord ulcer was associated only with congenital duodenal atresia or jejunal atresia, but not with ileal atresia. Although the prenatal diagnosis of duodenal or upper jejunal atresia has been established, the prenatal diagnosis of this complication has not been reported. In such cases, detailed examination of the umbilical cord by ultrasonography may be useful for the prenatal diagnosis of this disease.

Ultrasonographic prediction of clinical pulmonary hypoplasia: measurement of the chest/trunk-length ratio in fetuses.

Pulmonary hypoplasia is involved in patients with various surgical diseases. The aim of this study was to evaluate the clinical usefulness of measurement of the chest/trunk-length ratio (C/T) for predicting pulmonary hypoplasia in patients with congenital anomalies, with the exception of mass-like lesions in the thorax such as diaphragmatic hernia and cystic lung diseases. For measurement of C/T on fetal ultrasound, the sagittal section of the body trunk, including the spine, was analyzed. C/T was calculated as the chest length, defined from the top of the thorax to the top of the diaphragm, divided by the trunk length, defined from the top of the thorax to the bottom of the urinary bladder. From 1986 to 2000, measurements of C/T were undertaken in 49 healthy fetuses from 17 to 37 weeks of gestation and 98 fetuses with congenital anomalies, with the exception of intra-thoracic mass lesions, omphalocele, and fetal hydrops. Pulmonary hypoplasia was clinically assessed by the following criteria: (1) a lung-to-birth-weight ratio of 0.012 or less; (2) patients who required high-frequency oscillatory ventilation with mean airway pressure of 15 cmH(2)O or more with pure oxygen and/or who died presenting respiratory failure without evidences of meconium aspiration, congenital pneumonia, sepsis or hyaline membrane disease. For a predicting value for pulmonary hypoplasia to be obtained, sensitivity, specificity, positive predictive value and negative predictive value were quoted between C/T in patients with pulmonary hypoplasia and those without pulmonary hypoplasia. Healthy fetuses revealed the mean value as 0.38+/-0.03, with no significant change after 20 weeks of gestation. Pulmonary hypoplasia was assessed in 25 fetuses with urethral atresia and stenosis, renal agenesis, polycystic kidney, cloacal anomalies, diaphragmatic eventration, bronchopulmonary foregut malformation, chest deformity, meconium peritonitis and sacrococcygeal teratoma. As a predicting value for pulmonary hypoplasia, 0.32 or less of the maximum value of C/T indicated good accuracy, with a sensitivity of 92.0%, specificity of 95.9%, positive predictive value of 88.5% and negative predictive value of 97.2%. Ultrasonic measurement of C/T is useful in predicting postnatal respiratory conditions with regard to pulmonary hypoplasia.

Case of congenital bronchial atresia detected by fetal ultrasound.

Congenital bronchial atresia is an anomaly characterized by a mucocele associated with a blindly terminating segmental or lobar bronchus. We report on a case of congenital atresia of the left superior segmental bronchus (B6) followed by fetal ultrasonography, which showed a large simple cyst with a surrounding small echogenic area. A large cyst and persistent lung fluid in the affected segment were noted in the early neonatal period.

Usefulness of endoscopic ultrasonography in the diagnosis of congenital esophageal stenosis.

BACKGROUND/PURPOSE: Endoscopic ultrasonography (EUS) is considered a potentially useful tool to investigate structural abnormalities of the esophagus in pediatric patients, as in adults. The aim of this study was to evaluate the usefulness of EUS for the diagnosis of congenital esophageal stenosis. METHODS: High-frequency catheter probe EUS was performed under general anesthesia in 2 patients who had congenital esophageal stenosis. RESULTS: A 4-year-old boy with anorectal anomaly showed tapered narrowing in the distal esophagus, which was not ameliorated with balloon dilatation. High-frequency catheter probe EUS showed hypertrophy of the muscular layer in the esophageal wall at the narrowed portion, but no images suggested the presence of tracheobronchial remnants. The histologic diagnosis of fibromuscular hypertrophy was confirmed at esophagoplasty. A 5-month-old boy with Gross C-type esophageal atresia and symptomatic gastroesophageal reflux showed tapered narrowing in the middle esophagus on esophagography. The symptoms of stenosis were not ameliorated by balloon dilatation performed 4 times. High-frequency catheter probe EUS showed hyperechoic lesions suggesting cartilage at the esophageal narrowing. The diagnosis of tracheobronchial remnants was confirmed by the finding of 2 pieces of cartilage in the specimen obtained at the time of esophageal resection. CONCLUSION: EUS can be applied to show structural abnormalities of the esophageal wall even in pediatric patients with congenital esophageal stenosis and is useful for planning the therapeutic strategy.