Surgical treatment of congenital hyperinsulinism.

A multidisciplinary approach to patients with congenital hyperinsulinism (HI) can distinguish focal from diffuse HI, localize focal lesions, and permit partial pancreatectomy with cure in almost all focal patients. Surgery does not cure diffuse disease but can help prevent severe hypoglycemia and brain damage. Surgery can be curative for insulinoma and for some cases of atypical HI.

Prenatal surgery for myelomeningocele: review of the literature and future directions.

Open spina bifida or myelomeningocele (MMC) is one of the most common serious congenital malformations. Historically, this condition has been treated with closure of the MMC defect shortly after birth. The goal of postnatal closure is to cover the exposed spinal cord and prevent infection. However, postnatal surgery does not reverse or prevent the neurologic injury seen in MMC, reverse hindbrain herniation, or prevent hydrocephalus. The neurologic defects result from primary incomplete neurulation and secondary chronic prenatal damage to the exposed neural elements through mechanical and chemical trauma. In a hope to reduce the numerous surgical procedures, medical complications, and lifelong disabilities associated with MMC, the proposal of prenatal closure was put forth more than two decades ago. After promising results in animal models and some clinical series, a randomized controlled trial, the Management of Myelomeningocele Study (MOMS), was conducted. The MOMS trial demonstrated that closure during the prenatal period could be performed relatively safely and can result in significant benefit to the child. Specifically, prenatal closure results in improved motor function, reduced hindbrain herniation, and reduced need for a cerebral spinal fluid diversion. Long-term outcomes of the patients in the MOMS trial continues in the MOMS 2 study as these children grow. Additionally, investigations are underway on modifications to the open fetal MMC closure techniques.

Pulmonary hypertension in giant omphalocele infants.

BACKGROUND: Pulmonary hypoplasia has been described in cases of giant omphalocele (GO), although pulmonary hypertension (PH) has not been extensively studied in this disorder. In the present study, we describe rates and severity of PH in GO survivors who underwent standardized prenatal and postnatal care at our institution. METHODS: A retrospective chart review was performed for all patients in our pulmonary hypoplasia program with a diagnosis of GO. Statistical significance was calculated using Fisher's exact test and Mann-Whitney test (p<0.05). RESULTS: Fifty-four patients with GO were studied, with PH diagnosed in twenty (37%). No significant differences in gender, gestational ages, birth weight, or Apgar scores were associated with PH. Patients diagnosed with PH were managed with interventions, including high frequency oscillatory ventilation, and nitric oxide. Nine patients required long-term pulmonary vasodilator therapy. PH was associated with increased length of hospital stay (p<0.001), duration of mechanical ventilation (p=0.008), and requirement for tracheostomy (p=0.0032). Overall survival was high (94%), with significantly increased mortality in GO patients with PH (p=0.0460). Prenatal imaging demonstrating herniation of the stomach into the defect was significantly associated with PH (p=0.0322), with a positive predictive value of 52%. CONCLUSIONS: In this series, PH was observed in 37% of GO patients. PH represents a significant complication of GO, and management of pulmonary dysfunction is a critical consideration in improving clinical outcomes in these patients.

Longitudinal neurodevelopmental and neuromotor outcome in congenital diaphragmatic hernia patients in the first 3 years of life.

OBJECTIVE: The objective of this study was to longitudinally evaluate the neurodevelopmental (ND) outcome in congenital diaphragmatic hernia (CDH) survivors during the first 3 years of life. STUDY DESIGN: The study cohort consists of 47 CDH survivors that were enrolled in our prospective, follow-up program between July 2004 and September 2010, and underwent serial ND evaluations during the first 3 years of life. ND outcomes were evaluated using the Bayley Scales of Infant Development (BSID)-II or BSID-III. Persistent ND impairment was defined as a score that remained 79 for the cognitive, language and psychomotor domains at the most recent follow-up visit compared with the first assessment. RESULT: The median age at first and last evaluation was 8 (range, 5 to 15) and 29 (range, 23 to 36) months, respectively. During the follow-up, ND scores improved to average in 17%, remained average in 60%, remained delayed in 10%, improved from severely delayed to mildly delayed in 2% and deteriorated from average to delayed in 15%. Motor scores improved to average in 26%, remained average in 55%, remained delayed in 8% and improved from severely delayed to mildly delayed in 11%. Intrathoracic liver position (P=0.004), preterm delivery (P=0.03), supplemental O2 requirement at day of life 30 (P=0.007), age at discharge (P=0.03), periventricular leukomalacia (PVL; P=0.004) and initial neuromuscular hypotonicity (P=0.01) were associated with persistent motor delays. No relationship was found between patient's characteristics and the risk of persistent cognitive and language delays. CONCLUSION: (1) The majority of children with CDH are functioning in the average range by early preschool age, (2) most children who had early delays showed improvement in their ND outcome, (3) children showing delays in all the three domains were the least likely to show improvement and (4) CDH severity appears to be predictive of persistent psychomotor delays.

Fetal pulmonary malformations: defining histopathology.

Although classification schemes have sought to categorize congenital cystic lung malformations, studies including the pathology of pulmonary malformations occurring specifically during the fetal period are limited. To better characterize such histopathology, we reviewed a total of 23 fetal lung malformations seen at the Children's Hospital of Philadelphia from 1996 to 2004. Twenty-one of the 23 fetal pulmonary malformations could be categorized into 1 of 3 groups based upon the predominant histologic features present within each lesion. Group 1 (9/21) demonstrated tubular airspaces lined by columnar epithelium. Group 2 (6/21) contained airspaces lined by cuboidal epithelium and surrounded by smooth muscle with abundant interstitial mesenchyme. Group 3 (6/21) showed a mixture of relatively mature-appearing airspaces lined by flattened epithelium and scattered dilated bronchiole-like structures. Cysts were of variable size but in all cases showed a respiratory-type lining. Gestational ages ranged from 21 5/7 to 38 2/7 weeks. Patients in groups 1 and 2 were generally younger than those in group 3; however, morphology did not seem to correlate entirely with normal stages of fetal lung development, and group 2 lesions in particular were the least akin to normal fetal lung. In 4 cases a systemic vascular supply to a lobe of lung was identified, providing evidence that such vasculature is embryonic in origin. The histopathology of fetal lung malformations highlights the variability seen in such lesions at all ages, and it is hoped that continued investigations will provide further insight into these enigmatic lesions.

A mediastinal window approach to aortopexy.

Between 1989 and 1994 six infants underwent aortopexy for symptomatic tracheomalacia via an anterior mediastinal window. This approach avoids a thoracotomy by using a small transverse incision over the second and third intercostal spaces followed by subchondral excision of these costal cartilages to expose the mediastinum. All patients had stridor and significant respiratory difficulty preoperatively; all experienced significant improvement in symptoms after aortopexy. There were no significant complications attributable to the procedure. The authors recommend this approach for aortopexy.

Scarless human fetal skin repair is intrinsic to the fetal fibroblast and occurs in the absence of an inflammatory response.

The fetus heals skin wounds without scar formation. Human fetal skin that is transplanted to a subcutaneous location on an adult athymic mouse and subsequently wounded heals without scar formation, whereas the same skin heals with scar formation when transplanted to a cutaneous location. In situ hybridization with species-specific DNA probes and immunohistochemistry were performed to characterize the healing process of human fetal skin in these two locations. Species-specific human and mouse DNA probes were constructed and used to probe graft wounds under high stringency in situ hybridization conditions. Immunostaining for species-specific fibroblasts, macrophages, and neutrophils was also performed. We found that the cutaneous human fetal grafts healed with scar and showed an influx of mouse fibroblasts and macrophages. In contrast, subcutaneous human fetal grafts showed exclusively human fetal fibroblasts in the wound environment, an absence of inflammatory cells, and scar-free repair. We conclude that the highly organized collagen deposition in scarless human fetal wound repair appears to be intrinsic to the human fetal fibroblasts and occurs in the absence of an adult-like inflammatory response.