[Show abstract][Hide abstract] ABSTRACT: To review the clinical and molecular genetic characteristics of 16 patients presenting a suspected diagnosis of Kabuki syndrome (KS) in the first year of life, to evaluate the clinical handles leading to a prompt diagnosis of KS in newborns. Clinical diagnosis of KS can be challenging during the first year of life, as many diagnostic features become evident only in subsequent years.
Archives of Disease in Childhood 10/2014; · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective To describe short-term neurodevelopmental outcome of infants operated on for congenital anomalies (CA) and assess the impact of type of CA on the outcome.Study Design From 2008 to 2010 newborns operated on for CA were enrolled in a cross-sectional follow-up study including three distinct groups: infants of 6 months (group A), infants of 12 months (group B), and children of 24 months (group C). Each group was divided into five subgroups: (1) esophageal atresia; (2) congenital diaphragmatic hernia; (3) midgut malformations; (4) abdominal wall defects; (5) colorectal malformations. Each group of patients underwent a neurodevelopmental evaluation with Bayley III.Results In all, 150, 156, and 84 babies were enrolled in groups A, B, and C, respectively. Mean (standard deviation) Mental Scale score was 94.65 (8.75), 98.76 (11.03), and 100.60 (12.04) in groups A, B, and C. Mean (standard deviation) Motor Scale score was 96.89 (11.62), 99.23 (14.83), and 103.60 (12.90) in groups A, B, and C. No significant differences were found among the five subgroups considered.Conclusion Regardless of type of malformation, short-term neurodevelopmental outcome of children with gastrointestinal anomalies including diaphragmatic hernia falls within normal range, suggesting that neither being born with a CA nor its type is per se a risk factor for neurodevelopmental delay.
American Journal of Perinatology 04/2013; · 1.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In neonatology unit 40 to 80% of the drugs are used as off-label or unlicensed, particularly in Neonatal Intensive Care Unit (NICU), where it has been described that in a single patient up to 60 parenteral drugs can be administered. The course of a drug inside the organism can be defined in 4 different phases: absorption, distribution, metabolism, elimination; for each of these phases the newborn infant has different characteristics than child and adult. In the last years much more attention has been put in pharmacological research specific for the neonatal age and a good trial design should take into account the following points: (1) to define the pediatric disease in terms of natural history, prevalence, severity, treatment and impact of the new drug; (2) to avoid the "try and error" method based on the adult dose corrected for weight or age; (3) to use adapted methodologies (pharmacokinetics); (4) to avoid small clinical trials (limited number of patients), the use of Randomized Controlled Trials rather than observational studies; (5) to consider ethics providing clear information and reducing pain and stress to the baby and its family.
The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 10/2011; 24 Suppl 1:44-6. · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We assessed whether physical activity could influence the performance and perception of dyspnea in children who were operated on for high risk congenital diaphragmatic hernia (CDH). We hypothesized that CDH children with normal activity would have better lung function and exercise performance level when compared to sedentary CDH subjects. We studied 18 children (11 males and 7 females, mean age 6.6 ± 2.6 years) who were surgically corrected. All children underwent physical examination, ECG at rest, and a maximal exercise stress test on a treadmill to measure the duration of exercise, maximal heart rate and blood pressure, maximal oxygen uptake (VO(2) max and VO(2) ml/kg/min). Lung function testing to measure forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV(1) ), and peak expiratory flow (PEF) was also performed. Following the stress test, the Dalhousie dyspnea and effort scale was shown to children as a pictorial panel with three groups of increasing (from 1 to 7) levels of effort perception, throat discomfort, and chest dyspnea. Children were divided into group A (sedentary) and group B (regular physical participation). There was no difference in CDH severity between the two groups. Group A had a statistically significant lower duration of exercise (P < 0.01), maximal oxygen consumption (VO(2) max P < 0.0001), VO(2) ml/kg/min (P < 0.001), higher throat closing feeling (P < 0.004), chest dyspnea (P < 0.001), and effort perception (P < 0.04) compared to group B. No differences were found in lung function tests. In conclusion, our data may suggest that children with a history of CDH who are active maintain a higher level of performance with less perception of dyspnea and effort.
[Show abstract][Hide abstract] ABSTRACT: The increased survival rate reached in infants with congenital diaphragmatic hernia (CDH) has shown a concomitant increase in late morbidity. A recent report from CDH Study Group showed that dimension of diaphragmatic defect is the only independent risk factor of mortality. However, the influence of defect size on late morbidity is still controversial. The aim of the study was to evaluate the influence of patch repair (proxy of diaphragmatic defects size) on midterm morbidity.
All high-risk (prenatal diagnosis and/or respiratory symptoms within 6 hours of life) CDH survivors treated at our institution from 2004 to 2008 were followed up in a multidisciplinary outpatient clinic as part of a longitudinal prospective study. Auxological, gastroesophageal, pulmonary, and orthopedic evaluations were performed at 6, 12, and 24 months of age. Patient outcomes were compared with respect to +/- patch repair.
Of 70 survivors, 61 (87%) were enrolled and prospectively evaluated in follow-up. Poorer auxological outcome, increased rate of gastroesophageal reflux, and altered pulmonary function test were observed during follow-up.
Patch repair correlates with higher pulmonary, auxological, and gastroesophageal morbidity without increasing chest wall deformities at long-term follow-up.
Journal of Pediatric Surgery 01/2011; 46(1):52-6. · 1.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose: While mortality is decreasing for infants with major anomalies in many advanced centers, long term morbidity is frequently reported in these patients with particular concern about neurodevelopmental outcomes. To date, only few studies report short and medium term neurodevelopmental outcomes in pre-school children. The aim of this study is to investigate the neuropsychological development of preschool children who underwent major surgery at birth or during infancy.
Methods: Patients who underwent surgery for major congenital anomalies at birth or during infancy were prospectively evaluated for neuropsychological development in a dedicated follow up clinic. Tests used to assess cognitive evolution included the Leiter-R, lexical comprehension and production (Phono-Lexical test-TFL), receptive syntax (modified Rustioni test), visual-motor integration (Visual-motor integration-VMI). Correlations between the patient's scores and indicators of disease severity (gestational age; birth weight; diagnosis of congenital diaphragmatic hernia; length of hospital stay) were also evaluated and statistically analyzed by Pearson's test. Medians (interquartile range) are presented. p<0.05 was considered significant.
Results: The study cohort consists of 24 patients. Results of neuropsychological development are shown in the table. Median age at testing was 60 (59-65) months, gestational age 38 (37-39) weeks, birth weight 2.98 (2.51-3.35) kg, length of hospital stay 19 (14-30) days. Thirteen patients had congenital diaphragmatic hernia (54,2%), five esophageal atresia (20,8%), five congenital pulmonary anomalies (20.8%), one gastroschisis (4.2%). A significant direct correlation was found between birth weight and VMI (r2=0.19, p=0.032), as well as an inverse correlation between length of hospital stay and both Leiter-R (r2=0.16, p=0.049) and VMI (r2=0.31, p=0.005).
Conclusion: In our cohort of surgical patients, birth weight and length of hospital stay are significantly correlated with the neuropsychological outcome, in particular the VMI and cognitive evolution. However, children who underwent surgery at birth or during early infancy because of a major congenital anomaly will often have a normal neuropsychological profile at preschool age. Further studies, with a larger patient population are necessary to confirm our data.
Table: main findings in neuropsychological outcome. Results are medians (interquartile ranges).
TFL-lexical comprehension (centile)
TFL-lexical production (centile)
2010 American Academy of Pediatrics National Conference and Exhibition; 10/2010
[Show abstract][Hide abstract] ABSTRACT: One of the more common chest wall anomalies seen in children is pectus excavatum, which may present at birth, or more commonly during the teenage growth spurt. Symptoms of lack of endurance, shortness of breath with exercise, or chest pain are frequent. Although pectus excavatum may be a component of some uncommon syndromes, patients usually are healthy. Evaluation should include careful anatomic description with photographs, radiography to demonstrate the depth of the depression, extent of cardiac compression, or displacement, measurement of pulmonary function. Indications for surgical treatment include two or more of the following: a severe, symptomatic deformity; progression of deformity; paradoxical respiratory chest wall motion; computer tomography scan with a pectus index greater than 3.25; cardiac compression/displacement and/or pulmonary compression; pulmonary restrictive disease; mitral valve prolapse; or failed previous repair(s). The correlation between diaphragmatic hernia and the appearance of pectus excavatum, from etiopathogenesis point of view, may be attributable to several hypotheses: excessive tension in the plastic reconstruction of the diaphragmatic defect; absence of the flexibility of the thoracic cage when goretex patchs are used for the correction of the defect; use of the thoracotomy in the correction of the defect; secondary ipoplasia of the hemithorax due to ipsilateral lung ipoplasia. In our experience 36% of cases of congenital diaphragmatic hernia are complicated by PE.
Paediatrics and Child Health 12/2009; · 1.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The assessment of lung volumes, particularly functional residual capacity (FRC), is crucial for understanding lung development during infancy in CDH patients.
To evaluate changes in lung function during infancy in subjects with CDH treated with a "gentle ventilation" technique and delayed surgery strategy in the neonatal period.
13 CDH infants were studied twice and compared with a population of 28 healthy infants (HI). Tidal-Volume (Vt), respiratory rate (RR) and time to peak expiratory flow/expiratory time ratio (tPTEF/Te) were measured with an ultrasonic flow meter; Compliance (Crs) and Resistance (Rrs) of the respiratory system were studied with the single occlusion technique; FRC and Lung Clearance Index (LCI), were assessed with the sulfur hexafluoride (SF6) wash-in/wash-out technique. The differences between the first (T1) and second (T2) measurement in the CDH group were assessed by the Student's t-test for paired values. For each set of measurement (T1 and T2) the values were compared with HI by Student's t-test.
Mean age at test was 7.5 +/- 5.2 months for HI, 4.5 +/- 2.5 at T1 and 11.9 +/- 4.5 months at T2 for CDH infants. At T1 there were no significant differences between CDH infants and HI in Vt, Crs, and FRC, while tPTEF/te ratio was lower and RR, Rrs, and LCI were higher in CDH patients than in HI. At T2 Vt, Crs, and FRC remained normal in CDH patients as well as RR that, at this time was not different between CDH and healthy infants; tPTEF/te remained below and Rrs and LCI remained above normal ranges, indicating a persistent impairment in lower airways patency.
Lung function in infants with severe CDH is characterized by a persistent impairment in airways patency and significant inhomogeneity of ventilation, suggesting a peripheral bronchial obstruction even if the other lung function tests are within normal ranges.
[Show abstract][Hide abstract] ABSTRACT: Despite surgical refinements, perioperative use of tracheobronchoscopy (TBS) as part of surgical approach to esophageal atresia (EA) is still controversial. The purpose of this study was to evaluate the influence of preoperative TBS in newborns with EA in preventing complications and improving diagnosis and surgical treatment.
In the period ranging from 1997 to 2003, 62 patients with EA underwent preoperative TBS. The procedure was carried out with flexible bronchoscope maintaining spontaneous breathing. When a wide carinal fistula was found, this was mechanically occluded by Fogarty catheter and cannulated with rigid bronchoscopy. Type of EA, surgical procedure variations caused by TBS, and associated anomalies not easily detectable were recorded.
Before TBS, the Gross classification of the 62 patients was as follows: type A, 9 patients; type B, none; type C, 51 patients. At TBS, however, 3 of 9 type A patients had an unsuspected proximal fistula (type B). These 3 patients, plus the 2 with H-type fistula, were repaired through a cervical approach. In 4 patients, previously undetected malformations of the respiratory tree (2 aberrant right upper bronchus and 2 hypoplastic bronchi) were found at TBS. Carinal fistulas in 14 type C patients were occluded by Fogarty catheter to improve ventilation during repair. No complications were observed. Overall, TBS was clinically useful in 28 (45.2%) of 62 patients, including 15 (24.2%) of 62 infants in whom it was crucial in modifying the surgical approach.
Tracheobronchoscopy is a useful and safe procedure and should be recommended in tertiary centers for babies with EA before surgical repair.
Journal of Pediatric Surgery 07/2006; 41(6):1054-7. · 1.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Wolf-Hirschhorn syndrome (WHS) is a well-known genetic condition characterized by typical facial anomalies, midline defects, skeletal anomalies, prenatal and postnatal growth retardation, hypotonia, mental retardation, and seizures. Affected patients with a microdeletion on distal 4p present a milder phenotype that lacks congenital malformations. WHS is rarely associated with congenital diaphragmatic hernia (CDH), and only 8 cases are reported in the literature. In almost all cases of CDH and WHS a large deletion of the short arm of chromosome 4 is present.
A microdeletion of 2.6 Mb on distal 4p associated with CDH and multiple congenital malformations (i.e., cleft palate) is reported for the first time.
Such a microdeletion should prompt a molecular study for WHS when in a fetus/newborn with CDH the association with cleft lip/palate and typical facial appearance (flat facial profile, hypertelorism) is found.
Birth Defects Research Part A Clinical and Molecular Teratology 04/2006; 76(3):210-3. · 2.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite improvements in clinical management, mortality of congenital diaphragmatic hernia (CDH) remains high. Early prediction of mortality risk helps in comparing strategies and/or performances of different centers. Birth weight (BW), Apgar Score at 5 minutes, and modified McGoon Index (MGI) calculated by the ratio between the diameters of pulmonary arteries and the descending aorta have been used to determine mortality of CDH.
The purpose of this study is to evaluate the relationship between early detectable variables and survival in newborns with CDH intubated at birth, managed with "gentle" ventilation and delayed surgery.
All medical records of patients affected by high-risk CDH and treated with a standardized protocol at Bambino Gesù Children's Hospital, Rome, Italy, between January 2002 and September 2004 were reviewed. Prenatal diagnosis, gestational age, BW, sex, side of hernia, and MGI were recorded on admission. The relationship with mortality of each variable was evaluated by univariate analysis. Subsequently, a predictive model of mortality was developed using a logistic regression: the explanatory variables, BW, and MGI were dichotomized in high (HBW and HMGI) and low (LBW and LMGI) according to the best cutoff found with receiver-operating characteristic curves.
Thirty-four newborns with CDH, treated with a standardized protocol, were studied. The main characteristics of the 34 patients were BW, 2886 g (1500-3620 g); gestational age, 37.7 weeks (32-42 weeks); male/female, 22/12; right/left, 8/26; prenatal diagnosis, 29; MGI, 1.31 (0.9-1.85). Only BW and MGI were significantly (P < .05) associated with mortality at the univariate analysis. The best cutoff values were 2755 g for BW (sensitivity, 70%; specificity, 74%) and 1.25 for MGI (sensitivity, 73%; specificity, 78%). Using these limits, BW and MGI resulted independently associated with mortality in the multivariate analysis. Using the 4 possible combinations, the LBW associated with the LMGI presented the highest prediction of mortality (80%).
Birth weight and MGI, variously combined, were predictive of mortality. Because they are not influenced by subsequent modalities of care, they can be considered as valid early severity scores in CDH and used for comparing strategies and/or performances of different centers.
Journal of Pediatric Surgery 02/2006; 41(1):25-8; discussion 25-8. · 1.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cardiorespiratory stabilization is recommended before surgical repair of congenital diaphragmatic hernia (CDH) because surgery may induce a transitory deterioration of chest compliance and gas exchange. It is not known if surgical intervention can affect cerebral circulation and oxygenation.
The aim of the study was to assess noninvasively, by near-infrared spectroscopy, the possible changes in cerebral hemodynamics and oxygenation associated with surgical repair of CDH.
Twenty-five newborns with severe CDH (birth weight, 3057 +/- 354 g; gestational age, 37.8 +/- 1.8 weeks; male/female newborns, 15/10; left/right CDH, 19/6) were sedated, paralyzed, and mechanically ventilated by conventional gentle ventilation and surgically corrected at a median age of 2.7 days (min-max, 2-14 days) after cardiorespiratory stabilization.
Heart rate (HR [beats per minute]), preductal transcutaneous oxygen saturation (tcSaO2 [%]), carbon dioxide tension (tcPCO2 [Torr]), and mean arterial blood pressure (mm Hg) were continuously monitored. Inspired fractional oxygen concentration (FIO2) was adjusted to maintain and preductal tcSaO2 of greater than 80%, whereas the ventilator's settings were kept unchanged throughout the surgical procedure. Cerebral hemodynamics was assessed by near-infrared spectroscopy (NIRO 300, Hamamatsu Photonics, Japan), recording continuously and noninvasively the relative changes in concentration of oxygenated (DeltaO2Hb [micromol/L]), deoxygenated (DeltaHHb [micromol/L]), and total (DeltatHb [micromol/L]) hemoglobin; the tissue oxygenation index (TOI [%]) was also calculated (TOI = O2Hb/O2Hb + HHb). Total hemoglobin concentration is considered to be representative of cerebral blood volume. Arterial blood gases were also measured at the beginning (T1) and at the end of surgery (T2). For all measurements, results at T1 and at T2, as well as the differences between T1 and T2, have been expressed as means or medians and SDs or 95% confidence intervals or ranges. The differences between T1 and T2 were considered statistically significant for a P value of less than .05 by the Student t test for paired values.
At T1, mean tcSaO2% was 94.1 % (SD, 4.6) with a FIO2 of 0.25 (SD, 0.1); at T2, to obtain similar values of tcSaO2 (93.4%; SD, 4.4), it was necessary to increase the FIO2 to 0.37 (SD, 0.14; P < .001). Mean HR at T1 was 149.5 beats per minute (SD, 9.1) and increased significantly (P < .05) at T2 (165.2 beats per minute; SD, 14.2). Mean arterial blood pressure was 54.7 mm Hg (SD, 7.7) at T1 and did not change appreciably at T2 (55.6 mm Hg; SD, 8.1). Moreover, tcPCO2 did not change significantly during the procedure (mean tcPCO2 = 49.9 Torr [SD, 12.8] at T1 and 57.3 mm Hg [SD, 17.9] at T2). O2Hb and tHb decreased (P < .001 and <.005) and HHb increased (P < .05) significantly during the surgical procedure (mean Delta [SD]: DeltaO2Hb= -10.9 micromol/L [9.7], DeltatHb = -7.5 micromol/L [11.7], and DeltaHHb = -3.5 micromol/L [6.8]). Mean TOI was 70% at T1 (normal values >60%) and decreased significantly at T2 (mean DeltaTOI = -6.1% [SD, 10.6]). In all infants, the greatest changes occurred when the viscera were positioned into the abdomen.
Notwithstanding the initial cardiorespiratory stabilization, surgical repair of CDH was associated with a rise in HR and oxygen requirement and a drop in cerebral tHb and O2Hb, suggesting a reduction in cerebral blood volume and oxygenation. These events were probably due to the combined effects of an increase in right to left shunting (as indicated by the increased oxygen requirement) and a decrease in venous return (possibly due to compression of the inferior vena cava by the viscera positioned into the abdomen). These preliminary results reinforce the importance of achieving a good cardiorespiratory stability before undertaking surgical correction of CDH to minimize the possible interference of the procedure with cerebral circulation and oxygenation.
Journal of Pediatric Surgery 11/2005; 40(11):1748-52. · 1.31 Impact Factor