Nonimmune hydrops fetalis caused by G6PD deficiency hemolytic crisis and congenital dyserythropoietic anemia.

We present a case of a female neonate who had a nonimmune hydrops fetalis and severe hemolytic anemia due to a rare combination of glucose-6-phosphate dehydrogenase (G6PD) deficiency and congenital dyserythropoietic anemia. We conclude that in severe cases with persistent anemia one should search after delivery for a second reason other than G6PD deficiency alone.

p63 Gene mutations in eec syndrome, limb-mammary syndrome, and isolated split hand-split foot malformation suggest a genotype-phenotype correlation.

p63 mutations have been associated with EEC syndrome (ectrodactyly, ectodermal dysplasia, and cleft lip/palate), as well as with nonsyndromic split hand-split foot malformation (SHFM). We performed p63 mutation analysis in a sample of 43 individuals and families affected with EEC syndrome, in 35 individuals affected with SHFM, and in three families with the EEC-like condition limb-mammary syndrome (LMS), which is characterized by ectrodactyly, cleft palate, and mammary-gland abnormalities. The results differed for these three conditions. p63 gene mutations were detected in almost all (40/43) individuals affected with EEC syndrome. Apart from a frameshift mutation in exon 13, all other EEC mutations were missense, predominantly involving codons 204, 227, 279, 280, and 304. In contrast, p63 mutations were detected in only a small proportion (4/35) of patients with isolated SHFM. p63 mutations in SHFM included three novel mutations: a missense mutation (K193E), a nonsense mutation (Q634X), and a mutation in the 3' splice site for exon 5. The fourth SHFM mutation (R280H) in this series was also found in a patient with classical EEC syndrome, suggesting partial overlap between the EEC and SHFM mutational spectra. The original family with LMS (van Bokhoven et al. 1999) had no detectable p63 mutation, although it clearly localizes to the p63 locus in 3q27. In two other small kindreds affected with LMS, frameshift mutations were detected in exons 13 and 14, respectively. The combined data show that p63 is the major gene for EEC syndrome, and that it makes a modest contribution to SHFM. There appears to be a genotype-phenotype correlation, in that there is a specific pattern of missense mutations in EEC syndrome that are not generally found in SHFM or LMS.

Biochemical, clinical, and morphologic studies on lungs of infants with bronchopulmonary dysplasia.

We correlated clinical, biochemical, and morphologic findings in the lungs of 48 infants dying of either bronchopulmonary dysplasia (BPD) or hyaline membrane disease (HMD) to obtain a better idea of the disease process. The infants ranged from 24 weeks of gestation to 1 1/2 postnatal years. The lungs of BPD and HMD infants had higher contents of DNA, alkalisoluble protein, hydroxyproline, and desmosine, as well as increased concentrations of DNA, hydroxyproline, and desmosine when compared with the lungs of 72 control infants. BPD was classified histologically into 4 groups: Group I was a phase of acute lung injury, Group II the proliferative phase; Group III the phase of early repair, and Group IV the phase of late repair. We saw a significant increase in hydroxyproline concentration in Groups II and III. The ratio of type I/III collagen decreased in BPD Groups II to IV. Desmosine was significantly higher only in Group III than in controls. When the pathological classification was related to biochemical and clinical features of BPD, the classification showed dependence on the number of days the infant survived postnatally and not on the gestational age of the infant. The number of days on assisted ventilation was a slightly better predictor of the disease classification than days on > 60% oxygen. A statistical model correctly predicted the pathologic classification 83% of the time.

Waxing and waning hyperinflation in congenital cystic adenomatoid malformation of the lung.

This report describes a newborn with respiratory distress, waxing and waning left lung hyperinflation, and pulmonary hemorrhage. This atypical presentation of congenital cystic adenomatoid malformation of the lung has not been previously reported, posed a major diagnostic problem, and delayed potentially lifesaving surgery.

Midfacial hypoplasia associated with long-term intubation for bronchopulmonary dysplasia.

Six preterm infants with bronchopulmonary dysplasia were nasotracheally intubated for 68 to 243 days. Gestational age at birth ranged from 24 to 35 weeks. Endotracheal tube size was changed to account for growth and varied from 2.5 to 4.0 mm. These infants developed features of midfacial hypoplasia, namely, depressed nasal bridge, small-tipped nose, long philtrum, underdeveloped malar areas, and carplike mouth. These features have not been associated with long-term intubation in premature infants. We suggest that features of prolonged nasotracheal intubation, such as direct compression by the tube and the method of tube fixation, decreased air flow through the developing nares and sinuses and reduced faciomuscular activity, resulting in the observed midfacial hypoplasia. The degree to which growth corrects these deformations is unknown.

Increased compliance in response to salbutamol in premature infants with developing bronchopulmonary dysplasia.

We compared the effect of salbutamol and placebo in a double-blind study of preterm infants with bronchopulmonary dysplasia, using a randomized, crossover design with several replicates per subject. Sixty-two tests were performed on 20 ventilator-dependent infants weighing less than 1500 gm. Patients were entered as early as the first week of life and studied for at least 4 weeks or until extubation. Each subject was his own control subject and was randomly assigned to a placebo-salbutamol or salbutamol-placebo sequence administered on 2 consecutive days of each week. Static compliance, expiratory resistance of the respiratory system, and changes in transcutaneous oxygen and carbon dioxide tension were measured. Static compliance improved by 0.240 ml/cm H2O/kg (35.3%) after salbutamol and by 0.010 ml/cm H2O/kg (2.8%) after placebo (p less than 0.0001). The presence of a predetermined decrease in carbon dioxide tension correlated with large changes in static compliance per kilogram and with the need for a high level of fractional inspired oxygen. The magnitude of the clinical and physiologic improvement observed, and the early response suggest that long-term bronchodilator therapy starting as early as the second week of life may be beneficial for very low birth weight infants with early bronchopulmonary dysplasia.

Randomized, double-blind, controlled trial of long-term diuretic therapy for bronchopulmonary dysplasia.

The effects of continuous therapy with hydrochlorothiazide and spironolactone on pulmonary function in 34 premature infants with severe bronchopulmonary dysplasia were assessed in a randomized double-blind controlled trial. Subjects were greater than or equal to 30 days old, were supported by mechanical ventilation in greater than or equal to 30% oxygen, and had radiographic evidence of bronchopulmonary dysplasia. The treatment group (n = 19) and the placebo group (n = 15) were similar in all respects except for distribution of gender. Anthropometrics, ventilatory measurements, and the results of pulmonary function tests were evaluated at study entry and at 1, 4, and 8 weeks into therapy. Poststudy chest radiographs were compared with those obtained before the study. The proportion of infants alive at discharge was significantly increased (84%) in the treatment group compared with the placebo group (47%) (p = 0.05). There were no statistically significant differences in total hospital days or in total ventilator days. Total respiratory system compliance at 4 weeks was higher in the treatment group (0.61 +/- 0.18) than in the placebo group (0.45 +/- 0.13) (p = 0.016). No difference in outcome was detected between male and female infants in the treatment group. These results suggest that long-term diuretic therapy improves outcome in infants with bronchopulmonary dysplasia.