Pulmonary hypertension in preterm infants: results of a prospective screening program.

OBJECTIVE: Determine prevalence and associations with pulmonary hypertension (PH) in preterm infants. STUDY DESIGN: Prospective institutional echocardiographic PH screening at 36 to 38 weeks' corrected gestational age (GA) for infants born <32 weeks' GA who had bronchopulmonary dysplasia (BPD; group BPD), and infants without BPD who had a birth weight (BW) <750 g, or clinical suspicion for PH (group NoBPD). RESULTS: Two hundred and four infants were screened (GA 25.9±2 weeks, BW 831±286 g). The PH prevalence in group BPD was higher than in group NoBPD (44/159 (28%) vs 5/45 (11%); P=0.028). In group BPD, BW and GA were lower in infants with PH compared with NoPH. Following correction for BW and GA, necrotizing enterocolitis (NEC), severe intraventricular hemorrhage (IVH), atrial septal defect (ASD), and mortality were independently associated with PH in infants with BPD. In group NoBPD, NEC was the only identified factor associated with PH. Altogether, screening only those infants with NEC and infants with BPD who also had a BW <840 g would have yielded a 84% sensitivity for detecting PH, and reduced the number of screening echocardiograms by 43%. CONCLUSIONS: PH in prematurity is associated with NEC in infants with and without BPD. In infants with BPD, smaller GA and BW, severe IVH, ASD and mortality are also associated with PH. Infants without identified PH-associated factors may not require routine echocardiographic PH screening.

Novel TFAP2B mutations that cause Char syndrome provide a genotype-phenotype correlation.

To elucidate further the role, in normal development and in disease pathogenesis, of TFAP2B, a transcription factor expressed in neuroectoderm, we studied eight patients with Char syndrome and their families. Four novel mutations were identified, three residing in the basic domain, which is responsible for DNA binding, and a fourth affecting a conserved PY motif in the transactivation domain. Functional analyses of the four mutants disclosed that two, R225C and R225S, failed to bind target sequence in vitro and that all four had dominant negative effects when expressed in eukaryotic cells. Our present findings, combined with data about two previously identified TFAP2B mutations, show that dominant negative effects consistently appear to be involved in the etiology of Char syndrome. Affected individuals in the family with the PY motif mutation, P62R, had a high prevalence of patent ductus arteriosus but had only mild abnormalities of facial features and no apparent hand anomalies, a phenotype different from that associated with the five basic domain mutations. This genotype-phenotype correlation supports the existence of TFAP2 coactivators that have tissue specificity and are important for ductal development but less critical for craniofacial and limb development.