RESUMO
OBJECTIVE: To characterize different phenotypes of early pulmonary hypertension (PH) in preterm infants and their respective associations with bronchopulmonary dysplasia (BPD) and survival. STUDY DESIGN: A prospective cohort study in a tertiary university medical center from June 2016 until March 2019. Infants with a gestational age <30 weeks and/or a birth weight <1000 g were included. Echocardiographic assessment for PH was performed at 3-10 days after birth. Subsequent development of BPD at 36 weeks postmenstrual age and mortality were assessed. RESULTS: Early PH was identified in 55% of 104 included infants, including 21% with persistent PH of the newborn (PPHN), 61% with flow-associated PH, and 18% PH without shunt. Only PPHN was associated with placental fetal vascular malperfusion, lower gestational age, and low Apgar score. Both PPHN and flow PH were associated with the development of BPD. Early PH was associated with poorer survival, driven by PPHN. CONCLUSIONS: Early PH is highly prevalent (55%) in preterm infants and associated with the development of BPD, independent of the phenotype of PH. Infants with PPHN had the poorest survival. Early PH presents in various phenotypes characterized by differences in etiology, pathophysiology, and associated long-term sequelae.
Assuntos
Displasia Broncopulmonar , Hipertensão Pulmonar , Recém-Nascido , Humanos , Feminino , Gravidez , Recém-Nascido Prematuro , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/complicações , Estudos Prospectivos , Placenta , Displasia Broncopulmonar/complicações , Displasia Broncopulmonar/diagnóstico , Idade GestacionalRESUMO
OBJECTIVE: To describe the prevalence of pulmonary arterial hypertension (PAH)-associated gene mutations, and other genetic characteristics in a national cohort of children with PAH from the Dutch National registry and to explore genotype-phenotype associations and outcomes. STUDY DESIGN: Children (n = 70) diagnosed with idiopathic PAH, heritable PAH, PAH associated with congenital heart disease with coincidental shunt (PAH-congenital heart disease group 3), PAH after closure of a cardiac shunt (PAH-congenital heart disease group 4), or PAH associated with other noncardiac conditions were enrolled. Targeted next-generation sequencing was performed on PAH-associated genes (BMPR2, ACVRL1, EIF2AK4, CAV1, ENG, KCNK3, SMAD9, and TBX4). Also, children were tested for specific genetic disorders in case of clinical suspicion. Additionally, children were tested for copy number variations. RESULTS: Nineteen children (27%) had a PAH-associated gene mutation/variant: BMPR2 n = 7, TBX4 n = 8, ACVRL1 n = 1, KCNK3 n = 1, and EIF2AK4 n = 2. Twelve children (17%) had a genetic disorder with an established association with PAH (including trisomy 21 and cobalamin C deficiency). In another 16 children (23%), genetic disorders without an established association with PAH were identified (including Noonan syndrome, Beals syndrome, and various copy number variations). Survival rates differed between groups and was most favorable in TBX4 variant carriers. CONCLUSIONS: Children with PAH show a high prevalence of genetic disorders, not restricted to established PAH-associated genes. Genetic architecture could play a role in risk-stratified care management in pediatric PAH.