Rare variants in the T-box transcription factor 4 gene (TBX4) have recently been recognised as an emerging cause of paediatric pulmonary hypertension (PH). Their pathophysiology and contribution to persistent pulmonary hypertension in neonates (PPHN) are unknown. We sought to define the spectrum of clinical manifestations and histopathology associated with TBX4 variants in neonates and children with PH.We assessed clinical data and lung tissue in 19 children with PH, including PPHN, carrying TBX4 rare variants identified by next-generation sequencing and copy number variation arrays.Variants included six 17q23 deletions encompassing the entire TBX4 locus and neighbouring genes, and 12 likely damaging mutations. 10 infants presented with neonatal hypoxic respiratory failure and PPHN, and were subsequently discharged home. PH was diagnosed later in infancy or childhood. Three children died and two required lung transplantation. Associated anomalies included patent ductus arteriosus, septal defects, foot anomalies and developmental disability, the latter with a higher prevalence in deletion carriers. Histology in seven infants showed abnormal distal lung development and pulmonary hypertensive remodelling.TBX4 mutations and 17q23 deletions underlie a new form of developmental lung disease manifesting with severe, often biphasic PH at birth and/or later in infancy and childhood, often associated with skeletal anomalies, cardiac defects, neurodevelopmental disability and other anomalies.

The American College of Medical Genetics guidelines for microarray analysis for constitutional cytogenetic abnormalities require abnormal or ambiguous results from microarray-based comparative genomic hybridization (aCGH) analysis be confirmed by an alternative method. We employed quantitative real-time polymerase chain reaction (qPCR) technology using SYBR Green I reagents for confirmation of 93 abnormal aCGH results (50 deletions and 43 duplications) and 54 parental samples. A novel qPCR protocol using DNA sequences coding for X-linked lethal diseases in males for designing reference primers was established. Of the 81 sets of test primers used for confirmation of 93 abnormal copy number variants (CNVs) in 80 patients, 71 sets worked after the initial primer design (88%), 9 sets were redesigned once, and 1 set twice because of poor amplification. Fifty-four parental samples were tested using 33 sets of test primers to follow up 34 CNVs in 30 patients. Nineteen CNVs were confirmed as inherited, 13 were negative in both parents, and 2 were inconclusive due to a negative result in a single parent. The qPCR assessment clarified aCGH results in two cases and corrected a fluorescence in situ hybridization result in one case. Our data illustrate that qPCR methodology using SYBR Green I reagents is accurate, highly sensitive, specific, rapid, and cost-effective for verification of chromosomal imbalances detected by aCGH in the clinical setting.

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ronchopulmonary dysplasia (BPD) is the most common morbidity of preterm birth affecting 50% of infants born less than 30 weeks' gestation in the US. 1 Despite preventive efforts, the incidence of BPD is increasing owing to the improved survival of infants born extremely preterm. 2 Recent studies suggest racial disparities may adversely affect outcomes for preterm infants experiencing common neonatal morbidities, including respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis, during the initial neonatal intensive care unit (NICU) hospitalization. [3][4][5] However, our knowledge of the association of racial disparities with outcomes for preterm infants with BPD remains unclear.Multiple prospective cohort studies have determined that Black maternal race is independently associated with a de-creased risk of severe BPD at 36 weeks' postmenstrual age (PMA), when the diagnosis of BPD is made. 6,7 Additional analyses of these cohorts, however, also identify Black maternal race as an independent risk factor for increased respiratory morbidity in early childhood. 6,8,9 The mechanisms underlying the finding that preterm infants born to Black mothers are at decreased risk of developing severe BPD but are nonetheless at increased risk of early childhood respiratory morbidity remain unknown.The 2001 National Institutes of Health (NIH) consensus criteria define severe BPD in infants born less than 32 weeks' gestation as the need for supplemental oxygen for 28 days or more and a fraction of inspired oxygen greater than 0.3 and/or positive pressure at 36 weeks' PMA. 10 Short-and long-term outcomes for patients with BPD are highly variable. In this study, IMPORTANCE Bronchopulmonary dysplasia (BPD) is the most common serious morbidity of preterm birth. Short-term respiratory outcomes for infants with the most severe forms of BPD are highly variable. The mechanisms that explain this variability remain unknown and may be mediated by racial disparities.OBJECTIVE To determine the association of maternal race with death and length of hospital stay in a multicenter cohort of infants with severe BPD.

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With advances in neonatal care, survival of premature infants at the limits of viability has improved significantly. Despite these improvement in mortality, infants born at 22–24 weeks gestation are at a very high risk for short- and long-term morbidities associated with prematurity. Many of these diseases have been attributed to abnormalities of tissue oxygenation and perfusion. Near-infrared spectroscopy utilizes the unique absorption properties of oxyhemoglobin and deoxyhemoglobin to provide an assessment of regional tissue oxygen saturation, which can be used to calculate the fractional tissue oxygen extraction. This allows for a non-invasive way to monitor tissue oxygen consumption and enables targeted hemodynamic management. This mini-review provides a brief and complete overview of the background and physiology of near-infrared spectroscopy, practical use in extremely preterm infants, and potential applications in the neonatal intensive care unit. In this mini-review, we aim to summarize the three primary application sites for near-infrared spectroscopy, disease-specific indications, and available literature regarding use in extremely preterm infants.