Univariate and multivariate analyses assessing the risk of PH as a function of CHD category, presence of an abnormal karyotype and the presence of a malformation likely to interfere with lung growth (IUGR, renal hypoplasia, omphalocele, thoracic dystrophy, or hydrothorax).

<p>Univariate and multivariate analyses assessing the risk of PH as a function of CHD category, presence of an abnormal karyotype and the presence of a malformation likely to interfere with lung growth (IUGR, renal hypoplasia, omphalocele, thoracic dystrophy, or hydrothorax).</p

Pulmonary Hypoplasia Associated with Congenital Heart Diseases: A Fetal Study

<div><p>Background</p><p>Abnormalities of the fetal pulmonary vasculature may affect lung morphogenesis. Postnatal studies have suggested that pulmonary hypoplasia (PH) may be associated with congenital heart diseases (CHDs).</p><p>Objective</p><p>To determine the prevalence of PH associated with CHDs, and to evaluate whether CHDs with right outflow obstruction were associated with the highest risk of lung growth impairment.</p><p>Methods</p><p>Between January 2006 and December 2010, fetuses with CHD obtained following the termination of pregnancies due to fetal abnormalities were examined in a prospective manner for the detection of heart and lung defects. CHDs were classified into five pathophysiological groups. Lung weight (LW), body weight (BW), and LW/BW ratio were analyzed for each case. The expression of CD31 and VEGF in the lung was evaluated by immunohistochemistry.</p><p>Results</p><p>Fetuses with CHDs and right outflow obstruction had significantly lower LW for a given BW, and significantly lower LW/BW ratios for a given gestational age. When defining PH as a fetal LW/BW ratio <0.015 before 28 weeks, and <0.012 after 28 weeks, PH was detected in 15 of the 119 fetuses analyzed (13%). It was significantly associated with CHD with right outflow obstruction, independently of chromosomal abnormalities and associated extracardiac abnormalities (<i>p</i><0.03). Right outflow obstruction was detected in 60% of the fetuses with CHD and PH, but in only 32% of those with CHD but no PH. In fetuses with right outflow obstruction, no difference was observed between those with PH and those without PH, in terms of the ratio of pulmonary artery diameter to aortic diameter, lung CD31 expression, or lung VEGF expression.</p><p>Conclusion</p><p>CHDs with right outflow obstruction are a significant risk factor for prenatally acquired PH. The occurrence of fetal PH is not correlated with abnormalities of the pulmonary vasculature, suggesting the involvement of perfusion-independent mechanisms.</p></div

Characteristics of the fetuses, assigned to two subgroups according to the association of PH with CHD.

<p>Values are medians (IQR) or <i>n</i> (% of each subgroup). BW: body weight; LW: lung weight.</p><p>*<i>P</i> value<0.05;</p><p>**<i>P</i> value<0.0001.</p

Characteristics of fetuses with CHD and PH.

<p>Characteristics of fetuses with CHD and PH.</p

VEGF immunohistochemistry.

<p>Original magnification×10, and ×40 magnification of the area identified by a rectangle. VEGF (brown) and counterstaining with hematoxylin. Fetuses with PH (A, C, E) were compared withfetusesof a similar gestational age without PH (B, D, F). A: Fetus with right ventricular hypoplasia and a septal defect, 18 weeks, LW/BW = 0.010; B: Fetus with pulmonary atresia and a septal defect, 16 weeks, LW/BW = 0.024; C: Fetus with tetralogy of Fallot, 22 weeks, LW/BW = 0.005; D: Fetus with atrioventricular septal defect, 17 weeks, LW/BW = 0.027; E: Fetus with pulmonary atresia and tricuspid atresia, 36 weeks, LW/BW = 0.009; F: Fetus with tetralogy of Fallot, 33 weeks, LW/BW = 0.029.</p

Individual residual values.

<p>Fetuses are classified into four categories on the basis of the CHD. Values are deviations of each observation from the sample mean. Horizontal bar: median value in each subgroup. Kruskal-Wallis test: <i>p</i> = 0.008. *<i>p</i><0.05 for the comparison between subgroups.</p

CHD diagnosis (<i>n</i> = 119).

<p>CHD diagnosis (<i>n</i> = 119).</p

Individual PA/Ao values.

<p>Values were available for 35 fetuses with CHD and right outflow obstruction, and 45 fetuses with CHDs of other types. Horizontal bar: median value in each subgroup. Dashed horizontal line: expected normal AP/Ao value (i.e. 1.2). <i>p</i><0.0001 for comparisons between subgroups.</p

CECs are increased in irreversible and idiopathic pediatric PAH patients.

<p>CEC counts were significantly increased in irreversible and idiopathic PAH (iPAH). Effects of the group and their interaction on CEC variability were tested using ANOVA (***p = 0.0005 and **p = 0.01 for irreversible and idiopathic patients versus controls (reversible PAH), respectively.</p

Effect of SC treprostinil therapy on functional and hemodynamic status.

†<p>Deceased.</p