Prenatal diagnosis of primary pulmonary hypoplasia in fraternal twins

Abstract

CASE REPORTA 38-year-old woman, gravida 2 para 1, was referred for fetal echocardiography for evaluation of abnormal cardiac axes in a set of twins. The woman had previously delivered a term male infant who died at 1 month of age from severe respiratory distress despite aggressive mechanical support. Autopsy revealed bilateral lung hypoplasia with arrested acinar development, small pulmonary arteries and a radial alveolar count of four. The couple was not consanguineous.The mother presented to our program at 18 weeks' gestation with dizygotic twins (female and male), products of in-vitro fertilization. General fetal ultrasound examination revealed a right-sided subependymal hemorrhage in the female, and mildly decreased thoracic circumference and normal amniotic fluid levels in both twins. Fetal echocardiography in both demonstrated normal cardiac anatomy and function. Both had a leftward cardiac axis (female, 90 • ; male, 80 • ) and an increased cardiothoracic diameter ratio (female, 60%; male, 50%), and the female had a small pericardial effusion (Figure 1). Both fetuses had hypoplastic branch pulmonary arteries (0.9-1.2 mm in female and 1.3-1.5 mm in male vs. 1.8 mm expected). Flow could not be demonstrated in the pulmonary arteries or pulmonary veins by color or pulsed Doppler imaging in either twin. The findings of hypoplastic branch pulmonary arteries with decreased flow and increased cardiothoracic diameter ratios suggested pulmonary hypoplasia. The parents requested elective termination of the pregnancy.The twins were delivered at 19 weeks' gestation, weighing 169 g (male) and 127 g (female). In both, the diaphragms were intact and there were no cardiac malformations, skeletal dysplasia or renal malformations. The lungs were normally configured but extremely small. In the male, the lungs weighed 1.6 g (expected 5.6 g). In the female, the lungs weighed 1.4 g. Both had markedly hypoplastic extrapulmonary branch pulmonary arteries.The lungs of each fetus showed similar histopathology: there was a lobular architecture with thickened connective tissue septa and prominent lymphatics. In contrast to cuboidal epithelium expected at this developmental stage, the distal sac epithelium of the twins appeared intermediate between columnar and cuboidal epithelium, with low columnar epithelium containing dark nuclei. There was a striking paucity of terminal airspaces within each lobule, and the mesenchymal interstitium was thicker than normal. Peripheral airways were larger than those observed in controls. The findings suggested persistent pseudoglandular stage. The cartilaginous airways were found closer to the pleura than normal, suggesting failure

Primary Fetal Lung Hypoplasia (PFLH): Imaging and Clinical Characteristics

“…The presence of a small BPA in these fetuses can be explained by the histology. In our two cases and in both twins reported by Chen [17], a similar histology of acinar dysplasia was found. This form of diffused lung maldevelopment represents a very early arrest of lung maturation during the pseudoglandular stage of embryology, around 8 -16 weeks of gestation [25].…”

“…The observation of a small BPA in a fetus with PFLH was also reported in the only case published in the literature [17]. However, the authors were pediatric cardiologists and they were aware of the fact that the same patient had a sibling who died from lung hypoplasia with a small pulmonary artery in the autopsy.…”

“…We classified them into two groups: bilateral and unilateral. A thorough review of the literature could reveal only one case report with prenatal diagnosis of bilateral lung hypoplasia [17], and a few case reports describing unilateral lung hypoplasia [18,19].…”

Prenatal Diagnosis of Isolated Right Pulmonary Agenesis Using Sonography Alone

“…A recent online publication reported the first cases of antenatal diagnosis of multiple recurrences of this disease 36 . In this review, 17% of the mothers had something remarkable in their medical or obstetric histories, including 3 cases 3 , 27 , 33 with problems in previous pregnancies: 1 stillbirth of unknown cause and 2 cases with previous children who had congenital anomalies (1 with bilateral lung hypoplasia), 2 cases with teratogenic exposure (sodium valproate [a well‐known teratogen] 22 and hemodialysis [associated with a high risk of congenital anomalies] 4 ), and 1 case of parents who were first cousins 2 . Bilateral agenesis of the lung is 25 times less frequent than the unilateral form.1 In our review, there was a 1:7 relationship, which may be explained by the relatively small sample (n = 36) or because it may be easier to diagnose a bilateral lesion than a unilateral agenesis of the lung antenatally.…”

“…Among the 35 mothers (1 set of twins), the medical and obstetric histories were unreported in 22 cases (63%) and unremarkable in 7 cases (20%). Six cases (17%) presented something remarkable: 1 patient with a previous neonatal death at 1 month with bilateral lung hypoplasia and arrested acinar development, small pulmonary arteries, and a radial alveolar count of four 33 ; 1 patient receiving chronic hemodyalisis due to chronic renal failure 4 ; 1 multiparous patient, who continued during sodium valproate (1000 mg/d) during pregnancy to control grand mal epilepsy 22 ; 1 patient with a previous child with severe psychomotor retardation due to partial agenesis of the corpus callosum 3 ; 1 case in which the parents were first cousins 2 ; and a multiparous patient with a previous stillbirth of unknown cause, hypertension, and poorly controlled asthma 27 . Of the 36 included cases in this review, 31 (88.6%) had the diagnosis confirmed postnatally (details in online Appendix).…”