Letters to the Editor

Abstract

11 December 2008 Dear Editor, UNILATERAL LUNG AGENESIS: COINCIDENCE OR ASSOCIATION WITH MATERNAL VALPROATE THERAPY? Management of epilepsy in pregnant women is a complex issue as use of antiepileptic medications increase the risk of congenital malformation in the foetus.1 The antiepileptic drug, sodium valproate, is a known teratogen with a constellation of recognised facial features and congenital malformations described in foetal valproate syndrome.2 Infants of mothers receiving valproate more than 1000 mg are at increased risk of congenital malformation, particularly neural tube defects.1 Exposure of foetus to valproate uncommonly results in pulmonary anomalies. Bilateral pulmonary hypoplasia with immature histology was reported in a series of three cases as a possible teratogenic effect of valproate.3 Other reported but rare pulmonary malformations in foetal valproate syndrome include tracheomalacia, abnormal lobulation of right lung, severe laryngeal hypoplasia and oligaemic right lung.4 Association of unilateral lung hypoplasia with maternal exposure to a combination of phenytoin and carbamazepine has been reported.1 A male infant was born at 38 weeks gestation with a birth weight of 2915 grams. The mother was a 32-year-old multiparous lady. During pregnancy, she continued to take sodium valproate, 1000 mg/day, to control grand mal epilepsy. This pregnancy was complicated by the detection of a possible left congenital diaphragmatic hernia on antenatal ultrasound at 18 weeks gestation. An amniocentesis performed at 19 weeks gestation demonstrated a normal male karyotpye. A foetal magnetic resonance imaging scan performed at 21 weeks gestation suggested hypoplasia of the left lung with a normal diaphragm. The infant delivered normally with Apgar scores of 6 and 6 at 1 and 5 min, respectively. There were no dysmorphic features of foetal valproate syndrome. He was managed in a neonatal intensive care unit with continuous positive airway pressure (CPAP) and received a single dose of surfactant. He was treated with phenobarbitone to manage symptoms of valproate withdrawal at approximately 24 h of age. Chest X-rays demonstrated dense opacification with loss of lung volume in the left hemithorax. The computed tomography scan showed absence of lung, bronchial tree, pulmonary artery and veins on the left side (Fig. 1). Echocardiogram showed a structurally normal heart with absence of the left pulmonary artery and left pulmonary veins. He was treated with nasal mask CPAP support for 7 weeks and was weaned successfully to room air at the age of 8 weeks. A polysomnography study showed no oxygen desaturation or hypercapnia while ventilating in room air. He was discharged home with paediatric respiratory follow-up. Computed tomography scan of chest showing absence of carina and left lung. Pulmonary agenesis is complete absence of carina, bronchial tree and lung tissue, and the trachea continues as main bronchus. In pulmonary aplasia, carina and rudimentary main bronchus are present, but lung tissue is absent.5 Pulmonary agenesis is a rare malformation. The prevalence of agenesis of lung was reported to be 0.0034% among hospital admissions.6 The aetiology of lung agenesis is not certain, but possible genetic predisposition has been described.6 Our literature review did not find any other case of unilateral lung agenesis in association with maternal valproate intake. Given the rarity of pulmonary agenesis, it is possible that the foetal exposure to valproate in this report is a chance association. However, this observation will add to previously known pulmonary pathologies seen in association with maternal valproate use and could be relevant from a prenatal counselling point of view.