Prenatal tests of neonatal lung function are limited. Those are based on .... The other two neonates were diagnosed with situs inversus and a BPS respectively.
In: Handbook of Prenatal Diagnosis: Methods, Issues… ISBN: 978-1-60741-254-0 Editor: Elian Pereira and Juliano Soria © 2009 Nova Science Publishers, Inc.
Chapter 12
Hyperoxygenation Study as a Predictor of Neonatal Outcome in Congenital Cystic Adenomatous Malformations Kristin Riley1, Neil S. Seligman1*, Dennis C. Wood1, Kevin Dysart2 and Stuart Weiner 1
Department of Obstetrics and Gynecology, Thomas Jefferson University, Philadelphia, PA 2 Department of Pediatrics, Thomas Jefferson University/Nemours Foundation, Philadelphia, PA
Abstract Objective Neonatal morbidity from congenital cystic adenomatoid malformation (CCAM) is related to mass effect causing pulmonary hypoplasia and hydrops. Maternal hyperoxygenation has been used to evaluate fetal pulmonary vascular reactivity. The purpose of our study was to determine whether pulmonary reactivity predicts the absence of lethal pulmonary hypoplasia in neonates diagnosed with CCAM in-utero.
Methods Retrospective cohort review of 11 women carrying fetuses diagnosed with CCAM underwent a hyperoxygenation test as part of a comprehensive fetal echocardiogram at >30 weeks gestational age. Pulmonary artery Doppler studies were performed before and after 10 minutes of maternal exposure to oxygen (60% FiO2). The presence of pulmonary vascular reactivity was defined as >20% decrease in the pulmonary artery pulsatility index after oxygen exposure. Neonatal outcome was assessed for the presence of lethal pulmonary hypoplasia.
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Kristin Riley, Neil S. Seligman, Dennis C. Wood et al. Results Pulmonary vascular reactivity was present in 10 fetuses. There was only one false positive result. The table shows the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).
Comment In fetuses diagnosed with CCAM, the presence of pulmonary vascular reactivity reliably predicts the absence of lethal pulmonary hypoplasia. Maternal hyperoxygenation testing after 30 weeks gestation may be offered to women carrying fetuses diagnosed with CCAM as an indicator of prognosis.
Introduction A congenital cystic adenomatoid malformation (CCAM) is an idiopathic bronchopulmonary malformation which presents as an intrathoracic mass in the fetus or neonate [1]. These masses are characterized by a lack of normal alveoli and increased proliferation and cystic dilatation of terminal respiratory bronchioles, seen on fetal ultrasound as dense echogenic areas in the lung with or without cysts. Incidence of this malformation is not well known, however reports from Australia and Canada estimate the incidence to be between 1:10,000-35,000 [2,3]. Improved sensitivity and increased utilization of ultrasonography in the prenatal period may account for an increase in the prenatal diagnosis of many congenital anomalies including CCAM. Figure 1 shows the typical appearance of a CCAM on ultrasound. The treatment of CCAMs is surgical removal in the first six months of life [4,5,6,7,8]. Untreated neonates can have long term complications including pneumothorax and recurrent pneumonia. There have also been case reports of malignant degeneration in both children and adults. Antenatal and short term neonatal complications are a result of mass effect. Space occupying lesions of the fetal chest may cause mediastinal shift leading to effusions, ascites, and hydrops. Similarly, these lesions may disrupt normal lung development during the pseudoglandular and canalicular phases between 6 and 26 weeks gestation causing pulmonary hypoplasia. The risk of preterm delivery and intrauterine fetal demise is also increased but the exact mechanism is unknown [9,10,11,12]. Pulmonary hypoplasia is a potentially lethal complication of CCAM. Pulmonary hypoplasia is described as inadequate development of lung tissue and is characterized by decreased capacity for gas exchange [13]. Etiologies include mass effect causing compression of the lung, decreased lung fluid due to restricted fetal breathing movements or low amniotic fluid. The definitive diagnosis is made by pathologic criteria involving wet lung-to-body ratio or by the histologic criteria of reduced alveoli count and DNA content [14]. The incidence of pulmonary hypoplasia due to all causes is 11-14:10,000 live births. However, the incidence is higher in autopsies of premature infants at 7% to 14% [15]. The exact incidence of pulmonary hypoplasia in neonates with CCAM is unknown but the overall mortality is 25-30%.
Hyperoxygenation Study as a Predictor of Neonatal Outcome…
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Prenatal tests of neonatal lung function are limited. Those are based on anatomical measurements using two- or three-dimensional ultrasound and magnetic resonance imaging formulae. We believe that physiologic tests of fetal pulmonary function more accurately predict neonatal outcome. The increase in blood flow through the pulmonary arteries in response to an increase in fetal oxygen content correlates to the normal postnatal adaptation of the lung to neonatal life [16,17,18,19]. Our objective was to test the value of our maternal hyperoxygenation test in predicting lethal pulmonary hypoplasia in fetuses diagnosed with CCAM.
Methods We performed a retrospective review of women carrying fetuses diagnosed with a CCAM who underwent a hyperoxygenation test. This study was approved by the institutional review board. Only women who delivered at Thomas Jefferson University Hospital were included. Data for six women carrying fetuses diagnosed with CCAM were obtained from the fetal cardiology database and by querying the R4 ultrasound reporting system (The CSC Group, Strongsville, OH) for the terms “congenital cystic adenomatous malformation,” “hyperoxygenation test,” and “oxygen test.” The hyperoxygenation test is used at our institution to assess fetal pulmonary vascular reactivity in fetuses >30 weeks gestational age in whom there is an increased risk for pulmonary hypoplasia. These conditions include but are not limited to thoracic masses (CCAM, bronchopulmonary sequestration (BPS), hydrothorax and congenital diaphragmatic hernia), oligohydramnios (secondary to preterm premature rupture of membranes, twin-twin transfusion syndrome, renal disease), and skeletal dysplasia. The hyperoxygenation test is performed consistently using a protocol that was previously published at our institution [18,20]. All ultrasounds were performed and Doppler measurements were recorded by one of the authors (DCW). Doppler measurements in the first branch of a pulmonary artery were recorded with the mother breathing room air and then and following ten minutes of hyperoxygenation (figure 2A and 2B). Oxygen was administered at a fraction of inspired oxygen of 60%. This was achieved by partial non-rebreather mask at 8 liters per minute of 100% oxygen. The administration of oxygen was stopped immediately after the repeat Doppler measurements were captured. All measurements were captured with image-directed pulsed and color Doppler equipment capable of transducing at 5-MHz (Accuson 128XP; Accuson, Mountain View, California and GE Voluson E8 Expert; GE Healthcare, Chalfont St. Giles, UK). All measurements were taken in real time with at least three cardiac cycle measurements analyzed. Measurements were repeated twice with several minutes between each measurement. High-pass filter was set at 100 Hz and spatial peak temporal average power and pulsed Doppler imaging was kept below 100mW/cm2.
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Kristin Riley, Neil S. Seligman, Dennis C. Wood et al. Table 1. Hyperoxygenation test results and presence of lethal pulmonary hypoplasia. Case
GA at test
∆ PIa
Reactiveb
1 2 3 4 5 6 7 8 9 10 11
33 36 33 35 34 31 31 33 34 33 32
6% 33% 52% 64% 41% 34% 25% 46% 48% 33% 28%
No Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Lethal pulmonary hypoplasia Yes Yes No No No No No No No No No
GA; gestational age. a Percent decrease in pulsatility index b Reactive defined as ≥20% decrease in PI
Figure 1. Ultrasound appearance of congenital cystic adenomatous malformations.27 week gestation fetus with dominantly macrocystic CCAM in the left hemithorax. R lung; Right Lung.
The target vessel was one or both of the first branch pulmonary arteries. The angle
