Total anomalous pulmonary venous return: Familial and environmental factors
Authors: Correa‐Villaseñor Adolfo , Ferencz Charlotte , Boughman Joann A. , Neill Catherine A. ,   The Baltimore‐Washington Infant Study Group
Published: June 2005

In total anomalous pulmonary venous return (TAPVR), the intrapulmonary venous plexus has failed to connect to the left atrium, so that the pulmonary veins drain into right atrial tributaries, frequently resulting in early postnatal circulatory distress. The Baltimore‐Washington Infant Study (BWIS), a population‐based exploratory case‐control study of cardiovascular malformations (CVM), identified 41 cases of TAPVR during 1981–1987:1.5% of all CVM (N = 2659), a regional prevalence of 6.8/100,000 live births. Of the TAPVR infants, 68% were diagnosed as neonates, 88% had surgery, and 51.2% were alive at 1 year of age. Noncardiac malformations were present in nine cases (22%); the male‐female ratio was 0.78 (18:23). Compared with a control group representative of the birth cohort (N = 2,801), more TAPVR patients had low birthweight (<2,500 g: 16.2% vs. 6.9%), short gestational age (<38 weeks: 18.9% vs. 9.3%), and intrauterine growth retardation (IUGR) (26.8% vs. 5.8%). Sociodemographic findings were similar to those of controls, except that fewer TAPVR mothers received private pregnancy care (59.5% vs. 71.4%). Family history revealed no other TAPVR‐affected members, but a significant linear trend of increased risk was found over the ordered malformation categories (familial noncardiac, cardiac, both). Bivariate analysis of TAPVR and exposure in life‐style, hobbies, and work showed possible associations for exposure to lead (OR 2.9; 99% confidence interval [CI]: 1.2, 7.2), painting/paint stripping (OR 3.3; 99% CI: 1.3, 8.4), lead soldering (OR 13.3; 99% CI: 1.8, 99.2), and pesticides (OR 2.7; 99% CI: 1.2, 6.4). Multivariate analysis suggested an interaction between pesticide exposure and family history and, thus, a possible familial susceptibility to environmental teratogens. Although the number of TAPVR cases is small, this epidemiologic study identifies hypotheses that may be further explored in morphogenetic and epidemiology studies.

Total anomalous pulmonary venous return (TAPVR) constitutes a well‐defined clinical entity in which the pulmonary veins fail to enter the left atrium and instead drain into the right atrium or its systemic venous tributaries (Neill, '56; Rowe et al., '81). During intrauterine life, the malformation does not compromise the fetal circulation, since the pulmonary arterial resistance is high and the patent foramen ovale provides easy access of right atrial blood to the left side of the heart. At birth, however, the pulmonary vascular resistance begins to fall, and the presence of a severe hemodynamic disturbance becomes increasingly evident (Ferencz et al., '71). Neonatal symptoms may be ominous and require urgent cardiac care. The classic clinical discriptions of this anomaly (Brody, '42; Snellen, '52; Keith et al., '54; Gathman and Nadas, '78; Oelert et al., '86; Yee et al., '87; Limb et al., '88), comprised patient groups in select specialty centers that were concerned with diagnostic and therapeutic, but not with entologic aspects of the disorder.

This report describes 41 liveborn infants with TAPVR ascertained in a population‐based case‐control study of cardiovascular malformations (CVM) over a 6‐year period. Descriptive analyses of sociodemographic, genetic, and environmental risk variables compare the TAPVR group with the concurrently observed infants with other structural abnormalities of the heart and to controls. The findings in this small case group illustrate the manner in which an exploratory case‐control study leads to hypotheses regarding potential risk factors, and the difficulties encountered in searching for teratogenic effects in rare malformations.