Tetralogy of Fallot is a severe type of CHD and it is characterized by the hemodynamic alterations due to anatomic abnormality, with varied degree of comprised cardiac functions, including ventricular dysfunction, right ventricular systolic dysfunction, right ventricular dilation, outflow tract obstruction, and pulmonary hypertension . After surgical repair of TOF, the majority of young women could survive into their reproductive age. But it is generally known that heart disease constitutes a leading nonobstetric cause of maternal mortality, especially in patients with the cyanotic and complex shunt lesions . Previous studies for pregnant women with TOF showed that pregnancy confers a considerable risk to these patients. The adverse cardiovascular events may be associated with right ventricular dysfunction, severe pulmonary hypertension, and severe pulmonic regurgitation with RV dysfunction [3, 11]. It has been demonstrated that abnormal uteroplacental Doppler flow (UDF) was associated with right ventricular function parameters, suggesting that maternal cardiac dysfunction contributes to defective placentation and/or placental perfusion, which subsequently increases the incidence of obstetric and neonatal complications .
With emerging more advanced diagnostic and therapeutic approaches, the overall prognosis of TOF patients has been remarkably improved in the past decades. However, we occasionally encountered that women with uncorrected TOF got pregnant. Due to the extra cardiac load during pregnancy, women with uncorrected TOF had much higher maternal and perinatal morbidity compared to general population [1,2,3,4,5, 9]. These cases are relatively rare and almost all of published studies for these patients in the literature were case reports. Thus far, no standard regimen has been established to manage these patients. Accordingly, it will be extremely beneficial to study these cases in a comprehensive manner. This study was for the first time to collect over 30 cases of TOF patients from a single center and perform comparative analysis between uncorrected cases and surgically repaired cases.
It is worthwhile to stress that right ventricular dilation were found in all uncorrected patients but in less than half patients in the surgically repaired group. In addition, no incidence of thromboembolism and endocarditis were found in studied subjects, which may explain the overall good clinical outcomes in spite of different degrees of arrhythmias. Women with NYHA class > III have a relatively poor prognosis during pregnancy . Of note, one uncorrected patient with NYHA class IV was the only patient with limited left ventricular systolic function and pulmonary arterial hypertension. The pregnancy was terminated in that patient at 27+ 6 weeks due to severe ventricular failure. The data obtained from the current study collectively implied that the high degree of right ventricular dilation and high NYHA classification are the most relevant factors for negative outcomes.
It has been demonstrated that women at childbearing age with surgical repair for TOF have lower pregnancy-related risks, and the changes in ventricular dimensions and NYHA class are consistent with normal pregnancy adaptation . In the literature, it has been demonstrated that pregnant patients even with corrected TOF still have a higher risk and poorer outcome than otherwise healthy women. The increased risk may be attributed to the extra haemodynamic burden and exacerbation of residual cardiovascular lesions, or recurrence of right ventricular outflow obstruction, right ventricular dilatation, pulmonary regurgitation, the right ventricular dilatation and failure, as well as atrial and ventricular arrhythmia [15,16,17]. In the current study, the residual shunt at VSD patches were present in two patients following operations and their NYHA class were grade III. In addition, 6 patients (31.58%) had pulmonary regurgitation and about two-thirds of patients had arrhythmia at different degrees. Our data support the notion that pregnant women with the surgically repaired TOF are still in high risk, depending on the degree of the cardiac functional adaption during pregnancy.
Regarding the functional adaption of pregnant women with corrected TOF, Egidy et al monitored the quantitative volumetric changes, and concluded that that those women with successful pregnancy appeared to experience an accelerated rate of right ventricular remodeling (an increase in end-diastolic volume) . In our study, the moderate or severe right ventricular dilation was found in all of uncorrected patients (100%), but in less than half of the patients in surgically repaired group (47.37%). In addition, the right ventricular hypertrophy and pulmonary valve stenosis were also been found in all of uncorrected patients (100%), but much less in the surgically repaired patients. The comparisons between the corrected and uncorrected patients revealed that the risk of the women with corrected TOF might be divided to two groups, high-risk and low-risk patient groups according to the degree of right ventricular dilation/hypertrophy and the pulmonary valve stenosis. Further study with a large number of cases that are sufficient to stratify data for high-risk and low-risk patients is necessary to define their actual prognostic value.
Maternal condition and mortality has significant effects on fetal outcome in CHD patients . Recently, Ramage et al. reported 2114 births to women with adult congenital heart disease (ACHD) and suggested an association between several adverse neonatal/maternal outcomes and ACHD . Their results showed that preterm births (< 37 weeks gestation) were 1.4 times higher in women with ACHD than those without ACHD. Women with ACHD also had a higher odd of having a preterm birth with a gestation less than 32 weeks. In addition, 12.8% women with ACHD and 8.7% of women without ACHD delivered an SGA infant. Consistent with the study conducted by Ramage, the complications were more frequently present in the uncorrected group in our study. Although all of the patients have survived, most all of them suffered cardiac and obstetric complications at varying degrees. The low maternal cardiac output, intrauterine growth restriction and the SGA may occur even after the surgical repair of TOF .
In consideration of high complication risks, woman with cardiac disease may be safer with a C-section delivery to avoid prolonged laboring time . In this study, one patient with intrauterine fetal death undergone transvaginal complete curettage of uterine cavity, other uncorrected patients delivered by C-section successfully. Women at highest risk may benefit from preconception counseling and close clinical monitoring during pregnancy . Careful interdisciplinary management among the cardiologist, obstetrician, anesthetist, and neonatologist, and detailed plans for delivery may improve the prognosis [22, 23]. Although the differences of outcomes between 19 surgically repaired and 12 uncorrected cases were significant, the impact of other clinical parameters was not achieved in the current study due to the small number of cases in the subgroups. Further research with a large number of cases to determine the relationship between the outcomes and other clinical parameters may be helpful to establish more beneficial management regimen for TOF patients, especially for those without surgical repair. In addition, it will be beneficial to study the each pregnancy outcome of these TOF patients (with or without repair) in instead of per woman. However, it has not been performed in the current study due to the limitation to retrieve complete medical record for previous pregnancies and no record for new pregnancies in these patients.