TOF 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 with TOF 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 those cyanotic and complex shunt lesions . Previous studies on 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 and 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 [1-5, 9]. These cases are relatively rare and almost all 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 and perform comparative analysis between uncorrected cases and surgically corrected cases.
It is worthwhile to stress that right ventricle dilation were found in all the uncorrected patients but in less than half patients with corrected TOF. 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. This patient had to terminate pregnancy at 27+6 weeks due to ventricular failure. The data obtained from the current study collectively implied that the high degree of right ventricle 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 ventricle 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 recurrent right ventricular outflow obstruction, right ventricular dilatation, and pulmonary regurgitation, the right ventricular dilatation and failure, atrial and ventricular arrhythmia [15-17]. 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 have different degrees of arrhythmia. Our data support the notion that pregnant women with corrected TOF are still in high risk, depending on the degree of the cardiac status adaption during pregnancy.
Regarding the functional adaption of pregnant women with corrected TOF, Egidy et al monitored the quantitative volumetric changes in pregnancy women after repaired TOF, 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 revealed right ventricle dilation was found in all of uncorrected patients (100%), by contrast, more than half of the patients after surgery repaired or just 47.37% still had right ventricle dilation. In addition, the right ventricular hypertrophy and pulmonary valve stenosis were also been found in all of uncorrected patients (100%), and the proportion in corrected TOF patients were lower. The comparisons between the corrected and uncorrected patients indirectly implied that the risk of the women with corrected TOF may be divided to two groups, high-risk and low-risk patient groups according to the degree of right ventricle 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 and maternal outcomes and ACHD . They results showed that preterm births (<37 weeks gestation) were associated with 1.4 times higher odds among women with ACHD compared with those without ACHD. Women with ACHD also had higher odds of having a preterm birth at less than 32 weeks’ gestation. Almost 12.8% of women with ACHD delivered an SGA infant compared with 8.7% of women without ACHD. Similar to the results of this study, all the patients in our study have survived although most all of them suffered varying degrees of cardiac and obstetric complications, and the complications were more frequent in the uncorrected group. The low maternal cardiac output, intrauterine growth restriction and the small for gestational age may unavoidably occur .
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 can 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 have improved the prognosis . Although the differences of outcomes between 19 repaired cases and 12 uncorrected were significant, additional result analysis and statistical comparison to determine the impact of other clinical parameters was not achieved 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 due to the limitation to retrieve complete medical record for previous pregnancies and no record for new pregnancies in these patients.