In the management of pregnant women with PH, especially PAH, multidisciplinary collaboration has been repeatedly stressed by expert consensus and clinicians, whereas there have been rare comparative studies to determine the role and value of the MDT. Although the maternal mortality rate was as high as 10.2% in the pre-MDT group, there were no deaths after the implementation of the MDT in our hospital. As revealed by the above result, the MDT contributed to the reduction of maternal mortality, consistent with existing reports. Our MDT was formed in December 2012, consisting of obstetrician, PH specialist, cardiologist, anesthesiologist, cardiac surgeon, neonatologist and critical care specialist, aiming at streamline treatments and improving maternofetal outcomes in pregnant women with PH (Fig. 1 to be modified), the MDT focused on and weighed the risks and benefits of continuing or terminating pregnancy and the life of mother and fetus, and make decisions timely. To determine whether and how MDT centered on pregnant women with PH affects the maternal treatment and outcomes, the first larger group was presented based on the comparison of the characteristics, treatments and outcomes of PH patients before and after the introduction of the MDT.
Therapeutic abortion and postpartum care
Changes in cardiovascular system during pregnancy and delivery lead to PH worsening in women with PH since their compensatory mechanisms for the changes may be inability. Plasma volume and cardiac output (CO) will start to increase early in pregnancy and reach the peak around 32 gestational weeks at values 40-50% above pre-pregnancy values[18, 19]. Moreover, the second trimester has been generally confirmed as the earliest period of deterioration of heart function for pregnant women with PH. Accordingly, consensus guidelines have recommended women with PH to avoid pregnancy, and the first trimester to terminate pregnancy is considered the safest time[9, 14]. After the MDT was established, the percentage of therapeutic abortion increased from 19.7% of pre-MDT to 38.4% (p = 0.014), accompanying with the decline in the rate of material mortality and cardiac complications. Notably, in PH patients, pregnancy termination may lead to pregnant death and should be performed at an experienced center[5, 21]. In women with PH, most pregnant deaths occur in the early postpartum period [11-13], which are largely caused by right heart (RV) failure and cardiovascular collapse[12, 22, 23]. In the group of this study, four women died of right heart (RV) failure in 2 weeks after delivery, and the another one died suddenly on the third day after being discharged from the hospital. As a result, the postpartum management was specially strengthened after the MDT was established. In general, pregnant women with PH, particularly associated with severe PH and NYHA FC III/IV, were carefully monitored in an intensive care unit (ICU) at least 24 h after delivery or after hemodynamics became stable.
Management of pregnant women with PH
Regular Follow-up and General Therapy
All women with PH insisting to continue pregnancy are required to monthly or weekly visit PH experts and obstetrics who evaluate pregnant heart function and PAP by echocardiograph. After the implementation of the MDT, the rate of regular clinic visits significantly increased to 79.6% associated with decline of material complications. In addition, pregnant patient with signs of worsening RV function, NYAH FC, or PAP was admitted into the hospital and received supported therapy including oxygen, diuretics and digoxin if indicated. Fig. 1 illustrates the treatment steps for women with PH after the implementation of the MDT at our PH center. Furthermore, severity of PH and NYHA FC might be correlated with adverse effects on the maternal and fetal/neonatal outcomes, as presented in Fig. 2 (a) (b). Thus, PAP/sPAP and NYHA FC were vital predictors for maternal prognosis.
Seven pregnant women (one in the pre-MDT group) with mitral valve stenosis underwent percutaneous balloon mitral valvuloplasty (PBMV) for severe lung congestion and dyspnea before delivery. Subsequently, the symptom rapidly relieved and successfully delivered. The risk and benefits of anticoagulants should be carefully evaluated. Prophylactic low molecular weight heparin (LMWH) might be considered for pregnant women with rest on bed.
Pulmonary-specific Therapy for Pregnancy with PAH
Not all pregnant women with PH underwent targeted drug therapy only for patients with group 1 PH (e.g., idiopathic, CHD, connective tissue disease-associated PAH). If the increase of PAP was evaluated through echocardiograph, pulmonary vascular specialist would conduct PAH-specific therapy for continued pregnancy women with PAH or hospitalization. Although there have been rare adequate, well-controlled studies of pulmonary-specific drugs for pregnant women, the data from retrospective literature suggested that pulmonary-specific therapy had improved maternal prognosis in pregnant PAH patients[15, 24]. The current PAH-specific drugs allowed for the treatment of pregnant women consist of prostaglandin analogue (e.g., epoprostenol, treprostinil and iloprost) and phosphodiesterase 5 inhibitors (e.g., sildenafifil and tadalafifil), whereas endothelin receptor antagonists (e.g., ambrisentan, bosentan, and macitentan) are contraindicated during pregnancy for potential teratogenic effects[7, 12].
A Japanese study suggested that among the patients with higher prepregnant PAP, the mPAP increased with the progress of pregnancy . Thus, prepregnant sPAP can be referenced for initiating the PAH-specific therapy. In the group of this study, the sPAP of 6 of 8 pregnant women receiving PAH-specific therapy was evaluated over 60mmHg by echocardiogram in the pre-MDT group and 19 of 22 also over 60mmHg in the post-MDT group. Early use of pulmonary vasodilators has been found to prevent clinical worsening in nonpregnant patients with PAH[26, 27], and deterioration frequently occurs between weeks 20 and 24. Thus, our team has usually recommended pregnant women to receive monotherapy for the control of PAP during the second trimester. In the perinatal period, if a pregnant woman has high-risk factors, the MDT will add prostaglandins or carry out early termination of pregnancy.
Mode and Timing of Delivery
Cesarean section may be the advisable mode of delivery in pregnancy complicated by PH compared with vaginal delivery[9, 10, 20]. There has always been a stubborn attitude to cesarean section in pregnant women with PH. Although 5 pregnant women with cesarean section died after delivery in the pre-MDT group, 4/5 deaths were severely unstable hemodynamics or obstetric indication. Moreover, after the implementation of the MDT, no deaths occurred in pregnant women with cesarean because of the regular follow-up, PAH-specific therapy, as well as meticulous postpartum care.
Our team have recognized that vaginal delivery is generally correlated with fewer postpartum hemorrhage and infections in general population, while the hemodynamic and physiological variations during labor may easily induce RV failure in pregnant women with PH. Cesarean section is favored by our obstetricians for the following possible reasons: (1) cesarean section avoids further increase in CO and hemodynamic swings associated with labor; (2) planned cesarean section allows the MDT to develop the relatively optimal delivery plan (e.g., stabilization of hemodynamics and evaluation of anesthesia); (3) the material mortality risk of cesarean delivery may be higher after failed trials of labor.
The optimal timing of elective delivery in women with PH has been controversial. Although there was no significant difference in the median delivery time in two groups, the post-MDT had a higher rate of preterm (55.6% vs. 34.7%, p = 0.034). Most preterm births were discussed and determined by the MDT. It is noteworthy that the mean baby weight of the post-MDT group was slightly heavier than that in the pre-MDT group (2469±652 vs. 2481±679 g, p = 0.752), probably because the number of IUGR of the former was significantly lower than that of the former. Furthermore, although the post-MDT group increased in iatrogenic preterm births, the fetuses of 75.7% (n = 25/33) were delivered in the near term (between 34 - 36 weeks of gestation)
Anesthesia Selection and Challenge
Epidural anesthesia perhaps is considered preferred anesthesia for PH pregnant women, while there has been rare robust evidence demonstrating that general anesthesia significantly increases maternal mortality[28, 29]. Before the MDT was established, three patients died under general anesthesia, and two died under epidural anesthesia (n=3/18, 16% vs. n=2/20,10%, p = 0.595), whereas no deaths were found in planned cesarean section with general anesthesia. In the post-MDT group, general anesthesia tended to be the major with invasive arterial blood pressure monitoring by radial artery line in all patients if available. In addition, the central venous pressure (CVP) of 70 patients were monitored, with no infection complications founded. As revealed by the positive results, general anesthesia may be a safe anesthesia for pregnant women with PH with adequate preoperative preparation and intraoperative monitoring. General anesthesia is capable of more effectively controlling the changes of patients' condition during operation, except that it is likely to affect the fetus. However, the time from anesthesia to fetal delivery is usually very short, and our anesthesiologists adopts general anesthesia more.