In two large series identifying predictors of maternal cardiac complications during pregnancy in women with heart disease, pulmonary hypertension did not emerge as a predictor of adverse outcome [
7,
8]. This is probably due to low prevalence since women with pulmonary hypertension are generally advised against pregnancy. Based on disease-specific literature, there is no doubt that pulmonary hypertension is associated with severe maternal complications and high mortality. Two systematic literature reviews have described the outcome of pregnancy in women with pulmonary hypertension, covering a total period of almost 30 years and comprising 198 pregnancies [
9,
10]. The mortality of women with Eisenmenger syndrome (
N = 102) was 36% in the first review (1978–1996) and 28% in the second review (1997–2007). Most women died in the first month after delivery and the main causes of death were heart failure and sudden death, while pulmonary thromboembolism was another frequent cause. In women with idiopathic pulmonary hypertension (
N = 56) mortality was 30% in the first and 17% in the second review. Again most women died after delivery and heart failure was an important cause of mortality. Women with other causes of pulmonary hypertension (
N = 40) had a mortality of 56% and 33% respectively. Nearly all fatalities occurred early post-partum and death was mainly due to heart failure while sudden death and thromboembolism also contributed. Total mortality was significantly higher in the earlier period (1978–1996) compared with the last 10 years (1997–2007), 38% versus 25% (
p = 0.047). However, since many case reports or very small series were included in the reviews, publication bias can not be excluded. In the first review (1978–1996), late diagnosis of pulmonary hypertension (
p = 0.002, odds ratio 5.4) and late hospital admission (
p = 0.001, odds ratio 1.1 per week of pregnancy) were independent predictors of maternal mortality. In the second review (1997–2007), primigravidae and women who received general anaesthesia at delivery had a higher risk of death. Women with previous pregnancies may have had a lower risk because they had less severe disease, since they have already survived a pregnancy. The higher risk for women who had general anaesthesia may be due to the inherent risks of general anaesthesia, or because general anaesthesia was more often applied in women with a more grave clinical condition [
10].
It is not known if women with lower pulmonary pressures and resistance are at lower risk. Systolic or mean pulmonary artery pressures did not predict mortality in either of the reviews, but this is possibly explained by missing data. In the first review (1978–1996) diastolic pulmonary artery pressure was a univariate risk factor for adverse outcome. In both reviews, the majority of women who died had severe pulmonary hypertension, but also some women with mild or moderate pulmonary hypertension deteriorated. A safe cut-off value is not known [
1,
2,
9,
10].
In the period covered by the second review, advanced therapy for pulmonary hypertension was becoming increasingly available, but though a significant percentage of women were treated with NO or prostacyclin analogues, the institution of advanced therapy did not predict a better outcome. The authors comment that advanced therapy was in most cases commenced late in the course of the disease, when patients were unstable or had refractory heart failure [
10], and that an earlier start of these therapies will possibly improve outcome. Until recently, no evidence concerning this subject was available. In 2010 a single-centre series of 10 consecutive pregnancies during 2002–2009 reported improved outcomes. A multiprofessional approach was applied to all women, with early institution of targeted therapy (nebulised prostanoid therapy, changing to intravenous prostanoid when clinical deterioration or insufficient response occurred). Planned caesarean delivery with epidural or combined epidural/spinal anaesthesia was performed at 34 weeks, or earlier when clinical deterioration occurred. Most women received therapeutic or prophylactic anticoagulation therapy. All 10 pregnancies resulted in live births, and no maternal mortality occurred during pregnancy or early after delivery. One woman died 4 weeks after delivery, after stopping her therapy at home and declining hospital admission when she deteriorated. This series is small, but the results are promising. The authors state that the risk of pregnancy remains high and despite their results, women with pulmonary hypertension should be advised against pregnancy and when they become pregnant, termination should be offered [11.]
Neonatal outcome is also compromised in women with pulmonary hypertension. The rate of premature labour and premature delivery is high. Offspring mortality occurs in about 10%, and seems higher in Eisenmenger syndrome [
9,
10,
12]. In Eisenmenger syndrome, there is also a high percentage of small for gestational age children [
12].