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J R Soc Med. 2001 October; 94(10): 523–525.
PMCID: PMC1282209

Primary pulmonary hypertension in pregnancy

P S C Wong, MD MRCP, S Constantinides, ChB MRCP, V Kanellopoulos, MB ChB, C R Kennedy, MB ChB FRCOG, D Watson, MB ChB FFARCSI, and M F Shiu, MD FRCP

The diagnosis of pulmonary hypertension in pregnancy requires early investigation and difficult judgments.


A woman aged 31, in the 24th week of her third pregnancy, reported haemoptysis for the preceding day. Before this pregnancy she had smoked 20 cigarettes a day; she had noticed mild dyspnoea on exertion over the preceding 12 months. 8 years earlier she had used three different slimming pills over a period of 3 months. Her two previous pregnancies, 14 and 11 years previously, had been uncomplicated. There was no personal or family history of thromboembolic disease. On physical examination there was central cyanosis, pulse 97/min, blood pressure 131/68 mmHg, normal jugular venous pulse. The precordial right ventricular impulse was exaggerated with a prominent pulmonary second heart sound. The lung fields were clear. There was no ascites or peripheral oedema, and signs of deep venous thrombosis were absent. Haematological and biochemical indices were normal apart from a mildly raised white cell count consistent with pregnancy (14 × 109/L, neutrophils 73%, lymphocytes 19%, eosinophils 1%). The C-reactive protein was normal. The 12-lead electrocardiogram showed right axis deviation, right ventricular hypertrophy and strain with an incomplete right bundle branch block. On chest radiography there was bilateral proximal enlargement of the pulmonary vasculature and peripheral vascular pruning (Figure 1). Pulmonary hypertension was diagnosed. Arterial blood gases, with the patient breathing room air, were PO2 8.4 kPa and PCO2 3.2 kPa; pH was 7.4, bicarbonate 17.7 mmol/L and base excess -3.5. Pulmonary embolism became an unlikely explanation when a radionuclide ventilation perfusion lung scan (VQ) was reported normal together with a fibrin degradation product D-dimer of 0.1 mg/L (normal <0.3). Transthoracic echocardiography showed a dilated and hypertrophied right atrium and right ventricle (Figure 2), without septal defect or thrombus. The peak velocity of tricuspid regurgitation was 4.3 m/s with a calculated peak pulmonary artery (PA) pressure of 74 mmHg (normal 15-25). After careful consideration of the possible causes of pulmonary hypertension (Box 1), primary pulmonary hypertension was felt the most likely diagnosis. This was supported by findings at right-heart catheterization, when the absence of a step-up O2 saturation excluded a significant left to right shunt; moreover, the PA pressure was 94/44 mmHg (normal systolic 15-25, diastolic 8-15) and pulmonary capillary wedge pressure was 8 mmHg (normal 4-12). The response of the pulmonary vasculature to O2 and nifedipine was tested and there was no significant fall in the PA pressure.

Figure 1
Radiograph showing bilateral proximal enlargement of pulmonary vasculature and peripheral pruning
Figure 2
Echocardiography findings of dilated and hypertrophied right atrium and ventricle RV=right ventricle; RA=right atrium; LV=left ventricle; LA=left atrium

Box 1 Causes of pulmonary hypertension

Cardiac diseases

  • Congenital: left to right shunts (e.g. atrial septal defect, ventricular septal defect, persistent ductus arteriosus)
  • Acquired: left ventricular failure, mitral valve disease, left atrial thrombus or tumour

Respiratory diseases

  • Chronic obstructive pulmonary diseases (e.g. chronic bronchitis, emphysema, asthma, bronchiectasis)
  • Chronic parenchymal lung diseases (e.g. pulmonary fibrosis, pneumoconiosis, extrinsic allergic alveolitis)
  • Cystic fibrosis
  • Obstructive sleep apnoea
  • Thoracic cage abnormalities

Pulmonary thromboembolism

Pulmonary vasculitides (e.g. lupus erythematosus, scleroderma, rheumatoid disease)

Hyperviscosity syndromes (e.g. multiple myeloma)

Infections (e.g. human immunodeficiency virus, schistosomiasis)

Portal hypertension


Pulmonary veno-occlusive disease

Primary pulmonary hypertension, including drug-related (e.g. appetite suppressants, cocaine)

When primary pulmonary hypertension was diagnosed, a multidisciplinary team comprising a cardiologist, obstetrician, intensive-care anaesthetist, paediatrician and midwife was assembled to manage the patient. Since she had reached the 26th week of gestation and was stable with no suggestion of right heart failure, pregnancy was cautiously continued with close monitoring of the maternal and fetal condition. At the 28th week she was transferred to the intensive-care unit. A pulmonary artery flotation catheter was inserted and PA pressure was 97/43 mmHg (systemic blood pressure 140/65 mmHg). Nebulized Iloprost 15 μg lowered the PA pressure to 72/33 mmHg, an effect lasting 3 hours; systemic blood pressure was unaffected. The patient was then transferred to theatre where a lumbar epidural catheter was inserted. Nebulized Iloprost 15 μg was administered and the PA fell from 100/40 to 83/33 mmHg. Epidural anaesthesia was established and a girl weighing 1.1 kg (Apgar scores 9 at 1 min and 9 at 5 min) was delivered by lower-segment caesarean section. After delivery the mother remained in the intensive-care unit for 5 days; nebulized Iloprost (20 μg 4-hourly) was continued for 16 days and gradually tailed off. The mother was discharged 20 days later accompanied by her daughter in good condition. 18 months after delivery, she was receiving warfarin and supplemental oxygen, and was being followed up by a specialized pulmonary hypertension clinic. She was dyspnoeic on mild exertion but had been able to return to work with the aid of a wheelchair.


Primary pulmonary hypertension is a rare disease that particularly affects women of childbearing age1. It is characterized histologically by the presence of medial hypertrophy, intimal fibrosis and often fibrinoid necrosis, arteritis and plexiform lesions in the pulmonary vasculature2. This disease can be defined clinically by a persistently raised PA pressure (mean pressure >25 mmHg at rest or >30 mmHg during exercise) without an obvious aetiology3. Most of the secondary causes of pulmonary hypertension were effectively excluded in our patient, with the exception of her previous exposure to appetite suppressant drugs.

In a recent overview4 the maternal mortality of primary pulmonary hypertension in pregnancy was said to be 30%, and it was as high as 56% in an earlier study5. Most of the deaths were in the third trimester, with the highest risk in the first 10 days postpartum. In view of the high maternal mortality, preconceptional counselling is of vital importance if feasible. In cases of unplanned pregnancy or diagnosis early in pregnancy, termination should be considered3. If pregnancy is to be continued, further management will require a multidisciplinary team.

Pulmonary embolism is an important differential diagnosis of pulmonary hypertension and a major cause of maternal mortality. It can be diagnosed from a positive VQ scan showing high probability (low sensitivity) and a raised D-dimer (low specificity); an unequivocally normal VQ scan and D-dimer virtually exclude the diagnosis. Alternatively, computed tomographic pulmonary angiography can be used to diagnose pulmonary embolism (sensitivity 0.8, specificity 0.9), but the radiation dose is tenfold higher. Apart from excluding the presence of a cardiac shunt, right heart catheterization can measure cardiac pressures and indicate potential benefits from various drugs (see below), and pulmonary angiography will demonstrate emboli if present. In our patient, pulmonary angiography was not performed because of severe pulmonary hypertension. It is necessary to discuss with the mother the importance of performing these investigations and the potential radiation hazards to her and the fetus. Once in possession of information on the pulmonary and systemic circulation and the state of the fetus, the multidisciplinary team can determine the optimum time for delivery.

Vasoconstriction from a reduction of nitric oxide and prostacyclin, together with an increase in endothelin and thromboxane in the vascular endothelium and smooth muscle, is important in the pathogenesis of primary pulmonary hypertension. Various vasodilator treatments have been tried in the past, and agents showing benefits include O2, oral calcium channel blockers, continuous intravenous prostacyclin, inhaled nitric oxide, and nebulized prostacyclin or its stable analogue Iloprost. Responsiveness to these treatments can be evaluated at the time of cardiac catheterization. In our patient we chose nebulized Iloprost because of its proven efficacy, relative ease of administration and direct delivery to the lungs with few systemic effects6.

Clinicians who encounter pregnant women with primary pulmonary hypertension would benefit from access to national and international databases. These patients should usually be followed up by specialized centres, so that their treatment and possible need for transplantation can be monitored closely.


We thank Dr R J Elton, consultant anaesthetist, Walsgrave Hospital, and Mr E W A Needham, research officer, University of Warwick, for advice.


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Articles from Journal of the Royal Society of Medicine are provided here courtesy of Royal Society of Medicine Press