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Please cite this paper as: Curry R, Fletcher C, Gelson E, Gatzoulis M, Woolnough M, Richards N, Swan L, Steer P, Johnson M. Pulmonary hypertension and pregnancy—a review of 12 pregnancies in nine women. BJOG 2012;119:752–761.
Objective To report outcomes in a recent series of pregnancies in women with pulmonary hypertension (PH).
Design Retrospective case note review.
Setting Tertiary referral unit (Chelsea and Westminster and Royal Brompton Hospitals).
Sample Twelve pregnancies in nine women with PH between 1995 and 2010.
Methods Multidisciplinary review of case records.
Main outcome measures Maternal and neonatal mortality and morbidity.
Results There were two maternal deaths (1995 and 1998), one related to pre-eclampsia and one to arrhythmia. Maternal morbidity included postpartum haemorrhage (five cases), and one post-caesarean evacuation of a wound haematoma. There were no perinatal deaths, nine live births and three first-trimester miscarriages. Mean birthweight was 2197 g, mean gestational age was 34 weeks (range 26–39), and mean birthweight centile was 36 (range 5–60). Five babies required admission to the neonatal intensive care unit, but were all eventually discharged home. All women were delivered by caesarean section (seven elective and two emergency deliveries), under general anaesthetic except for one emergency and one elective caesarean performed under regional block.
Conclusions Maternal and fetal outcomes for women with PH may be improving. However, the risk of maternal mortality remains significant, so that early and effective counselling about contraceptive options and pregnancy risks should continue to play a major role in the management of such women when they reach reproductive maturity.
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Pregnancies in women with pulmonary vascular disease are rare, with an estimated incidence of 1.1 per 100 000 maternities.1 The maternal mortality reported in the 1990s was 30–56%,2 probably because of the limited ability of women with pulmonary hypertension (PH) to adapt to the cardiovascular changes of pregnancy. The outcome for the fetus was also reported to be poor, with high rates of preterm delivery, fetal growth restriction and perinatal mortality.3 Published data on pregnancy with PH are limited to case reports or series; however, a recent review suggested that because of improved management, and in particular advanced therapies, maternal mortality may now be lower, in the region of 25%. Although current guidelines recommend discouraging pregnancy4,5 and the use of maximally effective contraception, with early termination should pregnancy occur, some women with PH still choose to become pregnant, or to continue with an unplanned pregnancy. Because data on pregnancy in these women are sparse, we report the maternal and fetal outcomes of 12 pregnancies in nine women with PH under our care.
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There were 12 pregnancies in nine women. Their baseline characteristics, together with maternal and neonatal outcomes, are recorded in Table 1. Their mean age at the initial clinic visit was 27 years (median 25 years, range 19–38). There were seven primigravidas. In four women (A, B, D and E) the diagnosis of PH was made using echocardiography during the index pregnancy. The remaining women were diagnosed before pregnancy at cardiac catheterisation, with the exception of patient I who was diagnosed by echocardiography, but not referred to our centre until she became pregnant. The PH aetiologies were varied—one each for idiopathic, HIV, left heart disease and primary lung disease and five congenital heart disease.
Table 1. Baseline characteristics, maternal and neonatal outcomes
|Year||Patient (pregnancy no.)||Age||Parity||Gestation at diagnosis||Aetiology||WHO class||PASP (mmHg)||RV function||Gestation at delivery||Mode of delivery||EBL (ml)||BW (g)||BW centile||Maternal complications||Maternal outcome||Neonatal complications||Neonatal outcome|
|1995||A||28||0||Pre-pregnancy||CHD (VSD, Eisenmenger)||I||104||Moderately impaired||26||Emergency LSCS||1000||620||5||Fulminating pre-eclampsia||Death D15 PAH Crisis||PTD SGA NICU||Alive and well|
|1998||B||33||0||Pre-pregnancy||CHD (Secundum ASD closed with Dacron patch aged 19)||I–II||55–60||Good||36 + 4||Emergency LSCS||300||2570||35||Non-sustained VT—3rd trimester Sustained SVT at LSCS||Intra-operative death||PTD||Alive and well|
|2003||C||24||0||24 weeks||CHD (ToF variant with complex pulmonary atresia and MAPCAs)||III||Assumed to be systemic||Good||34||Elective LSCS||600||2080||27||PPH||Still living||PTD NICU||Alive and well|
|2007||D(1)||19||0||Pre-pregnancy||L heart disease (restrictive LA)||II||38||Good||Misc. 6/40 ERPC|| || || || ||Nil||Still living|| || |
|2007||E||25||0 + 1||Pre-pregnancy||iPH||II||106||Severely impaired||32||Elective LSCS||400||1650||37||Worsening RV function||Still living||PTD NICU||Alive and well|
|2007||F||38||2||23 + 5 weeks||Thromboembolic/ primary lung disease (emphysema)||III||102||Mildly impaired||33 + 2||Elective LSCS||500||2090||50||Return to theatre to evacuate wound haematoma||Still living||PTD NICU||Alive and well|
|2008||G(1)||24||1||36 weeks||CHD (Repaired PDA, VSD; absent LPA and hypoplastic L lung)||II||65||Good||37||Elective LSCS||800||2356||9||PPH||Still living||SGA||Alive and well|
|2008||G(2)||25||2||Pre-pregnancy||CHD (Repaired PDA, VSD; absent LPA and hypoplastic L lung)|| || || ||Misc. 12/40|| || || || ||Nil||Still living|| || |
|2008||H||28||0||23 weeks||CHD (AVSD with Eisenmenger physiology)||I–II||90||Good||34||Elective LSCS||1000||2184||50||PPH||Still living||PTD NICU||Alive and well|
|2009||D(2)||21||0 + 1||Pre-pregnancy||L heart disease (restrictive LA||III||60||Good||Misc. 7/40 ERPC|| || || || ||Atrial tachycardia Thyrotoxicosis||Still living|| || |
|2009||I||32||1||Pre-pregnancy||HIV||I–II||45||Good||39||Elective LSCS||800||3440||60||PPH||Still living||Nil||Alive and well|
|2009||G(3)||26||2 + 1||Pre-pregnancy||CHD (Repaired PDA, VSD; absent LPA and hypoplastic L lung)||II–III||70||Mild dysfunction||37||Elective LSCS||1000||2786||50||PPH Post-op. ileus||Still living||Nil||Alive and well|
Maternal mortality and morbidity
There were two maternal deaths, both before 1999. Patient A (1995) died on postnatal day 15 following a PH crisis, having been delivered at 26 weeks gestation for fulminating pre-eclampsia. Patient B (1998) died at caesarean section having developed intractable supraventricular tachycardia following manual delivery of the placenta and administration of repeated bolus doses of oxytocic drugs (policies which have since been changed). All women were delivered by caesarean section (seven elective and two emergency deliveries), all under general anaesthetic except for one elective and one emergency caesarean performed under regional block. Estimated blood loss at delivery ranged from 300 to 1000 ml (mean 711). In the five most recent cases the third stage was managed with a low-dose oxytocin infusion rather than a bolus and in four women uterine compression sutures were also used.6 In one case the third stage was managed with compression sutures alone, and no oxytocics were given.
Symptomatic and functional assessment, echocardiographic measurements at baseline, during pregnancy and at follow up, are summarised in Table 2. Patients were monitored throughout their pregnancies by echocardiography and clinical examination. Estimations of pulmonary artery pressure were assessed from the tricuspid and pulmonary artery Doppler. Detailed assessments of right ventricular size and function were the key drivers of management. Medical treatment is summarised in Table 3. Patient A received intravenous unfractionated heparin following delivery only. Subsequently, seven women were anticoagulated with subcutaneous low-molecular-weight heparin (LMWH). Their level of anticoagulation was determined by their thrombotic risk; patients E, F and H (who had been taking warfarin before pregnancy) received therapeutic doses of LMWH and were monitored by measurement of anti-Factor Xa levels. The other women were given prophylactic doses of LMWH. Patient A received intravenous iloprost postpartum. Six of the nine women (all from 2007 onwards) were treated with sildenafil throughout pregnancy; one of them (E) was given add-on therapy with nebulised iloprost during the pregnancy because of a significant deterioration in her symptoms. Table 3 also reports the anaesthetic management at delivery. Six cases had invasive monitoring with peripheral arterial lines and central venous pressure lines. In five cases, cardiac output was monitored intraoperatively using transoesophageal echocardiography.
Table 2. Functional and echocardiographic assessment
|Year||Patient (Pregnancy no.)||WHO Class||RVSP||RV Function|
|Baseline||Worst during pregnancy||6–12 month follow up||Baseline||Worst during pregnancy||6–12 month follow up||Baseline||Worst during pregnancy||6–12 months follow up|
|1995||A||I||I–II||N/A||104||104||N/A||Moderately impaired||Moderately impaired||N/A|
|2003||C||III||III||II||Assumed systemic (120)||Systemic||*||Good||Good||*|
|2007||E||II||II–III||III||106||120||110||Severely impaired||Severely impaired||Severely impaired|
|2007||F||III||II–IV||III||102||102||101||Mildly impaired||Mildly impaired||Mildly impaired|
|2008||G(2)||Spontaneous miscarriage—no data available|
|2009||G(3)||II–III||III–IV||III||70||80||51||Mild dysfunction||Mild dysfunction||Good|
Table 3. Medical, obstetric and anaesthetic management
|Year||Patient (Pregnancy No.)||Medical therapy||Third stage||GA/RA||CO Monitoring||Pre-induction||Lines||Induction||Maintenance||Vasoconstrictors||IV fluids||Intraoperative Complications|
|1995||A||IV UFH (PN) IV iloprost (PN) ||Oxytocin bolus × 2||GA||None||Ranitidine Maxolon NaCitrate Diazepam||CVC Arterial line||Fentanyl Etomidate Vecuronium||ETT IPPV with O2/N2O/halothane Diazepam||Phenylephrine boluses||Crystalloid 1000 ml Colloid 1750 ml RBCs 4 units||Sinus tachycardia Treated with Esmolol|
|1998||B||Diltiazem||Oxytocin bolus × 2||RA (labour epidural topped up)||None|| ||CVC Arterial line||14 ml 0.5% bupivicaine (3-ml aliquots over 30 minutes) 100 μg fentanyl||N/A||Phenylephrine boluses||Crystalloid 1000 ml||SVT 5 minutes post 2nd dose syntocinon during removal of placenta, hypotension and asystole Intubated and CPR Initiated. Resuscitation for >1 hour |
|2003||C||SC LMWH|| ||GA||Anaesthetic notes not available|
|2007||D(1)||SC LMWH Sildenafil||Miscarriage|
|2007||E||SC LMWH Sildenafil Nebulised iloprost Furosemide||Compression suture||GA||TOE|| ||Wide bore peripheral access Arterial line||Fentanyl Etomidate Suxamethonium||Propofol infusion Atrcurium Fentanyl Morphine Paracetamol Ilio-inguinal blocks|| || ||Bradycardia after induction|
|2007||F||SC LMWH Sildenafil||Oxytocin infusion Compression suture||GA||TOE Trans-oesophageal doppler|| ||Wide bore peripheral access Arterial line PAC introducer||Fentanyl Etomidate Suxamethonium||ETT IPPV with O2/isoflurane Vecuronium Morphine Paracetamol Ilioinguinal blocks|| ||Crystalloid 1000 ml||Bradycardia after induction|
|2007||G(1)||SC LMWH Sildenafil||Oxytocin infusion Compression suture||GA||TOE||Ranitidine NaCitrate||Large bore peripheral Arterial line CVC PAC introducer||Etomidate Fentanyl Suxamethonium Atropine||ETT IPPV with O2/isoflurane Morphine Paracetamol Ilioinguinal blocks|| ||Minimal crystalloid Colloid 500 ml RBCs 2 units||Persistant Tachycardia|
|2008||G(2)||SC LMWH Sildenafil||MISCARRIAGE|| || || || || || || || || |
|2008||H||SC LMWH Sildenafil ||Oxytocin infusion Compression suture||GA||TOE||Ranitidine NaCitrate||Large bore peripheral Arterial line CVC PAC introducer||Etomidate Fentanyl Suxamethonium Atropine||ETT IPPV with O2/isoflurane Morphine Paracetamol Vecuronium Ilioinguinal and rectus sheath blocks|| ||Crystalloid 500 ml Colloid 500 ml||None|
|2009||D(2)||SC LMWH Sildenafil||MISCARRIAGE|| || || || || || || || || |
|2009||I||SC LMWH Sildenafil Antiretrovirals||Oxytocin infusion Compression suture||RA (Spinal)||None||Ranitidine||16G peripheral||Spinal of 2.5 ml 0.5% heavy bupivicaine, 300 mcg diamorphine||N/A||Phenylephrine 300 mcg||Crystalloid 1000 ml Colloid 500 ml||None|
|2009||G(3)||SC LMWH Sildenafil Furosemide||Oxytocin infusion||GA||TOE||Anaesthetic notes not available|
Perinatal mortality and morbidity
Three pregnancies resulted in miscarriage (two in patient D, one attributed to the development of thyrotoxicosis) and nine pregnancies resulted in a surviving child. Five women were delivered iatrogenically preterm because of maternal decompensation, their babies requiring admission to the neonatal intensive care unit (NICU). Two of the babies were small for gestational age (5th and 9th centiles). None of the babies in this series had any congenital abnormalities.
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Although PH is rare, ours is one of the largest consecutive series to be reported, so it adds significantly to the reported experience of managing this challenging condition. Nonetheless, small numbers limit the conclusions that can be drawn. Prospective, multicentre registry data are required to shed further light on both outcome and prognosis for this high-risk condition.
Maternal and fetal outcomes for women with pulmonary hypertension seem to be improving,3,35 but maternal risk remains extremely high, so timely and effective counselling on contraception and the hazards of pregnancy remain vital. PH pregnancies should be managed in a tertiary setting with a multidisciplinary team.
Disclosure of Interests
During the last 5 years Philip Steer has received funding and honoraria to support speaking at meetings from: Ferring Pharmaceuticals; Alliance Medical; Pfizer; Milupa; the Obstetric Anaesthetist’s Association; The University of Copenhagen; the North Midlands Urogynaecological Society; Postgraduate Education and Academic Affairs Department, National Guard Health Affairs, Riyadh, Saudi Arabia; the University of Copenhagen; and BabyLifeline. He has received funding to defray the expenses of attendance at meetings from FIGO (speakers honorarium), Bristol Hospitals Healthcare Trust, the Icelandic Medical Association, Capetown University, Rome University, the 3rd Military Hospital Chonqing, AsiaPacific Congress of Fetal/Maternal Medicine, the British Maternal and Fetal Medicine Society, the British Association of Perinatal Medicine, the European Congress of Perinatal Medicine, the Swedish Society of Obstetricians and Gynaecologists, the National Perinatal Society of Jordan, the National Perinatal Society of Turkey, Zurich University, Leuven University, the RCOG, the University of Nottingham and the International Association for Adult Congenital Heart Disease. He has received reimbursement for travel expenses and honoraria for examining from the Universities of Hong Kong, Lund and Stockholm. He has been treated to dinner while attending a meeting with representatives of Hewlett Packard Ltd. to discuss fetal monitoring. He has received fees for medicolegal opinions from the Welsh Health Legal Authority, Northwick Park Hospitals NHS Trust, Her Majesty’s Police, and various solicitors. He receives publication royalties from Elsevier, and ALCS. He chairs the medical advisory panel of ‘Group B Strep Support’ (unpaid). His research is funded by public bodies in the UK (including the HTA). The other authors did not report any potential conflicts of interest.
Contribution to authorship
RAC, CF, EG, MW and NR were responsible for the acquisition of the data. RAC and CF wrote the paper which was subsequently revised and edited by RAC, MAG, LS, PJS and MRJ.
Details of ethics approval
This study received approval from the Brompton, Harefield and NHLI Research Ethics Committee, REC reference 09/H0706/14.
No external funding was obtained for this review.