Johanna Trinder

Low‐molecular‐weight heparin or warfarin for anticoagulation in pregnant women with mechanical heart valves: what are the risks? A retrospective observational study

Please cite this paper as: Basude S, Hein C, Curtis S, Clark A, Trinder J. Low‐molecular‐weight heparin or warfarin for anticoagulation in pregnant women with mechanical heart valves: what are the risks? A retrospective observational study. BJOG 2012;119:1008–1013.

Current trends in the management of heart disease in pregnancy

BACKGROUND The management of heart disease in pregnancy is highly specialized. Guidelines are based on observational studies. This paper describes our experience of these patients, including adverse cardiac events, adherence to guidelines, and areas of suboptimal management. METHODS Patients referred to the service between 01/05/1999 and 30/06/2005 were identified using clinic lists and keyword searches in databases. A list of 40 management standards was created from European Society of Cardiology and the Confidential Enquiry into Maternal and Child Health guidelines. Adherence to these was recorded and adverse cardiac events noted. RESULTS There were 177 pregnancies in 155 women with a mean age of 28+/-6 years. Service referrals increased linearly throughout the study period. Of 131 cardiac pregnancies 101 had congenital heart disease (77.1%). Pulmonary oedema, deteriorating functional class, sustained arrhythmia or cardiac intervention occurred in 13 pregnancies (10.2%), though not always in high risk cases. Management guidelines were largely followed, though areas of suboptimal management included lack of pre-conception advice and inadequate post-partum follow-up. Controversial areas include the use of beta-blockade in coarctation of the aorta and the use of elective Caesarean section in high risk patients. CONCLUSIONS Cardiac pregnancies are increasing, mainly due to the rise in patients with congenital heart disease. Some patients will experience adverse cardiac events, including low risk patients. Pre-conception advice and post-partum follow-up should be improved. In the absence of prospective studies, management is likely to be driven by observational studies.

Endometriosis and infertility: The debate continues

A causal relationship between minor endometriosis and infertility or subfertility has not yet been demonstrated, although a significant association is shown by prevalence studies. This article critically reviews the evidence for pituitary-ovarian dysfunction as a cause for subfertility in women with minor endometriosis. The lack of fertile controls with endometriosis presents a methodological problem. Group comparison in studies using tubal infertility cases as controls has demonstrated impaired follicular growth, reduced circulating oestradiol concentrations during the preovulatory phase and oestradiol and progesterone during the early luteal phase, and disturbed luteinizing hormone (LH) surge patterns. LH concentration in preovulatory follicular fluid is also reduced, and granulosa cells collected at the same time have impaired steroidogenic capacity in vitro. However, these findings are not consistent in published studies. Significantly lower oocyte fertilization rates (49%) are found compared with controls (69%), even after maximum stimulation with exogenous follicle-stimulating hormone and human chorionic gonadotrophin (52% versus 69%). The implantation rate is also lower (11% versus 13%). An inherent disorder of follicular function seems likely, and LH surge impairment is probably a secondary effect. Impairment of oocyte fertilization would thus contribute substantially to the natural subfertility associated with endometriosis, but in vitro fertilization is still successful as excess numbers of oocytes are available.

Cardiac outcome of pregnancy in women with a pacemaker and women with untreated atrioventricular conduction block

AIMS The natural history and outcome of pregnancy in patients with a pacemaker or those presenting with atrioventricular conduction block in pregnancy are unknown with only a limited number of case reports published. METHODS AND RESULTS This study examines the progress and outcome of 25 pregnancies in 18 women who were either paced or presented with untreated atrioventricular conduction block during pregnancy. All patients were seen in a single referral centre between 1998 and 2008 and were evaluated at regular intervals with ECG, echocardiography, and 24 h Holter. Four women (4 pregnancies) had new-onset atrioventricular block, 3 women (5 pregnancies) had previously diagnosed atrioventricular block who had not undergone pacing, and 11 women (16 pregnancies) had known atrioventricular block with a pacemaker prior to pregnancy. Of the four patients presenting for the first time in pregnancy, the frequency or severity of atrioventricular conduction block increased during pregnancy. One required pacing during and one after pregnancy. In two patients the conduction disturbance resolved postpartum. In the three patients who had known but untreated atrioventricular block before pregnancy, this progressed during each pregnancy but did not require pacing. In patients paced before pregnancy, there were no complications as a result of the pacemaker, but maternal complications were seen in patients with underlying structural heart disease. CONCLUSIONS Atrioventricular block in pregnancy is progressive; pacing is not always required but all patients should be closely monitored during and after pregnancy. In patients paced before pregnancy, pacing is well tolerated.

Pregnancy outcome and follow-up cardiac outcome in women with aortic valve replacement

Objectives To compare the maternal, fetal and cardiac outcomes in women who have undergone aortic valve replacement. Method Retrospective observational study of all women with aortic valve replacement, who underwent a pregnancy (1998–2012). Maternal-, fetal- and valve-related cardiac outcomes were assessed. Results Thirty-two pregnancies in 16 women with aortic valve replacement (nine bioprosthetic, six Ross and 17 mechanical) were evaluated. There were no adverse maternal events in the bioprosthetic and Ross groups but three in the mechanical group. Fetal loss rate was highest in the mechanical valve pregnancies (53%). One woman in the bioprosthetic group needed valve re-operation, and one woman in the mechanical valve group died. There was no difference in the change of Vmax over the follow-up between the valves (p = 0.25). Conclusions There was no difference in deterioration between aortic valve replacements during and after pregnancy. The highest risk of maternal and fetal complications occurred in the mechanical valve group.

Warfarin versus low molecular weight heparin: a comparison of adverse outcomes in pregnant women with mechanical heart valves

A consensus is yet to be reached regarding the anticoagulation regimen that is both safe for the fetus and effective for women with mechanical heart valves in pregnancy. We compared the outcomes and adverse events in women with mechanical heart valves attending the tertiary cardiac antenatal clinic (University Hospitals Bristol, 2003–2010). Women were offered anticoagulation with low molecular weight heparin/aspirin(LMWHa), Warfarin or a Combination regimen(LMWHa from 6 weeks/warfarin 14–36 weeks/LMWHa 36+). All women were informed that warfarin was likely to be the safest option for them, although not for the fetus. Results A total of 30 pregnancies in 15 women were identified. Aortic (13), aortic/mitral (2), mitral (12), tricuspid (3). Women were anticoagulated with LMWHa (3), Warfarin (21) and Combination (6). Rates of pregnancy loss before 24 weeks were 0/3 LMWHa, 16/21 Warfarin (dose range 4–13 mg), 3/6 Combination (two 2nd trimester after restarting warfarin). Live births were achieved in 2/3 women (LMWHa), 5/21 (Warfarin) and 3/6 (Combination). There were eight adverse maternal events: TIA (Combination) at 9 weeks while on LMWHa (the patient was non-compliant), maternal death from a parietal haemorrhage at 8 weeks (LMWHa) and a mitral valve thrombosis at 35 weeks (LMWHa), both patients were compliant with peak Anti-Xa 1.0–1.2 IU/ml. Postpartum or postspontaneous abortion haemorrhage occurred in five women (3/21 Warfarin, 1/3 LMWHa, 1/6 Combination). Conclusions Warfarin is associated with an unacceptably high fetal loss rate, but severe adverse maternal outcomes are associated with LMWHa, even when therapeutic peak anti-Xa levels are achieved. A national database to collect this information is recommended.

Pregnancy and lactation during long-term total parenteral nutrition: A case report and literature review

There is a paucity of clinical data regarding the management of pregnancy and lactation in women requiring long-term total parenteral nutrition with complex nutritional needs. This case report and literature review highlights common challenges in care and presents evidence which can guide the obstetrician’s approach to care.

Use of beta-blocker medication in cardiac disease in pregnancy- a retrospective case-control study

Background Beta-blockers have been used for many decades in pregnancy: to treat hypertension, supraventricular and ventricular tachycardias and as prophylaxis against aortic root dilatation. Evidence suggests that the use of beta-blockers is associated with intrauterine growth restriction (IUGR), oligohydramnios and premature labour. It has been proposed that this could be the result of underlying hypertension. Aims To assess if beta-blocker medication is an independent risk factor for IUGR in non-hypertensive women with heart disease. Design Retrospective case-control study. Method A case note and data base review was undertaken at a tertiary referral centre from January 2002- August 2011. Women requiring beta blockade in pregnancy for non-hypertensive heart disease were compared to age and race matched controls. Women with left sided obstructive heart disease and impaired systemic ventricular function were excluded. Main Outcome Measures Primary Birth weight standardised for gestational age. Secondary: Perinatal morbidity, admission to SCBU, gestation of delivery, hypoglycaemia, mode of delivery. Results 26 women taking beta-blockers were compared to 34 controls. Compared to controls, taking beta-blockers was associated with smaller birth weight (3015g v 3423g, p= 0.004, corrected for centile, p= 0.03). There was a trend towards increased IUGR < 10th centile (19% vs 6% p= 0.119), increased SCBU admissions (15% vs 3% p= 0.156), and neonatal hypoglycaemia (19% vs 3% p = 0.075). Conclusion Beta blockade in pregnancy results in low birth weight, and a trend to neonatal complications in non-hypertensive women. The drugs themselves cause significant fetal complications independent of maternal hypertension and should be avoided in pregnancy if possible.

Pregnancy outcomes in women with cystic fibrosis

Recent improvements in medical care have enabled women with cystic fibrosis (CF) to achieve a greater life expectancy and aspire to a greater expectation from life. Literature reporting pregnancy outcome in women with CF is sparse and focuses on women with mild disease. There remains a legacy of advising women with significant disease (FEV1<60%) to avoid pregnancy. Pregnancy data was reviewed from all women with CF receiving care at a tertiary centre between 2003–2011. Input into hospital antenatal care was provided by a CF respiratory physician, an obstetrician in maternal medicine, a CF dietician, a CF physiotherapist and an obstetric anaesthetist. Individualised multidisciplinary plans were made for antenatal, delivery and postpartum care in all women. CF was managed aggressively with optimisation of nutrition, prompt treatment of infection and inpatient admission if necessary. Results A total of 14 pregnancies in 12 women were identified. Mean age of pregnancy was 29.5(26–36). FEV1 at booking ranged from 27–80% (mean=62.8%). Diabetes was present in 9/14 women(three pre-pregnancy). The average gestation at delivery was 37+3(30–41). Vaginal delivery was advised in all cases (no obstetric contraindication), with elective epidural, oxygen support and passive management of the second stage. There was a 100% vaginal delivery rate (11 spontaneous vertex, 2 ventouse, 1 forceps). Average birth weight was 2.97 kg (2.2–3.83 kg). There were no postpartum complications. Conclusion With careful multidisciplinary management, successful outcomes with vaginal deliveries have been obtained in this small series of women with CF, with a mean FEV1 of just over 60%.