Maternal and fetal outcomes in pregnancies complicated by Marfan Syndrome

Matthew Cauldwell1*, Philip J Steer1, Stephanie Curtis2, Aarthi R Mohan3, Samuel Dockree4, Lucy Mackillop4 ,

Helen Parry5, James Oliver5 ,Monique Sterrenburg6, Suzanne Wallace7, Gemma Malin7, Gemma Partridge8, Leisa

Freeman9, Aidan Bolger10, Farah Siddiqui11 , Dirk Wilson12, Margaret Simpson13, Niki Walker13, Ken Hodgson14,

Kathryn Thomas14,Foteini Bredkai15, Rebecca Mercaldi16, Fiona Walker16**, Mark R Johnson**, 1

1. Academic Department of Obstetrics and Gynaecology, Chelsea and Westminster Hospital, 369 Fulham

Road, London, SW10 9NH, United Kingdom

2. Adult Congenital Heart Disease Service, University Hospitals Bristol NHS Foundation Trust, Bristol, United

Kingdom

3. Department of Obstetrics, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom

4. Women’s Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom

5. Department of Adult Congenital Heart Disease, Leeds Teaching Hospitals NHS Trust, Leeds, United

Kingdom

6. Department of Human Development and Health, Princess Anne Hospital, University of Southampton,

United Kingdom

7. Maternity Department, University Hospitals NHS Trust, Nottingham, United Kingdom

8. Department of Obstetrics, Norfolk and Norwich Hospital, United Kingdom

9. Department of Adult Congenital Heart Disease, Norfolk and Norwich Hospital, United Kingdom

10. Department of Adult Congenital Heart Disease, Glenfield Hospital, Leicester, United Kingdom

11. Department of Obstetrics, Royal Leicester Infirmary, Leicester, United Kingdom

12. Department of Paediatric Cardiology, University Hospitals Wales, Cardiff, United Kingdom

13. Scottish Adult Congenital Cardiac Service, Golden Jubilee National Hospital, Glasgow, United Kingdom

14. Department of Obstetrics, Newcastle upon Tyne, United Kingdom

15. Department of Obstetrics, University College Hospital, London, United Kingdom

16. Department of Adult Congenital Heart Disease, Bart’s Heart Centre, London, United Kingdom

Keywords: pregnancy, congenital heart disease

Conflict of Interest: None

Word count: 3020

*Corresponding author

** Joint Senior Authors

Acknowledgements: None

Funding: Nil

Conflict of Interest: None declared

Abstract

Background

The information on which to base counselling and managementpregnancy in of women with

Marfan Syndrome (MFS) in pregnancy is limited.

Objective

To provide data for counselling and management.

Methods

Retrospective observational study of women with MFS delivering between January 1998

and March 2018 in 12 UK centres reporting data on maternal and neonatal outcomes.

Results

Data on 164 pregnant women with MFS were analysed. In total, there were 258 pregnancies

in 164 women with MFS, including 226 pregnancies ≥24 weeks (two sets of twins), 20

miscarriages and 12 pregnancy terminations. Excluding miscarriages and terminations, there

were 221 livebirths in 139 women. Only 50% of women received preconception counselling.

There were no deaths, but five women experienced aortic dissection (1.9%; one type A and

four type B). Five women required cardiac surgery postpartum. No predictors for outcome

were found. Nineteen19 women had prior aortic root replacements, and one had a Type B

dissection at 12 weeks and terminated the pregnancy. The babies of the 131 (65.8%) women

taking beta-blockers were on average 316g lighter (p<0.001). Caesarean section rates were

high (50%), particularly in women with dilated aortic roots. In 55 women had aortic imaging

was available pre and post pregnancy, there was a small but significant average increase in

aortic root size of 0.9mm. The use of aAortic imaging in pregnancy increased in frequency

following the 2011 European Society of Cardiology guidelines.

Conclusion

There were no maternal deaths and thean aortic dissection rate wasof 1.9% (mainly type B).

There with no factors associated with dissection. Pre-conception counselling rates were low

and need improvement. Aortic size measurements increased marginally following

pregnancy.

249 Words

Keywords: Marfan, Pregnancy, dissection

Introduction

Marfan Syndrome (MFS) is an autosomal dominant condition caused by a mutation in the

FBN1 gene encoding fibrillin (1), causing connective tissue fragility. Internationally

recognised criteria define the condition (1, 2). Cardiovascular complications associated with

MFS are responsible for the associated increased mortality, predominantly related to aortic

dissection (AOD); but aortic and mitral valve regurgitation also contribute, as does MFS-

associated cardiomyopathy (3). Several series of pregnancy in women with MFS have been

described, but most are small and lacking in detail with regards to maternal and neonatal

complications (4-6).

Pregnancy appears to increase the risk of aortic dissection (AoD) in women with MFS, which

is furthermore increased by pregnancy-related complications such as hypertension (7). Both

the European Society of Cardiology (ESC) and the American Heart Association provide

guidance for the management of pregnancy in women with MFS, although this guidance

draws from a limited number of relatively small studies (8, 9). The modified World Health

Organisation (mWHO) classification is advised for risk stratification, (described by ESC

pregnancy guidelines), regards women without evidence of aortic root (AoR) dilatation to be

risk category II (small increased risk of maternal mortality). This risk increases to category III

(high risk) with an AoR diameter of between 40-45mm and category IV (highest

risk/extremely high risk of maternal mortalitycontraindication for pregnancy), with an AoR

diameter >45mm. They suggest that delivery in women with an AA of greater than 45mm

should be by Caesarean section (Level C evidence). Whilst it is logical to assume that those

with greater AoR diameters are at greatest risk of AoD, there are few data to support such

arbitrary cut offs in pregnancy; furthermore other factors such as family history of dissection

may need to be considered as is advised in the recent ESC guidelines (10)

A retrospective study of 69 women with MFS in pregnancy described an increase in aortic

dimensions that failed to return to baseline following pregnancy (11). In contrast, a

prospective study by Meijboom et al of 23 pregnant women (33 pregnancies) before and

after pregnancy found no difference in aortic dimensions compared with 22 matched

childless women (12). Beta-blocker use in MFS in pregnancy to reduce the risk of AoD is

inconsistent and their effectiveness unproven (13, 14). Outside pregnancy, the beneficial

effect of beta-blockers is unclear, with only one published randomised trial (15). Shores et al

showed a significant reduction in the rate of aortic dilatation in those receiving beta-

blockers, but there was no significant reduction in the rate of AoD. Beta-blocker use during

pregnancy is associated with lower birthweight and can impair the neonatal response to

hypoglycaemia (16, 17). Nevertheless,The 20118 ESC guidance recommended beta-blocker

use in Marfan patients during pregnancy (8).

We carried out a multicentre study of pregnant women with MFS to investigate 1) the

occurrence of cardiovascular complications, and searched for possible related factors, 2)

fetal outcomes and birthweight, 3). In addition pre- and post-pregnancy echocardiographic

examinations were analysed to assess the impact of pregnancy on aortic diameters and 4).

The use of pPreconception counselling was reviewed.

Methods

Twelve specialist UK centres providing joint specialist care for pregnant women with

congenital heart disease were invited by email in September 2017 to participate in a joint

study. Participating centres identified pregnancies in women with an established diagnosis

of MFS according to modified Ghent criteria, including assisted conceptions and

miscarriages or terminations. Cases were identified from January 1998 until March 2018 and

data collected from a detailed review of the medical and obstetric notes. Pseudo-

anonymised (all personal identifiers omitted) data were amalgamated into a single dataset.

The study protocol was approved by the local research governance team at Imperial College

Healthcare.

Demographic data collected included maternal age, race/ethnicity, New York Heart

Association class (NYHA), height, pre-pregnancy weight and body mass index. Data were

obtained on family history of MFS and family history of AoD or death attributed to MFS.

Information was also obtained on previous surgical interventions and medication use pre-

pregnancy. Data on echocardiographic assessment of aortic dimensions up to one year pre-

pregnancy and 6-12 weeks postpartum were obtained whenever possible. We looked for

documented evidence of pre-conception counselling.

The primary outcome was the occurrence of AoD during pregnancy or up to 6

months postpartum. Secondary cardiac outcomes included the occurrence of cardiac

surgery, venous thromboembolism, stroke or deterioration in left ventricular function in

pregnancy or up until 6 months postpartum. Obstetric outcomes included gestational

hypertension (GH; ≥140 mm Hg systolic or ≥90 mm Hg diastolic after 20 weeks’ gestation),

pre-eclampsia (GH with proteinuria >0.3 g/24 hours), preterm delivery (delivery at <37

weeks of gestation) and post-partum haemorrhage (PPH, blood loss ≥500 mL at delivery).

Neonatal outcomes were small for gestational age (SGA, defined as birth weight (BW) <10th

centile for sex and gestational age by the Aberdeen centiles), stillbirth (fetal demise ≥24

weeks’ gestation) and neonatal unit admission. We also assessed practice with regard to the

2011 ESC guideline, determining the number of women who received preconception

counselling, imaging of the aorta in pregnancy, betablockers and delivery by caesarean

section.

Statistics

Data were analysed using SPSS V.23/25 for Windows. Categorical data are presented as

frequencies (numbers) and percentages. Data that approximate to a Gaussian distribution

(maternal age, BMI) are presented as mean values +/- SD. Non-Gaussian data are presented

as medians with inter-quartile range. Correlations were calculated using Pearson’s product

moment if variables were continuous and Spearman’s rank-order correlation if either of the

variables was ordinal. Differences between continuous variables were assessed with the

Mann Whitney U test if they were not normally distributed. All tests were two tailed and

p<0.05 was considered statistically significant.

Results

Twelve centres provided data on 164 pregnant women with MFS. In total there were 258

pregnancies; 226 pregnancies ≥24 weeks (two sets of twins), 20 miscarriages and 12

terminations of pregnancy. The following data refer to women having pregnancies ≥24

weeks.

85 women (37%) had one recorded pregnancy, 88 (45%) had two recorded pregnancies, 15

(14%) had three recorded pregnancies, and two (2%) had four recorded pregnancies. Table

1 shows the demographics of women having their first ongoing pregnancy (nulliparous).

There were 221 livebirths in 139 women, one intrauterine death and four neonatal deaths;

134 women were white European, 8 were south Asian, 2 were black African and 2 were

mixed race. The median gestational age at delivery was 39 weeks (IQR 37-40, range 24-42

weeks, data missing in 3 cases).

Data on preconception counselling were recorded in 210 pregnancies. 64/127 (50.4%)

women in their first recorded pregnancy had documented preconception counselling (PCC);

this rose to 40 of 59 women (67.8%) by the second recorded pregnancy (p=0.028) and 14 of

19 (73.7%) by the third recorded pregnancy (p=0.78). Before the 2011 ESC guidelines the

rates for first recorded pregnancies was 32 of 66 (48.5%) and afterwards was 32 of 61

(52.5%), an insignificant change (p=0.724). For second recorded pregnancies the

corresponding rates were 17 of 23 (73.9%) and 23 of 36 (63.9%).

Two women had assisted conception using preimplantation genetic diagnosis to ensure that

they had a baby unaffected by MFS. A small number of women (n=5) had invasive testing

during 10 pregnancies to determine whether their pregnancies were affected by MFS. Only

one pregnancy was terminated as result of a positive test. Two further tests were positive,

but the women continued with their pregnancy.

There were 28 pregnancies in 19 women who had had a prior ascending aorta replacement

(AAR). One of these women had a Type B dissection in the first trimester (See Table 2).

Associations with aortic dissection

There were 5 acute AoD - 1 Type A and 4 Type B. Table 2 provides information relating to

these events. Analysis of factors including family history of AoD, use of betablockers, AoR

size prior to delivery, prior ARR, pre-eclampsia and gestational hypertension showed that

none of these factors were significantly associated with dissection, although small numbers

means that even moderate associations cannot be excluded.

Other cardiac complications

Table 3 shows demonstrates the other cardiac complications recorded during the study

period.

Echocardiography

Excluding women with prior ARR, there was a total of 55 women who had AoR assessment

prior to pregnancy and at postnatal follow up. Median AoR size prior to pregnancy was

36mm (IQR 33mm-39mm) and following pregnancy it was 37mm (IQR 35mm-37mm). There

was small but significant increase in AoR size at follow up compared with the prepregnancy

value - mean change 0.9mm (p=0.034) (Figure One). This change was not significantly

modified by the use of beta blockers; the mean increase in the 16 women not using beta

blockers was 0.75 mm (SD 1.53) compared with 0.87 (SD 2.47) in the 39 women using them

(p=0.86). Following the introduction of the 2011 ESC guideline, significantly more women

had aortic imaging during pregnancy. Recorded size estimation by echocardiography in the

first trimester increased from 31% (34/111) to 48% (55/115) (p=0.008), from 40% (44/111)

to 59% (68/115)(p=0.003) in the second trimester and 41% (45/111) to 60% (69/115)

(p=0.004) in the third trimester.

Delivery

Excluding one patient with an AoR diameter of 81mm pre-pregnancy who declined early

delivery and women with ARR prior to conception, there was a statistically non-significant

trend towards earlier delivery in women with larger pre-pregnancy AoR dimensions

(R=0.175, p= 0.065).

If the maximum AA diameter prior to pregnancy was <40mm the ELCS rate was 27.3%

(27/99), compared with 59.4% (19/32) if it was >=40mm (p<0.001). Excluding women with

previous AOR replacement (and the woman with an AA of 81mm), the ELCS rate was 27% if

the AA diameter was <40mm (N=89), compared with 64% if it was >=40mm (N=25)

(p=0.001).

Data on postpartum blood loss was available in 180 of 226 deliveries (79.6%). Median blood

loss at spontaneous vaginal birth was 350ml (IQR 150, minimum 50ml maximum 2300ml), at

assisted vaginal birth it was 450ml (IQR 300, minimum 100ml maximum 3000ml), at

emergency CS it was 600ml (IQR 410, minimum 220ml maximum 2000ml) and at elective CS

it was 600ml (IQR 300, minimum 233ml maximum 1800ml). Defining postpartum

haemorrhage (PPH) as an estimated blood loss of 500ml or more, the incidence of PPH was

12/55 (21.8%) for vaginal birth, 19/39 (48.7%) for assisted vaginal delivery, 13/21 (61.9%)

for emergency CS and 54/65 for elective CS (83.1%)(Chi 2 46.01, p<0.001).

Birthweight was known in 202 cases (89.4%). Median birthweight was 3100g (IQR 2672.5 to

3492.5, minimum 850 g and maximum 4400g). The median BW centile (corrected for

gestational age, sex and gender) was 41 (IQR 16-70); 27 infants were born small for

gestational age (13.8%). Gestational age at delivery was known in 221 cases (97.8%).

Median gestational age at delivery was 39 weeks (IQR 37-39, minimum 24 and maximum

42). Preterm birth occurred in 34 cases (15.4%); 21 (62%) of these were born at 34-36 weeks

(late preterm), 17 (50%) due to elective early delivery. 17 of 221 (8%) surviving neonates

were admitted to the special care baby unit, primarily because of prematurity. Table 4 lists

the obstetric and neonatal complications for all pregnancies ≥24 weeks gestation.

Beta-blocker use was known in 199 cases (88%) and they were used in 65.8% of these

pregnancies. Table 5 shows the different types of beta-blockers used both prior to

pregnancy and during pregnancy. Median birthweight and birthweight (BW) centiles were

significantly lower in women taking beta-blockers during pregnancy (2960g [IQR 760] vs.

3310g [IQR 810], p=0.001; BW centile 30 (IQR 49) vs 50 (IQR 48), p=0.008). Figure 2 shows

the distribution of birthweights with different beta blockers used; women taking atenolol

had infants with the lowest BW.

Discussion

Dissection during pregnancy and the puerperium overall was 1.9%, falling to 1.6% when

including only pregnancies >24weeks gestation. Furthermore, there were no maternal

deaths in our study. Importantly dissections were mainly type B, which are known to be

associated with lifelong complications such as vascular ischaemia and organ malperfusion,

but have lower mortality. Predicting which women are at particular risk of dissection

remains challenging, as we did not find any factors that were significantly associated,

although this is likely due to the low absolute number of dissections. The rate of dissection

in our study was lower than a recent published cohort study by Roman et al of 3.1% (18)

and Pacini et al at 4.4% (4, 14). It is notable that there were 34 (..%) pregnancies where the

maternal aortic diameter prior to pregnancy was 40mm or greater. There were two

dissections (one type A and one Type B) in this group (rate 5.9%). We did not witness any

dissections in the third trimester or around delivery, which is considered a high-risk period.

It is possible that this is because of the greater use of beta-blockers in our cohort compared

with other studies such as Lind et al (6). In their cohort of 44 women (147 pregnancies >24

weeks gestation), there were five dissections and no women took beta-blockers. It may also

have been due to chance. It is notable that there were no factors significantly associated

with dissection, although this is likely due to the low absolute number of dissections.

Our study showed a significant, albeit small increase in AoR size at pregnancy followup, in

keeping with the findings of Donnelly et al (11). Interestingly, the change in aortic size did

not correlate with the use or non-use of beta-blockers , although our study was

underpowered to draw definite conclusions. Our study was retrospective, and ideally to

assess changes in aortic measurements women should be followed prospectively with

standardised imaging and timing protocols.

It was disappointing that only 50% of women had evidence of documented preconception

counselling (PCC) in their first pregnancy, rising to only 58% if subsequent pregnancies are

included. Surprisingly, there was no significant increase in the proportion of women having

received PCC after the ESC guidelines (the first in relation to Marfan syndrome and

pregnancy) were published in 2011. PCC is particularly important because cardiac disease

remains the leading cause of indirect maternal death (19); clinicians therefore have a duty

to provide women with congenital cardiac disease with individualised, accurate and

contemporary data regarding their risk of a pregnancy (20). It is particularly important that

women with MFS receive counselling because they need to be aware that during pregnancy

the risk of dissection is increased. They should be informed about the risks both for the

mother and for the baby, also including the 50% inheritance risk, so that they can make

informed decisions regarding pregnancy and its management. For those who have a dilated

aorta, prophylactic ARR prior to pregnancy maybe considered, although root replacement

does not necessarily prevent all cardiac complications. A recent Japanese case series

reported that the rate of peripartum Type B dissection in women with previous ARRs who

had a pregnancy was 60%, however, in our study this occurred in only one of 29 women

(3.4%). A North American series of 3 women with Loeys Dietz syndrome, all with prior

elective ARR because of aneurysmal disease, showed that two out of three suffered AoD in

pregnancy in the puerperium (Ref Braverman A AJMG 2016). A large Dutch study involving

600 patients with MFS reported that prior ARR was an independent risk factor for Type B

dissection(21), but pregnancy was not included in their predictive model. Our study is the

largest to date of women with MFS and prior ARR but there remain only limited data for

counselling and management of these women throughout pregnancy. Registries enabling

large prospective studies are urgently required.

Our data showed a clear association between beta-blockers and low birthweight. ESC

guidance from 2011 recommended their use for MFS, acknowledging their benefit was

uncertain. 2018 guidance now states that beta-blockers should be considered, while still

accepting that their benefit is unproven (10). We did not find any increase in the use of

beta-blockers following the 2011 ESC guidance, suggesting that some clinicians consider

their use as beneficial while others do not. Data from our own group has illustrated that

women with many forms of heart disease have significantly smaller infants than healthy

women and even after adjusting for confounding factors, beta-blockers were associated

with a 238g lower birthweight(22). Atenolol had the strongest association with lower

birthweight. Lydakis et al showed that, in a cohort of women with pregnancy induced

hypertension, when atenolol was compared to other antihypertensive agents used to treat

gestational hypertension, women who received atenolol had infants with significantly lower

birthweights (23). The use of beta-blockers to prevent aortic dilatation remains

controversial (24), with only one small randomised trial study showing a benefit (15). At

present there are no reported studies in pregnancy which have assessed the impact of beta-

blockers on the rate of dissection. In our study, all women who suffered a dissection had

been prescribed beta-blockers during pregnancy and the puerperium. Women should be

advised that the evidence for the use of beta-blockers to prevent aortic dissection in

pregnancy is limited, although their use is recommended to treat GH.

In our study the overall Caesarean section rate was almost fifty percent; higher than the

41% reported in women with cardiac disease by the Registry of Heart Disease and

Pregnancy (25). Many of the women in our cohort were managed prior to the publication of

the ESC guidelines in 2011, which suggested that delivery by Caesarean section should be

performed if the AoR is >45mm. Our data showed that the overall the rate of ELCS remained

unchanged in spite of this guidance and there is currently no clear evidence which

demonstrates that Caesarean section for women with MFS is of benefit. 2018 guidance

suggests a more individualised approach to the mode of delivery. It remains unclear why

dissection is more common in the immediate postpartum period and there is no evidence to

suggest labour itself increases the incidence of dissection. However, cardiac output does

increase progressively as labour advances, peaking around the time of delivery (26), which

may increase aortic shear stress (27). Nevertheless aortic dissection occurring in labour is

very seldom reported (28); and so decisions around mode of delivery should be

multidisciplinary involving the patient and counselling should be transparent about the lack

of data with regard to aortic dissection and mode of delivery.

Peripartum hemorraghe (PPH) complicated forty 40%percent of deliveries in our study. This

is double the rate from a systematic review analysing the overall rate of PPH in the general

obstetric population in many different regions worldwide (29). One possible explanation for

greater blood loss is the management of the third stage of labour. Ergometrine, a powerful

vasoconstrictive agent used routinely to reduce blood loss at delivery is often avoided in

women with MFS because of its vasopressor activity, resulting in marked hypertension (30).

However, as a result women are likely to experience a greater of blood loss at delivery.

The rate of preterm delivery was also relatively high in our cohort, although comparable to

that found in ROPAC (25) which reported that women with cardiac disease who were

delivered by planned Caesarean were delivered earlier, with higher rates of infants being

admitted to the special care baby unit. Our data shows that 21 (62%) of the infants born

preterm were late preterm deliveries (between 34-37weeks), 17 (50%) due to elective early

delivery. Decisions regarding delivery should be multidisciplinary and should involve the

patient and her family, as even late preterm birth has an adverse effect on child health up to

5 years of age (31).

Limitations

This study has several limitations. It is retrospective in nature and so data may be missing or

incomplete. The study only included patients managed in tertiary centres and so may have

introduced selection bias. Furthermore, whilst we had data on aortic measurements both

before and after pregnancy in 55 cases, these would have been performed by different

individuals and not to a standardised proforma, so increasing the likelihood of inter-

observer variability.

Conclusion

The risk of aortic dissectionAoD in women with MFS in pregnancy, managed within 12

specialist centres in the UK was 1.9%. AoR sizeAscending aortic size increased significantly

by 0.9mm from pre to post pregnancy. There were no obvious risk factors, other than MFS

itself, that were significantly associated with dissection. The rate of obstetric and neonatal

complications was high. The introduction of ESC guidance in 20112 was associated with a

significant increase in the proportion of women having aortic imaging during pregnancy but

no change in the use of beta-blockers (which was associated with lower birthweight) or

providing preconceptional counselling.

Table 1 Baseline maternal characteristics at first recorded pregnancy

Demographics (n=139) N (%) unless

otherwise stated

Age in years, median (interquartile range) 28 (24-33)

(minimum and maximum) (14-42)

Body Mass Index (median and interquartile range) 22 (20-26.4)

(minimum and maximum) (15-40)

Functional status

NYHA Class 1 132

NYHA Class 2 3

NYHA Class 3 and 4 0

Genotype positive 96

Family history of MFS 81

Family history of dissection 51

Previous ascending aorta replacement 19

AoR prior to pregnancy <40mm (echo) 99

AoR prior to pregnancy 40mm – 44.9mm (echo) 27

AoR prior to pregnancy >=45mm (echo) 7

Table 2 Details of Dissection during pregnancy and postpartum

Age Type Dissection Root Size Timing ManagementPre-pregnancy

Patient A+ 37 Type A 42mm Day 10pp* Bentall procedure

Patient B 36 Type B 41mm Day 14pp* Beta-blockade

Patient C++ 30 Type B Not imaged Day 4pp* Beta-blockade(41mm 1st Trimester)

Patient D 26 Type B 6monthspp* Beta-blockade

Patient E 30 Type B Previous AoR 12 week Pregnancy replacement and mechanical termination and aortic valve beta blockade

+=Patient managed outside specialist centre and referred at 37 weeks gestation

++=Patient only referred to specialist centre for pregnancy care*pp= postpartum

Table 3 All other cardiac complications during pregnancy and postpartum

Total pregnancies (n=226) N (%)

Cardiac Surgery 6 (11.3)

Patient E Valve sparing ARR 23 weeks- Root 47mm

Patient F Valve sparing ARR- 8 days postpartum- Root 46mm post delivery

Patient G Valve sparing ARR- 4 weeks postpartum- Root 53mm third trimester

Patient H Valve sparing ARR 4 weeks postpartum- Root 81mm pre-pregnancy

Patient I Aortic Valve and root replacement 6 months postpartum worsening

aortic regurgitation

Venous Thromboembolism 2

Patient I Iliac deep vein thrombus

Patient J Lower limb thrombus

Marfan cardiomyopathy 2

Patient K Previous AoR replacement-Developed

severely dilated left ventricle at 36 weeks,

managed conservatively

Patient L Dilated left ventricular size with impaired

function (ejection fraction at 34 weeks 36%-

managed conservatively)

Stroke

Patient K Left insular infarct, 4 weeks postpartum,

presumed cardioembolic

Patient M Right Middle Cerebral artery stenosis at 36

weeks gestation

Table 4 Obstetric and Neonatal Complications

Obstetric Complications (total pregnancies n=226) N (% to nearest whole number)*

Postpartum Haemorrhage 46 (20)

Pre-eclampsia 2 (1)

Gestational hypertension 3 (1)

Mode of Delivery

Spontaneous Vaginal 71 (31)

Assisted vaginal 45 (20)

Elective CS 27 (12)

Emergency CS 80 (35)

No record 3 (1)

Neonatal complications (total births n=226) (% to nearest whole number)

Intrauterine death 2 (1)

Neonatal death 4 (2)

SGA (<10th Centile) 29 (13)

Preterm Prelabour Rupture of Membranes 11 (5)

Preterm delivery 34 (17)

Neonatal Unit Admission 27 (12)

Table 4 – Beta-blockers prescribed prior to and during pregnancy in women not having a miscarriage or termination of pregnancy

Total births (n=226) N (% to nearest whole number)

Prior to pregnancy

No betablockers 108 (48)

Atenolol 52 (23)

Bisoprolol 33 (15)

Metoprolol 23 (10)

Propranolol 5 (2)

Beta-blockers given but type no specified 2 (1)

No record 3 (1)

During pregnancy

No betablockers 79 (35)

Bisoprolol 43 (19)

Atenolol 54 (24)

Metoprolol 23 (10)

Labetalol 18 (8)

Propranolol 2 (1)

Beta-blockers given but type no specified 2 (1)

No data recorded 5 (2)

Figure 1- Change in Aortic Root Size (N=55)

Before After25

30

35

40

45

50

Before and after pregnancy

Asce

ndin

g ao

rta

diam

eter

(m

m)

Figure 2

Box and whisker plot showing distribution of birthweight in relationship to type of beta-

blockers used during pregnancy..

The graph shows median (line) with interquartile range (box). The whiskers represent 1.5 times the overall height of the box which with a

normal distribution equates to approximately the 95% confidence intervals of the population distribution, except that in cases with no

outliers (circles) beyond the whisker, the whisker represents the minimum or maximum value

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