1. Top of page
  2. Abstract
  7. References

Objective To improve life expectancy and prevent premature mortality in women with Marfan's syndrome.

Methods During the development of a regional genetic register for Marfan's Syndrome the outcome of 91 pregnancies in 36 women with this condition was established retrospectively and the cardiovascular and obstetric complications documented.

Results No patient had a significant cardiovascular abnormality limiting function before her pregnancy. Of 36 women, four had an aortic dissection relating to pregnancy and two others required aortic surgery following delivery. Thirty women had uncomplicated gestational histories. The incidence of obstetric complications did not exceed expectation.

Conclusions Women with Marfan's syndrome are at significant risk of aortic dissection in pregnancy even in the absence of preconceptional cardiovascular abnormality. Aortic root dilatation may be a predictor of risk but dissection may occur without significant dilatation. Guidelines for obstetric care are suggested and preconceptional assessment recommended.


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  2. Abstract
  7. References

Marfan's syndrome is an autosomal dominant disorder of connective tissue caused by mutations within the fibrillin gene on chromosome 151–3. The condition is characterised by musculoskeletal, cardiovascular and ocular manifestations. The cardiovascular features of this condition include mitral valve prolapse, mitral regurgitation, aortic root dilatation and aortic incompetence. Life expectancy in this condition is reduced: the mean age of death is in the early thirties, and the most common cause of death is aortic dissection or rupture4. Aortic dilatation usually precedes dissection and the advent of surgical techniques to replace the ascending aorta electively with a composite graft once the aortic root dimension reaches 5.5 cm has improved life expectancy5–8. Medical literature suggests that pregnancy increases the risk of aortic dissection9–12. Pyeritz13 reviewed 32 case reports of women with Marfan's syndrome who had had at least one pregnancy, describing the occurrence of aortic dissection relating to pregnancy or the puerperium in 20 of these women, most of whom had pre-existing cardiovascular abnormalities. The high incidence of cardiovascular complications of Marfan's syndrome in pregnancy documented in published reports is subject to bias, in that uncomplicated cases are underreported. During the establishment of a regional register for Marfan's syndrome, set up with the aim of preventing premature mortality from the cardiac complications of this connective tissue disorder, the outcome of 91 pregnancies in 36 women was determined. In this report we describe the maternal risks of pregnancy in a representative sample of women with Marfan's syndrome exhibiting wide phenotypic heterogeneity, with the aim of providing guidelines for preconceptional assessment of risk and development of appropriate obstetric care.


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  2. Abstract
  7. References

A regional genetic register was established with the aim of improving life expectancy and preventing premature mortality in Marfan's syndrome. Probands were identified by a review of the casenotes in the departments of medical genetics and cardiology, and the first degree relatives at 50% risk of this autosomal dominant condition were traced and screened by physical examination, echocardiography and slit lamp examination. Thirty-six women with a diagnosis of Marfan's syndrome, as defined by clinical criteria in the Berlin Nosology14, who have undergone at least one pregnancy were ascertained. The course and outcome of each pregnancy was established retrospectively by interviewing each woman and reviewing her medical records. Subsequent cardiovascular events and the family history of aortic involvement were established.


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Outcome of pregnancy

Thirty-six women who had had one or more pregnancies were identified (Table 1). There were 89 singleton and two twin pregnancies. Of 91 pregnancies, there were 75 live births.

Table 1.  Obstetric history. Values are given as n and mean (SD).
Total no. of women36
Total no. of pregnancies91
Pregnancies per woman2.5 (1.3)
No. of live births75
No. of live infants with Marfan's syndrome41
Mean age at first conception (years)24.0 (4.1)
Mean age at last conception (years)28.1 (3.6)

One twin pregnancy resulted in a second trimester miscarriage at 22 weeks. The second twin pregnancy resulted in premature labour with the birth of two live infants at 32 weeks of gestation. One intrauterine death occurred at 20 weeks; no abnormality was found in the foetus. One stillbirth secondary to anencephaly was recorded in a 21 year old primigravida. One neonatal death occurred after premature delivery at 36 weeks of gestation with hypoplastic lungs.

Of the 75 live births, 41 infants inherited Marfan's syndrome. One infant with Down's syndrome but unaffected with Marfan's syndrome was born to a 24 year old woman. Two first trimester and six second trimester miscarriages occurred. There were seven terminations of pregnancy, four of which were for fetal abnormality. Three terminations were performed in one woman after amniocentesis results and ultrasound scans suggested a recurrent neural tube defect. In one case termination of pregnancy was performed for maternal cardiac problems relating to pregnancy. No patient requested prenatal diagnosis for Marfan's syndrome (Table 2).

Table 2.  Obstetric outcome and complications.
Live births75
First trimester miscarriages2
Second trimester miscarriages6
Intrauterine death1
Termination of pregnancy7
Postpartum haemorrhage7

Obstetric complications

Two patients had recurrent miscarriages. One woman had a stillbirth due to anencephaly, three terminations of pregnancy and three subsequent second trimester miscarriages. After two miscarriages at 20 weeks of gestation, a second patient underwent insertion of a Shirodkar suture for two subsequent pregnancies which she carried to term. In one woman who had received fertility treatment for two years before conceiving at the age of 35 years, the pregnancy was complicated by pre-eclampsia. One patient had well-controlled essential hypertension for nine years prior to two uncomplicated pregnancies. Premature labour occurred in 5/75 pregnancies resulting in live births. In four women labour began during the 36th week of pregnancy and in the 5th case, a twin pregnancy, labour began at 32 weeks. Elective caesarean section was performed for two women with cephalopelvic disproportion. One vaginal delivery was complicated by a breech presentation and one by shoulder dystocia. The summaries in Table 3 are the methods of delivery. Seven pregnancies were complicated by postpartum haemorrhage necessitating blood transfusion; haemorrhage was associated with a retained placenta in one woman.

Table 3.  Methods of delivery.
  1. *1 breech.

Normal vaginal62*
Forceps vaginal5
Ventouse vaginal1
Caesarean section under epidural anaesthesia3
Caesarean section under general anaesthesia4
Vaginal delivery under epidural anaesthesia8

Cardiovascular events during pregnancy

None of the 36 women had symptoms relating to cardiovascular abnormality before conception. Echo-cardiographic data were not available on all women before pregnancy but has been obtained subsequently on all living patients. Two patients were known to have mitral valve prolapse and mild mitral regurgitation before conceiving. No murmurs consistent with aortic regurgitation were documented at the antenatal booking clinic. No episodes of arrhythmia or bacterial endocarditis relating to pregnancy were documented. Significant aortic events occurred in six individuals. Aortic dissection occurred in four women, in two of whom the diagnosis of Marfan's syndrome was not established until the aortic event occurred. Two other women developed progressive aortic root dilatation without dissection. The pregnancy histories of these six patients are summarised below.

  • Case 1. A 29 year old woman with Marfan's syndrome had an uncomplicated first pregnancy. She had a normal chest X-ray two months before conceiving her second pregnancy. Intrauterine death occurred at 20 weeks. She developed chest pain during prostaglandin induction of labour and after vaginal delivery of the fetus, aortography showed that she had a Type 1 aortic dissection beginning above the origin of the right coronary artery with the distal re-entry point below the left femoral artery. The ascending aorta measured 4.2 cm. After repair of her aortic root with a composite graft she had two further episodes of dissection, the last resulting in rupture of the aortic arch and death at the age of 37.

  • Case 2. A 30 year old primigravida with no previous cardiac history and no murmurs documented at booking remained well and normotensive during the first eight months of pregnancy. The diagnosis of Marfan's syndrome was not established until she presented with a Type 1 aortic dissection at 38 weeks of gestation. She developed pulmonary oedema in association with acute left ventricular dilatation and severe aortic regurgitation. She was delivered of a live male infant by caesarean section under general anaesthetia. Subsequently a successful replacement of her ascending aorta with a composite graft was performed. At the time of surgery the ascending aorta measured 8.6 cm. She died two years later from a sub-arachnoid haemorrhage.

  • Case 3. A 35 year old woman who had undergone fertility treatment prior to conception developed hypertension at 25 weeks of pregnancy. A caesarean section was performed at term for fetal distress and uncontrolled hypertension. Despite adequate control of blood pressure following delivery she presented 14 days postpartum with a Type 1 aortic dissection resulting in aortic rupture and death. A postmortem diagnosis of Marfan's syndrome was made. No measurements of her aortic root were recorded.

  • Case 4. A 30 year old primigravida, who was diagnosed as having Marfan's syndrome at 20 weeks of pregnancy, remained under close observation during pregnancy with monthly echocardiography. The aortic root measured 4 cm at the time of diagnosis and did not change during pregnancy. Her blood pressure remained well controlled throughout, but in view of the history of aortic dissection in pregnancy in her elder sister (Case 2), she was treated with beta blockade and had an elective caesarean section at 38 weeks under general anaesthetic; the indications were cephalo-pelvic disproportion and a mildly dilated aortic root. Sixteen days after delivery she presented with a Type I11 aortic dissection. Initially this was managed conservatively, but when aneurysmal dilatation of the thoracoabdominal aorta occurred 18 months after the dissection surgical repair was performed. The woman did not survive the prolonged surgical procedure despite the use of deep hypothermia with circulatory arrest.

  • Case 5. A 28 year old woman in her second pregnancy was diagnosed as having Marfan's syndrome at 25 weeks of pregnancy following the death of her 29 year old brother from an aortic dissection. An aortic root dimension of 4.3 cm was found but progressive aortic root dilatation continued to 4.9 cm, despite beta blockade and adequate control of blood pressure. She had an elective caesarean section at 36 weeks under general anaesthesia. Postpartum dilatation of the ascending aorta continued rapidly with the aortic root dimension reaching 7 cm. Uncomplicated elective aortic root repair with a composite graft was performed 18 weeks after delivery. At the time of surgery there was no evidence of dissection.

  • Case 6. A dilated aortic root of 4.5 cm was diagnosed at 18 weeks of gestation in a 28 year old woman carrying a twin pregnancy. At 22 weeks she suffered a second trimester miscarriage; the aortic root at this time measured 4.9 cm. Measurements of the aortic root remained stable over the next four months, and elective aortic root replacement was planned. When admitted for surgery she was found to be seven weeks pregnant and the aorta had dilated to 5.6 cm. Termination of pregnancy was performed on the grounds of maternal cardiovascular risk, and she subsequently had uncomplicated aortic surgery.

Subsequent cardiovascular events

This cohort of 36 women have been followed up after their last pregnancy for a mean of 10.4 years (SD 9.2), with their mean age at the time of writing being 38.5 years (SD 10.1). Five of these women have had an aortic dissection, which was fatal in one case, and three have had elective aortic root replacement. In two women these events have occurred within four years of the last pregnancy. The remaining 22 women have aortic root dimensions ≤ 4.3 cm.


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  2. Abstract
  7. References

In the study group described the incidence of obstetric complications in terms of miscarriage and postpartum haemorrhage did not exceed expectation. As expected from an autosomal dominant condition, 41 out of 75 live births (54.7%) resulted in a child affected with Marfan's syndrome. The mean number of pregnancies per woman was 2.5 (SD 1.3) which suggests that women with Marfan's syndrome were not limiting family size. For most women a safe vaginal delivery was possible. Caesarean section was performed for obstetric reasons such as pre-eclampsia or cephalopelvic disproportion, with the exception of those women with an identified cardiovascular problem.

Four of the 36 women had an aortic dissection relating to pregnancy, which was immediately fatal to one. Two other women experienced significant aortic dilatation in pregnancy which resulted in elective aortic surgery following delivery. None of these six women had a significant cardiovascular problem which limited function prior to pregnancy. Aortic dissection occurred in two women who did not have significantly dilated aortic roots (4.0 and 4.2 cm) and whose pregnancies were not complicated by hypertension. Eight women subsequently have had major cardiovascular involvement and have had either an aortic dissection or elective repair of an aneurysmal aortic root. The remaining 22 women with uncomplicated gestational histories who, after a mean follow up period of 10.4 years (SD 9.2), do not have evidence of severe aortic disease all have aortic root dimensions ≤ 4.3 cm.

Marfan's syndrome is a dominantly inherited disorder of connective tissue which is associated with reduced life expectancy4. It is the cardiovascular complications of this multi-system disorder which result in premature death secondary to aortic dissection or rupture. Data presented by Murdoch et al. reports the mean age of death in patients with Marfan's syndrome as 32.0 years (SD 10.4). Marfan's syndrome predisposes women to premature death in their reproductive years and few women with Marfan's syndrome will limit family size knowing the risks of bearing an affected child13 therefore perhaps coincidental occurrence of pregnancy and aortic dissection could be expected. There are 27 case reports of pregnancy-related aortic dissection in Marfan's syndrome reported in medical literature, but ascertainment bias distorts the true incidence of severe aortic complications relating to pregnancy as uncomplicated cases12,15-34 are under-reported; many women with Marfan's syndrome have uneventful gestational histories13.

The phenotypic heterogeneity in Marfan's syndrome is well established. In order to accurately assess the risks of aortic dissection in pregnancy a more representative sample of patients is needed. A retrospective analysis13 of 105 pregnancies in 26 women with Marfan's syndrome in a national referral centre reported a low prevalence of cardiovascular complications and suggested that women affected by Marfan's syndrome who have minimal cardiovascular involvement seem to tolerate pregnancy without serious problems. In the same study Pyeritz suggests that in women with moderate or severe cardiovascular disease before pregnancy the risk of life-threatening cardiovascular complications during pregnancy is high. This was demonstrated by a review of the case reports of 32 women, 20 of whom had a fatal aortic dissection during pregnancy or the puerperium. Most of these women were known to have significant cardiovascular disease before pregnancy. The only available prospective evaluation of outcome in pregnancy in women with Marfan's syndrome, reported the outcome in 21 women who had undergone 45 pregnancies; there were three cases of aortic dissection36. The limitation of this study is the inherent absence of randomisation. Patients who are assessed and counselled regarding pregnancy-related risks and who choose to proceed with pregnancy may represent a subset at lower risk for cardiovascular complications. A control group is difficult to obtain in such a prospective study because of occult bias in women electing not to undertake pregnancy and because of the strong feelings of women regarding reproductive rights.

In our study, therefore, maternal cardiovascular risk in pregnancy has been assessed retrospectively in a group of 36 women with Marfan's syndrome ascertained during the systematic development of a regional register for this condition. As all these women are followed in one clinic, they represent a more random sample of women with Marfan's syndrome, illustrating the phenotypic heterogeneity for which this condition is renowned.

At the present time the only guidelines for identifying nonpregnant women most at risk from aortic dissection is the aortic root dimension. A threshold of 5.5 cm is taken as that for which aortic dissection is considered so likely to occur that planned surgery in a symptom-free patient6-8,35 is undertaken. It is accepted, however, that in some families and individuals that dissection is not always preceded by this degree of dilatation29,31. Twelve of the 36 women reported were sporadic cases of Marfan's syndrome and therefore a family history was not useful as a predictor of major aortic involvement. Of the 24 remaining women who represented familial cases of Marfan's syndrome, 20 had a family history of aortic dissection or need for elective aortic surgery in first or second degree relatives, whose ages ranged from 21 to 59 years. The group of women who dissected or dilated their aorta during pregnancy included familial and sporadic cases. It has been established that Marfan's syndrome is caused by mutations within the fibrillin gene on chromosome 151. With one exception, all described mutations have been family-specific which explains in part the interfamilial phenotypic heterogeneity. Intra-familial variability is also apparent in studies of large kindreds and therefore direct prediction of phenotype from genotype is not possible as a means of identifying women at increased risk in pregnancy. It is interesting, however that two out of six patients with aortic complications in this study group were from the same family.

It is evident from the cases described in this and other series that an event-free pregnancy can not be guaranteed to any woman with Marfan's syndrome. Ideally, the diagnosis of this condition should be made before pregnancy so that a full cardiovascular assessment can be performed and the obstetric implications discussed. It should be remembered that a single measurement of aortic root dimension does not give an appreciation of the rate of change in diameter which may be an important predictor of risk even though the absolute measurement may be < 4.0 cm, the figure. below which previous authors have suggested the risk of aortic dissection in pregnancy is small13.

We counsel our patients that there are likely to be significant risks in undergoing pregnancy if the aortic diameter is ≥ 4.0 cm or if there has been a steady increase in the aortic root dimension over preceding visits. We recommend monthly transthoracic echocardiography during pregnancy as the changes in cardiac output and plasma volume start as early as the sixth week of gestation37 and the occurrence of significant aortic events is not confined to the third trimester, labour and the puerperium29,30,34. We recommend a vaginal delivery with epidural anaesthesia for women with stable aortic measurements < 4 cm during pregnancy. Epidural anaesthesia helps to limit the rise in systolic and diastolic blood pressure which occurs with the pain and anxiety accompanying uterine contraction but does not prevent the associated rise in cardiac output37–38. For this reason we recommend elective caesarean section with epidural anaesthesia for those women with changes in aortic root dimension during pregnancy and for patients with aortic root dimensions ≥ 4 cm. Hypertension, an additional risk factor for aortic dissection during pregnancy, must be treated aggressively, ideally with betablockade11,39-40. A recent prospective randomised trial suggests that there are some patients with Marfan's syndrome in whom long term use of prophylactic betablockade will slow the rate of aortic dilatation therefore consideration should be given to the use of betablockade from mid trimester onwards in those women with evidence of aortic dilatation40. Although the incidence of bacteraemia associated with uncomplicated vaginal delivery has been reported to be low (0–5%) and the routine use of antibiotic prophylaxis for infective endocarditis in patients without prosthetic valves is not mandatory41, many institutions do administer prophylactic antibiotics during delivery to patients at risk of endocarditis, which in the case of Marfan's syndrome would include women with mitral valve prolapse associated with mitral regurgitation42.

The cornerstone of management is diagnosis and evaluation before conception so that maternal cardiovascular risk can be assessed. Progressive aortic dilatation and an aortic root dimension ≥ 4 cm suggest increased gestational risk of aortic dissection. The mean age at which aortic events occur in all patients with Marfan's syndrome (32 years (SD 16.4))4, suggests that women with this condition should be encouraged to complete their reproduction in their early 20s. Where minimal cardiovascular involvement is noted, many women with Marfan's syndrome will tolerate pregnancy without adverse effects although the risk is significant. Each pregnancy should be managed as high risk with combined obstetric and cardiological care and the 50% risk of transmitting the condition to the offspring should be explained.


This project was supported by a Medical Innovation Fund Grant from the North West Regional Health Authority.


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  2. Abstract
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