Marfan syndrome and pregnancy: what you need to know

Marfan syndrome is a rare genetic disease, with autosomal dominant transmission, which affects both women and men. This type of genetic transmission means that, “when a parent is affected, the risk for each child of being affected is 1 in 2 (50%), regardless of gender”, Explains Dr Sophie Dupuis Girod, who works at the Marfan Disease and Rare Vascular Diseases Competence Center, within the CHU de Lyon. It is estimated that one in 5 people is affected.

“It is a disease called connective tissue, that is to say, supporting tissues, with an impairment that can affect several tissues and several organs”, Explains Dr Dupuis Girod. It affects the body’s supporting tissues, which are particularly present in the skin, and large arteries, including the aorta, which can increase in diameter. It can also affect the fibers that hold the lens, and cause dislocation of the lens.

People with Marfan syndrome are not always recognizable, although it has been found that these are often tall, with long fingers and rather skinny. They can show great flexibility, ligament and joint hyperlaxity, or even stretch marks.

However, there are carriers of the genetic mutation who have few signs, and others who show a lot of signs, sometimes within the same family. One can be reached with a very variable severity.

Can we consider pregnancy with Marfan syndrome?

“The vital element in Marfan’s disease is the rupture of the aorta: when the aorta is too dilated, like a balloon that has been inflated too much, there is a risk that the wall will be too thin. and breaks”, Explains Dr Dupuis-Girod.

Due to the increased blood flow and the hormonal changes it induces, pregnancy is a risky period for all affected women. Because these changes could be accompanied byan increased risk of dilation of the aorta or even dissection of the aorta in the expectant mother.

When the aortic diameter is greater than 45 mm, pregnancy is contraindicated because the risk of death from ruptured aorta is high, says Dr. Dupuis-Girod. Aortic surgery is then recommended before a possible pregnancy.

Below 40 mm in aortic diameter, pregnancies are allowed, whilebetween 40 and 45 mm in diameter, you have to be extremely careful.

In their recommendations for the management of pregnancy in a woman with Marfan syndrome, the Biomedicine Agency and the National College of Gynecologists and Obstetricians of France (CNGOF) specify that the risk of aortic dissection exists “whatever the aortic diameter”, But that this risk“is considered small when the diameter is less than 40mm, but considered large above, especially above 45mm“.

The document specifies that pregnancy is contraindicated if the patient:

• Presented with an aortic dissection;
• Has a mechanical valve;
• Has an aortic diameter greater than 45 mm. Between 40 and 45 mm, the decision is to be made on a case-by-case basis.

How does a pregnancy go when you have Marfan syndrome?

If the mother is a carrier of Marfan syndrome, an aortic ultrasound by a cardiologist familiar with the syndrome should be performed at the end of the first trimester, at the end of the second trimester, and monthly during the third trimester, as well as about a month after childbirth.

The pregnancy must proceed on beta-blocker therapy, in full dose if possible (bisoprolol 10 mg for example), in consultation with the obstetrician, notes the CNGOF in its recommendations. This beta-blocker treatment, prescribed for protect the aorta, should not be stopped, including during childbirth. Breastfeeding is then not possible because of the passage of the beta blocker in the milk.

It should be noted that treatment with a converting enzyme inhibitor (ACE) or sartans is contraindicated during pregnancy.

If only the spouse is affected, the pregnancy will be followed as a usual pregnancy.

What are the risks and complications of Marfan syndrome during pregnancy?

The major risk for the mother-to-be is to have a aortic dissection, and having to undergo emergency surgery. For the fetus, if the mother-to-be has a very severe complication of this type, there is a risk of fetal distress or death. If ultrasound surveillance reveals a significant risk of aortic dissection or rupture, it may be necessary to perform a cesarean section and deliver the baby prematurely.

Marfan syndrome and pregnancy: what is the risk that the child is also affected?

“When a parent is affected, the risk for each child to be affected (or at least a carrier of the mutation) is 1 in 2 (50%), regardless of sex”, Explains Dr Sophie Dupuis Girod.

The genetic mutation linked to Marfan’s disease is not necessarily transmitted by a parent, it can also appear at the time of fertilization, in a child of which neither of the parents is a carrier.

Can a prenatal diagnosis be made to identify Marfan syndrome in utero?

If the mutation is known and identified in the family, it is possible to make a prenatal diagnosis (PND), to know if the fetus is affected, or even a pre-implantation diagnosis (PGD) after in vitro fertilization (IVF).

If the parents do not wish to carry the pregnancy to term if the child is affected, and they wish to have recourse to a medical termination of pregnancy (IMG) in this case, a prenatal diagnosis can be undertaken. But this DPN is only offered at the request of the couple.

If the couple is considering an IMG if the unborn child has Marfan syndrome, their file will be analyzed in the Prenatal Diagnostic Center (CDPN), which will require approval. While knowing full well thatit is not possible to know how much damage the unborn child will be, only if he is a carrier or not of the genetic mutation.

Can a pre-implantation diagnosis be made to prevent the fetus from being affected?

If one of the two members of the couple is a carrier of the genetic mutation linked to Marfan syndrome, it is possible to have recourse to preimplantation diagnosis, in order to implant in the uterus an embryo which will not be a carrier.

However, this implies having recourse to in vitro fertilization and therefore to a course of medically assisted procreation (MAP), a long and medically heavy procedure for the couple.

Pregnancy and Marfan syndrome: how to choose maternity?

Pregnancy with Marfan syndrome requires follow-up in a maternity hospital where staff are experienced in caring for pregnant women with this syndrome. There are all a list of referral maternities, published on the website marfan.fr.

“In the current recommendations, there must be a center with a cardiac surgery department on site if the aortic diameter in early pregnancy is greater than 40 mm”, Specifies Dr Dupuis-Girod.

Note that this specificity has nothing to do with the type of maternity (I, II or III), which is not a criterion for choosing maternity here. In the facts, referent maternities for Marfan syndrome are generally in large cities, and therefore level II or even III.

Pregnancy and Marfan syndrome: can we have an epidural?

“It is necessary that the anesthetists likely to intervene are warned, because there can be either a scoliosis or a dural ectasia, that is to say a dilation of the sac (dural) which contains the spinal cord. You may need to do an MRI or CT scan to assess the possibility or not of having epidural anesthesia”, Says Dr Dupuis-Girod.

Pregnancy and Marfan syndrome: is childbirth necessarily triggered or by cesarean section?

The type of delivery will depend, among other things, on the aortic diameter and should be discussed again on a case-by-case basis.

“If the maternal cardiac situation is stable, birth should not be considered as a rule before 37 weeks. Childbirth can be carried out vaginally if the aortic diameter is stable, less than 40 mm, provided that an epidural is possible. An expulsion aid by forceps or suction cup will easily be offered to limit the expulsive efforts. Otherwise the delivery will be carried out by cesarean section, always taking care to avoid variations in blood pressure.”, Adds the specialist.

Sources and additional information:

• https://www.marfan.fr/signes/maladie/grossesse/
• https://www.agence-biomedecine.fr/IMG/pdf/recommandations-pour-la-prise-en-charge-d-une-grossesse-chez-une-femme-presentant-un-syndrome-de-marfan-ou-apparente.pdf
• https://www.assomarfans.fr