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Marfan Syndrome In Pregnancy

Paddy Jim Baggot, M.D. and M. G. Baggot M.D.

Marfan syndrome is alleged to have a high mortality in pregnancy. On that basis maternally-indicated abortion is often recommended for Marfan syndrome (Vermillion and Newman, 1998). Nelson et al (1996) estimate maternal mortality as 50% with aortic dilation and aortic valvular regurgitation. Nelson et al (1996) indicate maternal mortality is 5% in cases with a normal aortic root. Based on these numbers, abortion is often recommended for Marfan syndrome in pregnancy.

This presents a problem for Catholic and/or pro-life patients, since ‘ abortion to save the life of the mother’ is not consistent with Catholic medical ethics (Wojtyla, 1995). This paper will review recent literature in order to formulate a more humane and compassionate approach, which will also be consistent with Catholic teaching.

Marfan syndrome is inherited in an autosomal dominant fashion. It is caused by a mutation in the fibrillin gene on chromosome 15. It is characterized by tall stature, skeletal abnormalities, dislocation of the ocular lens and cystic medial necrosis of the arteries. The latter causes aortic dissection and rupture, and cardiac valve abnormalities.

Patients thought to have Marfan syndrome should be carefully examined by a geneticist. Marfan syndrome can easily be confused with Stickler syndrome, which is much more common. Another disorder which can be confused with Marfan syndrome is homocystinuria. Correct genetic diagnosis is a first step in preventing (unjustified) abortions.

Older literature on Marfan syndrome in pregnancy was based on case reports. The articles based on case reports suffered from bias of ascertainment, leading to overestimation of risk. This is because reports of entirely normal outcome may not seem worth reporting, and editors may not feel they are sufficiently newsworthy to publish. Many older case reports date from a time when there was no medical or surgical therapy available for Marfan syndrome.

A recent review of case reports (Elkayam et al, 1995) discusses a group of patients who had a very high complication rate. Many (7/10) had major vascular repair during or immediately after pregnancy. Most of these (6/7) survived major vascular repair. One had an abortion, one had medical therapy and one had sudden death. All patients had a complication. The outcomes in this group included 7/10 successful fetal outcome (one had Marfan syndrome), 3/10 fetal losses (one abortion), and 2/10 maternal deaths.

A more accurate picture of risk can be gleaned from studies which are not based on case reports. Due to the substantial divergence between the studies and reviews of case reports, the study data is described below. Two of the studies are from a prominent genetic clinic.

The study of Pyeritz was based on medical records of the Medical Genetics Clinic at Johns Hopkins in Baltimore, Maryland. More than 400 records were reviewed (1976-1981), and affected relatives were included. Involvement of at least two of the three organ systems was required (ocular, cardiovascular and skeletal). The study of Rossiter et al (1995) was a prospective evaluation of all pregnancies arising in the same clinic from 1983-1992. The study of Lipscomb et al (1997) was based on a regional genetic register for Marfan syndrome based in Manchester, UK. Table I summarizes outcomes from these three studies.

The more recent studies indicate that of 239 pregnancies, 75.7% resulted in live births, 23.8% resulted in fetal loss (miscarriage or stillbirths) and 0.8% resulted in a maternal death. One was lost to follow up (LFU). Both maternal deaths occurred in the postpartum period, after birth of healthy infants.

Maternal findings include an overall survival of 99%. Ninety-five percent of pregnancies had a benign course. Five percent of pregnancies had a complicated course. Mortality was 1% overall. Mortality was about 20% of complicated cases. Mortality was 0% in the uncomplicated cases. These figures indicate that pregnancy in Marfan syndrome is not as hazardous as it was formerly thought to be.

Among eleven patients with acute decompensation during pregnancy, two died. R-S and R-T had abortions, and L-3 was not diagnosed with Marfan syndrome until autopsy. To judge maternal safety, R-S and R-T are excluded; L-3 is arbitrarily included. Both maternal deaths were post-partum. One must be cautious in drawing conclusions from such a small group of patients. Based on this imprecise estimate, it appears that even mothers with acute decompensation in pregnancy will usually survive (7/9) without abortion.

Does pregnancy worsen Marfan syndrome? Adult patients with Marfan syndrome have a shortened lifespan and a high mortality, regardless of pregnancy. Rossiter et al (1995) found that cardiovascular outcomes in pregnant patients with Marfan syndrome were not different from similar Marfan patients who were not pregnant. Pyeritz (1981) found pregnant patients with Marfan syndrome had cardiovascular complications which were similar to mothers of patients with Marfan syndrome. Rossiter et al (1995) performed serial echocardiography on their pregnant patients with Marfan syndrome. Only one patient had a significant progressive dilatation of the aorta (R-P). These studies suggest that pregnancy does not significantly increase vascular complications above the already elevated rate seen in non-pregnant patients with Marfan Syndrome.

Four of the patients had abortions. Three of these four had subsequent surgical repair, and one of the four died of endocarditis sixteen months later. These cases indicate that abortion does not improve the underlying vascular disease nor prolong the patient’s life. From the maternal perspective abortion, is an unnecessary operation.

In the distant past, operative mortality for acute aortic dissection was about 50%. Operative mortality had fallen to less than 5% by 1984 (Kirklin, J.W. and Barrett-Boyes, 1993). Downing and Koushoukas (1997) reported an operative mortality of 2.2%. The review of Elkayam confirms that major vascular surgery can be undertaken in pregnancy, even on an emergent basis. . In the event of an vascular emergency, vascular repair should be performed.

Elective surgery is safer than emergency surgery. Several authors have reported series with no operative deaths for elective surgery (Treasure 1993; Gott et al, 1995). Elective vascular repair before the onset of a crisis is encouraged.

A number of patients had chronic conservative (non-operative) management. This option involves the use of beta-blockade (Lipscomb et al, 1997; Rossiter et al 1995) which slows the progression of vascular disease. This measure can be used to temporize if the fetus is not mature, or to prevent complications from occurring.

Maternal risks should neither be overestimated or underestimated. Abortion should be discouraged, because it is harmful to the baby, and because it does nothing for the mother’s underlying vascular disease. For mothers without acute decompensation, the likelihood of a healthy mother and a healthy baby is close to 99%. Even for mothers with acute decompensation, maternal mortality in pregnancy was only 2/9. If there is a need to temporize, chronic conservative management and beta-blockade is recommended. If the vascular condition becomes critical, surgical repair of the vasculature is recommended. Elective vascular repair before the onset of a crisis encouraged.

The assistance of Suzanne Baggot is gratefully recognized.

Downing, SW and Kouchoukos, NT (1997). Ascending aortic aneurysm. Cardiac Surgery in the Adult. edited by LH Edmunds. McGraw-Hill, New York and London, pp. 1165-1197. Gott, VL, Gillinor, AM, Pyeritz, RE et al. Aortic root replacement. Risk factor analyses of a seventeen year experience with 270 patients. J Thorac Cardiovascular. 1995. 109:536. Kirklin JW and Barratt-Boyes (1993). Acute aortic dissection. Cardiac Surgery:Morphology, Diagnostic Criteria, Natural History, Techniques, Results, and Indications. Churchill Livingstone publishers, New York and London. Pp. 1721-1748. Lipscomb, KJ, Smith, JC, Clarke, B, Donnai, P, Harris, R (1997). Outcome of pregnancy in women with Marfan’s syndrome. Brit J Obstet Gynecol. Feb 104(2):201-206. Isada NB, Drugan A, Johnson MP, and Evans MI (1996). Maternal Genetic Disease. Appleton and Lange, Stamford Connecticut. Page 102.  Pyeritz, RE (1981). Maternal and fetal complications of pregnancy in the Marfan syndrome. Am J Med Nov. 71(5):784-90. Rossiter, JP, Repke, JT, Morales, AJ, Murphy, EA, Pyeritz, RE (1995). A Prospective longitudinal evaluation of pregnancy in the Marfan syndrome. Am J Obstet Gynecol. Nov. 173 (5):1599-1606. Treasure, T (1993). Elective replacement of the aortic root in Marfan’s syndrome. Br Heart J Feb 69 (2):101-3. Vermillion, ST and Newman, RB (1998). Managing maternal cardiac defects during pregnancy. The Female Patient. 23:29-42. Wojtyla, C. (Also known as Pope John Paul II) 1995. Evangelium Vitae. Times Books, Random House. New York, NY. Paragraph 58.

TABLE In Outcome of Pregnancy in Marfan Syndromen