Preeclampsia was increased in women with Marfan syndrome, however only significantly in women not yet diagnosed with Marfan syndrome. The increased risk was also present among women diagnosed with Marfan syndrome, although this result did not reach significance. Reports of preeclampsia in a woman diagnosed with Marfan syndrome has been published previously.14Reassuringly, we found no association between having Marfan syndrome and experiencing preterm births. However, this is unexpected since insufficiency of connective tissue is associated with preterm birth.15
Foetal death was significantly increased among the undiagnosed Marfan syndrome women, however as none of the registrations were among women diagnosed with Marfan syndrome, the consequences of this finding in relation to Marfan syndrome is limited. We could not find any further information of this result in the registries.
In Denmark, legal abortion is a possibility until 12th week of gestation on mother’s request and after 12th week of gestation if permission is granted from the regional abortion council. Indications for a late abortion are for instance mother’s health, congenital malformations, and genetic indications including Marfan syndrome. The significantly increased proportion of late abortion in the diagnosed Marfan syndrome women suggests that a diagnosis of MFS in a foetus is followed by application of legal late abortion in pregnant Marfan women. This could be a contributing cause of the reduced birth rate among diagnosed Marfan syndrome women.
The level of cardiac surveillance of the diagnosed Marfan women during pregnancy in Denmark seems appropriate. It is even likely that some women with Marfan syndrome, perhaps unnecessarily when scrutinizing the present data, refrain from becoming pregnant, or choose abortion, due to careful guidance from the clinical and cardiac Marfan syndrome centres16. However, we do not have detailed information concerning the clinical status of the women with diagnosed Marfan syndrome that chose not to be become pregnant, and it may therefore be possible that some of these individuals, choosing not to become pregnant, and then voluntarily infertile, indeed are very high risk patients17. We anticipate that no cardiac surveillance program was instituted for the previously undiagnosed women with Marfan syndrome.
The difference in outcome shows the importance of a pre-pregnancy diagnosis. Whether some of the associations identified during pregnancy are driven by historical reports, thus emphasising the clinicians’ need to observe and register the complications, can only be considered among the women diagnosed with Marfan syndrome, and not among those not yet diagnosed. However, there is a possibility that the musculo-skeletal symptoms, known to be present in Marfan syndrome, are already present in the undiagnosed women, and as such, the clinicians have an increased awareness and register these complications.
Whether affected connective tissue because of FBN1 mutations in the uterine system, also can explain the findings with cervical complications, remains to be determined. The understanding of the association of an increased risk of preeclampsia in the women not yet diagnosed, remains to be elucidated, and clinical vigilance is recommended. It is possible that the pregnant women diagnosed with Marfan syndrome are treated medically with antihypertensive drugs, thus reducing the risk of preeclampsia.